WORLD TRADE WT/DS26/R/USA
18August 1997
ORGANIZATION(97-3368)
Original: English
ECMeasures Concerning Meat andMeat Products (Hormones)
Complaint bytheUnited States
Report ofthePanel
Thereport ofthePanel onECMeasures Concerning Meat andMeat Products (Hormones) -Complaint
bytheUnited States -isbeing circulated toallMembers, pursuant totheDSU. Thereport isbeing
circulated asanunrestricted document from 18August 1997 pursuant totheProcedures forthe
Circulation andDerestriction ofWTO Documents (WT/L/160/Rev.1). Members arereminded that
inaccordance with theDSU only parties tothedispute may appeal apanel report, anappeal shall be
limited toissues oflawcovered inthepanel report andlegal interpretations developed bythepanel,
andthatthere shall benoexparte communications with thepanel orAppellate Body concerning matters
under consideration bythepanel orAppellate Body.
Note bytheSecretariat: This Panel Report shall beadopted bytheDispute Settlement Body (DSB) within 60days after thedate ofitscirculation
unless aparty tothedispute decides toappeal ortheDSB decides byconsensus nottoadopt thereport. IfthePanel Report isappealed
totheAppellate Body, itshall notbeconsidered foradoption bytheDSB until after thecompletion oftheappeal. Information onthecurrent
status ofthePanel Report isavailable from theWTO Secretariat.i-i-
I. INTRODUCTION ..........................................1
II. FACTUAL ASPECTS ........................................2
1. The measures atissue ...................................2
2. The substances atissue (hormones) ..........................4
3. The Codex Alimentarius standards ..........................5
(a) The elaboration ofCodex standards ....................5
(b) Codex standards forfivehormones atissue ...............6
4. History ofevents ......................................8
5. History ofevents under theGATT ..........................11
III. CLAIMS OFTHE PARTIES ...................................12
IV. ARGUMENTS OFTHE PARTIES ...............................14
1. Relationship between GATT 1994 andtheSPS Agreement ..........14
2. The SPS Agreement ....................................16
(a) Article 2.2oftheSPS Agreement ......................21
(b) Article 2.3oftheSPS Agreement ......................34
(c) Article 3.1oftheSPS Agreement .....................37
(d) Article 3.3oftheSPS Agreement ......................42
(e) Articles 5.1and5.2oftheSPS Agreement ...............50
(i) Nature andmode ofaction ofthehormones ..........57
(ii) Metabolites ...............................71
(iii) Combinations ofhormones andmultiple exposure ......73
(iv) Detection andcontrol .........................75
(v) Administration anduseofhormones ...............80
(vi) Risks arising from other parameters ...............81
(vii) The precautionary principle .....................83
(viii) Animal health protection .......................86
(f) Article 5.4oftheSPS Agreement ......................88
(g) Article 5.5oftheSPS Agreement ......................88
(h) Article 5.6oftheSPS Agreement ......................90
(i) Article 5.7oftheSPS Agreement ......................93
3. Agreement onTechnical Barriers toTrade .....................94
4. GATT 1994
............................................................96
(a) Article III:4 ofGATT .............................96
(b) Article I:1ofGATT ...............................101
V. THIRD PARTIES SUBMISSION ................................104
1. Australia ...........................................104
2. Canada ............................................106
3. Norway ............................................108
4. New Zealand ........................................109
VI. PANEL 'SCONSULTATION WITH SCIENTIFIC EXPERTS ..............112
Panel procedures with regard toscientific expertise ....................113
Views ofthescientific experts ..................................114
VII. INTERIM REVIEW
............................................................159WT/DS26/R/USA
Page 1
I. INTRODUCTION
1.1 On26January 1996, theUnited States requested consultations withtheEuropean Communities,
pursuanttoArticle4oftheUnderstandingonRulesandProceduresGoverningtheSettlementofDisputes
("DSU"), Article 11oftheAgreement ontheApplication ofSanitary andPhytosanitary Measures
("SPS Agreement"), Article 14oftheAgreement onTechnical Barriers toTrade ("TBT Agreement"),
Article 19oftheAgreement onAgriculture andArticle XXII oftheGeneral Agreement onTariffs
andTrade 1994 ("GATT"), regarding theCouncil Directive Prohibiting theUseinLivestock Farming
ofCertain Substances Having aHormonal Action andrelated measures (WT/DS26/1).
1.2 On2February 1997, pursuant toArticle 4.11 oftheDSU, Australia (WT/DS26/3) andNew
Zealand (WT/DS26/2), followed on8February byCanada (WT/DS26/4), requested tobejoined in
these consultations. The European Communities accepted these requests on19March 1996
(WT/DS26/5).
1.3 On27March 1996, theUnited States, Australia, Canada and New Zealand held joint
consultations with theEuropean Communities butfailed toreach amutually satisfactory solution.
1.4 On25April 1996, pursuant toArticle 11oftheSPS Agreement, Article 14oftheTBT
Agreement, Article 19oftheAgreement onAgriculture, Article XXIII:2 oftheGATT, andArticle 6
oftheDSU, theUnited States requested theDispute Settlement Body ("DSB") toestablish apanel
with standard terms ofreference (WT/DS/26/6). TheUnited States claimed thattheECmeasures:
"...adversely affect imports ofmeat andmeat products andappear tobeinconsistent with
theobligations oftheEuropean Communities under theGeneral Agreement onTariffs and
Trade 1994, theAgreement ontheApplication ofSanitary andPhytosanitary Measures, the
Agreement onTechnical Barriers toTrade, andtheAgreement onAgriculture. Theprovisions
ofthese agreements with which these measures appear tobeinconsistent include, butarenot
limited to,thefollowing:
(1) General Agreement onTariffs andTrade 1994, Article IIIorArticle XI;
(2) Agreement ontheApplication ofSanitary andPhytosanitary Measures,
Articles 2,3and5;
(3) Agreement onTechnical Barriers toTrade, Article 2;and
(4) Agreement onAgriculture, Article 4.
These measures alsoappear tonullify orimpair thebenefits accruing totheUnited States directly
orindirectly under thecited agreements".
1.5 On20May 1996, theDSB established aPanel inaccordance with therequest made bythe
United States. Theagreed standard terms ofreference ofthePanel were (WT/DS26/7):
"Toexamine, inthelight oftherelevant provisions ofthecovered agreements cited bythe
United States indocument WT/DS26/6, thematter referred totheDSB bytheUnited States
inthat document and tomake such findings aswill assist theDSB inmaking the
recommendations oringiving therulings provided forinthose agreements".
1.6 Australia, Canada, New Zealand andNorway reserved their rights toparticipate inthePanel
proceedings asthird parties.WT/DS26/R/USA
Page 2
1.7 On2July 1996, thePanel wasconstituted with thefollowing composition:
Chairman: Mr.Thomas Cottier
Panellists: Mr.JunYokota
Mr.Peter Palecka
1.8 ThePanel metwith theparties on10October 1996 and11November 1996. Itmetwith third
partieson10October1996.ThePanelconsultedscientificandtechnicalexpertson17-18February1997
inameeting held jointly with thepanel proceeding brought byCanada onthesame ECmeasures.1
1.9 On28November 1996, theChairman ofthePanel informed theDSB thatthePanel would
notbeable toissue itsreport within sixmonths. Thereasons forthatdelay arestated indocument
WT/DS/26/8.
1.10 ThePanel issued itsinterim report totheparties on7May 1997. Following arequest made
bytheEuropean Communities pursuant toArticle 15.2 oftheDSU, thePanel held afurther meeting
with theparties on4June 1997. ThePanel issued itsfinal report totheparties tothedispute on
30June 1997.
II. FACTUAL ASPECTS
1. The measures atissue
2.1 This dispute concerns EC measures, inparticular Council Directive 81/602/EEC
("Directive 81/602/EEC"), Council Directive 88/146/EEC ("Directive 88/146/EEC") andCouncil
Directive 88/299/EEC ("Directive 88/299/EEC").2
2.2 Directive 81/602/EEC prohibits theadministering tofarm animals ofsubstances having a
thyrostatic action orsubstances having anoestrogenic, androgenic orgestagenic action; theplacing
onthemarket orslaughtering offarm animals towhich these substances have been administered; the
placing onthemarket ofmeat from such animals; theprocessing ofmeat from such animals andthe
placing onthemarket ofmeat products prepared from orwith such meat. TheDirective provides
twoexceptions totheprohibition: oneexception isprovided forsubstances with anoestrogenic,
androgenic orgestagenic action when they areused fortherapeutic orzootechnical purposes and
administered byaveterinarian orunder aveterinarian 'sresponsibility. Theother exception wasfor
oestradiol-17 ,progesterone, testosterone, trenbolone acetate (orTBA) andzeranol -when they were
used forgrowth promotion purposes andtheir usewasgoverned according totheindividual regulatory
schemes maintained byECmember States. This exception wasmade pending anexamination ofthe
effects ofthese hormones onthehealth ofconsumers andtheadoption ofanECrule. ECmember
States areobliged toapply their regulatory schemes toimports from third countries inamanner not
more favourable than thatapplied tointra-EC trade.
2.3 Directive 88/146/EEC extends theprohibition imposed byDirective 81/602/EEC tothe
administration tofarm animals oftrenbolone acetate andzeranol foranypurpose, andoestradiol-17 ,
testosterone andprogesterone forfattening purposes. However, theDirective maintains thepermission
1WT/DS48/6.
2OthermeasuresrelevanttothedisputearecontainedinDirectives72/462/EEC, 81/602/EEC, 81/851/EEC, 81/852/EEC,
85/358/EEC, referencedinDirective88/146/EEC; thedecisions,controlprogrammeandderogationsreferredtoinArticle6(2),
Article 6(7)andArticle 7,respectively, ofDirective 88/146/EEC; andanyamendments ormodifications, including Directives
96/22/EC and96/23/EC.WT/DS26/R/USA
Page 3
toadminister these three natural hormones toanimals fortherapeutic andzootechnical purposes under
prescribed conditions; inparticular, therapeutic treatment isdefined tomean theadministering toan
individual animal ofanyofthesubstances which areauthorized totreat afertility problem diagnosed
onexamination byaveterinarian. Theproducts which areused fortherapeutic treatment may be
administered only byaveterinarian, intheform ofaninjection (totheexclusion ofimplantation) to
farm animals which have been clearly identified. Such treatment must beregistered bytheveterinarian
andthese animals may notbeslaughtered before expiry oftheperiod fixed. Inthecase ofanimals
attheendoftheir reproductive career, thetreatments areprohibited from being administered during
thefattening period following theendoftheir breeding life. Article 4ofdirective 88/146/EEC explicitly
requires thatundertakings intheECmember States producing theprohibited hormones, those companies
authorized tomarket these hormones forwhatever purposes andundertakings producing pharmaceutical
andveterinary products based onthose substances, must keep adetailed register recording (in
chronological order) thequantities produced oracquired andthose soldorused fortheproduction of
pharmaceutical andveterinary products. Theimportation from third countries ofanimals andmeat
from animals towhich have been administered substances with thyrostatic, oestrogenic, androgenic
orgestagenic action isprohibited.3However, under certain conditions, Article 7ofDirective
88/146/EEC allows trade inthose animals andmeat from those animals treated fortherapeutic or
zootechnical purposes, including imports from third countries.4
2.4 Directive 88/299/EEC laysdown theconditions forapplying thederogations, provided for
inArticle 7ofDirective 88/146/EEC, from theprohibition ontrade incertain categories ofanimals
andtheir meat. Thefirst derogation oftheDirective requires ECmember States toauthorize trade
inanimals intended forreproduction andreproductive animals attheendoftheir career (and ofmeat
ofsuch animals) which, during their reproductive career, have undergone oneoftwocategories of
treatments: Thefirstcategory istherapeutic treatment with oneofthefollowing substances: oestradiol-
17,testosterone andprogesterone; andthose derivatives which readily yield theparent compound
onhydrolysis after absorption atthesiteofapplication which appear inalistofapproved products.
Thesecond category istheadministration ofsubstances having anoestrogenic, androgenic orgestagenic
action forsynchronization ofoestrus, termination ofunwanted gestation, theimprovement offertility
andthepreparation ofdonors andrecipients fortheimplantation ofembryos, provided thattheproducts
inwhich theyarecontained appear onalistofapproved products andwiththerespect ofstrict conditions
ofuseconcerning, inparticular, therespect ofthewithdrawal period, themonitoring ofthose conditions
ofuseandofthemeans ofidentification oftheanimals. Inaddition, Articles 3and4ofthisDirective
provide thattrade between theECmember States oftheEuropean Communities inanimals intended
forreproduction andreproductive animals andmeat from such animals isallowed only ifallthe
conditions laiddown intheDirective arerespected, inparticular asregards thewaiting period and
therequirement thatanimals have notreceived anyoftheabove treatments with anyoftheabove
substances during thefattening period following theendoftheir breeding life. TheECstamp may
beaffixed tothemeat only ifthewaiting time ended before theanimals areslaughtered. Thesecond
3Article 6(7)ofDirective 88/146/EEC requires theestablishment ofacontrol programme asregards imports from third
countries toensure thatimports donotreceive more favourable treatment thanECproducts. This control programme also
provides forrules onthefrequency ofcontrols onimports from each third country andonguarantees offered bytheinspection
regulation ofthird countries. Such checks onimports arenow carried outinaccordance with Directives 91/496/EEC and
90/675/EEC.
4Article 7ofDirective 88/146/EEC allows derogations inrespect totrade inanimals intended forreproduction and
reproductive animals attheendoftheir career (and inrespect ofmeat from these various animals, taking intoaccount the
guarantees given), which inthecourse oftheir existence have been treated under theprovisions ofArticle 4ofDirective
81/602/EEC. Thisarticleauthorizestheadministrationtofarmanimalsofsubstanceswithoestrogenic,androgenicorgestagenic
action approved inaccordance withtheDirectives onveterinary medical products (other thansubstances referred toinArticle 3
ofDirective 81/602/EEC) fortherapeutic use,synchronization ofoestrus, termination ofunwanted gestation, theimprovement
offertility andthepreparation ofdonors andrecipients fortheimplantation ofembryos. Theadministering ofthese substances
shall beeffected byaveterinarian, however, ECmember States mayallow thesynchronization ofoestrus andthepreparation
ofdonors andrecipients fortheimplantation ofembryos tobedone notbyaveterinarian butunder hisdirect responsibility.WT/DS26/R/USA
Page 4
derogation inDirective 88/299/EEC allows imports from third countries oftreated animals andmeat
ofsuch animals under guarantees equivalent tothose fordomestic animals andmeat.
2.5 Directive 96/22/EC willreplace Directives 81/602/EEC, 88/146/EEC and88/299/EEC asfrom
1July 1997. Itwillmaintain theprohibition ontheuseofthese hormones forgrowth promotion
purposes; extend theprohibition ontheuseofbeta-agonists; restrict theuseofthehormones atissue
fortherapeutic orzootechnical purposes, reinforcing inparticular theroleoftheveterinarian; and
reinforce theprovisions oncontrol andtesting. Penalties andsanctions incase ofviolations areto
beincreased where checks detect thepresence ofprohibited substances orproducts orresidues of
substances administered illegally. Such substances orproducts willbeconfiscated andanytreated
animals ormeat placed under official supervision until penalties have been applied.
2. The substances atissue (hormones)
2.6 Hormones (chemicals) produced bythebodies ofhumans andanimals arecalled endogenous
ornatural hormones. (Phyto-hormones areproduced bysome plants.) Compounds chemically
synthesized tomimic theeffect ofnatural hormones arecalled synthetic orxenobiotic hormones. Natural
hormones aresecreted intotheblood stream byspecialized cells andtravel throughout thebody.
Hormones actbybinding protein receptors present inhormone-responsive tissues. Thereceptor
undergoes aconformational change, binds tospecific DNA sequences andregulates specific genes within
acell. Synthetic hormones maydiffer from endogenous (natural) hormones intheir rateofmetabolism
andexcretion.
2.7 Hormones function infourbroad areas: reproduction; growth anddevelopment; maintenance
oftheinternal environment; andproduction, utilization andstorage ofenergy. One hormone can
have multiple actions. Forexample, themale hormone testosterone controls many processes from
thedevelopment ofthefetus tolibido intheadult. One function may becontrolled bymultiple
hormones: themenstrual cycle involves oestradiol, progesterone, follicle-stimulating hormone and
luteinizing hormone.
2.8 Ofthesixhormones involved inthisdispute, three arenaturally occurring hormones produced
byhumans andanimals: oestradiol-17 ,progesterone andtestosterone (hereafter alsoreferred toas
natural hormones). Oestradiol-17 isasexsteroidal hormone withoestrogenic action (i.e., responsible
forfemale characteristics); testosterone isasexsteroidal hormone with androgenic action (i.e.,
responsible formale characteristics); progesterone isasexsteroidal hormone with gestagenic action
(i.e.,responsibleformaintainingpregnancy).Thesethreehormonesareproducedthroughoutthelifetime
ofeach individual andarerequired fornormal physiological functioning andmaturation. Hormone
levels vary with thetissue, with thespecies ofanimal andwith thesexandindividual. Hormone levels
vary most dramatically with puberty, pregnancy andcastration.
2.9 Theotherthreehormonesinvolvedinthisdisputeareartificiallyproducedhormones:trenbolone,
zeranol andmelengestrol acetate (MGA) (hereafter alsoreferred toassynthetic hormones). These
hormones mimic thebiological activity ofthenatural hormones. Trenbolone mimics theaction of
testosterone; zeranol mimics theaction ofoestradiol-17 ;andMGA mimics progesterone.
2.10 IntheUnitedStates,thethreenaturalhormonesmaybeusedformedicaltreatment(therapeutic).
Oestradiol-17 isalsopermitted forzootechnical purposes. IntheUnited States thesixhormones are
alsoapproved forgrowth promotion purposes. Three ofthehormones used forgrowth promotion
purposes, trenbolone, zeranol, andMGA, have nozootechnical ortherapeutic uses. Forgrowth
promotion purposes, fiveofthese hormones (except MGA) areformulated aspellets (with approved
andfixed amounts ofcompound) designed tobeimplanted intheearoftheanimal. Theearisdiscarded
atslaughter. MGA isadministered asafeed additive.WT/DS26/R/USA
Page 5
3. The Codex Alimentarius standards
2.11 TheSPSAgreement makes reference, inanumber ofprovisions, to"therelevant international
standards, guidelines andrecommendations". Annex A:3(a) oftheSPS Agreement states thatthe
international standards, guidelines andrecommendations relevant forfood safety arethose established
bytheCodexAlimentariusCommissionrelatingtofoodadditives,veterinarydrugandpesticideresidues,
contaminants, methods ofanalysis andsampling, andcodes andguidelines ofhygienic practice.
2.12 TheCodexAlimentariusCommission(hereafterthe"CodexCommission")isajointFAO/WHO
advisory body established toimplement theJoint FAO/WHO Food Standards Programme. Thepurpose
ofthisprogramme istoprotect thehealth ofconsumers andtoensure fairpractices infood trade through
theelaborationoffoodstandards.Thesestandards,togetherwithnotificationsreceivedfromgovernments
with respect totheir acceptance orotherwise ofthestandards, constitute theCodex Alimentarius. The
Codex Alimentarius (hereafter "theCodex") isthusacollection ofinternationally adopted food standards
presented inauniform manner.
2.13 Membership oftheCodex Commission isopen toallmember Nations andAssociate members
ofFAO and/or WHO andiscomposed ofgovernment representatives ofthese members. Most ofits
members, including theUnited States andtheECmember States, areWTO Members. TheEuropean
Communities hasanobserver status intheCodex Commission. TheCodex Commission hasestablished
anumber ofsubsidiary bodies, including theCodex Committee onResidues ofVeterinary Drugs in
Food ("CCRVDF").
2.14 Thetechnicalandscientificanalysisofveterinarydrugs,foodadditivesandsomeothersubstances
infoods andbeverages isnotundertaken bytheCodex Commission itself butindependently bythe
Joint FAO/WHO Expert Committee onFood Additives ("JECFA"). TheJECFA iscomposed of
independent scientists whoserve intheir individual capacities asexperts, notasrepresentatives oftheir
governments ororganizations. Thegoal oftheJECFA evaluation ofveterinary drugs is:
"toestablish safelevels ofintake bysetting Acceptable Daily Intakes (ADI) andtodevelop
maximum residue limits when veterinary drugs areused inaccordance with good veterinary
practice".5
(a) The elaboration ofCodex standards
2.15 Theelaboration ofCodex standards involves an8-step process:
Step 1:TheCodex Commission decides toelaborate astandard andidentifies which subsidiary
body orother body should undertake thework, taking into account the"Criteria forthe
Establishment ofWork Priorities andfortheEstablishment ofSubsidiary Bodies". Decisions
toelaborate standards mayalsobetaken bysubsidiary bodies oftheCodex Commission subject
tosubsequent approval bytheCodex Commission oritsExecutive Committee.
Step 2:TheCodex Commission secretariat arranges forthepreparation ofa"proposed draft
standard". Inthecaseofveterinary drugs, JECFA isincharge ofpreparing recommendations
formaximum residue levels.
Step 3:The secretariat distributes the"proposed draft standard" tothemembers ofthe
Commission forcomments.
5Codex Alimentarius, Vol.3, Residues ofVeterinary Drugs inFoods, p.vi.WT/DS26/R/USA
Page 6
Step 4:Thecomments received aresentbythesecretariat totheCCRVDF which considers
thecomments andprepares, ifappropriate, aproposed draft standard.
Step 5:The proposed draft standard issubmitted through thesecretariat totheCodex
Commission ortotheExecutive Committee with aview toitsadoption asa"draft standard".
Step 6:The"draft standard" issentbythesecretariat toallmembers andinterested international
organizationsforcommentsonallaspects,includingpossibleimplicationsofthe"draftstandard"
fortheir economic interests.
Step 7:Thecomments received aresentbythesecretariat totheCCVDRF, which considers
such comments andmay amend the"draft standard".
Step 8:The"draft standard" issubmitted through thesecretariat totheCodex Commission
together with anywritten proposals received from members andinterested international
organizations foramendments atStep 8with aview toitsadoption asa"Codex standard".
Adoption ofstandards isnormally done onthebasis ofaconsensus decision, however, if
requested, avote may betaken. Inthiscase, adecision bythemajority ofCodex members
isrequired. Anaccelerated elaboration procedure may beused when there isanurgent need
forastandard.
2.16 TheCodexCommissionkeepsunderreviewandmayreviseCodexstandards,generallyfollowing
procedures similar tothose used fortheelaboration ofstandards. Codex standards arepublished and
senttogovernments foracceptance andtointernational organizations towhich competence inthematter
hasbeen transferred bytheir ECmember States. Acceptance ofthestandards isvoluntary andCodex
members arenotrequired toindicate formal acceptance ofCodex standards, guidelines or
recommendations. Theimplementation ofCodex standards atthenational level istheresponsibility
ofmembers.
(b) Codex standards forfivehormones atissue
2.17 Codex standards forveterinary drugs arenormally stated interms ofanAcceptable Daily Intake
("ADI") andaMaximum Residue Limit ("MRL"). AnADI is"anestimate byJECFA oftheamount
ofaveterinary drug, expressed onabody weight basis, thatcanbeingested daily over alifetime without
appreciable health risk(standard man =60kg)".6AnADI isderived from theexperimental No
Observable Effect Level ("NOEL") inthemost appropriate animal species, byapplying anappropriate
safety factor. Toaccount forsensitivity variabilities between humans andanimals, anddietary
variabilities among humans, asafety factor istypically applied. When datafrom long-term animal
toxicity studies areavailable, asafety factor of100isgenerally applied. Larger safety factors, up
to1000, may beused incertain cases.
2.18 ACodex MRL isoneofthetools forensuring thatintake does notexceed theADI andthat
"Good Practice intheuseofVeterinary Drugs" ("GPVD") isobserved. Itisthemaximum concentration
ofresidue resulting from theuseofaveterinary drug (expressed inµg/kg orµg/kg onafresh weight
basis) thatisrecommended bytheCodex Commission tobelegally permitted orrecognized asacceptable
inoronafood. Test animals arefirsttreated with thedrug inaccordance with proposed GPVD and,
onthebasis ofthisusage, tentative MRLs aresetforvarious tissues. These MRLs arethencompared
with theADI, considering dietary food intake. IftheMRL established onthebasis ofproposed GPVD
would cause theADI tobeexceeded, theMRL willbelowered toalevel which ensures thattheADI
isnotexceeded, andtheproposed GPVD willalsobemade stricter. If,ontheother hand, theproposed
6Ibid.,p.65.WT/DS26/R/USA
Page 7
MRL would notcause theADItobeexceeded (asismost frequently thecase), theMRL willbeproposed
foradoption. Thus, MRLs arefrequently setatlevels below (even farbelow) thetheoretical safelevels
determined from anADI. AnMRL may alsobereduced tobeconsistent with theGPVD asapproved
bynational authorities orincreased (toalevel stillbelow thesafelevel) tobedetectable using practical
methods.
2.19 "Good Practice intheUseofVeterinary Drugs" (GPVD), isdefined as:
"the official recommended orauthorized usage including withdrawal periods, approved by
national authorities, ofveterinary drugs under practical conditions."7
According totheCodex expert advising thePanel, theterms "good veterinary practice" and"good
veterinary andhusbandry practice", when used inJECFA reports, aresynonyms forGPVD.
2.20 Forthehormones atissue, JECFA considered fiveofthesixsubstances (allexcept MGA)
andmade recommendations onfour ofthem (excluding trenbolone) during its32nd Session in1987.
Fortrenbolone, further datawassought andaJECFA recommendation made in1989. TheCCRVDF
considered theJECFA recommendations atitsmeetings in1987 andrecommended draft standards
forthethree endogenous hormones andzeranol. These draft standards were approved bytheCodex
Commission atStep 5in1989. Standards forthese four hormones were considered atStep 8bythe
Codex Commission inJune 1991, but,following avote onthematter, were notadopted. Adraft
standard fortrenbolone atStep 5wasadopted on1991. InJune 1995, theCodex Commission adopted
standards, atStep 8,forthefivehormones, onthebasis ofavote. These standards apply exclusively
with respect tocattle, andmeat andmeat products ofbovine origin, when these hormones areused
forgrowth promotion purposes.
2.21 With respect tothethree natural hormones indispute, oestradiol-17 ,progesterone and
testosterone, similar Codex standards apply. Forthese three hormones itwasconsidered "unnecessary "
toestablish anADI orMRL.8Specifically, theCodex states that:
"Establishing anADI andan[MRL] forahormone thatisproduced endogenously atvariable
levels inhuman beings wasconsidered unnecessary bytheCommittee. Residues resulting
from theuseofthissubstance asagrowth promoter inaccordance with good animal husbandry
practice areunlikely topose ahazard tohuman health."9
2.22 The32nd JECFA Report of1988 ("1988 JECFA Report"), onwhich theCodex standards are
based, concluded thatresidues arising from theuseoftestosterone andoestradiol-17 asagrowth
promoter inaccordance with good animal husbandry practice areunlikely topose ahazard tohuman
health andthattheamount ofexogenous progesterone ingested inmeat from treated animals would
notbecapable ofexerting anhormonal effect, andtherefore, anytoxic effect, inhuman beings. Since,
according toJECFA, thepotential toxic effect ofresidues ofthese hormones isdirectly related totheir
hormonal effect, thereport concluded thattheadditional residue levels intreated animals arenotcapable
ofexerting anytoxic effect. Onthebasis ofthissafety assessment andinview ofthedifficulty of
determining thelevels ofresidues attributable totheuseofthese hormones forgrowth promoting
purposes incattle (residues ofendogenous natural hormones inmeat cannot bepractically distinguished
from those exogenously administered), JECFA concluded thatitwas"unnecessary" toestablish an
ADI orMRL forthese hormones.
7Ibid.
8Codex Alimentarius, Vol. 3-1995, Section 1,pp.7, 12and14.
9Ibid.,Section 1,footnote, pp.7, 12and14.WT/DS26/R/USA
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2.23 With respect totwoofthesynthetic hormones atissue, zeranol andtrenbolone, theCodex
standards arethefollowing: anADI of0-0.5 and0-0.02 µg/kg body weight, respectively, andforboth
hormones anMRL of2µg/kg inbovine muscle and10µg/kg inbovine liver.
2.24 The1988 JECFA Report, onwhich theCodex standard forzeranol isbased, noted thatzeranol
wasaweak oestrogen which mimicked theaction ofoestradiol-17 .TheReport concluded thatthe
toxic (incasu tumorigenic) effect ofzeranol isassociated withitshormonal (i.e.oestrogenic) properties
andthatanADI could thusbeestablished onthebasis ofano-hormonal-effect level. Adopting what
itconsidered tobeaconservative approach byusing asabasis studies onovariectomized female
cynomolgus monkeys (highly sensitive tooestrogenic substances) andusing asafety factor of100,
JECFA setanADI forhuman beings of0-0.5 µg/kg ofbody weight. Fora70kgperson consuming
500gofmeat daily over anentire lifetime, themaximum permissible orsafelevel ofzeranol residues
inmeat would then, according toJECFA, be70µg/kg ofedible tissue. However, theReport noted
thatwhen zeranol isadministered tocattle according togood animal husbandry practice, themaximum
mean residue levels didnotexceed 0.2µg/kg inmuscle, 10µg/kg inliver, 2µg/kg inkidney, and
0.3µg/kg infatatanytime after implantation. These residue levels obtained onthebasis ofgood
animal husbandry practice arethusbelow themaximum permissible level of70µg/kg. However, in
order tosetalevel which isdetectable byroutine residue analysis methods, theCodex MRL was
increased to2µg/kg inmuscle andsetat10µg/kg inliver.
2.25 Trenbolone acetate isthechemical form orester used fortheadministration oftrenbolone.
Trenbolone, ortrenbolone acetate ("TBA"), anandrogen which mimics theaction oftestosterone, is
rapidly hydrolysed after administration tocattle. Themajor metabolite (i.e. compound intowhich
TBA breaks down bychemical activity after entering thebody) is occurring inter alia
inliver, and -trenbolone present inmuscle. With respect toTBA, the1988 JECFA Report concluded
thatitspotential toxic effects only arise asaconsequence ofitshormonal activity. Thereport further
concluded that, therefore, anADI could beestablished onthebasis ofano-hormonal-effect level.
Adopting what itconsidered tobeaconservative approach byusing asabasis studies oncastrated
male rhesus macaque monkeys (which arehighly sensitive tocompounds withantigonadotropic activity)
andpigs(which areasensitive model forassessing hormonal effects ofTBA) andusing asafety factor
of100, JECFA later setanADI forhuman beings of0-0.02 µg/kg ofbody weight (34th JECFA Report
of1989). Themaximum ADI fora60kgperson would thus be1.2µgofTBA residues. JECFA
then setMRL 'sfor -trenbolone inmuscle and inliver of2µg/kg and10µg/kg,
respectively, based onaverage residue levels inheifers at15-30 days after implantation of300mg
TBA, noting thatconcentrations would beeven lower atproposed GPVD. According toJECFA, the
MRL 'sthusobtained onthebasis ofconservative estimates should notexceed theCodex ADI orsafe
level atanytime after implantation ofthedrug, thatis,irrespective ofthewithdrawal period used.
4. History ofevents
2.26 European consumers 'concern over theuseofhormones forgrowth promotion purposes in
livestock grew steadily throughout the1970s astheresult oftheillegal useofdethylstilboestrol,
commonly known asDES (seeparagraph 4.123), invealproduction inFrance andincidents, particularly
inItaly, where adolescents hadbeen reported tobesuffering from hormonal irregularities andveal
hadcome under suspicion asapossible cause. European consumer organizations called foraboycott
ofveal, andthemarket forveal wasseverely affected. On20September 1980, theECCouncil of
(Agriculture) Ministers adopted adeclaration infavour ofabanontheuseofoestrogen andendorsed
theprinciple ofgreater harmonisation oflegislation onveterinary medicines andofgreater control
onanimal rearing, both attheproduction andslaughtering stages.
2.27 On31October 1980, theECCommission proposed legislation aimed atbanning theuseof
allhormone products (COM (80)614), except fortherapeutic purposes. This proposal wasexpanded
later bydocuments COM(80)920 andCOM(80)922, presented on6January 1981. These allowed forWT/DS26/R/USA
Page 9
thecontrolled usefortherapeutic andzootechnical purposes ofthree natural hormone products, and
introduced anumber ofcontrol measures ontheproduction andhandling ofsuch products, together
with proposals onthetesting ofanimals. On13February 1981, theEuropean Parliament adopted
the"Nielsen Report" approving theCommission proposals. TheECEconomic andSocial Committee
endorsed theproposals inFebruary 1981. However, three ECmember States (Belgium, Ireland and
theUnited Kingdom) sought tohave thethree natural hormones remain available both astherapeutic
drugs andasgrowth promotion agents, andIreland andtheUnited Kingdom alsoargued fortheretention
ofthesynthetic hormones, trenbolone andzeranol. Moreover, third countries, including Argentina,
Australia, Canada, New Zealand, South Africa andtheUnited States, alsoraised questions concerning
theimpact ofanybanontheir exports totheEuropean Communities.
2.28 The ECCouncil ofMinisters adopted itsfirst Directive ontheissue (81/602/EEC) on
31July 1981. InthatDirective, andinregard tofiveofthehormones atissue (allbutMGA), the
Council directed theCommission toprovide, notlater than 1July 1984, areport ontheexperience
acquired andscientific developments, accompanied, ifnecessary, byproposals taking intoaccount these
developments. Accordingly, theCommission setupaScientific Group onAnabolic Agents inAnimal
Production, chaired byProfessor G.E. Lamming (the"Lamming Group"). Thequestion addressed
totheLamming Group was:
"Does theuseforfattening purposes inanimals ofthefollowing substances: oestradiol-17 ,
testosterone, progesterone, trenbolone andzeranol present anyharmful effect tohealth".10
TheLamming Group issued aninterim report on22September 1982 (the"Lamming Report"). The
Lamming Report concluded asfollows:
"The Scientific Working Group isoftheopinion thattheuseofoestradiol-17 ,testosterone
andprogesterone andthose derivatives which readily yield theparent compound onhydrolysis
after absorption from thesiteofapplication would notpresent anyharmful effects tothehealth
oftheconsumer when used under theappropriate conditions asgrowth promoters infarm
animals.
"Evaluation ofdataon"trenbolone" and"zeranol" revealed thatsome data onthehormonal
non-effect-level andthetoxicology ofthese compounds andtheir metabolites arestillmissing.
"The Scientific Working Group considers itnecessary thatadditional information beprovided
before afinal conclusion canbegiven ontrenbolone andzeranol.
"Proper programmes tocontrol andmonitor theuseofanabolic agents areessential.
"Itisnecessary tocontinue scientific investigations ontherelevance ofthepresent useofthe
"no-hormone-effect" level related totheharmful effects ofanabolic agents".
2.29 The ECScientific Veterinary Committee gave itsreaction totheLamming Report on
9November1982,followedbytheECScientificCommitteeforAnimalNutritionon17November1982
andbytheECScientific Committee forFood on4February 1983. These Committees supported the
conclusions andrecommendations oftheLamming Report, butstressed theneed tolaydown provisions
regarding theestablishment ofproper programmes tocontrol andmonitor theuseofanabolic agents
with regard, inparticular, toinstructions foruse, surveillance programmes andanalysis methods.
InJanuary 1984, theCommission asked agroup ofexperts within theECScientific Committee on
AnabolicAgentstoreviewtheinformationontrenboloneandzeranol.On12June1984,theCommission
10Report ofthe(EC) Scientific Veterinary Committee, Scientific Committee forAnimal Nutrition andtheScientific
Committee forFood ontheBasis oftheReport oftheScientific Group onAnabolic Agents inAnimal Production, pp.1 and12.WT/DS26/R/USA
Page 10
published aproposal (COM(84)295 final) foraCouncil Directive amending Directive 81/602/EEC,
which envisaged thecontrolled useofthethree natural hormones forgrowth promotion purposes and
proposed re-examining thebanonthetwosynthetic hormones after their scientific evaluation hadbeen
completed. However, theEuropean Parliament, theECEconomic andSocial Committee andtheEC
Council ofMinisters rejected theCommission 'sproposal.
2.30 TheECCommissionamendeditsproposalaccordinglyandon31December1985theECCouncil
adopted Directive 85/649/EEC. This Directive banned theuseofallthesubstances concerned for
growth promotion purposes andestablished more detailed provisions concerning authorized therapeutic
uses. TheDirective waschallenged intheEuropean Court ofJustice, which annulled itonprocedural
grounds. Theproposals were re-introduced bytheECCommission andre-adopted bytheECCouncil
asCouncil Directive 88/146/EEC on16March 1988.
2.31 Followingreportsofsignificantuseofillegalgrowth-promotinghormonalsubstancesinanumber
ofECmember States, on26September 1988 theEuropean Parliament established a"Committee of
Enquiry intotheProblem ofQuality intheMeat Sector". TheReport ofthisCommittee (the"Pimenta
Report") endorsed thebanontheuseofhormones andwasadopted bytheEuropean Parliament on
29March 1989 (seeparagraphs 4.36-4.39). Theessential findings ofthePimenta Report were that
theprohibition ofhormonal substances fornon-therapeutic (i.e.growth-promoting) purposes must be
maintained andexpanded because:
(i) thiswastheonly way torestore consumer confidence inthemeat sector;
(ii) 10outof12national veterinary experts indicated thatatotal banwould facilitate
implementation andcontrol;
(iii) Thescientific conclusions regarding theuseofnatural hormones rested upon strict
conditions ofusewhich itbelieved could notinreality beattained. TheCommittee
wasoftheopinion thatuseofthenatural/nature-identical hormones carries therisk
ofinexperienced application, incorrect dosage andunsupervised injection which could
pose arisktotheanimal andtheconsumer, andalsonoted doubts with regard tolong-
term cumulative andinteractive potential carcinogenicity. Inaddition, theCommittee
believed thatproven necessity andsocio-economic desirability should becriteria of
acceptability fortheuseof(bio)chemical growth promoters inanimal-rearing;
(iv) The Committee didnotaccept theargument thatprohibiting theuseforgrowth
promotion ofsome natural ornature-identical hormones would result inanincrease
intheuseofother, more dangerous growth-promoting substances tothedetriment of
theconsumer;
(v) TheCommittee believed thattheCommission should promote theconcept ofanimal
welfare inagricultural production.
2.32 TheEuropean Parliament adopted another report ontheissue ofuseofhormones foranimal
growth promotion, the"Collins Report" of7February 1989.11This report argued that:
"Current licensing systems fortheregulation ofveterinary medicines (including atpresent,
growth promoting products) require thatanewproduct satisfy three criteria: safety, quality
andefficacy. These criteria may well besatisfactory fortherapeutic drugs. They arebyno
11European Parliament, Committee ontheEnvironment, Public Health andConsumer Protection, Report on"The USA's
Refusal tocomply with Community legislation onslaughterhouses andhormones andtheconsequences ofthisrefusal",
EP128381/B, 7February 1989, named after itsreporter Mr.Collins, MEP.WT/DS26/R/USA
Page 11
means sufficient forgrowth promoting products. Forthelatter itisproposed here thatthe
Community 'sveterinary medicine licensing system beadapted toinclude a"fourth hurdle",
entailing anobjective socio-economic and environmental impact assessment" .Inthe
Commission 'sJuly 1988 draft proposals forthereform ofveterinary medicine licensing in
theCommunity thisidea was accepted inprinciple. The final version oftheproposals
(December 1988) does notinclude thisconcept. Itisclear, however, thatthesocial, agricultural
andenvironmentalimplicationsoftheuseofgrowthandyieldpromotingpharmaceuticalsrequire
alicensing system somewhat different from thatwhich exists forthese products when used
fortherapeutic purposes".
2.33 The ECCommission organized ascientific conference onthissubject inBrussels from
29November to1December 1996. With regard tothenatural hormones, the1995 ECScientific
Conference onGrowth Promotion inMeat Production (the"1995 ECScientific Conference") concluded
that:
"Atpresent, there isnoevidence forpossible health risks totheconsumer duetotheuseof
natural sexhormones forgrowth promotion, since:
Residue levels ofthese substances measured inmeat oftreated animals fallwithin the
physiological range observed inmeat ofcomparable untreated animals.
Thedaily production ofsexhormones byhumans ismuch higher than theamounts
possibly consumed from meat, even inthemost sensitive humans (prepubertal children
andmenopausal women).
Due toanextensive first-pass metabolism, thebioavailability ofingested hormones
islow, thus providing afurther safety margin."12
With regard tothesynthetic hormones, zeranol andtrenbolone, the1995 ECScientific Conference
concluded that:
"Atthedoses needed forgrowth promotion, residue levels [oftrenbolone andzeranol] are
well below thelevels regarded assafe(theMRLs). There are,atpresent, noindications of
apossible human health riskfrom thelowlevels ofcovalently-bound residues oftrenbolone."13
5. History ofevents under theGATT
2.34 InMarch 1987, theUnited States raised theissue oftheECbanunder theTokyo Round
Agreement onTechnical Barriers toTrade ("TBT Agreement"). Bilateral consultations between the
UnitedStatesandtheEuropeanCommunitiesfailedtoresolvethedispute.ArguingthattheECDirective
wasnotsupported byscientific information, theUnited States requested theestablishment ofatechnical
experts group ("TEG") under Article 14.5 oftheTBT Agreement toexamine thequestion. This request
wasdenied following theECresponse thattheuseofgrowth promotants wasaprocess andproduction
method (PPM), andthatparties totheTBT Agreement only hadanobligation nottousePPMs to
circumvent theAgreement. TheEuropean Communities favoured theestablishment ofapanel "to
12"Assessment ofHealth Risk -Working Group II",in1995 ECScientific Conference Proceedings,
pp.20-21.
13Ibid.WT/DS26/R/USA
Page 12
evaluate therights andobligations ofParties deriving from Article 14.25 (oftheTBT Agreement)".14
Thedispute went unresolved.
2.35 On1January1989,theUnitedStatesintroducedretaliatorymeasuresintheformof100percent
advalorem duties onalistofproducts imported from theEuropean Communities. TheEuropean
Communities consequently asked fortheestablishment ofapanel. This request wasdenied bythe
United States. In1989, ajoint US/EC Task Force agreed oncertain measures which allowed imports
intotheEuropean Communities ofUSmeat certified tohave notbeen produced with hormones. This
resulted intheUnited States withdrawing some products from theretaliation list.Theother ECproducts
figuring inthelistremained subject totheretaliatory action. On19June 1996, theEuropean
Communities requested theestablishment ofapanel toexamine thismatter. On15July 1996, after
thisPanel wascomposed, theUnited States terminated itsretaliatory action initsentirety.
III. CLAIMS OFTHE PARTIES
3.1 TheUnited States claimed thattheECbanontheimportation andsaleofanimals, andmeat
derived from animals, thathadbeen administered anyofthesixhormones atissue forgrowth promotion
purposes (oestradiol-17 ,progesterone, testosterone, trenbolone, zeranol andmelengestrol acetate
(MGA)) wasinconsistent with theSPS Agreement andtheGATT.
3.2 Arguing thattheECmeasures were sanitary measures, theUnited States claimed, with regard
totheSPS Agreement, thatthese measures: directly andindirectly affected international trade; were
notbasedonanassessmentofriskandwereconsequentlyinconsistentwithArticle5.1oftheAgreement;
were maintained without sufficient scientific evidence incontravention ofArticle 2.2; were notjustified
asa"provisional" measure under Article 5.7; breached Articles 2.2and5.6inthatthey were not
based onscientific principles; were notapplied only totheextent necessary toprotect human lifeor
health andwere more trade-restrictive than required toachieve theappropriate level ofsanitary
protection; arbitrarily orunjustifiably discriminated between Members where identical orsimilar
conditions prevailed, incontravention ofArticle 2.3;constituted adisguised restriction oninternational
trade, inbreach ofArticle 2.3; contravened Article 3.1because they were notbased ontherelevant
internationalstandards,guidelinesorrecommendationsandthatthisdeparturefrominternationalstandards
wasnotjustified byArticle 3.3; andwere based onarbitrary orunjustifiable distinctions inthelevels
ofprotection indifferent situations, resulting indiscrimination oradisguised restriction oninternational
trade incontravention ofArticle 5.
3.3 The United States claimed thattheECmeasures discriminated against imports andwere
inconsistent with Article IIIofGATT. Arguing thatUSmeat andanimals were "like" ECmeat and
animals, theUnited States claimed thattheECmeasures were inconsistent with Article III:4 ofGATT
because theyprohibited theimportation andsaleofcertain imported meat andanimals, while permitting
thesaleoflikedomestic products. TheECmeasures therefore treated USimports lessfavourably
than domestic production. TheUnited States further claimed thattheEuropean Communities hadno
legitimatepolicypurposefordiscriminatingagainstUSmeatandanimals.TheUnitedStatesalsoclaimed
thattheECmeasures were inconsistent withArticle I:1ofGATT because theyfailed toaccord toimports
from theUnited States theadvantages, favours, privileges orimmunities granted tolikeanimals and
meat originating intheterritories ofother countries. Finally, theUnited States argued thattheEC
measures could notbejustified byresort toArticle XXofGATT, inparticular Article XX(b), because
theEuropean Communities hadputforward noevidence tosupport itsmeasures onhealth grounds,
andthemeasures were "applied inamanner which would constitute ameans ofarbitrary orunjustifiable
discrimination between countries where thesame conditions prevail, oradisguised restriction on
international trade". TheUnited States claimed thatiftheECmeasures were notsanitary measures,
14GATT document TBT/M/Spec/7, p.9, para. 34.WT/DS26/R/USA
Page 13
they would beinconsistent with theTBT Agreement; inparticular they were technical regulations
within themeaning oftheTBT Agreement, andwould beinconsistent with Articles 2.1,2.2,and5.1.1
and5.1.2.
3.4 TheEuropean Communities submitted thattheanalysis oftheSPSand/or TBT Agreements
should takeplace only ifalleged violations ofGATT Articles were found. Therefore, intheir defense,
theEuropean Communities firstinvoked GATT. With regard tothealleged violation ofArticle III:4
ofGATT, theEuropean Communities argued thattheanimals towhich thehormones atissue hadbeen
administered forgrowth promotion, andmeat from those animals, were not"like" other animals and
meat from those animals, respectively. Furthermore, theEuropean Communities argued thateven
ifthey were found tobe"like", imported products were notgiven "less favourable treatment" than
domestic products. Therefore, theEuropean Communities claimed thatitsmeasures didnotinfringe
Article III:4 ofGATT. TheEuropean Communities claimed thatincase itsmeasures were found to
becontrary toArticle III:4, they were justified byArticle XX(b), which didnotaffect thepower of
aMember toadopt apolicy inorder toprotect human andanimal health.
3.5 With regard tothealleged violation ofArticle IofGATT, theEuropean Communities claimed
thatsuch violation wasnotmentioned inthePanel 'sterms ofreference, wasnotmentioned inthe
documents bywhich theUnited States requested consultations andwas notdiscussed during the
consultations thatwere held subsequently. TheEuropean Communities claimed thateven ifanimals
andmeat from animals towhich thehormones atissue hadbeen administered forgrowth promotion
were found tobe"like" (quod non), themeasures atissue applied without distinction toallimports
ofmeat irrespective oftheir country oforigin andnotonly toimports originating intheUnited States.
Accordingly, theEuropean Communities argued thatitsmeasures didnotviolate Article I:1ofGATT.
3.6 TheEuropean Communities claimed thatthemeasures atissue, inanyevent, didnotviolate
anyprovision oftheSPS Agreement because they satisfied alltheconditions imposed byit.The
measures were based onscientific principles asrequired byArticle 2.2oftheSPS Agreement, and
ariskassessment hadbeen performed which established thescientific basis forregulatory action. The
European Communities observed thattheSPS Agreement recognized aMember 'sright toestablish
thelevel ofprotection which theMember determined tobeappropriate. TheEuropean Communities
claimed thatthemeasures atissue aimed atachieving alevel ofprotection which washigher thancould
beachieved iftherecommendations ofCodex Alimentarius forthese hormones were followed. Italso
claimed thatWTO dispute settlement panels were notcompetent tojudge itslevel ofsanitary protection
northescientific evidence upon which itwasbased, butonly whether itsmeasures were inconformity
with theprovisions oftheSPSAgreement. Itfurther claimed thattheUSarguments infactattacked
theECchosen level ofprotection, notitsmeasures, because they suggested thatresidues ofthese
hormones, above naturally present levels, didnotpose anyrisktohealth and,therefore, didnotwarrant
theapplication ofanymeasures tocontrol them. TheEuropean Communities alsoclaimed thatits
measures were based ontheprecautionary principle. Moreover, itclaimed thattheUnited States had
failed todischarge itsburden ofproof because ithadfailed toshow thatthemeasures atissue were
nomore trade restrictive than required toachieve theECappropriate level ofsanitary protection.
TheEuropeanCommunitiesclaimedthatitsmeasureswereappliedinexactlythesamewaytoallanimals
treated with these hormones andmeat from such animals intended forconsumption intheECmarket,
whatever itsorigin; there wasconsequently nodiscrimination nordisguised restriction oninternational
trade. TheEuropean Communities didnotsubmit arguments onTBT because itconsidered thatthe
measures atissue fellwith theSPSAgreement. TheEuropean Communities claimed thatbecause the
measures atissue didnotviolate anyoftheprovisions oftheSPS Agreement, they should befound
alsotobeinconformity with therules ofGATT, inparticular Article XX:b, incase aviolation of
oneofitsprovisions were tobefound.WT/DS26/R/USA
Page 14
IV. ARGUMENTS OFTHE PARTIES
1. Relationship between GATT 1994 andtheSPS Agreement
4.1 TheEuropeanCommunitiesconsideredthattheSPSAgreementwouldapplyonlyifaviolation
oftheArticles ofGATT were tobeestablished. TheEuropean Communities argued thattheGeneral
Interpretative Note toAnnex 1AoftheWTO Agreement provided that:
"Intheevent ofconflict between aprovision oftheGeneral Agreement onTariffs and
Trade 1994 andaprovision ofanother agreement inAnnex 1AtotheAgreement
Establishing theWorld Trade Organisation ....,theprovision oftheother agreement
shall prevail totheextent oftheconflict" (emphasis added).
4.2 TheEuropean Communities argued thattheSPSAgreement codified, asthelastrecital ofits
preamble stated, thedesire oftheMembers "toelaborate rules fortheapplication oftheprovisions
ofGATT which relate totheuseofsanitary orphytosanitary measures, inparticular theprovisions
ofArticle XX(b)". Furthermore, itwaswell established GATT lawandpractice thatGATT 1947
didnotaffect thepower ofitsMembers tosetuparegulatory policy which they deemed necessary
inorder toprotect human, animal orplant health. Buttheconformity ofthemeasures itapplied for
thatpurpose could bereviewed under GATT.15Itwas, therefore, admitted thataviolation ofGATT
byameasure should beestablished first, before recourse topossible justifications (e.g. under
Article XX(b)) could beconsidered. Insuch anevent, thePanel could review themeasure butnot
theunderlying policy objective onwhich itwasalleged tobebased. TheEuropean Communities noted
thatthere were several new provisions intheSPS Agreement thatestablished aseries ofrights and
obligations forMembers. However, theSPS Agreement reaffirmed theright ofMembers toadopt
orenforce measures theMember deemed tobenecessary toprotect human, animal orplant health
(recitals 1and6ofpreamble). Itcould therefore beargued thatmost oftheobligations created by
theSPSAgreement were already applied under GATT 1947 through interpretations ofArticle XX(b)
bypanel reports andtheCONTRACTING PARTIES.
4.3 TheEuropean Communities claimed thatArticle 2.4oftheSPS Agreement established that
SPS measures which conformed totheAgreement were "presumed" tobeinaccordance with the
obligations oftheMembers "under theprovisions ofGATT which relate totheuseofsanitary or
phytosanitary measures, inparticular theprovisions ofArticle XX(b)" (emphasis added). Despite
thefactthatthewords "inparticular" appeared inArticle 2:4,itwashard toimagine other provisions
ofGATT "which relate totheuseofsanitary orphytosanitary measures".
4.4 TheEuropeanCommunitiesnotedthat,intheir"StatementofAdministrativeAction",theUSTR
hadexplained that:
"The S&P negotiations initially began asanattempt toelaborate ontheprovisions of
Article XX(b). TheAgreement extends beyond aninterpretation ofexisting GATT provisions,
however, andincludes new obligations -inparticular, transparency requirements such as
providing notice of,andanopportunity tocomment on,proposed S&P measures."16
Therefore, iftheSPSAgreement were tobedefined asaself-standing agreement thiswasnotbecause
itinterpreted provisions ofGATT other thatArticle XX(b), butonly because itlaiddown additional
procedural requirements. Thesubstantive roleoftheSPSAgreement, wastointerpret Article XX(b)
15See, e.g.thepanel report on"Thailand -Restrictions onImportation ofandInternal Taxes onCigarettes", adopted
on5October 1990, DS10/R.
16USStatement ofAdministrative Action, p.87.WT/DS26/R/USA
Page 15
ofGATT. Inother words, recourse tothesubstantive provisions oftheSPSAgreement could bemade
only under thesame conditions under which recourse could bemade toArticle XXofGATT, that
wasonly after aviolation ofanother provision ofGATT wasfirstestablished. Asfarastheadditional,
procedural obligations laiddown bytheSPS Agreement were concerned, these could beexamined
bythePanel directly andindependently ofanyneed toestablish firstaviolation oftheprovisions of
GATT.
4.5 TheUnited States claimed thattheECbanwassubject totheSPS Agreement because the
Agreement applied to"allsanitary andphytosanitary measures which may, directly orindirectly, affect
international trade"17andtheECmeasures were sanitary measures, asdefined bytheSPSAgreement,
which directly andindirectly affected international trade. TheSPSAgreement wasspecifically tailored
toSPSmeasures andwasthelexspecialis inthisinstance. Itmade sense tolook firsttotheagreement
most specifically designed toaddress thetypes ofmeasures andissues involved. TheSPSAgreement
applied toallSPSmeasures, andapplied whether ornotaMember wasinvoking aGATT exception
forsuch measures. Itimposed requirements additional tothose inArticle IIIandtotheconditions
forjustifying theapplication oftheexception inArticle XX(b). Forinstance, Article 3.2oftheSPS
Agreement provided that anSPS measure conforming tointernational standards, guidelines or
recommendations waspresumed tobeconsistent with the"relevant provisions" ofnotonly GATT,
butalso theSPS Agreement itself. The Agreement stood independently from GATT. Thus, a
complaining party didnotneed tofirstshow thatanSPSmeasure wasinconsistent with GATT before
itmight invoke theprovisions oftheSPS Agreement.
4.6 TheUnited States submitted thatthenegotiating record confirmed thattheSPS Agreement
wasintended togobeyond GATT andtoimpose requirements additional tothose inGATT. Inthe
earliest phases ofnegotiations onSPS issues, thediscussions hadfocused onfurther definition of
Article XX(b). UptotheDunkel Draft text(MTN.TNC/W/FA of20December 1991), theSPStext
wasphrased asaDecision oftheCONTRACTING PARTIES interpreting theGATT, simply because
participants hadwished theproposed disciplines toapply toallGATT contracting parties andonly
aDecision (asopposed toanoptional-membership Code) would accomplish thatresult.18However,
inApril 1992, when thepossibility emerged ofusing theMTO Agreement (later renamed theWTO
Agreement) totietheUruguay Round results together intoa"single undertaking", negotiators had
agreed tochange theform ofthetext toafree-standing Agreement inAnnex 1AoftheMTO
Agreement.19Incontrast, thevarious Understandings onGATT Articles began asdecisions interpreting
theGATT andwere finally incorporated into GATT. Had thenegotiators intended thattheSPS
Agreement benothing butaclarification oftheGATT, inwhole orinpart, theUnited States argued,
they would have given itsprovisions thesame form as,forinstance, theUnderstanding onthe
Interpretation ofArticle XVII oftheGATT. TheEuropean Communities 'suggestion thattheSPS
Agreement could bedivided between provisions thatapplied toallSPSmeasures (and applied under
17Article 1.1oftheSPSAgreement.
18"Given thedesire ofparticipants fortheapplication oftheproposed disciplines toallcontracting parties, thisdraft has
been presented intheform ofaDecision oftheCONTRACTING PARTIES ontheApplication ofSanitary andPhytosanitary
Measures. However, thisiswithout prejudice tothefinal form theagreement might take." MTN.GNG/NG5/WGSP/7,
20November 1990, p.1.
19P.21 ofdocument 707dated 15April 1992, "Review ofIndividual Texts intheDraft Final Act(Texts onAgriculture),
Informal Note bytheSecretariat" (Secretariat proposal torectify theform tochange itfrom adecision toanagreement),
andp.19 ofdocument 963dated 10June 1992, "Review ofIndividual Texts intheDraft Final Act, Informal Note bythe
Secretariat" (record ofrectifications agreed intheLegal Drafting Group inApril 1992, including thischange inform). The
paragraphing ofthetextwasrearranged intoarticle format during thelegal drafting process fortheMarrakesh Final Act
inFebruary 1994. Secretariat proposals forrectifications atp.71 ofMTN/FA/Corr.2 dated 18February 1994, andagreed
rectifications inMTN/FA/Corr.5 dated 11March 1994.WT/DS26/R/USA
Page 16
allcircumstances), andother provisions which only applied ifanSPS measure violated theGATT,
hadnobasis inthetextoftheSPS Agreement.
2. The SPS Agreement
4.7 TheUnitedStatesclaimedthataccordingtothedefinitionofsanitaryandphytosanitarymeasures
intheSPS Agreement, whether ameasure wasasanitary measure depended onitspurpose20.The
United States noted thatthepurported sanitary purpose oftheECmeasures wasstated inthetexts of
theECCouncil Directives themselves, andwasapparent from thehistory oftheECmeasures and
subsequent statements oftheEuropean Communities, including statements toContracting Parties of
theGATT 1947. Inreviewing theproposal forDirective 81/602/EEC, theEuropean Economic and
Social Committee hadrecognized that"there isanurgent need todraw upECprovisions inorder to
protect human health".21Similarly, thedebate oftheEuropean Parliament ontheproposal for
Directive 88/146/EEC underscored theclaim thattheECmeasures were designed toprotect human
health from risks associated with theuse ofthehormones atissue.22The preamble to
Directive 81/602/EEC stated inpart: "Whereas, duetotheresidues thatthey leave inmeat, certain
substances with athyrostatic, oestrogenic, androgenic orgestagenic action may bedangerous for
consumers" and"Whereas, moreover, theharmless orharmful effects oftheuseofOestradiol-17 ,
Progesterone, Testosterone, Trenbolone andZeranol stillhave tobeexamined indetail." This concern
forhuman health wascarried forward with Directive 88/146/EEC.23Inaddition, during thediscussion
intheTokyo Round Committee onTechnical Barriers toTrade concerning theECmeasures, theEC
representative hadstated thattheEuropean Communities "adopted theDirective asthebestway of
avoiding anyhealth risks connected with theuseofhormonal substances".24TheUnited States argued
thatalthough theEuropean Communities hadstated thatthepurpose ofitsmeasures wasasanitary
purpose, ostensibly toprotect human lifeorhealth within theEuropean Communities from risks arising
from additives, contaminants, ortoxins infood, themeasures were notlegitimate sanitary measures.
4.8 TheEuropean Communities agreed with theUnited States thatthemeasures challenged were
betterdefinedasmeasuresfallingwithinthescopeoftheSPSAgreementratherthantheTBTAgreement.
20Article2.1oftheSPSAgreement.TheUnitedStatesarguedthattheEuropeanCommunitieswasmistakeninitsperception
ofthecoverage oftheSPSAgreement. TheECclaim thatsanitary andphytosanitary measures were defined based inpart
onthetype ofproduct towhich themeasure applied wasincorrect. Nothing intheSPSAgreement limited itscoverage by
thetypeofproduct. TheSPSAgreement applied toanysanitary orphytosanitary measure. Forexample, measures restricting
theimportation ofconstruction equipment toensure thatitwasnotcarrying soilwith plant pests ordiseases, orthatitdid
notharbour plant pests, were phytosanitary measures, even though theyapplied toconstruction equipment. Thesame would
betrueformeasuresapplicabletolawnfurnituretoensurethatitdidnotharbourcocoonsofaplantpest,ormeasuresapplicable
totires tomake sure they didnothost mosquitoes carrying infectious diseases forhumans.
21Paragraph 1.2oftheopinion, ECOfficial Journal NoC138/29, 9June 1981. This opinion iscited inthepreamble
toDirective 81/602/EEC.
22Debate published intheAnnex totheECOfficial Journal No2-330 of10October 1985, beginning, p.232.
23Directive 88/146/EEC states that:
"Whereas theadministration tofarm animals ofcertain substances having ahormonal action isatpresent regulated
indifferent ways inthemember States; whereas while their immediate effect onanimals from thefarmer 'spoint
ofview isclear, assessments oftheir effect onhuman health vary andthisisreflected intheregulations governing
their use;whereas thisdivergence distorts theconditions ofcompetition inproducts thatarethesubject ofcommon
market organizations andisaserious barrier tointra-EC trade."
24Paragraph 12,TBT/M/Spec/7 (Committee onTechnical Barriers toTrade, Minutes ofMeeting held on23Julyand
28July1987). Seealsoparagraph 6ofTBT/M/Spec/7 ("The complaint oftheUnited States should notdeter hisauthorities
from applying themeasures thattheyhadadopted toprotect thehealth andsafety oftheir population."), aswellasparagraphs
9and24. Seealsoparagraphs 11through 13ofTBT/M/Spec/5.WT/DS26/R/USA
Page 17
TheEuropeanCommunitiesnotedthatanessentiallinkoftheSPSdisciplineswiththeregulatoryfreedom
oftheparties wasthatthemeasures applied were ofconcern totheSPS Agreement (and theWTO
system) only iftheyaffected international trade. Moreover, theSPSAgreement defined themeasures
towhich itapplied onthebasis oftheobjective ofthemeasure andthetype ofproduct towhich it
wasapplied.
4.9 TheUnited States claimed thattheECmeasures ontheir faceapplied toimports ofanimals
andmeat, prohibiting imports ofanimals towhich anyofthehormones atissue hadbeen administered
forgrowth promotion purposes, andimports ofmeat from such animals. They clearly affected
international trade and, when they were applied, they closed market access forsignificant quantities
ofimports from theUnited States25andother Members andcontinued toblock imports ofanimals
andmeat.
4.10 TheUnited States observed thatUSexports ofbeef andveal totheEuropean Communities
inthethree years prior totheban(1986-88) averaged inthehundreds ofmillions ofdollars, andtrade
totheEuropean Communities during the1985-87 period wasgrowing atabout 30percentperyear.26
In1989, when thebanwent intoeffect, USexports plummeted tonearly zero. Moreover, asaresult
ofvarious rounds ofmultilateral trade negotiations, theEuropean Communities hadbound itstariffs
onallproductsaffectedbythemeasuresatissue.IntheTokyoRoundofMultilateralTradeNegotiations,
concluded in1979 prior totheadoption oftheECmeasures atissue here, theUnited States negotiated
aquota for10,000 tonnes ofhigh-quality beef subject toatariff of20percent advalorem andfree
ofanyvariable levy. IntheUruguay Round, this10,000-tonne quota wasconverted toatariff-rate
quota andthevariable levyonbeefimported inexcess of10,000 tonnes was"tariffied". TheEuropean
Communities alsohadbound duties onoffal products (e.g., hearts, livers, andkidneys). Asaresult
oftheECbeef import ban, USexports ofthese products totheEuropean Communities hadbeen
substantially impaired.
4.11 TheUnited States argued thattheSPS Agreement wasdesigned toensure thatnoMember
maintained protectionist barriers totrade intheguise ofSPSmeasures andthatArticle 1.1required
thatsanitary measures "bedeveloped andapplied inaccordance withtheprovisions ofthisAgreement".
Therequirement thatmeasures be"developed" inaccordance with theSPSAgreement didnotapply
here since theECmeasures were developed prior totheentry intoforce oftheWTO. However, the
European Communities were stillrequired to"apply" these measures inaccordance with theprovisions
oftheSPS Agreement.
4.12 Moreover,inordertodifferentiatebetweenlegitimateSPSmeasuresandothertypesofmeasures,
theUnited States noted thattheSPSAgreement provided anumber ofdisciplines forsanitary measures.
These included anobligation thateach sanitary measure:
(i) bebased onanassessment, asappropriate tothecircumstances, oftherisks tohuman,
animal orplant lifeorhealth27;
(ii) notbemaintained without sufficient scientific evidence28;
25According toatable provided bytheUnited States, anaverage 70percentofallUScattle were treated with oneor
more ofthese hormones.
26TheUnited States estimated in1988 thattheECmeasures cutoffapproximately $100 million inUSexports.
27Article 5.1oftheSPSAgreement.
28Ibid.,Article 2.2.WT/DS26/R/USA
Page 18
(iii) bebased onscientific principles29;
(iv) notbemore trade-restrictive thanrequired toachieve theappropriate level ofsanitary
protection, taking intoaccount technical andeconomic feasibility30;
(v) notarbitrarily orunjustifiably discriminate between Members where identical orsimilar
conditions prevailed31;
(vi) notbeapplied inamanner thatwould constitute adisguised restriction oninternational
trade32;and
(vii) bebased oninternational standards, guidelines orrecommendations, where they
existed33.
TheUnited States claimed thattheECmeasures failed each ofthese requirements. TheECbanwas
notalegitimate sanitary measure because itseverely restricted international trade, wasnotapplied
only totheextent necessary toprotect human lifeorhealth, wasnotbased onscientific principles,
wasmaintained without sufficient scientific evidence, wasnotbased onanassessment oftherisks,
andwasmore trade-restrictive than required toachieve theappropriate level ofprotection. Italso
constituted adisguised restriction oninternational trade.
4.13 TheEuropean Communities responded that, asenvisaged intheEClegislation, imports might
takeplace from third countries provided thatguarantees were offered thatnoanimal andnomeat coming
from ananimal towhich hormonal substances hadbeen administered would beexported totheEuropean
Communities. TheEClegislation inquestion didnotimpose abanonUSmeat oronmeat from any
other origin. TheUSexported fresh meat notdestined forhuman consumption andexported tothe
European Communities hormone-free meat products forhuman consumption onthebasis ofmeasures
agreed bythejoint US/EC Task Force. TheUSexports ofmeat totheECmarket fortheyears 1989
to1994 were asfollows: 1988: 72,557 tonnes, 1989: 8,380 tonnes, 1990: 3,617 tonnes, 1991:
1,156 tonnes, 1992: 6,320 tonnes, 1993: 6,833 tonnes, 1994: 6,594 tonnes, 1995: 8,499 tonnes.34
4.14 TheEuropean Communities agreed thattheSPSAgreement imposed thedisciplines enumerated
bytheUnited States andconsidered thatitsmeasures satisfied allthose disciplines. When theEC
Commission hadfirstproposed totheECCouncil in1980 totakemeasures inthisareaaswell asin
1988, ithadfound itself facing certain factual, legal andscientific situations. From thefactual point
ofview, consumer concerns over theuseofhormones forgrowth promotion inlivestock were very
high. Despite thetraditionally cautious approach totheregulation ofdangerous substances followed
bytheECmember States, consumer confidence inscience andregulators (especially among well-
informed consumer organisations andgroups) wasvery low. This factual situation hadnotchanged
during theentire period thathadpreceded theadoption ofDirective 96/22/EC. Consumer concerns
were even higher today.
29Ibid.,Article 2.2.
30Ibid.,Article 5.6.
31Ibid.,Article 2.3.
32Ibid.,Article 2.3.
33Ibid.,Article 3.1.
34TheEuropean Communities explained thatthefigures were based onEurostat statistics.WT/DS26/R/USA
Page 19
4.15 TheEuropean Communities noted thatfrom thelegal point ofview, theuseofhormones in
animal growth promotion hadlong been prohibited inmost ECmember States; only some ECmember
States allowed theuseofsome ofthese substances under certain conditions.35With theprogressive
establishment ofthecommon market, thedivergence inthelegislation ofECmember States was
inhibiting freetrade within theEuropean Communities inanimals andmeat from animals treated with
some ofthese hormones, anddistorting theconditions ofcompetition among ECmeat producers.
4.16 Furthermore, theEuropean Communities observed thatfrom thescientific point ofview, the
situation wasvery unclear intheearly 1980s. Therelevant international organizations -FAO, WHO,
theOffice internationale desépizootics (OIE) andtheCodex Commission -hadstarted toseriously
examine thesafety ofthese hormones inmeat production only during the1980s. Thefirstsubstantive
andcomprehensive scientific report hadbeen published byOIE in1983. JECFA haddiscussed and
issued asubstantive andcomprehensive scientific report onthese hormones onlyin1988. Furthermore,
none ofthese scientific reports established beyond doubt thattheuseofthese hormones inanimal growth
wassafeforhuman health. Forexample, inthe1983 OIE Scientific Report itwasstated:
"Even though many unknown influences stillexist with regard tothedetails ofthemechanism
ofaction, particularly with reference tohowthemessage brought bythereceptor istranslated
intoaction inthecellnucleus, wearenevertheless beginning tohave some understanding of
how anabolics work" (page 62).
With regard tothethree so-called "natural" hormones, theEuropean Communities noted thatallof
theabove scientific reports suggested thatthey were "unlikely topose ahazard tohuman health" if
used"inaccordancewithgoodveterinaryoranimalhusbandrypractice".36Asregardstheotherso-called
"synthetic"hormones,reliabletoxicologicaldatawerestillmissinginthe1988JECFAReport(page26).
Their useforanimal growth promotion hadbeen provisionally recommended inaccordance with good
animal husbandry practice andresidue checking inorder toensure thattheso-called Acceptable Residue
Levels (ARLs) provisionally recommended were notexceeded. TheEuropean Communities argued
thateven today thestate ofscientific knowledge wasnotmuch different from what itwasin1981 and
1988 when thechallenged measures hadbeen adopted (asshown bythe1995 ECScientific Conference).
4.17 TheUnited States argued thatalthough thepurported major objective oftheECbanwasto
protecthumanhealth,therealpurposewastoprotectECmeatproductionfromthird-countrycompetition.
Noting thattheEuropean Communities cited asthepurposes ofthese measures (i)protection ofhuman
health and(ii)adesire toalter theterms ofcompetition foranimals andmeat inorder torender these
conditions"largelyidentical"withintheECmarket,theUnitedStatesclaimedthatneitherreasonoffered
avalid justification under theWTO agreements. Furthermore, indeveloping thehormone ban, the
European Communities were alsomotivated bythefactthatthebanwould helpreduce surplus supplies
ofmeat intheEuropean Communities andlower thecostoftheECCommon Agricultural Policy.
TheUnited States argued thatthisattempt toprotect domestic production from more competitive imports
wasprotectionism andwasinconsistent with ECWTO obligations.
4.18 TheUnited States noted inthisregard thatinApril 1984, theEuropean Communities had
introduced milk quotas toreduce theoversupply ofmilk, which resulted inanincrease incattle slaughter.
35TheEuropean Communities indicated that4or5ECmember States allowed theuseofsome ofthese hormones for
growth promotion until their prohibition atEClevel. The information onlevel ofuse, ifavailable atall,would only be
known tothose individual ECmember States. OneECmember State, theUnited Kingdom, hadindicated thatanecdotal
evidence suggested thatgrowth promoting hormones might have been used upto40percentoftheUnited Kingdom cattle
prior totheban.
361988 JECFA Report, pp.19 etseq.WT/DS26/R/USA
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ECintervention stocks ofbeef, which were slightly lessthan400,000 tonnes inNovember 1983, soared
toover 800,000 tonnes bytheendof1985.
4.19 TheEuropean Communities rejected theUSargument thattheECmeasures hadbeen adopted
inorder toprotect domestic production from foreign competition. Thereference tothedivergence
inthelegislation oftheECmember States which distorted theconditions ofcompetition andaffected
freecirculation ofproducts inintra-EC trade (1stand2ndparagraphs ofDirective 88/146/EEC), was
made forthesolepurpose ofjustifying theneed totakeaction attheEClevel. Because ofitsinternal
constitutional structure, theEuropean Communities wasobliged totakeaction inorder toeliminate
distortions intheconditions ofcompetition andtoincrease freeintra-EC trade.37Thepreamble of
theDirective thus clearly explained thattheunderlying objective wastorespond inanharmonized
waytotheeffect ofthese hormones onhuman health. This objective, however, wasnotinitself
independent ormore important than theobjective ofsafeguarding against risks tohuman andanimal
health resulting from thesubstances atissue.
4.20 TheEuropean Communities further argued thataction attheEClevel wasexplicitly permitted
byArticle XXIV:8(a) ofGATT. Itsubmitted thatwhen theEuropean Court ofJustice examined the
object andpurpose ofDirective 85/649/EEC (invalidated onprocedural grounds andsubsequently re-
enacted inDirective 88/146/EEC) ithadnoted that"theaimoftheDirective, according totherecitals
initspreamble, istoprotect human health andconsumer interests with aview toeliminating the
distortion ofconditions ofcompetition andbringing about anincrease inconsumption oftheproduct
inquestion".
4.21 Furthermore,theEuropeanCommunitiesassertedthatthehistoricalrecordclearlydemonstrated
thatthepurpose oftheECmeasures wastoprotect human andanimal health from risks arising from
theuseofthehormones atissue. TheEuropean Communities noted thattheEuropean Parliament
hadproposed abanonimports ofmeat from animals treated withgrowth promoting hormones primarily
because "scientific information about these substances isfarfrom complete andthatconsiderable doubt
therefore exists about thedesirability oftheir useandoftheir effect onhuman health".38Serious health
concerns hadbeen clearly stated indifferent MEP reports, including the"Nielsen Report", the"Pimenta
Report" andthe"Collins Report", andtheEuropean Parliament hadremained constantly opposed to
theauthorization ofallthese hormones foranimal growth promoting purposes forreasons ofpossible
hazards tohuman andanimal health. TheEconomic andSocial Committee hadalsorejected theuse
ofthese hormones forgrowth promotion purposes onhealth grounds. TheEuropean Communities
claimed that, from theabove sequence ofevents which hadeventually ledtotheadoption of
Directive 88/146/EC, itwasclear thattheEuropean Communities hadexamined carefully thepotential
risks tohuman andanimal health from theuseofthese hormones foranimal growth promotion purposes;
considered thatscientific evidence, whilst suggesting thatthese substances, ifused inaccordance with
good veterinary practice, didnotseem topose risks tohuman andanimal health, didnotexclude beyond
doubt thattheyposed nopotential risks tohuman health; examined carefully alloftheavailable options
forharmonizing theconditions ofuseofthese substances before concluding that, atpresent, theban
ontheir usewastheonly scientifically, technically andeconomically feasible option.
4.22 TheEuropean Communities rejected theUSreferences tomilk quotas andobserved thatthe
increaseintheECinterventionstocksofbeefwasunrelatedtotheobjectiveandpurposeofthechallenged
measure. Such high intervention stocks ofbeefdidnotexist intheECmember States thatintroduced
theprohibition ontheuseofthese hormones asearly as1961; such high intervention stocks ofbeef
didnotexist in1981 when thisprohibition wasforthefirsttime imposed atEClevel; andsuch high
37TheEuropean Communities noted thatthisobligation resulted from Articles 100and100A, inconjunction, inthiscase,
with Articles 30and36oftheECTreaty.
38Point EofParliament 'sResolution, ECOfficial Journal No288, 11November 1985, p.158.WT/DS26/R/USA
Page 21
intervention stocks ofbeef didnotexist inApril 1996 when theEuropean Communities adopted
Directive 96/22/EC which re-enforced theprohibition ontheuseofthese hormones. TheEuropean
Communities further submitted thatthefactthattheDirective offered equal access totheECmarket
forthird-country meat wasadditional proof thatthere wasnoprotectionist purpose intheECmeasures.
Statistics showed thattheEuropean Communities hadcontinued toimport about thesame quantities
ofmeat asbefore theapplication oftheban, itwas, however, meat from animals towhich hormones
forgrowth promotion purposes hadnotbeen administered.
(a) Article 2.2oftheSPS Agreement
4.23 TheUnitedStatesrecalledthatArticle2.2requiredMemberstoensurethatanysanitarymeasure
wasapplied onlytotheextent necessary toprotect human oranimal health, based onscientific principles
andnotmaintained without sufficient scientific evidence. TheUnited States argued thattheEuropean
Communitieshadfailedtofollowscientificprinciples,andlackedanyscientificevidencetogivecredence
toitsasserted health concerns. TheEuropean Communities presented noevidence tocontradict the
long established scientific determination thatthesixhormones were safeforuseasgrowth-promotion
substancesandthatconsumptionofmeatcontainingtheminutequantitiesofresiduesfromtreatedanimals
wasnotharmful toconsumers.
4.24 The United States claimed thatwhile thenegotiators hadnotdefined precisely "scientific
principles",ataminimumthistermincorporatedthescientificmethod,whichrepresentedthoseprinciples
andprocesses universally regarded asnecessary forscientific investigation, inparticular procedures
for:
(i) theobservation ofphenomena innature orunder controlled conditions;
(ii) thesystematic classification ofempirical data;
(iii) themeasurement ofempirical quantities andforcalculating probable errors and
significant deviations;
(iv) forming ahypothesis;
(v) analysing experimental results using logic andmathematics; and
(vi) many other related techniques andprocesses.
4.25 TheEuropean Communities responded thattheUSexplanation oftheconcept of"scientific
principles" wasacaricature of"the scientific method" which could have been taken straight from a
school textbook circa 1960. There wasabsolutely noreason tosuppose thattheMembers oftheSPS
AgreementhadthelistpresentedbytheUnitedStatesinmindwhensigningit.Thereweremanytheories
ofscience andthe"scientific method"; theEuropean Communities relied onbiological principles when
assessing therisks ofusing hormones forgrowth promotion. Measures must bebased onscientific
principles, asopposed tonon-scientific ones, such assuperstition. Ifameasure wasaimed atreducing
oreliminating arisktohealth, then itmust actually address thatriskinamanner which could be
scientifically justified. If,forexample, themeasure wasaimed ateliminating apathogenic organism
fromafood,therewereseveralmethods,e.g.heating,salting,pickling,etc.whichcouldbescientifically
proven tobeeffective. If,however, aMember required prayers tobesaidover thefood, oraritual
dance tobeperformed around it,thatwould notbecompatible with theSPSAgreement because such
methods could notbescientifically proven tobeeffective.
4.26 TheEuropean Communities further argued thatduring themeetings ofthePanel with scientists
on17and18February 1997, anumber ofexperts advising theEuropean Communities explained theirWT/DS26/R/USA
Page 22
views onthepotential dangers tohuman andanimal health from theuseofthese hormones forgrowth
promotion. None oftheexperts advising thePanel argued thattheexperts referred tobytheEuropean
Communities didnotemploy scientific principles intheir research. TheUSStatement ofAdministrative
Action stated thatArticle 2.2oftheSPS Agreement didnotrequire thebestscience northeweight
ofscientific evidence tobetaken intoaccount; itonly stipulated thatthere should be"scientific
principles" and"sufficient" (not absolute) scientific evidence. TheEuropean Communities further
argued thatforexample, Dr.Lucier hadagreed with theconclusions oftheECscientists thatboth
thenaturalandsynthetichormoneswerecarcinogenicatlowlevels(thenaturalhormonesarecarcinogenic
even atexisting physiological levels). Some ofthescientists who attended themeetings ofthePanel
(and those ofJECFA 1988) might notagree with theconclusions ofthescientists advising the
European Communities orwith Dr.Lucier, butthiswasnotrelevant forthepurposes ofArticles 5.2,
2.2and3.3oftheSPSAgreement. What wasimportant waswhether, inthescientific research employed
bytheECscientists (orthescientific reports towhich theymade reference intheir reports), theminimal
attributes ofscientific inquiry were respected. TheEuropean Communities hadnotheard theopposite
from anyofthescientists advising thePanel norfrom theUnited States andCanada. Therefore, the
European Communities wasallowed totake intoaccount their scientific views (ortheviews ofthe
scientists towhich they referred intheir reports) initsassessment oftherisks ofthese hormones for
growth promotion.
4.27 TheEuropeanCommunitiesindicatedthatalogicalconsequenceoftherequirementformeasures
tobebased onscientific principles wasthatthey must notbemaintained without scientific evidence .
AllMembers hadmeasures inplace before theSPSAgreement wasdrawn up,andintheabsence of
thisrequirement itcould have been argued thattherequirement forbasing measures onscientific
principles could notbeapplied retrospectively. TheSPS Agreement understandably didnotdefine
theterm "scientific evidence". Itwaseasier toargue thatthere were scientific principles, scientific
methods, scientific experiments andscientific data. Butitwasdifficult todefine what was"scientific
evidence", since itscontent wasrelative interms oftime andwasdependent ontheprinciples, methods,
experiments anddatamentioned. Forexample, what might beanacceptable scientific method forone
scientist might notsatisfy another, who might bemore interested incertain other scientific principles
oraspects totally neglected oronly partially examined bythefirstscientist. Forthatreason theSPS
Agreement only required "sufficient", notclear orcertain, scientific evidence (Article 2.2).39The
SPS also required Members, intheir risk assessment, totaken into account "availabl escientific
evidence". Butfrom the"available" scientific evidence, aMember wasentitled torelyonthatwhich
itsownscientists saidwasappropriate andsufficient, anddisregard other available evidence. Itfollowed
thatneither thePanel noranyother member might judge theadequacy ofthescientific evidence upon
which aMember based itsmeasure inorder toachieve itslevel ofsanitary andphytosanitary protection.
Forthesame reasons, aCodex group ofscientific experts could notjudge theadequacy ofthescientific
evidence used byaMember oftheSPS Agreement.40Inother words, ifthe"weight" ofavailable
scientific evidence indicated thatasubstance wasnotdangerous tohuman health, butanother small
orminority partofavailable scientific evidence (ofthesame Member) argued thatthere maybepotential
risks tohuman health, thatMember wasentitled under theSPS Agreement totake aprecautionary
approach andbaseitsmeasure onthelatter partoftheavailable scientific evidence. AstheUnited States
hassaidintheStatement ofAdministrative Action, itissufficient ifthe"government maintaining the
measures hasascientific basis forit"(emphasis added).
4.28 Thescientific basis oftheECDirectives 81/602 and88/146 were thefollowing:
39Ontheother hand, theEuropean Communities noted thattheterm "scientific evidence" hadadifferent meaning from
therequirement toprovide "evidence" inalegal trial.
40See,forexample, thearticle byD.A. Wirth (1994), "The roleofScience intheUruguay Round andtheNAFTA Trade
Disciplines", 27Cornell International Law Journal, 817-859, at856-57.WT/DS26/R/USA
Page 23
(i) the1982ReportoftheScientificVeterinaryCommittee,ScientificCommitteeforAnimal
Nutrition andtheScientific Committee forFood onthebasis oftheReport ofthe
Scientific Group onAnabolic Agents inAnimal Production (theLamming Report);
(ii) the1983 OIE Scientific Conference Report;
(iii) the1988 JECFA Report;
(iv) thevarious works ofrelevant international institutions, such astheInternational Agency
forResearch onCancer (IARC);
(v) thescientific works byindividual scientists relevant totheissue ofuseofhormones
ingeneral andforanimal growth inparticular; and
(vi) information ontheuseofthese hormones forgrowth promotion available from other
countries, when relevant.
4.29 Fortheadoption ofDirectives 81/602/EEC, 88/146/EEC and92/22/EC, apart from theabove
scientific evidence, additional technical information hadbeen taken intoaccount. This information
consisted mainly oftheinternal studies oftheECCommission, thereports oftheEuropean Parliament,
thereports oftheEconomic andSocial Committee andthedeliberations oftheCouncil ofMinisters.
Fortheir deliberations, theMinisters were assisted byscientific groups andindividual scientific experts,
including experts from therelevant administrations oftheECmember States. Fortheadoption of
Directive 96/22 of29April 1996, the1995 ECScientific Conference Proceedings hadalsobeen taken
intoaccount.
4.30 TheEuropean Communities noted thatinitsfirstproposal totheCouncil onthese substances,
theECCommissionhadexplainedthatcontrolswereneeded"...inviewoftheeffectsofthesesubstances
inrelation tocarcinogenicity, physiological effects andmeat quality. Thelatter aspect isalsoimportant
asregards useofnatural substances since physiological effects may also occur when exposure to
exceptional levels incidentally takes place".41Initssecond submission totheCouncil ofMinisters
theECCommission hadexplained the(zero) tolerance levels which were being proposed andtheneed
totakeintoaccount thenatural levels oftheendogenous hormones which might occur inanimals.42
Initsthird expanded submission totheCouncil ofMinisters, theECCommission hadexplained the
proposed therapeutic andzootechnical uses ofthenatural hormones, including thesystem ofcontrol
ofuseandmarketing.43
4.31 TheEuropean Communities indicated that, with respect toDirective 88/146/EEC in1982,
theCommission hadcreated anad-hoc Scientific Committee ofExperts onAnabolic Agents inAnimal
Production (chaired byProfessor Lamming). This Committee had issued aninterim report on
22September 1982 (the"Lamming Report"). TheECScientific Veterinary Committee gave itsreaction
on9November 1982. This wasfollowed bytheECScientific Committee onAnimal Nutrition on
17November 1982, andbytheECScientific Committee forFood on4February 1983. Inessence,
these Committees supported controlled useofnatural hormones, butwere opposed totheuseof
trenbolone andzeranol. On12June 1984, theECCommission published itsproposal (COM(84)295)
which envisaged thecontrolled useofthethree natural hormones forgrowth promotion andproposed
re-visiting theprohibitions onthetwosynthetic hormones after completion oftheir scientific evaluation.
41COM(80)614 of31October 1980.
42COM(80)920 of6January 1981.
43COM(80)922 of6January 1981.WT/DS26/R/USA
Page 24
4.32 TheEuropean Commission 'sproposal wasrejected bytheEuropean Parliament based onthe
report oftheCommittee ontheEnvironment, Public Health andConsumer Protection andontheopinion
oftheCommitteeonAgriculture,FisheriesandFood.44TheEuropeanParliament,whichdidnotapprove
theproposed authorization ofthethree natural hormones except fortherapeutic purposes, hadexplained
that:
"...Considering thatscientific information about these substances isfarfrom complete and
thatconsiderable doubt therefore exists about thedesirability oftheir useandoftheir effect
onhuman health ...
"...whereas, inparticular, there seems tobedoubt astotheeffects ontheimmunity against
various diseases ofanimals treated with hormone cocktails andthatthisinturn may leadto
anincreased useofantibiotics ...
"...Recognizesthatthereisconsiderabledifficultyinvolvedincheckingwhethersuchsubstances
have been used because, where they have been properly administered, themeasurable residue
concentrations arewell within normal physiological limits relatively soon after application;
"Believes, therefore, thatthepermitted useofhormones fortherapeutic purposes must bestrictly
controlled anddocumented. ...
"Rejects theauthorization ofartificial andnatural hormones asgrowth promoters".
4.33 TheEuropeanCommunitiesconcludedthat,therefore,theEuropeanParliamentandthescientific
experts advising their members hadcarefully reviewed thescientific evidence presented toitbythe
European Commission andbyitsownexpert committees, andhaddecided toreject theCommission 's
proposal.TheEconomicandSocialCommitteehadalsoreviewedtheEuropeanCommission'sproposal,
taking into account avery wide range oftechnical andscientific expertise, andinitsopinion
(29November 1984) stressed that:
"...even thelifting ofthebans onthethree endogenous anabolics (oestradiol-17 ,testosterone
andprogesterone) inrespect offoodstuffs ofanimal origin cannot beregarded asunobjectionable
from thepoint ofview ofthesafety, health andwell-being ofthepopulation, until they have
been proved harmless onthebasis ofsound experience covering, inter alia,conditions ofuse..."
4.34 TheEuropean Commission 'sproposal wasalsorejected bytheCouncil ofMinisters. Asa
result, theCommission amended itsproposal andon31December 1985 theCouncil adopted
Directive 85/649/EEC. This Directive confirmed abanontheuseofallthesubstances concerned for
growth promotion purposes andestablished more detailed provisions concerning authorized therapeutic
use. This Directive waschallenged intheEuropean Court ofJustice, which annulled itonpurely
procedural grounds. Re-introduced, theproposal wasre-adopted bytheCouncil on16March 1988
(Council Directive 88/146/EEC), prohibiting theuseinlivestock farming ofsubstances having a
hormonal action.
4.35 TheEuropean Communities noted thatin1987, Professor Lamming hadpublished anaccount
offurther work undertaken bymembers ofhisgroup onzeranol andtrenbolone which concluded that
these substances would probably besafewhen used inaccordance with"accepted husbandry practice".45
TheEuropean Communities argued thatthereport hadnotdefined thisconcept, andthatitsconclusion
wasbased ontheunsupported assumption thattheir carcinogenicity wasrelated totheir hormonal effects.
44European Parliament Doc. A2-100/85 of11October 1985.
45TheVeterinary Record, 24October 1987, p.389.WT/DS26/R/USA
Page 25
4.36 TheEuropean Communities indicated thatsubsequently, in1988, following discoveries of
significant useofillegal growth-promoting hormonal substances incertain ECmember States, the
European Parliament hadestablished a"Committee ofEnquiry intotheProblem ofQuality intheMeat
Sector".ThisCommitteehadreceivedsubmissionsfromawiderangeofscientificexperts,organisations
andinstitutions, including meat trade andfarmers 'organisations, third country producers, the
pharmaceutical industry andconsumers 'organizations. Theoutcome ofthework oftheCommittee
ofEnquiry intotheProblem ofQuality intheMeat Sector (the"Pimenta Report"), wasadopted by
theEuropean Parliament on29March 1989. Thereport observed thatthere wasnodiscernable health
riskintheuseofthethree endogenous hormones atissue where these were, inparticular, administered
tocastrated steers andwhere they were administered intheform ofslow-release implants inapart
oftheanimal which wasnotconsumed (e.g. theear)andwhere aspecific withdrawal period was
observed before slaughter. Ofthetwoother hormonal substances, zeranol wasregarded asbeing as
safeasthethree endogenous hormones referred to,while with regard totrenbolone acetate, asmall
residualdoubtregardingpotentiallong-termcarcinogenicitypersisted.ThePimentaReportalsoindicated
thattheCommittee hadbeen impressed with thethoroughness andobjectivity with which thescientists
concerned hadproduced andpresented their findings. Nonetheless, theCommittee endorsed theban
ontheuseofhormones, noting examples where scientific knowledge onthesafety ofsubstances had
subsequently been reversed andthat"[t]he scientific evidence does notaddress thequestion ofpotential
interaction ofthese substances with other substances orthemultiplier effect ofthese substances ina
worst-case scenario (e.g. theadministering ofhormones toananimal with analready high level of
endogenous hormones andtheingestion ofthemeat (ormilk) ofthatanimal byafemale taking the
oestrogen-based contraceptive pill" (page 6).
4.37 The European Communities noted thatthePimenta Report hadconcluded thatsuccessful
regulations could notbebased solely onscientific information, partly because ofthe"current state
ofknowledge" argument, andpartly because theregulatory process hadtoresolve social andpolitical
conflicts thatextended beyond scientific considerations. Although thedecision-making process in
controversial socio-economic andenvironmental issues hadtotakeintoaccount thescientific evidence,
itwasessential thatthefinal decision restwith society itself through itselected representatives. The
report noted thatwhat might appear tobeapublic rejection ofscience wasmore plausibly related to
aquestion ofconfidence intheadequacy ofregulatory control. TheCommittee wasunconvinced that
thelegalization ofthefivenatural/nature-identical hormones forgrowth-promotion would prevent the
useofharmful black-market alternatives. Itobserved thatproducers were stillusing easily-detectable
synthetic substances because ofthecontinued attractiveness ofthese products andtheeconomic gain
tobeobtained from their use. These were alsoincentives nottofollow theconditions foradministration
specified bytheLamming Committee.
4.38 Inthisrespect, thePimenta Report noted that"upstream" controls were essential, beginning
withtesting blood andurine samples ofliveanimals onthefarm. Theprocesses ofmetabolism, dilution
andexcretion intheliving animal meant thatthelonger theinterval between administration ofthe
substance andtesting oftheliveanimal orcarcass, themore difficult itwastodetect themetabolites
characteristic oftheuseofillicit substances. Inaddition, once thecarcass wasslaughtered andbutchered,
detection ofmetabolites andtracing back totheanimal became very difficult. However, testing for
synthetic substances posed nosignificant problems, although thedegree ofcapability andsophistication
ofdetection varied enormously between ECmember States. Inaddition, methods ofchemical masking
andother sophisticated techniques were being increasingly used. While testing forthethree natural
hormones posed aproblem inthattherange oflevels ofthese hormones produced naturally inthebody
oftheanimal wassolarge andvariable, ranges oflevels could bedrawn up,taking intoaccount the
sex,age, oestral cycle andcondition oftheanimal. Iftests showed thatananimal, fornoapparent
reason, wasatorabove theupper limit, then testing onother animals intheherd could provide valid
evidence since thestatistical possibility ofanentire herd possessing above-average hormone levels
wasminute.WT/DS26/R/USA
Page 26
4.39 TheCommittee reported thattenoutoftwelve veterinary authorities from theECmember
States agreed thatatotal banonadministered hormones would beeasier topolice than apartial ban,
because veterinarians could generally tellbyvisual signs when ananimal hadbeen treated withhormones
(theshape oftheanimal andthesexual organs were altered) butnotwhether thishadbeen atreatment
with legal versus illegal substances. Furthermore, psychologically, atotal banwasmore effective than
apartial oneinthatregulators, producers andconsumers were leftinnodoubt thattheadministration
ofanyhormonal substance forgrowth promotion purposes wasnotallowed. Thecontrol ofthewhole
meat production chain inEurope would have tobeequally rigorous whether allhormonal substances
oronly some hormonal substances were banned forgrowth promotion purposes. Inspection would
need tobejustascomprehensive andrigorous. ThePimenta Report concluded thatsevere sanctions
would have tobeimposed onthose flouting thebantoovercome thestrong economic incentives to
usegrowth promotion substances, andthatthisproblem hadtobetackled inorder forabantobe
effective andforconfidence toberestored inthemeat sector (page 13).
4.40 TheEuropean Communities added thattheEuropean Parliament hadadopted another important
report ontheissue ofuseofhormones foranimal growth promotion, the"Collins Report" of
7February 1989.46This report proposed thattheECveterinary medicine licensing system beadapted
toinclude a"fourth hurdle", entailing anobjective socio-economic andenvironmental impact assessment
inaddition tosafety, quality andefficacy criteria. Itargued that thesocial, agricultural and
environmentalimplicationsoftheuseofgrowthandyieldpromotingpharmaceuticalsrequiredalicensing
system different from thatwhich existed forthese products when used fortherapeutic purposes.
4.41 TheEuropean Communities indicated thattheEuropean Commission, inclose cooperation
with ECmember States, hadcontinued toreview theapplication ofDirective 88/162 intheappropriate
scientific andmanagement committees. After theentry intoforce oftheSPSAgreement, theEuropean
Communities haddecided toreview once again thesituation from thescientific point ofview. For
thatreason, ithadorganized the1995 ECScientific Conference inBrussels. Inlight ofthefindings
ofthatconference andother evidence, theEuropean Commission hadproposed totheCouncil of
Ministers tomaintain theprohibition ontheuseofthese hormones forgrowth promotion, tofurther
restrict their usefortherapeutic orzootechnical purposes, toreinforce theprovisions oncontrol and
testing,andtoincreasesubstantiallythepenaltiesandsanctionsincaseofviolations.47BoththeEuropean
Parliament48andtheEconomic andSocial Committee49approved theCommission 'sproposal. The
Council ofMinisters adopted thenewDirective 96/22 of29April 1996, which willreplace Directive
88/146/EEC andtheother relevant Directives asfrom 1July 1997.
4.42 TheUnited States argued thattheEuropean Communities hadfailed tocomply withArticle 2.2
which prohibited aMember from maintaining sanitary andphytosanitary measures "without sufficient
scientific evidence". The proposal foraCouncil Directive submitted bytheECCommission on
13June 1984 explicitly admitted that"onscientific grounds, itappears thattheuseofoestradiol-17ß,
testosterone andprogesterone, andthose derivatives which readily yield theparent compound on
hydrolysis after absorption from thesiteofapplication, would notpresent anyharmful effects tothe
health oftheconsumer norharm theconsumer byaltering thecharacteristics ofmeat when used under
46European Parliament, Committee ontheEnvironment, Public Health andConsumer Protection, Report on"The USA's
Refusal tocomply with ECLegislation onSlaughterhouses andHormones andtheConsequences ofthisRefusal", EP128
381/B, 7February 1989, named after itsreporter Mr.Collins, MEP. Seepara. 2.32.
47ECOfficial Journal C302, 9November 1993, p.8andC222, 10.8.1994, p.16.
48ECOfficial Journal C128, 9May 1994, p.105.
49ECOfficial Journal C52,19February 1994, p.30.WT/DS26/R/USA
Page 27
theappropriate conditions asgrowth promoters infarm animals".50TheUnited States added thatthere
wasabsolutely nonew scientific evidence considered bytheCommission prior tothechange inthe
proposed Directive tobantheuseofthese hormones. Indeed, inresponse tothe1995 ECScientific
Conference Proceedings, ECAgriculture andRural Affairs Commissioner Fischler hadconfirmed that
these hormones didnotpose adanger tohealth when used inbeef production. However, rather than
deciding tomodify thebantoreflect thescientific evidence, Mr.Fischler hadindicated thatthiswas
apolitical matter andhadnoted thata10million ECU advertising campaign extolling thevirtues of
eating hormone-free meat hadbeen launched andthattheECCouncil would bepressed tointroduce
tougher monitoring measures. TheUnited States concluded that, intheabsence ofanyidentifiable
riskfrom these hormones andwithout anysupporting scientific evidence fortheban, theECmeasures
were not"applied only totheextent necessary toprotect human, animal orplant lifeorhealth" and
were not"based onscientific principles", contrary toArticle 2.2. Indeed, theECapproach wascontrary
toscientific principles.
4.43 TheEuropean Communities responded thatMembers were notobliged todemonstrate a
scientifically confirmed adverse effect from aparticular hazard before theymight takemeasures. The
SPSAgreement could nothave been intended tooperate insuch awaythatMembers must wait until
people were actually sickordying before being allowed totakemeasures. Forexample, ithadbeen
recently reported thatscientists only nowhaddiscovered theexact mechanism bywhich smoking could
cause cancer. Butgovernments allover theworld hadbeen taking measures toprevent orreduce
smoking, even intheabsence ofsuch clear scientific evidence.51TheEuropean Communities added
thattheclosest theSPSAgreement came todefining sufficient "scientific evidence" wasinthefootnote
toArticle 3.3. Itfollowed from thatdefinition inthatscientific justification required anexamination
andevaluation ofavailable scientific information, based onscientific principles. Butattheenditwas
stilltheprerogative oftheMember inquestion todecide whether theinternational standard, guideline
orrecommendation wassufficient toachieve itsappropriate level ofsanitary protection. Thelevel
ofprotection wasdecided bytheMember alone anditwasnotajudgment thatmust bebased onscientific
principles orscientific evidence. Moreover, itwasincorrect tostate, astheUnited States did,that
thechoice ofameasure wasapurely scientific judgement. Measures must bebased onscientific
principles andnotmaintained without scientific evidence (conditions which theECmeasures clearly
meet) butthese conditions could bemetbyanumber ofmeasures which could allachieve thesame
level ofprotection. IfaMember wasfaced with choosing between several equally effective and
scientifically justified measures, theSPS Agreement laiddown other criteria, i.e.degree oftrade-
restrictiveness and technical and economic feasibility. This was thechoice faced bythe
European Communities inthepresent case; either abanonuseforgrowth promotion ortheimposition
ofstrictveterinarycontrols.Anassessmentoftrade-restrictivenessandtechnicalandeconomicfeasibility
clearly showed thatabanontheuseofhormones forgrowth promotion wastheonly measure available
toachieve itschosen level ofprotection.
4.44 TheEuropean Communities indicated thatMr.Fischler hadbeen much more cautious onthe
possible risks tohuman andanimal health arising from thenature andimproper useofthese hormones
foranimal growth promotion than suggested bytheUnited States.
4.45 TheEuropean Communities claimed thatthequestion waswhether thescientific evidence on
which thecontested measures were based was"sufficient" inthesense ofArticle 2.2. TheEuropean
Communities observed thattheterm "sufficient" wasnowhere defined intheSPSAgreement andnoted
thatitwasgenerally agreed that"sufficient" could notmean other thanthe"minimal" level ofscientific
50COM(84)295 final, clause 13ofthepreamble, 29June 1984, Official Journal C170, p.4seq.
51TheEuropean Communities noted that, forexample, theGATT panel onThailand -Restrictions onImportation of
andInternal Taxes onCigarettes (1991) hadaccepted that"smoking constitutes aserious risktohuman health" and,therefore,
fellwithin thescope ofArticle XX:B ofGATT 47.WT/DS26/R/USA
Page 28
evidence required.52None ofthepublicly available scientific reports established beyond doubt that
theuseofthese hormones inanimal production wassafeforhuman health. TheEuropean Communities
alsoclaimedthatasregardedthethreeso-called"natural"hormones,allofthescientificreportssuggested
thatthey were unlikely topose ahazard tohuman health ifused inaccordance with good veterinary
oranimal husbandry practice. Thescientific evidence forthenecessity tomaintain itsmeasure was
theevidence from the1995 ECScientific Conference thatthere wasstillalack ofinformation on,
forexample, themode ofaction, theeffect ofadministering combinations andtheeffect ofingesting
residues over alongperiod. Forexample, theUnited States, intheStatement ofAdministrative Action,
hadchosen theso-called Delaney Clause toexplain thedifferences between thebasic concepts ofthe
level ofprotection thatagovernment chooses andthemeasure thatthegovernment used toachieve
thatlevel ofprotection:
"[T]he Delaney Clauses, inthefirstinstance, establish alevel ofprotection. They reflect a
decision bytheCongress thatthere should benoriskofcancer tohumans from thesubstances
those clauses cover .... Adetermination thataparticular food additive poses ahealth risk
ismade onscientific grounds... Importantly, "risk assessment" asused intheSPSAgreement
isnotlimited toquantitative riskassessment, which isaparticular typeofriskassessment used
toevaluate thepotential forcarcinogenesis. TheDelaney Clauses areentirely consistent with
theAgreement 'srequirements inthisregard. Thedetermination thataparticular substance
poses ariskofcancer isascientific determination, based onanevaluation ofthepotential for
asubstance toinduce cancer. Based onscientific principles, theUnited States hasdetermined
thatifasubstance induces cancer inanimals, itposes some riskofhuman carcinogenesis .
AndsincethelevelofprotectionunderDelaneyrequiresthattherebezeroriskofcarcinogenesis,
theUnited States prohibit thesubstance" (pages 94-95).
4.46 TheUnitedStatesreplied thatconclusions ofanyscientific review could notbeabsolute because
science wasnotabsolute. Experimental results might either disprove orlend support toaparticular
hypothesis, butnever prove it,andcertainly would never prove it"beyond doubt". YettheEuropean
Communities appeared toclaim foritself theright tomaintain their banbecause scientific reports had
not"established beyond doubt" thattheuseofthese hormones forgrowth promotion wassafe. Science
could beused todetermine whether there wasariskassociated with theuseofaparticular substance;
itcould noteliminate thepossibility thatapotential riskmight befound inthefuture. The SPS
Agreement required aMember tobase itsmeasures onariskassessment andprohibited aMember
from maintaining SPSmeasures without sufficient scientific evidence. TheAgreement didnotprovide
thatmeasures might bemaintained without scientific evidence ofariskuntil such time asscience proved
"beyond doubt" thatthere wasnorisk. Moreover theUnited States noted thatthelackofknowledge
could notitself bethebasis fortaking asanitary measure. TheSPSAgreement required theEuropean
Communities todemonstrate scientific evidence ofaparticular risk. Scientists didnotclaim toknow
everything about everything. Scientific knowledge wasalways progressing andevolving. Accordingly,
toclaim thataMember wasjustified inbanning anactivity wherever there were stillareas forscience
toexplore would betorender theSPSAgreement meaningless -there were always areas forscience
toexplore. Furthermore, intheUSview, scientists knew more about thenature andmode ofaction
ofhormones than they didabout most, ifnotall,other classes ofcompounds.
4.47 TheEuropean Communities claimed thatthere were three possible methods bywhich itcould
achieve itschosen level ofprotection: bytheimposition ofcontrols onhormone usetoprevent misuse,
byabanonhormone use,andbyacombination ofcontrols andaban. After acareful andextensive
evaluation oftherisks tohuman health andthetechnical andeconomic feasibility ofeach, the
European Communities hadchosen thethird option, forthereasons explained inparagraphs 4.127
to4.201. TheEuropean Communities alsoargued thattheUSclaim that"itisimportant todistinguish
52D.A. Wirth (1994) "The roleofScience intheUruguay Round andtheNAFTA Trade Disciplines", 27Cornell
International Law Journal, 817-859, p.856.WT/DS26/R/USA
Page 29
between having ariskassessment andbasing ameasure onthatriskassessment" revealed nothing.
TheEuropean Communities based itsmeasures ontheriskassessment itconducted forthatpurpose.
Neither the1982 ECExpert Report northe1988 Lamming Committee Report, northe1988 JECFA
Report constituted inthemselves "risk assessment" inthesense ofArticles 5.1to5.6oftheSPS
Agreement; they only formed partof"available scientific evidence." Theother factors mentioned
inArticle 5.2andinparagraphs 3to6thereof, were notdealt with bythescientific reports onwhich
theUnited States wasbasing itsclaim. Indeed, theassessment ofthese factors wasnotascientific
question inthestrict sense, andthus they fellwithin theresponsibility oftheappropriate political
authorities ofeach Member.
4.48 TheEuropean Communities further argued thattheUnited States hadfailed toappreciate the
difference between theriskassessment required bytheSPSAgreement when adopting measures ,and
thehazards against which members setalevel ofprotection. Paragraphs 4.127 to4.201 examined
thehazards from hormones which were asource ofrisktohuman health, irrespective ofthewayin
which they were used. TheEuropean Communities wasnotobliged bytheSPS Agreement toset
different levels ofprotection against hormones used forgrowth promotion andhormones used forother
purposes; onthecontrary, oneofthefewrequirements intheSPSAgreement inrespect ofthelevel
ofprotection wasthatitbeconsistent (Article 5.5). TheSPSAgreement imposed more, andstricter,
disciplines onmeasures thanitdidonthelevel ofprotection. This wasbecause measures were capable
ofbeing judged against objective universal criteria, while thelevel ofprotection wasnot.Thechoice
ofthelevel ofprotection might legitimately beinfluenced byfactors such aspolitical andfinancial
priorities. AstheUnited States hadsaidinitsStatement ofAdministrative Action, "itisasocietal
value judgment". However, once alevel ofprotection hadbeen decided, themeasures used toachieve
itcould beanalyzed scientifically. TheEuropean Communities claimed thatthepoint wasnotthat
science didnotknow everything about hormones. Thepoint wasthatitknew alot,including thefact
thatthey were carcinogenic. Theproblem wasthatscience didknow exactly how, andunder what
circumstances, thiscarcinogenic effect occurred. This waswhy theEuropean Communities took a
precautionary approach.
4.49 TheUnited States indicated thatintheUnited States, asinother countries, hormones were
regulated asanimal drugs when theywere intended foruseinanimals foreither therapeutic orproduction
purposes. Theuseofhormones forgrowth promotion purposes hadbeen approved bymore than 20
countries, including theUnited States, Canada, Australia, New Zealand, Japan, Korea, thePhilippines,
South Africa, Mexico andmost Latin American countries, andhadbeen under intense scrutiny by
scientists world-wide forover 15years. TheUnited States affirmed thatnoscientific review hadever
concluded thatthere wasabasis forbanning thesaleofanimals towhich oneofthese hormones had
been administered inaccordance with good animal husbandry practice orforbanning thesaleofmeat
from such animals. Thereports which theEuropean Communities hadrelied on,including the1983
OIE Scientific Report andthe1988 JECFA report, aswell asitsinternal reports, hadallconcluded
thatthese hormones were safewhen used forgrowth promotion purposes inaccordance with good
animal husbandry practice. Thefactthatthescientists, intheir study ofthese hormones, hadalso
reviewed thedataontheeffects ofhormones athigh doses orunder other methods ofadministration
didnotconstitute evidence thattheapproved usesforanimal growth promotion purposes were unsafe.
TheUnited States contended thattheissue wasnotwhether anyhormone wassafeforallconceivable
purposes atanyconceivable level ofconcentration. Theissue waswhether theECbanontheimportation
ofanimals, andmeat derived from such animals, thathadbeen administered thehormones inaccordance
with good animal husbandry practice, wassupported bysufficient scientific evidence. TheEuropean
Communities hadoffered absolutely noevidence thatsuch useofthese hormones presented anyrisk
tohuman health. TheUnited States noted thattheexperts advising thePanel hadconfirmed thatthere
wasnoscientific evidence tosupport theECban.
4.50 TheUnited States pointed outtheLamming Committee report forthethree natural hormones
hadfound that: "Thus noquestions ofsafety arise inrelation totheproper useofoestradiol-17 ,WT/DS26/R/USA
Page 30
progesterone andtestosterone inanappropriate form ofpreparation" (emphasis added, page 7). In
thisregard, Part BofthePimenta Report stated onpage 6that:
"The present scientific evidence indicates thatthere isnodiscernable health riskintheuse
ofthethree endogenous hormones where these are,inparticular, administered tocastrated
steers (whose hormone levels aretherefore considerably lower than normal) andwhere they
areadministered intheform ofslow-release implants inapartoftheanimal which isnot
consumed (e.g. theear)andwhere aspecific period withnofurther administration ofhormones
isobserved before slaughter."
Asindicated inparagraph 2.33, thescientific experts andother interested parties which theEuropean
Communities hadcalled together forthe1995 ECScientific Conference hadconcluded thatthere was
noevidenceofpossiblehealthrisksfromtheuseofthenaturalhormonesforgrowthpromotingpurposes.
The1995 ECScientific Conference hadfurthermore concluded that:
"Atthedoses needed forgrowth promotion, residue levels [oftrenbolone andzeranol] are
well below thelevels regarded assafe(theMRLs). There are,atpresent, noindications of
apossible human health riskfrom thelowlevels ofcovalently-bound residues oftrenbolone."
TheUnited States claimed thatthese conclusions were consistent with other scientific reviews ofthe
hormones byscientists around theworld, including thereviews conducted fortheCodex Commission.
4.51 TheUnitedStatesobservedthattheconceptofthe"appropriatelevelofsanitaryorphytosanitary
protection" or"acceptable level ofrisk" wasoneofthekeyconcepts oftheSPSAgreement. Thelevel
ofprotection orriskrelated tothechance orprobability ofanadverse health effect resulting from a
particular activity. Forexample, alevel ofprotection orriskmight beexpressed asariskof1in
1million, meaning thatoutofevery 1million humans intherelevant population, oneperson could
beexpected tosuffer theadverse health effect from engaging inaparticular activity. Theappropriate
level ofprotection oracceptable level ofriskwasthemaximum level ofriskthatwasconsidered
tolerable. TheUnited States repeated thatthechoice ofwhat level ofprotection wasappropriate was
asocial value judgement, notascientific determination. There wasnoscientific basis forchoosing
onelevel ofprotection over another. Forexample, science could notsaywhether ariskofonein
onemillion ofkidney failure from aparticular activity wasacceptable, orwhether ariskofonein
1,000 oronein10million should beacceptable. Thelevel ofprotection wasthegoal theMember
sought toachieve interms ofhealth protection. Sanitary andphytosanitary measures were themeans
toachieve thatgoal.
4.52 TheEuropean Communities claimed thattheterms "appropriate level ofprotection" and
"acceptable level ofrisk" were alternative ways ofexpressing theconcept buttheywere notsynonymous.
Inthecase inquestion, theEuropean Communities hadalevel ofprotection butnoacceptable level
ofrisk, because itdidnotaccept anylevel ofresidues ofadded hormones inmeat. Itrejected theUS
suggestion thatlevel ofprotection equalled level ofrisk; intheECview, itdidnot.Thelevel of
protection wasnotthe"chance orprobability" ofanadverse effect. Itwasparticularly incorrect to
saythattheappropriate level ofprotection wasthemaximum level ofriskthatwasconsidered acceptable.
TheEuropean Communities didnot"accept" anyriskfrom adding carcinogens tofood forthesake
ofalittle extra profit forfarmers anddrug companies. TheEuropean Communities wasaware, of
course, thatdespite itsmeasures there might beoccasions when such contaminated meat slipped through
itsdetection system, butthatdidnotalter thefactthatitsobjective ,insetting itslevel ofprotection,
wastoprevent anysuch residues. The"risk" (i.e. the"potential foradverse effects onhuman and
animal health") from theuseofhormones hadbeen explained indetail bytheEuropean Communities,
especially inparagraphs 4.127 to4.201. The1988 JECFA, onwhich theUnited States wasarguably
basing itscontention, hadalsofound thatthere wasapotential risktohuman health: ifthere wereWT/DS26/R/USA
Page 31
nosuch potential risk, theJECFA would have recommended noADI andMRL forthetwosynthetic
hormones. Forthethree natural hormones, JECFA hadnotrecommend ADIs andMRLs because
ofproblems indetecting thelevel ofresidues inmeat. TheEuropean Communities further claimed
thatanADI oranMRL recommended byCodex could never beconsidered tobeameasure forthe
purposes oftheSPS Agreement. Thus, science might help insetting astandard, guideline or
recommendation (i.e.ADIorMRL) designed toexclude theprobability thatanindividual would develop
cancer after alifetime ofexposure toaparticular chemical substance, ortolimit thatprobability to
nomore than onechance inamillion. Thechoice ofwhere tosettheprobability, forexample the
one-in-a-million asopposed toone-in-a-thousand orzerochance, wasoneofpublic policy andbelonged
tothecompetent democratic authorities oftheMembers. Thelevel ofprotection wassubject only to
Articles 5.4and5.5,nottothewhole ofArticle 5.Contrary totheUSview, theEuropean Communities
argued thatasanitary measure wasnotameasure to"limit therisk"; itwasameasure toprotect human
oranimal lifeorhealth, etc. Inthecase inquestion, theECmeasure wasaimed ateliminating the
potential foradverse effects bypreventing theoccurrence ofresidues inmeat.
4.53 TheUnited States claimed thattheECreliance onitssupposed appropriate level ofprotection
asajustification fortheir banwasmisplaced. First, theEuropean Communities hadnever articulated
what their appropriate level ofprotection wasinrespect ofthesixhormones. Therequirement of"no
residues", which theEuropean Communities claimed tobeitslevel ofprotection, wasameasure
(essentially ameasure thatsetamaximum residue limit, or"MRL", ofzero) notalevel ofprotection.
Moreover, thiswasameasure which infactwasnotmaintained bytheEuropean Communities. The
European Communities permitted residues ofthese hormones inmeat. First, allmeat hadresidues
ofthenatural hormones ("residues" included amounts inthemeat resulting from theanimal ’snatural
production ofhormones). Second, theECderogation forherd management andother purposes meant
thatmeat would alsohave residues ofadministered hormones. TheUnited States observed thatthe
experts advising thePanel hadconfirmed thatthere wasnoscientific justification, where theconcern
waswith residues ofasubstance, foronly banning oneuseofthesubstance andnotregulating residues.
TheUnited States argued thattheECstatement thattheaimoftheECDirectives wastoprotect human
andanimal health by"seeking alevel ofprotection which requires thepresence ofnoresidues inmeat"
suggested thattheECpurported "level ofprotection" wasreally awaytojustify their total ban. In
theUSview, aside from thefactthatitwasphysically impossible torequire thepresence ofnoresidues
ofhormones inmeat, thiswasacase ofthemeasure driving thelevel ofprotection, rather than, as
itshould be,theother way around.
4.54 TheUnited States submitted thatalevel ofprotection with respect toanimal drug residues
inmeat might be"noriskofcancer inhumans". Ifthatwere theECappropriate level ofprotection,
thentheEuropeanCommunitiescouldassesswhethertherewereanyriskspresentedbyhormoneresidues
inlight ofthislevel ofprotection. ButthatwasnottheECappropriate level ofprotection. The
European Communities studiously avoided naming alevel ofprotection (naming instead themeasure
ithadestablished), perhaps because naming alevel ofprotection made clear thattheECbanwas
unjustified. Indeed, there wasnoscientific evidence thatthere wasariskofcancer tohumans consuming
meat from animals towhich anyofthesixhormones hadbeen administered forgrowth promotion
purposes inaccordance with good animal husbandry practice. Quite theopposite, there wasscientific
evidence thatthelevels ofresidue under discussion didnotpose ariskofcancer inhumans. Inother
words, there wasnoappropriate level ofprotection thatwould justify theECban. A"zero risk" level
ofprotection wasthemost stringent level ofprotection possible. Since thebanned animals andmeat
already achieved thislevel ofprotection, then thebancould notbejustified onthebasis oftheEC
appropriate level ofprotection.WT/DS26/R/USA
Page 32
4.55 TheUnited States further argued thattheECown guidelines forthecontrol ofresidues of
oestradiol andtestosterone were inconsistent with theECposition inthisdispute.53Foroestrogen,
theECguideline was 40picograms ("pg")/ml (40parts pertrillion); fortestosterone, itwas
10nanograms ("ng")/ml (10parts perbillion) inmale cattle younger than 6months and30ng/ml in
males 6-18 months; innon-pregnant females itwas0.5ng/ml (noguideline level hadbeen setfor
progesterone.) Many animals thathadnotbeen administered anyofthesixhormones forgrowth
promotion purposes violated theECguidelines. Forexample, recent datawere available tosuggest
thatthevery means ofslaughter might cause increases inthese hormones above these identified limits.
Atthesame time, levels ofhormones inanimals towhich anyofthesixhormones hadbeen administered
forgrowth promotion purposes fellbelow theguideline levels setbytheEuropean Communities. This
wasbecause, ashadbeen confirmed bytheexperts advising thePanel, theresidues inmeat ofthethree
natural hormones, when administered forgrowth promotion purposes inaccordance with good animal
husbandry practices, were within thenormal physiological levels.
4.56 TheUnited States noted thatthiswasinpartrelated tothefactthatproducers inECmember
States raised bulls (non-castrated adult male cattle) tomaximize thegrowth ofanimals, whereas in
theUnited States steers (castrated adult male cattle) were predominantly raised andhormones were
administered toobtain more efficient growth. Bulls naturally hadfarhigher levels ofhormones than
steers, including steers towhich hormones hadbeen administered forgrowth promotion purposes.
Similarly, intheEuropean Communities there were quite anumber ofpregnant animals entering the
normal slaughter process.54Like bulls, pregnant animals alsohadfarhigher than average levels of
hormones. Inother words, theagricultural practices intheEuropean Communities, inlight ofthe
ban, resulted inconsumers being routinely exposed tofarhigher levels ofnatural hormones intheir
meat ofECorigin thanmeat ofother origins. Theselective ECbanwasnotjustified even under their
ownprofessed approach. Ifonewere toaccept theECclaim thatanyresidue ofthese hormones would
pose ariskofcancer, then theEuropean Communities would berequired toprohibit theuseofthe
hormones forherd management andother purposes. However, theEuropean Communities permitted
these uses. TheUnited States further noted thatmeat could have residues identical tothose ofzeranol,
even though zeranol hadnotbeen administered totheanimal, iftheanimal hadeaten feedcontaminated
with thecommon mould Fusarium.
4.57 TheEuropean Communities claimed thatthere wasnoobligation tofollow scientific principles
ortouseriskassessment insetting thelevel ofprotection. AstheUnited States hadsaidintheStatement
ofAdministrative Action: "The SPSAgreement thusexplicitly affirms theright ofeach government
tochoose itslevels ofprotection, including a"zero risk" level ifitsochooses. Agovernment may
establish itslevels ofprotection byanymeans available under itslaw, including byreferendum." It
was, ofcourse, implicit thatinorder toneed alevel ofprotection there must besome hazard against
which aMember needed toprotect. However, thisonly implied theidentification ofahazard, not
anassessmentoftheprobabilitythatitwouldcausedamage.Manydifferentkindsofbiological,chemical
orphysical hazards might occur infoods, andgovernments hadtodecide towhat degree they aimed
toprotect their populations from these hazards. These decisions were taken, aswere anypolitical
decisions, inthelight ofanumber offactors including thepotential danger tohealth andthecostand
feasibility ofachieving effective protection. Forexample, inthecaseofasubstance which wasfatally
poisonous,orwhichcausedaveryseriousorfatalconditionsuchascancer,governmentswouldgenerally
53"Residues infood producing animals andtheir products; Reference materials andmethods", Final Report, Directorate-
General forAgriculture, Commission oftheEuropean Communities, 1992. Discussed atp.552 ofthe1995 ECScientific
Conference Proceedings.
54B.Hoffmann "Problems ofResidues andHealth Risks ofAnabolic Agents with SexHormone-like Activities", 1995
ECScientific Conference Proceedings, p.284. Note alsotheconclusion onthatsame page that: "Thus, duetothelackof
formation ofextra residues, inprinciple noriskforpublic health canbeseen following thepresently recommend useof
endogenous sexhormones asanabolic agents, atleast incattle".WT/DS26/R/USA
Page 33
setavery high level ofprotection, i.e.they aimed toavoid thepresence ofsuch asubstance infood
altogether. However, inthecaseofalesser hazard, such asanorganism which caused anuncomfortable,
buttransient andnonlife-threatening effect, governments might setalevel ofprotection which aimed
tominimize, butnotnecessarily eliminate, thepresence oftheorganism infood. There would obviously
bedifferences between governments intheir approach tosetting alevel ofprotection, asafunction
oftheir economic priorities andcultural habits. Forexample, adeveloped country might consider
itdesirable tosetahigh level ofprotection against contamination offoods bywaste material from the
chemical industry, whereas adeveloping country might consider itahigher priority toencourage the
establishment ofachemical industry rather than, forthepresent, worry about some chemical residues
infood. This wasparticularly thecase forcountries where food supply wasmore ofaproblem than
food quality .Similarly, cultural habits such astheeating ofcertain foods inarawstate might cause
agovernment tosetahigher level ofprotection against some pathogens than would bethecase for
agovernment whose population cooked thesame food thoroughly before eating it.Foreconomic
andcultural reasons, thedecision onwhere tosetthelevel ofprotection wasnotapurely scientific
one, anditwasnotonewhich could besubject tointernational rules, given thegreat diversity among
theMembers oftheWTO.
4.58 TheEuropeanCommunitiespointedoutthat,contrarytotheUSallegations,ithadstatedclearly,
onseveral occasions, thatitaimed toavoid thepresence ofresidues ofadded hormones inmeat. The
reference to"zero risk" wasmisleading. TheECinterpretation of"zero risk" inthiscontext wasthat
itwasnotprepared toaccept anyresidues ofadded hormones forgrowth promotion.
4.59 TheEuropean Communities further clarified thatithadargued thattheCodex recommendation
wasalevel ofprotection asopposed toameasure .However, itwasbynomeans clear thattheMRLs
were "standards", astheywere adopted under aheading of"Standards andrelated texts"; they could
better beregarded asguidelines orrecommendations. Itwasinteresting thatnow theUnited States
didnotrefer toCodex MRLs as"measures" inthesense oftheSPS Agreement.
4.60 TheEuropean Communities noted thatthedivergencies intheregulatory approach ofMembers
regarding theuseofthehormones atissue demonstrated thatcountries viewed andappreciated differently
thepotential risks tohuman andanimal health resulting from theuseofthese hormones forgrowth
promotion purposes. While theUnited States allowed theuseofallsixhormones, Canada allowed
theuseofallofthese hormones except trenbolone55;Australia, New Zealand andSouth Africa allowed
theuseofallofthese hormones except MGA56;Argentina allowed theuseofzeranol andtrenbolone,
butnottheother fourhormones; andatleast 25meat-producing countries (other thanthe15ECmember
States) prohibited theuseofthese hormones forgrowth promotion.
4.61 TheUnited States claimed thattheissue inthisdispute wastheECban, notthemeasures
ofother Members. Differences among countries intheregulation ofthese hormones were notscientific
evidence supporting theECban. AsAustralia andNew Zealand hadindicated, ahormone might not
beregistered due, forexample, toalackofinterest associated with differences inproduction practices.
Moreover, itcould notberuled outthattheECbanhadinfluenced other countries toforgo approving
theuseofthehormones forgrowth promotion purposes inorder toensure access totheECmarket
formeat.
4.62 TheEuropean Communities replied thatwhat wassignificant wasthatbyvirtue ofthefact
thattheyregulated hormones, allofthese countries must consider thatariskexisted. Thedifferences
inregulation reflected different opinions about thedegree ofrisk. Itwasuntrue thattheECrules had
influenced other countries duetofears about atrade ban; there wasnot,andnever hadbeen, aban
55Canada corrected theECclaim thatCanada does notpermit theuseoftrenbolone (seeSection V,para. 5.12).
561995 ECScientific Conference Proceedings, pp.597-598.WT/DS26/R/USA
Page 34
ontrade. Itwasentirely possible thatother countries hadcarefully considered thescientific evidence
andcome tothesame conclusion astheEuropean Communities.
(b) Article 2.3oftheSPS Agreement
4.63 TheUnited States recalled thatArticle 2.3required Members toensure thattheir sanitary and
phytosanitary measures (a)didnotarbitrarily orunjustifiably discriminate between Members where
identicalorsimilarconditionsprevailed,includingbetweentheirownterritoryandthatofotherMembers;
and(b)were notbeapplied inamanner which would constitute adisguised restriction oninternational
trade. TheUnited States argued thattheECbanarbitrarily orunjustifiably discriminated between
Members where identical orsimilar conditions prevailed anddiscriminated against imported animals
andmeat, both compared todomestic products andtoproducts imported from other Members. The
ECbandiscriminated between Members thatpermitted theuseofthehormones forgrowth promotion
purposes andthose thatprohibited their useorpermitted theuseofthenatural hormones fortherapeutic
purposes (including theEuropean Communities itself); thequestion forpurposes ofArticle 2.3was
whether thediscrimination wasjustifiable. TheUnited States argued thatthere were norelevant
differences intheconditions prevailing intheUnited States compared totheEuropean Communities
orother supplying Members with respect tothese animals ormeat andthatthere wasnoscientific or
other basis fortheEuropean Communities 'discrimination against USmeat andanimals. TheECban
wasdesigned, inpart, toremove anycompetitive advantage arising from theuseofthehormones at
issue forgrowth promotion purposes andtothereby protect domestic production. AstheEuropean
Court ofJustice hadjudged, "the possibility ofareduction insurpluses was indeed taken into
consideration during theprocess leading totheadoption oftheDirective".57Furthermore, theEC
Parliament, incalling fortheEuropean Communities toadopt itsban, hadexplicitly cited thefactthat
"there isoverproduction ofmeat andmeat products intheEuropean Communities which adds
considerably tothecostoftheCAP".58InMarch 1989, thedraft ofthePimenta Report hadalsomade
itclear thatcontrol ofbeef supply wasoneofthetrue motives forthisDirective: "The Inquiry
Committee believes thatonlyatotalbanontheuseofgrowth-promoters isconcordant with thestrategic
aims now adopted fortheCommon Agricultural Policy, inparticular thereduction ofsurpluses and
thesafeguarding ofaviable regionally-diversified farming community ”.Finally, Directive 88/146/EEC
itself cited thedesire toalter theconditions ofcompetition inthemeat sector.
4.64 TheEuropean Communities responded thatEuropean Court ofJustice hadpronounced itself
twice ontheaimofDirective 88/146/EEC. Inthefirstcase, theCourt ofJustice found thattheaim
oftheDirective wastoprotect human health andconsumer interests.59This objective waspursued
with aview toimproving thequality ofmeat through regulating theconditions fortheproduction and
marketing ofmeat. TheUnited States hadtotally disregarded thispartoftheCourt 'sjudgment and
cited selectively from theother judgment oftheCourt.60Furthermore, theCourt ruling cited bythe
United States hadconcluded that"itdoes notfollow thatsuch areduction, which isnotcited inthe
preamble totheDirective asoneoftheobjectives pursued, wasinfacttheexclusive ormain purpose
oftherules adopted". This made evident thatthereduction inmeat surpluses wasnomore than a
possibility, andanyMember wasentitled toevaluate thesideeffects ofanactitadopted forother
57"The Queen v.TheMinister forAgriculture, Fisheries andFood andtheSecretary ofState forHealth" (Case C-331/88),
Judgment oftheCourt atp.I-4065.
58Resolution "closing theprocedure forconsultation oftheEuropean Parliament ontheproposal from theCommission
oftheEuropean Communities totheCouncil foraDirective amending Directive 81/602/EEC concerning theprohibition
ofcertain substances having anhormonal action andofanysubstances having athyrostatic action," para. I.(Doc. A2-100/85,
11November 1985, ECOfficial Journal No.C288, p.158 etseq.).
59Case 68/86, United Kingdom v.Council (1988) ECReports p.855, p.897, para. 20.
60Case 331/88, Fedesa andothers (1990) ECReports p.I-4023, p.4065.WT/DS26/R/USA
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purposes. Moreover, surpluses ofmeat hadnotexisted inApril 1996 when theEuropean Communities
haddecided tomaintain theprohibition byadopting Directive 96/22/EC. Furthermore, theevidence
clearly showed that even thefirst EC Directive 85/649/EEC, which had been replaced by
Directive88/146/EEC,hadnotinfactcontributedtoreducingthesmallbeefsurpluses.Statisticsshowed
thattheEuropean Communities hadcontinued toproduce domestically about thesame quantities and
hadcontinued toimport from third countries about thesame quantities ofmeat asbefore theprohibition.
Theonly difference, after theadoption ofthese Directives, wasthatthenature andcomposition of
meat destined forhuman consumption intheEuropean Communities changed (i.e.came from animals
towhich nohormones forgrowth promotion hadbeen administered).
4.65 TheEuropean Communities alsonoted thatthere were several countries which didnotallow
theuseofanyormost ofthese hormones foranimal growth promotion, butsome ofthem didnotimpose
anyrestrictions onimports ofhormone-treated meat because they hardly imported anymeat astheir
domestic production sufficed tocover demand. Argentina, forinstance, which wasamajor beef
producer, didnotallow theuseofthethree natural hormones forgrowth promotion (because residues
ofthese hormones could noteasily bedetected), butdidnotapply aprohibition onimports ofanimals
ormeat treated with these three hormones asthere were virtually noimports taking place. Incontrast,
theEuropean Communities hadalways imported large quantities ofmeat andhadtoadopt themeasures
inquestion inorder toensure thattheobjectives ofitsdomestic sanitary policy were notcircumvented
through imports from third countries.
4.66 TheEuropean Communities argued thatitsmeasures offered equal opportunities ofaccess to
theECmarket forallthird-country animals andmeat from animals towhich nohormones hadbeen
administered forgrowth promotion purposes. Ofthe31countries which were authorized toexport
meat totheEuropean Communities, onlysixapparently allowed theuseofsome orallofthese hormones
forgrowth promotion purposes. Allofthese 31countries (including theUnited States) hadcontinued
toexport totheEuropean Communities animals andmeat from animals towhich nohormones had
been administered forgrowth promotion purposes. Thus, overall thesame competitive pressure as
before wasmaintained from third-country imports ondomestic meat production andUSallegations
tothecontrary were unfounded. Theintention oftheECmeasures atissue, therefore, wasnottoshield
domesticmeatproductionfromforeigncompetition.TheEClegislationdiddistinguishbetweencountries
which permitted theuseofhormones forgrowth promotion andthose which didnot,butthiswasa
justified distinction inview ofthechosen EClevel ofprotection. Theargument thatitsmeasures were
adisguised restriction ontrade wasunsubstantiated. TheECmeasure didnot,therefore, contravene
Article 2.3.
4.67 The United States noted thattheEuropean Communities admitted todistinguish between
Members thatpermitted theuseofthehormones forgrowth promotion andthose thatdidnot. The
United States considered thattheECclaim thatthisdistinction could bejustified byitschosen level
ofprotection wasunfounded. TheEuropean Communities hadnotdemonstrated anyscientific basis
orother basis forthediscrimination, anditwasnotjustified byanyhealth risks. None oftheexperts
advising thePanel gave anyresponse which would justify adetermination thatanimals towhich any
ofthesixhormones hadbeen administered forgrowth promotion purposes, andmeat from such animals,
should beconsidered "unlike" other animals ormeat. TheEuropean Communities hadadmitted that
residues ofhormones resulting from implants could beimpossible todetect, andscientists hadconcluded
thatsuch residues were meaningless given thevariation indifferent meat sources andthelevels of
hormone production inhumans. Moreover, theEuropean Communities hadnotdemonstrated that
itschosen level ofprotection wasanydifferent from thatofanyoftheMembers who hadapproved
theuseofthese hormones forgrowth promotion. More importantly, theright ofaMember toselect
itsown appropriate level ofprotection wasnotajustification forabreach ofitsobligations under
Article 2.3. TheUnited States concluded thattheEuropean Communities hadfailed toshow how its
asserted defense waseven relevant. This discrimination wasconsequently notjustified byanyhealth
risks, itwasarbitrary andunjustifiable. Accordingly, theUnited States concluded thattheECbanWT/DS26/R/USA
Page 36
unjustifiably discriminated between Members where identical orsimilar conditions prevailed andwas
inconsistent with theobligations oftheEuropean Communities under thefirstsentence ofArticle 2.3.
4.68 Furthermore, theUnited States contended, thebanconstituted adisguised restriction on
international trade, inbreach ofArticle 2.3,asdemonstrated bytherecord which showed thateconomic
reasons related toreduction ofmeat surpluses andtoaltering theconditions ofcompetition intheEC
market were animportant purpose oftheban. Moreover, theECDirectives required theECmember
States topermit widespread useofhormones forpurely economic reasons connected with efficient
herdmanagement. TheECmeasures depended ondrawing adistinction between, forinstance, domestic
beeffrom cattle injected with hormones forherd-management purposes andimported beeffrom cattle
implanted with hormones forgrowth promotion purposes. Inthisconnection theUnited States noted
thatthedoses ofhormones used fortherapeutic andzootechnical purposes were equivalent to,orin
some cases higher, thantheaverage daily dose used forgrowth promotion purposes. TheUnited States
stated thatiflowlevel residues ofthehormones caused adverse health affects, asclaimed bythe
European Communities, thentherapeutic andzootechnical usesshould bebanned aswell. These facts
confirmed thatthehormone banwasnotavalid health-based measure, butaneconomic measure, and
ameansofprotectingECproducersagainstimports.TheECmeasuresweredesignedtoprotectdomestic
production. Insum, since theECmeasures were notapplied only totheextent necessary toprotect
humanlifeorhealth,werenotbasedonscientificprinciples,weremaintainedwithoutsufficientscientific
evidence, were notbased onanassessment oftherisks, andwere more trade-restrictive than required
toachieve theappropriate level ofprotection, itwasapparent thatthemeasures were notlegitimate
sanitary measures. Instead, they were measures designed toprotect domestic production intheguise
ofsanitary measures. That wastheessence ofadisguised restriction oninternational trade.
4.69 TheEuropean Communities responded that, although theEClegislation permitted theuse
ofthethree natural hormones fortherapeutic orzootechnical reasons, thiswasallowed under strict
conditions. Thus, thethree hormones might beadministered, fortherapeutic orzootechnical reasons,
(i)only byaveterinarian, (ii)only byinjection orvaginal spiral (totheexclusion ofimplantation),
and(iii)only tofarm animals which hadbeen clearly identified. Furthermore, such treatments must
beregistered bytheveterinarian andthese animals could notbeslaughtered formeat production before
awaiting period long enough toensure thatnoresidues were present intheir meat. Thedoses ofthese
hormones required fortherapeutic orzootechnical purposes were several times lower than thedoses
required foreffective growth promotion. Inthecase ofanimals which were attheendoftheir
reproductive career, such treatments were prohibited during thefattening period following theend
oftheir breeding life.Allthese conditions ensured thatthehormones were administered properly and
thatnoresidues ofhormones, other than those naturally produced bytheanimals themselves, were
present inthemeat destined forhuman consumption.
4.70 TheEuropean Communities noted thatthe1988 JECFA Report hadalsorecognized thataclear
distinction should bedrawn between theuseofhormones fortherapeutic orzootechnical reasons and
animal growth promotion, indicating that"...residues leftafter theuseofadrug forgrowth promotion
should beconsidered separately from residues leftafter theuseofthatdrug forother purposes".61
4.71 TheEuropean Communities claimed thatitwasmisleading tostate thatthere waswidespread
useofhormones fortherapeutic orzootechnical purposes intheEuropean Communities. Although
theEuropean Communities didnotpossess theexact figure ofthenumber ofanimals treated forthese
purposes, ofthose ECmember States which kept records62,itwasestimated thatonly between 1per
cent and2percentofbreeding cattle intheEuropean Communities were treated each year forsuch
purposes. This percentage corresponded toabout thesame proportion oftotal bovine meat ofECorigin
611988 JECFA Report, p.16.
62E.g. Denmark, theNetherlands andFinland.WT/DS26/R/USA
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consumed intheEuropean Communities, towhich once intheir breeding lifesuch treatments may
havebeenadministered.Regardlessoftheinsignificantquantitiesinvolved,whatneededtobeunderlined
wasthatallowingtheadministrationofthethreenaturalhormonesfortherapeuticorzootechnicalreasons
wasinfullcompliance with theECpolicy ofensuring noresidues ofhormones inmeat forhuman
consumption since thestrict conditions imposed byEClaweffectively ensured itspolicy objective (no
residues atall). Furthermore, theEuropean Communities pointed outthatmeat from animals which
had, atsome time intheir life, been treated with hormones fortherapeutic orzootechnical reasons,
under thestrict conditions laiddown intheEClaw, might bemarketed forhuman consumption in
theEuropean Communities. Equally, animals treated fortherapeutic orzootechnical reasons andmeat
ofsuchanimalswereallowedtobeimportedfromthirdcountriesunderguaranteeswhichwereequivalent
tothose applied fordomestic animals andmeat from such animals. Therefore, thisprovision ofEC
lawapplied regardless ofthecountry oforigin oftheanimals ormeat ofsuch animals. TheUnited States
hadnotbrought forward anyevidence toshow thatanimals andmeat from animals treated inthe
United States fortherapeutic orzootechnical purposes, iftheycomplied with theconditions laiddown
inEClaw, were notallowed tobeimported into theEuropean Communities. The European
Communities further contended that"identical orsimilar conditions" didnotprevail between the
United States andtheEuropean Communities inrespect oftheuseofhormones forgrowth promotion.
Neither were theproducts similar oridentical. Ameasure might beapplied only totheextent necessary
toprotect lifeorhealth. If,forexample, itcould bedemonstrated thatpasteurizing milk at72Cfor
15seconds wassufficient tokilltuberculosis, aMember would notbejustified inrequiring milk to
beheated toahigher temperature foralonger timeforthepurpose ofprotecting against thesame hazard.
Butinthiscase, theEuropean Communities haddemonstrated thatifithadfollowed theUSexample
inapplying theCodex recommended MRLs inthewaytheywere applied intheUnited States, itwould
have certainly failed toachieve itslevel ofprotection, which wasnoresidues ofthese hormones in
meat forhuman consumption andalsotoprotect animal health, inview ofthevery limited number
oftests carried outbytheUnited States andthenumber ofviolations found even inthislimited number
oftested samples.
4.72 TheUnited States noted thattheECclaims thatithadnosolid information about thepercentage
ofmeat produced intheEuropean Communities from animals towhich hormones hadbeen administered
forherdmanagementandotherpurposeswasatoddswiththeEuropeanCommunities'constantreference
tothestrict controls onsuch useandtheneed toidentify every single animal towhich hormones had
been administered. Industry sources intheEuropean Communities hadindicated totheUnited States
that3.75 to4percentofallcattle were treated each year based onanaverage ofnumbers inBelgium,
France, Germany, theNetherlands andtheUnited Kingdom. Inaddition, about 6percentofsheep
intheEuropean Communities were treated each year. In1995, from onecompany alone, 2million
doses ofhormones hadbeen sold(forsheep) and½million doses were soldforcattle. Furthermore,
theoneguess thattheEuropean Communities offered wasmisleading. Bystating thathormones were
administered to1to2percent oftheECherd each year, theEuropean Communities failed tonote
thatthisfigure should bemultiplied bythenumber ofyears thattheanimals intheherd remained in
production inorder todetermine thequantity ofthemeat supply from animals that, during their lifetime,
hadbeen administered these hormones. Forexample, ifthehormones were administered todifferent
animals each year, then over thecourse of5years, 5to10percent oftheherd would have been
administered these hormones. Alternatively, ifthehormones were administered tothesame animals,
then ananimal might have received five separate setsoftreatment. Furthermore, there was no
requirement thatthehormones administered always bethesame substances. Nothing prevented an
animal intheEuropean Communities from having been exposed tomultiple hormones (orintheEC’s
words, “combinations ”or“cocktails ”ofhormones).
(c) Article 3.1oftheSPS Agreement
4.73 TheUnited States claimed that, contrary totherequirements ofArticle 3.1tobase itssanitary
measures oninternational standards, guidelines orrecommendations where theyexist, theECbanwasWT/DS26/R/USA
Page 38
notbased ontherelevant international standards. Therelevant international standards inthisrespect
were those oftheCodex Commission. TheCodex standards foroestradiol-17 ,progesterone and
testosterone infoods ofbovine origin stated thatthere wasnoneed tosetanyAcceptable Daily Intake
level (ADI) oranyMaximum Residue Limit (MRL).
4.74 Codex hadbased itsdecision nottosetADIs andMRLs forthese three hormones onthebasis
ofthe1988 JECFA Report63,which hadfound thatresidue levels intreated animals fellwell within
thenormal range oflevels found inuntreated bovine animals ofdifferent types andages. JECFA thus
deemed itunnecessary tosetanADI forhormones thatwere produced endogenously inhuman beings
andshowed marked physiological variations inlevels according toageandsex, andhadconcluded
thatresidues arising from theuseofoestradiol-17 ,testosterone andprogesterone forgrowth promotion
purposes inaccordance with good animal husbandry practice were unlikely topose ahazard tohuman
health. JECFA, initsassessment ofthehormones, haddefined what wasmeant byanMRL not
specified. Itmeant that: "Available dataontheidentity andconcentration ofresidues oftheveterinary
drug inanimal tissues indicate alarge margin ofsafety forconsumption ofresidues infood when the
drug isused according togood practice intheuseofveterinary drugs. Forthatreason, andforthe
reasons stated intheindividual evaluation, theCommittee hasconcluded thatthepresence ofdrug
residues inthenamed animal product does notpresent ahealth concern andthatthere isnoneed to
specify anumerical MRL".64
4.75 Withrespecttotrenboloneandzeranol,theUnitedStatesnotedthattheCodexstandardsspecified
both anADI andanMRL. TheCodex definition ofanMRL wasasfollows:
"...themaximum concentration ofresidue resulting from theuseofaveterinary drug (expressed
inmg/kg orµg/kg onafresh weight basis) thatisrecommended bytheCodex Alimentarius
Commission tobelegally permitted orrecognized asacceptable inoronafood.
"Itisbased onthetype andamount ofresidue considered tobewithout toxicological hazard
forhuman health asexpressed bytheAcceptable Daily Intake (ADI), oronthebasis ofa
temporary ADI thatutilizes anadditional safety factor. Italsotakes intoaccount other relevant
public health risks aswell asfood technological aspects.
"When establishing anMRL, consideration isalsogiven toresidues thatoccur infood ofplant
origin and/or theenvironment. Furthermore, theMRL may bereduced tobeconsistent with
good practices intheuseofveterinary drugs andtotheextent thatpractical analytical methods
areavailable."65
TheCodex standard fortrenbolone andzeranol wasanMRL of10µg/kg ofbovine liver and2µg/kg
ofbovine muscle.
4.76 TheUnited States noted thatasearly asDecember 1987, theCCRVDF agreed onMRLs for
trenbolone andzeranol, andagreed thatnoMRLs were necessary forthethree endogenous hormones.
AttheJune 1991 biennial meeting oftheCodex Commission, four ofthehormones (oestradiol,
progesterone, testosterone, andzeranol) were attheendofthelengthy 8-stage approval process of
which thedecision bytheCCRVDF wasakeypoint. Atthatstage intheprocess, thescience ona
particular drug hadbeen thoroughly reviewed, andCodex Commission members hadbeen provided
numerous chances tovoice concerns about thescientific assessment ofthese hormones -either inwriting
631988 JECFA Report, p.19.
64Fortieth report oftheJoint FAO/WHO Expert Committee onFood Additives, pp.5-6.
65Codex Alimentarius, Vol. 3,Residue ofVeterinary Drugs inFoods, Rome 1993, pp.65-66.WT/DS26/R/USA
Page 39
totheCodexCommissionsecretariatoratCCRVDFplenarymeetings.So,theUnitedStatescontended,
thescientific consensus onthefour hormones wasclear bythetime they came before theCodex
Commission. However, theissue continued tobecome politicized. TheUnited States stressed that
in1994, theCodex Alimentarius Executive Committee (which includes amember from theEuropean
Communities) developed four principles clarifying, inter alia,that"[t]he food standards, guidelines
andother recommendations oftheCodex Alimentarius Commission shall bebased ontheprinciple
ofsound scientific analysis andevidence, involving athorough review ofallrelevant information, in
order thatthestandards assure thequality andsafety ofthefood supply." Despite theECopposition,
these principles were adopted bytheCodex Commission inJune 1995. This paved theway forthe
Codex Commission tofinally adopt standards forthefivehormonal substances (bythistime, trenbolone
was also attheStep 8oftheCodex Commission procedures) recommended bytheCCRVDF.
Notwithstanding theadoption ofthestandards, theUnited States noted thattheEuropean Communities
hadmaintained itsbanand, infactwasexpanding itsbanforexample byexpanding ittonewspecies.
4.77 The European Communities argued that atthetime ithad adopted and applied
Directive 88/146/EC (1January 1989), there existed noCodex standards onthehormones. Moreover,
theCodex hadnever studied scientifically thehormone MGA andhadnever adopted anystandard on
itsuse. Furthermore, theEuropean Communities argued thattheCodex standards onthefivehormones
atissue hadbeen adopted byamajority ofonly 33votes infavour, 29votes against and7abstentions
(i.e. aminority ofthose participating), thatwasavery close vote infavour oftheadoption ofthe
standards. There were, therefore, atleast 14countries other than the15ECmember States which
hadvoted against thestandard. This close voteclearly indicated thattheissue ofhormones hadbeen,
andcontinued tobe,very controversial both from thescientific andtheregulatory policy point ofview.
TheEuropean Communities argued that, despite thefactthattheUnited States knew ofthestrong and
wide opposition totheadoption ofthese recommendations onhormones forgrowth promotion purposes
throughout thepreparation oftheCodex Commission 'sdecision ofJuly 1995, ithadstillinsisted on
andpressed, theissue foreconomic reasons, anddespite thelong established practice oftheCodex
Commission toadopt decisions onMRLs byconsensus. Infact, theunusual procedure ofvoting by
secret ballot hadbeen requested inthiscasebytheUnited States.66TheEuropean Communities argued
thateven today, noCodex member hadnotified Codex ofitsacceptance ofthestandards adopted in
July1995 onthehormones.67TheUnited States itself seemed tosupport Codex standards, guidelines
andrecommendations onavery selective basis, only when they favoured their strict economic and
trade interests.68
4.78 TheEuropeanCommunitiesaddedthatArticle3.1madeitplainlyclearthattherewasnoabsolute
obligation onMembers toalways follow standards onSPSmeasures adopted byCodex. There was
nodoubt thatthetwosystems oftheCodex andtheSPSAgreement didnotinteract properly, because
amember ofCodex, which haddifferent views about other considerations (e.g. health concerns of
consumers) andingood faith abstained from blocking theadoption ofaCodex standard knowing in
advance thatindoing soitwould notberequired tofollow thestandard whose adoption itdidnotblock,
would later finditself tohave anobligation tofollow under theSPSAgreement. This wasaninherent
contradiction inthefunctioning ofthetwosystems, ofwhich both Codex andWTO Members were
well aware andefforts were now being made toresolve itinanappropriate way.
66Report ofthe21stSession oftheCodex Alimentarius Commission, Rome, 3-8July1995, Alinorm 95/37, paras 45-46.
67Inthemeantime, South Africa notified acceptance oftheMRLs forveterinary drugs (Codex response towritten questions
raised bythePanel.).
68TheEuropean Communities noted thataCodex press release (Codex Facts, 05-95) hadexplained that"[t]he countries
which voted infavour ofthehormone MRL areprimarily meat-producing/ exporting countries where thecostofproduction
iseither notsubsidised orissubsidised toalesser extent thanintheEU.Production efficiencies, therefore, exercised amajor
influence ontheCodex Commission. Theanimal health industry (commercial producers ofthehormones) wasalsopleased
with theCommission 'sdecisions forobvious reasons".WT/DS26/R/USA
Page 40
4.79 TheEuropean Communities further observed thatJECFA could notpropose anADIfornatural
hormones because when ithadconsidered thematter, intheearly andmid-1980s, thetechnology for
measuring increases inlevels ofthenatural hormones wasnotsufficiently advanced tobeappropriate
forroutine use. Noting thattheUnited States itself setlimits forlevels ofthenatural hormones in
meat above those naturally present, butdidnotcheck annually forthepresence ofresidues from these
hormones, theEuropean Communities further argued thattheonly "international standard, guideline
orrecommendation" relevant totheECmeasure wasthe"Codex Code ofPractice forControl ofthe
UseofVeterinary Drugs". TheMRL laiddown byCodex wasalevel ofprotection, notameasure ,
andthere wasnoobligation intheSPSAgreement toadopt Codex recommended levels ofprotection.
TheEuropean Communities recalled itsearlier arguments thatneither thePanel noranyother Member,
noraCodex Alimentarius group ofscientific experts, could judge theadequacy ofthescientific evidence
used byaMember. Inview ofthepotential hazards tohuman health presented bythemisuse of
hormones infood animals, theEuropean Communities considered thattheyshould onlybeadministered
forthepurposes andunder theconditions defined inDirective 96/22/EC, which were inaccordance
with the"Codex Code ofPractice forControl oftheUseofVeterinary Drugs".
4.80 With respect tothesynthetic hormones, theEuropean Communities observed thatJECFA (on
whose scientific advice Codex hadbased itsrecommended MRLs) hadestablished anADI forzeranol
of0-0.5µg/kg body weight, andfortrenbolone of0-0.02 µg/kg body weight. TheEuropean
Communities wastherefore justified, inrespect ofzeranol andtrenbolone, inaccepting thelower limit,
i.e.anADI ofzero.Codex hadmade norecommendation forMGA. TheEuropean Communities
argued thatitwascontrary tocommon logic toclaim (asitwasargued bytheUnited States) thatan
MRL of2mg/kg ofbovine meat forzeranol wasa"measure" inthesense oftheSPS Agreement.
Scientists haddefined theMRL asthequantity ofaparticular residue inmeat thatwould notexceed
theADI fortheparticular substance concerned, ifitsadministration wasdone inaccordance with the
required practice. Thedecision where tosetthelevel, i.e.at2mg/kg orat10mg/kg ofbovine meat,
wasadecision onthelevel ofprotection, nota"measure" asdefined inAnnex AoftheSPSAgreement.69
Moreover, theEuropean Communities claimed thatasthere wasnointernational standard relevant
toitsmeasure, there wasnocontravention ofArticle 3:1. Codex hadnotestablished standards for
fiveofthehormones atissue; allithaddone wastorecommend maximum residue levels forthetwo
synthetic hormones anddecided thatitwastoodifficult todosoforthethree natural ones. Maximum
residue levels were only ofrelevance toMembers which accepted residues ofthese hormones inmeat.
TheEuropean Communities didnot. Furthermore, assixofthescientists advising theEuropean
Communities hadpointed outintheir written opinions tothePanel70,theJECFA Report onthebasis
ofselected studies inlaboratory animals had"concluded" thatthecarcinogenic effect ofprogesterone
(andoestradiol andtestosterone) waslinked insome waytoitshormonal effect, sothatifitwaspresent
inaconcentration insufficient toproduce ahormonal effect inanimals itwould notbecarcinogenic;
they hadthen extrapolated thisassumption tohumans. ButtheJECFA Report hadnoscientific basis
formakingthisassumption;contrarytotheirownstatedintent(section2.1.2ofthe1988JECFAReport)
they hadnotknown (and adecade later itwasstillnotwell known) how these hormones produced
69ThedefinitionofSPSmeasuresinAnnexAoftheSPSAgreementspecifiesthat"(...)[s]anitaryorphytosanitarymeasures
include allrelevant laws, decrees, regulations, requirements andprocedures including inter aliaendproduct criteria; processes
andproductionmethods;inspection,certificationandapprovalprocedures;quarantinetreatmentsincludingrelevantrequirements
associated withthetransport ofanimals orplants, orwiththematerials necessary fortheir survival during transport; provisions
onrelevant statistical methods, sampling procedures andmethods ofriskassessment; andpackaging andlabelling requirements
directly related tofood safety."
70Dr.Liehr, Adlercreutz, Cavalieri, Letzler, Pinter andEpstein. TheEuropean Communities indicated thatDr.Liehr,
forexample, inhisscientific advice onthisissue hadstated thefollowing:
"Inthe1988 JECFA Report, theauthors considered onlythehormonal receptor-mediated activities ofthenatural
hormones. Inview oftheconsiderable amount ofscientific evidence which hasaccumulated since therelease of
thatReport,particularlyinrespectofthegenotoxicityofoestradiol,theReportcannolongerbeconsideredapplicable
toariskassessment oftheuseofhormone growth promoters."WT/DS26/R/USA
Page 41
their effects. Nevertheless, onthebasis ofthese unjustified extrapolations andassumptions, andbecause
detection wastoodifficult, they had"deemed" itunnecessary tosetanADI.
4.81 TheUnited States claimed thattheEuropean Communities appeared tomisunderstand Article 3
andconfused alevel ofprotection with ameasure when itclaimed thattheMRLs established byCodex
were a"level ofprotection" rather than ameasure. TheUnited States submitted thatanMRL was
ameasure, notalevel ofprotection. Ifagovernment wished toensure, forexample, thatitspublic
wasnotexposed toariskofmore than 1in10million ofnerve damage from lead infood, the
government could establish anMRL tolimit total exposure. However, theMRL wasnotthelevel
of"protection", itwasthemaximum limit ofresidue. What level ofprotection itachieved would depend
inlarge partonwhere theMRL wasset. Inother words, thelevel ofprotection determined where
tosettheMRL.
4.82 TheUnited States rejected theECargument thatArticle 3.1didnotapply toitsbanbecause
Codex didnothave astandard fortheuseofthese hormones, only fortheir residues. TheUnited States
argued thatarequirement tobaseameasure ontherelevant international standard included arequirement
tobase theform ofthemeasure ontheinternational standard. Otherwise, itwould beeasy toevade
therequirementsofArticle3.1bydeliberatelyadoptingameasuredifferentinformfromtheinternational
standard. Under thatapproach, assoon asaMember hadchosen toadopt ameasure different from
theinternational standard, there would nolonger beanyrequirement tobase itsmeasure onthe
international standard. Inother words, Article 3.1would cease toapply assoon asaMember acted
inconsistently with it.TheUnited States added thattoclaim, astheEuropean Communities did,that
since theCodex ADI wasarange from zero to0.5µg/kg body weight, setting anADI ofzero was
“based on”theCodex standard, wasadistortion oftheinternational standard. TheADI wasexpressed
asarange because itreferred tothe"acceptable" daily intake. Inthatregard, anintake ofzero of
these residues wasacceptable, butitwasnottheCodex standard.
4.83 The European Communities responded that international standards, guidelines or
recommendations were based onacertain concept oflevel ofsanitary protection. TheSPSAgreement
explicitly allowed Members nottofollow theinternational standards, guidelines orrecommendations
inorder toachieve their appropriate level ofprotection. Theobjective ofArticle 3.1wastoharmonize,
asfaraspossible, thesanitary orphytosanitary measures ofMembers, given thatadifferent level of
protection might require different types ofmeasures. AnADI orMRL recommended byCodex could
therefore, never beconsidered tobeameasure, because measures were adopted byMembers. Science
might help insetting astandard orrecommendation (i.e. ADI orMRL) designed toexclude the
probability thatanindividual would develop cancer after alifetime ofexposure toaparticular chemical
substance, ortolimit thatprobability tonomore than onechance inamillion. Butthechoice where
tosettheprobability, forexample one-in-a-million asopposed toone-in-a-thousand orzero chance,
wasachoice ofpublic policy, andbelonged tothecompetent democratic authorities oftheMembers.
Itwasagoalofpublic policy, notofscientific nature. TheECpolicy incaseofpotentially carcinogenic
substances likethese hormones aimed toavoid exposing consumers tothem. Therefore, theEuropean
Communities would notconsider alevel ofprotection of1inonemillion tobeacceptable. That was
why itslevel ofprotection inthiscase aimed atreducing thatprobability tozero.
4.84 TheEuropean Communities argued thatthe"appropriate level" aMember decided toapply
initsterritory didnothave tobeexpressed inthesame technical fashion, i.e.asanMRL. There were
usually several ways ofdealing withanygiven hazard, andtheSPSAgreement didnotrequire Members
tochange thetypeofmeasures theychose. Forexample, oneofthemany ways oftackling pathogenic
organisms infood wasirradiation, andsome Members allowed ittobeused forcertain foods. Codex
hadadopted standards forirradiation offoods butthisdidnotmean thatevery Member wasnowobliged
toallow irradiation offoods. Similarly, ifaMember chose alevel ofprotection against acontaminant
onthebasis ofanMRL, thisdidnotmean thatitshould setitsMRL atthelevel recommended by
Codex. Also, ifaMember chose nottoallow anyresidues ofdangerous substances infood, thisdidWT/DS26/R/USA
Page 42
notmean thatitwasobliged tobase itsprotection ontheconcept ofanMRL recommended byCodex,
ifthere existed oneforthatsubstance. Oneoftheweaknesses oftheSPSAgreement wasthatameasure
inconformity with aCodex standard orrecommendation wasdeemed tobeconsistent with Article 3.2.
Unfortunately, many Codex standards were quite outofdate, having been adopted decades before the
development ofsophisticated analytical methods.
(d) Article 3.3oftheSPS Agreement
4.85 TheEuropean Communities argued thatArticle 3.3permitted Members to"...introduce or
maintain sanitary orphytosanitary measures which result inahigher level ofsanitary orphytosanitary
protection thanwould beachieved bymeasures based ontherelevant international standards, guidelines
orrecommendations, ifthere isascientific justification, orasaconsequence ofthelevel ofsanitary
orphytosanitary protection aMember determines tobeappropriate ..."TheCodex recommendations
were designed toachieve alevel ofprotection which waslower than thatapplied intheEuropean
Communities forthehormones atissue. Moreover, Codex andtheother relevant international
organisations mentioned intheSPSAgreement might issue standards, guidelines orrecommendations,
butthey were relevant only forthose Members which chose tofollow them andbase their measures
onthem. IfaMember elected nottofollow them because ithadadifferent level ofsanitary protection,
theMember wasentitled totake another type ofmeasure necessary toachieve itschosen level of
protection. Insuch acase theSPS Agreement only required theMember torespect theprovisions
ofArticles 5.1to5.8thereof.
4.86 TheEuropean Communities claimed thatthe"Codex Statements ofPrinciple Concerning the
Role ofScience intheCodex Decision -Making Process andtheExtent towhich other Factors are
taken intoAccount", approved onJuly1995, explicitly recognized thatother legitimate factors, relevant
forthehealth protection ofconsumers, could betaken intoaccount when elaborating anddeciding
food standards.71Inaddition, Members which haddifferent views about other considerations (e.g.
health concerns ofconsumers) could abstain from accepting therelevant standards. TheSPSAgreement
permitted departure from international standards forthesame reasons forwhich Codex standards,
guidelines orrecommendations were voluntary andcould notbemade legally binding, i.e., because
each Member wasfreetodecide itsappropriate level ofsanitary orphytosanitary protection. This
was notascientific judgment andscientific committees orexpert groups could notreplace the
democratically elected authorities ofMembers.
4.87 TheUnited States argued thattheECbanwasnotcovered bytheexceptions inArticle 3.3
totherequirements ofArticle 3.1. TheEuropean Communities hadnotshown thatitslevel ofprotection
wasdifferent from thatachieved byapplying theCodex standards. Infact, theEuropean Communities
hadnoteven identified itsown level ofsanitary protection. Noting thattheSPSAgreement defined
71Alinorm 95/37, Appendix 2.The"Statements ofPrinciple" isanannex tothereport ofthe21stSession oftheCodex
Alimentarius Commission. The"Statements ofPrinciple "provide:
"1. Thefood standards, guidelines andother recommendations ofCodex Alimentarius shall bebased onthe
principle ofsound scientific analysis andevidence, involving athorough review ofallrelevant information, inorder
thatthestandards assure thequality andsafety ofthefood supply.
"2. WhenelaboratinganddecidinguponfoodstandardsCodexAlimentariuswillhaveregard,whereappropriate,
toother legitimate factors relevant forthehealth protection ofconsumers andforthepromotion offairpractices
infood trade.
"3. Inthisregard itisnoted thatfood labelling plays animportant roleinfurthering both ofthese objectives.
"4. When thesituation arises thatmembers ofCodex agree onthenecessary level ofprotection ofpublic
health buthold differing views about other considerations, members mayabstain from acceptance oftherelevant
standard without necessarily preventing thedecision byCodex."WT/DS26/R/USA
Page 43
"appropriatelevelofsanitaryorphytosanitaryprotection"as"[t]helevelofprotectiondeemedappropriate
bytheMember establishing asanitary orphytosanitary measure toprotect human, animal orplant
lifeorhealth within itsterritory", theUnited States submitted that"level ofprotection" referred to
protection from aparticular sanitary orphytosanitary risk.Forthelevel ofprotection toform thebasis
fortaking action, there must first beidentified some activity which gave risetotheidentified risk,
andtheactivity must present alevel ofsuch riskhigher thanthelevel deemed acceptable bytheMember.
4.88 TheUnited States submitted thatthelevel ofprotection didnotrefer toprotection from foreign
competition, nordiditrefer toprotection from aparticular substance oractivity perse,only from
theriskassociated with thatactivity. Thus, forexample, aMember might deem achance of1in1
million tobetheappropriate level ofprotection from theriskoftheestablishment ofaparticular plant
pest, or1in10million tobetheacceptable level ofriskofharm tonerves from theingestion oflead
infood. Incontrast, themeasures taken toachieve thatlevel could forexample, inthecase ofthe
plant pestrisk, involve quarantine toensure thepestwasnotharboured onimported plants orplant
material, orfumigation. Inthecaseofthenerve damage risk, themeasures could consist ofamaximum
residue limit forleadinfoods, oraprohibition ontheuseofleadinceramic glazes forfood utensils
such aspitchers orglasses. Finally, theUnited States agreed thatthechoice oftheappropriate level
ofprotection wasasocietal value judgment. TheSPSAgreement imposed norequirement toestablish
ascientific basis forthechosen level ofprotection because thechoice wasnotascientific judgment.
4.89 TheEuropean Communities responded thattheUnited States 'arguments were contradictory.
Itfollowed from these arguments thatfortheUnited States, theconcept of"measures" forthepurpose
oftheSPS Agreement included quarantine, fumigation orprohibition ontheuseofasubstance. In
criticizing theECformulation of"noresidue atall", theUnited States hadalsoadmitted thatthiswas
alsoameasure, notalevel ofprotection. However, theUnited States hadalsoargued thatanMRL
wasameasure. IfanMRL wasameasure, then what wasaprohibition laiddown inlawontheuse
ofhormones forgrowth promotion?
4.90 TheEuropean Communities noted thatthere were twoexceptions provided inArticle 3.3.
Thefirst exception wasfulfilled when theinternational standard wasinadequate, faulty orobsolete
from ascientific point ofview. According tothesecond exception, aMember wasinanycaseentitled
tointroduce ormaintain measures which aimed atachieving itsappropriate level ofprotection, tobe
determined inaccordance with Article 5oftheSPSAgreement. TheEuropean Communities agreed
thattoinvoke either oftheoptions inArticle 3.3,which were available toaMember when taking a
sanitary orphytosanitary measure ,there must exist "apotential riskforadverse effects". Butthe
SPS Agreement leftMembers freetodefine thelevel ofprobability theywanted toassume: thismight
range "from zero toinfinite" anditalsoleftthem freetodecide thetypeofmeasure theymight choose
toensure thatthelevel ofprotection they considered tobeappropriate wasachieved. TheEuropean
Communities further agreed thatthechoice oftheappropriate level ofprotection wasasocial value
judgement andthattheSPSAgreement didnotimpose arequirement toestablish ascientific basis for
thechosen level.
4.91 TheUnited States argued thatboth exceptions contained inArticle 3.3hadthesame effect,
since both referred toasituation where thebasis fordeparting from therelevant international standard
wasthattheinternational standard wasnotsufficient toachieve theMember 'sappropriate level of
protection. Theconcept oftheappropriate level ofprotection interlaid anumber oftheprovisions
oftheSPSAgreement. Forexample, Article 5.6used theappropriate level ofprotection todetermine
ifsanitary orphytosanitary measures were more trade-restrictive thanrequired. Article 3.3alsoused
thisconcept inpermitting aMember tointroduce ormaintain asanitary orphytosanitary measure that
wasmore stringent thantherelevant international standard where theinternational standard would not
besufficient toachieve theMember ’sappropriate level ofprotection. IntheUSview, none ofthe
different ECformulations forthepurported level ofprotection wasappropriate forpurposes ofthe
SPS Agreement. Forexample, ontheonehand, theEuropean Communities hadstated thatitsWT/DS26/R/USA
Page 44
appropriate level ofprotection was"theassurance thatmeat willnotcontain residues ofadministered
hormones". Elsewhere theEuropean Communities hadstated thatitslevel ofprotection wasthe
"guarantee thatECconsumers didnotingest residues ofadded hormones inmeat". Inyetanother
place, theEuropean Communities hadstated thatitslevel ofprotection was"noresidue atall".
4.92 TheUnited States argued thatthefirstformulation, "theassurance thatmeat willnotcontain
residues ofadministered hormones" wasnotalevel ofprotection from sanitary risk. Prohibiting certain
residues wasameasure ,notalevel ofprotection. This formulation saidnothing about whether those
residues posed arisk. Infact, theUnited States could only assume thatitwasamisstatement since
theEuropean Communities permitted hormones tobeadministered forherd management andother
purposes. Nordidthisformulation sayanything about howanyresidues from administered hormones
compared toother residues, such asresidues ofhormones thatwere naturally occurring inmeat. The
second formulation, "guarantee thatECconsumers didnotingest residues ofadded hormones inmeat",
suffered from thesame deficiencies andmisstatement asthefirstformulation. Thethird formulation,
"noresidue atall"wasalsoameasure, notalevel ofprotection. TheUnited States alsoassumed that
thisso-called "level ofprotection" applied only tothesynthetic hormones since meat would always
have residues ofthenaturally occurring hormones. Infact, theECmeasure wasnotarequirement
thatthere benoresidue ofthese substances. TheECmeasure wasabanontheuseofthesubstances
forgrowth promotion irrespective ofanyresidue.
4.93 TheEuropean Communities contended thatitwasobvious thattheEClevel ofprotection
inthiscase wasnoresidue ofadded hormones inmeat. This level resulted from theprovisions of
theECDirectives which prohibited theadministration tofarm animals, byanymeans whatsoever,
of"substances having athyrostatic action orsubstances having anoestrogenic, androgenic orgestagenic
action"; ortheslaughter orsaleofanyanimal towhich theabove-mentioned substances hadbeen
administered, orofthemeat ormeat products from such animals. Theaimofthese provisions was
toprotect human andanimal health byseeking alevel ofprotection which required thepresence of
noresidues inmeat. Incontrast, thelevel ofprotection ofCodex wastherecommended MRLs. The
European Communities noted furthermore thatitsmeasure applied notonly tothesixhormones in
dispute, buttoallhormones, substances andcombinations thereof which exerted theabove-mentioned
action onallfarm animals (i.e.notonly onbeefcattle). Conversely, theMRLs recommended byCodex
didnotexclude, when followed byaMember, thatthyrostatic, oestrogenic, androgenic andgestagenic
actions could beexerted onfarm animals. Moreover, theEClevel ofprotection wasconcerned only
with added hormones, over andabove those which occurred naturally; thereference tonatural levels
wasirrelevant tothiscase. Itsrulewere strict andavoided thepresence ofresidues inanimals treated
fortherapeutic orzootechnical purposes. SothefactwasthattheECrules didnotpermit residues
ofadded hormones atall.
4.94 TheUnitedStatesclaimedthattheECbanwasnotdesignedto,nordidit,achieveanyparticular
level ofprotection. Meat naturally hadwidely varying residues oftheendogenous hormones, and
many foods hadlevels ofresidues which were orders ofmagnitude greater thanthatfound inthebanned
meat (asshown inthefollowing tables).WT/DS26/R/USA
Page 45
Comparative androgen intakes
Food Weight ofportion (g) Androgen intake (ng)
Unimplanted bullmeat
Steer orfemale implanted w/trenbolone1
Heifer implanted w/testosterone500
500
5001,560
135-150
35
1Assuming 25percent fat,75percent muscle
ng=nanograms
Comparative oestrogen intakes from food sources
Food Weight ofportion (g) Oestrogen intake (ng)
Unimplanted steer meat1
Oestradiol-Implanted steer meat1
Zeranol-Implanted steer meat3
Cow meat1,2
Hen'segg
Cabbage
Peas
Wheat germ
Soybean oil
Milk500
500
500
500
50-60
100
100
10
10ml
500ml61.1
11.4
7*
75(7.2-540)*
1,750*
2,400*
400*
200*
20,000*
75*
E.g. 1eggequivalent inoestrogen content to76.5 kgofimplanted steer beef
1Assuming 25percent fat,75percent muscle
2Oestrone only
3Muscle tissue only
*Oestradiol equivalents
ng=nanograms
4.95 TheUnited States noted thattheEuropean Communities permitted thesaleandconsumption
ofmeat without regard tothelevels ofendogenous hormones; didnotregulate exposure tohormones
found inanyother foods, andfinally, permitted thesaleandconsumption ofmeat from animals that
hadreceived thenatural hormones forpurposes other than growth promotion. Ifthesupposed health
problem wasexposure toresidues ofanyofthese hormones, then theEuropean Communities should
regulate dietary exposure toresidues ofthenatural hormones. Forthesame reasons, theEuropean
Communities could notclaim thatitsappropriate level ofprotection was"zero", since if"zero risk"
wasintended torefer tothefivecategories ofriskidentified bytheEuropean Communities (discussed
inparagraph 4.126 below), thenachieving zeroriskwasimpossible. Forexample, twoofthecategories
referred tobytheEuropean Communities were risks arising from detection andcontrol (ormore
accurately arising from difficulty indetecting thepresence, orcontrolling theuse,ofthese hormones)
andrisks arising from theadministration anduseofhormones (ormore accurately from incorrect
administration ormisuse ofthese hormones). Inboth cases theactivity ofconcern totheEuropean
Communities wasalready illegal intheEuropean Communities andwith respect toexports tothe
European Communities. Asaresult, there wasnoreason tobelieve thatlifting thebanwould mean
thatthere would beariskthatwasnotnow already present. TheUnited States stated thatitwould
alsobeinterested intheECexplanation ofhow itcould guarantee thatthere wasazero probability
thatillegal activity would occur. TheUnited States argued thathistory (including thehistory ofthe
European Communities ’ownfailure toprevent illegal useofhormones byECproducers) showed that
itwasimpossible toguarantee thatthere wasazero probability thatillegal activity would occur.WT/DS26/R/USA
Page 46
4.96 TheEuropean Communities claimed thatitdidnotinsist on"zero risk"; itaimed toprevent
anyresidues. TheEuropean Communities have never claimed to"guarantee" a"zero probability that
illegal activity willnotoccur". There wasalways apossibility thatanycontrols would beevaded but
thatdidnotmean thatthecontrols should beabandoned. Forexample, there were measures inthe
United States which banned murder, andthesale ofheroin, butapparently these measures were
sometimesevaded.Thisdidnotmeanthatthemeasuresshouldbedropped.TheEuropeanCommunities
contended thatthesixth preambular paragraph oftheSPSAgreement made clear thatitdidnotrequire
Members tochange their appropriate level ofprotection orto"downward" harmonize them toless
stringent Codex sanitary andphytosanitary measures. Also Article 3.3clearly indicated thataMember
wasnotrequired toaccept international standards thatwould result inalower level ofprotection than
theMember haddetermined tobeappropriate. Under Article 3.2,ifasanitary orphytosanitary measure
conformed toarelevant international standard, itwasthen deemed tobenecessary toprotect human
health, andpresumed tobeconsistent with therelevant provisions oftheSPSAgreement andofGATT.
However, astheUSTR itself hadstated: "...thefactthatasanitary orphytosanitary measure differs
from arelevant international standard, guideline, orrecommendation does not,initself, create any
adverse presumption concerning thatmeasure" .72
4.97 TheEuropean Communities noted thattheapproach adopted bytheSPS Agreement wasin
conformity with previous GATT lawandpractice, andwasasensible approach forthepurpose of
establishing multilateral rules anddisciplines toguide thedevelopment andprogressive harmonisation
inorder tominimize thenegative effects ontrade from national sanitary andphytosanitary measures.
This approach wasalso inconformity with democratic regulatory procedures, where frequently a
dichotomy wasoperated inthedecision making process between riskassessment ,which established
strictly thescientific basis forregulatory action andriskmanagement which wastheprocess bywhich
thecompetent authority ofaMember decided what action totakeinthefaceoftheassessment submitted
toitbythescientists. Such action wasbased onfactors such aspublic health andenvironmental
protection, relevant legislation andlegal precedent, application ofsocial, economic andpolitical values
andconsumer concerns. TheEuropean Communities argued thattheriskmanagement phase, therefore,
inademocratic legislative system, expressly recognized theimportance ofsocial value choices.
4.98 TheEuropean Communities argued thatitsinterpretation ofthedisciplines theSPS Agreement
imposed onMembers wasapparently also supported bytheUnited States intheUSStatement of
Administrative Action, presenting totheUSCongress theresults oftheUruguay Round forapproval,
which stated asfollows:
"The S&P Agreement thusexplicitly affirms theright ofeach government tochoose itslevels
ofprotection, including a"zero risk" level ifitsochooses. Agovernment may establish its
levels ofprotection byanymeans available under itslaw, including byreferendum. Intheend,
thechoice oftheappropriate level ofprotection isasocietal value judgement .TheAgreement
imposes norequirement toestablish ascientific basis forthechosen level ofprotection because
thechoice isnotascientific judgement"73(emphasis added).
72USStatement ofAdministrative Action, p.92.
73USStatementofAdministrativeAction,point3(b).TheEuropeanCommunitiesnotedthatthisStatementusedtheexample
oftheso-called "Delaney clause" toillustrate thepoint :
"TheDelaney clauses areentirely consistent with theAgreement 'srequirement inthisregard. The
determination thataparticular substance poses ariskofcancer isascientific determination, based onanevaluation
ofthepotential forasubstance toinduce cancer. Based onscientific principles, theUnited States hasdetermined
thatifasubstance induces cancer inanimals, itposes some riskofhuman carcinogenesis. Andsince thelevel of
protectionunderDelaneyrequiresthattherebezeroriskofcarcinogeneses,theUnitedStatesprohibitsthesubstance."
(point 9).WT/DS26/R/USA
Page 47
Inanother public document alsosubmitted bytheUSTR toCongress itwasstated that:
"... therequirement forascientific basis applies toSPS measures ;itdoes notapply tothe
level offood safety thatthose measures aredesigned toachieve. TheSPSAgreement explicitly
recognizes theright ofgovernments tochoose thelevel offood safety thatthey consider
appropriate.
"...Moreover, byrequiring thatameasure bebased onscientific principles (rather than, for
instance, requiring thatameasure bebased onthe"best" science oronthe"weight ofevidence")
theAgreement recognizes thefact that scientific certainty israre and many scientific
determinations require ajudgement among differing scientific views. TheSPS Agreement
preserves theability ofgovernments tomake such judgments."
4.99 TheEuropean Communities argued thatthetable offoods such aspotatoes andLima beans
wasirrelevant. Inthefirstplace, consumers hadalways been exposed toacertain amount ofhormones,
orhormone-like substances intheir diet; humans evolved alongside them andcould cope with them.
This wasnotthecase foradded hormones. Secondly, thefigures inthetable were fictitious, inthe
sense thattheywere examples andmight bearlittle ornorelation tothesituation where growth hormones
were used inpractice. Thirdly, plant substances were notidentical totheanimal hormones (seein
thisregard thestatement ofoneoftheECscientific experts, Dr.Liehr, inthetranscripts ofthemeeting
of18February1997,paragraphs757-758.TheEuropeanCommunitiesalsoclaimedthatthecomparison
which theUnited States cited initstable wasincorrect because itcompared meat from atreated heifer
with meat from anuntreated bull.Thecorrect comparison (which hadbeen omitted inthetable) must
bewith anuntreated heifer (notbull). This comparison could befound inthe1995 ECScientific
Conference Proceedings (page 278, table 3):
-meat from untreated bull-1560ng;
-meat from untreated heifer -8ng;
-meat from treated heifer -35ng.
Thehuman dietnormally contained avariety ofmeat; evidently ifallthemeat came from treated
animals theamount ofhormone residue ingested would besignificantly increased (more than fourfold
ontheabove comparison). Ifaproper comparison were tobemade involving male animals, itwould
have tobebetween treated anduntreated males toseehow much thelevels offemale hormones were
increased inmale animals. According totheUSargument, heifer meat would be"within thenormal
range" ifitcontained asmuch testosterone asbullmeat.
4.100 TheUnitedStatesinsistedthattheUSStatementofAdministrativeAction(SAA)didnotsupport
theECban. TheUSposition inthisdispute wasfully consistent with theSAA. TheUnited States
explained thattheSAA wasacommunication between thePresident andtheCongress oftheUnited
States describing thePresident 'sinterpretation, andintentions with respect totheimplementation, of
theUruguay Round Agreements. Itwasnotadocument thatwasapplicable forpurposes ofthegenerally
accepted rules oftreaty interpretation embodied inArticle 31oftheVienna Convention ontheLaw
ofTreaties. Forexample, itwasnotpartofthetextoftheMarrakesh Agreement Establishing the
WorldTradeOrganization("WTOAgreement")norwasitaninternationalagreementmadeinconnection
with theWTO Agreement. However, theSAA confirmed theunderstanding oftheUSnegotiators
thatanSPS measure must bebased onscientific principles, have abasis inscience, bebased onan
assessmentoftherisks,andnotbemaintainedwithoutsufficientscientificevidence.Buttheseobligations
were clearly setforth intheSPSAgreement itself, which should beconstrued inaccordance with the
ordinary meaning tobegiven totheterms ofthatAgreement intheir context andinthelight ofits
object andpurpose. TheECbanfailed tomeet anyofthese obligations, andnothing intheSAA relieved
theEuropean Communities ofthose obligations. Incontrast, theSAA clearly reflected theUS
understanding thattheSPSAgreement fundamentally required anexamination ofwhether ameasureWT/DS26/R/USA
Page 48
wasadopted with abasis inscience andbased onariskassessment, rather than asaprotectionist
measure. TheUnited States noted thatthisdispute would nothave arisen iftheEuropean Communities
hadfollowed theSPSrules referred tointheSAA. TheEuropean Communities hadnotarticulated
itsappropriate level ofsanitary protection, norhaditbased itsbanonscientific grounds. Incontrast,
theSAA noted thatthedetermination thataparticular substance "poses ahealth riskismade onscientific
grounds". The United States consequently claimed that, forallthese reasons, theECbanwas
inconsistent with Article 3(and Articles 2and5)oftheSPS Agreement.
4.101 TheEuropean Communities responded thattheStatement ofAdministrative Action itself
explained thatit"represents anauthoritative expression bytheAdministration concerning itsviews
regarding theinterpretation andapplication oftheUruguay Round Agreements, both forpurposes of
USinternational obligations anddomestic law", andthatthe"Administration willobserve andapply
theinterpretations andcommitments setoutinit".When approved bytheUSHouse ofRepresentatives,
theSAA wassaid"tocarry particular authority". TheEuropean Communities concluded thattheSAA
wasahighlyinformativepieceofevidencewhichindicatedthewaytheSPSAgreementhadbeinterpreted
officially bytheUnited States intempore nonsuspecto .TheEuropean Communities didnotcontest
thatArticle 3.3required ascientific justification forthemeasures taken byaMember asaconsequence
ofthelevel ofprotection itdeemed appropriate. However, thefootnote toArticle 3.3confirmed the
prerogative which theSPSAgreement lefttoMembers tomake riskmanagement decisions thatreflected
social value choices distinct from thestrict scientific process ofriskassessment.74Thepurpose of
thefootnote toArticle 3.3wastoclarify what wasmeant by"scientific justification" inArticle 3.3,
nottodefine thejustification forchoosing alevel ofprotection. Thelevel ofprotection wasdecided
bytheMember alone anditwasnotajudgement thatmust bebased onscientific principles orscientific
evidence. The European Communities noted thattheSPS Agreement specified thatsanitary and
phytosanitary measures must be"necessary fortheprotection ofhuman, animal, orplant lifeorhealth",
must beapplied only totheextent necessary toprotect human, animal orplant lifeorhealth", must
not"arbitrarily orunjustifiably discriminate between Members where identical orsimilar conditions
prevail", must not"beapplied inamanner which would constitute adisguised restriction oninternational
trade", andmust notbe"more trade restrictive thanrequired toachieve [aMember 's]appropriate level
ofprotection, taking into account technical andeconomic feasibility". The application ofthese
requirements didnotaddress thescientific underpinnings foranational regulatory requirement. Instead,
these tests targeted thechoice bynational regulatory authorities among avariety ofpotential measures,
asdeterminedbysuchfactorsasimpactsoninternationaltrade,discriminatoryeffect,economicefficiency
andtechnical feasibility, andtherelationship between theregulatory goal andthemeasure chosen.
4.102 TheEuropean Communities further argued thatunder Article 13,national governments were
fully responsible fortheobservance oftheAgreement bysub-national governments. However, nothing
intheSPSAgreement required thatstate orlocal governments adopt, orcomply with, federal sanitary
orphytosanitary measures. Thereasons forthiswere twofold. First, because itwasquite possible
thatwithin asingle Member with federal constitutional structure there could exist different levels of
protection anddifferent types ofsanitary andphytosanitary measures. Second, theinability ofthe
federalgovernmentofthatMemberandoftheWTOdisputesettlementpanelstosubstitutetheirscientific
judgment forthatofthelocal government onthelevel ofprotection andthemeasures applied toachieve
itschosen level ofprotection. TheEuropean Communities claimed thatifsuch differences might exist
within onesingle Member, itwasobvious thatsuch differences were alsolikely toexist between different
Members with different perceptions ofwhat constituted risktopublic health.
74Footnote 2toArticle 3.3reads asfollows: "For thepurposes ofparagraph 3ofArticle 3,there isascientific justification
if,onthebasis ofanexamination andevaluation ofavailable scientific information inconformity withtherelevant provisions
ofthisAgreement, aMember determines thattherelevant international standards, guidelines orrecommendations arenot
sufficient toachieve itsappropriate level ofsanitary orphytosanitary protection".WT/DS26/R/USA
Page 49
4.103 TheEuropeanCommunitiesarguedthattheUnitedStatesattackednotonlythelevelofprotection
chosen bytheEuropean Communities, butalsoitsmeasures, byinsisting thatresidues ofhormones
above naturally present levels didnotpose anyrisktohealth and, therefore, didnotwarrant the
application ofanymeasures tocontrol them other than theMRLs recommended byCodex. Ifthis
argument were tobeaccepted, thenitwould inthefuture beopen toanycountry tooppose anyhealth
measure which wasbased ontheprecautionary principle. There were very fewexamples ofhealth
hazards where allscientists agreed onthedegree ofrisk, andcountries must beallowed tomake
judgments astowhat degree ofriskthey were willing toaccept. TheEuropean Communities argued,
bywayofexample, thatthere wasnoscientific proof thatbovine spongiform encephalopathy (BSE)
wastransmissible tohumans; there wasonly a"likelihood" based ontheappearance ofavery small
cluster ofhuman cases intheonly country with ahigh incidence ofthedisease incattle. Nevertheless,
theEuropean Communities (and most other countries) hadtaken severely trade-restrictive measures
toprotect public health asaprecaution, because ifBSE were transmissible tohumans theconsequences
would bedevastating.
4.104 With regard toMGA, theEuropean Communities noted thatitwasauthorized forgrowth
promotion only intheUnited States andCanada, butapparently nowhere else. Codex hadnever
scientifically examined thishormone andhadnever recommended anystandard. Still, theUnited States
inessence argued thattheEuropean Communities should accept meat treated with MGA andcheck
only forresidue limits asthey were setbytheUnited States .This argument flew inthefaceofthe
SPS Agreement, which explicitly allowed theEuropean Communities toadopt alevel ofprotection
which itdeemed appropriate (inthiscase, noresidue atall).
4.105 TheEuropean Communities insisted thattheUSposition inthiscase contrasted sharply with
thelegalpositionoftheUnitedStateswhenithadpresentedtheSPSAgreementtoCongressforapproval,
andwasdictated byshort-sighted economic interests (ofmaximum US$80 peranimal), regardless of
thedanger tohuman andanimal health posed bytheuseofthese hormones forgrowth promotion.
Allcountries, including theUnited States, regulated theuseofhormones infarm animals, andthe
difference between theEuropean Communities andtheUnited States inthisrespect wastheextent to
which their usewasregulated. TheEuropean Communities concluded thatthisdifference indegree
ofregulation wasareflection ofthedifferent levels ofconsumer protection adopted bytheEuropean
Communities andtheUnited States. TheEuropean Communities hadtaken aprecautionary approach,
placing theattainment ofahigh level ofconsumer protection before thecommercial interests offarmers
andpharmaceutical companies. Where there existed adoubt over thesafety ofaproduct, theEuropean
Communities gave thebenefit ofdoubt totheconsumer, especially incases where thepotential risks
might affect very large parts ofthepopulation. TheEuropean Communities claimed that, inthecase
ofgrowth hormones, theUnited States hadtaken anopposite approach, giving thebenefit ofdoubt
totheproducer. Itnoted thata1986 report onHuman/Food Safety andRegulation ofAnimal Drugs,
approved bytheUSHouse ofRepresentatives, hadconcluded that"theFood andDrug Administration
(FDA) hasconsistently disregarded itsresponsibility, because ithasrepeatedly putwhat itperceives
areinterests ofveterinarians andthelivestock industry ahead ofitslegal obligation toprotect consumers
thus jeopardizing thehealth andsafety ofcustomers ofmeat, milk andpoultry".75These criticisms
appeared equally valid inthepresent case.
4.106 TheUnited States rejected theECargument thatbecause there wasnoguarantee thatscience
would notonedayidentify ariskassociated with residues resulting from theuseofthesixhormones
forgrowth promotion purposes, theEuropean Communities were justified tousea"precautionary
approach" tobansuch use. Speculation thatsome daythere might beariskidentified, even ifthere
wasnone now, wasnotabasis forbanning something. Ifitwere, then Members could bananything.
Toinvoke theprecautionary principle, there stillmust besome scientific information indicating arisk,
75USCommittee onGovernment Operations, 27th Report, 99th Congress, 31December 1985.WT/DS26/R/USA
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notjustmere speculation, buttheEuropean Communities hadproduced nosuch scientific information
with respect totheir ban. Ontheother hand, toinvoke theexception ofArticle 3.3, theEuropean
Communities wasrequired tocompare itslevel ofprotection against thatafforded byameasure based
ontheCodex standard andshow thatitsbanwasaconsequence oftheEClevel ofprotection being
more stringent than thelevel achieved byuseoftheCodex standard.
4.107 TheUnited States alsostated thatthefinal sentence ofArticle 3.3provided, however, that
even ifArticle 3.3applied, themeasure atissue might notbeinconsistent with anyother provision
oftheSPSAgreement. Thus, Article 3.3waslimited only tojustifying adeparture from international
standards anddidnotjustify abreach ofanyother obligation arising under theSPSAgreement. As
aresult, thefactthattheECbanwasinconsistent with Articles 2and5oftheSPSAgreement meant
thattheECbanwasnotjustified under Article 3.3even iftheEuropean Communities could establish
thattheCodex standards would notachieve theECappropriate level ofsanitary protection.
4.108 TheEuropean Communities responded thatahazard (cancer) hadbeen identified andalack
ofscientific knowledge ontheexact mechanisms bywhich itarose wasnotasufficient excuse forfailing
totakestrict measures toprevent it.Article 5.7wasnotapplicable tothiscase because ECmeasures
were notbased oninsufficient knowledge andwere nottemporary. TheEuropean Communities knew
about thehazard andhadtaken measures toprevent it.Infact, there wasclear evidence, from IARC,
JECFA andothers, thatthese hormones were carcinogens. They posed ariskandtheEuropean
Communities wastherefore justified inacting. There wasnotenough scientific evidence toconclude
thatthese hormones, particularly when used byfarmers without anyofficial control, didnotpose a
risktohuman health. TheEuropean Communities added thatinternational standards, guidelines or
recommendations were based onacertain concept oflevel ofsanitary protection. Butadifferent level
might require different type ofmeasures. This waswhat theEuropean Communities applied inthe
case ofthese hormones: toachieve itslevel ofprotection, theonly reasonably available andless
restrictive measure wastoapply aprohibition ontheuseofthese hormones forgrowth promotion.
TheCodex recommendations were designed toachieve alevel ofprotection which waslower than
thatapplied intheEuropean Communities.
(e) Articles 5.1and5.2oftheSPS Agreement
4.109 TheUnited States recalled thatArticle 5.1reads asfollows:
"Members shall ensure thattheir sanitary orphytosanitary measures arebased onanassessment,
asappropriate tothecircumstances, oftherisks tohuman, animal orplant lifeorhealth, taking
intoaccount riskassessment techniques developed bytherelevant international organizations".
TheUnited States claimed thatthecentral concept underlying theSPS Agreement was"risk". With
limited exceptions notapplicable tothisdispute, agovernment must scientifically demonstrate the
existence ofanidentified risktothelifeorhealth ofhumans, animals orplants resulting from aspecific
activity before thatgovernment could impose ormaintain asanitary measure. While theSPS Agreement
didnotdefine "risk" assuch, itdefined "risk assessment" with respect tofood safety as"theevaluation
ofthepotential foradverse effects onhuman oranimal health arising from thepresence ofadditives,
contaminants, toxins ordisease-causing organisms infood, beverages orfeedstuffs" (Annex Aofthe
SPSAgreement). TheUnited States concluded that, asaresult, inthecontext ofthepresent dispute
"risk" consisted ofthe"potential foradverse effects onhuman health" arising from thepresence in
meat ofresidues resulting from theadministration toanimals ofanyofthesixhormones forgrowth
promotion purposes.
4.110 The United States claimed thattheEuropean Communities hadnever performed anyrisk
assessment, orrelied onanyriskassessment, thatcould serve asabasis foritsbanwith respect to
thesixhormones. Ifthere wasnoriskfrom asubstance, then itcould notbesaidthatasanitary orWT/DS26/R/USA
Page 51
phytosanitary measure wasnecessary toprotect against ariskposed bythesubstance. Bydefinition,
inorder tobealegitimate "sanitary" measure, ameasure must protect against oneormore specified
risks.TheUnitedStatessubmittedthattheremarkablecharacteristicofthepublicdebateintheEuropean
Communitiesonthesehormoneswasthatthe“risk”wasusuallydescribedintermsofconsumeranxieties
rather than anyobservable adverse effect onhuman health. During theconsultations, theEuropean
Communities hadfailed toidentify anyspecific risktohuman oranimal lifeorhealth against which
thebanwasdesigned toprotect. Ontwooccasions, theEuropean Communities hadformed groups
ofscientists toexamine thesafety ofthehormones (excluding MGA), butboth theLamming Group
convened in1982 andthe1995 ECScientific Conference hadconcluded thatthese hormones were
safewhen used forgrowth promotion purposes inaccordance with good animal husbandry practice.
TheUnited States submitted thattheEuropean Communities hadfailed toidentify ariskassessment
onwhich itsbanwasbased and, while suggesting thatariskassessment (orriskassessments) hadbeen
performed by"scientific groups and/or conferences" orby"groups ofexperts established bytheEC
member States andtheEuropean Communities", they hadfailed toprovide thetime orplace ofany
such risk assessment, thenames ofthescientists who hadconducted theriskassessment, orthe
documentary evidence oftheresults. Furthermore, although theEuropean Communities hadargued
before thePanel thatthere wasnewscientific evidence nowavailable, theEuropean Communities had
notrelied onanyofthestudies ofthescientific experts whom itclaimed hadnewordiffering evidence
when itintroduced thebanin1989, norwhen ithadpromulgated itsnewDirectives in1996. Indeed,
theEuropean Communities hadapparently notconsulted anyofthose scientists until itwaswell into
aWTO dispute settlement proceeding toreview itsban. Arisk assessment bytheEuropean
Communities 'own regulatory scientists hadnever been produced.
4.111 TheUnited States claimed thattheEuropean Communities could notjustassert thatthere was
ariskassociated with these sixhormones when used forgrowth promotion andthenprohibit their use.
Article 5.1required thataMember base asanitary measure onanassessment oftherisks tohuman
oranimal lifeorhealth. TheEuropean Communities hadfailed toproduce anything resembling an
assessment oftherisks thatwould form thebasis foritsban. TheEuropean Communities hadinfact
rejected every scientific review ofthesixhormones andhadbeen unable toproduce anyscientific risk
assessment ofthese hormones thatitdidaccept. Itwasimportant todistinguish between having arisk
assessment, andbasing ameasure onthatriskassessment. This wasnotasituation inwhich there
wasnoriskassessment. Tothecontrary, theEuropean Communities certainly hadriskassessments
available foritsuse.
4.112 TheUnited States noted thatduring theArticle XXIII consultations, theEuropean Communities
hadstated thattheriskassessment onwhich ithadbased itsbanwasthereport ofthe1995 ECScientific
Conference. Subsequently, theEuropean Communities hadindicated thatthe1995 ECScientific
Conference "was nottoperform foritariskassessment, buttoprovide apublic forum fordiscussion
ofthescientific aspects oftheuseofgrowth promoters", astatement which concurred with theUS
view oftheConference. Inanycase, theUnited States argued thatthe1995 report failed tosatisfy
therequirements ofArticle 5.1inatleast twokeyways: first, the1995 ECScientific Conference
hadfound thatthefivehormones itreviewed were safeforuseasgrowth-promoting hormones and
thatthere wasnobasis forbanning animals, ormeat from animals, towhich these hormones hadbeen
administered forgrowth promotion; andsecond, the1995 ECScientific Conference hadnotlooked
atallsixhormones -ithadnotdiscussed MGA. Accordingly, itcould notconstitute ariskassessment
forMGA. Infact, the1995 ECConference didnotappear tohave actually performed ariskassessment
onanyofthehormones; itsimply "discussed thesafety assessment" ofthefivehormones. The
United States contended thatinthecase ofthesixhormones, since theEuropean Communities had
failed toestablish through anassessment oftherisks thatthere wasinfactanyidentifiable riskposed
bythese hormones, there wasnobasis fortheECbanontheimportation ofanimals towhich hadbeen
administered these hormones ormeat from those animals. TheUnited States consequently claimed
thattheECbanwasnotsupported byanassessment ofriskandwasconsequently inconsistent with
Article 5.1.WT/DS26/R/USA
Page 52
4.113 TheEuropeanCommunitiesrespondedthatCodexhadnotdevelopedriskassessmenttechniques.
Intheabsence ofsuch international guidelines, each Member must apply itsown methodology. That
followed bytheEuropean Communities was, andhadbeen throughout theconsideration ofthehormone
issue, toobtain thebestscientific information available, tohave thatinformation evaluated bytechnical
experts andfortheECCommission tomake aproposal based onanassessment ofthatscientific and
technical advice. Inassessing theadvice anddrawing upitsproposals, theEuropean Communities also
tookaccount ofthefactors setoutinArticle 5.2,including "relevant processes andproduction methods".
Livestock production intheEuropean Communities andinmost ofthecountries which exported to
theEuropean Communities wascharacterized bylarge-scale intensive production inafreemarket.
Ifproducers were atliberty toadminister hormone growth promoters attheir owndiscretion there was
aconsiderable riskthatmistakes andmisuse would occur. There wasnoguarantee thatthecorrect
products ordoses would always beused orthatanimals would beinjected orimplanted inthecorrect
site. There wasalso ariskthatanimals would beslaughtered forhuman consumption soon after
treatment if,forexample, themarket price suddenly became favourable. Article 5.2alsorequired
Members totakeintoaccount "relevant inspection, sampling andtesting methods". Duetothescale
oflivestock production, itwasnotpossible tocarry outregular inspections oflivestock holdings to
check thatuniversally available growth promoters were being used properly. Sampling andtesting for
these substances wasextremely expensive andtime-consuming and,inthecaseofsubstances analogous
toendogenousnaturalhormones,itmightbedifficulttodistinguishmarginalcasesofmisuse.Moreover,
there wasnothing inthetextofthecontested measures, thelegislative history orinanyother document
tosuggest that"consumer anxieties" wasthepurpose forwhich themeasures were adopted, although
itwaslikely thatconsumer concerns hadbeen taken intoconsideration during the"risk management"
phase, since consumer concerns onpotential risks tohuman health resulting from theuseofhormones
were very high atthattime (and theywere even higher today). There waslittle question thatconsumer
concerns about safety andother issues alsoinfluenced theUSagencies 'decisions, even where there
wasarguably little, ifany, basis forthose concerns.
4.114 TheEuropean Communities argued thatithadconsidered anumber ofscientific reports and
judgements regarding thepotential risks from thehormones atissue. Aspreviously indicated76,this
included:
(i) the1982ReportoftheScientificVeterinaryCommittee,ScientificCommitteeforAnimal
Nutrition andtheScientific Committee forFood onthebasis oftheReport ofthe
Scientific Group onAnabolic Agents inAnimal Production (theLamming Report);
(ii) the1983 OIE Scientific Conference Report;
(iii) the1988 JECFA Report;
(iv) thevarious works ofrelevant international institutions, such astheInternational Agency
forResearch onCancer (IARC);
(v) thescientific works byindividual scientists relevant totheissue ofuseofhormones
ingeneral andforanimal growth inparticular;
(vi) information ontheuseofthese hormones forgrowth promotion available from other
countries, when relevant.
Fortheadoption ofDirectives 81/602/EEC, 88/146/EEC and92/22/EC, apart from theabove scientific
evidence, additional technical information hadbeen taken intoaccount. This information consisted
76Seeparas. 4.28-4.29.WT/DS26/R/USA
Page 53
mainly oftheinternal studies oftheECCommission, thereports oftheEuropean Parliament, thereports
oftheEconomic andSocial Committee andthedeliberations oftheCouncil ofMinisters. Fortheir
deliberations, theMinisters were assisted byscientific groups andindividual scientific experts, including
experts from therelevant administrations oftheECmember States. Fortheadoption ofDirective 96/22
of29April 1996, the1995 ECScientific Conference Proceedings hadalsobeen taken intoaccount.
4.115 TheEuropean Communities submitted thatithadbased itsmeasures ontheriskassessment
ithadconducted forthatpurpose. Neither the1982 Lamming Report, northe1988 JECFA Report
constituted inthemselves "risk assessment" inthesense ofArticles 5.1to5.6oftheSPSAgreement.
They only formed partof"available scientific evidence." Theother factors mentioned inArticle 5.2,
andinparagraphs 3to6thereof, were notdealt with bythose scientific reports onwhich the
United States hadbased itsclaim. Theassessment ofthese factors wasnotascientific question in
thestrict sense, andthus they fellwithin theresponsibility oftheappropriate political authorities of
each Member.
4.116 TheEuropean Communities further argued thatthe1988 JECFA Report hadfound thatthere
wasapotential risktohuman health because ifthere were nosuch potential risk, theJECFA would
nothave recommended anyADI andMRL forthetwosynthetic hormones. Forthethree natural
hormones, JECFA hadnotrecommended anADI andMRL because ofproblems indetecting thelevel
ofresidues inthemeat onaroutine basis. Moreover, the1988 JECFA Report, apart from being deficient
inseveral respects from thescientific point ofview, hadnotperformed a"risk assessment" inthesense
ofArticle 5.Allithaddone wasto"evaluate thesafety ofhormones used forgrowth promotion".
This evaluation wasnotaproper riskassessment forthepurposes ofArticle 5,since itdealt only
withoneoftheelements required byArticle 5.2,i.e.itformed partofthe"available scientific evidence"
butdidnotconstitute theonly relevant scientific evidence available. Inaddition, itdidnottakeinto
account relevant process andproduction methods, relevant inspection, sampling andtesting methods
andrelevant ecological andenvironmental conditions, asrequired byArticle 5.2. Even iftheEuropean
Communities wastoassume thattheydid(quod non), stilltheEuropean Communities considered that
Article 3.3explicitly permitted ittoadopt alevel ofsanitary protection itdetermined tobeappropriate
initsterritory. TheEuropean Communities added thatithadexplained inthescientific opinions which
ithadsubmitted tothePanel andinthemeetings of17and18February several defects ofthe1988
JECFA Report from thescientific point ofview, inparticular theso-called hormonal effect level at
which these hormones considered tobecarcinogenic, itsfailure tosetADI values forthethree natural
hormones anditsincorrect figures cited forthedaily production ofoestradiol-17 forprepubertal boys.
(See transcript ofthemeetings with scientific experts, paragraphs 315-318. Seealsoparagraph 740
with regard toprepubertal boys).
4.117 TheEuropean Communities claimed thatanother point where theJECFA Report wasdeficient
related tothequestion whether ADI (and consequently MRL) values could evebefixed forthethree
natural hormones. The European Communities referred toanofficial letter which theEuropean
Communities received from theUSGovernment in1988, where itwasstated thattolerance levels were
setintheUnited States even forthethree natural hormones, butmeat would notbemonitored for
residues. TheEuropean Communities further claimed thatasDr.Lucier hadargued on18February,
ADIscouldhavebeenestablishedinthe1987JECFAReport.Buttheyhadnotbeenestablishedprecisely
because thescientific approach ofJECFA wastoexamine only thehormonal effect levels ofthese
hormones, because only atsuch levels were they supposed byJECFA scientists tobecarcinogenic.
Butthislineofargument hadbeen shown tobeincorrect oratleast there wasasubstantial partof
thescientificcommunitywhichdidnotagreewiththisview(seealsoparagraphs469-479ofthetranscript
ofthe17February meetings with scientific experts) TheEuropean Communities added thatinthis
case thequantification oftheriskwassaidbyDr.Lucier, oneofthescientific experts advising the
Panel, torange between 0and1peronemillion. This wastheminimum riskfrom theuseofthese
hormones inaccordance with good veterinary practice .TheEuropean Communities argued thatthis
riskwould certainly behigher ifgood veterinary practice wasnotrespected, andwould beeven muchWT/DS26/R/USA
Page 54
higher ifsynergistic andlong-term exposure risks were taken intoaccount. (See thestatement of
Dr.Lucier inthisregard inparagraph 742ofthetranscript ofthe18February meetings with scientific
experts. Seealsotheopinion ofDr.Epstein, ascientist advising theEuropean Communities, inthe
case ofprepubertal boys inparagraph 214. Asregards thequantification oftheriskofcancer, the
European Communities also drew theattention ofthePanel totheopinion ofthePanel expert,
Dr.Lucier, reflected inparagraphs 6.110 and6.111, aswell astotheopinion ofDr.Liehr, anEC
scientist, inparagraph 330ofthe17February meeting with thescientific experts.
4.118 TheEuropean Communities noted inthisregard thatscientists hadsaidthat"theADI-model
isnotariskmodel anddoes notpredict theriskoftheoccurrence ofadverse effects, when ADI-values
areexceeded".77Thesame wasbasically truefortheMRL-model, "which specifies thequantity of
aparticular residue inmeat that, even indietary extremes, would notexceed theADI fortheparticular
substance concerned".78TheEuropean Communities concluded thattheMRL wasbased onthenotion
thatthere wasarisk, butiftheproposed threshold wasobserved theprobability oftheadverse effect
arisingfromtheuseofhormoneswouldnotmaterialize.Inthiscase,theJECFArecommendedstandards
which would achieve "alevel ofprotection" against therisk. ButtheSPS Agreement allowed Members
todetermine another level, i.e.thelevel theydeemed appropriate. This level might behigher orlower.
TheEuropean Communities argued thatalltheabove scientific data, reports, papers, conferences and
other relevant information constituted abody ofscientific evidence which wascarefully considered
bythecompetent ECinstitutions andtheECmember States.
4.119 TheEuropean Communities claimed thatthere were substantial differences inthearguments
notonlybetweentheEuropeanCommunitiesandtheUnitedStatesandCanada,butalsointhearguments
between Canada and the United States. Canada had argued on19February that the
European Communities didnothave anyofthescientific evidence presented tothepanel bythescientists
advising theEuropean Communities inthiscase, when itdecided toperform ariskassessment. Canada
saidthattheEuropeanCommunitieshaddiscoveredthisscientificevidencesomeweeksearlier,searching
foranexpostfactojustificationofthemeasuresithadtakenbefore.TheEuropeanCommunitiesclaimed
thatthisargument ofCanada wasnotcorrect anddidnotcorroborate with what theUnited States had
said, because astheUnited States hadexplained thattheviews ofDr.Liehr were already mentioned
twice inthe1988 JECFA report (footnotes 34and35). Dr.Liehr wasalsomentioned inthe1995
ECScientific Conference Proceedings (e.g., atpage 386). Theviews ofDr.Liehr were therefore
known totheEuropean Communities before, andwere notdiscovered some weeks earlier asCanada
hadargued. Thework ofalmost allofthescientists thatprovided advice totheEuropean Communities
inthese disputes were aware totheresponsible ECauthorities, such asthework ofDr.Epstein and
Dr.Hertz whowere mentioned inthebook ofOrville Schell of1985, Dr.Liehr wasalready mentioned
inthe1988 JECFA Report andinthe1995 ECConference, Dr.Metzler whohasbeen doing research
inthisarea since along time andDr.Adlercreutz.
4.120 TheEuropean Communities saidthatthereason why theUnited States hadnever requested
Codex toseta"standard" forMGA wasthatMGA waspossibly even more dangerous than theother
fivehormones. TheEuropean Communities noted thattheUnited States applied aso-called "safety
factor" of200, instead oftheusual 100, andargued that, apart from itscarcinogenicity, MGA exerted
amore powerful progestagenic effect thanprogesterone. Itsprincipal usewasinfattening heifers which
were kept under abnormally intensive conditions andcould injure themselves ortheir inexperienced
handlers when theycame intooestrus andstartmounting eachother. MGA, although notaveryeffective
growth promoter, wasvery effective atsuppressing oestrus andwasadded tothefeedmainly forthis
purpose. Although ithadawithdrawal period, there wasastrong incentive onthehandlers notto
observe itsince theheifers would startcoming intooestrus before going toslaughter. Itwas, therefore,
77H.A. Kuiper, "Risk Assessment Strategies forXenobiotics", 1995 ECScientific Conference Proceedings, p.375.
78"Report andConclusions", 1995 ECScientific Conference Proceedings, p.4.WT/DS26/R/USA
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probable thatmeat from heifers regularly contained significant residues ofthispowerful sexhormone.
TheEuropean Communities alsoclaimed thatasregarded oestrogens, progestins andcombinations
thereof (i.e. mainly oestradiol-17 ,progesterone andMGA), the1987 IARC Report explained that
"Steroid hormones areessential forthegrowth, differentiation andfunction ofmany tissues inboth
animalsandhumans.Ithasbeenestablishedbyanimalexperimentationthatmodificationofthehormonal
environment bysurgical removal ofendocrine glands, bypregnancy orbyexogenous administration
ofsteroids canincrease ordecrease thespontaneous occurrence oftumours ortheinduction oftumours
byapplied carcinogenic agents ....Theincidence oftumours inhumans could bealtered byexposure
tovariousexogenoushormones,singlyorincombination"(emphasisadded).TheEuropeanCommunities
further claimed thattheUnited States wasoffering asolution tosafeguard against thepotential risk
tohuman health from theuseofthese hormones forgrowth promotion which theEuropean Communities
hadconsidered carefully andrejected, because itdidnotmeet itsappropriate level ofprotection. It
stressed thatthehormone MGA wasauthorized forgrowth promotion onlyinUnited States andCanada,
butapparently nowhere else. Codex hadnever scientifically examined thishormone andhadnever
recommended anystandard. Still, theUnited States inessence argued thattheEuropean Communities
should accept meat treated with MGA andcheck only forresidue limits astheywere setbytheUnited
States .TheEuropean Communities submitted thatthisargument contradicted theSPS Agreement,
which explicitly allowed theEuropean Communities toadopt alevel ofprotection which itdeemed
appropriate (noresidue atall).
4.121 TheEuropean Communities argued thattheLamming Committee hadnotconsidered itself
competent tomake recommendations totheEuropean Commission ontheconditions under which these
hormones could beallowed tobeused forgrowth promotion purposes. This showed thattheLamming
Committee could notbeconsidered competent toperform arisk assessment fortheEuropean
Communities inthesense ofArticle 5,because riskassessment could only beperformed bythe
governments ofMembers. TheLamming Committee hadnotprovided anything other than scientific
advice, which theresponsible ECinstitutions hadused aspart oftheavailable scientific evidence in
their riskassessment. TheEuropean Communities further argued thattheUSclaim thattheEuropean
Communities stated during theconsultations thatitbased its"ban" onthe1995 ECScientific Conference
wasclearly wrong. Asthepurpose ofthe1995 ECScientific Conference wasnottoperform forit
ariskassessment, buttoprovide apublic forum fordiscussion ofthescientific aspects oftheuseof
growth promoters, thereference toArticle 5.1andrelated comments were irrelevant aswell as
inaccurate.
4.122 TheUnited States claimed thattheCodex riskassessment andother scientific reviews stood
insharp contrast totheECpurported riskassessment. YettheEuropean Communities took thecurious
position thattheCodex andother scientific reviews were not"risk assessments" forpurposes ofthe
SPSAgreement because they didnot"constitute theonly relevant scientific evidence available". The
United States argued that, first, under theSPSAgreement, ariskassessment wasto"take intoaccount"
available scientific evidence (Article 5.2); itwasnotsupposed to"constitute" scientific evidence.
Second, theEuropean Communities suggested thatCodex hadnottaken intoaccount alltheelements
listed inArticle 5.2,without explaining why elements which were omitted would berelevant tothe
riskassessment. Yettheelements listed bytheEuropean Communities were taken intoaccount by
Codex, asreflected intheCodex definition ofanMRL. TheUnited States observed thattheexperts
advising thePanel confirmed thatthere wasnoscientific basis fortheECrefusal tousetheCodex
standards asabasis fortheECmeasures. Third, under Article 3.2,measures thatconformed toCodex
standards were presumed tobeconsistent with therelevant provisions oftheSPSAgreement. This
would include Articles 5.1and5.2,sothattheCodex riskassessment might bepresumed under the
SPSAgreementtobeconsistentwiththoseArticles.Fourth,theECapproachwastoselectivelymisquote
parts ofvarious riskassessments while ignoring theconclusions ofthose riskassessments aswell as
those portions andthescientific evidence thatdidnotsupport itsban. TheEuropean Communities
didnotexplain how thisapproach ofselectively ignoring thescientific evidence could beconsidered
totakeintoaccount therelevant scientific evidence. Furthermore, theEuropean Communities couldWT/DS26/R/USA
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notestablish thattheCodex standards would notachieve theECappropriate level ofsanitary protection.
TheEuropean Communities hadsuggested thatithadadopted "zero risk" astheappropriate level of
protection, andthis"zero risk" level would justify itsmeasures under Article 3.3. TheUnited States
submitted thatan"appropriate level ofsanitary protection" wasalevel ofprotection from ariskand
thattheEuropean Communities hadnotidentified anyparticular riskfrom these hormones, which were
allsafe.
4.123 TheEuropean Communities claimed thatitwasnotrequired toaccept only thetwoscientific
reports which theUnited States contended hadcarried outaproper riskassessment, i.e.theLamming
Report andtheCodex assessment. These were justtworeports ofacertain scientific orientation, but
there were other scientific reports byindividual scientists, scientific conferences, (e.g. the1995 EC
Scientific Conference) andresponsible international institutions (eg.IARC) which didnotentirely agree
with them. Some ofthescientific reports onwhich theEuropean Communities hadbased itsmeasures
questioned thevery basic scientific assumptions onwhich thereports supported bytheUnited States
were founded, including thecarcinogenic effects ofthese hormones when used foranimal growth
promotion.TheECscientificevidencewasthereforeconstitutedbythescientificstudieswhichconcluded
thatthese hormones could becarcinogenic irrespective ofthedose administered because theymayalone
orincombination be"genotoxic" (i.e. actdirectly onthegenome tocause cancer). TheEuropean
Communities added thatthiswasexactly what some scientists hadfeared forthehormone DES. It
hadwarned theUSauthorities atanearly stage, butthose authorities hadfailed topayattention in
time.79Moreover, thesanitary policy oftheEuropean Communities onthese hormones foranimal
growth promotion purposes wasexactly thepolicy pursued bytheUnited States under theso-called
Delaney Clause fordangerous food additives.
4.124 TheEuropean Communities noted thatthe"Delaney Clause" wasthemost notable example
oftheadoption bytheUnited States ofazero-risk policy. Enacted in1958 inthecontext ofpublic
fearoverthegrowing incidence ofcancer, theDelaney Clause provided that"noadditive shall bedeemed
tobesafeifitfound toinduce cancer when ingested bymanoranimal."80TheDelaney Clause required
thatallcarcinogenic food additives bebanned, regardless oftheir degree ofriskoroffsetting benefits.
TheDelaney Clause hadbecome anincreasing burden toregulatory agencies since itspassage in1958.
Thescientific methods available then didnothave thesensitivity oftoday 'stechnology, which could
detect minimal carcinogenic effects orminimal "migration" ofsubstances from packaging materials
tofood. TheDelaney Clause therefore banned chemicals with insignificant carcinogenic properties,
withoutpermittingagenciestoconducttheusualrisk/benefitanalysisemployedwhenconsideringapproval
ofnewsubstances. TheUnited States had-with only modest exceptions -aninflexible, zerotolerance
policy forcarcinogenic substances added tothefood supply. Nomatter what itsconcomitant benefits,
asubstance having apossible carcinogenic effect could notbeapproved asafood additive.
79TheEuropean Communities explained thatDiethylstilboestrol (DES) wasasynthetic hormone which improved both
rateofgainandfeedefficiency inpoultry, cattle andsheep. DES wasperhaps themost widely known ofoestrogenic growth
promoting agents. Itwasfirstused intheUStherapeutically inpregnant women inthe1940 'stoprevent abortion. TheUS
Government approved itsuseasafeed additive forpoultry in1947, forcattle in1954 andlater forsheep. In1971, its
carcinogenic effects inhumans andinlaboratory animals wasclearly established. Additional studies showed thatDES had
other effects ondaughters andsons ofmothers treated with it,themost common being vaginal adenosis andother gross
abnormalities ofthereproductive tract. Atthetime (1976) these studies were published, anestimated 25million cattle and
7million sheep were being treated withDES. Still, itscomplete withdrawal from theUSmarket wasachieved only in1978,
while inthemeantime theUSFDA wastrying todiscover andfixacceptable "noresidue" limits.
8021U.S.C. §348(c)(3)(A). TheEuropean Communities noted thattheDelaney Clause alsoapplied tocolour additives
(U.S.C. §379e(b)(5)(B)) andcompounds administered tofood-producing animals (21U.S.C. §360b(d)(1)(I)). On
3August 1996, newlegislation hadbeen enacted which changed USregulation ofpesticides andencouraged international
harmonization ofpesticide tolerances (Food Quality Protection Actof1996, Pub. L.No104-170). This newlegislation did
notaffect food additives other thanpesticides residues. Thus, theDelaney Clause stillgoverned theregulation byFDA of
food additives andcompounds administered tofood-producing animals.WT/DS26/R/USA
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4.125 TheEuropean Communities argued thatnone ofthescientific reports theUnited States had
cited hadconcluded infavour ofanunqualified useofthese hormones foranimal growth promotion.
Allthese reports hadconcluded thatallthese hormones individually were potentially dangerous tohuman
andanimal health ingeneral aswell aswhen used forgrowth promotion purposes andthatallthese
hormones individually were notlikely topose risks tohuman oranimal health onlyifused inaccordance
with good agricultural/animal husbandry/veterinary practice. Moreover, the1982 Lamming Report
andthe1988 JECFA Report hadnotexamined thepotential risks arising from these hormones when
used incombination with other hormones, and had not explained what constituted good
agricultural/animal husbandry practice.
4.126 TheEuropean Communities contended thatavailable scientific evidence showed theuseofthe
natural andsynthetic hormones subject tothisdispute could bedangerous tohuman andanimal health.
Thepotential danger resulted from (i)their nature andmode ofaction; (ii)theaction oftheir metabolites;
(iii)combinationsofhormonesandmultipleexposure;(iv)problemslinkedtotheirdetectionandcontrol;
and(v)problems linked totheir administration. Insubmitting itssupporting arguments, theEuropean
Communities indicated thatitfocused onthepotential risks tohuman beings, butthatthisdidnotimply
thatthere were norisks foranimal health.
(i) Nature andmode ofaction ofthehormones
4.127 The European Communities claimed thateven though theprecise mode ofaction ofthe
hormones atissue hadonly been partly understood, allscientists agreed thatthese hormones were
dangerous. Theprinciple sexhormone inmen, testosterone, contributed toacne, baldness, prostatic
disease, coronary heart disease andpeptic ulceration. Oestrogens, andtoalesser extent progesterone,
exposed women topremenstrual tension, dysmenorrhoea, some disorders ofthereproductive system
andanincreased tendency todevelop gallstones. More importantly, these hormones alsoplayed a
major roleinthedevelopment oftumours insex-hormone dependent tissues (forexample prostatic
cancer, breast cancer, cancer oftheuterus andneoplastic liver disease).
4.128 TheEuropean Communities noted thatthecarcinogenic risks from these hormones waswell
known. Forinstance, inthe1983 OIE Scientific Report ascientist hadconcluded that"although it
isunlikely thatthesmall amounts ofanabolic steroids which might beingested inagricultural produce
could (cause cancer), thispossibility should notbeignored entirely". Moreover, thesame 1983 OIE
Scientific Report stated that: "...However, aspointed outbyWilliams, theinitiation-promotion concept
does notadequately explain allcarcinogenic mechanisms. Therefore, itisnotpossible tostate with
anycertainty thatanabolic steroids actonly aspromoters ininduction ofcancers inother hormone
dependent tissues such asprostate, uterus andbreast, although present evidence suggests thatlevels
ofendogenous steroids areprobably notsufficient toinitiate carcinogenesis inthose tissues" (emphasis
added).
4.129 TheEuropean Communities further noted thatthecarcinogenic effects ofhormones onhumans
(and animals) hadbeen documented byseveral reports oftheInternational Agency forResearch on
Cancer (IARC). IARC hadclassified steroidal oestrogens (including oestradiol) inGroup 1,meaning
theagent wascarcinogenic tohumans; androgenic (anabolic) steroids (including testosterone) in
Group 2.A, agents probably carcinogenic tohumans andprogestins inGroup 2.Boragents possibly
carcinogenic tohumans.81A1987 IARC Report indicated that, inthecase ofandrogens:
"The factthatcastration palliates prostatic cancers suggests thattestosterone may beinvolved
inthegenesis ofthese tumours, andanumber ofepidemiological observations suggest that
increased testosterone levels may increase theriskforprostatic cancer" (page 96). ...The
81IARC Monographs, Supplement 7,pp.31, 96and280(1987).WT/DS26/R/USA
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evidencethatanabolicsteroidscancausebothbenignandmalignantlivertumoursisquitestrong.
However, because noanalytical epidemiological study hasbeen done, theWorking Group felt
constrained toclassify theevidence forcarcinogenicity inhumans asnomore than "limited"
(page 97).
TheEuropean Communities noted that, according tothesame IARC Report, inthecaseofoestrogens,
however, theevidence wasclear:
"Anumber ofstudies, utilizing avariety ofdesigns, have shown aconsistent, strongly positive
association between exposure toanumber ofoestrogenic substances andriskofendometrial
cancer ,with evidence ofpositive dose-response relationships both forstrength ofmedication
andduration ofuse" (page 280).
TheEuropean Communities added thatinarecent article published inthereview Science82,theauthor
argued thatoestrogen 's(natural hormone) mode ofaction may bedifferent from what itwasthought
tobeuntil now:
"...while itisstilltooearly totelljusthowmany alternate paths there are,other recent results
arefurther undermining theidea thatthere isasingle main pathway foroestrogen action."
4.130 TheEuropeanCommunitiesassertedthatthescientificassumptionthat,despitetheircarcinogenic
potential,thesehormoneswerenotlikelytocauseproblemstohumanhealthwasbasedontheassumption
that"thecarcinogenic effect ofthese hormones isrelated tothehormonal activity ofthese compounds,
i.e.anincrease intumour incidence intissues ofanimals with highlevels ofspecific hormone receptors,
which would notoccur atnormal physiological levels".83Butscientists could notdefine what those
"normal physiological levels" were since theyvaried widely from animal toanimal, andforthatreason
these hormones were considered bysome scientists tobe"promoters rather thatprimary inducers of
cancer inhormonally sensitive tissues".84According totheEuropean Communities, itwasonthis
assumptionthatwasalsobasedthe1988JECFAReport,onwhichCodexhadbaseditsrecommendations.
With regard tooestradiol-17 ,the1988 JECFA Report stated that"[t]he results ofstudies ...[showed
that] ....[o]ral andparenteral administration ofoestradiol -17ß canincrease theincidence oftumours
inexperimental animals. These tumours largely occur intissues with high levels ofspecific hormone
receptors thatarenormally responsive tostimulation bytheparticular hormone concerned. The
Committeeconcludedthatthecarcinogenicresponsewasrelatedtothehormonalactivityofoestradiol-17ß
atlevels considerably higher than those required foraphysiological response" (page 18).85
4.131 TheEuropeanCommunitiesarguedthatthegeneralscientificassumptionwasthatthesesubstances
were not"genotoxic"86,butexerted only "epigenetic" action. Butthiswasanassumption which had
82Science Vol. 273, 30August 1996.
83H.A. Kuiper, "Risk Assessment Strategies forXenobiotics", 1995 ECScientific Conference Proceedings, pp.370-371.
84H.A.Miller,J.K.Leighton,"RiskAssessmentStrategiesforHormonesandHormone-likeSubstances",1995ECScientific
Conference Proceedings, p.386, and1983 OIE Scientific Report, p.339 sqq.
85TheEuropean Communities noted thatthesame assumptions were made inthe1988 JECFA Report forprogesterone
(p.20), testosterone (p.22), trenbolone acetate (p.24), andzeranol (p.27).
86"Genotoxic carcinogens" were defined bytheEuropean Communities as"chemicals whose mode ofaction ismediated
byaseries ofmolecular events, initiated bydirect interaction ofthecompound oractivated reactive intermediate species
withcellular DNA eventually leading touncontrolled cellreplication andformation oftumours". TheEuropean Communities
added thattheconcepts ofNOEL (noobserved effect level) andADI (acceptable daily intake), onwhich forinstance was
(continued...)WT/DS26/R/USA
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notyetbeen clearly proved. Scientists hadagreed that"further development ofmetabolic studies is
required, particularly with regard toexogenous anabolic agents (synthetic hormones). Such advanced
studies would lead toabetter understanding oftheir mechanism ofaction andanytoxic effects".87
TheEuropean Communities alsoclaimed thatthedistinction between agents which acted astumour
initiators andthose considered astumour promoters wasover-simplistic. This distinction permitted
some scientists tomake some predictions byextrapolating tumour incidence observed intestanimals
athigh exposure levels topotential human exposure tolowlevels ofsuch hormones. However, other
scientists hadagreed that"these models donotindicate atrueriskbutprovide acalculated riskfor
theoccurrence ofthe(carcinogenic) effect. Therelevance ofthese models isquestionable since the
biological basis forhigh tolowdose extrapolation islacking".88TheEuropean Communities submitted
thatitwasonthisdisputed extrapolation, based onthenohormonal effect level, thatJECFA hadbased
its1988 Report andCodex itsJuly1995 recommendations. Theexample ofDES illustrated thedanger
ofsuch anapproach (seeparagraph 4.123, footnote 79).
4.132 TheUnited States rejected theECclaim that"allscientists agree thatthesixhormones are
dangerous"andsubmittedthatinstead,hormonesusedforgrowthpromotionpurposeswerenotinherently
safeordangerous, butprotection ofpublic safety depended upon thedose ofthecompound, itstoxicity
andthemanner ofhuman exposure. Under theconditions ofuseintheUnited States, these hormones
were safewhen used forgrowth promotion purposes. Thesafety ofthehormones asgrowth promotants
wasconfirmed bythefactthatthey hadbeen registered foruseinmore than 20countries (including
thelargest meat-producing countries). These countries hadstrong food safety laws. The1983 OIE
Scientific Report hadreviewed trenbolone andzeranol andhadalsocome totheconclusion thatthese
hormones were safewhen used forgrowth promotion. The1983 OIEScientific Report hadconcluded
that:
"1. Hormonesgenerallyposenocancerriskwhereexposureistolevelsbelowthoserequired
fordetectable hormonal activity.
"2. Mutagenicity andcarcinogenicity testdatafortrenbolone andzeranol suggest thatthese
agents andtheir metabolites areneither mutagenic norclastogenic andthatthey would only
influence cancer risk-either increase itordecrease it-ifthere wasexposure tohormonally
effective levels.
"3. Therefore, injudging whether itissafetousetrenbolone orzeranol asanabolic agents
inmeat production theemphasis needs tobeonmaking sure thatanyresidue ofthese agents
inmeat arebelow thelevels thatcould have anyhormonal effect onthemeat-eater. ..."89
86(...continued)
based the1988 JECFA report, were notapplicable tosuch genotoxic agents Recently (1990), oestrogen induction ofDNA
adduct formation hadbeen described (1995 ECScientific Conference Proceedings, Kuiper, p.373, Miller andLeighton, p.386,
with areference toastudy byJ.G. Liehr, "Genotoxic Effects ofOestrogens", 1990). "Epigenetic" agents were believed
nottoinduce gene mutations buttooperate viaother mechanisms likecytotoxicity, cellproliferation, peroxisome proliferation
orhormone disbalance, andinterference with hormone production. These effects were considered asdose-dependent for
which athreshold level (NOEL) might beestablished (ibid, Kuiper, p.374). Once aNOEL hadbeen setup,then anADI
level orMRL (maximum residue limit) wasusually established.
871983 OIE Scientific Report, pp.263-269.
881995 ECScientific Conference Proceedings, p.373.
89F.J.C. Roe, “Anabolics inAnimal Production ”,Symposium held atOIE, February 1983, p.339.WT/DS26/R/USA
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4.133 Furthermore, theUnited States noted thattheIARC work hadbeen reviewed byJECFA.90
IARC 'swork didnotsupport theECargument because IARC hadnotlooked toseeifthere would
beariskatthelowlevels ofresidues involved inthisdispute. TheIARC hadspecifically stated that
"[t]he operating principle istodetermine theability ofthechemical toproduce cancer orother genetic
andrelated effects without thestrictures ofmode ofhuman useorthemagnitude ofthedoses"91(emphasis
added). TheIARC work involved looking atmuch higher doses, anddifferent modes ofadministration,
than those involved intheuseofhormones inlivestock forgrowth promotion purposes. The
United States explained thatforthese sixhormones, onecould notextrapolate from high doses tolow
doses. Inscientific terms, thiswasreferred toashigh-to-low dose orlinear extrapolation, anditwas
notageneral principle oftoxicology orpharmacology butwasinstead onemodel used toexplain
experimental observations. This model wasalsoused insome approaches toriskassessment. An
alternative approach toexplain scientific datawould betouseathreshold model. Under athreshold
model some minimal amount ofacompound wasnecessary before anyresponse occurred. These were
notcontradictory models; experimental data forsome compounds were better explained bylinear
extrapolation whereas dataforother compounds, including thehormones involved inthisdispute, could
bebetter explained using athreshold approach. Thethreshold approach implied thatano-effect level
could bedetermined through scientific studies, anapproach thathadbeen determined tobevalid for
theimplant hormones used forgrowth promotion bytheLamming 'sCommittee92andthe1995 EC
Scientific Conference.93MGA hadnotbeen notexamined inthose reports, buttheUSFood andDrug
Administration hadconducted scientific reviews ofMGA andhaddetermined thatthethreshold approach
applied toMGA aswell.
4.134 TheEuropean Communities noted thattheIARC testswere notnecessarily only athighdoses.
IARC didnotdifferentiate between theeffects ofthesubstance athigh doses versus lowdoses. With
regard tooestrogens, progestins andcombinations thereof (i.e. mainly oestradiol-17 ,progesterone
andMGA), the1987 IARC Report explained that:
"Ithasbeen established byanimal experimentation thatmodification ofthehormonal
environment bysurgical removal ofendocrine glands, bypregnancy orbyexogenous
administration ofsteroids canincrease ordecrease thespontaneous occurrence of
tumours ortheinduction oftumours byapplied carcinogenic agents... Theincidence
oftumours inhumans could bealtered byexposure tovarious exogenous hormones,
singly orincombination .
"These statements make explicit thefacts thatoestrogens andprogestins occur naturally,
andthatthehormonal milieu anddose-effect relationships aregenerally inextricably
involved inthecarcinogenic effects ofoestrogens andprogestins.
...
"Thus, there isabasic incongruity between thehuman data and theanimal
carcinogenicitydata.Asnotedearlier,however,theeffectsofthesechemicalsinhumans
appear, atleast inmost cases, tobelinked tothehormonal milieu" (emphasis added).
901988 JECFA Report, pp.17, 20and21.
91IARC Monographs, Supplement 7,p.272.
92Veterinary Record, 24October 1987, pp.389-392
93Assessment ofHealth Risk Working Group II,pp.19-21.WT/DS26/R/USA
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Itfollowed thatthefindings oftheIARC reports aimed atestablishing thecarcinogenic orother effects
ofthese substances irrespective ofthemodes ofhuman useandthemagnitude ofthedoses. Furthermore,
thephrase "atleast inmost cases" didnotmean in"allcases" andunder allconditions.
4.135 TheEuropean Communities argued thattheUSstatement thatthethreshold approach implied
a"no-effect" level deliberately concealed thefactthatinrespect ofthehormones under discussion
thescientific groups towhich theUnited States referred looked only fora"nohormonal effect" level.
They didnotlookfora"notoxic effect" level; theJECFA report stated thatnotoxicological monograph
wasprepared foranyofthehormones which they considered. The"rationale" forthisapproach was
thatanytoxic effects inhumans, including cancer, would belinked tothehormonal effects inlaboratory
animals; without thelatter theformer would notoccur. However, thiswasamere guess. There was
noscientific justification forsuch anassumption. Noting thattheUnited States hadbanned DES without
requiring such alink, theEuropean Communities concluded that ifthehormones exerted their
carcinogenic effects byacting directly onthegenome, there wasno"safe" level. Theevidence for
thiswasincreasingly strong, particularly inthecase ofoestradiol.
4.136 TheUnited States contended thataninternational scientific consensus hadevolved onthesafety
andefficacyofthenaturalhormones(oestradiol,progesteroneandtestosterone)andtheirmimics(zeranol,
MGA andtrenbolone) foruseasgrowth promoting agents inbovine animals when used according
togood veterinary practice. TheUnited States recalled thatafter imposing theban, theEuropean
Communitieshadtwiceconvenedgroupsofscientificexpertstoreviewtheuseofthesehormones(except
MGA) andthatonboth occasions theEuropean Communities ’own chosen scientific experts had
concluded thatitwassafetousethese hormones forgrowth promotion purposes (asreflected inthe
Lamming Report andinthe1995 ECScientific Conference proceedings). Moreover, Codex had
reviewed these hormones, with theexception ofMGA forwhich JECFA hadnever been requested
toperform asafety assessment, andhadconcluded thatthey were safetopromote growth incattle.
Codex standards hadbeen adopted94after anextensive review oftherelevant science including studies
onbiological activity, carcinogenicity, embryo toxicity, andmutagenicity; usepatterns; residues in
animals;analyticalmethodology;toxicologicaldatafromlaboratoryanimalexperiments;andobservations
inhumans. TheCodex process hadafforded theopportunity forinput byscientists around theworld.
4.137 TheUnited States added thatafter thorough review, theUSFood andDrug Administration
(FDA) hadalsoapproved oestradiol, progesterone, testosterone, trenbolone andzeranol foruseasear
implants topromote growth incattle and,inaddition, FDA hadapproved MGA foruseasafeedadditive
forincreasedweightgain,improvedfeedefficiencyandsuppressionofoestrus.Oestradiol,progesterone,
andtestosterone hadbeen approved inthe1950 's,zeranol hadbeen approved in1969, trenbolone in
1987, andMGA in1968. Inthecase ofthethree synthetic hormones, theFDA review hadincluded
astandard battery oftoxicology tests including studies designed toassess each compound ’stoxicity,
carcinogenicity, mutagenicity andanyreproductive effects. FDA hadalsorequired special studies
designed toexamine thehormonal action ofthecompound.95
4.138 TheUnited States claimed thatoestradiol, progesterone andtestosterone occurred naturally
inallmammals andthattheamount produced daily varied widely among species andamong animals
ofthesame species, andwasinfluenced byfactors such asageandbreed. Furthermore, endogenous
hormonal substances were alsofound inavariety ofnon-meat foods thatformed apartofthenormal
human diet. Over 300species ofplants thatwere used forfood were recognized ashaving oestrogenic
substances, including soybeans, cherries, apples, green beans, alfalfa, palms andlicorice. Moreover,
these hormones occurred atmuch higher levels insome ofthese other foods. Forexample, ahen’s
94ALINORM 91/31 APPENDIX IV,asadopted bythe21st Session oftheCodex Alimentarius Commission.
95TheUnited States submitted anexplanation oftheFDA review ofthese hormones aswellasatable providing details
ontheapproved uses ofthese hormones intheUnited States.WT/DS26/R/USA
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egghadahigher concentration ofoestradiol equivalents thanmeat from animplant-treated steer. The
relative concentration inaneggwasmore than onethousand times higher than thatinthesteer, and
thetotal amount ingested byconsuming ahen’segg, even considering thedifference inquantity
consumed, wasslightly greater than600times thatfrom consuming meat from animplant-treated steer.96
Many fruits, vegetables, grains andnuts contained substantial quantities ofphytoestrogens.97
4.139 TheEuropean Communities argued thatconsumers hadalways been exposed toacertain
amount ofhormones, orhormone-like substances intheir diet; they hadevolved alongside them and
could cope with them. This wasnotthecaseforadded hormones. Furthermore, theplant substances
referred tobytheUnited States were notidentical totheanimal hormones.
4.140 TheUnitedStatesfurtherobservedthatwidevariationsoccurredintheproductionofoestradiol,
progesterone andtestosterone inhumans andatamounts considerably greater thantheamounts ofthese
hormones inmeat from treated animals. While human production ofoestradiol, progesterone and
testosterone wasmeasured inmicrograms perday, ingestion ofthese hormones wasmeasured in
nanograms orpicograms (one thousand toonemillion times less, respectively, than amicrogram).
Thus, ingestion ofresidues ofoestradiol, progesterone andtestosterone inmeat wasvery small when
compared tothose amounts produced byhumans, whether ornotthemeat wasfrom ananimal towhich
hormones hadbeen administered. These amounts were sosmall thatthey didnothave anyeffects
onhumans. Inaddition, theresidues ofthenatural hormones hadvery lowbiological activity when
ingested because more than 90percent oftheresidues (including metabolites ofthethree natural
hormones)passedthroughanindividualandwererapidlyexcreted.Thusover90percentoftheresidues
were notabsorbed, sothey could nothave anyeffect ontheconsumer. Finally, theUnited States
submittedthatanyresiduesofthenaturalhormonesinmeatfromanimalstowhichoneofthesehormones
hadbeen administered could notbedistinguished from theresidues resulting from theendogenous
production ofthese hormones.
4.141 TheEuropean Communities argued thatthevarious assessments orreviews undertaken by
groups ofscientists, conferences, etc.were notariskassessment intheterms ofArticle 5.Article 5
required Members toensure thattheir measures were based onariskassessment. Itdidnotprovide
forthem todelegate thisresponsibility toscientific groups. Article 5.2specifically required Members
to"take intoaccount available scientific evidence" asoneofanumber offactors. Itdidnotsaythat
Members should adopt without question theconclusions ofwhatever scientific group hadhappened
topassanopiniononthesubject.Nodemocraticsystemofgovernmentcouldabdicateitsresponsibilities
totechnicians inthismanner. Moreover, theconclusion ofallscientific experts didnotsupport an
unqualified andfreeuseofthese hormones forgrowth promotion, aswasthepractice intheUnited
States. They allconcluded cautiously that, under thepresent state ofscientific knowledge, theuse
ofthefivehormones forgrowth promotion wasnotlikely topose risks tohuman oranimal health,
ifused inaccordance with good agricultural husbandry (veterinary) practice.
4.142 TheEuropean Communities contended thattheUnited States apparently sided (ashaddone
the1988 JECFA report andtheCodex) with those scientists who believed thatthese hormones caused
cancer duetotheir hormonal activity andthat, therefore, they were promoters rather than inducers
ofcancer inhormonally sensitive tissues. Butthiswasthebelief ofjustonepartofthescientific
96J.Riboleau (1983), "Teneur ensubstances oestrogènes del’oeuf vierge etl’oeuf faconde despietaux". Compt. Redn.
Sco. Biol, 129-914; V.C. Craknell, andF.L. Mauld "Anabolic Agents inAnimal Production" (unpublished Lilly Research
Ltd.); J.B.etal.Tarr (1984), "Pharmaceutical metabolic andtissue residue studies of3H-Zeranol incattle" (unpublished).
97K.andR.Vertual, D.S. (1990), "Naturally Occurring Oestrogens inPlant Foodstuffs--A Review". Journal ofFood
Production,Vol.43,pp.577.581;A.N.Booth,S.M.Tithoff,andC.M.Hehier,(1960),"Oestrogen-likeActivityinVegetable
OilsandMilk By-products",. Science, Vol. 131, p.1807; E.L. Monk, R.E. Erf,andT.A. Mellest (1975), "Relationships
between Immunoreactive Oestrone andOestradiol inMilk, Blood andUrine ofDairy Cows", Journal ofDairy Science,
Vol. 44,pp.34-40.WT/DS26/R/USA
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community. Intheabsence ofclear evidence tothecontrary, theEuropean Communities considered
thatitwasentitled tofollow acautious approach andsided with theother body ofscientists whoplaced
moreattentiononthecarcinogenicrisksarisingfromthepossible"genotoxic"98actionofthesehormones,
irrespective ofthedose inwhich theywere administered toanimals forgrowth promotion. This choice
wasincompliance with theproper definition oftheconcepts of"risk" and"risk assessment" which
theSPSAgreement hadexplicitly established inArticles 5.1to5.6andinAnnex A(4). Inthisrespect,
theEuropean Communities referred toanumber ofscientific opinions.
4.143 TheEuropean Communities observed, forexample, thatDr.Liehr argued that"oestrogens
have been implicated forsome time intheinduction ofhuman cancers, andthere isincreasing evidence
ofasimilar roleforprogesterone andtestosterone".99Inparticular, Dr.Liehr hadstated:
"Inthecase ofoestradiol, experiments have shown thatitshormonal potency isnotlinked to
itscarcinogenic activity. Investigations ofthemetabolic pathways ofoestradiol have revealed
thatfreeradicals arecontinuously produced, andDNA damage bythese freeradicals, aswell
asDNA adduct formation, hasbeen demonstrated inarange oftissues. Asdamage toDNA
andDNA adductformationareknowntobeassociatedwithtumourformation,theseexperiments
provide strong evidence thatoestradiol isagenotoxic carcinogen. Inthecaseofprogesterone
andtestosterone, itisnotclear whether their carcinogenic effects aremediated bytheir action
onspecific receptors intarget tissues orduetomutagenic DNA damage.
"Inthepresent state ofknowledge, itisvery difficult andinanycasenotadvisable todetermine
asafe threshold dose ofhormone below which tumour formation will not occur.
Hormone-associated tumours inthebreast, uterus orprostate maybeinduced byacombination
ofexogenous andendogenous hormones and/or their metabolites. Asthetotal amount of
hormone ormetabolite necessary fortumour induction isnotknown, theamount ofexogenous
hormone ormetabolite necessary fortumour induction inaddition tounknown amounts of
endogenous hormone ormetabolite hasnotyetbeen determined. Inthe1988 JECFA report,
theauthors considered only thehormonal receptor-mediated activities ofthenatural hormones.
Inviewoftheconsiderableamountofscientificevidencewhichhasaccumulatedsincetherelease
ofthatReport, particularly inrespect ofthegenotoxicity ofoestradiol, theReport cannolonger
beconsidered applicable toariskassessment oftheuseofhormone growth promoters."100
4.144 Inaddition theEuropean Communities argued thatDr.Adlercreutz indicated that:
"...the1987 JECFA report must now beregarded astooold. Themain problem with this
report isthatitrelates anynegative effects ofhormonal drugs totheir hormonal effects, i.e.
ifacompound occurs inamounts notgiving clear "hormonal" responses itisregarded assafe.
Theanabolic steroid trenbolone hasboth anabolic andoestrogenic effects anditisnotclear
which effects areconsidered. Itisfrequently used incombination with oestradiol andalsowith
zeranol, which areoestrogenic. Furthermore, testosterone andtrenbolone seem alsotoaffect
theglucocorticoid receptor andtestosterone increases growth hormone andgrowth factor
concentrations andboth affect steroid biosynthesis. Many other hormonal effects ofthefive
compounds dealt with areknown. When studying hormonal effects only gross effects are
considered, butnowadays itisobvious thateffects may occur atthecellular level atlow
concentrations ofhormones andwithout being observable bytherelatively coarse methods
used intoxicology invivo studies. Such effects maybeobservable inhuman subjects firstafter
98J.G. Liehr (1990), "Genotoxic effects ofoestrogens"; andthe1995 ECScientific Conference Proceedings, p.386.
99J.Liehr, "Potential genotoxicity ofHormones", 23December 1996.
100Ibid.WT/DS26/R/USA
Page 64
many years oreven longer time. Another problem isthattheJECFA report does notdealwith
ordiscusses very little thecarcinogenicity ofmetabolites ofhormones, particularly those of
oestrogens. Atthetime when the1987 JECFA Report waswritten very little wasknown about
thegenotoxic effects particularly ofestrogen metabolites. Since thereport waswritten ithas
alsobeen more andmore obvious thathormones have nongenomic effects notrelated totheir
hormonal effect viathereceptors andthatsteroid hormone metabolites may beasimportant
oreven more important with regard tovarious effects onbiochemical orgenotoxic events than
theparent compound.
"Allthese hormones have been shown tocause cancer invarious experimental systems ifgiven
inhigh amounts butitisobvious thattheeffect isnotalways duetotheir hormonal activity.
Foroestrogens andtrenbolone ithasbeen shown thatalsoother mechanisms occur andthe
mechanisms bywhich theother hormones cause cancer isfarfrom clear.
(...)
"Anabolic steroids inmeat hasbeen shown toresult inpositive doping tests. Acompound
giving positive doping tests cannot beadministered formeat production because these may
result inlifetime problems foranysportsman orsportswomen who iscaught with apositive
doping testwithout having used anydoping agents.
"The 1987 JECFA report isdefinitely toooldanddoes nottakeintoaccount recent scientific
evidence changing ourview onthecarcinogenicity ofoestrogens anddoes nottakeintoaccount
non-hormonal andother negative effects oftheadministration ofsteroids toanimals intended
forhuman consumption".101
4.145 TheEuropean Communities alsopresented theargument ofDr.Cavalieri that:
"...thepresently available knowledge about tumour induction inhormone-responsive tissues
suggests aspecific pathway ofoestrogen metabolism, namely 4-hydroxylation followed by
oxidation toE-3, 4-Qandreaction DNA. This DNA damage isresponsible forgenerating the
critical mutations thatcanleadtotumour formation, iftheappropriate mechanisms ofpromotion
occur. Therefore, oestrogens, inparticular oestradiol, have genotoxic effects andnothreshold
dose canbeestablished. Inaddition, theeffects oftheother natural andsynthetic hormones
used formeat production onthemetabolism ofoestrogens arenotknown. Thus, Acceptable
Daily Intakes andMaximum Acceptable Levels cannot beestablished forresidues ofthese
hormones inmeat forhuman consumption.
"The 1988 and1990 FAO/Codex Alimentarius expert group reports recommended ADIs and
MRLs forthese hormones based ontheir hormonal effects. Genotoxic effects were unknown
atthattime and, thus, were notconsidered. Inlight ofthenewknowledge about thegenotoxic
effects ofoestrogens, theentire subject ofthese residues inmeat forhuman consumption must
bereassessed."102
4.146 Furthermore, theEuropean Communities argued thatDr.Metzler reported thattheavailable
data show that:
101H.Adlercreutz, "Evaluation oftheThirty-Second Report oftheJoint FAO/WHO Expert Committee onFood Additives,
andDiscussion ofDr.J.Liehr 'sReport onthisTopic", 7January 1997.
102E.Cavalieri, "Genotoxicity andPotential Carcinogenicity ofHormones Administered toAnimals forPromotion of
Growth inMeat Production", 7February 1997.WT/DS26/R/USA
Page 65
"17-oestradiol, 17-trenbolone andzeranol canbemetabolically activated toproducts capable
ofcovalent DNA binding. Thelevel ofDNA binding islowascompared totypical chemical
carcinogens, butmay have significant toxicological implications, asdiscussed below.
"17-oestradiol andsome oftheir metabolites have thepotential tocause aneuploid andare
therefore chromosomal mutagens. For17-trenbolone, thereports about aneuploidogenic
potential arecontroversial. Forzeranol anditsmetabolites, aneuploidogenic potential hasnot
been studied adequately.
"The metabolism of17-trenbolone andzeranol inhumans andthegenotoxicity ofthe
metabolites have notbeen fully elucidated.
"The mechanisms ofhormonal carcinogenesis arenotyetfully understood. Thehormonal
andgenotoxic effects ofanagent may well actinconcert. Therefore, itisconceivable that
anhormonallyactivecompoundisretainedintargetcellsbythehormonereceptorandstimulated
celldivision, which inturnmakes thecellmore vulnerable fortheinduction ofgene mutations
andaneuploid. Xenobiotic hormones have longer half-life andmayaccumulate tohigher levels
after repeated exposure.
"The standard systems used intoxicology forassaying genotoxicity maynotbesuitable todetect
therather subtle genotoxic effects ofcarcinogenic hormones. Asthehormones under
considerationand/orsomeoftheirmetabolitesexhibitbothDNA -damagingandaneuploidogenic
potential, itisnotpermissible toestablish values forNo-Adverse-Effect-Levels andfor
Acceptable Daily Intake. The conclusions andrecommendations ofthe1988 and1990
FAO/Codex Alimentarius Reports aresolely based onthehormonal activities oftheagents
under consideration. Astheevidence forgenotoxic effects ofthese agents hasincreased
considerably over thepastyears, anupdate isrequired which takes these recent findings into
account."103
4.147 TheEuropean Communities alsoreferred tothereport submitted byDr.Epstein inwhich he
argued that:
"...there issubstantial evidence challenging thevalidity ofclassifying carcinogens asepigenetic,
forwhich thresholds orAcceptable Daily Intake (ADI) levels areclaimed, orgenotoxic. Apart
from this,hormonal anabolics aremutagenic inmammalian testsystems andarethusgenotoxic.
There isalso substantial scientific evidence challenging theexistence ofthresholds forany
carcinogen. This evidence iseven more persuasive forexposures involving infants andyoung
children, inview oftheir enhanced sensitivity tocarcinogens andforexposures involving
unpredictable synergistic interactions. There isnoscientific basis forclaims thatADI levels
canbesetfornatural andsynthetic anabolic carcinogens, orforclaims thatADI levels can
bebased on"no-hormonal-effect levels" ofsynthetic anabolic carcinogens (FAO/WHO, 1990).
"Theseconclusionsonthehormonaleffectsofanabolicsareconsistentwith,andanamplification
of,those detailed inanearlier review ofendocrine factors inhuman carcinogenesis. Inalmost
allcases twopostulated mechanisms: "alteration ofthesusceptibility oftissues totheinitiation
ofcancer" and"promotion ofthedevelopment ofcancer from initiated cells", could notbe
separated. Thecarcinogenic effects ofDES inrelation tobreast cancer were considered to
be"more inkeeping with aneffect oninitiation rather than onpromotion". Itmay further
benoted thatnomechanism ofaction, whether promotion, initiation orother, could be
determined forthecarcinogenic effects ofoestrogens onsalivary, ovarian, renal andthyroid
103M.Metzler, "Genotoxic Potential oftheNatural SexHormones 17-oestradiol andTestosterone, andoftheSynthetic
Compounds 17-trenbolone andZeranol", 6February 1997.WT/DS26/R/USA
Page 66
cancers, andmalignant melonoma inhumans. Amost recent report hasfurther summarized
evidence thatparent oestrogens andtheir catecholamine metabolites induce several types of
DNA damage, adduct formation, andgene mutations. Additionally, theauthor concluded,
onthebasis ofexperimental evidence, that"hormonal activity ofoestrogens wasconsidered
tobenecessary butnotsufficient fortumour induction tooccur".
"Thereisnoscientificbasisformakingdistinctionsbetweengenotoxicandepigeneticcarcinogens
onthebasis ofavailable bioassay data. Thus, there isnobasis forattempts toderive threshold
levels forhormonal anabolics, orother carcinogens, from such data. ...
"Itshould further beemphasized thatextrapolation from high dose bioassay dataislikely to
underestimate, rather than overestimate, thecarcinogenic effects oflowdose chronic human
exposure. Arecent publication endorsed thisconclusion with particular reference tometabolic
considerations. "Limited evidence would indicate thatproportionately lessactive metabolite
isformed athigh concentrations where Phase 2enzymes predominate, while atlower
concentrations pathways leading toactive metabolites arefavoured. Theoverall effect would
leadtoanunderestimate ofriskfrom high dose animal experiments when extrapolating tolow
level, chronic human exposure".
"Apart from theinvalidity ofdistinctions between genotoxic andepigenetic carcinogens, it
isgenerally accepted thatthreshold levels cannot bedetermined forgenotoxic carcinogens.
While hormonal anabolics areinactive inbacterial gene tests, andhence dismissed asepigenetic,
theyarenevertheless clastogenic inmammalian evidence ofgenotoxicity isclearly more relevant
tohuman cancer than aredata based onbacterial gene tests.
"There areother cogent reasons forrejecting thethreshold hypothesis. These include:
- Theenhanced sensitivity ofneonatal rodents tothecarcinogenic effects ofanabolic
hormones, supported bysubstantial evidence ontheincreased susceptibility ofinfant
rodents andhumans toawide range ofcarcinogens, including natural anabolics and
diethylstilbestrol. (IARC, 1989, NRDC, 1989)
- Synergistic interactions between different anabolics administered incombination.
Illustrative, arethesynergistic effects ofoestrogen andprogesterone intheinduction
ofmammary tumours inmice. (IARC, 1987)
- Thepossibility ofadditive and/or synergistic interactions between natural andsynthetic
anabolic carcinogens andendogenous hormones, particularly ininfants.
- Synergistic interactions, notasyetinvestigated, between anabolic carcinogens and
carcinogenic and/or xenoestrogenic contaminants inmeat products, such aschlorinated
hydrocarbon pesticides.
- Theabsence ofroutine monitoring andresidue analysis forparent anabolics following
their legal administration, andofsensitive andpractical analytic techniques further
preclude attempts toestimate threshold orAcceptable Daily Intake levels forhormonal
anabolics. Stillfurther complicating problems ofresidue analysis istheimpracticality
ofassaying forbiologically active oestrogen metabolites."104
4.148 TheEuropean Communities alsopresented thearguments ofDr.Pinter that:
104S.S. Epstein, "Report totheEConCancer Risks from Hormonal Meat Products", 5February 1997.WT/DS26/R/USA
Page 67
"...there isevidence thatendogenous andexogenous hormones represent potential carcinogenic
risktohumans. Theriskisassociated with thelevel ofhormones, thetime ofexerting the
hormonal effect andthegeneral status ofthehormone-responsive organs. Exogenously
administered hormones have been proved tobecarcinogenic toexperimental animals andthere
isalsoevidence forhormones tobecasually associated with human tumours. Incontrast to
many animal carcinogens, inthecaseofhormones, onehastobear inmind thatwedealwith
"human" carcinogens. Therefore, anyconsideration should bedealt with more seriously than
with "animal" carcinogens. Although thelevel ofendogenous hormones varies greatly during
thelifetime, there isnoevidence thatlowlevel ofadditional hormones donotrepresent
additional risk.
"Oestrogens and/or their metabolites canreact with DNA causing DNA damages, canalter
proteins including tubulin, resulting inaneuploid. There isalsoevidence thatthiseffect is
differentfromthehormonalone,thereforerelyingonno-hormonaleffectmightbeinappropriate.
Administration ofoestrogens andprogestins inhumans isproved tobetumorigenic. Incase
ofhormone mixtures andtheir residues, itispossible thatsimilar risks exists. Although the
level ofadministered oringested mixtures may bedifferent, thetumorigenic hazard should
notbeexcluded.
"Alleffort should bemade toavoid additional hormonal effect unless itisabsolutely necessary
(mediation, etc.). Theriskassociated with consumption ofhormone-containing meat products
canberegarded asunnecessary riskwhich canbeavoided."105
4.149 TheUnitedStatesarguedthattheworkreferencedbytheEuropeanCommunitiesdidnotprovide
evidence ofanyriskinvolving residues ofthesixhormones when used forgrowth promotion purposes.
Contrary totheECsuggestion insubmitting thereports ithadrequested from individual scientists,
oestradiol-17ß wasnotgenotoxic when administered bytheoralroute. Most ofthestudies cited in
these reports involved compounds thatwere genotoxic butwere notrelated tooestradiol-17ß (orto
anyoftheother fivehormones involved inthedispute) either structurally orbiologically. Theonly
studiespresentedasevidencethatoestradiol-17ßwasgenotoxicdiscussedaSyrianhamstermodelsystem.
Thehamsters were given oestradiol-17ß atdoses millions oftimes higher than thelevels present in
food, asshown below. Theroute ofadministration wasdirectly intotheanimal (systemic) notoral.
Thepurported DNA damage (adduct formation) wasattributed toaminor metabolite ofoestradiol-17ß,
notoestradiol-17ß perse.Thestudies failed todemonstrate thattheadducts were permanent and
irreparable- anecessity forcompounds thatwere genotoxic. Rather thestudies suggested thattheDNA
changes were secondary tothecell’sinability toinactivate these extremely highdoses ofoestradiol-17ß,
acommon finding intoxicology.
4.150 TheUnited States observed thatthedosage used inDr.Liehr ’sstudy was61µg/day inmale
Syrian hamsters weighing approximately 100g.This was610µg/kg/day. Fora60kgadult human
male, thiswas theequivalent to36.6 mg/day. Onaverage anadult male produced 48µgof
oestradiol/day. This meant thatDr.Liehr ’sstudy involved delivery tomale hamsters of762.5 times
more than thecomparable average daily production rateinadult men. Theaverage daily production
rateinmenwas, inturn, 15,000 times more thantheresidue ofoestradiol inmeat from treated animals.
Thedifference between thedose used intreatment ofSyrian hamsters andtheresidue in500gofmeat
from treated animals wasapproximately 11.5 million. Inother words, ifoneextracted alltheoestradiol
outof11.5 million 500gportions ofmeat, andinjected allthisquantity ofoestradiol every dayfor
anumber ofmonths intohuman males, onewould replicate thedose used byDr.Liehr.
4.151 TheUnited States maintained thatthefinal stepinthescientific process wastodetermine that
thedatagenerated inamodel system accurately predicted theadverse effects inhumans. Thescientific
105A.Pinter, "Some Aspects ofHormonal Carcinogenesis", 5February 1997.WT/DS26/R/USA
Page 68
dataontheoralactivity ofoestradiol-17ß demonstrated thattheresults obtained intheSyrian hamster
modelsystemwerenotrelevantforassessingthetoxicityofoestradiol-17ßadministeredorallytohumans.
4.152 TheUnited States argued thatamore definitive test, atwo-year rodent bioassay, hadalready
been conducted foroestradiol-17ß andtheresults ofthebioassay together with theresults ofother
short-term tests hadbeen reviewed byvarious scientific experts andused indetermining thesafety
ofoestradiol-17ß. Based ontheresults ofthese tests andother relevant scientific data, ithadbeen
determined thatoestradiol-17ß wasnotagenotoxic carcinogen. Since long-term invivocarcinogenicity
tests hadalready been conducted forthese hormones, theresults ofadditional short-term assays were
oflittle value. Thefullscientific process necessary tomake theregulatory decision thatoestradiol-17ß
wasnotagenotoxic carcinogen hadbeen completed. Thevery lowlevels ofoestradiol-17ß present
infood were notadding tothecancer riskofwomen, children ormen.
4.153 Furthermore, theUnited States observed thatoestradiol was thesame whether produced
endogenously inwomen, naturally present infood ofanimal origin, orpresent asaresult oftreatment
ofanimals fortherapy orgrowth promotion. Oestradiol-17ß waspresent inmilk, including human
breast milk. Oestradiol content wasvery high inhuman breast milk early inlactation. Although infants
andyoung children were very susceptible togenotoxic agents, there wasnoevidence thatoestradiol-17ß
wasgenotoxic inthisvery sensitive population. Genotoxic agents caused irreparable damage tocells.
Newborn human infants were orally exposed torelatively large doses ofoestradiol-17ß inhuman breast
milk with absolutely noevidence ofgenotoxic orother harmful effects.
4.154 TheUnited States alsoargued thatthere wasnoevidence thatuseofthehormones inquestion
resulted inadverse health effects totreated animals.
4.155 TheUnitedStatesacknowledgedthatscientistsdidnotclaimtoknoweverythingabouteverything
andnoted thatscientific knowledge wasalways progressing andevolving. However, lackofknowledge
could notitself bethebasis fortaking asanitary measure. TheSPSAgreement required theEuropean
Communitiestodemonstratescientificevidenceofaparticularrisk.Accordingly,toclaimthataMember
wasjustified banning anactivity wherever there were stillareas forscience toexplore would beto
render theSPS Agreement meaningless: there would always beareas forscience toexplore.
4.156 TheEuropean Communities responded thatithadnotargued inthiscasethatlackofknowledge
byscientists ofallaspects ofhormones 'mode ofaction could alone justify theprohibition ontheir
useforgrowth promotion. What theEuropean Communities hadargued wasthatitwasconcerned
with substances which scientists knew were potentially carcinogenic. This scientific evidence, coupled
with theother possible sources ofrisks, enabled aMember toadopt aprecautionary approach by
prohibiting their useforgrowth promotion. This was allthemore sowhen under aproper risk
assessment, performed inaccordance with what wasnowrequired byArticles 5.1to5.6,theEuropean
Communities hadconcluded thatnoother measure wasreasonably available toit,taking intoaccount
technical andeconomic feasibility, thatwould have achieved itsappropriate level ofsanitary protection
andwhich would have been significantly lessrestrictive totrade.
4.157 TheEuropeanCommunitiesemphasizedthattherealpolicyquestiononhowregulatoryauthorities
should treat hormones depended onthedefinition oftheterms "harm" and"risk". Ifriskwasdefined
as"the probability (either measured orestimated) thatharm might occur from exposure tothese
hormones"106,Members were freetodecide whether such measured orestimated risks were desirable
from their regulatory policy point ofview. Noscientific report todate, including the1988 JECFA
Report onwhich Codex hadbased itsrecommendations, hadeversuggested thatthere wasnopotential
106J.BridgesandO.Bridges,"HazardsofGrowthPromotingAgentsandStrategiesofRiskAssessment",1995ECScientific
Conference Proceedings, p.247 seq.. and"Risk Assessment Strategies forXenobiotics", 1995 ECScientific Conference
Proceedings, p.365 seq.WT/DS26/R/USA
Page 69
risk from theuseofthese hormones. The simple factthatCodex hadconsidered itnecessary to
recommend MRLs forsome ofthese hormones wassufficient proof initself thatthere wassuch arisk.
Such ariskmight alsoresult from their administration, ifthiswere notdone inaccordance with good
veterinary practice.
4.158 TheUnited States argued thattheEuropean Communities attempted toimply thatthere were
large gaps intheknowledge about hormones, andthatthisgapcompared unfavourably toscientific
knowledge about other types ofcompounds. However, intheUSview, scientists knew more about
thenature andmode ofaction ofhormones than they didabout most, ifnotall,other classes of
compounds. TheUnited States asserted thattheEuropean Communities waswrong inclaiming that
thefactthatthere were ADI levels orMRLs forasubstance wasevidence thatthere wasariskfrom
thesubstance atlevels below thatADI orMRL. Theconcept ofADIs andMRLs wasonly applicable
toresidues ofsubstances thatdidnotoccur naturally, such astrenbolone andzeranol. TheUnited States
explained thatusing laboratory animals, scientists determined atwhat level thehormones hadanyeffect
onanimals (notnecessarily anadverse health effect, butsimply where thehormone started tohave
ahormonal effect). Then, using alarge safety margin (100 times oreven 200times), thescientists
calculated what level ofthese hormones themost sensitive member ofthehuman population could
beexposed toevery dayoftheir lives andstillhave noeffect. This wastheADI level (acceptable
daily intake level). Thescientists then determined what wasthemaximum residue level (MRL) that
food could contain andstillensure thattheADI wasmet. This MRL wascalculated using conservative
consumption estimates, forexample assuming thataperson ate500grams ofbeef perday. There
were noevidence thatthere wasanyriskofharm tohuman health atlevels below theADI andMRL.
Moreover, theEuropean Communities 'claim assumed thatifthere wasanyriskofharm from hormones
athigh levels ofconsumption, then there must bearisk, albeit smaller, from lowlevels. The
United States argued thatthiswasunsupported byevidence andwasalsountrue inthecaseofanumber
ofcommon foods. These common foods were safeatnormal levels ofconsumption, butposed arisk
ofharm tohuman health atvery high levels. Some examples ofthiswere potatoes, which contained
alkaloids which were toxic inhigh quantities; lima beans, which contained cyanide which wastoxic
inhigh quantities; andryeandother small grains, which inEurope often contained ochratoxin-A that
athigh levels could cause kidney disease andcancer.
4.159 TheEuropean Communities responded thatthe"safety factor" applied when setting thevalues
ofADI andMRLs didnotprovide thenecessary protection, especially inthecase ofpotentially
carcinogenic substances whose mode ofaction wasnotclear, astheexample ofthehormone DES had
shown. The"safety factor" wasinreality nomore than auseful toolandapplied tothose scientific
reports which depended onextrapolations from imperfect dataonlaboratory animals tosetting ADIs
andMRLs forhumanbeings.TheEuropeanCommunitiesarguedalsothattheuseofsimplisticexamples
ofanumber ofcommon foods (eg.potatoes, lima beans, ryeandother small grains) bore norelevance
whatsoever tothescientific issues indiscussion. TheUnited States hadnotexplained how many
kilogrammes ofpotatoes onewould have toconsume firstbefore absorbing alkaloids intoxic quantities.
Conversely, avery minuscule portion ofmeat from ananimal towhich these hormones hadbeen
improperly administered might contain avery high dose ofresidues which were dangerous tohuman
health. TheEuropean Communities argued thattheexample ofthepremature sexual development
andovarian cysts involving about 3,000 Puerto Rican infants andchildren demonstrated theabove
point.107Inaddition, potatoes, lima beans andtheother products mentioned bytheUnited States had
always formed partofthenormal dietofhuman beings andnaturally-occurring substances inthese
products hadentered themetabolism ofthehuman body throughout thecourse ofhuman evolution
andcould notbecompared with exogenously administered carcinogenic substances given toanimals
forgrowth promotion purposes. TheEuropean Communities argued that, faced with theidentified
cancer risks, itwasentitled tobeascautious aspossible andnoted thattheUnited States actually applied
107A.Pérez-Coma, C.A. Saenz, "Anomalous Sexual Development inPuerto Rico -28Years ofExperience".WT/DS26/R/USA
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thesame typeofsanitary andphytosanitary policy withregard topotentially carcinogenic food additives
through the"Delaney clause".
4.160 TheUnited States clarified thatitdidnotapply azeroriskpolicy toallpotential risks presented
bytheuseofafood additive. Toreceive approval foruseintheUnited States, thesponsor ofafood
additive must demonstrate thattheadditive was"safe" foritsintended uses. Under USlaw, "safe"
didnotmean theabsence ofallriskbutrather a"reasonable certainty" thatnoharm would result from
theintended useoftheadditive. Thesame standard alsoapplied tothesetting oftolerances forpesticide
residues inrawagricultural commodities andprocessed foods. This concept ofsafety wasarticulated
inboth theUSSenate andHouse reports tothe1958 billenacting theFood Additives Amendment,
which stated that"[t]he concept ofsafety used inthislegislation involves thequestion ofwhether a
substance ishazardous tothehealth ofmanoranimal. Safety requires proof ofareasonable certainty
thatnoharm willresult from theproposed useofanadditive. Itdoes not-andcannot -require proof
beyond anypossible doubt thatnoharm willresult under anyconceivable circumstance".108
4.161 TheUnited States noted thattheEuropean Communities inessence hadargued thatthere was
notathreshold level below which residues ofthese hormones would besafe.109Inother words, the
European Communities claimed that anyresidue, nomatter how infinitesimal, posed arisk of
carcinogenicity. YettheEuropean Communities hadnotprovided scientific evidence tosupport this
position. Moreover, iftheEuropean Communities truly believed thatthere wasnothreshold, andwere
unwilling toaccept anyriskfrom residues ofthese hormones, then theEuropean Communities would
have tobantheuseofhormones forherd management andother purposes. ButtheEuropean
Communities didpermit theuseofhormones forherd management andother purposes. IntheUS
view, theEuropean Communities ’own arguments belied itsposition. Forexample, theEuropean
Communities hadclaimed thatthelevels ofhormones thatoccurred naturally inmeat andother foods
were notarisktohuman health because humans evolved alongside them. Thisconclusion, while lacking
anyscientific foundation, nonetheless demonstrated thattheEuropean Communities believed thatthere
wasathreshold ofexposure below which there wasnorisk.
4.162 TheEuropean Communities contended thatitdidnotpermit theadministration ofthethree
natural hormones "toentire herds ofcattle". Although theEuropean Communities didnotpossess
theexact figure ofthenumber ofanimals treated fortherapeutic orzootechnical purposes, partly because
some oftheECmember States didnotkeep such adetailed statistical record, itcould beestimated
fromthoseECmemberStateswhichdidkeepsuchrecords(e.g.Denmark,TheNetherlandsandFinland)
thatonlybetween 1percentand2percentofbreeding cattle intheEuropean Communities were treated
each yearforsuch purposes. This percentage corresponded toabout thesame proportion oftotalbovine
meat ofECorigin consumed intheEuropean Communities. This might bepartly explained bythe
factthatthere were nowbetter treatments available which were notbased onthese hormones. Regardless
oftheinsignificantquantitiesinvolved,whatneededtobeunderlinedwasthatallowingtheadministration
ofthethree natural hormones fortherapeutic orzootechnical reasons wasinfullcompliance with the
European Communities 'policy ofensuring noresidues ofhormones inmeat forhuman consumption
since thestrict conditions imposed byEClaweffectively ensured itspolicy objective (noresidues at
all).
4.163 TheUnited States responded thatitwaswishful thinking, notfact, tothink there were no
residues present attheendofawithdrawal period. Ashadbeen confirmed bytheexperts advising
thePanel, residues might bebelow thelevel ofdetection, butthere would always besome amount
left. This wasbecause hormones (asalmost allcompounds, with very fewexceptions) depleted by
first-order kinetics. Thismeant thatafter onehalf-life, only50percentoftheoriginal amount remained;
108H.R. Rep. No.2284, 85th Cong., 2dSess. (1958); S.Rep. No.2422, 85th Cong., 2dSess. (1958).
109Seepara. 4.135 with respect toECarguments regarding thethreshold approach.WT/DS26/R/USA
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after 2half-lives, 25percentoftheoriginal amount remained, andsoonuntil theamount remaining
became vanishingly small butstillpresent. TheECclaim only demonstrated theoverbroad nature
oftheECban. IftheEuropean Communities hadbeen correct inthinking thatthere were noresidues
after aparticular waiting period, then theEuropean Communities ataminimum would nothave been
entitled toprohibit allimports ofmeat from animals towhich anyofthesixhormones hadbeen
administered forgrowth promotion purposes, butonly meat from animals thathadnotbeen subject
toasufficient waiting period. Similarly, instead ofprohibiting imports ofallanimals, theEuropean
Communities could have prescribed awaiting period forthose animals prior toslaughter. TheEC
view would have meant there wasnobasis foranabsolute banwith respect tothethree synthetic
hormones either, since under thatview there would benoresidue ofthese hormones after asufficient
waiting period.
4.164 TheUnited States alsoresponded thattheECclaim thatithadnosolid information about the
percentage ofmeat produced intheEuropean Communities from animals towhich hormones hadbeen
administered forherd management andother purposes wasatodds with theconstant ECreference
tothestrict controls onsuch useandtheneed toidentify every single animal towhich they hadbeen
administered. Industry sources intheEuropean Communities informed theUnited States that3.75
to4percentofallcattle were treated each year, based onanaverage ofinformation, known inBelgium,
France, Germany, theNetherlands andtheUnited Kingdom. Inaddition, about 6percentofsheep
intheEuropean Communities were treated each year. In1995, from onecompany alone, 2million
doses ofhormones were sold(forsheep) and½million doses were soldforcattle. Furthermore, by
stating thathormones were administered to1to2percent oftheECherd each year, theEuropean
Communities failed tonotethatthisfigure should bemultiplied bythenumber ofyears thattheanimals
intheherd remained inproduction inorder todetermine thequantity ofthemeat supply from animals
that, during their lifetime, hadbeen administered these hormones. Forexample, ifthehormones were
administered todifferent animals each year, then over thecourse of5years, 5to10percent ofthe
herd would have been administered these hormones. Alternatively, ifthehormones were administered
tothesame animals, then ananimal may have received fiveseparate setsoftreatment. Furthermore,
there wasnorequirement thatthehormones administered always bethesame substances. Nothing
prevented ananimal intheEuropean Communities from having been exposed tomultiple hormones
(orintheECview, "combinations" or"cocktails" ofhormones).
(ii) Metabolites
4.165 TheEuropean Communities argued thatother risks arose from thehormones atissue because
oftheir metabolites. When drugs were introduced intothebody, their pharmacological andtoxic effects
were directly correlated totheir concentration intissues andfluids. Theconcentration ofadrug was
afunction ofitsresorption, excretion andmetabolism. Drugs were metabolized (broken down) and
their metabolites might alsohave pharmacological effects, which might differ from theeffect ofthe
parent drug. Metabolites might have different sideortoxic effects. Anabolic steroids hadalarge
variety ofmetabolites, some ofwhich were only recently identified. Thepharmacological andtoxic
behaviour ofmany ofthese metabolites were stillunknown. Inaddition, thesame parent substances
might produce different metabolites indifferent species, making theextrapolation from studies on
laboratory animals tohumans unreliable.
4.166 TheEuropean Communities asserted thatthere were scientists whoargued thatknowledge about
thetoxicity ofthemetabolites ofthese hormones wasasyetvery limited. Moreover, metabolites of
such substances which, even inlowconcentrations, might have highly toxic effects were generated
inthehuman body.110These scientists argued that"theuseofhormones ingrowth promotion ofanimals
should notbeallowed, asitcannot beexcluded thatunchanged agents, their metabolites and, above
all,unknown highly effective andtoxic metabolites aredistributed with themeat which ispurchased
110W.Schänzer, "The Illegal useofAnabolic Agents inSport", 1995 ECScientific Conference Proceedings, p.352.WT/DS26/R/USA
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byconsumers".111Moreover, insome oftheexperimental studies onwhich the1988 JECFA Report
wasbased, noextensive research andriskassessment ofthepotential risks arising from themetabolites
ofthehormones under consideration hadbeen carried out.112Noting thatdespite alltheuncertainties,
JECFA haddecided toestablish atemporary ADI fortrenbolone acetate while requesting additional
information tobesubmitted toitby1990, theEuropean Communities argued thatinlight ofthe
arguments advanced bysome scientists, itwasquestionable whether thedecision oftheJECFA could
beregarded asareasonable one. TheEuropean Communities remarked thattheUnited States had
already approved theuseoftrenbolone forlivestock growth promotion in1987, whereas Codex had
established itsfinal recommendation only in1995. In1987, theStanding Commission onHormone
Toxicity oftheGerman Society forEndocrinology andtheCommission forToxicology oftheGerman
Society forPharmacology andToxicology hadstated that"thepresent information inrespect toalikely
genotoxic potential didnotallow afinal evaluation fortrenbolone".113
4.167 TheUnited States argued thatECclaim thatthere were health risks arising from metabolites
ofthehormones were unfounded. TheEuropean Communities appeared tosimply relyonthefact
that"there arescientists whoargue" that"knowledge isverylimited" andmetabolites "may have adverse
effects", with noevidence ofanysuch adverse effects, much lessinrelation tospecific hormones or
tothelevels ofexposure from theuseofhormones forgrowth promotion purposes. Furthermore,
theEuropean Communities cited studies ontheillegal useofanabolic hormones inathletes which had
nothing todowith residues ofhormones inmeat. TheUnited States disagreed thatCodex hadfailed
toexamine potential risks from metabolites. Theadditional studies onmetabolites requested bythe
1988 JECFA report hadbeen performed andaccepted in1989. TheLamming Committee hadalso
examined thesafety ofthemetabolites forthehormones ithadreviewed andhadfound them tobe
safe. Moreover, intheUnited States, metabolism ofacompound wasanintegral partofthesafety
assessment ofallanimal drug products prior toapproval ofthedrug orthesetting ofafinal MRL for
thehormone products. Allscientific evidence showed thatthere were norisks ofharm tohuman or
animal health duetoresidues ofanymetabolite ofthesixhormones when used forgrowth promotion.
4.168 TheEuropean Communities responded thatdataderived from thedirectly-observed effects
ofthese hormones onhuman beings (whether fortherapeutic purposes orbyathletes) wasequally or
even more important than dataderived from laboratory animals. Thefactthatthese anabolic steroids
were used "illegally byathletes" didnotdiminish therelevance oftheECargument, since themetabolites
ofthese substances, whether used legally orillegally, were thesame. The1988 JECFA Report on
which theUnited States based itscontentions inthiscasestated thatinformation from human casereports
ondrugs alsoused therapeutically inhuman beings "may provide important evidence ofpossible adverse
effects inhuman beings thatarenotdetectable inanimal models". TheCodex hadalsonoted that
"[h]uman data ofinsufficient extent may beconsidered inthesetting of[aCodex Acceptable Daily
Intake] onthebasis thatextrapolation ofdata from animal studies contain greater uncertainty".
111Ibid.,p.353.
112Asanexample, theEuropean Communities noted that, asregards trenbolone acetate (TBA), theJECFA hadstated
that"[i]n theabsence ofsatisfactory toxicological datatheCommittee wasunable toestablish aseparate no-effect level for
thea-TBOH metabolite. Italsonoted thatthismetabolite wasnotproduced insignificant amount intherat,which made
itinadvisable toextrapolate from data generated from ß-epimer, experiments inthatspecies".
113B.Hoffmann, "Problems ofResidues andHealth Risks ofAnabolic Agents withSexHormone-Like Activities", 1995
ECScientific Conference Proceedings, p.291.WT/DS26/R/USA
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(iii) Combinations ofhormones andmultiple exposure
4.169 Referring toscientists 'reports atthe1995 ECScientific Conference ofevidence oftheillegal
useofgrowth-promoting substances inmany European countries andelsewhere114,theEuropean
Communities submitted thattheillegal useofmixtures ofveterinary drugs andgrowth promoters might
result inunpredictable residue levels inedible foods, which might constitute ariskfortheconsumer.
This might beduetovariations inphysiological andpathological parameters, altering drug disposition
andelimination. Biotransformation patterns ofsynthetic drugs andhormones might differ markedly
depending ontheanimal species andgender. Interactions might occur between compounds ashad
been reported forsulphadimidine andoestrogenic andandrogenic hormones administered todwarf goats.
This might require longer withdrawal times inorder toarrive atsaferesidue levels. Forthose reasons,
the1995ECScientificConferencehadconcludedthat"theuseofcombinations(orcocktails)ofhormones
poses serious risks forthehealth ofconsumers because theuseofmixtures, which usually contain
illegal substances, ismade intheform ofinjections, rather than implants, andthisisanimpediment
totheirdetectionatslaughter.Thispotentiallyallowsthesaleofmeatcontainingveryhighconcentrations
ofhormones".115
4.170 IntheEuropean Communities, theterms "combinations" and "cocktails" were used
interchangeably todenote thehigher potency andmultiplied negative effects thatsuch substances exerted
when used incombination, compared towhen used individually. Whether thecombinations were legally
marketed wasirrelevant, asthere wasnothing toprevent anunscrupulous farmer from administering
one, two, three oreven more ofthese legally available substances, inanattempt toyield potentially
higher growth rates. TheEuropean Communities stressed thattheuseofcocktails intheUnited States
didnotappear tobesubject tostrict control, since anumber ofproducts were freely available onsale
inthemarket. Ontheother hand, several ofthelicensed products intheUSmarket were commercially
manufactured combinations ofhormones, with adjuvants (i.e.additives used tospeed uporslow down
theactive element ofthecombination).
4.171 TheEuropean Communities argued thatwhen JECFA hadestablished itsrecommendations
ontheADIs andMRLs ofthehormones atissue, ithadconsidered only information onthesingle
substances, although scientists hadagreed thattheconcept ofADI wasnotapplicable toassess the
riskfrom exposure tomixtures (orcocktails) ofcompounds. The1988 JECFA Report had, however,
pointed clearly totheneed toexamine theeffects ofcombinations:
"The Committee noted thatseveral ofthehormonally active substances ontheagenda were
used incombination onewith another, andrecommended that, where substances having similar
physiological activities were combined, evidence thattheir hormonal effects were additive,
rather than synergistic, should beprovided. TheCommittee agreed thatdataontheresidues
ofeachofthesubstances thatareused incombination should beavailable forevaluation, whether
ornottheir physiological activities were similar."
TheEuropean Communities concluded thatthere wasconsiderable potential riskarising from theuse
ofcombinations, containing authorized orunauthorized hormones, andthatexisting international rules
didnotdeal adequately with thispotential source ofrisk.
4.172 TheUnited States submitted thattheECclaims regarding health risks arising from theuse
ofhormonesincombinationwereunfounded.Therewasadifferencebetweencombinationsofhormones
andtheso-called "cocktails." Combination products contained onlyauthorized hormones andadjuvants.
114"Report andConclusions", Steering Committee, 1995 ECScientific Conference Proceedings, p.9.
115Ibid.,page 9,andH.A. Kuiper, "Risk Assessment Strategies forXenobiotics", 1995 ECScientific Conference
Proceedings, p.376.WT/DS26/R/USA
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Theproduct intended forcommercial salewastheproduct tested andreviewed intheUnited States
andsubjected toboth animal andfood safety analysis prior torelease forcommercial purposes.
Furthermore, theywere manufactured according torequired good manufacturing practices sothatthey
were consistent inidentity, strength andpurity. Since hormones might belegally purchased in
formulations thathadbeen demonstrated tobesafeandefficient, there wasnoreason forafarmer
orarancher tobuyother combinations andusethem illegally. Furthermore, because approved
formulations were tested foroptimal growth promotion effects, theaddition ofother hormones orhigher
dose levels, under conditions different from thelabel, didnotresult inadditional growth effects.
Accordingly, such usewould result inincreased economic costs with noaccompanying economic gain.
4.173 Ontheother hand, theUnited States observed thattheterm "cocktails" hadnolegal definition
andwasgenerally used torefer tothemixture ofillegal drugs prepared inunlicensed facilities that
were sold ontheblack market inECmember States. TheUnited States agreed thattheuseofsuch
cocktails wasdangerous andstressed thatthey were illegal foruseintheUnited States. Finally, it
wasnotclear how concern over theuseofillegal "cocktails" could justify theECbanontheuseof
strictly regulated single orcombination products, oreven howtheconcern over "cocktails" could justify
theECbanontheuseofallhormones forgrowth promotion purposes, including theadministration
ofsingle hormones.
4.174 TheEuropean Communities claimed thatillegal marketing ofhormones andveterinary drugs
ingeneral intheUnited States might beasgreat as,oreven greater than, intheEuropean Communities.
TheEuropean Communities referred toa1985 report produced bytheUSCongressional Committee
onGovernment Operations, entitled "Human Food Safety andtheRegulation ofAnimal Drugs". This
report noted that"...theproblem ofillegal veterinary prescription drug sales isofsuch magnitude
andpervasiveness thatitthreatens thecredibility oftheveterinary drug approval andtheregulatory
process". These conclusions were based onafocused investigation bytheUSFood andDrug
Administration which found that"indiscriminate saleofprescription veterinary drugs" was"pervasive"
throughout eastern Iowa, andthatother, ongoing investigations seemed toconfirm that"...theillegal
sales problem wasprobably nationwide inscope".
4.175 TheEuropeanCommunitiescontendedthattherisksthatmightpotentiallyarisefromthemultiple
exposure ofhumans tohormones andother chemical substances were similar tothose resulting from
theillegal useofcombinations (orcocktails) ofhormones. Allfoodstuffs, whether ofanimal orplant
origin, were likely tocontain trace amounts ofseveral substances derived from various sources, afact
currently notaddressed inanyriskassessment strategy forfood. Because theADI andMRL assessed
thesafety ofasingle compound andnottheexposure tomixtures ofcompounds, asufficient protection
ofhumans wasonly guaranteed iftheMRL wasnotexceeded. Thus, there wasasubstance-related
risktoconsumers iftheacute ingestion ofaresidue amount exceeded theestablished MRL andpossibly
theADI. Butthequestion alsoarose onhow toprotect consumers from apotential adverse effect
resulting from long-term treatment with growth- promoting substances. Such adverse effect wasthe
possibility thatthebiotransformation ofother compounds might bealtered, ashadbeen shown inthe
case ofsteroids. This might result inaltered residue kinetics forthose compounds.116TheEuropean
Communities claimed thattheideathatthere might beariskassociated with thelong-term exposure
toamixtureofsubstances,resultinginapossiblebiotransformationofothercompounds,wasaprecursor
totheso-called "precautionary" principle anditwasattheheart ofthepolicy followed bytheEuropean
Communities onsuch issues.
4.176 TheUnited States claimed thatwith respect tomultiple exposure, theEuropean Communities
hadonce again failed toidentify anyparticular risk orprovide anyevidence orrisk assessment
demonstrating arisk. Instead, theEuropean Communities hadsimply mused about the"idea thatthere
116Working Group II,"Assessment ofHealth Risk", 1995 ECScientific Conference Proceedings, p.20.WT/DS26/R/USA
Page 75
may bearisk". Inthismusing, theEuropean Communities hadalsochosen toignore thefactthat
oneofthereasons forapplying asafety factor of100(200 inthecaseofMGA) wastotakeintoaccount,
among other things, thepossibility ofexposure tomore than onecompound over alifetime.
4.177 TheEuropean Communities responded thattheCodex itself hadnoted that"[u]ncertainty
inthesafety evaluation process isprimarily addressed through theuseofsafety factors. Their respective
values arearbitrary andhave nomeasured biological significance, however, their appropriateness is
somewhat borne outbyexperience".117Thesafety factor, therefore, might notprovide thenecessary
protection, especially inthecaseofpotentially carcinogenic substances whose mode ofaction wasnot
clear, astheexample ofthehormone DES hadshown. The"safety factor" wasinreality nomore
thanauseful toolandapplied tothose scientific reports which depended onextrapolations from imperfect
data onlaboratory animals tosetADIs andMRLs forhuman beings. Although these concepts had
served well inthepastandwould continue todosointhefuture, aMember wasentitled todeviate
from these concepts asused byCodex inestablishing recommendations. Codex hadproven tobeuseful
insetting guidelines andrecommendations forfood additives precisely because ithadleftitsmembers
freetodecide whether they would accept itsrecommendations. TheSPSAgreement wascastlargely
onthesame basis, because itallowed Members todepart from international standards, guidelines or
recommendations under theconditions laiddown therein (e.g. Article 3.3).
(iv) Detection andcontrol
4.178 TheEuropean Communities noted thatnone ofthescientific conferences andexpert review
groups (including theLamming Report andthe1988 JECFA Report), which hadexamined thepotential
risks from theuseofthese hormones foranimal growth, hadconcluded infavour ofanunqualified
useofthese hormones forgrowth promotion purposes. This wasbecause theadministration ofthese
hormones tolaboratory animals, athigh doses butalsoatlowdoses insome experiments, hadcaused
serious health effects, including cancer. Furthermore, allthescientists which hadexpressed themselves
infavour ofallowing theuseofthese hormones atlowdoses forgrowth promotion purposes didnot
exclude risks tohuman andanimal health from improper administration orfrom combinations and
metabolites ofhormones andmultiple exposure. This critical caveat onconditions ofusehadbeen
recognized intheECCommission proposal (COM(84)295 final) which finally ledtotheadoption of
Directive 88/146/EEC. This Directive proposed toallow theuseofthethree "natural" hormones only
under thefollowing conditions inorder tosafeguard public health:
(i) only intheform ofanimplant tobeadministered inapartoftheanimal discarded
atslaughter (usually theear);
(ii) toanidentified animal only, toallow control ofthewithdrawal period;
(iii) only byaveterinarian;
(iv) substances allowed tobeadministered must beonanEClist, setting outclearly
conditions ofuse; and
(v) these substances must beshown tobeeffective andsafe.
4.179 TheEuropean Communities observed thattheLamming Report hadalsourged theattention
oftheEuropean Commission totheneed tolaydown certain essential provisions before thethree natural
hormones could beused forgrowth promotion, inparticular asregarded thefollowing:
117Codex Alimentarius Commission (1993), "Risk Assessment Procedures used bytheCodex Alimentarius Commission
anditsSubsidiary Advisory Bodies", p.11.WT/DS26/R/USA
Page 76
"(a) Instructions foruse:
1. Specification ofthedoses, thetype ofpharmaceutical preparation, thenumber and
frequency ofadministrations.
2. Association ofanabolic agents.
3. Localization ofimplant andablation ofzone treated.
4. Withdrawal period before slaughter.
5. Identification ofanimals treated, with indication oftheperiod oftreatment.
(b) Surveillance programme andanalysis methods
1. Control ofproduction andtrade inanabolic agents.
2. Veterinary control ofauthorized uses.
3. Means andmethods ofcontrol."
4.180 TheEuropean Communities noted thatJECFA hadrecognized thattheuseofthese hormones
wasunlikelytoposeahazardtohumanhealthifusedinaccordancewithgoodanimalhusbandrypractice,
butthatthere were nointernationally agreed rules onwhat constituted "good animal husbandry practice"
fortheadministration ofthese hormones. Asfaras"good veterinary practice" wasconcerned, the
1988 JECFA Report hadnoted thattheCode ofPractice fortheUseofVeterinary Drugs wasunder
preparation bytheCodex Committee. This Codex Code ofPractice hadfinally been adopted in1993.118
However, itwas notclear how strictly thisCode was adhered tobycountries. The European
Communities wondered what concrete measures theUnited States hadtaken inthecase ofhormones
tocomply with theCodex Code.
4.181 TheEuropeanCommunitiessubmittedthatdifficultiesarosebecausetheidentificationofanimals
ormeat from animals which hadbeen treated with thethree natural hormones wasdifficult duetothe
wide variation innatural levels ofthese hormones arising because offactors such assex, age, diet,
physiological condition, etc. While residue analysis fornatural hormones intreated animals could
experimentally show differences between them anduntreated animals, itwascurrently notpossible
through routine tests toidentify treated animals onthebasis ofassays ofedible tissue samples, and
itwasalsodifficult using blood, urine orfaeces. Acountry allowing imports ofanimals andmeat
from animals treated with hormones would have torelylargely onchecks andcontrols onuseof
hormones carried outbytheexporting country iftrade wasnottobeimpeded, buttheimporting country
would alsohave tocarry outchecks andcontrols inorder toensure thatitsconsumers atemeat which
conformed totherequisite standards. Detection andsurveillance ofhormones wasbased onscreening
methods,principallyimmunoassays(radioorenzymeimmunoassays)becausetheywererapid,relatively
lowcostandcould beapplied simultaneously toalarge series ofsamples.119However, theEuropean
Communities claimed thatalltheavailable methods used fordetection andcontrol hadtheir limits and
drawbacks. Furthermore, although Codex hadestablished anadhocworking group onthematter,
there were still nointernationally agreed rules forthemethods tobeused forresidue control
programmes.120TheEuropean Communities argued thatinlight ofthepotential risks tohuman and
animal health resulting from theuncertainties inresidue control programmes andtheabsence of
118International Code ofPractice forControl oftheUseofVeterinary Drugs, adopted byCodex in1993.
119M-L Scippo andGMaghuin-Rogister, "Methods ofDetection andSurveillance ofNatural SexSteroid Hormones",
1995 ECScientific Conference Proceedings, p.541 seq.
120TheEuropean Communities stressed thatin1991 theCodex Commission hadonly established provisional method s
toserve asapotential source ofuse.SeeJoint FAO/WHO Food Standards Programme, Residues ofVeterinary Drugs in
Food, Vol. 3,2ndEd., 1993.WT/DS26/R/USA
Page 77
internationally agreed rules, anyMember (including theEuropean Communities) wasentitled toadopt
aregulatory system toachieve thelevel ofprotection foritspublic thatitconsidered tobeappropriate.121
4.182 TheUnitedStatesclaimedthattheEuropeanCommunitieshadmovedtoadiscussionof"control,
inspection andapproval procedures" which were covered inArticle 8andAnnex CoftheSPS
Agreement, because ithadbeen unable toproduce anyriskassessment orevidence with respect to
thesubstances themselves tosupport itsban. Theexperts advising thePanel hadconfirmed thateven
where there wasafailure tofollow good animal husbandry orveterinary practice, resides ofthethree
natural hormones administered forgrowth promotion purposes might well stillbewithin thenormal
physiological range. TheEuropean Communities wasunable toidentify anyparticular riskorprovide
anyevidence orriskassessment demonstrating arisk. TheEuropean Communities could notexplain
why anyrisks from itsfailure toadequately detect residues ofhormones would behigher inthecase
thatitpermitted theimportation ofanimals towhich anyofthesixhormones hadbeen administered
forgrowth promotion purposes compared toitscurrent ban. TheUnited States stressed thatpresumably,
under itscurrent ban, theEuropean Communities stillrantheriskthatitwould notbeabletodetect
allbanned animals andmeat. Furthermore, theEuropean Communities hadnotexplained why itwas
unable toimplement MRLs forthesixhormones when itwasabletoimplement MRLs forother foods
andsubstances.
4.183 TheEuropean Communities agreed thatapotential formeat toslippastitsdetection systems
existed, andthat itcould notexpect todetect every instance ofillegal use. ButtheEuropean
Communities stressed thatitoperated comprehensive andcostly residue control programmes designed,
andeffectively applied, todetect, asfarastechnically possible andeconomically feasible, such residues
from allsources.122Thefactthatthere wasapotential forprohibited residues toevade itscontrol and
detection wasnotinitself areason fortheEuropean Communities toadopt theUSapproach onthis
issue. Tothecontrary, thisriskofresidues ofpotentially carcinogenic substances evading detection
wasanimportant factor incarrying outaproper riskassessment andseriously influenced, right from
thebeginning, thedecision ofcautious ECmember States insetting thelevel ofsanitary protection
they deemed appropriate intheir territory. TheEuropean Communities alsodidnotdispute thefact
thatMRLs were useful tools inregulating drugs andfood additives inappropriate cases. Butitwas
obvious thatinthecaseofmass medication ofthefood animal population, theamount oftesting required
toapply theEClevel ofprotection would bevery much higher than under thepresent EClegislation.
Itwasequally obvious thatthechance ofdetecting violations would bemuch lower. TheEuropean
Communities argued thatthedifficulties arose because exporting countries (like theUnited States) were
notwilling andcapable ofensuring, onareasonable basis, thattheADI andMRLs recommended by
Codex would notbeexceeded intheir exported meat. Thetechnical andfinancial burden hadtobe
shared mainly bytheimporting Members which wished toseetheCodex 'srecommendations strictly
observed.
4.184 TheEuropean Communities argued thatUSauthorities practically didnotcontrol thesaleof
these hormones either individually orascompounds, andnoted thattheywere freely available onsale,
even bymail. There wasnotesting andchecking ofresidues forthenatural hormones andforthe
121TheEuropean Communities noted that, forexample, Argentina prohibited theuseofthethree natural hormones (while
allowing theuseofthetwosynthetic ones), citing asanessential motive fortherestriction thelackofsuitable methods for
measuring hormone residue levels inmeat. 1983 OIE Scientific Report, p.411.
122Directive 88/146/EEC explicitly required thatundertakings intheECmember States producing theprohibited hormones,
those companies authorized tomarket these hormones forwhatever purposes andundertakings producing pharmaceutical
andveterinaryproductsbasedonthosesubstances,mustkeepadetailedregisterrecording(inchronologicalorder)thequantities
produced oracquired andthose soldorused fortheproduction ofpharmaceutical andveterinary products. These requirements
hadnow been tightened byrequiring thenames ofthepersons towhom such quantities hadbeen soldorfrom whom they
hadbeen purchased tobemade available tothecompetent authorities (Article 9ofDirective 96/22/EC). Inaddition, heavy
fines andpenal sanctions, including imprisonment, were imposed when violations were detected.WT/DS26/R/USA
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synthetic hormones. TheUnited States hadeven dropped thethree natural hormones from their control
programme, even though theUnited States applied MRLs onthem, indicating thatnotesting hadbeen
performed because implant-associated residues could notbedistinguished from normal background
concentrations. TheEuropean Communities added thatMGA hadbeen tested forthelasttime in1993,
when only22samples hadbeen checked ofwhich onehadtested positive. Zeranol hadbeen lastincluded
in1989 andtrenbolone hadnever been included inthecontrol programme. Moreover, theEuropean
Communities noted thattheUSFSIS hadreported anumber ofcases ofimproper useofhormones
in1986. More recently, in1993, theFSIS hadstated that"one fourth ofonepercentofanimals tested
showed positive forresidue violation. Inother words, almost 99.74 percentofanimals tested showed
noresidue violation". TheEuropean Communities argued thattheFSIS 1993 dataindicated thatnone
orvery fewofapproximately 130million head oflivestock slaughtered intheUnited States hadbeen
monitored forresidues ofnatural orsynthetic hormones.
4.185 TheEuropean Communities claimed thatthesituation onresidue controls andchecks inthe
United States wasnotclear andconcluded thatifithadfollowed theexample oftheUnited States in
applying theCodex recommended MRLs inthewaythey were applied intheUnited States, itwould
have certainly failed toachieve itslevel ofprotection which wasnoresidues ofthese hormones inmeat
forhuman consumption, anditwould also have failed toprotect animal health. The European
Communities wascorrect initsanalysis when performing itsriskassessment inthesense ofArticle 5,
thattheuseofthese hormones forgrowth promotion purposes under theconditions identified byall
scientific reports (i.e. inaccordance with good veterinary practice) would notbetechnically or
economically feasible. Therefore, theresponsible ECinstitutions hadrightly concluded thatprohibition
ofuseofthese hormones wastheonly reasonably available least trade-restrictive measure.
4.186 TheUnited States firstnoted thattheECclaim thatanMRL would notbefeasible because
oftheassociated amount oftesting forresidues wasdirectly atodds with theECclaim that"atleast
intheEuropean Communities there arecomprehensive andcostly residue control programmes designed
andeffectively applied todetect, asfarastechnically possible andeconomically feasible, such residues
from allsources". Second, theUnited States noted thatforpurposes oftheECbanitdidnotmatter
howstringent anexporting country 'srequirements were orwhat typeofprogramme wasinplace with
respect totheuseofthese hormones. Animals andmeat were banned, period. Theissue inthisdispute
wasnotwhether theUnited States subjected itsexports ofanimals andmeat toanyparticular controls
orwhether theUSsanitary measures were equivalent totheECmeasures123,butwhether theECban
wasinaccordance with theWTO Agreements.
4.187 TheUnited States then noted thatcontrary totheECallegations, ithadanextensive system
inplace toensure thatgrowth promoting hormones were used domestically according togood animal
husbandry practice. Sponsors were required todetermine conditions forsafeandefficacious useof
their products andtosupply thatdata tothegovernment forreview. Labels forproducts hadto
accurately describe these conditions foruseandbewritten inawaylikely tobefollowed inpractice.
Allsponsors were required tomanufacture their drug products according tospecifications andGood
Manufacturing Practices toensure consistency ofstrength, purity andidentity, andtheUnited States
inspected these manufacturing facilities periodically. TheUnited States alsorequired amanufacturer
tokeep records ontheamount ofproduct sold andtowhom (thespecific retailer); overselling ina
particular arearelative toneed could trigger investigative action. TheUnited States alsohadauthority
toinvestigate liveanimals onthefarm orfeedlot toensure correct useoftheproducts. TheUnited
States operated anadverse drug reporting system toensure thatproducts were being used inasafe
manner. Attheslaughterhouse, theUnited States inspected animals toensure theproper useofthe
hormones.
123TheUnited States noted thatissues ofequivalency were examined under Article 4oftheSPSAgreement.WT/DS26/R/USA
Page 79
4.188 These practices, along withdirected monitoring (“forcause ”inspections) andrandom sampling
through theResidue Monitoring Programme, ensured thatpublic safety wassafeguarded. TheUnited
States operated anational residue programme (NRP) aspart ofitsregulatory oversight ofmeat
production. TheNRP didnotapply tothenaturally occurring hormones because implant-associated
residues could notbedistinguished from normal background concentrations. Zeranol, trenbolone and
MGA were among thecompounds covered bytheNRP. Thecompounds actually tested under the
NRP varied from year toyear, with emphasis given tothose most susceptible toimproper use. The
most recent year inwhich hormone growth promoters hadbeen tested was1991, when 185steers and
129heifers were randomly selected nationwide atslaughter forDES/zeranol testing. Allfindings met
FDA tolerances. Thelastyear inwhich testing hadbeen done forMGA was1988. Allofthe373
randomly selected heifers were incompliance with FDA requirements. Testing could bereinstituted
ifaproblem were perceived. Inaddition, USslaughter establishments producing meat andoffal products
forexport toECmember States were required toparticipate inanexpanded residue testing programme
conducted byprivate laboratories. Under thisprogramme, thenumber ofsamples collected during
thelastfiveyears, forthecattle, sheep, swine andequine species, hadbeen approximately asfollows:
zeranol =3500; MGA =1300; trenbolone =3500; andDES =3500. Tothebestoftheknowledge
ofFSIS employees working closely with thatprogramme, allofthefindings metFDA tolerances.
4.189 TheUnited States clarified theconditions ofuseforthese hormones. Inthecase ofcattle in
theUnited States, hormones were notgenerally administered byindividual farmers. Instead, thevast
majority ofthehormones were administered when theanimal firstentered thefeedlot. Atthistime,
ateam under thesupervision ofaveterinarian assessed theoverall health oftheanimal andprovided
veterinary treatment asrequired. Animplant wasusually inserted byteam members atthistime. As
largecommercialoperations,thefeedlotshadgreatincentivetoproperlycarefortheseanimals,including
proper placement ofimplants, inorder toprovide theconsumer thehighest quality product possible.
Implants were developed forusewithspecial delivery devices designed forearimplantation. Therelease
rateofactive ingredient from theimplant wasmaximally effective forgrowth promotion purposes when
implanted intheear. Implantation atsites other than theearwasdifficult inpractice asthehide was
very tough andnoteasy topenetrate. Other implantation wasalsonotaseffective asearimplantation,
might damage thecarcass with scartissue thus decreasing itsvalue, andwould entail legal liability
andacondemned product. Therefore itwasinthefeedlot 'sinterests tousetheimplants under the
conditions ofusespecified onthelabel.
4.190 TheUnited States claimed thatwith respect toUSimports from third countries, anyexporting
country wasrequired tohave aprogramme inplace toensure thatfood produced from animals treated
with anydrug wassafeforconsumers. This programme hadtoachieve alevel ofprotection atleast
equal totheUSappropriate level ofsanitary protection. Theexporting country ’sprogramme must
include asystematic national residue testing programme. Exporting countries were required toreport
theresults oftheir NRP toretain eligibility toexport totheUSmarket. Toexport meat totheUnited
States, allforeign countries hadtoobtain anannual USresidue certification stating thatthecountry
maintained, among other requirements, acontrol programme toensure compliance with USstandards
forresidues inmeat destined fortheUnited States. One element oftheUSaudit ofresidue control
programmes wastheevaluation ofannual testing results supplied byeach country. TheUnited States
recommended thateach country determine which compounds should beincluded initsannual residue
sampling plan, andprovide information withtheplanthatexplained thedecisions toinclude (orexclude)
compounds. Theselection ofcompounds tobeincluded inthetesting planshould bebased onconditions
present inthecountry, e.g., availability ofspecific compounds, conditions thatwarranted use, and
theresidue hazard when used. Indetermining whether acountry maintained anacceptable residue
control programme, theUnited States considered thefollowing, inaddition totheresidue sampling
plan andtestresults: (i)USportofentry testing results; (ii)thefindings ofon-site reviews ofplants
exporting product totheUnited States, andlaboratories performing theanalytical testing; (iii)compound
selection, statistical design, andimplementation ofsampling plans; (iv)trace back andenforcement
procedures; and(v)timely receipt ofinvestigative reports following aUSport ofentry violation.WT/DS26/R/USA
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4.191 TheEuropean Communities submitted thatitdidnotargue thatitwas"unable" toimplement
MRLs forgrowth-promoting hormones, butthatitwasunwilling todoso. Inthisitwasacting
consistently, asitdidnotoperate MRLs forother drugs which hadpowerful adverse physiological
effects,includingcarcinogenicity,atlowconcentrations.Therefore,ifafterconductingariskassessment
aMember concluded thatitslevel ofsanitary protection could notbeensured byapplying theMRLs
recommended byCodex, thisMember wasallowed todepart from those MRLs. This wastheprinciple
onwhich both Codex andtheSPS Agreement were based.
4.192 TheEuropean Communities referred tothereports ofDr.Pérez-Comas inrelation todetection,
control andadministration ofhormones. Dr.Pérez-Comas argued that:
"...anomalous sexual development inPuerto Rico isamajor andserious public health problem.
(...)Wehave been detecting anincrease ofsuch cases since early in1969 (...)Uptothisdate
over 1,500 patients have been documented.
"From ourpatients, wehave deducted thatenvironmental contaminants areastrong factor
inetiology ofthecondition thataffects children ofboth sexes, different races andnationalities
residing inPR,andallages intheform ofAnomalous Sexual Development. (...)Wehave
documented clinical evidence ofincreased serum total oestrogens inasignificant number of
patients, with over 60percentofthefemales with ovarian cysts, variable levels ofFSH, LG
&Prolactin, thatrecede ordiminish inasignificant number ofpatients after ameat andpoultry
depletion diet.
"We have been informed thatanomalous sexual development cases areincreasing inChile,
Bolivia andColombia. Astoourknowledge nodefinite cause have been found, butpoultry
andmeat contamination isbeing considered, forinLatinamerica multiple useofgrowth
promoting hormones have been documented. Weconsider thatinPRtheAnomalous Sexual
Development inchildren iscomplex with different etiological factors such aszeranol, other
unknown oestrogenic substances, andpesticides. Serious emphasis must bedone onthecontrol
ofthese substances anditsavoidance inanimal husbandry. (...)"124
4.193 Finally, theEuropean Communities argued thattheUSunwillingness tocomply with theEC
measures wastheonly obstruction toitsexports. Buttheexperience ofthe"Interim Measure" showed
thatindividualfarmersintheUnitedStateshadnodifficultyincomplyingwiththeEClevelofprotection.
Thenumber ofcompanies intheUnited States which promoted their meat totheconsumer ashaving
been produced without theuseofhormones wassignificant andgrowing.
(v) Administration anduseofhormones
4.194 TheEuropean Communities claimed thatthere were additional risks tohuman andanimal
health arising from theadministration andpotential misuse ofhormones. Atthe1995 ECScientific
Conference, ithadbeen observed thatamisuse could behazardous toconsumers, ifinstead ofthe
authorized implant cheaper black-market products were administered totheanimals viainjections at
undefined parts oftheanimals 'bodies. Moreover, injection could begiven inaddition toanauthorized
implant. Such misuse would probably notbeanalytically detectable, andnotonly inthecase of
endogenous substances. Iftheuseofhormonally active substances were authorized, thiswould probably
alsoleadtoadramatic reduction ofthepossibilities toreveal such amisuse with thehelp ofdetected
injection sites, because there would nolonger beindications toselect animals during thepost-and ante-
mortem examination thatwere considered tobesuspicious. Onthecontrary, each animal would have
tobecontrolled forinjection sites. Since thiswascompletely unrealistic, arandomised selection of
124A.Pérez-Comas andC.A. Saénz, "Anomalous Sexual Development inPuerto Rico: 28Years ofExperience",
28February 1997.WT/DS26/R/USA
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thecarcasses wastheonly control forinjection sites. Consumers could thus besubject totheriskof
eatingundetected,maybehighlycontaminated,injectionsites.Irrespectiveoftheassessmentofanumber
ofhormonally active substances bytheCodex, theprinciple thatthehealth hazard ofasubstance
depended only onitsdosage continued tobevalid alsofortheriskofinjection sites. Particularly in
thecaseofillegally administered black-market products, thedosage wasnotpredictable. Inthecontext
ofpreventiveprotectionofconsumers'health,itwasnecessarytotakethemisusepotentialofasubstance
intoconsideration when assessing health risks. Ifhealth risks toconsumers could notbeexcluded when
asubstance wasmisused, single substances with anextreme misuse potential should alsobebanned
even ifthesubstances were nothazardous when legally used. Risks toconsumers 'health could not
beexcluded ifclenbuterol andhormonally active growth promoters were abusively administered. It
wasquestionable iftheauthorization ofthese substances asgrowth promoters would endtheir extreme
misuse potential; theauthorization ofasubstance distinctly restricted itscontrollability. Thus the
misuse ofauthorized substances washardly controllable. Because oftheeffect onsampling and
inspection, theauthorization ofasubstance always went hand-in-hand with afacilitated useofthe
corresponding black-market product.125
4.195 TheUnited States rejected theECattempt tojustify itsbanonthegrounds thatitcould not
besurethatthehormones would always beadministered correctly. Itwasnotclear totheUnited States
how thisdiffered from thepurported "detection andcontrol risks", since inboth cases theEuropean
Communities claimed tobeconcerned thatunauthorized meat would slippastitsdetection. Inany
event, thesame problems applied tothiscategory ofpurported riskasapplied totheECdetection and
control concerns. TheEuropean Communities didnotidentify anyparticular risk, nordiditproduce
anyriskassessment orevidence ofrisk. Furthermore, theEuropean Communities didnotexplain
why there wasnotalways apotential formeat containing prohibited residues toevade itsdetection,
even under itscurrent ban. TheEuropean Communities hadpermitted thesaleandconsumption of
domestic meat even inthefaceofadmitted andwell-publicized illegal useofhormones initsterritory.
TheEuropean Communities alsopermitted theimportation ofmeat, including meat from animals to
which hadbeen administered hormones forpurposes other thangrowth promotion. There could never
beanabsolute guarantee thattheEuropean Communities could detect every instance ofanincorrect
administration ofhormones. With regard tothepotential misuse ofthese products, theUnited States
claimed thatexperts hadacknowledged thateven ifmisused, theresidues ofthesixhormones might
wellbebelow theCodex (orFDA) MRLs (inthecaseofthethree synthetic hormones). Indeed, direct
injection (rather than useofanimplant) ofdoses 100times higher than approved doses stillresulted
inresidues well below theestablished ADI.
4.196 TheEuropean Communities responded thatithadnodifficulty inadmitting thatapotential
formeat toslippastitsdetection always existed anddidnotexpect todetect "every instance" ofillegal
use. Butatleast intheEuropean Communities there were comprehensive andcostly residue control
programmes designed andeffectively applied todetect, asfarastechnically possible andeconomically
feasible, such residues from allsources, unlike thepractice intheUnited States. Thefactthatthere
wasapotential forprohibited residues toevade itscontrol anddetection wasnotinitself areason for
theEuropean Communities toadopt theUSapproach onthisissue. Tothecontrary, thisriskofresidues
ofpotentially carcinogenic substances evading detection wasanimportant factor incarrying outaproper
riskassessment andseriously influenced, right from thebeginning, thedecision ofcautious Members
insetting thelevel ofsanitary protection they deemed appropriate intheir territory.
(vi) Risks arising from other parameters
4.197 TheEuropean Communities argued thatapotential source ofriskfrequently mentioned by
scientists stemmed from uncertainty about thenature andreliability ofthemethods used toestablish
125B.Jülicher, "Sampling Strategies", 1995 ECScientific Conference Proceedings, pp.537-539.WT/DS26/R/USA
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therelevant data. Theprocedure forcharacterising theriskfrom theuseofhormones hadremained
largelyunchangedfor30to40yearsandscientistshadarguedthattheprocessofthescientificassessment
oftheriskshould draw onthescience base toassess therisk, then address uncertainties, rather than
fuse these twoelements. However, amuch sounder scientific approach wastoencourage strongly
theinvestigation ofthemechanism oftoxicity ofeach newpromoter. Unless more effort were directed
tounderstanding whyaparticular adverse effect ofconcern occurred (i.e.assessment ofthemechanism
oftoxicity), riskassessment would always bevulnerable tothecriticism thatitsscientific basis was
flawed. Science continued tomake rapid advances andnoriskassessment could beregarded asthe
definitive statement foralltime. Aregular review procedure wasneeded, thefrequency ofwhich should
bedetermined bysuch factors astheavailability ofnew toxicological data; thelevel ofuncertainty
identified intheproducts 'riskassessment; andfindings from exposure monitoring investigations.
Alltoooften, further investigations oftheriskceased atthepoint atwhich aparticular promoter was
either accepted foruseorrejected. Means ofprogressing theknowledge base, intheareas where
substantial uncertainties existed, hadtobefound.126
4.198 TheEuropean Communities alsosubmitted thattheJECFA 1988 report stated that"insufficient
datawere available onnormal levels insome classes ofanimals likely tobetreated with oestradiol-17ß
would fallwithin thenormal ranges foruntreated animals ineach class". TheEuropean Communities
argued thatthislack ofdata, however, wasthought nottobeimportant andJECFA hadbased its
conclusions onextrapolations from other data. Intheend,JECFA didnotthink itnecessary toestablish
MRLs, because oftheimpossibility ofdetecting residues ofnatural hormones intreated meat.
4.199 Furthermore, theEuropean Communities argued thatscientists hadraised concerns withregard
totheconfidentiality ofdata. Ithadbeen suggested thataseparate riskassessment must beconducted
oneach growth promoting substance drawing onalltheavailable data, notsimply thatprovided by
acompany wishing tomarket aproduct. This required improved accessibility toinformation classified
asconfidential. Forthispurpose, ithadbeen suggested thatatime-limit should besetonthe
confidentiality ofsafety data.127TheEuropean Communities submitted thattherationale formaintaining
confidentiality wastomaintain commercial secrets. Thenormal procedure toobtain anauthorization
tomarket ananimal drug (forinstance asfollowed intheUnited States) wasforthedrug sponsor to
demonstrate totherelevant authority thatananimal drug wassafeandeffective inthetarget animals,
safeforhumans consuming edible products from treated animals, andsafefortheenvironment.
4.200 Moreover, theEuropean Communities observed thatfrequently therelevant authorities ofsome
countries were saidtooperate under a"zero risk" concept, although zero riskcould notbedetermined
andzero residues were probably notachievable.128Butforthegeneral public, theideathatzero risk
residues were notachievable wasdifficult toaccept. Rightly orwrongly, public perception frequently
wasthatrelying solely onsafety data provided byacompany wasunsound.
4.201 TheUnited States claimed thattheECarguments onuncertainty about thenature andreliability
ofthemethods used toestablish therelevant dataandtheir confidentiality wasmisplaced. TheEuropean
Communities hadonce more identified noparticular risk, offered noriskassessment showing anyrisk,
andproduced noevidence ofarisk. Itsreliance ongeneral uncertainty wasagain ageneralized concern
thatwasnomore thanunfounded speculation rather thananactual risk. Thefactthatthere were limits
126Dr.J.Bridges andDr.O.Bridges, "Hazards ofGrowth Promoting Agents andStrategies ofRisk Assessment", 1995
ECScientific Conference Proceedings, pp.258-259.
127Ibid.,p.262.
128TheEuropean Communities noted thattheUnited States wassupposed toapply a"zero" riskstandard forcarcinogenic
substancesundertheso-called"DelaneyClause".Furthermore,whenpresentingtheWTO AgreementtoCongressforapproval,
theUSFederal Drug Agency hadargued thatits"zero-risk" policy wasnotaffected bytheWTO Agreements.WT/DS26/R/USA
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toscience wasnotabasis under theSPS Agreement tomaintain ameasure. TheUnited States and
other Members agreed thatthere were limits toscience, buttheUruguay Round participants had
negotiated andagreed totheSPSAgreement with itsreliance onscience infullrecognition ofthose
limits. Moreover, tostate thatthe"evidence" onwhich theEuropean Communities relied tomaintain
itsmeasure was"alackofinformation on,forexample, themode ofaction, theeffect ofadministering
combinations andtheeffect ofingesting residues over along period" andclaim asitsevidence only
thathormones ingeneral exerted powerful physiological effects andwere associated, under certain
ill-defined circumstances, with adverse effects onhealth amounted tonomore than speculation and
scare tactics. IntheUSview, theEuropean Communities hadputforth noscientific evidence tosupport
theexistence ofthese risks.
(vii) The precautionary principle
4.202 TheEuropean Communities argued thatallcountries, including theUnited States, regulated
theuseofhormones infarm animals. Thedifference between theEuropean Communities andtheUnited
States inthisrespect wastheextent towhich their usewasregulated. This difference indegree of
regulation wasareflection ofthedifferent levels ofconsumer protection adopted bytheEuropean
Communities andtheUnited States. TheEuropean Communities tookaprecautionary approach, placing
theattainment ofahigh level ofconsumer protection before thecommercial interests offarmers and
pharmaceutical companies. TheUnited States took adifferent approach. Where there existed adoubt
over thesafety ofaproduct, theEuropean Communities gave thebenefit ofdoubt totheconsumer,
especially incases where thepotential risks might affect very large parts ofthepopulation. TheUnited
States had, inthecase ofgrowth hormones, given ittotheproducer.
4.203 TheEuropean Communities stressed thatthedifference indegree ofregulation between the
United States andtheEuropean Communities wasduetothegreater attachment oftheEuropean
Communities totheprecautionary principle.129Such anapproach wasrequired toavoid situations as
those portrayed bymany cases ofhealth hazards which only became apparent long after substances
orproducts hadbeen assumed tobesafe, such asThalidomide andDES. Two cases ofrecent interest
intheEuropean Communities illustrated thedesirability oftaking aprecautionary approach toconsumer
protection: E.Coli andBSE.130
129D.Freestone &E.Hey (1995), "The Precautionary Principle andInternational Law".
130TheEuropean Communities explained thatE.Coli wasabacterium which inhabited theintestines ofallanimals. In
theearly days offood bacteriology ithadbeen assumed tobeubiquitous andharmless. InthefirstFAO monograph onmeat
hygiene, published in1957, itwasstated that: "There arenotconvincing reports which directly implicate E.Coliinoutbreaks
offood poisoning". Thesecond report oftheJoint FAO/WHO Expert Committee onMeat Hygiene (1962) hadconsidered
thatknowledge oftheimportance ofE.Coli incausing food-borne disease waslacking andshould beinvestigated. Even
in1974, Thornton 'sTextbook ofMeat Hygiene stated thatanimal strains ofE.Coli were "unlikely tobecome established
inthehuman bowel". When theEuropean Communities, in1964, hadadopted itsfirstrules onmeat hygiene, ithadtaken
aprecautionary approach, requiring hygienic structures, equipment andhandling procedures with aview topreventing all
bacterial contamination ofmeat. This approach hadbeen strongly criticised bytheUnited States onthegrounds thatitwas
notnecessarytolaydowndetailedproductionandprocessingmethods,asconsumerprotectioncouldbeassuredbyend-product
testing fordangerous pathogens, which didnotinclude E.Coli. Subsequently, outbreaks ofbacterial food poisoning, including
several large E.Coli outbreaks inwhich children haddied, hadpersuaded theUnited States toreview andpropose radical
changes toitsmeat hygiene rules. Yet,onlytwenty years ago, E.Coliwasnotconsidered tobeasignificant danger tohuman
health.
With regard toBSE, theEuropean Communities noted thatthiswasanewdisease ofcattle. Ithadbeen firstrecognised
intheUnited Kingdom only 10years ago. When ithadbeen found tobeamember ofthegroup oftransmissible spongiform
encephalopathies, ithadbeen widely assumed tobethebovine form ofscrapie, adisease ofsheep recognised forover 250
years. Asthere wasnoevidence ofadanger tohuman health from eating meat from scrapie-affected sheep, ithadbeen
assumed insome quarters thatthere would similarly benodanger tohumans from BSE. That assumption hadrecently been
challenged bytheappearance ofacluster ofcases ofanew form ofCreutzfeldt-Jakob disease, ahuman spongiform
(continued...)WT/DS26/R/USA
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4.204 The European Communities noted thatDr.S.S. Epstein oftheSchool ofPublic Health,
University ofIllinois atChicago, hadexplained therisks from theuseofthese hormones foranimal
growth promotion asfollows:
"Although thecarcinogenicity ofDES intestanimals wasknown asearly as1938, itsuseas
afeedadditive wasapproved bytheUSDA andtheUSFDA, in1947 ....However, misleading
assurances ofsafety andstonewalling bytheFDA andUSDA, including thedeliberate
suppression ofresidue data, managed todelay aUSbanonDES until 1979.
"The meat industry thenpromptly switched toother carcinogenic additives, particularly natural
sexhormones, which areimplanted intheearsofcommercially raised feedlot cattle. Unlike
thesynthetic DES, whose residues canbemonitored andwhose usewasconditional onaseven-
daypreslaughter withdrawal period, residues ofnatural hormones arenotroutinely detectable
because they cannot bedifferentiated from thesame hormones produced bythebody. Since
1983, theFDA hasallowed virtually unregulated useforthese natural additives right upto
thetime ofslaughter, subject only tothenon-enforceable requirement thatresidue levels in
meat must belessthan 1percent ofthedaily hormonal production inchildren.
"Adramaticwarningofthedangersofgrowth-promotingadditiveswastriggeredbyanepidemic
ofpremature sexual development andovarian cysts involving about 3,000 Puerto Rican infants
andchildren from 1979 to1981. These toxic effects were traced tohormonal contamination
offresh meat products andwere usually reversed bysimple dietary changes. Using highly
specialized research techniques, independent testing found thatsamples ofthemeat products
were contaminated with oestrogen residues more than tenfold inexcess ofnormal ranges.
Additionally, elevated levels ofoestrogen andthesynthetic zeranol were found intheblood
ofaffected children. Increased rates ofuterine andovarian cancers inadult women were also
associated with theepidemic.
"More than adecade ago, Roy Hertz, then director ofendocrinology oftheNational Cancer
Institute andaworld authority onhormonal cancer, warned ofthecarcinogenic risks of
oestrogenic feed additives, particularly forhormonally sensitive tissues such asbreast tissue,
becausetheycouldincreasenormalbodyhormonallevelsanddisturbdelicatelypoisedhormonal
balances.Hertzpointedtoevidencefrominnumerableanimaltestsandhumanclinicalexperience
thatsuch imbalance canbecarcinogenic. Hertz alsowarned oftheessentially uncontrolled
andunregulated useforthese extremely potent biological agents, nodietary levels ofwhich
canberegarded assafe. Even adime-sized piece ofmeat contains billions oftrillions of
molecules ofthese carcinogens.
"VirtuallytheentireUSpopulationofconsumers,withoutanywarning,labelling,orinformation,
ingests unknown andunpredictable amounts ofhormonal residues inmeat products over a
lifetime. In1986, asmany ashalfofallcattle sampled infeedlots aslarge as600animals were
found tohave hormones illegally implanted inmuscle rather thantheearskin, toinduce further
increased growth. This practice results invery high residues inmeat, which even theFDA
hasadmitted could produce "adverse effects". Left unanswered iswhether such chronic and
uncontrolled oestrogen dosages areinvolved inincreasing cancer rates (now striking onein
three Americans), particularly thealarming 50percentincrease intheincidence ofbreast cancer
130(...continued)
encephalopathy, which experts considered waslikely linked toBSE. Inthiscase, itwasfortunate thataprecautionary approach
wastaken atanearly stage, despite thegenerally held view thatanyrisktohumans wasuncertain orextremely small. The
tissues known tocontain theBSE agent, aswell assome inwhich infectivity hadnotbeen demonstrated butwhich could
possibly beaffected, were removed from thehuman food chain. Atthetime, thisaction wascriticised insome quarters as
anover-reaction butitnow appeared tohave been far-sighted.WT/DS26/R/USA
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since 1965. These questions areoffurther concern inthelight ofrecent evidence confirming
theassociation between breast cancer andoralcontraceptives, whose oestrogen dosage over
afraction ofalifetime isknown andcontrolled, incontrast with thatfrom residues ofgrowth
hormones inmeat products."131
4.205 TheUnited States responded thatthearticle byDr.Epstein cited reports over adecade old,
inaccurate forseveral reasons, anddidnotconstitute scientific evidence insupport oftheECban.
First, Dr.Epstein hadnotcited anyevidence with respect tothesafety ofresidues ofthesixhormones
forgrowth promotion purposes. Second, Dr.Epstein ’sfacts were wrong. InthecaseofPuerto Rico,
incontrast toDr.Epstein 'sassertion, thecause ofthepremature development hadnever been identified
andtheinitial reports ofzeranol insamples ofpatients ’blood could notbeconfirmed.132Third, the
reference tothearticle byDr.Hertz wasnotrelevant. Dr.Epstein attributed conclusions toDr.Hertz
thathehadnever made. Also, thereference tofeed additives wasareference toDES, nottothesix
hormones. TheUnited States submitted thatwith almost 30years experience with theuseofzeranol,
there hadnotbeen anyadverse effects reported onhuman health resulting from thelegal useofthis
product incattle orsheep.
4.206 TheUnited States concluded thatthe"evidence" putforward bytheEuropean Communities
didnotsupport therisks italleged. Itnoted thatthereport ofthe1995 ECConference setforth on
page 4alistofthe"Principles ofrisk-assessment" which illustrated thattheEuropean Communities
hadstopped itsanalysis atwhat wassupposed tobethestarting point forariskassessment. Those
Principles stated that"the starting point inanyrisk-assessment istoidentify allthepotential (oreven
hypothetical) hazards (oruntoward outcomes) thatmaybecaused byeating meat containing residues
ofgrowth-promoting substances" .IntheUSview, theEuropean Communities hadfailed tomove
tothenext step. Asthereport notes: "Risk isadifferent concept; itisthechance, orthelikelihood,
thataparticular hazard willoccur asaresult ofeating meat containing residues ofgrowth-promoting
substances". TheUnited States argued thatbyfailing toconsider whether there wasachance or
likelihood ofanyofthehypothesized hazards, theECbanwasnotbased onan"assessment ofthe
relevant risks", asrequired byArticles 5.1and5.2.
4.207 Furthermore, theSPSAgreement required foranysanitary measure thatthere be"sufficient
scientific evidence" andan"assessment oftherisks" or,under Article 5.7, "available pertinent
information". The United States claimed thatthe"precautionary principle", which theEuropean
Communities attempted tousetojustify itsban, was notanapproach unique totheEuropean
Communities. Awide number oftheworld ’sgovernments hadsubscribed totheprecautionary approach
inPrinciple 15ofAgenda 21oftheRio Declaration onEnvironment andDevelopment (“Rio
Declaration”).Nonetheless,theUnitedStatesarguedthattheEuropeanCommunitieshadmisunderstood
theprecautionary approach. Theprecautionary approach called fortaking action based onpreliminary
orinconclusive scientific information where itmight beimportant toactintheabsence ofconclusive
scientific information. Oneexample oftheapplication oftheprecautionary approach wasglobal climate
change. Inthatinstance, preliminary scientific information indicated theneed toactasaprecaution
even though afullscientific understanding hadnotyetbeen achieved. TheUnited States claimed that
Article 5.7reflected theprecautionary approach, buttheEuropean Communities hadadmitted that
itsbanwasnotpursuant toArticle 5.7.
131S.S.Epstein (1990), "The Chemical Jungle: Today 'sBeef Industry", International Journal ofHealth Services, Vol. 20,
pp.278-279.
132Hannon etal.(1987), Archives ofEnvironmental Contaminants Toxicology, Vol. 16,pp.255-262.WT/DS26/R/USA
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(viii) Animal health protection
4.208 TheEuropean Communities argued thatoneoftheaims ofthemeasures atissue were to
protect animals from theuseofthese hormones forgrowth promotion. Inthepreparatory discussions,
theEuropeanParliamenthadconsidered"thepossibleadverseeffectsofthesesubstancesontheimmunity
against various diseases ofanimals andthatthisinturnmayleadtoanincreased useofantibiotics".133
Furthermore,thepreambleandtextofDirective88/146/EEC clearlyestablishedthatconcernsofpotential
risks toanimal health were alsotaken intoaccount. Thestrict conditions imposed bytheDirective
ontheuseofthese hormones fortherapeutic andzootechnical purposes hadasoneofitsobjectives
theprotection ofanimal health from improper administration. Article 5provided thattheECmember
States must ensure that"noanimals aredispatched from their territory tothatofanother member State
which have hadadministered tothem inanywaywhatsoever substances with athyrostatic, oestrogenic,
androgenic orgestagenic action...", except fortherapeutic orzootechnical purposes. Article 6(1)
provided that"member States shall prohibit importation from third countries ofanimals andofmeat
from animals towhich have been administered inanywaywhatsoever substances with athyrostatic,
oestrogenic, androgenic orgestagenic action", except fortherapeutic orzootechnical purposes and
under conditions equivalent tothose applied intheEuropean Communities. One objective ofthis
prohibition was toprotect animal health, since theprohibition ontrade insuch animals clearly
discouraged theadministration ofthese hormones inthefirst place.
4.209 TheEuropean Communities claimed thatscientists agreed thatdoses ofthese hormones atlevels
which produced ahormonal activity were carcinogenic tolaboratory animals. The1988 JECFA Report
haddocumented these carcinogenic effects. Ithadreported thatoralandparenteral administration
ofoestradiol-17couldincreasetheincidenceoftumoursinexperimentalanimals.Thesetumourslargely
occurred intissues with high levels ofspecific hormone receptors which were normally responsive
tostimulation byoestradiol-17 .JECFA hadalsonoted thattheincidence oftumours ofthemammary
gland, ovary, uterus andvagina were higher inanimals treated with progesterone alone thanincontrol
animals.Theincidenceofuterinetumourswas"surprisinglyhigh"andtheincidenceofprostatictumours
washigher inrodents treated withhighdoses oftestosterone, thanincontrol animals. JECFA concluded
thatthecarcinogenic responses were related tothehormonal activities ofeach ofthese three hormones.
4.210 TheEuropean Communities noted thatJECFA hadalsofound liver hyperplasia andtumours
inmice fedhigh doses oftrenbolone acetate andslight increases intheincidence ofislet-cell tumours
ofthepancreas ofrats, which JECFA concluded arose asaconsequence ofthehormonal activity of
thetrenbolone metabolites. TheJECFA review ofzeranol noted oestrogenic butnotcarcinogenic effects
inrats. Inmice, however, higher incidence ofanterior lobe tumours ofthepituitary gland occurred
than inmice inthenegative control group. JECFA reported thatsuch tumours rarely occurred
spontaneously inmice butwere known toresult from administration ofoestrogenic hormones. JECFA
again concluded thatthetumorigenic effect ofzeranol wasassociated with itsoestrogenic properties.
4.211 Thevarious carcinogenic effects mentioned bythe1988 JECFA Report onlaboratory animals
were explained more fully inthereports oftheInternational Agency forResearch onCancer (IARC).
IARC Monograph, Supplement 7,1987, reported sufficient evidence ofcarcinogenicity toanimals
from oestradiol-17 andprogesterone. IARC noted thatadministration tomice ofoestradiol-17 and
itsesters increased theincidence ofmammary, pituitary, uterine, cervical, vaginal, testicular, lymphoid
andbone tumours. Inrats, there wasanincreased incidence ofmammary and/or pituitary tumours.
Inhamsters, ahigh incidence ofmalignant kidney tumours occurred inintact andcastrated males and
inovariectomized females, butnotinintact females. Inguinea-pigs, diffuse fibromyomatous uterine
andabdominal lesions were observed. IARC reported thatprogesterone increased theincidence of
ovarian,uterineandmammarytumoursinmice.Dogstreatedwithprogesteroneforfouryearsdeveloped
133European Parliament 'sResolution, ECOfficial Journal, No.C288/158, 11November 1985.WT/DS26/R/USA
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adose-related incidence ofmammary-gland nodules. Importantly, IARC indicated thatthere was
evidence thatlowdoses ofprogesterone administered over long periods acted incombination with
carcinogenic agents, such assome viruses orchemicals, toenhance tumour developments. Therefore,
long-term administration ofsynthetic progestins could produce acomparable hazard byincreasing the
incidence oftumours duetoother agents.134
4.212 TheIARC hadalsofound thatzeralenone, ametabolite ofzeranol, inthedietoflaboratory
animals hadcarcinogenic effects135,andhadcaused other effects, including:
"...atrophy oftheseminal vesicles andtestes, squamous metaplasia oftheprostate gland,
osteopetrosis,myelofibrosisofthebonemarrow,cytoplasmicvacuolizationoftheadrenalglands,
hyperkeratosisofthevaginaandendometrialhyperplasia...pseudopregnancy[and]infertility."136
Inaddition, consumption ofzeralenone bypregnant animals caused areduction infetal weight and
anincreased prevalence ofskeletal problems andincidence ofstillbirths.137Asregards thecarcinogenic
effects ofthehormone MGA, published data documented theinduction ofastatistically significant
incidence ofmammary tumours infemale mice.138
4.213 TheEuropean Communities added thattheabove carcinogenic effects were nottheonlynegative
effects which theadministration ofthese hormones hadonanimals. The1995 ECScientific Conference
haddocumented anumber ofother effects which resulted from these hormones.139Such negative effects
included increases inliver abscesses, fertility problems, effects onmale reproduction, alteration of
gonadal function, decrease inpregnancy rates, increase ofembryonic orfetal mortality rates, etc.
Therisks toanimals ofthese negative effects were ashigh as(oreven higher than) therisks these
hormones posed tohuman beings, since they were administered directly totheanimals andimproper
usecould easily multiply thepotential negative effects.
4.214 TheUnited States noted thattheprotection ofanimal health wasirrelevant tothiscase. The
European Communities didnotclaim thatitsbanwasdesigned toprotect animal health intheterritory
ofother Members, andimports ofmeat inthiscase were notrelevant totheprotection ofthehealth
ofanimals within theEuropean Communities. Inanycase, datasuggested thatanimals towhich had
been administered these hormones forgrowth promotion purposes were infacthealthier.
4.215 TheEuropean Communities stressed thatitdidnotargue thatthemeasures atissue were
designed toprotect animal health intheterritory ofother Members (regardless ofhow desirable that
would have been). ButtheEuropean Communities believed thatithadtheright under theWTO rules
(and inparticular theSPS Agreement) toprohibit imports from third countries ofanimals towhich
these hormones hadbeen administered forthereasons explained above. This prohibition wasnot
discriminatory, asitapplied inexactly thesame way totrade insuch animals within theEuropean
Communities.
13421IARC Monographs, p.132.
13556IARC Monographs, p.431; and31IARC Monographs, p.287.
136Ibid.,p.417.
137Ibid.,pp.421-422.
138J.W. Lauderdale etal.(1977), "Studies ofaprogesterone (MGA) asrelated toresidues andhuman consumption",
Vol. 3,pp.5-33.
139R.Renaville,S.Massart,A.Prandi,U.Fazzini,M.Sindic,L.Nicolay,M.Falaki,A.Burny&D.Portetelle,"Aspects
ontheUseofAnablic Steroids inAnimal Production", 1995 ECScientific Conference Proceedings, pp.75-77.WT/DS26/R/USA
Page 88
(f) Article 5.4oftheSPS Agreement
4.216 TheEuropean Communities claimed thatArticle 5.4provided thatMembers should (notshall)
take intoaccount theobjective ofminimizing negative trade effects. This wascomplied with both
inrespect ofintra-Community trade andtrade with third countries. Only ahigh level ofprotection
chosen bytheEuropean Communities would have ensured theflow oftrade intheinternal market.
Theimposition ofveterinary controls ontheuseofhormones asgrowth promoters would have caused
insuperable barriers totrade with third countries. Moreover, agovernment wasnotobliged tolower
itslevel ofprotection below what itconsidered tobenecessary. Itshould onlykeep inmind theobjective
ofnotgoing beyond what wasnecessary.
(g) Article 5.5oftheSPS Agreement
4.217 TheUnitedStatesfurtherobservedthattheEuropeanCommunitiesalsoclaimedthatitsmeasures
were consistent with Article 5.5. This wasnotaccurate. TheUnited States hadshown thatthere was
noscientific evidence thatthere wasarisktohuman health from theresidues ofthehormones when
used forgrowth promotion. However, even ifonewere todisregard allofthescientific evidence and
riskassessments thathadbeen conducted andwere toassume instead thatthese residues didpose a
risk, theECbanwould stillbeinconsistent with Article 5.5. Article 5.5provided initsrelevant part
that"each Member shall avoid arbitrary orunjustifiable distinctions inthelevels itconsiders tobe
appropriate indifferent situations, ifsuch distinctions result indiscrimination oradisguised restriction
oninternational trade." Thus, Article 5.5established atwo-step testwithrespect todistinctions between
aMember ’sappropriate level ofprotection indifferent situations: wasthedistinction inthelevels
ofprotection (i)either arbitrary orunjustifiable and(ii)didthisdistinction result ineither discrimination
oradisguised restriction oninternational trade.
4.218 TheEuropean Communities argued thatArticle 5.5required consistency only interms of
avoiding arbitrary orunjustifiable distinctions inapplying thechosen level ofprotection, andthenonly
ifsuch distinctions resulted indiscrimination oradisguised restriction ontrade. Itcould notbe
interpreted asrequiring consistency insetting ordeciding thelevel ofprotection, since thetextwould
have specified it.This interpretation was consistent with thepreamble, which stated that the
harmonization ofSPSmeasures didnotrequire Members tochange their appropriate level ofprotection.
Itfollowed from thisthatArticle 5.5didnotrequire Members toachieve consistency between thelevel
ofprotection which they chose against different hazards tohuman, animal andplant lifeandhealth.
This would inanycasebeanillogical requirement; noMember protected individual plants tothesame
extent thatitprotected individual humans. Consistency ofapplication meant thatMembers must in
allcircumstances apply measures which were capable ofachieving thesame level ofprotection against
agiven hazard unless there wasjustifiable reason inaparticular situation toapply difference measures
toachieve adifferent level ofprotection.
4.219 TheEuropean Communities hadfollowed exactly thesame principles forother drugs andfood
additives asithadforhormones. Allsuch substances were evaluated onacase-by-case basis andwhere
substances were deemed toodangerous, orpotentially dangerous, toallow their residues infood, a
zero tolerance wasfixed. Asanexample, theuseofantibiotics inlivestock wasregulated inthe
European Communities byforbidding theuseasgrowth promoters ofthose antibiotics which were
oftherapeutic value inhumans, inorder toavoid problems ofantibiotic resistance.
4.220 TheUnited States argued thattheECclaim thatitsmeasures were applied inexactly thesame
waytoachieve thesame level ofprotection inrespect ofallmeat intended tobeplaced onthemarket
intheEuropean Communities, whatever itsorigin, wasnotaccurate. TheEuropean Communities in
factapplied different levels ofprotection todifferent meat. TheEuropean Communities hadsuggested
thatitsappropriate level ofprotection with respect tothesixhormones when used forgrowth promotion
purposes was"zero risk". However, ithadchosen adifferent, lessstringent, level ofprotection withWT/DS26/R/USA
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respect tocarbadox. Carbadox wasasubstance thattheEuropean Communities permitted tobeused
forgrowth promotion purposes intheproduction ofswine. Itwasafeed additive thatwasaknown
genotoxic carcinogen140,unlike thesixhormones. Theexperts advising thePanel allconfirmed that
carbadox wasgenotoxic. Genotoxic meant thatscientists considered carbadox toinduce cancer. By
permitting itsuseandthesaleandconsumption ofmeat from animals towhich carbadox hadbeen
administered, theEuropean Communities hadchosen anappropriate level ofprotection thatwasless
stringent than forthesixhormones involved inthisdispute. There wasnoprinciple orcriterion that
accounted forthedifferent treatment bytheEuropean Communities ofharmless residues, inthecase
ofthehormone ban, ascompared toresidues ofcarbadox. Ifthedifferent treatment resulted from
theECselection ofdiffering "appropriate" levels ofsanitary protection, andintheabsence ofany
principle orcriterion thataccounted forthedistinction, then thedistinction inthelevels ofprotection
wasarbitrary andunjustifiable.
4.221 TheUnited States noted thatArticle 5.5required thatifthechallenged distinction inlevels
ofprotection were arbitrary orunjustifiable, consideration must begiven tothesecond test, whether
thedistinction inlevels ofprotection resulted inadisguised restriction oninternational trade. Carbadox
wasused inswine production. Thesixhormones were used mainly incattle production. Itwasno
coincidencethattheEuropeanCommunitieshadbannedtheuseofthesixhormonesforgrowthpromotion
purposes while permitting theuseofswine growth promotants. TheECswine industry wasrelatively
more efficient andmarket-oriented than thebeef sector. Efficiency inbeef production wasnotas
important intheEuropean Communities, since thatsector relied more heavily onECdomestic price
supportmeasures,importprotectionandexportsubsidies.Unlikebeef,therewasvirtuallynoacquisition
ofpork under theECintervention scheme. Also, incontrast tobeef, ECpork could beexported to
theUnited States without theuseofexport subsidies. AstheUnited States haddemonstrated, the
European Communities clearly wanted toreduce beef supplies when itextended thehormone ban.
TheEuropeanCommunitieshadnocomparableconcernswithrespecttoitsporksector.Onthecontrary,
itneeded topreserve competitiveness inorder tomaintain export markets. Therefore, itcontinued
topermit theuseofgrowth promotants forswine. Asaresult, theEuropean Communities hadset
itsappropriate level ofprotection forthesixhormones atamore stringent level thanthatforcarbadox
because itneeded toprotect itsbeef industry from competition. Thedistinction intheEClevels of
protection resulted inadisguised restriction oninternational trade.
4.222 TheUnited States claimed thatdespite itsarguments tothecontrary, theEuropean Communities
must believe thatthere wasathreshold ofsafety forsynthetic hormones, since itpermitted theuse
ofsynthetic hormones, forexample allyl-trenbolone141(altrenogest), afeedadditive foroestrus control
inswine andhorses. Allyl-trenbolone wasasynthetic sexsteroid with progestational activity142,not
approved foruseintheUnited States. Inaddition, theEuropean Communities allowed theuseof
medroxyprogesterone acetate, notanatural progesterone, asavaginal implant foroestrus control in
sheep. Inallthese instances theEuropean Communities allowed meat from animals sotreated tobe
soldandconsumed. Furthermore, theEuropean Communities accepted thatthere wasathreshold for
harm inthecase ofother compounds administered tofarm animals. One such example was
sulfamethazine, which caused thyroid cancer inlaboratory animals, yettheeffect wasconsidered by
JECFA tooccur only above athreshold level. InthatcasetheEuropean Communities hadnodifficulty
accepting theJECFA assessment andhadsetanMRL forthiscompound. Sulfamethazine wasused
intheEuropean Communities forthetreatment ofrespiratory ailments inchickens, cattle andswine.
Apparently theEuropean Communities only believed thatthere wasnothreshold forharm when such
aposition assisted itindiscriminating against thebanned meat andanimals.
14036th report ofJECFA (1990), pp.45-50.
141ECDirective 96/22/EC, Art4,2(I).
142A.R. Peters (1992) "Endocrine Manipulation-Toxicological Frontiers", J.Reprod Feter Suppl 45,pp.193-201.WT/DS26/R/USA
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(h) Article 5.6oftheSPS Agreement
4.223 TheUnitedStatesrecalledthatArticle5.6requiredMembers,whenestablishingormaintaining
asanitary measure toachieve theappropriate level ofsanitary orphytosanitary protection, toensure
thatsuch ameasure wasnotmore trade-restrictive than required toachieve their appropriate level of
sanitary protection, taking intoaccount technical andeconomic feasibility.143TheECmeasures were
"more trade-restrictive than required toachieve their appropriate level ofsanitary orphytosanitary
protection"144,contrary toArticle 5.6. TheECbanwasnotintended toachieve anyparticular level
ofsanitary protection from anyidentified risk, andregulated meat based ontheproduction method
used rather than onanylevel ofresidues ofhormones inthemeat. FortheUnited States, thelevel
ofanyrisk, ifonecould have been identified, would have presumably been related tothelevel of
residues. Moreover, an"appropriate level ofsanitary orphytosanitary protection" required thatthere
beaparticular risktobeprotected against andtheEuropean Communities hadfailed toidentify any
particular riskfrom anyofthese hormones when used inaccordance with good animal husbandry
practice. TheUnited States submitted thattheECbanstopped meat with onelevel ofhormone residues
from being imported andsoldwhile permitting meat with higher levels ofresidues ofthesame hormone
tobesold, because itcontinued toallow thehuman consumption ofdomestically-produced meat from
animals administered hormones fortherapeutic purposes, aswell asmeat with levels ofendogenous
hormones higher than those found inmeat from animals administered thesame hormones forgrowth
promotion. Similarly, theEuropean Communities permitted meat from pregnant dairy cows orfrom
bulls andother food products (such asmilk, butter andeggs) tobeproduced, marketed, consumed
andused infood processing, although these products contained farhigher levels ofendogenous hormone
residues than meat derived from steers andheifers treated with thesixhormones. Consequently, the
European Communities permitted thehuman consumption ofendogenous hormone residues without
anylimitation while banning imported meat from animals administered safehormones forgrowth
promotion purposes. Furthermore, theECbanwasmore trade restrictive than required because it
severely restricted trade, although itwasnotdesigned toprotect against anyparticular risk, norto
achieve aparticular level ofprotection from thatrisk. TheECimport banapplied regardless ofwhether
thehormones were administered properly, regardless ofanywithdrawal period, andregardless ofthe
levels ofanyresidues ofthehormones inthemeat. Thus, theECmeasures were ofthemost extreme
form possible short ofatotal banonimports ofmeat.
4.224 TheEuropean Communities submitted thatfrom thesequence ofevents which hadledto
theadoptionofDirective88/146/EC,itwasclearthattheEuropeanCommunitieshadexaminedcarefully
thepotential risks tohuman andanimal health from theuseofthese hormones foranimal growth
promotion purposes. Ithadconsidered thescientific evidence which suggested thatthese substances,
ifused inaccordance with good veterinary practice, didnotseem topose risks tohuman andanimal
health, butwhich didnotexclude beyond doubt thatthey posed potential risks tohuman health. The
European Communities hadexamined carefully alloftheavailable options forensuring theproper
conditions ofuseandcontrol ofthese substances before concluding that, atpresent, thebanontheir
usewastheonly scientifically, technically andeconomically feasible option.
4.225 TheUnited States claimed that, even if(putting aside thelackofascientific basis fortheEC
ban) onewere toaccept theEC"scientific evidence", thebanwould beoverbroad andthuswasmore
trade-restrictive thanrequired toachieve theECappropriate level ofsanitary protection. TheEuropean
143Thefootnote toArticle 5.6reads: "For purposes ofparagraph 6ofArticle 5,ameasure isnotmore trade-restrictive
than required unless there isanother measure, reasonably available taking intoaccount technical andeconomic feasibility,
thatachieves theappropriate level ofsanitary orphytosanitary protection andissignificantly lessrestrictive totrade."
144"Appropriate level ofsanitary orphytosanitary protection" isdefined inparagraph 5ofAnnex AoftheSPSAgreement
as"[t]he level ofprotection deemed appropriate bytheMember establishing asanitary orphytosanitary measure toprotect
human, animal orplant lifeorhealth within itsterritory".WT/DS26/R/USA
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Communities didnotcontest thatanyhuman health riskfrom hormones inmeat would beduetothe
residues ofthehormones inthemeat. YettheEuropean Communities hadnotregulated residue levels
ofthesehormones.IftheEuropeanCommunitieshadseriousconcernsabouthealthrisksfromhormones,
then itwould have regulated thelevel ofresidues ofhormones. Instead, theEuropean Communities
banned selected usesofthese hormones while ignoring theactual levels ofresidues towhich consumers
were naturally exposed from meat orother dietary sources. This wasalsotruewith respect tothe
three synthetic hormones. TheEuropean Communities didnotregulate residue levels. According
totheEuropean Communities ’owninaccurate claim, after asufficient waiting time prior toslaughter,
therewouldbenoresiduesofthethreesynthetichormonesinmeatfromanimalstowhichthesehormones
hadbeen administered forgrowth promotion purposes. YettheEuropean Communities hadstillbanned
themeat. Inother words, ifitbelieved thathormones posed ahealth riskatexposures above aset
level, theEuropean Communities would have regulated thelevels ofhormones allowed infood inorder
toensure thatthesetlevel wasnotexceeded, rather than imposing anabsolute banontheuseofthese
hormones forgrowth promotion purposes with respect toanimals, andmeat thereof, exported tothe
European Communities. TheEuropean Communities hadfailed todoso,thuscasting doubts onthe
credibility ofitsarguments.
4.226 TheUnited States claimed thattheobvious waytoregulate thelevels ofresidues inmeat was
through MRLs (bearing inmind thatCodex hadconcluded thatitwasunnecessary toestablish anMRL
forresidues ofthethree natural hormones administered forgrowth promotion purposes inaccordance
with good animal husbandry practice). Topretend thatMRLs were nottechnically oreconomically
feasible wasdirectly atodds with theECclaim that"atleast intheEuropean Communities there were
comprehensive andcostly residue control programmes designed andeffectively applied todetect, as
farastechnically possible andeconomically feasible, such residues from allsources".
4.227 TheEuropean Communities argued thatitsappropriate level ofprotection wastheassurance
thatmeat would notcontain residues ofadministered hormones andthatthiswasachieved byrequiring
stringent veterinary controls ontheuseofhormones infood animals, including arestriction onsuch
usetocertain specified therapeutic orzootechnical applications. TheEuropean Communities considered
thatanexamination ofthepossibility ofextending thispermission totheroutine useasgrowth promoters
revealed thatthescale ofmeat production would render controls technically impossible, andthatin
anycase thecosts ofcontrol would besohigh astorender such useuneconomic.
4.228 TheEuropean Communities indicated thattherequired control andmonitoring system hadbeen
examined bythecompetent democratic institutions oftheEuropean Communities andrejected fora
number ofreasons. One concern wascosts :itwould besoexpensive torestrict thesupply and
administration ofhormone growth promoters byveterinarians thatthecosts would outweigh thebenefits.
Furthermore,controlwasaproblemduetothescaleoflivestockproductionandthefactthatimplantation
ofgrowth promoters must beperformed atcertain restricted times ofthegrowth period; itwould be
technically impossible toensure atalltimes, andatreasonable administrative andeconomic costs, a
proper administration ofhormones. Another concern related tothebureaucracy ;therecording ofthe
treatment ofindividual animals andtheir checking atslaughter forthepresence ofimplants (toensure
theyhadbeen correctly administered) would beaheavy andexpensive bureaucratic burden andwould
further addtothecostoftheprocess.
4.229 TheEuropean Communities argued thatinspection raised other problems. Theinevitable failure
tofindremnants ofimplants atslaughter insome animals (due tomigration from theimplant site, or
mal-administration) would entail further expensive examination andresidue testing, adding further to
thecost. Residue testing would, ofcourse, have toinclude thesame testing andcorresponding costs
mentioned above inrespect ofthird-country meat imported intotheEuropean Communities, asthe
European Communities would notbeable, intheabsence ofinternationally agreed rules oncontrols
andtesting, thewidely diverging practices ofMembers, andtheobvious andpowerful economicWT/DS26/R/USA
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incentives formeat producers todisregard therules, torelyentirely ontesting andcontrols carried
outbythird countries.
4.230 Furthermore, theEuropean Communities argued thattheinstallation andcontrol ofalabelling
system toensure integrity ofidentification from theliveanimal through slaughter andprocessing to
ameat product would alsobeextremely expensive andlaborious. Thecostwould have tobeborne
bytheproduct, which again would render thewhole process uneconomic. Retail premises, including
restaurants, which supplied unwrapped meat directly totheconsumer would have tocarry aprominent
warning thattheyused meat from animals treated with hormones. This would beastrong disincentive
tousing such meat andwould thusamount toarestriction ontrade. Inaddition, consumers would not
beable tomake reliable authentic choices (e.g. ofmeat served inrestaurants).
4.231 AlloftheseconsiderationshadledtheEuropeanCommunitiestoconsiderthattheonlytechnically
andeconomically feasible measure toensure thatitsappropriate level ofprotection wasmetwasthe
ban. Any other requirements would have hadtheeffect ofstopping trade. Theonly alternative, a
banontheuseofhormones forgrowth promotion purposes, however, hadpermitted trade inmeat
tocontinue.
4.232 TheUnited States considered theECarguments about technical feasibility andcosts tobe
unfounded. With respect toadministration costs ,there wasnojustification forlimiting thesupply
andadministrationofthehormonestoveterinariansinallcircumstances.Whoadministeredthehormone
hadnoconnection totheresidue level. TheEuropean Communities didnotrequire administration
byaveterinarian inallcircumstances ascould beseen forexample from Directive 96/22/EC,
Article 1.2(c)(I) andthesecond paragraph under Article 5.Furthermore, aconcern thatcosts might
outweigh thebenefits wasaconsideration forthemarketplace. ItwasnotfortheEuropean Communities
toprejudgethequestionbybanningtheimportationofanimalsandmeat.TheWTOagreementsprovided
forcompetitive opportunities ,andthequestion here waswhy theEuropean Communities would not
provide theopportunity tosupply animals andmeat.
4.233 TheUnited States argued thattheEuropean Communities hadprovided noreason toconclude
thatthecosts ofinspection under anMRL regime would bedifferent from thecosts under their current
ban. Oneassumed thattheEuropean Communities were exercising oversight andenforcement with
respect toimports ofanimals andmeat now toensure thatnobanned animals ormeat were imported.
Itwasdifficult tounderstand whythere would belessmonitoring inthecaseofabanthanthere would
beinthecase ofMRLs. TheEuropean Communities wassaying thatitdidnoteven have totryto
identify programmes thatwould permit importation. This wascontrary totheapproach taken inthe
report oftheAppellate Body onUnited States -Standards forReformulated andConventional Gasoline
(AB-1996-1). TheECclaims were alsodirectly atodds with itsstatement that"atleast intheEuropean
Communities there were comprehensive andcostly residue control programmes designed andeffectively
appliedtodetect,asfarastechnicallypossibleandeconomicallyfeasible,suchresiduesfromallsources".
4.234 With regard tocontrol ,theUnited States noted thattheEuropean Communities hadfailed to
make clear why thecostofcontrol programmes undertaken inproducing countries wasrelevant to
theimport ban. Countries hadalready undertaken expensive andextensive control programmes to
comply with thecurrent ban(forexample, Australia hadreported acostintheorder of$A10 million
peryear foritscontrol programme tocomply with theECban). These were notcosts thatwould be
borne bytheEuropean Communities. Why would these costs make anMRL regime notatechnically
oreconomically feasible alternative totheabsolute bancurrently inplace? Presumably acountry
exporting now totheEuropean Communities could choose nottoadopt anynew measures totake
advantage ofanytrade opportunities presented byanMRL regime, andthatcountry would benoworse
offthan atpresent.WT/DS26/R/USA
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4.235 TheUnited States dismissed theECarguments onbureaucracy .Any bureaucratic burden in
third countries thatmight result from anMRL regime didnotconstitute areason forconcluding that
theMRL regime wasnotatechnically oreconomically feasible alternative totheECcurrent ban.
Thesame criticisms thatapplied toinspection andcontrol alsoapplied tothisreasoning. TheUnited
States suggested thattheEuropean Communities could choose tomaintain itsbanwith respect to
domestically produced animals andmeat ifthatwaslesscostly fortheEuropean Communities, while
applying anMRL regime toimports ofmeat.
4.236 TheUnited States concluded thattheEuropean Communities hadnotexplained, andcould
notexplain, howitwasunable tocontrol theuseofthese hormones without acomplete banwhile other
countries managed toeffectively regulate theuseofthese hormones forgrowth promotion purposes
without enormous costs. Itwasclear thatthebanrestricted trade. Ithadseverely disrupted exports
ofmeat andanimals from theUnited States, andwasnotrequired forhealth protection. Therisk
assessments thathadbeen performed hadallconcluded thatthese hormones could besafely used for
growth promotion. TheEuropean Communities hadpresented nonewscientific evidence tocontradict
those scientific conclusions ortodemonstrate thatthebanwas required forprotection from any
identifiable risk. Ifthere hadbeen evidence ofrisks associated with certain levels ofhormone residues
inmeat, then theEuropean Communities should control thelevel oftheresidues rather than banning
theuseofthehormones altogether. Moreover, theEuropean Communities hadbeen unable toarticulate
anyparticular level ofprotection thatthebanwasrequired toachieve. Asaresult, intheabsence
ofanyclearly articulated level ofprotection, itcould bepresumed thattheECbanwasmore trade-
restrictive than required, incontravention toArticle 5.6.
4.237 TheEuropean Communities claimed thattheUnited States hadfailed todischarge itsburden
ofproof inthiscase. Inparticular, ithadfailed toestablish that, ontheface oftheoverwhelming
scientific evidence thattheuseofhormones foranimal growth promotion waspotentially verydangerous
topublic andanimal health, there were other typeofmeasures which, whilst significantly lessrestrictive
ontrade, were capable ofensuring thatthelevel ofprotection which theEuropean Communities had
choseninthiscase(zeroresidueofhormonesinanimalsandmeat)waseffectivelyachieved.Conversely,
theEuropean Communities hadexamined allofthealternatives in1984 andagain inApril 1996, and
hadconcluded thattheprohibition onuseofthese hormones inanimal growth promotion wastheonly
reasonably available andlesstrade restrictive measure.
(i) Article 5.7oftheSPS Agreement
4.238 TheUnited States argued thatiftheEuropean Communities could notjustify itsbanasfalling
within theexception provided inArticle 5.7,which dealt with "cases where relevant scientific evidence
isinsufficient" andpermitted aMember to"provisionally adopt sanitary orphytosanitary measures
onthebasis ofavailable pertinent information". These hormones hadallbeen thoroughly tested,
examined andreviewed. Thescientific community hadbeen abletoconduct thorough riskassessments
ontheuseofthese hormones. Theassessments hadallconcluded thatthese hormones didnotpose
anyidentified risktohuman lifeorhealth when used inaccordance with good animal husbandry
practices. Both groups ofscientists assigned bytheEuropean Communities toreview thehormones
hadbeen able toreach aconclusion thatthehormones were safe, based ontheavailable scientific
evidence. The United States concluded thattheEuropean Communities hadnever presented any
"available pertinent information" onwhich ithadbased itsban, asrequired byArticle 5.7. Itwould
alsobedifficult, over 10years after adoption andover seven years after they hadgone intoeffect,
todescribe theECmeasures as"provisional" ascalled forinArticle 5.7.
4.239 TheEuropean Communities responded thattheECmeasures were not"provisional". They
were definitive. Moreover, noriskassessment ofhormones hadbeen completely "thorough", due
tolackofinformation. TheEuropean Communities stressed thattheSPSAgreement required Members
tocarry outariskassessment, notthescientific community. More importantly, thescientific evidenceWT/DS26/R/USA
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concerning theneed toregulate theuseofhormones wasinitself sufficient tojustify itslegislation
andtheEuropean Communities didnotneed torely ontheexception provided forinArticle 5.7
concerning cases where relevant scientific evidence wasinsufficient. Nevertheless, theEuropean
Communities stressed thatallexpert opinion, including thatofthe1988 JECFA Report onwhich Codex
hadbased itsdecision, hadconcluded thatscientific evidence didnotexist concerning themode of
action, theeffect ofusing mixtures ofhormones andthelong-term effects ofexposure onconsumers.
TheEuropean Communities concluded thatitsmeasures were not"provisional" but,onthecontrary,
they were definitive.
3. Agreement onTechnical Barriers toTrade
4.240 TheUnitedStatessubmittedthattheAgreementonTechnicalBarrierstoTrade(TBTAgreement)
wasdesigned toensure thataMember 'stechnical regulations didnotcreate unnecessary obstacles to
trade. This wasreflected both inArticle 2.2oftheTBT Agreement andinclause 5ofthepreamble.145
TheTBT Agreement applied to"[a]ll products, including industrial andagricultural products"146,and
applied to"technical regulations" which were defined intheAgreement. TheAgreement established
anumber ofdisciplines designed toensure thataMember 'stechnical regulations didnotcreate
unnecessary obstacles totrade, including theobligations contained inArticles 2.1and2.2oftheTBT
Agreement.AlthoughArticle1.5oftheTBTAgreementrecognizedthatsomesanitaryandphytosanitary
measures mettheterms ofthedefinitions of"technical regulation", "standard" and"conformity
assessment procedure", thedrafters oftheTBT Agreement hadmade explicit thatwhere atechnical
regulation, standard, orconformity assessment procedure wasasanitary orphytosanitary measure,
theSPSAgreement, nottheTBT Agreement, applied.147Whether ameasure wasasanitary measure
under theSPS Agreement depended onthepurpose ofthemeasure. TheUnited States hadshown
thattheECmeasures were sanitary measures asdefined intheSPS Agreement. Accordingly, they
were notsubject totheTBT Agreement byvirtue ofArticle 1.5oftheTBT Agreement, butwere subject
totheSPSAgreement. However, theTBT Agreement ’sprovisions demonstrated thefulldegree to
which theECbanwasfundamentally incompatible with theECWTO obligations. Even iftheEC
bandidnotconsist ofsanitary measures, theEuropean Communities stillcould notmaintain theban
since itwould beinconsistent with theTBT Agreement.
4.241 TheUnited States submitted thattheECmeasures were technical regulations. They laiddown
mandatory process andproduction methods (PPMs) related toproduct characteristics foranimals and
meat. They prohibited thesaleofanimals towhich hadbeen administered anyofthesixhormones
forgrowth promotion purposes, andmeat from such animals. TheEuropean Communities didnot
contest thatitsmeasures were mandatory PPMs andduring thedebate onitsmeasures intheTokyo
Round Committee onTechnical Barriers toTrade, theEuropean Communities hadinsisted thatits
measures were "requirements which hadbeen drafted intheEEC Directive interms ofaPPM".148
145Article 2.2oftheTBT Agreement provides: "Members shall ensure thattechnical regulations arenotprepared, adopted
orapplied withaview toorwiththeeffect ofcreating unnecessary obstacles tointernational trade." Clause 5ofthepreamble
expresses thattheMembers enter intotheTBT Agreement "Desiring ...toensure thattechnical regulations ...donotcreate
unnecessary obstacles tointernational trade."
146Article 1.3oftheTBT Agreement.
147TheUnited States noted thatasimilar “carve-out ”wasprovided forgovernment purchasing specifications inArticle 1.4
oftheTBT Agreement .
148See,forexample, TBT/M/Spec/5 (Minutes ofMeeting held22May 1987), paragraph 9.Seealsothecommunication
fromtheEuropeanCommunities(TBT/Spec/21),of23July1987,inwhichtheEuropeanCommunitiesstates:"TheECDirective
constitutes aPPM. TheECDirective establishes theprinciple ofnon-administration ofhormonal substances forfattening
purposes toanimals ofwhich themeat isexported totheEC. Itthus constitutes aregulation intheform ofaprocess or
production method andnotastandard expressed interms ofproduct characteristics."WT/DS26/R/USA
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Similarly, theEuropean Communities ’own statements established thatthePPMs were related tothe
characteristics oftheproduct. Forexample, Directive 81/602/EEC cited theECconcern over "the
residues [thesubstances] leave inmeat".149TheUnited States claimed that(asdemonstrated bythe
discussion under Articles IandIIIofGATT) theECmeasures treated meat imported from theUnited
States lessfavourably than likeproducts produced within theEuropean Communities andoriginating
intheterritory ofother Members. Theterm "like product" wasnotdefined intheTBT Agreement,
butgiven thedirect parallel between thelanguage ofArticle 2.1oftheTBT Agreement andArticle III:4
ofGATT, theGATT approach to"like product" should apply. Similarly, given thedirect parallels
between Article 2.1oftheTBT Agreement andArticles IandIIIofGATT, atechnical regulation that
wasinconsistent with Articles IorIIIofGATT should alsobeinconsistent with Article 2.1oftheTBT
Agreement. Accordingly, forthesame reasons thattheECbanwasinconsistent with Articles Iand
IIIofGATT, itwould beinconsistent with Article 2.1oftheTBT Agreement.
4.242 TheUnitedStatesclaimedthatinherentinArticle2.2oftheTBTAgreementwastherequirement
thatatechnical regulation fulfil alegitimate objective. Protection ofdomestic production wasnota
legitimate objective. Thebenefits oftheWTO agreements would benullified orimpaired ifMembers
were permitted todesign their technical regulations inorder toprotect domestic production. This was
reflected both intheprohibition inArticle 2.2oncreating "unnecessary obstacles totrade" andinthe
statementinArticleIII:1ofGATTthatinternalmeasuresshouldnotbeapplied"soastoaffordprotection
todomesticproduction".Yet,asshowninthediscussionofArticleIIIofGATTandtheSPSAgreement,
theECmeasures were disguised protectionism, designed torestrict trade. Therefore, these measures
were more trade-restrictive than necessary tofulfil alegitimate objective.
4.243 TheUnited States stressed thattheEuropean Communities hadrequired under paragraph 7
ofArticle 6ofDirective 88/146/EEC thatconformity assessment procedures beestablished withrespect
toimports. However, thisprovision required that"[i]n accordance with theprocedure laiddown in
Article 8,acontrol programme shall bedrawn upregarding imports from third countries, toensure
thatimports donotreceive more favourable treatment than ECproducts."150Inother words, theEC
approachhadreversedthegeneralprinciplethatimportsweretobeaccordednolessfavourabletreatment
thandomestic production. Instead, treatment ofimports wastobesubverted totheobjective ofensuring
thatimportsreceivednomorefavourabletreatmentthandomesticproduction.Notonlywasthiscontrary
toArticle 5.1.1 oftheTBT Agreement, butitwasanapproach thatclearly required thattheEC
conformity assessment procedures with respect toimports beprepared, adopted orapplied with aview
to,orwith theeffect of,creating unnecessary obstacles tointernational trade. Requiring thatthe
conformity assessment procedures forimports bemade more onerous wherever necessary toensure
thatimports didnotreceive more favourable treatment than domestic production wasnotconsistent
with therequirement inArticle 5.1.2 oftheTBT Agreement that"conformity assessment procedures
shall notbemore strict orbeapplied more strictly than isnecessary".
4.244 TheEuropean Communities responded thatinthepresent case, itagreed thatthemeasures
challenged were better defined asmeasures falling within thescope oftheSPSAgreement rather than
theTBT Agreement. TheEuropean Communities therefore didnotrespond tothearguments made
bytheUnited States asregards theTBT Agreement.
149Clause 5ofthePreamble.
150TheUnited States noted thatsimilar language wasfound inArticle 6ofDirective 81/602/EEC.WT/DS26/R/USA
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4. GATT 1994
(a) Article III:4 ofGATT
4.245 TheUnited States claimed thatdespite therequirements ofArticle III:4 ofGATT, theEC
banprohibited theimportation andsaleofcertain imported meat, while permitting thesaleoflike
domestic products. TheECmeasures distinguished between:
(i) animals, andmeat from animals, towhich hadbeen administered anyofthehormones
atissue forgrowth promotion purposes; and
(ii) animals, andmeat from animals, towhich anyofthehormones hadnever been
administered, ortowhich thethree natural hormones hadbeen administered for
therapeutic purposes.
TheUnited States maintained thatthere wasnolegitimate basis fortheECdistinction. Notonly was
there nobasis fordistinguishing between these likeproducts duetoanyrisktohuman health, because
there wasnobasis forclaiming ahealth riskfrom meat produced using thesixhormones, butthe
European Communities 'other basis forthemeasures stated aproscribed purpose, theprotection of
domestic production.151
4.246 Althoughtheterm"likeproduct"hadnotbeendefinedinGATT1994,theUnitedStatesobserved
thatunder GATT 1947 andGATT 1994 theapproach hadbeen toexamine whether products were
"like" onacase-by-case basis. Inmaking adetermination whether products were "like", panels had
considered factors such asphysical characteristics, end-uses, tariff classification andsubstitutability.152
TheUnited States argued thatinthisinstance, animals, andmeat from animals, towhich hadbeen
administered anyofthehormones forgrowth promotion purposes were clearly "like" other animals
andmeat from other animals. Infact, inthecaseofthethree natural hormones, meat from ananimal
towhichthehormonehadbeenadministeredforgrowthpromotionpurposescouldbephysicallyidentical
tomeat from ananimal towhich nohormone hadbeen administered, ortowhich ahormone hadbeen
administered fortherapeutic purposes. There wasnodifference atallbetween such physically identical
products andthus nobasis todistinguish between them forhealth orother legitimate purposes.
4.247 TheUnited States claimed thatasithaddemonstrated inthediscussion oftheECmeasures
under theSPSAgreement, these hormones were naturally occurring infood animals, andtheir levels
varied widely even among animals ofthesame species. Thus, forexample, aheifer would naturally
have higher levels ofoestrogen than asteer towhich oestradiol-17 hadbeen administered. Whether
there wasaresidue didnotdepend onwhether thehormone wasadministered forgrowth promotion
orfortherapeutic purposes. Similarly, with respect tothesynthetic hormones, there wasnothing about
these hormones thataltered thephysical characteristics, end-uses, tariff classification orsubstitutability
inaway thatwould render animals, andmeat from animals, towhich these hadbeen administered
151Article III:1 ofGATT provides that:
"1.Thecontracting parties recognize thatinternal taxes andother internal charges, andlaws, regulations and
requirements affecting theinternal sale, offering forsale, purchase, transportation, distribution oruseofproducts,
andinternal quantitative regulations requiring themixture, processing oruseofproducts inspecified amounts or
proportions,shouldnotbeappliedtoimportedordomesticproductssoastoaffordprotectiontodomesticproduction"
(emphasis added).
152TheUnited States noted forexample thepanel reports on"United States -Measures Affecting Alcoholic andMalt
Beverages", DS23/R, BISD 39S/209; "Japan -Customs Duties, Taxes andLabelling Practices onImported Wines and
Alcoholic Beverages", BISD 34S/83; andparagraph 6.9ofthepanel report on"United States -Standards forReformulated
andConventional Gasoline", adopted on19June 1996, WT/DS2/R.WT/DS26/R/USA
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"unlike" animals, andmeat from animals, towhich they hadnotbeen administered. Thesynthetic
hormones were rapidly metabolized bytheanimals andanyremaining residues inthemeat were safe.
4.248 TheEuropean Communities responded thatbecause female animals aretreated forgrowth
promotion withmale hormones, andvice-versa, theresidues inananimal treated withanatural hormone
aredifferent from, aswell asgreater than, those which itwould otherwise contain. Thehuman diet
normally contained avariety ofmeat; evidently ifallthemeat came from treated animals theamount
ofhormone residue ingested would besignificantly increased. Ifaproper comparison were tobemade
involving male animals, itwould have tobebetween treated anduntreated males toseehow farthe
levels offemale hormones were increased inmale animals. According totheUSargument, heifer
meat would be"within thenormal range" ifitcontained asmuch testosterone asbullmeat.
4.249 TheUnited States argued thatArticle IIIofGATT hadbeen interpreted topermit governments
todistinguish between otherwise likeproducts forlegitimate regulatory purposes. Asstated inthe
panel report onUnited States -Taxes onAutomobiles: "Article IIIserves only toprohibit regulatory
distinctions between products applied soastoafford protection todomestic production. Itspurpose
isnottoprohibit fiscal andregulatory distinctions applied soastoachieve other policy goals. This
view hadbeen expressed inarecent panel report, which states:
"The purpose ofArticle IIIis...nottoprevent contracting parties from using their fiscal and
regulatory powers forpurposes other than toafford protection todomestic production.
Specifically, thepurpose ofArticle IIIisnottoprevent contracting parties from differentiating
between different product categories forpolicy purposes unrelated totheprotection ofdomestic
production. ThePanel considered thatthelimited purpose ofArticle IIIhastobetaken into
account ininterpreting theterm "like products" inthisArticle. Consequently, indetermining
whether twoproducts subject todifferent treatment arelikeproducts, itisnecessary toconsider
whether such product differentiation isbeing made "soastoafford protection todomestic
production".153
4.250 TheUnited States didnotcontest theright oftheEuropean Communities todistinguish between
products forlegitimate policy purposes. Members ’ability tosodistinguish wasconfirmed bythetext
andhistory ofArticle IIIofGATT andtheTBT Agreement. However, theUnited States didcontest
thelegitimacy ofthepolicy goal advanced bytheEuropean Communities foritsdiscrimination. The
European Communities hadclaimed health concerns asthebasis foritsban,butallsixofthehormones
involved inthisdispute hadbeen determined tobesafebyallthescientific experts thathadreviewed
them. Moreover, theEuropean Communities hadnever putforward anybasis tocontest thesafety
ofthese hormones. TheEuropean Communities hadalsostated acompetition rationale foritsban.
However, intheUSview, whatever themerits might beofharmonizing regulatory treatment within
aMember ’sterritory, such apolicy wasdifficult toreconcile with GATT when thepolicy wasapplied
toimports with noother health, environmental, orother legitimate policy purpose. Ithadbeen noted
that"aprimary purpose oftheGeneral Agreement wastolower barriers totrade between markets,
andnottoharmonize theregulatory treatment ofproducts within them".154TheUnited States further
claimed thattheECmeasures hadbeen motivated byadesire toreduce thesupply ofbeef inthe
European Communities andtheyhadworked toeasetheEuropean Communities ’over-supply problems.
Byrequiring thatforeign producers adopt thesame processes andproduction methods asECproducers,
theECmeasures hadseverely restricted imports, thus providing relief todomestic ECproducers.
4.251 TheUnited States claimed thatithadbeen common, prior totheentry intoforce oftheWTO
Agreement, forgovernments totakeaction torestrict imports aspartofaneffort tocontrol domestic
153Panelreporton"US-MeasuresaffectingAlcoholicandMaltBeverages",adopted19June1992,DS23/R,BISD39S/206.
154Paragraph 5.8ofthepanel report on"US -Taxes onAutomobiles", (DS31/R).WT/DS26/R/USA
Page 98
supplies ofagricultural products. Article XI:2(c) ofGATT provided anexception forthispurpose,
subject tostrict conditions.155However, aprimary component oftheAgreement onAgriculture was
toeliminate thispractice.156TheECmeasures, asapplied toimports, were yetanother example of
measures torestrict imports inorder tocontrol thetotal supply ofanagricultural product. Finally,
theUnited States argued thatnotonly animals, andmeat from animals, towhich hadbeen administered
thehormones forgrowth promotion were "like" other animals andmeat from other animals, butthe
ECmeasures resulted inlessfavourable treatment than thataccorded todomestic sales andimports
from other countries ofother animals, andmeat from other animals, inbreach ofArticle III:4 ofGATT.
4.252 TheEuropean Communities argued thatthemeasures atissue hadtheir domestic counterpart
intheprohibition ontheadministration ofthesame types ofhormones toanimals reared intheEuropean
Communities andintheprohibition onthemarketing ofthose animals andofmeat from those animals.
Themeasures applied todomestic products hadidentical scope andwere subject tothesame exceptions
asthemeasures applied totheimported products. Theonly difference between themeasures applied
todomestic products andthose applied toimported products wasthatwhile theformer were applied
atthestage ofproduction andsale, thelatter were enforced atthepoint ofimportation. Furthermore,
themeasures applied toboth domestic andimported products as"products", even iftheir scope was
defined interms ofprocesses andproduction methods ("PPM") rather than interms ofproduct
characteristics. Thepresent case wastobedistinguished from thesituation considered bythepanel
report onUS-Restrictions onImports ofTuna I,inwhich thepanel hadreasoned thattheNote ad
Article IIIcovered only those measures thatwere "applied toproducts assuch". Yet, according to
thepanel, theUSinternal regulations "could notpossibly affect tuna asaproduct ".157Incontrast,
inthepresent case thereason forprohibiting theimportation ofanimals which hadbeen treated with
certain hormones, andofmeat from those animals (aswell astheir domestic production andsale),
wasprecisely thatthistreatment, unlike thePPMs forfishing tuna prescribed bytheUSregulations,
modified thephysical characteristics andbiological composition oftheproducts.
4.253 TheEuropean Communities disagreed with theUSinterpretation of"like products". Inthe
ECview, adetermination of"likeness" must beexclusively based onobjective criteria related tothe
characteristics oftheproducts themselves. Thepurpose ofaregulatory distinction between "like
products" might only become relevant indeciding whether ameasure which wasinconsistent with
Article III:4 could bejustified under anyofthegeneral exceptions provided forunder Article XXof
GATT. TheEuropean Communities contended thatthepurpose ofthemeasures atissue wasnotto
afford protection todomestic production buttoprotect human andanimal health, aswellastheinterests
ofconsumers and, therefore, would not, inconformity with theUnited States 'own test, infringe
Article III:4. Although twoproducts need notbeidentical inorder tobe"like" forthepurposes of
Article III,previous panel reports hadtaken aconsistently narrow approach when interpreting this
term. InEuropean Communities -Measures onAnimal Feed Proteins, thepanel hadrejected aclaim
bytheUnited States totheeffect thatallproducts used forthepurpose ofadding proteins toanimal
feeds were "like". Thepanel noted, inter alia,thattheproducts concerned haddifferent protein contents
anddifferent origins (vegetal, animal orsynthetic).158More recently, thepanel report onJapan -Taxes
155TheUnited States noted thatthepanel report on"Japan -Restrictions onImports ofCertain Agricultural Products",
adopted on2February 1988 (L/6253 -35S/163), illustrated justhow strict these conditions were.
156Article 4.2oftheAgreement onAgriculture.
157Panel report on"US-Restrictions onImports ofTuna I",DS21/R (unadopted), dated 3September 1991, 39S/155,
pp.193-195, paras 5.8-5.14.
158Panel report on"EC -Animal Feed Proteins", atpara. 4.2. Theother panel report dealing witharegulatory measure
discriminating between non-identical products isthepanel report onUS-Measures affecting Alcoholic andMalt Beverages.
Inthiscase, thepanel found thatlowalcohol andhigh alcohol beer were "similar" interms ofphysical characteristics but
(continued...)WT/DS26/R/USA
Page 99
onAlcoholic Beverages, acase concerning theapplication ofArticle III:2 ofGATT, hadconcluded
that:
"...only vodka could beconsidered aslikeproduct toshochu since, apart from
commonality ofend uses, itshared with shochu most physical characteristics.
Definitionally, theonly difference isinthemedia used forfiltration. Substantial
noticeable differences inphysical characteristics exist between therestofthealcoholic
beverages atdispute andshochu thatwould disqualify them from being regarded as
likeproducts. More specifically, theuseofadditives would disqualify liqueurs, gin
andgenever; theuseofingredients would disqualify rum; lastly, appearance (arising
from manufacturing processes) would disqualify whisky andbrandy"159(emphasis
added).
4.254 TheEuropean Communities reaffirmed itsview thatmeat from animals towhich hadbeen
administeredanyofthesixhormonesatissueforgrowthpromotionhadsubstantiallydifferentproperties,
composition andappearance thanmeat from animals towhich those hormones hadnotbeen administered
ortowhich they hadbeen administered only fortherapeutic purposes. Moreover, meat from treated
animals wasperceived byEuropean consumers asadistinct product. Forthese reasons, animals treated
with hormones forgrowth promotion, andmeat from those animals, could not,inlight ofthecriteria
used byprevious panel reports, beconsidered as"like" toother animals, andmeat from those animals,
forthepurposes ofArticle III:4. TheEuropean Communities claimed thatanimals, andmeat from
animals, treated with anyofthehormones atissue forgrowth promotion were different from animals
andmeat from untreated animals orfrom animals treated fortherapeutic purposes, andreferred to
itsarguments with regard totheSPS Agreement. Taking intoaccount theconsumer 'sconcerns as
detailed with respect totheSPS Agreement, meat from animals treated with thehormones atissue
forgrowth promotion andmeat from untreated animals orfrom animals treated fortherapeutic purposes
were notsubstitutable formost European consumers and, accordingly, not"like" forthepurposes of
Article III:4.
4.255 TheEuropean Communities argued thateven ifanimals treated with hormones forgrowth
promotion, andmeat thereof, andother animals, andmeat thereof, were found tobe"like products",
itsmeasures would stillbeconsistent with Article III:4 because they afforded identical treatment to
imported products andtodomestic likeproducts. TheEuropean Communities disagreed with theUS
interpretation ofArticle III:4. IntheECview, Article III:4 didnotprevent Members from establishing
regulatory distinctions within agiven category oflikeproducts, provided thatsuch distinctions did
not,formally orineffect, givelessfavourable treatment toimported products thantodomestic products.
Forthispurpose, thecomparison must bemade between thetreatment given toallimported goods
asawhole andthetreatment accorded toalllikedomestic products asawhole. Thus, inthepresent
case therelevant comparison wasnotbetween imported products treated with hormones forgrowth
promotion anddomestic untreated products, butbetween imported meat anddomestic meat.
4.256 TheEuropean Communities submitted thatthewording ofArticle III:4 called foracomparison
between thetreatment given to"theproducts oftheterritory ofanycontracting party imported into
theterritory ofanyother contracting party ...."andthetreatment accorded to"likeproducts ofnational
origin..." andnotbetween thetreatment given to"anyimported product" andthetreatment accorded
to"any domestic likeproduct". Theordinary meaning ofArticle III:4 didnotrequire thatacomparison
bemade onanimport-by-import basis, butacomparison ofthetreatment given toallimported products
158(...continued)
were not"like" forthepurposes ofArticle III:4 because thedistinction wasnotapplied soastoafford protection todomestic
production, BISD 39S/206, pp.93-295, paras 5.70-5.77.
159Panel report on"Japan -Taxes onAlcoholic Beverages", para. 6.23.WT/DS26/R/USA
Page 100
asawhole vis-a-vis alldomestic likeproducts asawhole. IntheECview, theobject andpurpose
ofArticle IIIhadbeen made explicit inthegeneral principle setforth inthefirst paragraph ofthat
Article, which stated thatinternal taxes andregulations "should notbeapplied toimported ordomestic
products soastoafford protection todomestic production". Article III:4 gave effect tothisprinciple
with respect tointernal regulations, other than taxregulations andmixing regulations, andshould be
interpreted inconformity with it.Where aninternal regulation laiddown different requirements for
imported anddomestic products, itmight beassumed thatdomestic production was"protected" ifany
imported product received "less favourable treatment".160Thesituation wasdifferent where, asin
thepresent case, theinternal regulation didnotdistinguish between imported anddomestic products
butbetween different types oflikeproducts, irrespective oftheir origin. Themere factthataninternal
regulation accorded more favourable treatment tocertain types oflikeproducts vis-a-vis other types
oflikeproducts didnotnecessarily mean thatdomestic production ofthelikeproduct asawhole was
protected. Forthat, itwould benecessary thatthose types oflikeproduct which were accorded more
favourable treatment were inherently oratleast predominantly domestic and/or thatthetypes which
received lessfavourable treatment were inherently oratleast predominantly imported. TheECviews
found support inthepanel report onUS-Measures affecting Alcoholic andMalt Beverages, which
stated that:
"The panel recognized thatonthebasis oftheir physical characteristics, lowalcohol beer and
high alcohol beer were similar. Itthen proceeded toexamine whether, inthecontext of
Article III,thisdifferentiation intreatment oflowalcohol beer andhigh alcohol beer issuch
"astoafford protection todomestic production". Thepanel firstnoted thatboth Canadian and
United States beer manufacturers produce both high andlowalcohol beer. Itthen noted that
thelaws andregulations inquestion invarious states donotdifferentiate between imported
anddomestic beer assuch,sothatwhere astate lawlimits thepoints ofsaleofhigh alcohol
content beer ormaintains different labelling requirements forsuch beer, thatlawapplies to
allhigh alcohol content, regardless ofitsorigin. Theburdens resulting from these regulations
thusdonotfallmoreheavilyonCanadianthanonUnitedStatesproducers"161(emphasisadded).
4.257 Although intheECview thepanel report onUS-Measures affecting Alcoholic andMalt
Beverages erred byascribing theanalysis oftheeffects ofameasure tothedetermination whether two
products were "like" andnotexclusively onthecharacteristics oftheproducts, thispanel report
confirmed thatArticle III:4 wasnotinfringed unless aregulatory distinction between likeproducts
hadtheeffect ofprotecting domestic production.162TheEuropean Communities claimed thatincase
160Hence the"no-balancing" principle established byprevious panel reports which have dealt with formally discriminatory
internal regulations. Seepanel report onUS-Section 337oftheTariff Actof1930, adopted on7November 1989,
BISD36S/345,387,para5.14;andpanelreporton"US-StandardsforReformulatedGasoline",WT/DS2/R,paras6.14-6.15.
161Panel report on"US -Measures affecting Alcoholic andMalt Beverages", BISD 39S/206, para. 5.73.
162TheEuropean Communities indicated thatasnoted above, thepanel report on"EC-Measures onanimal feedproteins"
(theonlyother adopted panel report thathasapplied Article III:4 toanorigin neutral internal regulation) found thattheproducts
concerned were not"like" byreason oftheir differences inphysical characteristics and, therefore, didnothave toruleon
therelevance oftheeffects ofthemeasure. Nevertheless, itisworth noting thatthearguments made inthatcase bythe
US,acting asacomplainant, were based onthepremise thataninternal regulation which isnotapplied toalllikeproducts
does notinfringe Article III:4, unless itisshown tohave aprotectionist effect:
"TherepresentativeoftheUnitedStatestooktheviewthatthemeasuresfocusedtheimpactmoredirectlyonimported
vegetable proteins, particularly soybeans, because they didnotapply toanimal, marine andsynthetic proteins,
even though such proteins were, withvegetable proteins, substitutable foruseinfeeds. Hemaintained thatanimal,
marine andsynthetic proteins were excluded from themeasures because there wassubstantial domestic production
intheEEC andnotbecause these products were notlikeproducts, taking account oftheir generally higher protein
content andcertain technical advantages".
(continued...)WT/DS26/R/USA
Page 101
itsmeasures were found tobecontrary toArticle III:4, they were justified byArticle XX:(b) which
didnotaffect thepower ofaMember toadopt apolicy inorder toprotect human andanimal health.
Moreover, theEuropean Communities submitted thatincasethePanel were tofindthatitsmeasures
infringed Article III:4, forthereasons stated, they satisfied therequirements oftheSPS Agreement
and, consequently, must bepresumed tobeinaccordance with theGATT, andinparticular with the
provisions ofArticle XX(b).
(b) Article I:1ofGATT
4.258 TheUnited States noted thatArticle I:1ofGATT prohibited discrimination against products
fromoneMemberinfavouroflikeproductsfromotherMembers.However,theEuropeanCommunities
permitted theimportation andsalefrom other Members ofanimals, andmeat from animals, towhich
thethree natural hormones hadbeen administered fortherapeutic purposes ortowhich hormones had
notbeen administered. Noting that, asdemonstrated, thebanned beefwas"like" beeffrom ananimal
towhich hormones hadbeen administered fortherapeutic purposes andwaslikebeeffrom ananimal
towhich hormones hadnotbeen administered, theUnited States argued thattheECbandiscriminated
against thelikeUSproducts. Consequently, similar toallthereasons described under Article III,the
ECmeasures failed toaccord immediately toimports from theUnited States theadvantages, favours,
privileges orimmunities granted tolikeanimals andmeat originating intheterritories ofother countries.
4.259 TheUnited States claimed thattheECdiscriminatory measures could notbejustified byresort
toArticle XXofGATT, inparticular Article XX(b). TheEuropean Communities hadputforward
noevidence tosupport itsmeasures onhealth grounds, andasshown withrespect totheSPSAgreement,
these measures were "applied inamanner which would constitute ameans ofarbitrary orunjustifiable
discrimination between countries where thesame conditions prevail, oradisguised restriction on
international trade" within themeaning ofthechapeau toArticle XX. Furthermore, theSPSAgreement
elaborated "rules fortheapplication oftheprovisions ofGATT which relate totheuseofsanitary
orphytosanitary measures, inparticular theprovisions ofArticle XX(b)"163andsanitary measures that
complied with theSPSAgreement were presumed tobeinaccordance with Article XX(b) ofGATT.164
Ithadbeen shown above thattheECmeasures were inconsistent with theECobligations under the
SPSAgreement.TheEuropeanCommunitieshadfailedtoestablishthatitsbanwasjustifiedbyinvoking
Article XX(b).
4.260 Forallthese reasons, theUnited States claimed thattheECbanwasinconsistent with the
European Communities 'obligations under theGATT, inparticular Articles IandIII.
4.261 TheEuropean Communities argued thattheUnited States alleged violation ofArticle Iwas
aclaim which wasoutside thePanel 'sterms ofreference. Consequently, theECarguments were made
only inthealternative, incase thePanel were nottouphold theECargument. The European
Communities stressed again thatanimals towhich thehormones hadbeen administered forgrowth
promotion, andmeat from those animals, hadsubstantially different properties, composition and
appearance than other animals, andmeat from those other animals. Moreover they were perceived
byconsumers asadifferent product. Forthese reasons, they could notbeconsidered asbeing "like"
forthepurposes ofArticle I:1ofGATT. IntheEuropean Communities 'view, even iftheywere found
tobe"like", themeasures would stillnotinfringe Article I:1. Themost favoured nation principle
162(...continued)
(Panel report on"EC -Measures onanimal feed proteins", para. 3.39)
163Clause 8ofthepreamble totheSPSAgreement.
164Article 2.4oftheSPSAgreement.WT/DS26/R/USA
Page 102
contained inthat provision was concerned with discrimination between countries andnotwith
discrimination between products. Article I:1didnotprevent Members from giving different treatment
togoodsfallingwithinasinglecategoryof"likeproducts",aslongasthedistinctiondidnotdiscriminate,
formally orineffect, according tothecountry oforigin ofthegoods.
4.262 TheEuropean Communities maintained thatthisinterpretation hadbeen supported byalong
series ofprevious panel reports, including thepanel report onBelgian Family Allowances which had
found that"theBelgian legislation would have tobeamended insofarasitintroduced adiscrimination
between countries having agiven legal system offamily allowances andthose which hadadifferent
system ornosystem atall,andmade thegranting oftheexemption dependent oncertain conditions"165
(emphasisadded).AccordingtoDr.Jackson,thispanelreportstoodforthepropositionthat"permissible
distinctions between thetreatment ofgoods maybebased only oncharacteristics ofthegoods andnot
oncharacteristics oftheir country oforigin".166InEuropean Communities -Measures onAnimal Feed
Proteins, theUSclaim thatallfeed proteins were likeproducts andthatbyexcluding some types of
feedproteins from thescope ofthecontested measures theEuropean Communities haddiscriminated
between imports originating intheUnited States andimports oflikeproducts originating inthird
countries, thereby violating Article I:1,hadbeen rejected bythepanel which hadnoted that"asignificant
portion ofECimports oflikeproducts, including soybeans, subject tothemeasures originated from
contracting parties other than theUnited States."167
4.263 Inaddition, theEuropean Communities noted thatinSpain -Tariff Treatment ofUnroasted
Coffee, thepanel hadconcluded thatbyapplying different tariff rates todifferent varieties ofcoffee
which hadbeen previously found tobelikeproducts, Spain hadinfringed itsobligation under Article I:1.
Inreaching thisconclusion thepanel hadnoted thatthecomplainant, Brazil, exported toSpain mainly
thosevarietieswhichweresubjecttothehigherdutyrates.Thus,importsfromBrazilwerediscriminated
defacto vis-a-vis imports from other countries thatgrew mainly thevarieties subject tothelower duty
rates.168
4.264 Finally, theEuropean Communities pointed outthatinUnited States -Restrictions onImports
ofTuna Fish I,Mexico hadclaimed thatthelabelling provisions oftheDolphin Protection Consumer
Information Actviolated Article I:1because, inthecaseoftunaharvested intheEastern Tropical Pacific
Ocean ("ETP"), theright tousethelabel "dolphin safe" wasaccorded onlyifsuch tunawasaccompanied
bydocumentary evidence showing thatitwasnotharvested withcertain fishing techniques. Even though
there wasnoquestion thattuna caught intheETP byMexico was"like" anyother tuna, thepanel
rejected thisclaim byreasoning that:
"According totheinformation presented tothepanel, theharvesting oftuna byintentionally
encircling dolphins with purse-seine netswaspractised only intheETP [....] Byimposing
therequirement toprovide evidence thatthisfishing technique hadnotbeen used inrespect
oftuna caught intheETP theUnited States didnotdiscriminate against countries fishing in
thisarea.Thepanel noted that, under United States customs law, thecountry oforigin of
fishwasdetermined bythecountry ofregistry ofthevessel thathadcaught thefish; the
geographical areawhere thefishwascaught wasirrelevant foradetermination oforigin. The
labelling regulations governing tuna caught intheETP thus applied toallcountries whose
165Panel report on"Belgian Family Allowances", adopted on7November 1952, BISD 1S/59, p.60, para. 3.
166J.Jackson, "World Trade andtheLaw oftheGATT", pp.258-259.
167Panel report on"EC -Measures onAnimal Feed Proteins", para. 4.20.
168Panel report on"Spain -Tariff Treatment ofUnroasted Coffee", adopted on11June 1981, BISD 28S/102, pp.111-112,
para. 4.10.WT/DS26/R/USA
Page 103
vesselsfishedinthisgeographicalareaandthusdidnotdistinguishbetweenproductsoriginating
inMexico andproducts originating inother countries. "169(emphasis added).
4.265 TheEuropean Communities argued thatthemeasures atissue applied without distinction to
allimports ofmeat irrespective oftheir country oforigin andnotonly toimports originating inthe
United States. Furthermore, themeasures didnotdiscriminate defacto against USimports. Animals
treated with hormones forgrowth promotion, andmeat from those animals, were notaninherently
USproduct oraproduct which waspredominantly produced intheUnited States. Inaddition tothe
United States, there were other countries which authorized some oralloftheprohibited hormones.
Ontheother hand, untreated animals, andmeat from those animals were produced invirtually all
countries oftheworld, including theUnited States. Infact, imports from theUnited States andfrom
other countries which authorized theuseofallorsome oftheprohibited hormones accounted fora
major proportion oftheECimports.
4.266 TheEuropean Communities thus maintained thatthemeasures atissue were alsoconsistent
with Article I:1ofGATT. Incase thePanel were tofindthecontrary, theEuropean Communities
submitted that, forthereasons stated, they satisfied therequirements oftheSPS Agreement and,
consequently, must bepresumed toinaccordance with theGATT, andinparticular with theprovisions
ofArticle XX(b).
4.267 TheUnited States noted thattheissue oftheinconsistency oftheECbanwith Article I:1of
GATT waswithin theterms ofreference ofthisPanel, despite theECargument tothecontrary. The
Panel hadstandard terms ofreference established inaccordance with DSU Article 7.1andtheUnited
States request fortheestablishment ofthePanel cited GATT, which included Article I:1.Furthermore,
theUnited States hadmade explicit thatitsreference toArticle IIIorArticle XIwasanon-exhaustive
listing oftherelevant GATT articles.170Moreover, theECclaim raised ageneral issue ofinterpretation:
whether thephrase "cited bytheparties tothedispute" inthestandard terms ofreference intheDSU
modified thewords "covered agreement(s)" orwhether thisphrase modified thewords "relevant
provisions". IntheUSview, "cited bytheparties tothedispute" wasclearly meant tomodify "covered
agreement(s)". This conclusion wasclear from thetextandthecontext ofDSU Article 7.1.
4.268 Thenegotiating background ofArticle 7.1confirmed thismeaning. Theprovision onstandard
termsofreferenceinparagraphF(b)(1)oftheMontrealDecisionon"ImprovementstotheGATTDispute
Settlement Rules andProcedures" hadprovided thatapanel would examine thematter referred toit
bythecomplaining party "inthelight oftherelevant GATT provisions". This phrase hadbeen modified
to"inthelight ofthecovered Agreements cited bytheparties tothedispute" inthesection on"Terms
ofReference" atpage T.3ofMTN.TNC/W/FA (the"Dunkel Draft" of20December 1991) inthe
texton"Elements ofanIntegrated Dispute Settlement System". Thealteration wasmade inresponse
toaninitiative bytheEuropean Communities, inspired byitsdifficulties intheAirbus case. The
objective wastomake itpossible foradefending party to"cite" agreements additional tothose cited
bythecomplaining party, andtohave thepanel apply allagreements cited byboth sides.171Moreover,
theEuropean Communities 'own arguments inthisdispute contradicted itsterms ofreference claim.
Even though thepanel request didnotrefer toArticle XXofGATT, andtheEuropean Communities
didnot"cite" thisprovision either inadispute-related document orinDSB proceedings when thepanel
169Panel report on"US -Restrictions onImports ofTuna I",para. 5.43.
170Seeparas. 1.4and1.5
171TheUnited States noted texts dated 12December and17December 1991, inwhich thesame reference to“agreements
cited”interms ofreference appeared under thedescriptive subheading “Forum/Norm Shopping. ”This term hadbeen used
inearlier discussions in1990, inthewake oftheEuropean Communities 'inability toobtain terms ofreference intheTokyo
Round Subsidies Code Airbus dispute which would permit application oftheAgreement onTrade inCivil Aircraft aswell.WT/DS26/R/USA
Page 104
wasestablished, theEuropean Communities hadsought tohave thePanel examine theapplication of
Article XXinthiscase. TheEuropean Communities could nothave itboth ways.
V. THIRD PARTIES SUBMISSION
1. Australia
5.1 Australia submitted thatasamajor exporter ofmeat and, inrecent years, theworld 'slargest
beefexporter ithadamajor trade interest inthismatter. Stressing itsspecific interest intheECbeef
market, Australia noted thatithadmanaged tocontinue itstrade withtheEuropean Communities despite
theimplementation ofCouncil Directive 88/146/EEC bythedevelopment ofanHormone Growth
Promotion (HGP) control system. This system hadallowed Australian cattle producers who wished
tocontinue totrade with theEuropean Communities todoso,but,atthesame time, tobeabletoaccess
andusehormones forgrowth promotion purposes forother markets thatdidnotimpose suchrestrictions.
This hadbeen atacosttotheAustralian industry ofabout $A10million ayear. However, Australia
hadnever accepted thelegitimacy oftheECmeasures. Noting thatthepurpose ofthethree Directives
wastheprotection ofhuman lifeorhealth andthattheprohibition ontheimportation from third countries
ofmeat from animals towhich hormones hadbeen administered wasasanitary measure asdefined
bytheSPSAgreement, Australia claimed thattheconsistency oftheECmeasures with ECobligations
should beconsidered against theprovisions oftheSPSAgreement which required thatSPSmeasures
"shall bedeveloped andapplied inaccordance with theprovisions ofthisAgreement" (Article 1.1).
5.2 Australia argued thattheSPSAgreement established, inter alia,thebasic rights andobligations
ofMembers inrespect ofsanitary measures necessary fortheprotection ofhuman lifeandhealth which
may directly orindirectly affect international trade. Notwithstanding anyother WTO rights and
obligations, Australia considered thatifaMember were acting inconsistently with itsobligations under
theSPS Agreement, itstood inbreach ofitsWTO obligations. Inaddition, astheSPS Agreement
represented anelaboration oftheGATT inrespect ofSPS measures andasconformity with SPS
obligations gave risetoapresumption ofconformity with Article XX(b) oftheGATT, Australia
consideredthattheECmeasuresshouldbeexaminedinthefirstinstanceagainsttherightsandobligations
oftheSPS Agreement asitwasthisagreement which established thebasic rights andobligations of
Members inrespect ofSPS measures.
5.3 Australia placed particular stress onthefactthatinobserving thataninternational standard
asprovided forinArticle 3.1existed inrelation totheEChormone ban, theEuropean Communities
hadfailed todemonstrate itscompliance with Article 3.3. Inparticular, Australia argued thatthe
European Communities hadfailed todemonstrate either thatthere wasascientific justification forits
adoption ofmeasures resulting inahigher level ofprotection orthatithadcarried outanexamination
andevaluation ofavailable scientific evidence, including inaccordance with therelevant provisions
ofArticle 5toshow thattheinternational standard wasnotsufficient toachieve itsappropriate level
ofprotection.
5.4 Referring totheconclusions ofthe1995 ECScientific Conference [paragraph ...],Australia
argued thatalthough these conclusions provided clear support totheview thatthefivesubstances
considered attheConference were safetousewithin theconditions specified inAustralia andwithin
theCodex standards, theEuropean Communities hadconfusingly claimed that"...[t]he scientific
evidence forthenecessity tomaintain ourmeasures istheevidence from the1995 Scientific
Conference ...". TheEuropean Communities hadmade noattempt tosubstantiate thisassertion or
toexplain thecontradiction between thisstatement andtheConference conclusions.
5.5 Although theEuropean Communities hadasserted thatforthenatural hormones itwasknown
thatthey have adverse effects which, combined with alackofknowledge oftheir action, lackofdataWT/DS26/R/USA
Page 105
ontheeffect ofcombinations andthelack ofdefinition of"good veterinary practice", permit the
European Communities toadopt adifferent level ofprotection, i.e.ensure theECconsumers thatthere
arenoresidues leftother thanthenaturally produced ones bytheanimals themselves, Australia argued
thattheEuropean Communities hadfailed toestablish thatthese statements reflected thefindings of
ariskassessment oranexamination andevaluation ofavailable scientific information inconformity
with theprovisions oftheSPSAgreement. TheEuropean Communities hadalsonotestablished the
basis foritsclaim thatthere wasalackofdefinition of"good veterinary practice", which wasgenerally
taken tomean using veterinary chemicals inaccordance with conditions ofregistration, including
observing intended purpose, correct dose rates andwithholding periods thatwere determined bythe
technical registration process.
5.6 With regard totheECarguments thathormones hadserious adverse effects onhealth, including
cancer, Australia noted thatsuch claims hadalsobeen made inrespect ofdrugs containing hormonal
substances which were directly administered tohumans formedicinal purposes. The European
Communities hadnotexplained why itpractised azero riskpolicy intheissue under examination by
thePanel butnotinother comparable circumstances when itwasknown thatthehormonal product
would directly enter thehuman system. Good veterinary practice wasthebasis foruseofthehormones
atissue andtofocus only ontheworst case scenario astheEuropean Communities haddone could
render theuseofallveterinary chemicals illegal, justastheuseofallchemicals used inhuman medicinal
preparations might bebanned. Furthermore, thestatement thattheintensive large-scale production
ofmeatrenderedeffectivecontrolofhormonegrowthpromoterstechnicallyandeconomicallyunfeasible,
flew inthefaceofthefactthatmajor meat exporting nations apart from theEuropean Communities
were able toeffectively control inappropriate hormone usewithout theimposition ofatotal banon
theuseofthesesubstances.AllagriculturalandveterinarychemicalsusedwithinAustraliamustundergo
assessment andregistration prior todistribution anduse.Thisrequired athorough assessment ofdetailed
technical datapackages bytheNational Registration Authority. Theoutcome ofregistration wasto
control theuse,labelling, packaging andsupply oftheproduct. This wasunderpinned bylegislation,
with penalties where these conditions were notfollowed. Additionally, Australia backed upthesystem
with individual property identification ofcattle tothepoint ofslaughter, aNational Residue Survey
toassess compliance with MRLs, andaNational Vendor Declaration system forcattle through which
vendors must declare thechemicals used oncattle offered forsaleandthedate oftreatment.
5.7 Australia claimed thatthere wasnoevidence thattheEuropean Communities hadundertaken
arisk assessment onthismatter inaccordance with theprovisions ofArticle 5.The European
Communitieshadstatedthat"theEuropeanCommunitieshastwiceformedgroupsofscientiststoexamine
thehormones atissue". However, theyhadstated themselves that"thepurpose ofthe1995 ECscientific
Conference wasnottoperform foritariskassessment, buttoprovide apublic forum fordiscussion
ofthescientific aspects oftheuseofgrowth promoters". Therefore, theEuropean Communities had
explicitly accepted thatthisConference wasnotpartofariskassessment process. AttheCanada/EC
consultations on25July1996, atwhich Australia waspresent asathird party, theECrepresentative
hadsaidthatthere hadbeen noriskassessment done since theLamming Committee andthatnowork
hadbeen done inthisareasince 1988. However, nowhere within theECfirstsubmission inthiscase,
haditclaimed thattheLamming Committee hadundertaken ariskassessment process which could
beconsidered tohave mettherequirements ofArticles 5.1and5.2oftheSPS Agreement.
5.8 Emphasizing thatArticle 5.4required Members, when determining theappropriate level of
sanitary orphytosanitary protection, totakeintoaccount theobjective ofminimizing negative trade
effects, Australia submitted thatthere wasnoevidence tosuggest thattheEuropean Communities had
taken intoaccount negative trade effects when imposing theprohibition onimports ofmeat treated
with hormones forgrowth promotion purposes. This prohibition hadimposed significant compliance
costs ontheAustralian meat industry.WT/DS26/R/USA
Page 106
5.9 With regard toArticle 5.5, Australia argued thattheEuropean Communities hadfailed to
demonstrate itscompliance with thisprovision. "Consistency" didnotdemand aquantified level of
risk, orthatMembers must have thesame level ofriskinrespect ofevery measure. However, the
European Communities must justify why ithadadopted alower level ofriskinthiscase than in
comparable circumstances. Australia agreed thatinageneral sense itwastrue that, through risk
management, each country 'sacceptable level ofriskmight reflect societal values, but,asspecifically
stated byArticle 5.5,theacceptable level ofriskdetermined byacountry through thisprocess must
beapplied inaconsistent manner, andcould notbeapplied onanarbitrary orunjustifiable case-by-case
basis (forexample, theEuropean Communities choosing toaccept zero riskinthecase ofmeat from
animals treated with growth promoting hormones).
5.10 Australia furthermore argued thattheEuropean Communities hadfailed todemonstrate its
compliance with theobligation ofArticle 5.6. Itobserved thattheEuropean Communities hadclaimed
thatits"measures arenotprovisional: theyaredefinitive"172,andtherefore submitted thatArticle 5.7
wasnotrelevant inthiscase. Noting thatastheEuropean Communities hadfailed tocomply with
theprovisions ofArticle 3.3,failing todemonstrate thatthere wasascientific justification foritslevel
ofsanitary orphytosanitary protection orthatitsmaintenance ofalevel ofprotection higher than the
relevant international standard wasaconsequence ofthelevel ithaddetermined inaccordance with
theprovisions ofArticle 5,Australia concluded thatthere must beapresumption thattheECmeasures
were notinconformity with thebasic obligations ofArticles 2.2and2.3oftheSPS Agreement.
2. Canada
5.11 Canada stated thatithadnotonly asubstantial trade interest inthismatter, butavital interest
innovel questions oflegal interpretation thatarose inthiscase. This dispute wasthefirsttoexamine
theprovisions oftheSPSAgreement. Canada hadalsorequested theestablishment ofapanel onthe
same ECmeasures, which theDSB hadestablished on16October 1996, withsimilar terms ofreference
andthesame composition asthepresent Panel (document WT/DS48/5 refers).
5.12 Canada indicated thatallthesixhormones atissue were authorized inCanada forcattle growth
promotion. With respect tothe1995 ECScientific Conference ongrowth promotion inmeat production,
Canadian scientists hadexpressed concern thatthepublished report oftheConference proceedings
didnotreflect themost current scientific knowledge andthat, therefore, caution should beexercised
inmaking useoftheproceedings inscientific evaluation.
5.13 Canada agreed with theUSconclusion thattheECmeasures were inconsistent with theSPS
Agreement. Canada disagreed with theECpresentation ofthearguments inthiscase which, from
alegal point ofview, appeared tosuggest thattheSPS Agreement only became relevant after a
contravention ofGATT hadbeen determined andquestioned therelevance oftheGeneral Interpretative
Note toAnnex 1AoftheWTO Agreement cited bytheEuropean Communities insupport ofitsposition.
InCanada 'sview, GATT andtheSPSAgreement were agreements ofequal status contained inAnnex
1AoftheWTO Agreement (Article IIoftheWTO Agreement). Canada believed thatonemust first
examine theSPSandTBT Agreements because these contained rules thatwere more detailed andmore
precise than those ofGATT. Canada noted thatthelastpreambular paragraph oftheSPSAgreement
indicated thattheAgreement was, inpart, intended tobeanelaboration of"rules fortheapplication
oftheprovisions ofGATT which related totheuseofsanitary andphytosanitary measures inparticular
theprovisionsofArticleXX(b)".However,Articles3and4,oftheSPSAgreementon"Harmonization"
and"Equivalence", didnotcorrespond toanyprovision inGATT. Thefourth andsixpreambular
paragraphs, reflected thebroad scope oftheSPSAgreement. This reinforced thepoint thattheSPS
Agreement wasanindependent agreement.
172Seepara. 4.239.WT/DS26/R/USA
Page 107
5.14 Canada stressed thatthe"Basic Rights" ofMembers under theSPSAgreement were provided
inArticles 2.1and2.4. Article 2.1setoutalimited right totakesanitary orphytosanitary measures
andArticle 2.4confirmed oneroleoftheSPSAgreement asanelaboration oftherules fortheapplication
ofGATT which related totheuseofsanitary orphytosanitary measures, andinparticular theprovisions
ofArticle XX(b). The"Basic Obligations" oftheSPSAgreement were found inArticles 2.2and2.3.
Paragraph 2expanded ontheArticle XX(b) requirement thatthemeasure be"necessary", setting out
three conditions: thatanySPS measure beapplied only totheextent necessary toprotect human,
animal orplant lifeorhealth, bebased onscientific principles andnotmaintained without sufficient
scientific evidence, except asprovided forinArticle 5.7. Article 2.3wasbased ontherequirements
ofthechapeau ofArticle XX, clarifying thatthepoint ofcomparison for"where identical orsimilar
conditions prevail" included theterritory oftheMember taking themeasure.
5.15 Canada noted thatArticle 2byitsown terms wassaid toestablish the"Basic Rights and
Obligations" ofMembers. Theother provisions oftheAgreement setoutmore specific rights and
obligations, illustrative ofthese fundamental rights andobligations. Forexample, therequirements
setoutinArticle 5thatSPSmeasures must bebased onariskassessment andthattheassessment must
take intoaccount available scientific evidence, were rational extensions ofthebasic obligations in
Article 2.2toensure thatSPSmeasures were based onscientific principles andnotmaintained without
scientific evidence. Similarly, Article 5.6gave precision totheobligation inArticle 2.2thataMember
must ensure thatanySPSmeasure wasapplied only totheextent necessary toprotect human, animal
orplant lifeorhealth. Ineffect, Article 5.6setouthow aMember wastomeet thisbasic requirement
ofArticle2.2.Likewise,Article3.2providedaprescriptionforsatisfyingthepresumptionofconsistency
with GATT inArticle 2:4.
5.16 Canada argued thatinthepanel report onUnited States -Standards forReformulated and
Conventional Gasoline ("Reformulated Gasoline") (WT/DS2/AB/R refers) theAppellate Body had
reviewed thechapeau toArticle XXofGATT. Given theclose relationship between thetextofthe
chapeau andtheobligation inArticle 2.3,Canada submitted thattheAppellate Body 'sinterpretation
oftherequirement thatameasure shall "not beapplied inamanner which would constitute adisguised
restriction oninternational trade" wasapposite tothepresent case. TheAppellate Body found:
"Arbitrary discrimination", "unjustifiable discrimination" and "disguised restriction" on
international trade may, accordingly, bereadside-by-side; theyimpart meaning tooneanother.
Itisclear tousthat"disguised restriction" includes disguised discrimination ininternational
trade. Itisequally clear thatconcealed orunannounced restriction ordiscrimination in
international trade does notexhaust themeaning of"disguised restriction". Weconsider that
"disguised restriction", whatever elseitcovers, mayproperly bereadasembracing restrictions
amounting toarbitrary orunjustifiable discrimination ininternational trade taken under the
guise ofameasure formally within theterms ofanexception inArticle XX. Putinasomewhat
different manner, thekinds ofconsiderations pertinent indeciding whether theapplication of
aparticular measure amounts to"arbitrary orunjustifiable discrimination", mayalsobetaken
intoaccount indetermining thepresence ofa"disguised restriction" oninternational trade.
Thefundamental theme istobefound inthepurpose andobject ofavoiding abuse orillegitimate
useoftheexceptions tosubstantive rules available inArticle XX."173
InCanada 'sview, thisreinforced theassertion inparagraph 140oftheUSsubmission thataprotectionist
measure intheguise ofasanitary measure wastheessence ofadisguised restriction oninternational
trade.
5.17 Canada agreed with theUSconclusion thattheECmeasures contravened GATT andthat
Article XXcould notjustify these measures. Canada noted thattheinterpretation ofGATT Article III
173WT/DS2/AB/R, p.25.WT/DS26/R/USA
Page 108
wasbeing considered bytheWTO Appellate Body in"Japan -Taxes onAlcoholic Beverages" and
thatthereport oftheAppellate Body inthatcase might berelevant tothepresent case.
3. Norway
5.18 Norway argued thatthiscase concerned theright ofevery state tomake itsown sovereign
decision onthelevel ofprotection itafforded itscitizens with respect tohealth hazards. This principle
hadalways been partofGATT lawandseveral panels, when deciding disputes related toArticle XX(b),
hadreaffirmed such right.174TheSPSAgreement, within itsscope ofapplication, might beconsidered
anexemplification ofArticle XX(b). This wasnotacase ofdiscrimination between likeproducts,
ordiscriminationbetweenproducersfromdifferentcountries.Thequestionwaspurelyoneofreaffirming
theMember ’sright todecide, when arisktoitspopulation waspresent, thelimits totherisktowhich
itwould expose itscitizens, anditsfreedom tochoose themeasure toachieve thisprotection aslong
asthemeasure itself wasconsistent with WTO obligations. Inaneraofincreasing consumer concern
over thesafety offood andthepresence ofpotentially harmful residues from theuseofveterinary
drugs, pesticides etc., andatatime when old“scientific truths ”hadoften been overturned bynew
evidence, itwasofutmost importance thattheWTO uphold thisright oftheMember toprotect its
citizens against therisks connected with theuseofsuch substances.
5.19 Noting thattheSPS Agreement restated theright ofaMember tosetitshealth standards in
itspreamble andinArticle 3.3,Norway argued thatitwasclear thataMember hadtheright todetermine
thelevel ofprotection itconsidered appropriate foritspopulation, subject togeneral WTO requirements
with respect totheexistence ofarisk, andrequirements with respect tojustification ofthemeasure
theMember applied. Indetermining theappropriate level ofprotection, Norway argued theobligation
upon theMember wasonly toshow thatarisktoitspopulation waspresent. Aslong astheexistence
ofsuch ariskhadbeen established, theWTO wasonly concerned with thejustification ofthemeasure
theMember choose toapply toachieve thelevel ofprotection ithaddeemed appropriate. According
toArticle XX(b), aswellasArticle 5.2oftheSPSAgreement, aMember didnothave toscientifically
prove theextent oftherisk. TheMember only hadtoshow thatsuch ariskexisted (risk identification),
andthereafter itwasfortheMember todefine thelevel ofprobability ofharm itwanted toassume -
beitzero orgreater (risk management).
5.20 Norway submitted thataMember must consider present dayscientific evidence when making
ariskassessment. Such evidence might ascertain ordisprove therisk, andmight bemore orless
complete, butthiswasonly oneoftheelements tobetaken intoaccount intheriskassessment. Other
relevant elements might be,forinstance, theexistence ofadequate testing methods andinternationally
approved production methods orcontrol requirements. Norway argued thattheSPSAgreement did
notrequire aMember tobaseitslevels ofprotection solely onsuggested maximum tolerances presented
incurrent scientific evidence. Thecases referred bytheEuropean Communities initssubmissions
174Norway noted that, e.g.thepanel report on"US -Restrictions ontheImports ofTuna" stated that:
"The panel further noted thatArticle XX(b) allows each contracting party tosetitshuman, animal orplant life
orhealth standard .Theconditions setoutinArticle XX(b) which limits theresort tothisexception, namely that
themeasures taken must be"necessary" ...refer tothetrade measure requiring justification ...nottothelifeor
health standard chosen bythecontracting party. (...)."
Furthermore, theAppellate Body inthecase United States -Standards forReformulated andConventional Gasoline, inits
concluding remarks stated:
"Members have alarge measure ofautonomy todetermine their own policies ontheenvironment (including its
relationships with trade), their environmental objectives andtheenvironment legislation they enact andimplement. Sofar
asconcerns theWTO, theautonomy iscircumscribed onlybytheneed torespect therequirements oftheGeneral Agreement
andtheother covered agreements."WT/DS26/R/USA
Page 109
clearly showed from history how often oldscientific “truths ”hadbeen disproved bynew scientific
evidence. Ithadnever been theintention oftheGATT/WTO, norshould itbethetaskofthisPanel,
toinfringe upon aMember 'sright todecide tobeonthesafesidewhere current evidence didnotexclude
beyond doubt apotential risktohuman health.
5.21 NorwaystressedthatoncetherightoftheMembertodetermineitsappropriatelevelofprotection
wasreaffirmed, ithadtobeascertained thatthechosen measure complied with thegeneral obligations
spelled outinGATT ortheSPS Agreement. InNorway 'sview, thetesttobeapplied according to
Article XXofGATT andArticle 5oftheSPS Agreement wasthefollowing:
(i) themeasure wasnotapplied inamanner which would constitute ameans ofarbitrary
orunjustifiable discrimination between countries where thesame conditions prevailed;
(ii) themeasure was notapplied inamanner which was adisguised restriction on
international trade; and
(iii) themeasure wasnecessary, i.e.notmore trade restrictive than required toachieve
theappropriatelevelofprotection,takingintoaccounttechnicalandeconomicfeasibility.
Having applied thistesttothemeasure, itsconsistency with theWTO obligations should bereadily
ascertained.
5.22 Norway submitted thattheEuropean Communities hadtheright tosetitsownlevel ofprotection
inthiscase, andatthechosen level. Ithadclearly shown theuncertainties related tothepossible harmful
effect oflong term exposure tothesubstances atissue andhadclearly shown thatitsmeasure didnot
discriminate between countries, norhadthere been anydisguised restriction oninternational trade.
Themeasure hadbeen applied uniformly toallproducts containing thesubstances inquestion, bethey
domestic orforeign. Inselecting themeasure which wasnecessary tominimise thepotential risk(risk
management) soastoensure theappropriate level ofprotection (zero orother acceptable level ofrisk),
many factors hadtobetaken intoconsideration, ofwhich maximum residue levels (MRL) wasbut
one. Thetechnical feasibility ofensuring adequate control oftheuseofthehormones, i.e.strict
veterinary supervision ofeach implant, were ofutmost importance, aswellasthetechnical feasibility
ofcontrol oftheresidue level inallthemeat inquestion. Furthermore, theeconomic costofthemeasure
must betaken intoaccount. AnMRL system with extensive controls andverifications attheproducer
level andatpoint ofimportation might besoprohibitively expensive astoberuled out. TheEuropean
Communities hadshown thatother measures than thecontested banwere notavailable toachieve the
appropriate level ofprotection, which wasconsequently notmore trade restrictive than necessary.
4. New Zealand
5.23 New Zealand indicated thatitsthird party 'ssubstantial interest inthiscasewasduetothefact
thatNew Zealand wasanagricultural exporting nation, andmeat exports formed asignificant portion
ofitstotal exports. Intheyearending December 1995, primary produce (e.g., meat andmeat products,
dairy, fish, fruit andvegetables, etc.) accounted for72.1 percentofNew Zealand stotal merchandise
exports (NZ$ FOB). Forthesame period, meat andmeat products accounted for15.99 percentof
New Zealand stotal merchandise exports (NZ$ FOB). Accordingly, theproper implementation of
theSPS Agreement wasamatter offundamental importance toNew Zealand, andthepotential for
sanitary orphytosanitary measures tobeused asdisguised restrictions ontrade amajor concern.
New Zealand claimed thattheSPSAgreement wasanelaboration ofrelevant GATT provisions and
Articles 2.1and2.4established theprimacy ofthatAgreement indetermining theWTO legality of
sanitary orphytosanitary measures. Accordingly, thelegality ofameasure falling within thedefinition
ofa"sanitary orphytosanitary measure" wastobedetermined inaccordance with theprovisions of
theSPS Agreement.WT/DS26/R/USA
Page 110
5.24 Noting thattheEuropean Communities hadjustified theimport banonthebasis thatthe
importation ofmeat from animals treated with anyofthesubstances might pose arisktohuman health
andsafety175,New Zealand concluded thatthebanappeared tobeameasure thatfellwithin thedefinition
ofa"sanitary orphytosanitary measure" asdefined intheSPSAgreement.176New Zealand noted that
Article 1oftheSPSAgreement didnotmake provision foranyMember toexclude specific sanitary
orphytosanitary measures from theambit oftheAgreement. Moreover, theeffect ofArticle XVI:4
oftheWTO Agreement wastorequire Members toensure theconformity ofalltheir laws, regulations
andadministrative practices withtheSPSAgreement. Accordingly, theimport banandallother sanitary
orphytosanitary measures affecting international trade inplace within thejurisdiction ofanyMember,
were subject totherequirements oftheSPS Agreement.
5.25 With regard toArticle 2.2,New Zealand claimed thatnoevidence hadbeen produced ofan
appreciable riskofanadverse health effect arising from theuseofanyofthesubstances. Even ifit
were tobeshown thatthere wasanappreciable risk, theEuropean Communities would berequired
todemonstrate thattheimport banwasnecessary toaddress it.Inthisregard, New Zealand noted
thattheEuropean Communities hadexpressed particular concern about theperceived risks associated
with theinappropriate orillegal useofhormonal growth promotants, particularly when used in
"combinations" or"cocktails". However, even ifitwasdemonstrated thatanappreciable riskexisted
from such inappropriate orillegal use, theEuropean Communities would need todemonstrate that
abanonimports wasinfact"necessary" toaddress thisspecific concern. Finally, from thehistory
ofthescientific investigations intothefivesubstances, under intense scrutiny byscientists inthelast
twodecades, New Zealand didnotconsider thattheimportation bancould bepresented asbeing "based
onscientific principles" norsustained by"sufficient scientific evidence". Moreover, inthecase of
thesixth substance, MGA, New Zealand wasnotaware oftheexistence ofanyscientific information
which would warrant theimport baninitsregard.177
5.26 New Zealand submitted thatscientific evidence demonstrated thatthelevel ofhormones present
inmeat varied considerably. Meat from animals treated with thesubstances forgrowth promotion
hadasimilar range oreven lower hormonal residues thanmeat from some animals thathadnever been
treated. Additionally, theEuropean Communities allowed meat from animals thathadbeen treated
with thethree naturally occurring substances fortherapeutic purposes tobeproduced, imported and
175Inthiscontext, New Zealand noted thatinthepreamble ofECCouncil Directive 81/602/EEC of31July1981 the
banning ofnewlicences foranabolic agents forgrowth promotion wascharacterised asbeing inthe"interests oftheconsumer"
anditdiscussed thepotential "harmful effects" oftheuseofthesubstances inquestion. ECCouncil Directives 85/649/EEC
of31December 1985 and88/146/EEC of7March 1988 cited concerns relating totheeffect onhuman health from theuse
ofhormonal growth promotants. Thepreamble oftheProposal foraCouncil Regulation (93/C 302/06) on14October 1993
stated thatthepresence ofsuch substances "may bedangerous forconsumers andmayalsoaffect thequality offoodstuffs
ofanimal origin". Andfinally, ECCouncil Directives 96/22/EC and96/23/EC stated intheir preambles thatsuch substances
may bedangerous forconsumers.
176New Zealand argued thattheimport banwould alsobeinconsistent with Article 2.2oftheTBT Agreement were it
notthatAgreement explicitly noted (inArticle 1.5)thatitdoes notcover sanitary orphytosanitary measures. Intheevent
thattheimport banwere determined tobeneither asanitary measure, noratechnical barrier totrade, theprovisions ofGATT
would then need tobeconsidered.
177New Zealand indicated thatbecause ofdiffering userequirements andcommercial factors, there were differences in
therange ofagricultural chemicals (such asMGA) registered around theworld andhence differences inthestandards contained
innational laws. Theabsence ofaninternational standard foraparticular substance should notinitself beseen asjustification
foraparticular import ban. Inaddition, itshould benoted thatArticle 4oftheSPSAgreement encouraged Members to
mutually recognise, forthepurposes oftrade, theequivalence ofdifferent sanitary orphytosanitary measures injurisdictions
other than their own.WT/DS26/R/USA
Page 111
marketed within theEuropean Communities.178New Zealand considered thatforthese reasons, the
ECmeasures contravened Article 2.3oftheSPS Agreement.
5.27 New Zealand stressed thatCodex hadadopted international standards, satisfying itself thatthere
wassufficient scientific basis. Itwasunclear what "available scientific information" theEuropean
Communities could rely ontoprovide "scientific justification" fortheimport banandaselective
examination andevaluation ofavailable scientific information would notbesufficient tomeet the
requirements ofArticle 3.3. Moreover, there should beascientifically established risktohuman or
animal lifeorhealth before anydetermination could bemade astoaMember sappropriate level of
protection. Inthiscase, there didnotappear tohave been anyscientifically defensible determination
ofanappreciable riskinthecase oftheimport ban.
5.28 New Zealand claimed thattheSPSAgreement didnotallow fortheadoption ofasanitary or
phytosanitary measure thatprovided forahigher level ofprotection than aninternational standard in
theabsence ofascientific justification orariskassessment process thathadidentified anappreciable
risk. Inthecaseofallsixhormones, there would notappear tohave been anyECassessment meeting
therequirements ofArticle 5which hadidentified anysuch risk. While itwasevident thatconsumers
intheEuropean Communities might harbour concerns about theuseofthese substances, consumer
perceptions astoriskdidnotprovide abasis fortheadoption ofmeasures under Article 5.Furthermore,
New Zealand submitted thattheusual ECriskassessment andevaluation processes forveterinary
medicinal products179,which might otherwise have ensured aconsistent approach asrequired by
Article 5.5,didnotform thebasis fortheECmeasures.180Equally, given thatmany other products
freelymarketedwithintheEuropeanCommunitiescontainedmuchhigherlevelsofthehormonalresidues
thattheEuropean Communities were seeking toavoid through theimport ban, there would appear,
intheabsence ofevidence tothecontrary, tobearbitrary andanomalous levels ofprotection inplace.
Finally, Article 5.6made itclear thateven ifitcould beshown thatthere wasanappreciable riskto
health, given thesignificant trade implications oftheimport ban, theEuropean Communities would
have hadtoconsider whether there were alternative, lesstrade-restrictive measures thatcould beapplied
toaddress such arisk. Noting thattheEuropean Communities didnotseek torelyonArticle 5.7,
which wasamanifestation ofthe"precautionary principle", asthebasis foritsimport ban,New Zealand
emphasized thatthepresent situation appeared tobeoneinwhich thescientific evidence wasneither
insufficient norinadequate.181Accordingly, thiswasclearly notaninstance where the"sufficient
evidence" standard could besubstituted with theless rigorous standard of"available pertinent
information". ThefactthatCodex hadadopted aninternational standard would always create astrong
presumption thatsufficient scientific evidence existed.
178InNew Zealand 'sindicated thatitunderstood thattheEuropean Communities hadnotsetanyADIs orMRLs for
meat from animals treated fortherapeutic purposes.
179New Zealand clarified thattheguidelines forassessments ofveterinary medicinal products were contained, atthat
time, inECCouncil Directives 81/851/EEC and81/852/EEC. There were alsoguidelines presented inaproposed draft
directive entitled "Testing ofmedicinal products fortheir mutagenic potential" which waspublished asAnnex IIintheOfficial
Journal ofEuropean Communities ,C293/11, dated 5November 1984.
180New Zealand added that, furthermore, since thattime, theEuropean Communities hasnotutilised theapplicable
assessment andevaluation processes toassess theuseofthese substances forgrowth promotion although ithadassessed and
approved their useforother therapeutic purposes without stipulating anyMRLs forexample inCommission Regulation (EC)
3059/94 of15December 1994).
181New Zealand noted thateven the1995 Scientific Conference sponsored bytheEuropean Communities, which was
procedurallydefectiveasariskassessmentprocessinthatitexcludedcertainrelevantparticipantsandinformation,nonetheless,
concluded thatthere wassufficient scientific information todetermine thatthefivegrowth promotant substances could be
used safely.WT/DS26/R/USA
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VI. PANEL 'SCONSULTATION WITH SCIENTIFIC EXPERTS
6.1 TheUnited States noted thatArticle 11.2 oftheSPS Agreement referred toestablishment
ofan"advisory technical experts group". Intheview oftheUnited States, thisphrase referred to
anexpert review group established under Article 13.2 oftheUnderstanding onRules andProcedures
GoverningtheSettlementofDisputes(DSU).Thus,therulesrelevanttotheestablishmentandprocedures
forsuch agroup were those provided inAppendix 4oftheDSU. ThePanel 'sconduct oftheexpert
review process inthedispute should assure transparency, avoid conflicts ofinterest, affirm theintegrity
ofthedispute settlement process, andaidpublic confidence intheoutcome ofthedispute. Inthiscase,
thePanel wastoreview theECbantodetermine ifitwasbased onscientific principles andonarisk
assessment, andifthere wassufficient scientific evidence tosupport theban. Thescientific experts '
rolewasanarrow one, they might help thePanel determine ifthere wasascientific basis fortheEC
ban.
6.2 Asregarded theselection procedures andcriteria, theEuropean Communities considered
thattheuseofexperts bythePanel forthepurposes ofscientific andtechnical advice should respect
general principles oflaw. Inparticular, itshould betransparent, avoid conflicts ofinterest, affirm
theintegrity ofthedispute settlement process andaidpublic confidence intheoutcome ofthedispute182.
Inaddition, Appendix 4oftheDSU included general rules oflawrelating totheuseofexpert advice
onthepartofPanels. Even though theexperts would notconstitute anExpert Review Group butwould
beconsulted individually andseparately, such rules should beapplied byanalogy whenever relevant
andappropriate183.Inorder toensure thattheprinciples outlined above were respected, theEuropean
Communities believed thatanumber ofgeneral criteria should befollowed intheselection ofthe
scientific experts bythePanel.
6.3 TheEuropean Communities indicated that, first, theexperts nominated bythePanel should
notbenationals oftheparties tothedispute nornationals ofthird parties inthesame dispute. This
principle aimed atensuring afairandimpartial selection ofexperts andappeared allthemore necessary
inlight ofthepossibility given bythePanel totheparties tonominate oneexpert each, without any
limitation ofnationality. Second, thePanel, inselecting experts withdifferent fields ofexpertise, should
ensure thatalltheareas which ithadidentified were covered, sothatallthequestions ofthePanel
received replies tothefullest extent possible. Third, given thevery small number ofexperts thatthe
Panel would consult, only scientists with proven expertise intheuseofhormones ingeneral andfor
animal growth promotion should beselected. Fourth, theexperts should nothave served asmembers
oftheCodex/JECFA group which produced the1988 JECFA report ontheuseofhormones foranimal
growth promotion. Fifth, pastorpresent significant tieswith theindustry producing these hormones
would notprovide sufficient guarantees oflackofconflict ofinterest, ofintegrity andofaiding public
confidence intheoutcome ofthedispute. TheEuropean Communities considered thattheabove
comments constituted compelling reasons fortheEuropean Communities andunderscored thelimited
poolproposedbytheCodexsecretariatfromwhichthePanelwouldmakeitschoice,despitetheexistence
ofalarge number ofscientific experts onthese issues internationally. TheEuropean Communities
indicated thatPanel 'sfavorable response totheECrequest toaddafifth scientist with expertise in
theareaofcarcinogenic effects ofhormones inthiscaseaddressed oneoftheconcerns oftheEuropean
Communities.
6.4 Asregarded thepurpose ofrequesting information from, andthetypeandnature ofthequestions
tobeasked to,experts, theEuropean Communities stated thatthisshould be"tofurther thePanel 's
understanding ofthescientific facts relevant tothedispute". Inorder tofulfil thisobjective andbe
182TheEuropean Communities noted thatinaletter addressed tothePanel on21October 1996, theUnited States had
alsoagreed tothese general principles.
183TheEuropean Communities noted thatthishadalsobeen acknowledged inthePanel 'sletter of30October 1996.WT/DS26/R/USA
Page 113
inconformity with theprovisions oftheSPSAgreement andtheDSU, thequestions thePanel intended
toaskmust relate directly tothescientific issues ofthecase. These questions must beaddressed to
persons who onthebasis oftheir recognized fields ofexpertise, could provide direct, reliable and
verifiable information tothePanel. The questions should notconcern legal issues orissues of
interpretation ofanyoftheWTO Agreements under consideration, because itwasthesoleresponsibility
ofthePanel tointerpret thelegal provisions which hadbeen invoked bytheParties andtoapply them
tothefacts ofthepresent case. TheEuropean Communities observed thatthequestions thePanel
intended toaskshould alsonotaddress norrequest purefactual information, which wastheresponsibility
oftheparties tothedispute toprovide, inaccordance with theDSU rules anditsprovisions onburden
ofproof. They should notaddress issues oftrade policy either, which were again thesoleresponsibility
oftheparties andonwhich scientists were notcompetent andcould notbeexpected topronounce
themselves. TheEuropean Communities claimed thatscientists must beasked onlyscientific questions
directly relevant tothisdispute andinthelight ofthescientific arguments made bytheparties tothis
dispute. TheEuropean Communities recalled thatitwasthePanel 'sresponsibility tointerpret and
apply therelevant legal provisions. Accordingly, theEuropean Communities considered necessary
tostress thatitreserved allitsrights with regard totheconformity ofthePanel 'sapproach onthese
issues with therelevant provisions oftheSPS Agreement andtheDSU.
Panel procedures with regard toscientific expertise
6.5 Following consultation withtheparties, thePanel decided toseekscientific andtechnical advice
asforeseen inparagraph 1and2,firstsentence, ofArticle 13oftheDSU, andpursuant toparagraph 2,
first sentence, ofArticle 11oftheSPS Agreement.
6.6 Names ofindividuals expert inthesubject matter before thePanel were provided bytheCodex
Commission secretariat aswell asbytheInternational Agency forResearch onCancer ("IARC").
Brief curricula vitae were solicited from allexperts who were prepared toassist thePanel.
6.7 Theparties were provided theopportunity tocomment onthese potential experts onthebasis
ofthecurricula vitae, andinparticular tostate anycompelling objections theymight have with regard
toanyindividual. Theparties were invited tonominate oneexpert each, notnecessarily from thelist
provided bythePanel. ThePanel than selected twoadditional individuals from thelisttaking into
account thecomments oftheParties. Attherequest oftheEuropean Communities, thePanel decided
toselect anadditional expert inthearea ofcarcinogenic effects ofhormones, ontheunderstanding
thattheEuropean Communities agreed thatthePanel established attherequest ofCanada would seek
advice from thesame fiveexperts. These experts were requested toserve, intheir personal capacities,
asindividual advisers tothePanel. ThePanel alsosought information from theCodex Commission
secretariat.
6.8 ThePanel, inconsultation with theparties, prepared specific questions which itsubmitted to
each expert individually. Theexperts were requested toprovide their responses, inwriting, tothose
questions theyfeltqualified toaddress. Theparties agreed thattheir written submissions tothePanel,
including thewritten versions oftheir oralstatements, beprovided toeach oftheselected experts.
Written questions were alsosubmitted totheCodex Commission secretariat. Thewritten responses
oftheexperts andoftheCodex Commission secretariat were provided totheparties.
6.9 Theexperts were invited tomeet withthePanel andtheparties todiscuss their written responses
tothequestions andtoprovide further information. Asummary oftheresponses provided bytheexperts
ispresented below.
6.10 Theexperts selected toadvise thePanel were:
Dr.Francois André, Laboratoire desdosages hormonaux, FranceWT/DS26/R/USA
Page 114
Dr.Dieter Arnold, Deputy Director, Federal Institute forHealth Protection ofConsumers
andVeterinary Medecine, Germany
Dr.George Lucier, Environmental Toxicology Programme, National Institute of
Environmental Health Sciences, United States
Dr.Jock McLean, University ofSwinburne, ProVice Chancellor, Division ofScience,
Engineering andDesign, Swinburne University ofTechnology, Australia
Dr.LenRitter, Executive Director, Canadian Network ofToxocilogy Centres, University
ofGuelph, Canada
Dr.Alan Randell oftheCodex secretariat alsoadvised thePanel.
Views ofthescientific experts
Question 1:
Invarious JECFA andCodex references theterms "good animal husbandry practice", "good
veterinary practice" and"good veterinary andanimal husbandry practice" areused. Can you
define "good animal husbandry practice", "good veterinary practice" and"good veterinary and
animal husbandry practice"? What aretheimplications, interms ofresidue levels andpotential
hazards tohuman oranimal health, ofnon-application of"good veterinary andanimal husbandry
practices" forfiveofthehormones indispute?
6.11 Dr.André responded thatthese concepts related toquality assurance systems, however they
were notprecisely described orstandardized, andtheuseofsome ofthese concepts wasnotyet
widespread. "Good animal husbandry practice" wasdescribed invarious ways, such as"the stable
totable approach" which took intoaccount theuseofveterinary drugs such asinaHerd Health
Surveillance Programme (HHSP). Insuch arecording system, farmers, veterinarians andother people
concerned with allaspects ofprimary production should cooperate toensure good animal husbandry
practice.
6.12 "Good veterinary practice" described eachcountry 'snational orprofessional guidelines orrules
which provided guarantees forprofessional activities. Theuseofveterinary drugs wascontrolled by
means ofaninternational code ofpractice oftheCodex Alimentarius which described theuseof
veterinary drugs, from thenecessity ofapertinent diagnosis toresidue management (respect of
withdrawal periods) inmeat-producing animals. Dr.André noted thatspecial attention should bepaid
totheprescription andtousing thecorrect dosage, siteandroute ofadministration formedicines.
Moreover, specific conditions fortheuseofparticular drugs wasregulated; ie.,inEurope, ECDirective
96/22 described precisely theconditions oftherapeutical orzootechnical useofthehormones indispute.
6.13 Dr.André noted that"good veterinary andanimal husbandry practice" didnotappear tobe
well defined butcould beconsidered asacombination ofthetwoabove-mentioned practices. The
strict observance of"good veterinary andanimal husbandry practice" wastheonly waytoguarantee
thateach drug would beused according totheconditions forwhich ithadbeen registered. Any
disrespect ofsuch practices, interm ofdosage, injection route, withdrawal period orother conditions
specified foruse,would change theexpected level ofresidues. Concerning thehormones indispute,
itcould easily bedemonstrated thatoverdosage, shorter withdrawal periods (when defined), orliquid
solution injections instead ofimplants might leadtohigher residue levels. Potential hazards tohuman
andanimal health might then appear.WT/DS26/R/USA
Page 115
6.14 Dr.André indicated thattherealproblem wasoneofcontrol: howtoensure thatthese practices
were really respected. There were official control services charged with thiscontrol. Butnow more
andmore veterinarians, farmers, andfarmer organizations were taking thecontrol andwere ensuring
thatthey only used registered drugs asthey were officially meant tobeused.
6.15 Dr.Arnold observed that"good animal husbandry practice" wasabroad term relating tothe
proper management andhandling ofanimals. Particularly intensive production methods required good
management. Theterms management andhusbandry included, forexample, efforts toward improving
rateofgain andfeed efficiency andmanagement ofreproduction (e.g., hormonal control ofoestrus,
embryo transfer, treatment ofinfertility, prevention ofpregnancy, termination ofpregnancy, induction
ofparturition, etc.). Veterinarians were involved inthemanagement ofseveral ofthese conditions
andwere inter aliaresponsible thatcertain drugs were only administered after thorough diagnosis and
incompliance with theapproved label instructions. Itwasalsoafundamental requirement thatdrugs
(hormones, growth promoters, parasiticides andother substances) should notbeused toreplace good
veterinary andanimal husbandry practices.
6.16 Dr.Arnold indicated thatthehormones under discussions were notpersehazardous orinnocent
substances. Ifingested with food, their possible biological effects depended inter aliaontheamounts
ingested. Therefore, itwasimportant thatduring theapproval process conditions ofusewere established
which guaranteed thateven preferential consumption offood from treated animals would notleadto
theingestion ofresidues causing biological effects. Theessential issue wascompliance with the
establishedconditionsofusewhichwerenormallylaiddowninthelabelinstructions.If"goodveterinary
andanimal husbandry practices" were notapplied, inparticular if"good practices intheuseofveterinary
drugs" were notobserved when using these substances, residue levels higher thanthose resulting from
theauthorized conditions ofusemayoccur/were likely tooccur inedible portions ofthetreated animals.
These elevated levels didnotalways have biological effects -because theestablished margins ofsafety
were usually high.
6.17 Dr.Lucier indicated thathehadlittle expertise inthisarea, butitseemed reasonable toassume
thatnon-application ofsuch guidelines orinconsistent application ofthem would substantially increase
thechance thatacceptable residue levels could beexceeded, which would likely increase thepotential
risktohuman health.
6.18 Dr.McLean responded that"good practice" wastheoperative partofthese definitions. The
word "veterinary" implied thataveterinarian wasinvolved intheprocess astheprescriber, advisor
oradministrator. "Animal husbandry" wascaring foranimals andmight involve aveterinarian inthe
process. "Good practice" inrelation totheuseofhormones involved theuseofaregistered product
according totheprescribed instructions foritsuseandemploying good farming practice. Itmight
alsoinclude theuseofapproved administration apparatus andtheidentification oftreated animals.
6.19 Dr.McLean indicated thatdeparture from "good practice" wasundesirable andabreach of
theregistration conditions. However, inpractice, itwasunlikely thatminor departures from good
practice with registered products would cause significant increases inhormone levels inmeat.
6.20 Dr.Ritter indicated thatthese terms hadbeen elaborated inarecommended international code
ofpractice (Codex Alimentarius, 1993) intended tofoster thesafeuseofveterinary drugs infood
producing animals andtoensure that, inaccordance with theprinciples ofthiscode, residues of
veterinary drugs infood didnotexceed permitted levels andresidues didnotpose ahazard tohumans
consuming food commodities produced withtheaidofveterinary drugs. Inpractice, JECFA andCodex
hadnotutilized these terms, butrather hademployed theterm "good practice intheuseofveterinary
drugs", which hadbeen defined (Codex Alimentarius 1993) as"theofficial recommended orauthorized
usage including withdrawal periods, approved bynational authorities, ofveterinary drugs under practical
conditions. Themaximum residue limit forveterinary drugs may bereduced tobeconsistent withWT/DS26/R/USA
Page 116
good practice intheuseofveterinary drugs". Themaximum permitted residue wasbased onthetype
andamount ofresidue considered tobewithout toxicological hazard forhuman health while taking
intoaccount other relevant public health risks. When thehormones atissue were used inaccordance
with theprescribed useconditions, thelevels thatwere present were infactindistinguishable from
those which would bepresent inananimal which hadnotbeen treated atall.
6.21 Dr.Ritter further noted thattheprinciple orphilosophy ofgood veterinary andgood husbandry
practice alsoimplied thatallveterinary products tobeutilized infood producing animals should only
beadministered instrict compliance with relevant product information, approved bytheappropriate
regulatory authority, andinstrict accordance with instructions issued byqualified veterinarians.
Violations ofanyofthese principles might result inhigher than expected residues orresidues of
unexpected drugs. Theimplications ofsuch violations were proportional tothefrequency with which
they occurred, themagnitude oftheviolation andtheprevalence ofsuch violations within thefood
production system. Notwithstanding, given theexaggerated estimates ofsafety inherent intheapproach
totheestablishment ofMRLs, itwasunlikely thatoccasional violations could increase overall residue
levels tothose which, onaninfrequent exposure basis, could pose arisktoconsumers.
Question 2:
Canmeat produced with anyofthesixhormones indispute forgrowth promotion purposes (natural
and/orsynthetic)bephysicallydifferentiated,byconsumersorbyanyparticulardetectionmethods,
from meat produced without them? Areresidues ofthethree natural hormones administered
forgrowth promotion purposes chemically different from residues ofthese hormones administered
forpurposes permitted bytheEC?
6.22 Dr.André noted thatnophysical differences were observed between meat produced with or
without theuseofgrowth-promoting hormones, butquestions ofmeat quality could beraised asfar
asphysicochemical ororganoleptic criteria were concerned. Significant alteration ofeating quality
andlossoftenderness ofmeat produced with various implants hadbeen reported. These changes might
alsostem from differences inthechemical composition ofmeat. According tosexand/or implant type,
differences ofmoisture andfatrates were observed.
6.23 Furthermore, sophisticated detection methods allowed differentiation ofmeat produced with
orwithout synthetic hormones, even ifalong withdrawal period wasrespected. Fornatural hormones,
thisdifferentiation waspossible when esters ofnatural hormones were stillpresent inthemeat. In
some cases itispossible todistinguish thetwobyphysical means ofisotope relations, butitwould
bevery difficult todoatvery lowlevels, Theoretically, quantitative differences might beexpected
between thelegal useofnatural hormones asgrowth promoters (i.e. asanimplant) andtheir useas
veterinary drugs (i.e. usually asinjection); from thequalitative point ofview, chemical differences
could beexpected interms ofmetabolites and/or conjugates, owing tothedosage, theroute of
administration andthelength oftreatment.
6.24 Dr.Arnold responded thatitwasnotpossible tophysically differentiate meat from treated
animals from meat ofuntreated animals. However, many studies showed thatthecomposition ofthe
carcass wasimproved upon treatment interms ofmore leanmeat andlessfatthaninuntreated control
animals. Residues found inthemeat from treated animals forgrowth promotion purposes would be
qualitatively thesame asresidues found inmeat from animals treated with thesame substances for
purposespermittedbytheEuropeanCommunities,butquantitativelycouldbeslightlydifferentdepending
onthecompound administered, thedose, theroute ofadministration, etc.Ifthesubstances were used
according togood veterinary practices, there wasinitially aslight difference butatthetime ofslaughter
there wasnomeans todiscriminate between treated andnon-treated animals, irrespective ofwhether
forgrowth promotion orfortherapeutic andzootechnical purposes.WT/DS26/R/USA
Page 117
6.25 Ofthecategories ofresidues ofbiological concern, only theresidues oftheparent drug
administered totheanimals (e.g. thehormones itself oritsesters) could beanalytically differentiated
with currently available analytical methods. Theoretically, hormones could belabelled with stable
isotopes topermit discrimination between added hormones andendogenous hormones, butthishad
norelevance inpractice. Itwaspossible todiscriminate whether ornotanimals hadbeen treated with
exogenous hormones. Despite their short half-lives incirculation, itwaseven possible, butnotnormally
routinely feasible, tomeasure theconcentrations oftheesters atsites distant from theinjection site.
6.26 Itappeared thatthesubstances used forgrowth promotion intheUnited States were (with the
possible exception oftestosterone-propionate) also used intheEuropean Union fortherapeutic or
zootechnical purposes. Working-Group IIIofthe1995 ECScientific Conference hadconcluded that:
"While residue analyses fornatural hormones onanimals treated experimentally canshow differences
between them anduntreated animals, itisnotpossible inroutine usetoidentify treated animals on
thebasis ofassays ofedible tissue samples anditisdifficult inblood, urine orfaeces. Successful
identification oftreated animals may bemade byanalysis ofinjection sites ordetection ofesters (e.g.
oestradiol benzoate) inblood shortly after treatment. Identification ofanimals treated with natural
hormones onthebasis ofasingle time-point analysis isdifficult. Thesituation ismore complex for
food-producing animals, where typically amixture ofandrogen only isused. Identification ofmeat
from animals treated with natural hormones andimported from third countries isnotatpresent
possible"184.(emphasis added)
6.27 Dr.Lucier indicated that theresidues which occurred from thenatural hormones were
indistinguishable from those which occurred from thenatural endogenous materials. This wasnot
true, ofcourse, forthesynthetics. With appropriate analytical methods andappropriate residue levels
onecould detect residues ofthesynthetic materials here inquestion. Thehalflife, thebiological
persistence, oftheagents inquestion wasforthemost partrather short; they didnotstick around the
body very long. Half-life wasthetime ittakes forhalfthematerial todisappear. If,forexample,
something hadahalflifeofonedayand, ifyoustarted outwith 10units ofit,onedaylater youwould
have five, twodays later youwould have twoandahalfandsoforth. Soeven though several months
might elapse following anexposure toanagent even with arelatively short halflife,afewmolecules
might remain. Thenumber ofmolecules might beremarkably close tozero, probably notdetectable
byanalytical methods, butafewmolecules would likely remain. (See alsoresponse toquestion 5).
6.28 Dr.Lucier noted thatitwaslikely that, ontheaverage, meat from growth-promoted animals
would beleaner (i.e. lessfat)than meat produced without those agents. However, itwasunlikely
that, foragiven piece ofmeat, onecould physically differentiate whether ornotitwasfrom agrowth-
promoted animal. Residues arising from administration ofthethree natural hormones would notbe
chemically different from those inthebody ofnon-treated animals although theresidues were likely
tobeslightly higher inthegrowth-promoted animals.
6.29 Dr.McLean responded thatforallpractical nutritional andhealth purposes themeat wasthe
same regardless ofhow itwasproduced, although there might bevariations intheratio offattolean
meat. Theresidues ofthenatural hormones were generally similar when administered forgrowth
promotionorforotherpurposes.Becausethemodeofadministrationusedforgrowthpromotionresulted
inlower daily dosing, there might bequantitative andqualitative variations inthecomposition residues.
6.30 Dr.Ritter observed thatitwasgenerally known thatwhen used asgrowth promoters, the
naturally occurring gonadal steroid hormones -oestrogen, progesterone andtestosterone andtherelated
substances MGA, zeranol andtrenbolone, could increase thegrowth rate, theproportion ofleanmeat
tofatandfood conversion efficiency insome species. Overall theresponse might vary between
184Working Group III,Detection andSurveillance, in1995 ECScientific Conference Proceedings, p.31.WT/DS26/R/USA
Page 118
hormones, andmight bemaximized bytheuseofcertain combinations ofhormones. Ingeneral, the
leanmeat content ofthecarcass wasimproved andthefatcontent wasdecreased. Except inthecase
ofsome vealcalves, effects onmeat quality were generally notsignificant. Thus itwasmost unlikely
thatconsumers could differentiate physically between meat produced with orwithout these hormones.
JEFCA concluded thatitwould beverydifficult todetermine residue levels attributable totheexogenous
useofthenaturally occurring gonadal hormones.
6.31 While itwasmost unlikely thatconsumers could physically differentiate meat produced with
synthetic hormones, residues could bereliably detected well below those levels regarded assafe.
However, qualitatively theresidue would beindistinguishable. Quantitatively, theamount thatcould
bedetected would beafunction oftheamount thatwould have been administered either forgrowth
promotion ortherapeutic uses.
Question 3:
Ifanyoneofthesixhormones oracombination thereof isadministered totheanimal, willthere
always bearesidue ofthathormone inthemeat ofthatanimal, even ifitissosmall thatitcannot
bedetected? Question 32: Further toquestion 3,could thehormone load ingested byhumans
from other foodstuffs (including endogenous hormones) begreater than which occurs from the
consumption ofbeef derived from hormone-treated cattle?
6.32 Dr.André indicated thataspecific detection limit below which aresidue could notbeidentified
and/or quantified wasdefined foreach method. Itnever meant thattheresidue wasnotstillpresent
inagiven matrix. Thelower thedetection limit ofthemethod, thelower thelevel ofresidue which
could berevealed, butthelonger thetime ofpossible identification oftheresidue. Forsome growth
promoters thetime during which itwaspossible tofindresidues hadchanged from oneweek toone
month after substantial improvement ofthemethod (high resolution mass spectrometry instead oflow
resolution mass spectrometry forinstance). With thedevelopment ofsophisticated newmethods, it
waspossible toobserve residues remaining much longer than wascommonly known.
6.33 Other foodstuffs than meat from hormone-treated cattle contained hormones, especially
oestrogens. Thiswasthecaseofoffals, ofcertain plants, ofmeat from specific animals (such aspregnant
cows); allcontained high levels ofhormones. However, theconsumption ofthese foodstuffs was
always occasional andwould notenhance risks forhuman health. This wasnotcomparable tothe
systematic enhancement ofthehormonal content ofmeat.
6.34 Dr.Arnoldstatedthathewasnotconsideringtheendogenouslyproducedhormonesas"residues"
inhisanswer. Anyexogenously administered hormones present inthebody oftreated animals should,
however, beconsidered as"residues", even ifthere wasnodifference instructure andbiological activity
compared with theendogenously produced hormones. Theuseoftheterm "residue" didnotimply
thatthese residues were potentially harmful tohuman health.
6.35 Whether animals were slaughtered without anywithdrawal time orattheendofthelegally
established withdrawal time, there would always bearesidue. Theexogenous compound wasnotabsent
attheendofthewithdrawal time; however, thesumofboth theendogenous andexogenous molecules
would beatorwithin physiological limits. Ifthepresence ofresidues were toberegulated onthe
basis of"no-detectable-residues" (which wasimpossible because theendogenous hormones alone were
already above thelimit ofdetection), there would nonetheless bemore than 1000 billions molecules
oftheadministered exogenous hormone present inonekilogramme ofmeat atthelimit ofdetection.
Inother words, the"no-detectable- residue" concept wasafalse-zero-residue “concept. For anyof
thesixhormones,itwasimpossibletoestimatethewithdrawaltimesrequiredtoreachtrue"zero-residue"
levels even with theaidofthemost sensitive analytical methods.WT/DS26/R/USA
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6.36 Many foods ofboth plant andanimal origin contained natural hormonal substances insuch
amounts that, depending ontheactual diet, thedietary intake could belower, equal orhigher than
theamount ingested with beef from hormone-treated cattle. Iftheendogenous production wastaken
together with thedietary intake, itwould always bemuch higher. Given their natural presence infood,
hestated thatonecannot escape eating these hormonally active substances, orsimilar substances with
related biological potential.
6.37 Dr.Lucier responded thatbiological half-life datawasavailable foreach ofthese hormones,
soresidues could bereasonably predicted atvarious times after exposure hadceased. Inthecase of
zeranol thehalf-life wasapproximately oneday. Thus, ifasample contained 100ppbwhen exposure
ceased, 50ppbwould remain after oneday, 12ppbatthree days, three ppbatfivedays andsoon.
Although thelevels after several months would beextraordinarily small andvery likely non-detectable,
afewmolecules would remain.
6.38 Dr.McLean indicated thataminute residue, wellbelow anypresent method ofdetection, might
remain. This could bepostulated from aknowledge ofpharmacokinetics. This minute residue would
beofnosignificance when compared with endogenous production ofnatural hormones inthehuman
body, orthedietary intake ofnatural oestrogenic substances infood orcontaminants which were
oestrogenic.
6.39 Dr.Ritter observed thatinthecaseofthenatural hormones, andinaccordance withappropriate
useprocedures, hormone levels could beexpected todecline tolevels thatwould beassociated with
untreated control animals. Because these hormones were normally produced endogenously, itwould
beessentially impossible todistinguish these lowlevels asoriginating from anexogenous source, and
inanycase these levels fellwell within therange normally present inuntreated animals. Inthecase
ofthexenobiotic hormones, andinparticular trenbolone acetate andzeranol, residue levels ofthese
hormoneswouldnotnormallybeexpectedinuntreatedanimalsandhencecouldbedetectedinmonitoring
programmes. Itwaspossible that, depending onthewithdrawal period selected, some residues ofthe
xenobiotic hormones might remain, even ifbelow thelimits detectable byroutine methodology.
Question 4:
How dotheresidues from thethree synthetic hormones indispute differ, ingeneral, from those
ofthethree natural hormones indispute ifadministered inaccordance with good husbandry
practice andgood veterinary practice? And, inparticular, when used foranimal growth promotion
inaccordance with good husbandry practice and/or good veterinary practice? How doresidues
ofhormones naturally present inanimals, meat, meat products orhuman beings, differ from
those ofadditional hormones administered toanimals? Dothese differences, ifany, result in
different potential risks tohuman health?
6.40 Dr.André replied thatbecause thecompounds were notthesame, they ledtochemically
differentresidues.Theresiduesalsodifferedquantitativelyaccordingtothedosage.Levelsofoestradiol,
testosterone andprogesterone residues increased significantly inanimal tissues after treatment, when
compared with corresponding untreated animals. Usually, theincrease ofresidue levels wasmore
pronounced infatthan inmuscle andother edible tissues. Concerning trenbolone andzeranol the
approximate residue levels could beconsidered, forboth compounds, tobeclose totheppblevel.
6.41 Differences between natural occurring hormones atanatural occurring level andthesame
hormones atahigher level orsynthetic hormones (whatever their level ofresidue) resulted systematically
indifferent potential risks tohuman health, dueeither tothelevel ofresidue orthenature oftheresidue
(metabolites). According totheroute ofadministration ofadditional hormones, some differences in
metabolites patterns might appear. Metabolites could bespecies-specific: metabolites notformed in
cows might form inhumans andresult inpotential risks forhuman health. Thepotential induced riskWT/DS26/R/USA
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could beduetothehormonal activity ofresidues. The potential adverse effect could also bea
carcinogenic effect.
6.42 Within thephysiological range these hormones hadnodifferent biological effects onhuman
beings. Butifoneateonly meat from treated animals, there would beavery small enhancement of
themean offood hormonal intake andthiswould notbetransformed inclassical biological effects
forhuman beings. Theproblem wasthatsome other biological effects hadneeded tobestudied over
along time. Such effects included, forexample, changes inhuman fertility orchange inthesexratio,
whichwascurrentlychanginginsomecountries.Buttherewasnocurrentlyknownrelationshipbetween
these developments andthefactwhether these countries banned ornotthese hormones.
6.43 Dr.Arnold responded thatinchemical terms, there wasnodifference between endogenously
produced "natural hormones" andexogenously administered "nature-identical" hormones. There were,
however, clear chemical differences between the"natural" and"nature-identical" hormones onthe
onesideandthexenobiotic hormones ontheother side. Thexenobiotic hormones donotnaturally
occur inanimals, meat, meat products orhuman beings, soanyreliably detected residue ofthethree
synthetic (xenobiotic) hormones wasindicative ofatreatment oftheanimals. Iftheproducts were
administered inaccordance with the"good practices", such residues might frequently occur in
concentrations toolowtobedetectable inmeat.
6.44 Interms ofbiological activity, inprinciple, thepotential biological effects ofthe
"nature-identical" exogenous hormones were thesame asforthe"natural" endogenous hormones.
While theconcentrations ofendogenous hormones were, however, regulated depending one.g., sex,
age,developmental stage etc., theexogenous hormones could, inprinciple, beadded insuch amounts
astoeither gradually disturb or-athigh doses -even overwhelm theinternal regulatory mechanism.
Single high doses (e.g., resulting from theingestion ofa"full" injection site) would normally cause
transient effects. Repeated high doses (notreached through ingestion ofresidues resulting from uses
such asgrowth promotion, therapy, orzootechnical treatment) could significantly change thehormonal
balance oftheindividual.
6.45 Dr.Arnold summarized thatthepotential risks tohuman health arising from thehormonal
activity ofthexenobiotic hormones wasslightly different inquantitative terms. Thepotential risks
arising from other than hormonal actions were qualitatively different. These risks were assessed during
thereview andapproval process, andtheapproved conditions ofuseeliminated allunacceptable risks.
6.46 Dr.Lucier replied thattheresidues from thethree synthetics differed inseveral ways from
thenaturally-occurring hormones. First, thechemical structure wasdifferent. Second, anymetabolite
orbreakdown products would likely bedifferent. Third, thesynthetic hormone, although mimicking
thenatural hormone, might have additional biological properties notfound inthenatural hormone.
These differences could possibly result indifferent potential risks tohuman health.
6.47 Some biological effect could occur. Forexample, anormal woman might have 30percent
ofheroestrogen receptors occupied atsome given point intime. Atthatsame point intime, ifshe
wasconsuming meat thatcontained anadditional burden ofoestrogens because oftheuseofgrowth
promoters, thatreceptor occupancy might besomething like30.01 or30.001, averyverysmall increase.
This increase would notbedetectable, noteven close tobeing detectable, byanyexperimental tools
available today. Thus, abiological effect could beoccurring; ifitwasoccurring itwould notbe
detectable; andfinally therelationship between thatbiological effect (receptor occupancy) andatoxic
effect, saycancer orbirth defect orsomething likethat, would beunknown. Butifsuch aneffect
were occurring, itwould beextraordinarily small, close tozero.
6.48 Dr.McLean indicated thattheresidues from thesynthetic hormones differed from those of
thenatural hormones because theywere chemically different compounds andtherefore their metabolitesWT/DS26/R/USA
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would alsobedifferent. Inthecase ofthenaturally occurring hormones, theresidues inmeat and
humans would bevery similar. Any difference would notpose apotential risktohealth.
6.49 Inrelation tothenaturally occurring hormones, Dr.McLean noted thatitwasnotpossible
todifferentiate between theeffects ofmeat from treated animals against meat from untreated animals
because essentially they were inthesame biological range. Inthecaseofthenon-naturally occurring
hormones, inestablishing theADI very sensitive endpoints were derived from studies innon-human
primates, andthen thesituation ofsensitive members ofthepopulation wastaken intoaccount when
establishing safety factors. Thelevels inmeat were substantially below those causing anyeffects in
primates, andthere wasareasonably good correlation ineffects ofhormonal levels inprimates against
humans. Therefore thelevels present inmeat from animals thatwere treated with thetwonon-natural
growth promotants would notcause effects inhumans consuming themeat.
6.50 Dr.Ritter observed thatwhen introduced exogenously assubcutaneous implants, thenatural
hormones were absorbed andmetabolized inanidentical manner totheendogenous form thereby
producing aspectrum, both qualitatively andquantitatively, ofresidues which were indistinguishable
from thenormal endogenous hormones. Inthecase ofthesynthetic hormones, trenbolone acetate,
zeranol andMGA used asgrowth promoters, tissue residues were notnormally present andhence
detectable residues were attributable totheir use. Inthis case, maximum residue levels were
recommended only after careful andthorough evaluation ofthesafety file,food consumption factors,
selection ofappropriate withdrawal periods and, inconsideration thereof, residues remaining were
notconsidered topose arisktoconsumers ofmeat ormeat products containing these residues ator
below internationally recommended limits.
Question 5:
The EChasidentified certain potential health hazards ofconcern toit(ie., carcinogenicity,
synergistic effects, genotoxic effects, long-term useandexposure tocombination ofthehormones
inquestion). Towhat extent were these hazards taken into consideration inthecontext ofthe
1988 JECFA report orintheestablishment oftheCodex standards forthehormones inissue?
Towhat extent dotherisk assessments referred tobytheECassess these suggested hazards?
Had thesixhormones indispute been used asanimal growth-promoters over asufficient number
ofyears foranassessment ofthelong-term effects ofsuch hormones onhuman oranimal health
tobemade? Question 29:Further toquestion 5,towhat extent dotheADIs andMRLs established
byCodex foranyfood additive, pesticide, etc., take into account theeffects onhuman health
ofexposures tomixtures ofveterinary drugs, orexposure tothehormones inquestion originated
byother sources? Towhat extent dotheADIs andMRLs established byCodex take intoaccount
theeffects onhuman health ofexposure tomixtures ofveterinary drugs, orexposure tothe
hormones inquestion originated byother sources?
6.51 Dr.André indicated thatthepotential health hazards taken intoaccount byJECFA were based
ondataavailablein1988.Moreoveronlytoxicologicaleffectsofthesedrugswereevaluated.Synergistic
effects, long term useandcombination ofhormones were notfully evaluated. New results concerning
toxicological effects ofnatural andsynthetic hormones hadbeen published since 1990, most ofthem
in1995 and1996. Some ofthese newdatawere taken intoconsideration when preparing EC96/22
and96/23 Directives, however theywere nottaken intoaccount bythe1995 ECScientific Conference
because thebibliography fortheConference hadbeen prepared atthebeginning of1995. Many other
hazards forhuman health could beeither scientifically proven orexcluded. Owing tothenature of
these hormones, theresidue levels, andtheway they were ingested (assuming thatgood veterinary
practice andgood animal husbandry practice were respected), a30to50yearperiod might benecessary
toobtain substantial data (asfororalcontraceptives orasbestos inhalation).WT/DS26/R/USA
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6.52 When individual drugs were used incommon veterinary practice fortherapeutic purposes, the
probability ofthesimultaneous useoftwodrugs waslow; theprobability ofaninterference between
them waslower, andlower stillwastheprobability thatonecould influence theelimination rateof
another. Forthehormones used asgrowth promoters, theproblem wasdifferent. They were used
onavery large scale. Many animals were treated sothattheprobability tohave simultaneous
administration ofother drugs andofthese hormones became much higher. Agood riskassessment
should take thisintoaccount, buthewasnotaware ofthathaving been done either inthecountries
where these hormones were inuseorattheinternational level.
6.53 Dr.Arnold replied thatsynergistic (and antagonistic) interactions ofthese hormones atall
levels -from themolecular tohigher organisational levels -were keyelements oftheir normal biological
functions. Itwasdifficult toidentify what theoretical hazards might arise from theoretically possible
maximal changes intheorder of<0.1percent ofinternal hormone pools duetotheconsumption
ofmeat from animals treated with theapproved hormonal growth promoters. Long-term exposure
tohormones inlaboratory animals andhumans wasfully covered bytheJECFA evaluations (e.g. in
thecase ofzeranol andtrenbolone-acetate bythechronic/carcinogenicity studies reviewed). Data not
available tothe32nd JECFA were completed atthe34th meeting oftheCommittee.
6.54 IntheCommunity, thecompetent advisory body forthesafety evaluation ofoestradiol-17 ,
progesterone andtestosterone wastheCommittee forVeterinary Medicinal Products (CVMP), asection
oftheEuropean Medicines Evaluation Agency (EMEA). EMEA wasalso, inprinciple, thecompetent
authority forthereview ofapplications formarketing authorization ofveterinary medicinal products
used forgrowth promotion. Acentralised review process would bemandatory under theprovisions
laiddown inRegulation 2309/93. Theuseofanyhormonal substance forgrowth promotion was,
however, currently prohibited.
6.55 UndertheprovisionsofArticles7and14ofCouncilRegulation2377/902185,MaximumResidue
Limits (MRLs) had tobeestablished forthetherapeutic and zootechnical uses ofthethree
"nature-identical" substances before theendof1996. The EMEA reviewed (inaccordance with
regulation 2377/90) thetherapeutic uses ofoestradiol-17 incattle andhorses. Thepublic summary
report states:
"3.Toxicological effects found after oestradiol administration comprise hyperplasia ofthe
endometrium,behaviouralchangesandeffectsofmetabolicprocesses.Oestradioldoesnotinduce
gene mutations invitro,butconflicting results arefound inchromosomal aberration assays.
Following long term exposure theincidence oftumours intissues with ahigh level ofhormone
receptors isincreased (e.g. mammary tumours). Itisconcluded thatthetoxic effects including
carcinogenicity occur asanextension ofthephysiological effects ofoestradiol ...
7.Theconclusion oftheFAO/WHO Expert Committee onFood Additives (JECFA) thatno
ADI andMRLs foroestradiol need tobeestablished isadopted. Milk andplasma residue levels
after treatment with oestradiol benzoate andoestradiol valerate have shown tobeatorwithin
physiological limits. Although itislikely that tissue residue levels will also bewithin
physiological limits, this cannot beguaranteed, given the results with oestradiol
hexahydrobenzoate. Still, compared tothelowest human daily production rateofoestradiol
inprepubertal boys (6(µg/d)) andcompared totheamount ofoestradiol inother food stuffs
thatarepartofthehuman diet, theamount ofexogenous oestradiol thathumans willbeexposed
tothrough ingestion oftissue from treated animals isbiologically insignificant, andwillbe
incapable ofexerting ahormonal effect inhuman beings".
185Council Regulation (EEC) 2377/90, ECOfficial Journal L224/1 of18August 1990.WT/DS26/R/USA
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6.56 EMEA alsoevaluatedprogesteroneinaccordancewithregulation2377/90.Thepublicsummary
report consists of17paragraphs andshows thatthefollowing aspects hadbeen considered bythe
Committee: natural occurrence, veterinary uses, target animal safety, biological effects, endogenous
production inhumans, normal levels infood animals andinfood ofanimal origin, pharmacokinetics
and metabolism, acute and short-term toxicity inlaboratory animals, reproductive toxicity,
teratogenicity/embryotoxicity,andlong-termeffectsincludingcarcinogenicity.TheevaluationbyJECFA
ofthissubstance wasalsoconsidered.
With respect tocarcinogenicity itwasstated:
"9.According totheInternational Agency forResearch onCancer (IARC), progesterone does
notexhibit mutagenic activity inmost invitro andinvivo tests performed, butisknown to
increase thetumour incidence inendocrine target tissues (ovaries, uterus, mammae) after
continuous (parenteral) doses clearly above thephysiological levels. Progesterone isnot
carcinogenic perse,butactsviaanepigenetic mechanism associated withitsendocrine activity,
i.e.itsability tocause ahyperproliferative effect atcellular levels mediated bysteroid-hormone
receptor interaction. Hence, tumours willnotresult from ingestion ofprogesterone atlevels
thatdonotproduce anyhormonal effects".
Theevaluation process oftestosterone inaccordance with regulation 2377/90 wasstillongoing.
6.57 Sofarnocomplete riskassessment hadbeen conducted intheCommunity; themost competent
assessment wasmade bytheScientific Working Group onAnabolic Agents inAnimal Production
chaired byProfessor Lamming. This Committee comprehensively reviewed theavailable scientific
evidence, including industry data, concerning fiveofthesubstances under dispute. Itsrecommendations
were endorsed bytheScientific Committee onAnimal Nutrition, theScientific Committee onFood
andtheScientific Veterinary Committee oftheEC. However, when theinterim report waspublished,
long-term toxicity dataonthexenobiotic substances wasavailable only fortrenbolone acetate. The
reportalsodoesnotmentionthat"synergisticeffects"andexposuretocombinationshadbeenconsidered.
The"Pimenta Committee" didnotitself perform ascientific riskassessment butrather expressed views
onpublic perception ofscientific opinion, theroleofscience insociety, consumer preference, other
socio-economic factors andvarious aspects ofimplementation andcontrol ofaban.
6.58 The1995 ECScientific Conference hadnolegal mandate andtheSteering Committee was
entirely freetodesign theprogramme andtonominate invited participants. Alegal notice inthereport
clarified thatneither theEuropean Commission noranyperson acting onbehalf oftheCommission
wasresponsible fortheusewhich might bemade oftheinformation. TheConference didnotassess
thehazards referred tobytheECinthisdispute. With regard totheCodex process, Dr.Arnold noted
thatitwastruethattheEChadobjected tomove these MRLs tothenext stepintheprocedure, but
without raising anyhealth issues. TheEChadopposed because ithadspecific legislation prohibiting
theuseof,andconsumers didnotwish toeatmeat from, treated animals.
6.59 Sufficient time hadelapsed toallow anassessment ofthelong-term potential effects onthe
health ofthetarget animals. Iflong-term effects ofthese substances were tobestudied, theeffects
oftheendogenously produced amounts ofthese substances andoftheexogenously administered human
doses intherapy etc.were most relevant. Lifestyle andingestion asnormal food constituents could
alsobeimportant. Intheunlikely event thattheminute amounts added from residues would have any
effect onhuman health, itwould notbepossible todiscover thiseffect against thisbackground.
6.60 Inresponse tothefollow-up questions (inparticular, question 29),Dr.Arnold noted thatthe
primary mode ofexposure tofood additives wasthrough ingestion ofthesubstance inthefood supply.
JECFA considered, where applicable, theoccurrence ofthesubstances asnormal body constituents;
thenatural occurrence infoods; exposure from other uses; andinteractions with other food additives.WT/DS26/R/USA
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Forexample,whencanthaxanthinwasevaluated,theCommitteeconsideredalsotheusesofthissubstance
asfeed additive inanimal nutrition andasanorally administered pigmenting agent forhuman skin
inboth pharmaceutical andcosmetic applications. Early initsdeliberations about safety margins the
Committee hadconcluded thatthemargin ofsafety should allow for,inter alia,thepossibility of
synergistic action among food additives. TheADI forfood additives generally included thenatural
occurrence andthedeliberate addition tofood ofthesubstance. Testing of"mixtures" wasnotnormally
required. However, some food additives were bytheir very nature mixtures.
6.61 With regard topesticides, testing of"mixtures" wasalsonotrequired, neither intheframework
oftheactivities oftheFAO/WHO Joint Meeting onPesticide Residues norinthelegislation ofthe
European Communities aslaiddown inDirective 91/414/EEC Annex II,Part A(O.J. L230pp.15-18).
6.62 Forveterinary drugs, testing of"mixtures" wasnotrequired. However, thecomprehensive
basic pharmacological screening required foralldrugs could provide information requiring further
follow-up inspecifically designed tests. JECFA hadevaluated anumber ofsubstances where theADI
wasbased onapharmacological NoObserved Effect Level. Thelegislation oftheEuropean Union
also didnotrequire testing of"mixtures" (see Directive 92/18/EEC amending theAnnex to
Directive 81/852/EEC, O.J.L97of10April 1992, pp.1-23). However, there wasadifference between
"mixtures" andfixed combinations. Such combinations required justification onthebasis ofadequate
testing. Repeated dose toxicity testing could bemodified (i.e.reduced) incertain instances, forexample,
ifnewcombinations ofknown substances were proposed andnopotentiating effects hadbeen observed
during initial screening.
6.63 Dr.Arnold noted thattesting of"mixtures" ofhormones wasnotnormally required, unless
anunknown fixed combination wasadministered. Henoted thattheexperimental animals intoxicity
testing (orhumans, ifthere were usesinhuman therapy) were typically exposed toallhormones existing
inthebody. Virtually allcells were targets ofoneorseveral oftheapproximately 50known hormones
andtheir metabolites. Thesame hormone could have several targets; thesame cellmight have several
responses toasingle hormone. Thebattery oftests included exposure atallstages ofdevelopment
from embryonic tofetal toneonate toreproductive state until theendofthewhole lifespan, andthis
wayallsituations ofhormonal control were covered. This meant alsothatallxenobiotic hormonally
active substances hadbeen tested with respect topossible interactions with thehormone system. No
specific toxicity testing hadbeen performed with thefixed combinations authorized intheEuropean
Communities.
6.64 JECFA developed itsstrategies concerning theevaluation ofanabolic hormones inits25th
and26th Report. These indicated thatthetoxicological evaluation ofresidues ofanabolic agents that
arepresentinhumanfoodobtainedfromanimalstreatedwiththeseagentsmusttakeintoaccountwhether
theresidue wasidentical toahuman endocrine hormone. Inthelatter case, thepossible endocrinological
effects andcarcinogenic potential oftheresidue must beclosely examined. Inaddition, itwasnoted
thatchemically modified hormones, hormonally active agents from plants, andsynthetic anabolic agents
presented thefollowing specific problems:
(i) extreme potency andconsequently theneed toensure minimal residues;
(ii) potential tumorigenic activity; and
(iii) thepresence oftheir metabolites inanimal products thatmight beofendocrinological
ortoxicological consequence.
Theevaluation foracceptance oftheuseofxenobiotic anabolic agents inanimal food production
resembled inmany respects theevaluation ofpesticides, since thetwoessential elements required were:WT/DS26/R/USA
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(i) adequate, relevant toxicological data; and
(ii) comprehensive data about thekinds andlevels ofresidues when thesubstances are
used inaccordance with good animal husbandry practice, which required evidence as
totheefficacy oftheanabolic agent, theamounts used toproduce theeffect, theresidue
levels based onfield trials, andinformation about methods ofanalysis ofresidue levels
thatcould beused forcontrol ormonitoring purposes.186
6.65 Dr.Lucier responded thattheissues ofcarcinogenicity, synergistic effects, genotoxic effects
andchronic exposure appeared tobeconsidered intheJECFA report, although thebasis forthe
evaluation (ADI recommendation) wasbased primarily onhormonal effects inmonkeys because the
othereffectsorissueswereconsideredoflessrelevancetohumanhealthrisks.Thehormonesinquestion
hadbeen used longenough togetinformation onwhether ornottheyposed animal health risks, provided
thatgood records were available. However, there wasnotractable approach fordetecting human health
risks from long-term useasthehealth risks, ifany, would bequite small.
6.66 Thenumber ofmolecules thatremain following appropriate useofthese agents wasvery small,
particularly inrelation totheamount ofnaturally occurring oestrogens orandrogens. Sothe
accompanying risk that would beassociated byconsuming meat containing residues would be
extraordinarily small. Itwould bevery hard onscientific grounds tosaythattheriskwaszero, but
itwaslikely tobevery, very small. Itcould bezero.
6.67 Interms ofthecarcinogenic activity ofthehormones inquestion, itwasalready known that
naturally occurring physiological levels ofandrogens andoestrogens were carcinogenic. Therefore,
theissue ofthreshold wasirrelevant tothetoxicological evaluation ofthese agents. Ifahundred thousand
molecules ofsomething already exist inthebody andsome ofthose molecules were producing aDNA
damage event, there wassome possibility thatthesame damage event would occur ifanother molecule
wasadded toitbecause itwasthesame molecule. Itwould notbepossible todistinguish thatadditional
event from theones thatoccurred from thethousand molecules. Butitwould notbepossible tosay
thatnone ofthose events were related tothatadditional onemolecule. This would notbedetectable.
Thechances were very very small, butitwould beimpossible tosaythattheevent could notoccur.
6.68 With regard totheincreased incidence ofsome tumours occurring invarious countries inthe
world referred tobyDr.Epstein, itwasprobably truethatthere wasarealincrease intesticular cancer
andthisincrease appeared tobepredominant inyoung men which wasespecially disturbing. Why
thiswasoccurring, noonereally knew itscause. There wasnoreason tothink, however, thatitwas
associated with oestrogen. There were many other factors thatcould becausing that. Breast cancer
wasalsoontherise. However, onecould notnecessarily attribute thatincrease toexposure toexogenous
external oestrogens. There were many reasons whyexposure togenotoxic agents could beaccounting
fortheriseinbreast cancer rates; oneneeded tobecognisant ofother factors andnotjustblame the
exogenous oestrogens foreverything. Regarding theoralcontraceptive issue, Dr.Lucier indicated
thatDr.Epstein wasprobably right thatthere would beanincrease inbreast cancer riskforwomen
who started taking thepillvery young because thatextended theperiod oftime inwhich they were
exposed tohigh levels ofoestrogen andthiswasaknown riskfactor forbreast cancer. Thesame
exposures alittle bitlater probably would nothave anincrease, sowhen averaged out,there wasno
statistically significant increase inbreast cancer from oralcontraceptives. Noonechallenged thefact
thatoestrogens were carcinogenic.
6.69 With regard toDr.Metzler comments, Dr.Lucier noted thattheadducts thatmay arise from
synthetic materials were likely different andofmore concern, interms ofariskassessment, than the
ones thatarise from thenaturally occurring ones, because there already wasagiven body burden of
186Environmental Health Criteria 70,WHO, Geneva, 1987.WT/DS26/R/USA
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thenaturallyoccurringoestrogens.Thequestionofgenotoxicornon-genotoxicwasessentiallyirrelevant
heresincethedoseresponserelationshipsforoestrogenincreasesincelldivision(onepossiblemechanism
ofcarcinogenesis)waslikelytobelinearbecausenormallevelsofoestrogenwerecausingcellreplication.
6.70 Dr. McLean replied that the1988 and 1989 JECFA reports addressed theissues of
carcinogenicity andgenotoxicity andtheir findings were accepted byCodex. Thecompounds were
notgenotoxiccarcinogensandtheresponsesseenwererelatedtotheirhormonaleffects.Thesehormonal
effects were evaluated using sensitive end-points innon-human primates. Inthecase ofsynergistic
effects, itwasrecognized thatthelevels resulting from treatment with thenaturally occurring hormones
were significantly lessthan thenatural levels already present inthetreated animals. Inaddition, it
must berecognized thatallthree hormones occurred inmale andfemale animals andhumans. With
regard tomutagenicity, data forthenaturally occurring substances wasreviewed andreferenced in
theJECFA 1988 Report. Thereport wasnotsilent onthematter butitreferred tomutagenicity data
thatwasinthepublished literature. Inthecaseofprogesterone, testosterone andoestradiol-17 ,there
were anumber ofpublished documents thatJECFA didlook at,andthey arereferenced initsreport.
6.71 There wasalsohuman dataavailable from therapy withvarious natural andsynthetic hormones.
This therapy wascontinued inhumans formany years andtherisks have been evaluated. Thelevels
found inmeat after treatment aremany orders ofmagnitude lower than therapeutic levels, arepoorly
absorbed orally andsodonotrepresent ahazard. Thecompounds hadbeen used inmany countries
forlong periods oftime andthere wasnohuman epidemiological data which suggests anyhazard.
With regard toDr.Epstein 'sobservations related toincreasing numbers oftumours, Dr.McLean
observedthattheincreaseintumoursoccurredalsointhosecountrieswheretheuseofgrowthpromotants
wasnotwidespread andtheincrease began before thehormonal growth promotants received widespread
use.
6.72 Dr.Ritter noted thatdatarelating tocarcinogenicity andgenotoxicity were indeed available
totheJoint FAO/WHO Expert Committee onatleast fiveofthesixhormones under discussion (all
butMGA). Inallofthese cases, therelevant dataformed thebasis of:(i)thesafety evaluation, (ii)
thedecision bytheCommittee thatanADI need notbeallocated forthenatural hormones, and(iii)
theestablishment ofboth anADI andMRL ’sfortrenbolone acetate andzeranol.
6.73 With relation tooestradiol, progesterone andtestosterone, JECFA concluded thattheincreased
tumour incidence wasattributed tothehormonal activity ofthese hormones associated with thevery
high doses utilized intheexperiment. These effects were notconsidered relevant toanevaluation of
thesafety offood residues. TheReport wassilent ontheresults ofmutagenicity studies, which were
available totheCommittee forreview. With relation totrenbolone acetate, JECFA similarly concluded
thatthecarcinogenic effects detected were adirect consequence ofthehormonal effect associated with
thehigh doses utilized inthestudy andnotofdirest relevance totheinterpretation ofthesafety of
thefood residues. JECFA alsoconcluded thatthetumorigenic effect ofzeranol wasassociated with
itsoestrogenic properties atthehigh doses utilized inthecancer study, andtherefore asafeexposure
level tohumans could bedetermined.
6.74 Theissue ofpotential synergy wasaddressed, atleast inpart, byJECFA through theconduct
ofbiochemical studies directed attheeffect ofexcretion ofhormone combinations when compared
tosingle hormones alone. Although these studies didnotspecifically address issues related toaltered
toxicity duetosynergy, these limited datadidprovide evidence thatwhile administration ofhormone
combinations could beexpected toalter excretion kinetics quantitatively, there wasnoevidence of
important qualitative changes. Itwas, however, clear thatdefinitive studies relating togenotoxicity
orcarcinogenicity ofhormone combinations hadnotbeen carried out,even though thiswasfrequently
thepreferred method ofuse.WT/DS26/R/USA
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6.75 Dr.Ritter observed thattheuseofgonadal type hormones asanabolic agents hadbeen in
agriculturalpracticeforapproximately40yearsthroughmanypartsoftheworld.Regardingthesynthetic
hormones, both zeranol andMGA hadbeen used asanabolic drugs, atleast intheUnited States, for
approximately thirty years while trenbolone acetate hadbeen inuseforapproximately tenyears. At
least inthecase ofthenatural hormones andboth zeranol andMGA, broad scale usehadnow been
inplace formore than ageneration with only fewandisolated reports ofpotential adverse effects.
Theprimary potential concern with regards tohuman health effects hadbeen thatofcarcinogenicity.
While theuseofthegrowth promoting hormones forperiods aslong as40years should have been
sufficient toresult inanincreased cancer riskinthehuman population, anincrease which could be
attributable totheuseofthese hormones hadnotbecome apparent. Noting thatboth breast cancer,
particularly inpost-menopausal people, andprostatic cancer hadincreased sharply inaffluent countries.
Dr.Ritterpointedoutthatthisincreasewasthoughttobeprimarilyassociatedwithgeneticpredisposition
andsignificant alterations inlifestyle (Houghton andRitter, 1995).
6.76 Dr.A.Randell commented ontherelationship between theAcceptable Daily Intake (ADI)
andtheMaximum Residue Limit (MRL) andwhether ornotthese were measures ofacceptable risk.
Themaximum residue limit wasdefinitely notahealth-based limit. Itwasalimit established forthe
control ofveterinary drugs inactual practice. Theestablishment ofamaximum residue limit wassuch
thatthemaximum residue would never lead toresidues which would, inanormal ingestion ofthe
product, cause anyconsumer toexceed theacceptable daily intake. Therefore there wasanupper
boundary tothemaximum residue limit imposed bytoxicology considerations. Thelower limit was
normally derived from residue trials inpractice according totheproposed good veterinary practices
intheuseofthese drugs. However, inthecase ofzeranol, thislimit fellsofarbelow notonly the
toxicologicallyderivedlimitbutalsothelimitthatonecoulddeterminewithnormalmethodsofanalytical
chemistry, thatitwasincreased totakeintoaccount thefactthatifadecent control programme were
notgoing tobeoverly expensive, than thelimit must becontrollable byanalytical procedures rather
than byresidue trials. Theacceptable daily intake itself alsowasnotadirect riskassessment inthe
sense thatitprovided astatement ofquantitative risk. TheADI concept stated thatthere would be
noappreciable riskasaresult ofexposure tothechemicals concerned. This wastruewithin theJECFA
andJMPR framework, forfood additives, residues ofveterinary drugs andpesticide residues. (Dr.
Lucier 'scomment thattheriskwasprobably somewhere between zero andoneinamillion, provided
some sortofquantitative framework, butJECFA hadnever established aquantitative evaluation of
riskintheapplication oftheADI.)
Question 6:
Isthere anymore recent scientific evidence available with respect totheeffects onhuman oranimal
health oftheuseofanyofthesixhormones indispute especially when used forgrowth promotion
purposes, other than theevidence already taken into account byCodex? How reliable are
extrapolations from animal studies topossible adverse effects inhumans? Further toquestions
6and8,areyouaware ofnew scientific evidence showing that thecarcinogenicity, synergistic
effects, genotoxic effects, long-term useand/or exposure tocombinations ofthehormones in
question andtheir metabolites, ifanydonotonly depend onthehormonal activity ofthedose
administered? Would such evidence invalidate theADIs andMRLs established byJECFA/Codex?
6.77 Dr.André noted thatrecent reports oftheeffects onanimal health from theuseofthesix
hormones indispute asgrowth promoters confirmed andfinalized previous results.187Based on
anatomical orhistopathological observations, these results demonstrated theeffects ofcommercially
available implants onanimal behaviour, development andreproduction. Young bull behavioural
modifications hadbeen confirmed: young bulls treated with zeranol "spent more time idling, eating
187Renaville etal.(1987), Dehaan etal.(1990), Moran etal.(1988), (1990), Herenda (1987), Beal etal.(1988).WT/DS26/R/USA
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andruminating than controls".188Animal libido wassystematically altered. The changes inthe
behaviour ofbulls were usually correlated with histopathological modifications, well described inthe
1980s asatoolfortreatment diagnosis andmore recently confirmed inbulls.189Similar phenomenon
hadbeen recently studied inother species, astheeffect oftrenbolone inmale pigs.190Theinfluence
ofthese hormones used asgrowth promoters onreproductive tract development andreproduction had
been confirmed inbeefheifers: "The lower pregnancy rateinzeranol implanted heifers 100days after
exposure tobulls wascaused byfailure tocycle early inlifeand, inthose thatwere cycling, failure
toconceive andabortions between 25and45days ofgestation".191
6.78 First results ofrecent research work with mice ontheeffects ofhormones onanimal sexual
development andreproduction were published in1995. They concluded that"DES andZeranol
administered during midpregnancy leads todecrease fetal weight andsizeandlower numbers ofmale
offspring atbirth".192In1996, thesame authors demonstrated "that prenatal exposure tozeranol or
DES induced abnormal testicular differentiation inthemouse".
6.79 Concerning human health ,there wasadiscussion onthedecrease ofhuman sperm counts193,
anapparent increase oftheincidence ofhormonally-mediated diseases like breast cancer and
endometriosis, andadecrease inthemale/female ratio, which were thought tobeduetooestrogens
intheenvironment. Whether theuseofhormones forgrowth promotion wascontributing tothiscould
notbescientifically proven atthepresent time.
6.80 Extrapolations from animal tohuman wasanofficial tool fortoxicological andefficiency
evaluation ofdrugs under development. Ingeneral, they were regarded asconservative even ifthey
didalways contain acertain level ofuncertainty. Moreover, these tests onanimal models didnottake
intoaccountthemultipleexposuretomanydifferentcompounds(characteristicforhumandiet).Humans
were sometimes more sensitive foracertain effect than animals, andthey were notalways inasgood
health aslaboratory animals. Theaction offood processing onresidues wasnotchecked inanimal
experiments. Forsome effects ofchemicals onhumans, such aslong term effects over generations,
noanimal models existed. Inother cases, results onanimal models have sometimes been considered
asnotrepresentative. Forthese reasons, many drugs which hadbeen fully validated inanimal models
hadbeen banned after several years ofuseinhumans andthediscovery ofanunknown hazard.
6.81 Dr.Arnold indicated thatsince thelast(JECFA) evaluation, science hadmade further progress
inseveral areas, including themolecular mechanisms ofaction andtheepidemiology ofcancer. The
newly available information didnot,however, substantially change thebasis fortheevaluation ofthe
fivesubstances bytheCodex/ JECFA system. Although animal studies, ingeneral, could provide
useful information onpossible adverse effects onhuman health resulting from exposure tochemical
substances, thepossible health effects resulting from theoralingestion oftrace amounts ofresidues
ofthethree nature-identical hormones, (oestradiol-17 progesterone andtestosterone) could notbe
reliably andquantitatively predicted from theinformation contained inavailable studies.
188Legoshin etal.(1994).
189Tipirdamaz 1991, Ciftci (1990).
190Lopez-Bote etal.(1994).
191King etal.(1995).
192Perez-Martinez etal.
193Nimrod andBenson (1996).WT/DS26/R/USA
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6.82 Earlystudiesinmice,whichwereconductedbetween1940and1973,andwhichwerereferenced
intheIARC Monographs, were innoway designed toassess thehuman cancer riskresulting from
oralingestion oflowdoses ofoestradiol-17 .None ofthese studies used theoralroute ofexposure
inanyanimal species. None ofthem was conducted under GLP-like conditions oraccording to
contemporary testguidelines. Many ofthem were poorly documented. Theprincipal aimofthese studies
wastoexperimentally produce tumours under avariety ofcondition. Thetestsubstance wasusually
subcutaneously administered (frequently asimplant). Thedoses were often extremely high andnot
infrequently caused ahigh number ofearly deaths. Such dosing wasinadequate forcarcinogen testing
inrelation tothesafety evaluation ofresidues. Thestudies demonstrated thatsubcutaneous injection
orimplantation ofhigh doses ofoestradiol-17 orofitsesters alone orinthepresence ofother
carcinogenic factors resulted inincreased incidence ofmammary, pituitary, uterine, cervical, vaginal,
lymphoid andinterstitial-cell tumours inmice. TheIARC working group concluded onthebasis of
allanimal datathatthere wassufficient evidence forthecarcinogenicity ofoestradiol-17 inexperimental
animals.
6.83 Similarly theanimal studies withprogesterone which were reviewed byIARC were alsolimited
tosubcutaneous andintramuscular injections andsubcutaneous implantations ofhigh doses; inrats
andrabbits itwasalways given incombination withother sexhormones. Progesterone wasadministered
together with carcinogenic substances such asdimethylbenzanthracene, methylcholanthrene,
diethylstilboestrol orN-2-fluorenyl-diacetamide inthemajority ofthestudies reviewed. From these
studies IARC concluded: "There islimited evidence forthecarcinogenicity ofprogesterone in
experimental animals. Intheabsence ofepidemiological data, noevaluation ofthecarcinogenicity of
progesterone tohumans canbemade."
6.84 Similarly totheother twonature-identical steroid hormones, testosterone anditsesters were
tested inexperimental animals bysubcutaneous injection and/or implantation, andinrabbits by
intramuscular injection. Inthis case IARC concluded: "There issufficient evidence forthe
carcinogenicity oftestosterone inexperimental animals. Intheabsence ofadequate data inhumans,
itisreasonable, forpractical purposes, toregard testosterone asifitpresented acarcinogenic riskto
humans. Theonly related datainhumans, although insufficient foranevaluation, concern thepossible
long-term effects ofandrogenic anabolic-steroids."
6.85 Thecontribution ofinformation obtained from these animal studies wasoflittle relevance for
thequantitative assessment ofthepotential effects onhuman health oforally ingested, very lowresidual
amounts ofthese substances having noeffects onthephysiological hormonal balance. Inparticular
noadditional human cancer riskcould bededuced from these animal studies intheabsence ofother
relevant information. With reference tostudies conducted byother scientists, namely Dr.Liehr and
Dr.Cavalieri regarding different types ofDNA damage orgenotoxicity established foroestrogen, Dr.
Arnold agreed thatwithchemical methods allthese things could beproduced. Thequestion waswhether
itoccurred inliving cells, atwhat concentrations, what enzymes were involved, what was the
compartmentalization ofthese enzymes, etc. Inhisview, there were many gaps intheevidence. A
scientist could notexclude thatattheendsomebody might show thatoestrogens acted directly onthe
gene. Forthemoment, theevidence wasnotconvincing anddidnotinvalidate thebasic conclusions
ofJECFA 1988.
6.86 Inresponse tothefollow-up questions, Dr.Arnold indicated thathormonal activity wasa
necessary requirement ofhormonal carcinogenesis caused bythesubstances indispute. Hewasnot
aware ofanyevidence which would invalidate theADIs andMRLs established byJECFA/Codex.
6.87 Dr.Lucier indicated thatanimal datawere usually relevant forestimating human health risks,
particularly forhazard identification, andthere wasasubstantial body ofknowledge andpastrecord
tosubstantiate thisconclusion. However, itshould bekeptinmind thatthere isconsiderable uncertainty
inextrapolating high dose animal datatolowdose human risks. Over thelast5-10 years much hadWT/DS26/R/USA
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been learned about (i)themechanisms whereby hormones triggered responses intarget cells including
theinterplay orcross talkbetween receptor systems, (ii)thedevelopment ofcredible approaches for
dose-response evaluation, (iii)thespectrum oftoxic effects produced byhormonally-active agents,
and(iv)theroleofmetabolic activation ofhormones. There wasagrowing body ofknowledge that
some hormones could beconverted togenotoxic metabolites. However, itwasnotclear whether these
metabolites areinvolved inthecarcinogenic process.
6.88 Dr.McLean responded thathedidnotbelieve thatdata developed after 1989 would justify
arevision ofthepresent useofhormones forgrowth promotion. Forexample, studies ofinvitro
receptor binding assays inthepresence ofpesticides hadnotproduced evidence ofconcern. The
extrapolation inthecase ofthehormones wasarguably more reliable than with anyother class of
compounds because their mode ofaction andtheir metabolism wassimilar inboth animals andhumans.
Non-human primate andhuman datawasalsoavailable inmany cases. Inthecase oftrenbolone and
zeranol, theusual safety factors forinter- and intra-species variation were still applied. The
extrapolations from animal studies tohumans wasreliable inthiscase. Thecurrent ADI andMRL
would only beinvalidated ifnewdataestablished alower NOEL. Inthecaseoftrenbolone andzeranol,
theNOEL used wasconservative andtherefore low. Inanyevent, ifanynational body orgroup believed
thatitwastime forre-evaluation ofsome ofthehormones previously evaluated byJECFA itshould
approach theJECFA ashadbeen done onanumber ofoccasions with thenumber ofcompound of
varying chemical classes.
6.89 Dr.Ritter observed thattheJECFA review, andthesubsequent decisions byCodex, were
basedlargelyonreviewsconductedapproximatelyadecadeago.Inrespectofthethreenaturalhormones
(oestradiol, progesterone andtestosterone), the1995 ECScientific Conference generally recognized
thatthese substances could increase thegrowth rate, theproperties oflean meat tofatandthefeed
conversion efficiency ofsome species ofanimals. TheConference re-affirmed thattheresulting residues
inmeat were within thenormal physiological range andconcluded thattheconditions ofuseofthe
natural growth promoting hormones provided areasonable safeguard ofpublic health. Inrespect of
thesynthetic hormones utilized forgrowth promotion (trenbolone andzeranol), the1995 ECConference
advanced theview thatatdoses required forgrowth promotion, residue levels ofthese xenobiotic
hormones were well below thelevels regarded assafe. TheConference alsonoted theavailability
ofonly limited dataonpossible adverse effects intarget animals andemphasized theneed forfurther
study oftheeffects ofgrowth promoters administered incombination, asthepresence ofonemight
alter themetabolism oftheother.
6.90 Thevalidity ofextrapolations from animal studies tohumans wasthepre-eminent issue in
contemporary toxicological hazard andriskassessment andwasthebasis ofthehazard evaluation for
drugs, pesticides, food additives andother contaminants worldwide. Given thereliance bybothnational
regulatory authorities andinternational agencies onanimal studies forpredicting possible adverse effects
inhumans, itwould seem defacto thattheinternational scientific community hadplaced agreat deal
offaith inthevalidity ofthese extrapolations. Atthesame time, however, itwasalsoclear thatthe
validity ofanimal models inpredicting adverse human effects wasinfluenced bymany factors including
selection oftheappropriate animal model, dose selection, duration androute ofexposure andselection
ofappropriate riskmodels designed toestimate human risks resulting from theuseofasubstance under
realistic andpractical useconditions.
6.91 Recognizing theinherent limitations ofanypredictive model, Dr.Ritter indicated thatthe
scientific community hadelaborated ahazard andriskassessment paradigm thatinvolved evaluation
ofabroad range oftoxicological endpoints, selection ofthemost sensitive fordetermination ofaNOEL,
application ofanadditional uncertainty factor forderivation ofanADI andmodels forestimation of
dietary exposure which invariably substantially exaggerated intake levels. Theneteffect ofthisseries
ofoverly conservative calculations wasmost likely very conservative estimates ofrisk, intended to
compensate atleast inpart, forthelimitations inherent inthereliability ofanimal tohumanWT/DS26/R/USA
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extrapolations. Indeed, initsconcluding commentary, theSteering Committee ofthe1995 ECScientific
Conference noted thatthenature ofthecalculations described above wassuch thatadherence tothe
ADI provided ahigh degree ofconfidence thatadverse effects would notbecome apparent inpeople.
Inother words theEuropean Conference essentially reaffirmed andstrengthened theearlier conclusions
reached byJECFA thatinaccordance with operating procedures thatwere provided fortheuseofthese
substances, their usedidnotconstitute arisktoconsumers offood commodities produced with the
hormones atquestion, atleast forfiveofthesixsubstances.
6.92 Dr.Ritter noted thatDr.Liehr 'swork andthework ofmany investigators wastoproduce
aneffect. This wastothemost fundamental issue inpharmacology andintoxicology, theconcept
ofdose response. Dr.Liehr wasvery interested inunderstanding theinduction ofcancer asaresult
ofexposure tothese hormones. Therefore, hisprotocol would necessarily bedesigned insuch away
soastoproduce thedesired effect, inhiscase thetumour. Theintent inthecase offood residues,
wasobviously toavoid adose level which might constitute ahuman risk. Therefore, thelevels that
were present asresidues infood were thousands orhundreds ofthousands ormillions oftimes lower
than they would beinanexperiment which wasspecifically designed toinduce atumour. These two
experiments were completely atcross purposes with each other; they were from their very initiation
intendedtoproduceentirelydifferentresults.Tocompareaprotocolwhichhadbeendesignedtoproduce
atumour toafood residue theusepractice ofwhich wassetupinsuch awaysoastominimize the
presence oftheresidue, wasarelatively meaningless comparison. Moreover, noonecould reasonably
assure thatthepresence ofthese residues albeit atlowlevels constitutes zero risk; infactscientifically
itwould beimpossible toevertesttoacertainty. Butthepoint wasthatifthese lowlevels didconstitute
arisk, they constituted ariskofamagnitude which approached zero.
Question 7:
Isthere anyscientific evidence available which demonstrates that apotential foradverse effects
onhuman oranimal health arises from theadministration ofanyofthesixhormones indispute,
ingeneral, andinparticular foranimal growth-promotion purposes, ifadministered inaccordance
with good animal husbandry practice and/or good veterinary practice?
6.93 Dr.André replied thatthere wasnopublished scientific evidence thattheadministration, in
accordance with good animal husbandry practice and/or good veterinary practice, ofanyofthesix
hormones indispute ingeneral (i.e.fortherapeutical andzootechnical purposes) andinparticular for
animal growth promotion purposes, induced adverse effects onhuman health. This only meant that
during thelastdecades, incountries where they areinuseeither forgrowth promotion purposes or
fortherapeutical andzootechnical purposes, none oftheheath problems which could beduetotheir
use(such ascancers, reproduction problems ...)hadbeen scientifically related totheir use.However
thequestions remained whether thishadbeen studied andwhether theperiod ofusewaslong enough
(seeresponse toquestion 5above). Concerning animal health, seeresponse toquestion 6above.
6.94 Dr.Arnold indicated thathewasnotaware oftheexistence ofsuch evidence.
6.95 Dr.Lucierrespondedthat,tohisknowledge,therewasnopieceofscientificevidencetoindicate
thatanyofthesixhormones inquestion hadunequivocally caused adverse effects inhumans when
administered andused properly. However, there wassome information available which raised concern
foraslight effect onincidence ofhuman disease (seeresponse toquestion 8).
6.96 Dr.McLean stated thatthere didnotappear tobeanyevidence which unequivocally established
thatadverse effects hadbeen caused inanimals treated with hormonal growth promotants orinhumans
consuming meat from treated animals.WT/DS26/R/USA
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6.97 Dr.Ritter observed thatasearly as1982, aWHO appointed Working Group concluded that
when thenatural sexhormones were used inaccordance with instructions fortheir useingrowth
promotion, such usewould notpresent anyharmful effects toconsumers ofproducts which hadbeen
produced withtheaidofthese promoters. This Working Group alsoconcluded thatthelevels ofzeranol
andtrenbolone, andtheir major metabolites, found inedible tissue following appropriate useasgrowth
promoters, were substantially below thehormonally effective doses inanimal testsystems anddidnot
present ariskofharm tohumans. Overall, theWorking Group concluded thatthefivecompounds
were safeforuseintarget animals andinsubsequent consumers when they were used asprescribed
forgrowth promotion inmeat production.
6.98 TheEC1995 Scientific Conference concluded thattheeffects onanimals interms ofdisease
incidence, performance, general mobility andmeat producing efficiency were either unchanged or
improved. Theeffects onanimal welfare were negligible interms ofhealth, performance andeffects
onbehaviour, although itwasnoted thatthere might beatransient increase insexual activity for2-10
days insome adult steers receiving oestradiol.
Question 8:
Isthere anyscientific evidence available thatresidues ofanyofthesixhormones indispute could
have carcinogenic effects, even though inthecase ofthetwosynthetic hormones these residues
fallwithin theMRL levels established bytheCodex? Isthere anyscientific evidence concerning
thebiochemical andphysiological mechanisms bywhich thehormones subject tothisdispute exert
their carcinogenic effects? Please describe therelationship between thehormonal effect andthe
toxic effect ofthesixhormones. Isthere athreshold level below which there isnoscientific evidence
that residues ofthehormones would have adverse health effects onhumans? Aretheconcepts
of"Acceptable Daily Intake" and"Maximum Residue Level" valid for,orapplicable to,genotoxic
carcinogens?
6.99 Dr.André indicated thatprevious results onthecarcinogenesis ofhormones hadrecently been
confirmed. This wastrueforsingle hormones aswell asformixtures ofhormones, administered in
vivoandinvitro.Concerning themechanism bywhich thehormones exerted their carcinogenic effects,
themost important model wasoestradiol-17 itself. Ithadbeen proven thatoestradiol-17 ,which
wasinvolved inthedevelopment ofbreast cancer, stimulated thedevelopment ofmalignant cells. Recent
results showed thatoestradiol-17 enhanced genomic instability inmalignant cells, inducing deletions
oradditions inDNA. Itwas reported that natural oestrogens (mainly oestradiol) induced cell
transformation viaover expression andsynthesis ofoncoproteins. Some newinformation about the
potential role andmechanism ofaction ofprogesterone inbreast cancer induction andabout the
biochemical aspects ofpituitary oestrogen induced carcinogenesis were published; however, theydid
notdemonstrate achieved molecular induction process.
6.100 Recent dataonthemechanism ofthecarcinogenic effects ofhormones ledtotheconclusion
thathormones ortheir metabolites exerted adirect effect ontumour initiation byDNA damage; for
oestrogen-dependent tumours, catechol oestrogens andtheir quinone forms would appear tobeinvolved.
Further, hormones stimulated thegrowth oftumours intissues inwhich they hadspecific receptors.
They hadacomplex carcinogenic andgenotoxic effect. Thehormonal effect stemmed from receptor
binding, translocation tothenucleus andgene activation. Powerful oestrogens were strongly bounded
andconcentrated inthenucleus. Iftheir hydroxylation andoxidation induced potential genotoxicity
andcarcinogenicity, itwasnotsurprising thatthemore hormonally efficient they were, themore
genetoxic andcarcinogen they could be.
6.101 Dr.André concluded thathormones hadtobeconsidered asgenotoxic compounds andfor
such carcinogens, nothreshold level could bedefined; noADI andconsequently noMRL could be
established. This wasthegeneral opinion oftoxicologists (Kuiper, EC1995 Scientific Conference).WT/DS26/R/USA
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This opinion hadalsobeen adopted bytheUnited States Environment Protection Agency (EPA) for
acarcinogenic nongenotoxic dioxin, TCDD.
6.102 Dr.Arnold responded thatthere wasnoevidence available showing thatresidues ofanyof
thesixhormones indispute could have carcinogenic effects, even though inthecaseofthetwosynthetic
hormones these residues fellwithin theMRL levels established bytheCodex. Itwasnotpossible to
summarise briefly alltheknown facts published inthousands ofpapers inthelastdecades andin
particular inthepast5-20 years.
6.103 Steroid hormones primarily influence theexpression ofgenetic information atthelevel of
transcription bybinding to,andactivating, transcription factors. Theactivated transcription factors
interact with theregulatory orpromoter region ofthegenes. The hormone receptors arethese
transcription factors inthecase ofe.g., steroid andthyroid hormones. Thecomplete DNA sequence
ofthehuman oestrogen receptor wascloned forthefirsttime in1986 using thebreast cancer cellline
MCF-7. Inthemean time, thegenomic genes forallthree receptors (oestrogens (ER), progestins (PR)
and androgens (AR)) had been cloned. Dr.Arnold characterized the biochemical
hormone-receptor-interactions asfollows: receptors were present inlowconcentrations; their binding
sites were saturable atphysiological concentrations. Thebinding sites exhibited high specificity and
high binding affinity; binding wasreversible. Specific receptor binding wastheinitial andnecessary
stepinthesequence ofevents leading toahormonal effect although itwasnottheonly reaction the
hormones could undergo. Theeffects terminated upon dissociation ofthehormone-receptor complex.
6.104 Theinvolvement ofreceptors inhormonal signal transduction wasthusexplained bythefact
thatinaddition totherecognition domain forthehormone they possessed asecond functional domain
(about 70amino acids long) through which theycould bind toDNA. Steroid-hormone-regulated genes
hadatleast twodifferent regulatory elements, a"generic" promoter element and(a)hormone response
element(s) (itwasnotclear howmany response elements actually existed innaturally occurring genes).
Itbound thehormone-receptor complex more avidly than thesurrounding DNA did. The
hormone-receptor might alsoregulate several genes inthesame cellanddifferent genes indifferent
target cells. Metabolites andrelated exogenous synthetic hormones might work onadifferent setof
response elements. Thedetails ofhow theinteraction with DNA promoted transcription wasstillan
area ofinvestigation. However, thebasic principle waswell established.
6.105 Carcinogenesis could beoperationally described asamultistage process involving atleast three
stages: initiation, promotion andprogression. Theintermediate stage ofpromotion didnotappear
toinvolve structural alteration ofthegenome ofthecellbutrather depended onaltered gene expression.
Both oestrogens andandrogens hadbeen shown tobeeffective promoters intheir target cells aswell
asinliver. Incontrast toinitiation, promotion was areversible stage depending oncontinued
administration ofthepromoting agent. Besides tissue specificity, thegeneral characteristics ofhormonal
carcinogenicity were: long induction periods andprolonged exposure athigh levels with concomitant
severe derangements inhomeostasis. Thedose-response relationship ofpromoting agents (aswell as
thereceptor-hormone binding) exhibited sigmoidal curves with anobservable threshold andamaximal
effect.
6.106 Hormonal carcinogenesis inexperimental animals hadmainly been studied inrats, mice and
hamsters. Thepromotor model ofhormonal carcinogenesis hadbeen developed through studies of
avariety oftissues ofthese animals. Thequestion under dispute wasnotwhether these models were
stillvalid butrather whether genotoxic mechanisms could additionally exist orwould need tobe
considered inorder tofully explain thecarcinogenic potential ofhormones. Inarecent review
("Molecular Mechanisms ofOestrogen Carcinogenesis", J.D. Yager andJ.G. Liehr, Annual Review
ofPharmacology andToxicology 1996, Vol. 36,pp.203-32) itwasconfirmed thatthehormonal effects
ofoestrogens were necessary butnotsufficient toinduce tumours. One metabolite ofoestradiol
(16-Hydroxyoestrone) wasclaimed tobecapable ofbinding toDNA invitro butthiscould notbeWT/DS26/R/USA
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confirmed invivo(unpublished observations byoneoftheauthors). Itwasfurthermore postulated that
thecatechol-oestrogen formed byhydroxylation inposition 4oftheA-ring ofthemolecule could be
involved inthegeneration ofreactive oxygen species through redox cycling. Catecholoestrogens were
alsoable tobind toDNA invitro,afinding which wasnotconfirmed invivo.
6.107 Dr.Arnold further responded thataccording tocurrent scientific knowledge, threshold levels
below which residues ofthehormones hadnoadverse health effects didexist foragiven individual.
Theindividual threshold levels varied andthishastobeconsidered when setting exposure limits for
theentire population.
6.108 Dr.Arnold indicated thattheADI wasderived from a"No Observed Effect Level" (NOEL)
using appropriate safety factors. While itdidnotitself represent athreshold dose, itwasindirectly
related toanotprecisely known threshold dose. Therefore, theADI concept asdefined byJECFA
could notbeapplied inorder toestablish anexposure limit fordirect-acting genotoxic carcinogens
forwhich, atleast theoretically, nothreshold dose could exist. MRLs could beestablished, inprinciple,
toregulategenotoxiccarcinogens.Basicallythereexistedtwopossibilities:iftheresiduesweregenotoxic
carcinogens, alternative models, e.g., riskextrapolation, could beused tofindanMRL; inthecase
ofcarbadox, JECFA wasunable toallocate anADI because theparent drug wasconsidered tobea
genotoxic carcinogen. Inthiscase, however, theresidues were demonstrably notcarcinogenic under
approved conditions ofuse.Thus, anMRL could beestablished onthebasis ofregulating aninnocuous
metabolite.
6.109 Dr.Arnold noted thatMRLs primarily facilitated fairinternational trade andwere notdirectly
related tohealth effects. Only thetotal dietary intake oftheresidues ofconcern, taking intoaccount
allMRLs established forthesame substance andallrelevant commodities andtheir consumption by
thepopulation, could becompared with anexposure limit.
6.110 Dr.Lucierrespondedthatinthecaseofthenaturallyoccurringhormones,particularlyoestradiol-
17andtestosterone, there wasvery good evidence thatphysiological levels were carcinogenic. For
example, breast cancer would strike oneinnine women intheUnited States over their lifetime and
there wascompelling evidence thatphysiological levels ofoestradiol-17 were necessary forthiseffect.
Theevidence came from both animal experiments andhuman studies andwasderived from alarge
base ofpeer-reviewed published information. Inthecase ofoestrogen, early menarche andlate
menopause increased risk whereas ovariectomy was protective. Also, endometrial cancer was
dramatically increased byoestrogen replacement therapy ifunopposed byprogesterone. Inthecase
ofbreast cancer, consumption ofbeefwith elevated levels ofoestradiol-17 could increase riskslightly
ifthecarcinogenic riskwasnotalready saturated byphysiological levels ofoestrogen. Thequestion
ofthreshold wasirrelevant. Itwasknown thatexisting levels were already carcinogenic.
6.111 However, Dr.Lucier noted thatevaluation ofcarcinogenic riskinpeople consuming meat from
growth-promoted animals wascomplex. Forexample, progesterone might protect against endometrial
cancer. From adifferent perspective, oneknew thatdietwasacritical determinant ofbreast cancer
riskandthatfatinthedietwasariskfactor. Therefore, consumption ofmeat containing residues
ofgrowth-promoting agents might actually decrease riskbecause thatmeat contained lessfatthanmeat
from non-growth promoted animals. Onbalance, breast cancer andprostate cancer riskcould possibly
bedecreasedbyeatingmeatfromgrowth-promotedanimals.Moreover,exogenousoestrogensprotected
against osteoporosis andcardiovascular disease.
6.112 Dr.Lucier indicated thatsimple categorization ofagents asgenotoxic ornon-genotoxic, alone,
hadlittle value indetermining ifanADI approach oralinear approach wasmore valid forrisk
assessment. This opinion wassupported byanalysis of500cancer bioassays conducted bytheNational
Toxicology Programme (NTP).WT/DS26/R/USA
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6.113 Dr. McLean replied there wasnoevidence thattheresidues hadanycarcinogenic effect.
Inthecaseofthetwosynthetic hormones which hadaMRL, thiswasbased onaNOEL derived from
ahormonal end-point innon-human primates. There wasdata available which gave information on
themechanism bywhich hormones influence theoccurrence oftumours inanimals andhumans. This
wasavery active field ofresearch because oftheimportance oftumours ofvarious organs, such as
thebreast ortheprostate. Natural andsynthetic hormones exerted their effects bybinding tocell
receptors andcausing aseries ofbiochemical events which influenced themetabolism ofthetarget
tissues. Inaddition, cellproliferation and/or turnover might beinfluenced. Ifthelevel ofhormone
wasbelow thatrequired tocause these events, there would benoadverse effects. However, inthe
case ofthenatural hormonal growth promoters, thenormal levels ofhormones inthehuman body
were already many times greater than those from residues infood. Thesmall amount inmeat would
notinfluence thecourse ofevents andtherefore would notaffect human health. Indeed itwasvery
difficult todetermine exactly where ourhormone burden came from. Butthefactofthematter was
thathumans were constantly being exposed tovery significant levels ofhormones andthattheincidence
oftumours which were associated with hormones inhumans such as,forexample, thebreast orthe
prostate, hadnotsignificantly increased since thesurveying hadbeen carried out.
6.114 Dr.Ritter noted thatcarcinogenicity datahadbeen available andreviewed forthethree natural
hormones andforboth trenbolone andzeranol (seeresponse toquestion 5).Theissue ofincreased
tumour production with allfivehormones wastherefore more amatter oftheoretical consideration
than oneofpractical risk. Aswasthecasewith oestradiol, andindeed with theother hormones under
consideration, tumour induction associated with high exposure tothese substances wasamanifestation
oftissues with high levels ofspecific hormone receptors thatwere normally responsive tostimulation
bytheparticularhormone(JECFA,1988).Theseeffects,whentheyoccurred,weregenerallyconsidered
tobetheexpression ofvery high dose receptor stimulation andwere notbelieved tohave anyparticular
relevance fortheevaluation ofrisks associated with dietary exposure toresidues atmuch lower levels.
6.115 Itwasalsowidely recognized thattoxic effects which might typically manifest atconsiderably
lower levels thenthose required forreceptor stimulation andattendant tumorigenic effects were amore
appropriate basis forevaluation ofpotential adverse effects inhumans following exposure todietary
residues. Notwithstanding, some authors (Liehr, 1996, unpublished; Adlercreutz, unpublished; Arnold,
etal.,1996) hadrecently advanced alternative hypotheses regarding metabolism andmechanism of
action ofthegonadal hormones.
6.116 Historically, forchemicals which displayed carcinogenic properties inlaboratory animals, it
wasassumed thatathreshold dose didnotexist. This view wasdue, inlarge part, tothefactthat
early studies focused onverypotent carcinogens which manifested their effect bydirect covalent binding
toDNA; agents ofthistype which acted through direct covalent binding toDNA hadalsoreferred
toasgenotoxic. Thesubsequent hypothesis argued thateven asingle molecule ofasubstance might
cause aheritable change intheDNA structure which would ultimately leadtotumour formation. In
practice, itwas now recognized thatsuch ascenario was notlikely, andthatinanycase many
carcinogens acted through anon-genotoxic mechanism andhence didnottarget cellular macromolecules
such asDNA. This particular point hadbeen extensively elaborated with trenbolone, which wasthe
subject ofelaborate studies which demonstrated theabsence ofcovalent binding potential associated
with thishormone (JECFA, 1988). Itwasnow apparent thatNOELs could bedetermined formany
chemicals thatmay show some evidence ofcarcinogenicity under experimental conditions. Under
conditions where theeffect wasclearly non-genotoxic itmight bepossible toderive NOELs, establish
anADI andpropose anMRL. Chemicals which produced carcinogenicity through aclear genotoxic
mechanism should beregulated asifathreshold dose could notbederived andhence aNOEL, ADI
andMRL could notbeproposed. Inthecase ofnon-genotoxic carcinogens, there waslittle scientific
validity tothebelief thatthese chemicals should betreated orregulated differently thanchemicals which
produced other adverse effects through non-genotoxic pathways.WT/DS26/R/USA
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6.117 Dr.Ritter concluded thatthere wasnocompelling evidence tosuggest thatthese compounds
should beimmediately re-evaluated, onthebasis notonly ofthehistorical reviews which hadbeen
carried outbyJECFA andother organizations, butalsoonmuch more recent reviews, including those
published asaresult oftheEuropean Conference onGrowth Promotion inlate1995, early 1996, and
indeed onthebasis ofthestatements presented byDr.Liehr, Dr.Metzler andothers. Dr.Liehr 's
recent work andthework which others recently cited suggested thatthere were circumstances under
which adverse effects could bedemonstrated inassociation with amultitude ofthese compounds.
However, scientists were compelled tolook atthetotality oftheevidence asitwasavailable. In
Dr.Ritter 'sview, thetotality ofevidence, recognizing theinformation presented byDr.Liehr and
other scientists, aswellasthehistorical information, suggested thattheassessments thatwere provided
inJECFA 1988 continued toassure areasonable degree ofsafety toconsumers ofthese commodities.
This wasnotonly hisopinion, hestressed, butindeed alsotheconsensus conclusion ofthe1995 EC
Scientific Conference.
Question 9:
Isthere scientific evidence ofparticular human health effects incountries where meat produced
with theuseofanyofthesixhormones indispute forgrowth promotion purposes isallowed for
consumption ascompared tohealth effects incountries where theuseofsuch hormones is
forbidden?
6.118 Dr.André indicated thatthere wasnoknown scientific evidence ofsuch particular health
problems.Onlyserious,longtermepidemiologicalstudiescouldgiveinformativedata(seealsoresponse
toquestion 5).Furthermore, thecausal relation could bedifficult toidentify, i.e.ifcomparisons between
human health disorders wasbetween theUnited States population andtheCommunity population, there
were somany differences inlifestyle between thetwocontinents, thattheprobability toprove the
responsibility ofonecausal factor (like hormones) would bevery low. However, acorrelation between
breast cancer incidence andblood oestrogen levels intheNorth American andJapanese populations
wasdemonstrated. Other markers ofparticular human health effects could beprostatic cancer, human
fecondity orsexratios.
6.119 Dr.Arnold replied thatnosuch evidence existed. Such comparisons could probably notbe
made because other factors, such asgenetic differences ofpopulations, lifestyle differences, differences
intherapeutic uses ofsome ofthesubstances andnumerous other factors, would have much greater
influence ontheincidence ofpossible health problems.
6.120 Dr.Lucier stated thathedidnotbelieve thatgeographical patterns ofhuman disease offered
anapproach fordetermining ifresidues ofgrowth-promoting agents inmeat increased riskofthose
diseases.
6.121 Dr.McLean noted thathewasnotaware ofanyevidence thatthere wasanydifference between
thehealth ofhumans incountries where hormonal growth promoters were used andinthose countries
where they were notused. Thelife-span ofhumans incountries where hormonal growth promotants
were used hadsteadily increased foranumber ofyears. However, thereported incidence ofcancer
hadincreased because thepopulation wasolder, diagnostic capacity hadimproved andbetter nutritional
status increased cancer rates.
6.122 Dr.Ritter indicated thathewasunaware ofanydataorother evidence ofadverse human health
effects incountries where meat wasproduced with theaidofthehormones inquestion, when compared
tocountries where thehormones were notutilized formeat production.WT/DS26/R/USA
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Question 10:
How dothepotential adverse effects onhuman health from residues infood ingeneral, andmeat
inparticular, from pesticides administered inaccordance with good agricultural practice compare
with potential adverse effects from residues ofthesixhormones inquestion, when themeat is
from animals towhich have been administered these hormones forgrowth-promotion inaccordance
with good animal husbandry practice and/or good veterinary practice?
6.123 Dr. André noted thatthese parameters were notdeveloped with theaimofcomparing the
potential health riskofcompounds. Each compound with potential adverse effects onhuman health
wassubmittedtoindividualevaluations,soastodeterminespecificADIsandMRLs (infoodofconcern).
With regards topesticides, Dr.André pointed outthatsome ofthepesticides might facilitate adverse
effects ofoestrogens onhuman health.
6.124 Dr.Arnold responded thatpesticides hadbiocidal properties andwere frequently alsootherwise
very potent chemicals. Certain groups ofpesticides were also used asveterinary drugs, e.g. as
ectoparasiticides. These substances might have asignificant potential toharm human health ifnotused
according togood agricultural practices. TheMRLs established intheEUandelsewhere provided
sufficient consumer protection. Itappeared thatthemargin ofsafety applied when establishing Codex
MRLs forresidues ofveterinary drugs might besomewhat higher ifthefood baskets used andthe
calculated Theoretical Maximum Daily Intakes (TMDIs) were compared. JECFA/JMPR and
CRVDF/CCPR hadstarted harmonising MRLs forsubstances which were used inboth agriculture
andanimal production.
6.125 Dr.Lucier replied thatthetools ofriskassessment were notsufficiently accurate todetermine
ifpesticide residues orresidues ofanti-microbial agents posed agreater riskthan residues ofgrowth
promoting agents. Ineach case, theriskwassomewhere between zero andasmall number.
6.126 Dr.McLean observed thatthere have been veryfewdocumented cases ofadverse effects caused
bypesticide residues infood, when theywere administered inaccordance with "good practice". There
didnotappear tobeanyproven cases linked tohormonal growth promotants. Theuseoftheword
"potential" implied hypothetical cases. Given thathormones hadeffects onsexual characteristics and
metabolic processes, thenpotentially these would change, ifthechanges could beperceived ordetected.
6.127 Dr.Ritter indicated thatMRLs need notbeestablished forthenatural hormones, when used
inaccordance with good veterinary and/or agricultural practice (seeresponse toquestion 5).Inthe
case ofthesynthetic hormones, thenature ofthestudies used toestablish their safety, andthe
methodologicalapproachfortheestablishmentofMRLs ,includingdeterminationofaNOEL,calculation
ofanADI, establishing awithdrawal period andproposing MRLs, wasvirtually identical forboth
pesticide residues andhormone residues. Asaresult, onewould notexpect thatpotential adverse effects
onhuman health would belesser orgreater forhormone residues than might bethecaseforpesticide
residues.
Question 11:
How dothepotential adverse effects onhuman health from residues ofcarbadox (used inswine
production) differ from thepotential adverse effects arising from residues ofthesixhormones
inquestion when used forgrowth-promotion inaccordance with good animal husbandry practice
and/or good veterinary practice? Question 30:Further toquestion 11and26,would youconsider
thatthepotential adverse effects onhuman health and/ oranimal health from residues ofcarbadox,
monensin, olaquindox, avoparcin, benzylpenicillin, carazolol, ivermectin andorganophosphorous
compoundsarecomparabletothepotentialadverseeffectsarisingfromresiduesofthesixhormones
atissue when used forgrowth-promotion inaccordance with good animal husbandry practiceWT/DS26/R/USA
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and/ orgood veterinary practice? Areanyoftheabove mentioned substances carcinogenic? If
anyoneofthese substances oracombination thereof isadministered totheanimal, would there
always bearesidue ofthatsubstance inthemeat ofthatanimal, even ifitissosmall thatitcannot
bedetected?
6.128 Dr.André indicated thatcarbadox proved tobeagenotoxic compound, andconsequently no
ADI value hadbeen proposed byJECFA (seealsoresponse toquestion 10). Olaquindox wasknown
tobecarcinogenic. Dr.André wasnotfamiliar with theothers.
6.129 Dr.Arnold noted thataslong asthe"good practices" were observed, there wasnorelevant
difference. Ifthelengthy withdrawal time wasnotobserved inthecase ofcarbadox, potentially
genotoxic carcinogenic residues oftheparent drug andanother carcinogenic metabolite were likely
tobepresent inmeat oftreated animals. Inthecase ofthehormones, only thefrequent consumption
ofinjection sites orimplants would potentially cause effects onhuman health.
6.130 Olaquindox wasgenotoxic inanumber oftests. However theparent drug wasextensively
metabolised andwasnotpresent asaresidue if"good practices" were applied. Ivermectin wasextremely
potent against parasites, butitwassafely used inhumans forthetreatment ofe.g."river blindness"
atmuch higher than residue levels. Carazolol wasahazardous substance forhumans with chronic
bronchitiswhichwasasubstantialpartofthegeneralpopulation.Inaddition,carazololwasadministered
tothetarget animals byinjection. Benzylpenicillin wasabsolutely harmless forthegeneral population
butcould provoke allergic reactions insome sensitized people even atthelevel oftheMRL. Avoparcin
wasnotregistered asfeed additive ontheAmerican continent; itsuseintheEUhadrecently been
withdrawn. Strict adherence totheidentified "good practices" wasanabsolute requirement forthe
useofsome ofthese substances. Nearly allofthese substances leftdetectable residues inmeat oftreated
animals under conditions of"good practice intheuseofveterinary drugs". Attheoral hearing
Dr.Arnold added thatthere isacommercially available alternative forcarbadox mainly oxytetracycline.
6.131 Dr.Lucier indicated thatitwasdifficult toaccurately compare risks from carbadox residues
torisks from residues ofgrowth-promoting substances (seealsoresponse toquestion 10). However,
heexpressed concerns about carbadox residues andthattherisks from these residues were likely greater
than therisks associated with theuseofgrowth promoters.
6.132 Dr.McLean replied thatcarbadox anditsmetabolite desoxycarbadox were notpermitted in
meat, because thelatter compound wascarcinogenic. Inthecase ofcarbadox, awithholding period
wassettoachieve thesituation where there were nodetectable residues infood. Thethree naturally
occurring hormones were normally found inanimals andhumans. Thedata supporting theuseof
trenbolone andzeranol wasextensive, with toxicological end-points related totheir hormonal effects.
Finite residues were permitted fortrenbolone andzeranol. Inthiswayanyriskofadverse effects was
managed through theMRL andsafety toconsumers wasassured.
6.133 Dr.McLeanfurthernotedthatolaquindoxwasconsideredtobegenotoxicandnotoxicitystudies
were available onitsmetabolites, therefore JECFA was unable todetermine anADI orMRL.
Benzylpenicillin waswidely used asanantimicrobial agent inanimals andhumans. Allergenic potential
wasthemajor toxic effect anditwasrecommended thatthetotal intake bekept below 30micrograms
perdayforahuman. Benzylpenicillin showed nocarcinogenic potential. While carazolol showed
nogenotoxic orcarcinogenic potential, itwasapotent beta-adrenoceptor blocking agent. MRLs had
been established forpigtissues. However, ifcarazolol wasused inpigstoprevent stress during transport
toslaughter, there wasconcern thatresidues atthesiteofinjection could result inconsumers receiving
apharmacologically active dose ofthedrug. Thetoxicity andresidue data base forivermectin and
related compounds wasextensive andthedrug wasalsoused inhumans. Thecompound didnotshow
genotoxic orcarcinogenic potential andanADI andanMRL hadbeen established.WT/DS26/R/USA
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6.134 Theorganophosphoruscompounds(OP)weredescribedbyDr.McLeanaspowerfulneurotoxins,
andmost oftheuntoward effects were related tothedirect exposure ofoperators andothers. There
wasanewsyndrome oforganophosphate -induced delayed polyneuropathy -which wasofconcern
when there wasacute exposure.194TheOPhadbeen associated with carcinogenicity andthere were
reports ofacute poisoning associated with theconsumption oftreated food. Very lowlevels ofthe
parent compound and/or metabolites might remain, although they could notbedetected bysensitive
analytical techniques. Dr.McLean didnotcomment onmonensin oravoparcin because ofthelimited
amount ofregistration data available which wasinpublic domain.
6.135 Dr.Ritter observed thatcarbadox wasreviewed bytheJECFA in1990. Initsreview, the
JECFA considered datafrom short-term andlong-term carcinogenicity, mutagenicity andreproduction
studies with carbadox, anddatafrom mutagenicity andlong term studies ofitsmetabolites. JECFA
noted thatresults from several long term feeding studies inratsdemonstrated dose-related increases
inboth benign andmalignant tumours atdoses above 1.0mg/kg BW/day. Positive findings were also
noted in14ofthe15mutagenicity studies reported. JECFA concluded thatcarbadox appeared tobe
both genotoxic andcarcinogenic. Results from additional studies carried outwith quinoxaline- -
carboxylic acid, animportant metabolite ofcarbadox, indicated thatthere were noeffects onincidence
oftumours, even atdoses of100mg/kg BW/day. Inview ofthecarcinogenic andgenotoxic nature
ofcarbadox anddesoxycarbadox, ametabolite ofcarbadox, JECFA wasnotabletoestablish anADI.
Notwithstanding, theJECFA recommended MRLs of0.03 mg/kg inliver and0.005 mg/kg inmuscle
ofpigs, based onandexpressed asquinoxaline- -carboxylic acid.
6.136 Theestablishment ofanADI andrecommendation ofanMRL reflected scientific confidence
intheexpressed residue levels being essentially devoid ofrisktohumans exposed todietary residues
onalifetime basis. Therefore, neither carbadox northegrowth promoting hormones should pose
potential adverse human health effects asaresult ofexposure todietary residues atorbelow theMRLs
specifiedbyJECFA.Notwithstanding,itwasnoteworthythatcarbadoxandatleastoneofitsmetabolites
wasbothcarcinogenicandmutagenic,whilethehormoneswerenotconsideredcarcinogenicormutagenic
atbiologically relevant doses. Inaddition, reliable residue monitoring andriskestimation ofcarbadox
residues wassomewhat complicated bythepresence ofbound residues, while residues ofthehormones
either fellwithin normal physiological range orcould bereliably andeasily measured.
Question 12:
Areresidues ofthesixhormones inquestion found inmilk ormilk products? Ifyes, how do
thelevels ofthese residues compare tothose found inmeat from animals towhich hormones have
notbeen administered? How dotheresidue levels inmilk compare tothose found inmeat from
animals which have been administered these hormones forgrowth-promoting purposes? For
therapeutic orzootechnical purposes?
6.137 Dr.André replied thatresidues ofhormones ingeneral arefound inmilk. However, the
comparison with meat levels wasnotrelevant. Moreover, hormones were notsupposed tobeused
forgrowth promotion purposes inlactating cows, only inculled cows. Forspecific therapeutic or
zootechnical purposes, only individual animals were allowed tobetreated with hormones. Inthiscase,
themilk wasnottobedelivered forhuman consumption, aswasthecase formany other drugs.
6.138 Dr.Arnoldnotedthatafterinjectionofapprovedproducts(nature-identicalmolecules)permitted
foruseintheEUtolactating cows, residues would befound inmilk. Depending ontheproduct it
could take several milkings before theresidue levels would have returned tophysiological values.
194M.Lotti, Toxicology 21,(1992) p.465.WT/DS26/R/USA
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Residues found inmilk could behigher, equal orlower, depending onwhich tissues were compared
anddepending onmany other factors (dose, route, age, sex, withdrawal time etc.)
6.139 Dr.Lucier indicated thatifresidues ofthehormones inquestion existed inthehuman body,
then residues would alsobepresent inhuman milk.
6.140 Dr.McLean replied thathormones arelipid soluble andtherefore pass intothefatportion
ofmilk. More polar metabolites would alsopass intomilk, butitmust bestressed thatthehormones
should notbeused forgrowth promotion inlactating animals. When thevarious hormones were used
fortherapeutic orzootechnical purposes, thedoses were much higher, therefore thelevels inthetissues
were higher. Ithadtobeexpected thatthelevels inmilk would alsobehigher.
6.141 Dr.Ritter observed thatgrowth promoting hormones were generally only permitted foruse
inbeefcattle andvealcalves, andnotinlactating dairy cattle. Foxcroft andHess (1986) reported that,
atleast inthecase ofthenatural hormones, theresidue levels oftheadministered compound orit
metabolites inanimal products were insignificant incomparison tothelevels ofthesame steroids to
which human subjects might normally beexposed. This could occur either (i)asaconsequence of
theendogenous production rateofsexsteroids inhuman subjects or(ii)asaconsequence ofthesteroids
inmeat and/or milk products derived from untreated animals.
Question 13:
What factors andprocedures should scientists consider inestablishing anappropriate assessment
ofthepotential adverse effects onhuman health from theuseofthehormones inquestion?
6.142 Dr.André responded thatanappropriate assessment ofthepotential adverse effects onhuman
health stemming from theuseofthehormones indispute "should bemore rigorous than common
veterinary drugs because oftheduration oftheir useandthevery limited, ifany, health benefits to
thetarget species".195Scientists should consider alldataavailable atthepresent time indealing with
theadverseeffectsofeachcompound(seeresponsetoquestion8),theirmetabolitesandtheirmechanisms
ofaction, including their action atthelevel ofexposure. Species-specific metabolite patterns should
becompared, using (asfaraspossible) acombination ofinvivo andinvitro experiments. Studies
should include long-term feeding trials toaddress lifetime exposure. Allstudies should beperformed
with combinations ofthehormones indispute prior toregistration, toobtain valuable data. Theeffects
ofthetreatment onthekinetics ofother common drugs hadtobeassayed. Epidemiological studies
inhumans concerning cancer incidence andother hormone related diseases hadtobeinitiated.
6.143 Dr.Arnold indicated thefollowing should beconsidered: pharmacokinetic data including
metabolism intestanimals andtarget animals, where available inhumans; data(preferably quantitative
data) from adequately designed toxicity studies insuitable animal species, including information on
genotoxicity/carcinogenicity, andnohormonal effect levels; target animal safety studies; efficacy
trials; epidemiological studies andother relevant observations inhumans; kinetic residue studies;
natural occurrence andhuman exposure from allsources, including endogenous production ofthesame
orsimilarly acting substances; experience from thehistory ofuseinhuman andveterinary medicine
(ifapplicable); andknown orproposed conditions ofuse. Amarketing authorization should only
begiven tostrictly formulated products (nottotheactive substances). Conditions ofuseshould be
fixed inabinding manner intheapproval process.
6.144 Dr.Lucier replied thatthere were several factors thatshould besystematically studied or
evaluated ifinformation wasnotavailable forassessment ofrisks from thehormones inquestion.
195Bridges, 1995 ECScientific Conference Proceedings, p.250.WT/DS26/R/USA
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Ofspecial concern were potential risks forcancer andnon-cancer effects (reproduction, development,
cardiovascular disease, etc.). Additionally, information oneffects insensitive sub-population should
beconsidered. Sensitivity could beconferred bygenetic predisposition (presence orabsence ofcancer
susceptibility genes), age(fetus, children ortheaged), gender, existing disease status, nutrition, and
co-exposure toother chemicals. These factors needed tobeconsidered, although itwasunlikely that
information onthem would ever becomplete foranygiven substance.
6.145 Dr.McLeannotedthatthetestingprotocolsusedincountriessuchastheUnitedStates,Canada,
theUnited Kingdom, Australia andbyJECFA were adequate toassess theeffects oftheuseofhormones
onhuman health. Inaddition, there wasaneed forresidue monitoring programmes toensure that
residues inmeat were lessthan anyMRL which hadbeen established.
6.146 Dr.Ritter observed thatscientists considered awide array oftoxicological endpoints andrisk
assessment procedures inestimating potential adverse effects onhuman health from residues ofall
chemicals, including anabolic hormones, other veterinary drugs andpesticides. Theissue offactors
andprocedures which were appropriate totheassessment ofthepotential adverse effects onhuman
health included toxicity studies which established thefollowing: which organs and/or systems were
most vulnerable tothetoxic effects andunder what exposure conditions; thenature ofanydamage
and/or disease produced, andthedose response relationship; thetime course fortheonset andany
progression oftheadverse effect; themechanism responsible fortheadverse effect; therelevance
oftheadverse effect observed inexperimental animals tohumans; thepotential impact ofbiological
mechanisms which ledtotheadverse effect butwhich, byvirtue ofthedose utilized, were notrelevant
totheassessment ofthebiological effect inhumans (this wasparticularly important forthehormones
inquestion which were only associated with adverse effects atdoses which were notconsidered to
beofrelevance totheassessment ofhuman health effects arising from food residues); whether itwas
appropriate toconsider theadverse effects observed asafunction ofathreshold mechanism, orrather
ifagenotoxic mechanism wasmore likely andhence athreshold mechanism would beaninappropriate
riskmodel.
6.147 Inaddition, Dr.Ritter noted thatitmight alsoberelevant toestablish ifthenature oftheresidue
wasdistinguishable from normal endogenous levels -thiswasparticularly relevant fortheuseofthe
natural gonadal hormones which resulted inresidue levels typically intherange ofuntreated animals;
whether appropriate andreliable methods existed fortheestimation andmonitoring ofresidues ofthe
hormonesfollowingtheiruseasgrowthpromotingsubstances;andknowledgeoftheuncertaintyinherent
inthehazard andriskassessment paradigm.
Question 14:
What arethepotential hazards, ifany, tohuman oranimal health oftheuseoflarge quantities,
ordoses higher than those recommended, ofanyofthesixhormones indispute? And from the
administration ofthese hormones contrary togood animal husbandry practice and/or veterinary
practice? Can youthink ofanyincentives ordisincentives forfarmers tousequantities larger
than those specified inthelabel ofthemanufacturers ortoadminister these hormones contrary
togood animal husbandry practice and/or veterinary practice? Areyouaware ofanyevidence
ofsuch usebyfarmers?
6.148 Dr.André indicated that ahigher dosage, another route ofadministration than those
recommended fordelivery (other location forimplants, injectable solutions ofhormones, etc.), shorter
withdrawal periods, etc., inshort, anydisrespect ofgood animal husbandry and/or good veterinary
practices,mightinducehigherlevelsofresiduesorchangesinmetabolitepatterns.Thefirstconsequence
would probably beamodification inanimal behaviour and/or health. Itwasreasonable tothink that
ahigher residue content inmeat would enhance theriskofhazards tohuman health.WT/DS26/R/USA
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6.149 Theanabolic effect ofthehormones inquestion wasproportional tothedosage, withamaximum
effect.Farmerstriedtoobtainlargereffectsthroughadministrationofmoreimplantsthanrecommended,
although itwasnotevident thatadouble dose, even atonetime, gave abetter response. Insome cases,
aparenteral administration (e.g. intramuscular injection) produced amore rapid effect than implants,
andfarmers tried bythismean toobtain faster effects. Disincentives forfarmers touselarger quantities
would beadecrease ofthebenefit/cost ratio, butimplants were usually cheap. Incountries where
they were inuseforgrowth promotion purposes, penalties duetohigher residue levels detected in
meat products compared totheMRLs might alsohave dissuasive effects onfarmers. When fiveout
ofthesixhormones indispute were allowed inFrance, theexperience wasthatfarmers tried togive
asecond dose later. They didnotrespect thewithdrawal period andthey injected another dose athalf
waythrough thetheoretical withdrawal period. Clearly they sawbenefit todothisbecause theeffect
waslonger atthetime. Dr.André further reported thatduring thefour tofiveyears when these
hormones were allowed asgrowth promotants inFrance, themisuse ofother hormones continued and
theblack market wasalsopresent.
6.150 Dr.Arnold noted thatthere were considerable safety margins built intotheestablished MRLs
forthesyntheticresidues.Aslongas"goodpractices"wereobserved,thecalculatedtheoreticalmaximum
daily intakes ofresidues would range around 5percent oftheADI forboth zeranol andtrenbolone
acetate. Ithadbeen shown thattheimplantation ofapproximately fivetimes therecommended dose
ofzeranol would have almost noeffect onmaximum residue levels inthemuscle andliver ofsteers
slaughtered only fivedays after implantation. When atotal dose more than 100-times higher than the
recommended dose wasintravenously administered as6split doses over three days tosteers andthe
animals were slaughtered onthethird dayafter thelastdose, consumption ofthemeat ofthese animals
would stillnothave caused anabove-ADI intake ofresidues ofzeranol.196Thestudies available to
the32nd and34th JECFA showed thatresidues oftrenbolone were highest ifheifers were implanted
shortly (15days) before slaughter. With respect tothecalculated theoretical maximum intakes, there
wasnodifference whether thisimplant wasthefirst orthesecond which theanimal hadreceived.
From these data, itseemed unlikely thateven thefrequent useofhigher doses, orrepeat doses or
slaughtering theanimals atearlier thanrecommended times after implantation, could result inresidue
intakes inexcess oftheADI bytheconsumer. Forthethree nature-identical hormones, thesafety
margins (theoretical residue intakes compared with endogenous production rates ofthemost sensitive
sub-population) were much higher than forthesynthetic substances.
6.151 Dr.Arnold hadnoinformation with regard tomelengestrol acetate, norregarding incentives
ordisincentives forfarmers tousecombinations orillegal "cocktails" ofthese hormones. Although
these pellets andanother devices hadbeen developed togive optimum results when thedose was
respected,thisdidnotnecessarilypreventsomefarmersusingmoreimplants.Butthisdidnotnecessarily
cause higher residue levels inthecarcass. Ontheother side, itwasclear thatiftwice theamount was
injected directly, alllevels increased inplasma andintissues, notnecessarily inalinear way, but
significantly. That wasthedifference between aslow release device (like earimplant) andadirect
injection. Ontheother hand, thelong term release ofhigh doses might influence thepattern ofhormone
excretion intheanimal 'sbody andthiswastheintention ofusing such compounds.
6.152 Dr.Lucier indicated thatanyincrease inthemagnitude ofexposure would likely increase any
potential risks, buthedidnotconsider himself qualified toanswer therestofthisquestion.
6.153 Dr.McLean responded thatthehormones inquestion, with theexception ofMGA, were not
wellabsorbed when administered orally. Grossly excessive doses might have aneffect onconsumers
ofmeat, butthese effects were likely tobemild andtransient andcould pass without being noticed.
Thedose prescribed under "good practice" wassufficient toexert acommercially satisfactory response,
196Food andNutrition Paper 41,pp.44-45, FAO (1988).WT/DS26/R/USA
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andthere wasnoadvantage inexceeding thisdose. Thedose suggested bythesponsor gave theoptimum
response andtherefore, within limits, there wasnoneed orbenefit inadministering more than was
suggested. Theregulatory authorities alsoexamined theeffects ofoverdosing during theregistration
process. Most regulatory authorities, including JECFA, required thatdata forresidues setting did
take intoaccount dose rates thatwere inexcess ofwhat wasnormally used (generally atleast twice
andsometimes more) sothattheeffect ofoverdosing orvariations inuptake could beseen. Incountries
where theuseofthese compounds waspermitted, there were good educational campaigns forfarmers
astothecorrect useandthereasons whytheprescribed dose should notbeexceeded, andthepenalties
thatexisted ifonedid. Theresults from residues surveys showed that, byandlarge, there wasno
exceeding oftheMRL. InAustralia, trenbolone andzeranol hadbeen targeted inresidue surveys
very specifically looking forviolations, andtoallintents andpurposes violations didnotoccur. Even
ifthere wasmisuse, andthatwasdifficult toprove, there were stillnoresidues thatexceeded theMRL.
Asimilar situation existed withthenaturally occurring hormones, where itwasnotpossible todetermine
whether ornotaviolation hadoccurred because thelevels thatwere found inthecarcass fallwithin
thenormal range.
6.154 Dr.McLean observed, however, thatincountries where theusewasnotcontrolled andthere
wasnofarmer education campaign andwhere itwasdifficult toapply apenalty, then theMRL was
significantly exceeded. One oftheimportant factors oflegalizing these compounds wastoconduct
aneducation campaign andtoputinplace monitoring procedures toensure thattheMRL isnotexceeded.
What wasimportant with themaximum residue limit istounderstand thatitwasalegal limit andnot
ahealth limit. Inother words, exceeding oftheMRL didnotrepresent ahazard tohealth butrather
alimit atwhich theauthorities took action. However, toexceed theMRL would notbeconsidered
tobegood practice.
6.155 Dr.Ritter noted thatitwasvery difficult, ifnotimpossible, toestimate potential hazards which
might beassociated withtheadministration ofthehormones contrary togood practice, asthemagnitude
ofthepotential hazard would berelated tothenature, extent, frequency andmagnitude ofthe
inappropriate administration. Ithadbeen reported thatinthecaseoftheanabolic hormones andusing
commerciallyavailableimplants,repetitiveimplantationhadonlylittleinfluenceontheresidueprofile.197
Similarly, fullandhalf-dosages ledtosimilar hormone levels inedible tissues which, inthecase of
theendogenous hormones, were within thephysiological range. Further, unlawful andimproper use
ofoestradiol might result inresidue levels some 300-fold inexcess ofestablished tolerance limits, and
yetitwasvirtually impossible tovisualize anyhazard tohumans ingesting meat from animals treated
with zeranol.198Similarly, when steer calves were implanted with zeranol inaccordance with
recommended procedures, themargin ofsafety forconsumption ofedible products wasgreater than
25,000 and150,000 forliver andmuscle, respectively. While thiswork didnotspecifically address
theissue ofpotential abuse, thelarge margins ofsafety postulated bytheauthors suggested thateven
under limited circumstances ofabuse, itwasunlikely thatconsumers would beexposed tounacceptable
risks.199Incountries where useofthese hormones, thesixhormones inparticular, hadbeen permitted
foravery extended period oftime, most notably Canada andtheUnited States, monitoring and
complianceprogrammeswhichhadbeenconductedformanyyearsconsistentlydemonstratedthatresidue
levels were entirely within recommended limits andthatinstances ofviolative residues, thatwasresidues
which would indicate abuses taking place, hadalmost never been reported. Itseemed thatatleast in
those jurisdictions where usewaslawful, thepracticality ofabuse hadnever become areality. There
were fewandisolated examples ofviolative residues inthose countries where usehadbeen permitted.
197Hoffman andEvers (1986).
198Truhaut etal.(1985).
199Sundlof andStickland (1986).WT/DS26/R/USA
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Question 15:
What aretheconsequences interms ofpotential hazards tohuman oranimal health from the
useoflegally marketed combinations, ifthey exist, orillegal "cocktails" ofthesixhormones in
dispute foranimal growth promotion? Have legally marketed combinations been subject tothe
same testing regime aseach oftheir individual components? Isthere anyevidence ofsynergistic
effects ofcombinations ofhormones? Can youthink ofanyincentives ordisincentives forfarmers
tousecombinations orillegal "cocktails" ofthese hormones?
6.156 Dr.André replied thatspecific consequences stemming from theuseoflegally marketed
combinations were notknown. Ifthey existed potential hazards could beduetosynergistic and/or
additive effects oftheresidues. This answer wasalsovalid forillegal "cocktails" ofthesixhormones
inwhich more thantwocomponents could bepresent. However there wasanother important potential
hazard from thesystematic useofthese combinations: their usecould result inmodifications ofkinetic
parameters ofother drugs. Forexample, trenbolone andtestosterone were shown todramatically
decrease theelimination rateofsulfamethazine, trimethoprim andantipyrine ingoats, with opposite
experimental results inrats. Asaconsequence, residue levels could behigher than theMRLs at
slaughter, even when legal withdrawal periods were respected.200Recently, theincrease ofthelevel
ofbetaagonist residues inliver owing toconcomitant oestradiol treatment hadbeen demonstrated in
calves.201
6.157 Dr.André wasaware ofonly onecombination (TBA +oestradiol) having been assayed by
theJECFA inthecontext ofresidue determination insteers. Noother combinations hadbeen tested
whereas individual components hadbeen tested fortoxicological effects. Evidence ofsynergistic effects
ofcombinations ofhormones existed andwere well studied mechanisms. Forexample, concerning
endocrinological therapy inhumans, combinations ofoestrogen andprogestin hormones were used;
oestrogensinducedthesynthesisofspecificreceptorsforprogestins,whichcouldthenexerttheirspecific
action. Legally marketed combinations hadbeen developed onthebasis ofsynergistic effects oftheir
components ongrowth promotion.
6.158 Incentives forfarmers tousecombinations (legally marketed) orillegal "cocktails" ofthese
hormones were frequently reported byofficial control bodies, since farmers tended tothink thatthe
more hormones used, thebetter theanabolic effect. Moreover, interactions between these hormones
andother endogenous biochemical parameters (e.g. corticoids, IGF, etc.) were ofgreat importance
forhuman health andcould bedocumented.
6.159 Dr.Arnold noted thatfixed combinations were registered intheform ofstrictly formulated
veterinary medicinal products andwere different from illegal mixtures forwhich theterm "cocktail"
hadbeen coined inEurope. Fixed combinations were notonly used forgrowth promotion butalso
forthepurposes permitted intheEuropean Union. These combinations were approved andregistered
bythecompetent authorities under therespective rules governing veterinary medicinal products. The
applicant hadtojustify thecombination andhadtodemonstrate thequality, efficacy, target animal
safetyandconsumersafetyoftheseproductsbeforetheycouldbemarketed.Forthesetypesofregistered
products, there wasnoevidence ofahazard tohuman health.
6.160 Dr.Arnold reported thatthepharmacodynamic andtoxic effects ofpractically allpossible
combinations ofoestrogens, progestins andandrogens hadbeen studied inwhole animals, organs, tissue
andcellcultures, andother invitro systems under agreat variety ofconditions. There wasample
evidence ofboth synergistic andantagonistic effects. Such effects physiologically played important
200Van Miert (1988).
201Kuiper, 1995 ECScientific Conference proceedings, p.377.WT/DS26/R/USA
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rolesinendocrinologyandmetabolism.Thecurrentunderstandingofthesephenomenaclearlyindicated
thatconcerns over human health hazards arising from combinations ofminute amounts ofresidues
inmeat were notjustified.
6.161 Theflourishinggreymarketinotherveterinarymedicineswithin,forexample,Germanyshowed
thatfarmers tried bypassing official distribution channels when purchasing otherwise licensed high
quality products, mainly inorder tosave costs andprevent having topaytheveterinarian. Towhat
extent "good practices" intheusewere otherwise followed remained subject tospeculation. Itseemed,
however, thatnotallrules were violated atonetime. Thesituation with prohibited substances (e.g.
hormones, chloramphenicol) andwith abused substances (e.g., clenbuterol) wascompletely different.
There wasclearly ablack-market where the"dirty products" prevailed. Theavailability ofreasonably
priced legal alternative products could beanincentive formany farmers tolegalise their practices.
Whether thiswould eliminate illegal cocktails now thattheblack-market hasbeen well established,
remained entirely speculative.
6.162 Dr.Lucier indicated thatthere wasadefinite research need inarea ofsynergistic and/or
antagonistic responses tocombinations ofendogenous orexogenous hormones. Based oncurrent
knowledge, itwaslikely thatinteractions existed butitwasimpossible tosaywith anydegree of
confidenceforagivencombinationwhethertheinteractionwouldbesynergistic,additiveorantagonistic.
There waslimited evidence tosuggest thatsynergistic responses were occurring although therelevance
ofthese findings tohuman risks hadnotbeen shown. Dr.Lucier noted thatthesame combinations
ofhormones, atcertain levels, could have both some adverse health effects andsome positive ones.
6.163 Dr.McLean replied thatthelegally marketed combinations hadbeen examined byregulatory
authorities toensure thatresidues didnotexceed levels seen innormal animals ortheprescribed MRL.
There were synergistic growth promoting effects seenintreated animals. Illegal "cocktails" were mostly
found incountries where theuseofhormones wasprohibited, resulting intheestablishment ofanillegal
market. They were notnormally used where thefullrange ofdrugs wasavailable because there was
noadvantage intheuseofillegal drugs, andregistered products were usually cheaper andofconsistent
quality.
6.164 Dr.Ritter noted thatwhen growth promoting hormones were used ascombinations, thisuse
didnotalterexistingMRLs whichhadbeeneitherrecommendedinternationallyorestablishedbynational
regulatory authorities, andhence theuseofhormone combinations wasnotlikely tohave anydirect
adverse consequences interms ofhuman health. Inthecase of"illegal" cocktails, itwasimpossible
tospeculate onthepotential foradverse effects ineither humans oranimals, asthispotential would
beafunction ofthenature ofthecocktail, thespecies ofuse,thedose, frequency andduration ofuse,
andarange ofother factors which could notbeassumed.
6.165 Ingeneral, safety (toxicology) evaluations ofdrugs, pesticides andother food contaminants
were carried outonsingle compounds only, rather than ascombinations. There were several reasons
forthisapproach which included prior pharmacological andbiochemical knowledge thattoxicity
associated with combinations wasnotlikely toproduce effects greater than thesumoftheindividual
components. Onamore practical level, itwasdifficult tocontemplate thebroad range ofpossible
combinations which would bethesubject oftesting. Finally, asdifferent commercial interests might
beinvolved intheproduction andsaleofvarious growth promoting hormones, proprietary interests
would make itunlikely thatcombinations could beevaluated toxicologically. Insome cases, theefficacy
ofhormone combinations hadbeen evaluated. Inthecaseofcombinations oftrenbolone with zeranol
oroestradiol, forexample, itwasfound that(i)thecombinations were equivalent inyoung bulls and
steers, (ii)anabolics containing oestradiol were more effective invealcalves, and(iii)thecompositionWT/DS26/R/USA
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andquality ofthemeat wasnotmodified bytheuseofcombinations when compared tosingle use.202
Aswithanydrug orunlawful drug combination, farmers sometimes were under theincorrect impression
thatcombinations which hadnotbeen evaluated might provide significantly enhanced efficacy over
those which hadbeen approved foruse. Such improper useofillegal cocktails could affect withdrawal
times andresidue limits andmight, insome jurisdictions, result incompliance andenforcement as
disincentives totheunlawful useofnon-approved cocktails. Dr.Ritter noted thatitmust also be
recognized thatthequest forever improved yield could leadsome producers totheuseofunapproved
drug combinations.
6.166 Dr.Randell indicated thatthemonographs which were prepared byJECFA atthe32nd session
clearly indicated thattrials were done onmixed implants aswellasonsingle substance implants. JECFA
hadconsidered such mixtures asoestradiol together with testosterone, oestradiol together with
progesterone,oestradiolbenzoatetogetherwithtestosteronepropionateandalsooestradiolwithtrenbolone
acetate under theoestradiol evaluations. These were known toJECFA atthetime, andthepharma-
kcenetics ofthese substances asthey were gradually metabolized andexcreted bytheanimals were
studied bytheexperts atthattime. Moreover, theinformation which wasavailable toJECFA included
carcinogenicity studies forallofthesubstances concerned.
Question 16:
Which substances inaddition tothehormone compounds atissue arepresent inthecommercially
available products marketed foranimal growth promotion? Arethere anypotential adverse effects
onhuman oranimal health? Question 33: Further toquestion 16,arethere other substances
inhuman implants potentially dangerous tohuman health?
6.167 Dr.André noted thatifthequestion referred totheexcipient ortopotential sub-products of
synthesis, these data, asproperty ofmanufacturers, remained confidential. Concerning thesimultaneous
useofother drugs marketed forgrowth promotion (e.g. antibiotics), their residue levels could be
modified bytheuseofthehormones (seeresponse toquestion 15),sothatapotential adverse effect
onhuman health could appear.
6.168 Dr.Arnold indicated thatother growth promoters (antibacterials) were used under thefeed
additives legislation oftheEuropean Communities (e.g., flavomycin, virginiamycin, zincbacitracin,
salinomycin, monensin, lasalocid). Thereview process wascentralised. There were noknown potential
adverse effects onhuman oranimal health ifthese additives areproperly used. Theuseofglycopeptide
avoparcin was recently withdrawn asaprecautionary measure because ofsome suspicion that
glycopeptid-resistance selected bytheuseinanimal production could betransferred tohuman-pathogenic
enterococci.
6.169 Dr.Lucier responded thatthere aremany known cases ofthepresence ofoestrogenic substances
arising from plant products, pesticides andindustrial contaminants. Itwaslikely thattheoestrogenic
potency ofthese substances, taken together, exceeded thatfrom meat residues ofthesixhormones
inquestion.
6.170 Dr.McLean stated thatthere were anumber ofnon-active components used intheimplants
toensure thatthedrug wasdelivered over thelifeoftheimplant. These included acarrier forthe
drug andaninert matrix which made uptheimplant. Theformulation wasapproved bytheregulatory
authorities ineach country. The components were often used inhuman andother animal drug
formulations andtheir safety hadbeen established.
202Bouffault andWillemart (1983).WT/DS26/R/USA
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6.171 Dr.Ritterrepliedthatthecompositionofcommerciallyavailableproductswasgenerallyregarded
asproprietary information. Consequently, hehadnodirect knowledge oftheidentity ofthesubstances
other than thehormones which might bepresent incommercially available hormone preparations.
Question 17:
What aretheimplications forhuman oranimal health ofresidues from misplaced implants or
improper administration, i.e.when administered differently than indicated inthelabel ofthe
manufacturer, ofanyofthesixhormones indispute ?
6.172 Dr.André indicated thattheconsumption ofmeat (orofanymeat-containing food preparation)
containing amisplaced implant could beahazard forhuman health, inparticular forchildren, fetuses,
pregnant women orimmunodeficient people. Misadministration ofanyofthesixhormones indispute
could change thekinetics ofelimination ofthese hormones andinduce asubsequent higher level of
residues. This could become arealhealth hazard ifthere wassystematical misuse.
6.173 Dr.Arnoldobservedthattheremightbeaconcernonlywheremisplacement(growthpromotion)
orimproper administration (therapy, zootechnical treatment) leadtoconsumption ofawhole implant
orinjection site. Otherwise, residues remaining inthecarcass oftherespective animal would have
noeffects, even ifthey were higher than would beexpected if"good practices" hadbeen applied.
Theworst case assumption wasthatawhole fresh implant containing oestradiol oranester ofthis
hormone isconsumed, because theimplanted dose washigher than thedoses injected fortheother
purposes andorally active oestradiol-doses were lower thantherequired doses oftheother hormones.
Ifthisentire dose wasingested atonce, only transient effects onhormonal feedback mechanisms would
beexpected. Clear hormonal effects would occur ifanentire injection sitewasprocessed, e.g., into
ameat containing product andthesame person would eatthewhole product individed portions over
acouple ofdays.
6.174 Dr.Lucierstatedthatimproperormisplacedimplantscouldverywellincreaseresidues,thereby
increasing thepotential riskofthehormones inquestion. Preventive strategies formisuse needed to
involve veterinary supervision, educational programmes, monitoring andstiffpenalties forabuse.
6.175 Dr.McLean replied thattheimplants would likely bedetected ifthey were eaten because the
matrix could notbechewed. Ifswallowed, they would notbedigested butwould pass through the
human gastrointestinal tract largely unchanged. Theimplications ofmisplaced implants may notbe
ofgreat concern because they were often placed under theskin andremoved atslaughter orduring
processing. Inorder tofacilitate correct andeasy administration, applicators were generally available
from thepharmaceutical companies. Oneofthefeatures ofinjections subcutaneously intheearwas
thatthere wasnomassive reaction atthesite. Itwasspecifically designed, andalltheresidue studies
were carried out,with theimplant injected intheear. Theaimofinjecting itthere wastogetprolonged
andslow release atlowlevels over aperiod oftime. Itwasspecifically designed tobethatway.
Moreover, theinjections were usually implanted intheearbecause itwasvery easy topalpate apellet
oranimplant under theskin oftheearwhich wasasecond way ofidentifying treated animals.
6.176 Dr.Ritter responded thatthegrowth promoting hormones were generally administered asfeed
additives orasimplants. Intheevent that implants were implanted atsites other than those
recommended, itwaspossible thatthese sites contain unacceptably high residue levels ifutilized as
asource ofhuman food. Theselection oftheearasasiteofimplantation rather than other sites was
because itwasatissue which normally didnotenter thefood chain anditmade identification ofthe
source ofthematerial very easy. Injection siteresidues, which could bemuch higher than normal
tissue residue levels, were thus extremely unlikely toenter thefood supply. Theextent towhich
acceptable residue levels might beexceeded would depend ontheexact siteofimplantation andtheWT/DS26/R/USA
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withdrawal period involved. Theimplication forhuman health would inturnberelated tothese two
variables.
6.177 Dr.Ritter indicated thatillegal injection ofoestradiol preparation could produce injection site
residues which largely exceeded tolerances. Inthecase offeed additives, improper usemight imply
useofapproved drugs innon-approved species, improper dose, improper combinations, improper
duration ofuseandimproper withdrawal periods. However, theprovision ofhuman safety wasassured
through theestablishment ofmaximum residue levels, levels considered tobesafeifconsumed by
humans inthedietforanentire lifespan. Intheevent thatanyoftheimproper useconditions noted
above occurred, andtotheextent thatsuch improper usewould impact onfinal residue levels, human
safety wasassured through appropriate monitoring ofthefood supply forcompliance with approved
MRLs.
Question 18:
What aretheeffects ongrowth promotion oftheuseoffemale hormones onmale animals and
vice-versa? Arethere anypotential adverse effects onhuman oranimal health from such use?
6.178 Dr.André saidthattheeffects ofhormones ongrowth promotion wassex-dependent. The
useofmale hormones associated with female hormones (ratio 10:1) inheifers hadthebestanabolic
effect without sexual behaviour problems andvice-versa. Concerning thehuman health, thelevel of
residues hadtobetaken intoaccount, whatever thegender ofthemeat producing animals. Concerning
animal health, theuseofoestrogenic compounds inmale animals wasshown toresult insquamous
metaplasia, hyperplasia ofthecollecting ducts andfibromuscular hypertrophy intheprostate andbulbo-
urethral gland, fibromuscular hypertrophy andhypoplasia oftheepithelium intheseminal vesicles
andepididymis andimpaired testicular development. Infemale animals, oestrogen treatment resulted
insquamousmetaplasiaandfibromuscularhypertrophyintheBartholin'sgland,hyperplasiaandsecretory
activity inthevagina andcervix, andimpaired follicular developments intheovaries. Thelatter could
alsobeobserved when females were treated with androgens, impaired follicular developments inthe
ovaries sometimes resulted incystic ovaries.
6.179 Dr.Arnold indicated thatsupplemental oestrogens incastrated males increased growth rate,
presumably through anincrease ofendogenous levels ofgrowth hormone, improved feed efficiency
andreduced aggressive behaviour. Testosterone wasmainly used toslow down therelease rateof
oestradiol because blood levels required foranabolic effects could notbereached with implants. No
adverse effects were known onhumans. Theuseinanimals ofhormonally active growth promoters
might have behavioural side-effects inindividual animals.
6.180 Dr.Lucier observed thatsome effects, possibly adverse, could occur intheanimals receiving
thegrowth-promoted substances. These effects could include feminization ofmale animals and
masculinization offemale animals based onboth molecular andbiological endpoints. These effects
should notoccur inpeople eating meat containing residues attheMRL ofthehormones inquestion.
6.181 Dr.McLean commented thatthere wasawide range ofcombinations anddoses available for
arange oftypes ofcattle. Thecombinations were designed toensure maximum dose response inthe
target animals. These combinations hadbeen subjected tostudies toensure thattheresidue levels did
notexceed prescribed values.
6.182 Dr.Ritter indicated hehadnoexpertise inthisarea.WT/DS26/R/USA
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Question 19:
What differences exist between thetherapeutic orzootechnical useofhormones permitted bythe
ECand theuseofhormones forgrowth promotion purposes, aspermitted intheUSand in
accordance with good animal husbandry practice and/or good veterinary practice, interms of
administered quantities, residue levels andpotential adverse effects onhuman oranimal health?
Docommon therapeutic orzootechnical uses ofthehormones inquestion intheECinvolve large
scale (ie.,whole herd) orrepetitive treatments?
6.183 Dr.André observed thattheuseofthehormones fortherapeutic orzootechnical purposes
andforgrowth promotion purposes wasnotcomparable formany reasons. Thenumber ofanimals
treated wasdifferent, asfortherapeutic usevery fewanimals were treated. Forzootechnical purposes,
thenumber washigher butremained limited. There were nosystematic, repetitive treatments. For
growth promotion purposes, thenumber ofanimals seemed tobelarge.
6.184 Inaddition, Dr.André stressed thatthefuture oftheanimals treated either fortherapeutic or
zootechnical purposes orforgrowth promotion purposes wasvery different. Inthefirstcasetheanimals
usually remained onthefarm formonths oryears after treatment andtheproblem ofresidues was
notofconcern. Theonly comparable situation wasforoestradiol benzoate, forwhich, incase of
unsuccessful treatment inacow, awithdrawal period oftwomonths hadtobeobserved. Inthesecond
case, theanimals were slaughtered weeks ormonths after thetreatment. Furthermore, thedelivery
conditionsdiffered.IntheEC,thetherapeuticuseofthesehormoneswasparticularlyregulated.Finally,
Dr.André noted thatnone ofthese therapeutic/zootechnical uses would change thelevel ofresidues
ofhormones inmeat onlarge scale asoccurred from growth promotion use. Noscientist hadsaid
thatitwasabadthing tousethese hormones fortherapeutical use; their useonalarge scale forgrowth
promotion wasnotthesame thing.
6.185 Dr.Arnold replied thatthetotal dose contained inanimplant ofoestradiol-17 wasmuch
higher thanthedose injected fortherapeutic purposes because theimplant contained thequantity needed
over along time (e.g., 200days). Onadaily basis, however, thedose injected wasmuch higher,
andtherefore, tissue residues (excluding theinjection site)after treatment were much higher ifcompared
with theresidues measured atanytime after implantation. Norepresentative datawere available for
progesterone ortestosterone that would permit comparisons. With theexception ofoestrus
synchronisation, individual identified animals were treated.
6.186 Dr.Lucier indicated thatitwaspossible thatextraordinarily lowresidues (likely non-detectable)
ofthehormones could bepresent atslaughter iftheanimals hadreceived thehormones fortherapeutic
use(seeresponse toquestion 3).
6.187 Dr.McLean replied thatthetherapeutic useofhormones generally required theadministration
ofalarger dose, which inturnresulted ingreater levels ofresidues. Thepersistence ofthese residues
depended onthedose, formulation andsiteofadministration. Individual animals orgroups ofanimals
were often treated atonetime, butrarely thewhole herd. Treatments mayberepeated. Treated animals
should beidentified sothattheywere notslaughtered forhuman food until asuitable withdrawal period
hadelapsed. Itwasoften necessary towithhold milk. When hormones were used forgrowth promotion,
theimplants slowly released theactive ingredients andthere wasnever ahigh peak ofhormones in
thetissues. Inthecase oftherapeutic use, there often wasasignificant peak.
6.188 Dr.Ritter responded thattheprimary difference between thetherapeutic and/or zootechnical
uses ofthehormones permitted bytheCommunity when compared togrowth promoting uses related
primarily tothefrequency ofuse,dose, andthepotential number ofanimals tobetreated. Inallcases,
therapeutic and/or zootechnical uses would generally involve lower doses atlessfrequent intervals
infewer animals, and, inthecase oftheCommunity, wasrestricted toadministration byalicensedWT/DS26/R/USA
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veterinarian. Notwithstanding, atleast inthecase ofthenatural hormones, theapproach adopted by
theCommunity fortherapeutic/zootechnical usesprovided forresidue levels which fellwithin therange
oflevels normally found inuntreated animals. While thebasis foruseofthese hormones forgrowth
promotion purposes wasfundamentally different, theresulting residues appeared, nevertheless, toalso
fallwell within thenormal physiological range.
Question 20:
Doyouconsider that theconditions imposed bytheECforthetherapeutic orzootechnical use
ofthese hormones can achieve itsaimofavoiding anypotential adverse effects onhuman health
resulting from residues inmeat from animals treated forsuch purposes?
6.189 Dr.André commented thatthisquestion wasnotrelated toascientific expertise, andasa
consequence,hecouldonlygiveapersonalopinion.Whenusedfortherapeuticorzootechnicalpurposes,
these hormones were used by(orunder thecontrol of)veterinarians. This guaranteed thatthey were
used according totheindications forwhich theyhadbeen registered (i.e.dosage, route ofadministration,
withdrawal period). Moreover these hormones were used either onindividual animals orinwelldefined
herds, usually inorder tosynchronize oestrus. Inthiscase, theanimals were reproducting animals,
they hadahigh value andwould beslaughtered only several years after thetreatment. Theproblem
ofresidues wasnotofconcern forthese animals. Itcould notbecompared with theuseofthese
hormones forgrowth promotion. When used fortherapeutic purposes, these drugs were needed to
restore health andthebenefit/cost ratio wasvery high. When used forzootechnical purposes, the
consequence foragreat majority oftheanimals wastobecome pregnant and, exceptionally, tobe
slaughtered.
6.190 Dr.Arnold indicated thattheproducts which could beused were reviewed according tothe
criteria established fortheapproval process ofveterinary medicinal products, including established
withdrawal times. Iftheapproved conditions ofusewere observed, anypotential adverse effects on
human health resulting from residues inanimals treated forsuch purposes could beavoided.
6.191 Dr.LucierrepliedthattheECmeasuresforthetherapeuticorzootechnicaluseofthesehormones
could notguarantee "zero risk", although thepotential risks were likely lower than risks from their
useasgrowth promoter.
6.192 Dr.McLean responded thathewas notfully familiar with practices intheCommunity.
However, studies onantibiotic residues have shown thattheinvolvement ofveterinarians inthecontrol
andprescribing ofantibiotics onfarms didnotalways guarantee thatresidues would becontrolled.
Thesame situation would probably exist with hormones.
6.193 Dr.Ritter recalled thattheCommunity allowed theadministration ofoestradiol, testosterone
andprogesterone toanimals fortherapeutic andzootechnical purposes only under conditions which
restricted administration toaveterinarian, required registration oftreatments andasufficient withdrawal
period. Given thenature ofconditions imposed forsuch use,itwasunlikely thatresidues resulting
from exogenous application ofthegonadol hormones would bepresent asresidues. Notwithstanding,
growth promotion uses ofthenatural hormones similarly would notresult inresidue levels inexcess
ofthose expected inuntreated animals.
Question 21:
Isthere adifference interms ofpotential adverse effects onhuman oranimal health between
residues ofthese hormones administered asfeedadditives, compared toresidues ofthese hormones
which areimplanted orinjected?WT/DS26/R/USA
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6.194 Dr.André indicated thatasfarasheknew, themetabolism ofthese hormones administered
asfeed additives hadnotbeen studied. Toproduce residues meant thatthey were absorbed, andthat
they areefficient andmetabolised. Nevertheless, their useasfeed additives could induce ariskfor
people potentially incontact with these hormones (factories, farmers, children etc.), andariskfor
theenvironment.
6.195 Dr.Arnold responded thatmelengestrol acetate wasonly used asafeed additive. Zeranol
andtrenbolone acetate were used asimplants only. Oestradiol-17 ,progesterone andtestosterone were
administered bydifferent routes including injection andimplantation. Itwas difficult tomake
comparisonsaboutpotentialeffectsduetomeansofadministrationbecausethereweretoomanyvariables
intheequation (chemical nature, dose, route, formulation, target species). Ifalluseswere carried out
incompliance with theestablished conditions ofuse,theremaining residues could beregarded assafe.
Thesafety margins might vary from onecondition totheother andtheconsequences ofnon-compliance
might alsobedifferent.
6.196 Dr.Lucier commented thattheresidues would bethesame interms ofchemical structure,
although theresidue levels could bedifferent quantitatively.
6.197 Dr.McLean observed thatthecontrol oftheadministration ofhormones toanimals asfeed
additives wasbyremoving them from feedatagiven time. Inpractice, because ofcarry-over infeed
mixing plants andresidues instorage silos andfeeding stalls, there wasnotasharply defined cut-off
point. Inthecaseofantibiotics, itwasoften necessary touseadedicated mixing plant toavoid carry-
over from treated tountreated feed. Thedose absorbed could alsovary depending onfood intake and
absorption from thegut. There wasalsotheproblem ofaccurately mixing small amounts ofpotent
active ingredients through thefeed. Injection wasmore accurate andreliable, andonbalance themethod
ofchoice.
6.198 Dr.Ritter replied thatpotential adverse effects onhuman health invariably related toresidues
which exceeded acceptable limits. Proper useofgrowth promoting hormones aseither implants or
feedadditives might result inresidues which, ifused inaccordance with recommended andapproved
practice, should notexceed acceptable levels regardless ofthemethod ormeans ofadministration.
Henoted thatimproperly placed implants could result infailure toproperly identify implantation sites
atslaughter andcould thereby result inexcessively highresidues inthose tissues which would otherwise
beidentified andremoved. Properly located implants, when implanted inaccordance with approved
practice, should notresult inunacceptable residues andhence there should belittle impact onpotential
adverse human health effects regardless ofthemethod orroute ofadministration.
Question 22:
With respect toZeranol, Trenbolone andMGA, what arecurrently thetechnological limits of
detection and/or quantitation ofresidues? Ie.,what isthelowest level ofresidue which canbe
detected?
6.199 Dr.Andréobservedthatthesehormoneswereconsideredasclassicalbannedcompounds(within
theEC). They were controlled with methods whose limits ofdetection (LD) were equal orbetter than
2ppb. However, most methods inuseforscreening purposes ofthese hormones were immunological
ones. Their reallimits ofdetection were usually lower than 0.5ppb. Mass spectrometric methods
allowed confirmation ofresults atthislevel. Furthermore, using techniques with high performance
output such ashighresolution mass spectrometry orMS-MS, thelevel of10ppt.orsocould bereached.
6.200 Dr.Arnold replied thatthetechnological limitations would allow thequantification ofcertain
residues incertain tissues atconcentrations below 1ng/kg. This could not,however, beachieved in
routine monitoring. Moreover, thelimits ofdetection ofcurrent routinely applied methods may varyWT/DS26/R/USA
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from country tocountry (within certain limits). Only few methods had been internationally
collaboratively studied according tointernationally harmonised protocols. Only fewmethods were
fully validated inaccordance with thecriteria firstdefined bytheCodex Alimentarius andlater adopted
bytheEEC inDirective 85/592.
6.201 Dr.McLean explained thatthere were twobasic types ofassays used. Screening methods
were used todetect drugs formetabolites atthelevel ofinterest. These hadhigh sample throughput
andaimed toavoid false negative results. Confirmatory methods provided unequivocal identification
ofthedrug and/or metabolites atthelevel ofinterest. Thecostofanalysis wasconsiderably greater
than forscreening methods. These methods were constantly being reappraised.
6.202 Dr.Ritter responded thatmethodology forMGA hadbeen reported203with alimit ofdetection
of5ppb. andalimit ofquantitation of10ppb., both infat,thetarget tissue forthisresidue. LC
methodology forthetrenbolone acetate hadbeen reported204with alimit ofdetection of2ppbinmuscle
andliver for -trenbolone, andalimit ofquantitation of2ppbinmuscle and4ppbinliver for
trenbolone inliver andkidney. GC/MS methodology forzeranol hadbeen reported byCovey etal
(1988) with alimit ofdetection of0.1ppb. andalimit ofquantitation of0.2ppb. inliver ormuscle.
The Joint FAO/WHO Expert Committee onFood Additives (WHO, 1988) reported that
radioimmunoassays could detect freeandconjugated and -trenbolone atlevels of75ng/kg intissues.
Radioimmunoassays were generally regarded asappropriate screening methods only, while conventional
analyticalproceduressuchasgaschromatography/liquidchromatography/massspectrometryaregenerally
regarded assuitable forconfirmatory analysis.
Question 23:
Can youdescribe how theECbanisenforced intheEC'sinternal market both formally and
inpractice? How istheECbanenforced attheEC'sborders both formally andinpractice? How
aretheconditions linked totheexceptions totheban (i.e. administration ofhormones for
therapeutic andzootechnical purposes) enforced, both formally andinpractice, intheEC'sinternal
market andattheEC'sborders? What istheformal content andpractical effect oftheEC'scontrol
programme which ensures thatimported products donotreceive treatment more favourable than
domestic products?
6.203 Dr.André noted thatthisquestion wasnotrelated toscientific expertise. From apersonal
point ofview hebelieved thattheimportant number ofworkshops, international congresses (e.g.
Congress onAnabolizing Agents inGent :1992, 1993, 1994; Euroresidue Iin1990, Euroresidue II
in1993, Euroresidue IIIin1996), laboratory networks system, European research programmes, as
well asthedevelopment ofQuality Assurance Systems inEurope hadtobeconsidered.
6.204 Dr.Arnold replied thatsince itsentry intoforce Council Directive 86/469/EEC hadessentially
harmonised thecontrol ofresidues inliveanimals andmeat. Starting from 1987, ECmember States
presented anannual updated national residue control planforapproval bytheCommission. Theresults
ofresidue controls were alsoreported totheCommission. TheDirective wasvery clear andrelatively
inflexible inwhat concerned theidentification ofthesubstances andthespecies ofanimals tobechecked
andthenumber ofsamples tobetaken. Unfortunately, amajor partoftheanalytical capacities ofthe
laboratories oftheECmember States hadtobeused regularly tomonitor substances which didnot
necessarily present therealproblem areas (e.g., thestilbene oestrogens).
203Anderson andFesser (1996).
204Shih-Hsien Hsuetal.(1988).WT/DS26/R/USA
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6.205 Thescientific concept behind sampling, however, wasnotclear andwassubject todifferent
interpretations. Itseemingly mixed elements ofastatistically based monitoring system with other
concepts. Thereporting format wasonly semi-quantitative with respect tothereported residue contents
ofpositive samples. Inconsequence, theresults could notbeused tocompare thesituation intheEC
member States or,forexample, toconduct acrude assessment ofexposure ofEuropean consumers
toresidues ofanabolic substances.
6.206 Dr.Arnold further explained thatanetwork ofreference laboratories hadrecently been set
upwith anoutstanding European reference laboratory ontop. However, themoderate financial
contribution totheEuropean reference laboratories from theCommission wasgiven only onanannual
basis, leading todifficulties inensuring experienced permanent staff inthese institutes. Thequality
ofthenational reference laboratories co-ordinating theactivities oftheroutine laboratories carrying
outthedaily work could notbejudged. Although itwas notknown how many routine laboratories
were accredited nationally, itwas obvious thatsystems ofquality management hadnotyetbeen
established everywhere intheCommunity.
6.207 Theendogenous production intheanimals ofoestradiol-17 ,testosterone andprogesterone
causes difficulties inthecontrol oftheir use. MRLs have notbeen set,andcannot beset,forthe
therapeutic andzootechnical uses, because thedistribution ofthethree natural hormones inthethree
categories ofanimals (untreated animals, animals illegally treated forgrowth promotion, andanimals
legally treated forthepermitted purposes) largely overlap. Because withdrawal times could notbe
enforced onabroad scale anddistribution chains were insufficiently controlled, only limited attempts
-requiring alotofman-power andother resources -could bemade toenforce compliance. Ifthere
wasasuspicion, ofcourse, theanimal involved canbetraced back andtheproducer questioned about,
e.g., theprescription ofthedrug, theveterinarian involved etc. Themain difficulty wastoidentify
suspect animals inorder tostartfurther investigations andmeasures. Only thediscovery ofaninjection
siteoranimplant containing illegal substances could provide proof ofatreatment. Decision limits
forthelevels ofoestradiol-17 hadprovisionally been established inorder toidentify suspect animals.
6.208 Enforcement wasdifficult ifpeople didnotwant tocomply withthelegal rules -which otherwise
would perfectly guarantee consumer protection. Itappeared thatillegal anabolic hormones were readily
available. Theexpectation ofextra profits wasanincentive forthecontinued theuseofthese substances
includingbetaagonists,notonlyforfarmersbutalsoforparticipantsintheillegalnetworkofdistribution.
6.209 Dr.ArnoldrecalledthattherequirementsofDirective86/469/EEC alsoappliedtothirdcountries
exporting liveanimals andmeat totheCommunity. Missions were regularly senttothese countries
toevaluate their systems ofresidue monitoring andsurveillance. Attheborder, enforcement relied
entirely onthediscriminating power ofanalytical methods. This wasnotpossible inthecaseofmeat
from animals treated fortherapeutic orzootechnical purposes, because thismeat wasnotdifferent from
meat obtained from animals never treated ortreated with thesame substances forgrowth promotion.
Although domestically produced andimported products were formally treated equally, thepossibility
ofdetectingillegalpracticesofgrowthpromotion(illegalreferringtonon-compliancewithEUlegislation,
nottouses which were alsoprohibited inthecountry oforigin) wasprobably significantly greater for
domestically produced meat because ofthepossibilities toinspect production plants with ahistory of
non-compliance, totake samples from liveanimals, etc.
6.210 Dr.Ritter indicated thathehadnoexpertise with regard toECenforcement, inrelation to
adiscussion about thenumber ofanimals checked peryear intheEuropean Communities andother
countries. However, henoted thatthenumber ofsamples taken could bemisleading. Theintent of
anymonitoring programme wasthedevelopment ofaprogramme thathadthestatistical confidence
necessary todetect violations totheextent thatthecompound wasused, toidentify residue levels which
were outofcompliance. Therelevant question waswhether themonitoring programme wasstatistically
confident andabletodetect compliance. Most monitoring programmes were intended todetect a5perWT/DS26/R/USA
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centviolation rate95percentofthetime. Thenumber ofsamples thatwere required todothatvaried
from country tocountry andfrom commodity tocommodity because itwasafunction oftheusepractices
forthesubstances involved.
Question 24:
What analytical methods, orother technical means, ofresidue detection exist tocontrol theuse
ofthesixhormones indispute forgrowth promotion purposes inaccordance with good animal
husbandry practice and/or good veterinary practice. What means exist tocontrol theuseby
farmers ofthesixhormones indispute forgrowth promotion purposes inaccordance with good
animal husbandry practice and/or good veterinary practice? What aretheir respective cost
implications?
6.211 Dr.André replied thatsince these hormones were prohibited within Europe, their control was
included innational plans, theaimofwhich wastosurvey their misuse. Analytical methods were
available both forscreening purposes andconfirmatory purposes. Forscreening purposes, several
methods hadbeen developed. Research wasalsocarried outtoprove theexogenous origin ofnatural
hormones, when detected inurine samples, based onmethods used inhuman fordoping control. For
confirmatory purposes, different methods existed, with most oftheavailable methods being based on
GC-MS detection andidentification. These techniques hadbeen developed formatrices likeurine,
fat,tissue, faeces orinjection sites.
6.212 Dr.Arnold noted thattheanalytical community oftheEuropean Communities wasvery active.
Toprovide theappropriate methodology todetect illegal practices ofgrowth promotion -particularly
thepotentially hazardous practices involving black market drugs -wasagreat challenge forthescientists
working inboth academic andofficial laboratories. Asaresult, alarge number ofprobably valid -
although notalways validated -methods relying ondifferent principles wasavailable. Furthermore,
intheEuropean Communities itwaspossible toinspect farms andsample liveanimals, with the
consequence offines orlegal prosecution incase ofviolations.
6.213 Dr.McLean indicated thatdescriptions ofanalytical methods usewere published bythe
regulatory authorities ofmany countries. Control ofusebyfarmers wasdone through legislation which
detailed restrictions onthesale, possession anduseofthevarious hormonal preparations. Thecost
ofthese measures varied from country tocountry andthecostofanalysis depends onthedrug inquestion
andwhether screening orconfirmatory methods were employed.
6.214 Dr.Ritter responded thattheresidue detection methodology utilized tocontrol theuseofthe
sixgrowthpromotinghormonesgenerallyfollowedthoseproceduresdescribedinquestion22.Detection
methodologies forveterinary drug residues were largely described bytwomain types ofanalysis
(Blanchflower, 1995). Screening methods generally hadahigh sample throughout, permitting analysis
oflarge numbers ofsamples inarelatively short period oftime, andatminimal cost. They generally
hadalowprobability offalse negatives andcould detect, butnotaccurately quantify, potentially positive
samples. Screening methods forthegrowth promoters were typically represented bytheradio
immunoassays.Incontrast,confirmatorymethodswereusedtoconfirmunequivocally,andtoquantitate,
thepresence ofadrug residue. They were characterized byrelatively lowthroughput andhigh cost
both interms ofequipment andsupplies, andalowprobability offalse positives.
6.215 Control ofveterinary drugs used infood production byfarmers wasgenerally achieved by
national authorities through imposition ofregulations requiring thatdrugs ofthistype bedispensed
only onthewritten authority ofaproperly qualified veterinarian andincompliance with relevant use
information established byappropriate national regulatory authorities. Compliance wasfurther assured
through rigorous monitoring and, where appropriate, through enforcement activity. Cost implications
generally related totheincreased cost associated with therequirement that such drugs only beWT/DS26/R/USA
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administered under theauthority ofaproperly qualified veterinarian. Costs would alsobeproportional
totherigour with which amonitoring andcompliance programme wasdesigned andimplemented.
Question 25:
What analytical methods, orother technical means, exist tocontrol theuseofthesixhormones
indispute according totheconditions setoutintheproposal oftheECCommission in1984
(COM(84)295 final) andwhat aretheir respective cost implications?
6.216 Dr.AndrénotedthatthistwelveyearoldproposalhadbeenrejectedbytheEuropeanParliament.
6.217 Dr.Arnold recalled thatthisproposal hadenvisaged thecontrolled useofthethree natural
hormones forgrowth promotion andproposed re-visiting theprohibitions oftrenbolone acetate and
zeranol after ascientific evaluation ofthese substances. Inanalytical terms, theenforcement problems
would have been similar tothose oftoday because residues inmeat remaining after the(proposed)
legalised uses forgrowth promotion would nothave differed significantly from residues found after
illegal usesinmost cases. Thepharmaceutical industry could have applied formarketing authorization
ofstrictly formulated products, which would have been evaluated andapproved under theveterinary
medicines directives. There would have been competition between high-quality, efficacious andsafe
products andproducts oftheblack-market. However, Dr.Arnold could notjudge whether thiswould
have limited thegrowth ofthenow existing black market, thereby reducing thecosts ofenforcement.
6.218 Dr.McLean noted thatthemethods proposed inthatDirective were similar tothemethods
nowused inother countries. However, thepassage oftime hadpermitted better analytical technology
andtechniques andincreased automation, often resulting inincreased laboratory throughput atdecreased
cost persample. Farmers were also much better educated about theneed toavoid residues which
exceeded theMRL. TheCommunity would now beinamuch better position toscreen forresidues
inmeat products than itwasin1984.
Question 26:
Arethere other products (including veterinary drugs) commonly used intheproduction ofmeat
andanimal products which have comparable potential adverse effects onhuman oranimal health
asthesixhormones inquestion? Ifso,what analytical methods, orother technical means, of
residue detection exist tocontrol their useinaccordance with good animal husbandry practice
and/or good veterinary practices. What technical means exist tocontrol their usebyfarmers
inaccordance with good animal husbandry practice and/or good veterinary practice? How do
thecostimplications forcontrolling theuseofthese other products differ from those used tocontrol
theuseofthesixhormones inquestion?
6.219 Dr.André responded thattotheextent acompound wasactive asadrug, itcould exert toxic
effects. Drugs were submitted toregulation andwere registered forprecise indications, under precise
conditions, including data onMRLs anddefinition ofwithdrawal periods (see also response to
question 10). Several methods forcontrol were available. Drugs could only beregistered foruse
when amethod designed forresidue control existed. Networks oflaboratories andcontrol plans were
setupfordrugs according tothesame scheme astheoneused forillegal drugs.
6.220 Forproducts forwhich particular conditions ofusewere indicated, thecontrol wasusually
inthehands ofpractitioners. New recording systems were under development (see response to
question 1).Controls byofficial bodies (e.g. Veterinary Inspection Services) were effective insome
countries. Inother countries regulations were changing inorder toapply ECDirective 96/23, allowing
formore controls tobeperformed onthefarm itself. This wasparticularly trueforthehormones in
dispute, asforother banned compounds (chloramphenicol, rhonidazol, etc.).WT/DS26/R/USA
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6.221 Dr.Arnold indicated thatarather large number ofactive principles (probably afewhundred)
were used asveterinary drugs inoneorallcountries involved inthisdispute. Some substances were
soactive thattheir therapeutic doses were aslowasmicrograms perkilogramme ofbody weight of
theanimal. Other substances were used inboth veterinary medicine andincrop protection, with some
transfer ofresidues from animal feed viaproducts ofanimal origin tothehuman consumer.
Considerableprogresshadbeenmadetoregulatethesesubstancesonthebasisof"tolerances"forresidues
orMRLs. Many oftheunderlying ADIs hadbeen proposed byJECFA. More JECFA evaluations
hadindirectly been appreciated andfound acceptance (e.g., intheMRL setting process within the
European Union) asonewould conclude from thelistofsubstances which hadformally passed the
elaboration process oftheCodex Alimentarius Commission.
6.222 IntheEuropean Communities, nonew active principle hadbeen placed onthemarket since
1992 unless aCommunity MRL hadbeen established under theprovisions ofregulation 2377/90.
Newanimaldrugapplicationshadtobeaccompaniedbyaproposedregulatorymethodsuitabletoenforce
tolerances/MRLs. Themain performance characteristics (accuracy, precision, limit ofdetection, limit
ofquantification,specificity)andtheruggedness,practicability,applicability,susceptibilitytointerference
ofthemethods were reviewed together with theother documentation relating tothequality, safety
andefficacy ofthedrug.
6.223 The review oftheoldsubstances, however, was stillongoing. The evaluation oftheold
substances hadalsobegun inthepesticides sector. Themajority ofthese substances hadalong history
ofuses. Although theyhadnever been evaluated according tocontemporary safety requirements, they
could probably beregarded assafeinthelight oftheexperience with these substances. Should new
evidence indicate thathuman health hazards could arise from thepermitted uses ofthese substances,
thecompetent authorities would withdraw therespective products until theproblems were clarified.
There were some examples, however, where highly efficacious substances with along history ofuse
hadtobewithdrawn from themarket ofveterinary drugs forfood animals when more contemporary
standards were applied intheir re-evaluation (e.g., chloramphenicol, nitrofuranes, nitroimidazoles).
6.224 When oldsubstances were reviewed intheCommunity toestablish MRLs, theCommittee for
Veterinary Medicinal Products always considered theavailable analytical methodology. AnMRL was
notproposed ifnoanalytical method wasavailable. The review ofthemethods andinternational
harmonisation ofmethods suitable fortheenforcement ofCodex Standards wasconducted bythe
FAO/WHO Codex Committee forResidues ofVeterinary Drugs inFoods.
6.225 Themore difficult problem wastomonitor somany substances inallfoods ofanimal origin.
Thechemicalpropertiesofthesesubstancesweresodifferentthatitwasimpossibletoincludeallresidues
inafewmulti-residue methods. There were substances requiring special equipment fortheir detection.
Itwasnotpractically feasible tomonitor allpotential residues inallfood commodities every year.
Themost reasonable approach wastocategorise compounds according topotential hazard andthelikely
exposure ofconsumers totheresidues. Some compounds required inclusion inresidue-monitoring
programmes every year; others might beselected forlonger cycles. Forafewcompounds, perhaps
nomonitoring wasnecessary. Directive 86/469/EEC covered veterinary drug residues inmeat. Starting
in1988, ECmember States andcountries exporting meat totheCommunity hadtosubmit residue
control plans alsoforthese substances. ECmember States hadmore flexibility toadapt theplans to
theactual needs (e.g., areas ofrisk). Thenewlegislation adopted in1996 enlarged thescope tocover
other foods thanmeat. Anincreasing number ofscreening tests were nowavailable which were based,
e.g.onmicrobiological inhibition orimmunochemistry. These methods were suitable toidentify suspect
"positives" (samples violating MRLs) andexhibit alowrateof"false-negative" results. However,
animportant aspect ofthecontrol of"good practices" wasthecontrol ofdistribution; distribution
ofveterinary drugs wasnotharmonised intheCommunity.WT/DS26/R/USA
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6.226 Dr.McLean replied thatmany products used inanimal production hadthepotential tocause
adverse effects onhuman oranimal health. Thehazard wasidentified andmanaged through theuse
of"good practice", theapplication ofanMRL, residue surveys andlegal sanctions forviolations (see
alsoresponses toquestions 11,22and24). There wasnosignificant difference inthecostimplications
forcontrolling theuseofother veterinary drugs when compared with thehormones.
6.227 Dr.Ritterrepliedthattherewereavarietyofproducts,includingveterinarydrugsandpesticides,
which were utilized intheproduction ofmeat andanimal products. Establishment ofMRLs forother
production aids, including both veterinary drugs andpesticides, implied thatthese chemicals could
also beused essentially free ofpotential adverse effects inthehuman population, provided that
appropriate conditions hadbeen followed intheuseoftheproduction aid. Simply stated, once MRLs
hadbeen established, adherence tointernationally accepted maximum limits implied thatallproducts
carry similar risks, ormore appropriately stated, asimilar lackofrisk, asdidthehormones atissue
inthisdispute.
6.228 Control ofusewasgenerally accommodated through appropriate control ofsale(restriction
ofusegenerally associated with “prescription ”drugs) andrigorous monitoring andcompliance
programmes, further supported byappropriate enforcement action. Inregard toanalytical methodology
available fordetection andmonitoring purposes, bothscreening andconfirmatory methods were utilized.
Availability ofappropriate andreliable analytical methodology forother production aids, such as
veterinary drugs, varied somewhat with thespecific agent andmight range from difficulties ofbound
residues withcarbadox andnitrofuran, tothespecial andimportant considerations which were necessary
when assessing themicrobiological riskduetoresidues ofantimicrobial drugs infood.
Question 27:
What potential adverse effects onhuman health arise from theoccasional consumption ofmeat
containing residues inexcess oftheCodex MRL inthecase ofZeranol andTrenbolone?
6.229 Dr.André noted thatallofthepreviously described potential adverse effects onhuman health
may arise. With regard totheir hormonal effects, thelower thefrequency andthelevel ofresidue,
thesmaller istheriskofhealth hazards. With regard totheir potential carcinogenic effects, thefrequency
ofconsumption andthelevel ofresidue wasnotofconcern.
6.230 Dr.Arnold indicated thatiftheresidues were duetotreatment oftheanimals andnotto
contamination ofthemeat andthemeat wasnotaninjection sitesothatthecauses oftheviolation
oftheMRLs were limited tobiological variability oftheanimals response totreatment; hedidnot
know ofanyspecific adverse effect onhuman health which could arise from theoccasional consumption
ofsuch meat because ofnon-compliance with theestablished conditions ofuse,andifthiswasasingle,
rare oroccasional event. Any such event would, however, require regulatory action and-where
indicated -legal prosecution inorder toguarantee theintegrity ofthemargin ofsafety which hadbeen
found toberequired toensure themedium andlong-term protection oftheconsumers ’health.
6.231 Dr.Lucier responded thatitwould benecessary toconduct formal riskassessments toestimate
exposure-effect relationships following different levels ofexposure forthesixhormones. Inorder
tobeuseful, endpoints ofconcern needed tobedetermined (i.e., cancer, hormonal effects, etc.) and
dose response models applied and/or developed thatmade useofallavailable andrelevant information.
Itmight benecessary toconduct additional research toputtheriskassessments onacredible scientific
foundation. Itshould benoted, however, thatonewould never have allthescientific information needed
toremove alluncertainty inriskassessments. Priorities hadtobeagreed upon regarding which pieces
ofinformation aremost critical. Itwasalsoimportant tonote thatselection oftheriskassessment.
model could influence theresult. Threshold orlinear models might give different results although
if"mimicking ofhormone effects" were determinative, then theissue ofthreshold wasnotrelevantWT/DS26/R/USA
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since physiological levels ofthenatural hormone exceeded anythreshold thatmight exist (seeresponse
toquestion 8).Thesynthetic hormones could exert toxic effects notonly related totheir hormone
action butalsobecause ofother structural/functional properties.
6.232 Dr.McLean observed thattheoccasional consumption ofmeat containing levels inexcess
oftheCodex MRL wasofnohealth concern. Thedegree ofexcess would need tobedefined, but
thetype oftoxic response andNOEL would give some guidance. Itmust beremembered thatthe
NOEL wasderived taking intoaccount studies involving administration foralifetime, with thelowest
effect level based onaresponse which could beasminor asabody weight change.
6.233 Dr.Ritter replied thatinview ofseveral assumptions inherent inthemodels utilized todevelop
MRLs, which overestimated safety (NOEL, application ofsafety factors, assumption thatMRL was
always present andthatdietary exposure toresidues would occur daily foranentire lifespan), itis
most unlikely thatsignificant potential adverse effects onhuman health would arise from theoccasional
consumption ofmeat containing residues inexcess oftheCodex MRL forzeranol andtrenbolone.
Itwas, however, important tonotethatthepotential foradverse effects increased asafunction ofboth
thefrequency andexposure level regarding consumption ofresidues inmeat inexcess oftheCodex
MRL forboth trenbolone andzeranol.
Question 28:
How would youassess thefeasibility oflabelling with respect tomeat products from animals treated
with growth-promoting hormones? How does thiscompare with thefeasibility oflabelling in
other food safety contexts?
6.234 Dr.André indicated thatthisquestion wasnotrelated toscientific expertise, buttopolitical
decision. However, such labelling would beconsistent with thetraceability concept which wasrapidly
being improved inEuropean countries (ready tobeimplemented inFrance). However, thisimplied
thatanadequate control toqualify products would have tobeestablished; inthecase ofresidues of
hormones, detection inmeat didnotstand intheway offeasible labelling.
6.235 Dr.Arnold saidthatinhisview itwasnotfeasible tocontrol labelling, since itcould not
beconfirmed through laboratory testing whether ananimal hadeverbeen treated withgrowth promoters.
Iftheobjective wastoverify thatsomething hadnever been used, e.g., apesticide, thesituation was
similar. Thechances todetect food-irradiation, ontheother hand, were much better. Also, ifgenetically
modified organisms were involved infood production, itwassometimes possible toroutinely detect
thealtered genetic material. There seemed tobenogenerally valid answer tothisquestion.
6.236 Dr.Lucier replied thatmeat products could belabelled toindicate thattheywere from animals
treated with growth-promoting agents sothatconsumers would have asmuch information aspossible
todecide which meat tobuy. Ifgrowth-promoting agents produced meat with lower fatcontent, a
consumer with cardiovascular disease might specifically want tobuymeat from agrowth-promoted
animal.
6.237 Dr.McLean observed thattheeffective labelling oftreated meat would necessitate identification
oftheanimal atbirth, thefarm, sale, slaughter, processing andontotheconsumer. Thelogistics
oftheprocess would becomplex andmake itdifficult toregulate, especially inthecase ofprocessed
meat products. Thecostwould faroutweigh anyperceived benefit. Thesame problem arose with
thefeasibility oflabelling other foods, butbecause ofthecomplex process formeat processing, itwas
much more expensive. Inhisview, themoney spent onsuch alabelling process would bebetter spent
onensuring microbiological safety offood. Food contaminated with microbes andtheir toxins disabled
orkilled many people every year. Theadverse effects ofveterinary drugs oragricultural chemicals
were rarely reported, butreports offood poisoning from microbial contamination were very common.WT/DS26/R/USA
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Forexample, arecent outbreak ofEscherichia colifoodpoisoning inScotland made 400people seriously
illandkilled 17,while asimilar outbreak inJapan infected 10,000 andkilled 11(Coghlan, A(1997)
New Scientist 153(2066)7).
6.238 Dr.Ritter replied thattheissue oflabelling offood products wasthesubject ofintense public
debate, towhich there wasnoeasy resolution. Theissue with regard tothefeasibility oflabelling
inthecase ofthehormones could therefore relate asmuch totheobjective ofsuch astrategy asto
itsfeasibility.Useofthenaturalgonadalhormonesinmeatproductionproducedresiduelevelsconsistent
with those which might typically beexpected inmeat products from untreated animals. Other than
tofulfil a"right toknow" objective, labelling inthiscase would notappear toprovide information
ofvalue toconsumers inahealth related context. Particularly noteworthy wasthatasresidue levels
arecomparable inboth treated anduntreated animals, andasexogenous hormones are,inanycase,
quantitatively andqualitatively indistinguishable from those endogenously present, itwasunlikely that
alabelling programme could beimplemented atanypractical level.
6.239 Inthecase ofthesynthetic hormones utilized ingrowth promotion, atleast twohadbeen
subjected tointernational review andsaferesidue levels hadbeen recommended. Thepurpose ofsuch
alabelling programme would beunclear given thataninternational review hadalready concluded that
residues atorbelow proposed levels didnotconstitute arisktoconsumers, even under theexaggerated
calculations andassumptions utilized inthedevelopment ofMRLs.
Questions 29-34 were follow-up questions tothose presented earlier, andtheresponses tothefollow-
upquestions have been included with theresponses totheearlier questions.
Question 35:
With reference totherapeutic andzootechnical useofthenatural hormones atissue, doyoubelieve
that theECDirective 88/299 „ensures that there arenoresidues leftinmeat forhuman
consumption “(para 19,ECfirst submission intheCanadian complaint)?
6.240 Dr.Arnoldrepliedthatnosuchinsurancecanbegiven.Themeatwouldalwayscontainresidues
even ifwithdrawal times were observed. Theconcept of"noresidue" hadbeen largely abandoned some
20years agowhen itbecame evident that"noresidue" wasafunction ofthelimit ofdetection ofthe
analytical method. Allpermitted substances, including thehormones, were regulated onthebasis of
an"acceptable residue" intheEEC. The"noresidue" concept stillapplied tobanned substances, but
thiswastrivial. Inthecase ofhormones itwasacceptable ifthesum ofendogenous plus exogenous
hormones wasatorwithin physiological limits.
6.241 Theresponse ofDr.Ritter tothisquestion iscontained inhisresponse toquestion 20above.
VII. INTERIM REVIEW
7.1 On21May 1997, theEuropean Communities andtheUnited States requested thePanel to
review, inaccordance with Article 15.2 oftheDSU, theinterim report thathadbeen issued tothe
parties on7May 1997. TheEuropean Communities alsorequested thePanel tohold afurther meeting
with theparties todiscuss thepoints raised initswritten comments andother points which theywould
develop during thatmeeting.
7.2 Wedecided tohold concurrent interim review meetings with theparties forboth thisdispute
andtheparallel panel requested byCanada. This decision was, inter alia,based onthesimilarities
ofboth cases andthefactthattheinterim reports inboth cases only differ inthedescription ofthe
arguments oftheparties, whereas thesections dealing with thescientific experts andthelegal findingsWT/DS26/R/USA
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inthetwocases arealmost identical. Inlight ofthatdecision, wealsodecided, onCanada 'srequest
andafter consultations with theparties involved, tomake acopy ofthesections ofourinterim report
dealing with ourconsultation with scientific experts andourfindings, together with thecomments
submitted inthatregard bytheEuropean Communities andtheUnited States, available toCanada.
Byletterof3June1997,theEuropeanCommunitiesobjectedtobothdecisions,arguingthattheyaffected
dueprocess anditsrights ofdefense and, consequently, itsrights andobligations under theWTO
Agreement. Itmade, however, nospecific claims ofprejudice. Since wecould notseehowtheEuropean
Communities could beprejudiced bythese decisions, werejected thisobjection.
7.3 Inaletter dated 28May 1997, theUnited States requested that, during themeeting with the
parties, thePanel direct theEuropean Communities nottoraise anycomments thatwere notprovided
intheEC'sletter of21May 1997. Itfurther requested thatthePanel disregard anysuch comments,
including thecomments thattheEuropean Communities hassaidinpartCofitsletter thatitwillbe
submittingwithrespecttosomeunspecifiednumberofparagraphsinexcessof49paragraphsofsection7
oftheinterim report. TheUnited States argued thattodootherwise would create serious prejudice
totheUnited States, which could hardly beexpected tobeprepared torebut such comments.
7.4 Article 15.2 oftheDSU provides thefollowing:
"...Within aperiod oftime setbythepanel, aparty may submit awritten request
forthepanel toreview precise aspects oftheinterim report prior tocirculation ofthe
final report totheMembers. Attherequest ofaparty, thepanel shall hold afurther
meeting with theparties ontheissues identified inthewritten comments ..."(emphasis
added).
Itappeared tousthattheEuropean Communities, byonly enumerating thenumbers oftheparagraphs
ofthefindings section ofourinterim report inrelation towhich ithasconcerns andnotstating inits
written comments theprecise aspects itwishes thePanel toreview, didnotrespect thewording of
Article 15.2 oftheDSU. Weconsidered, however, thatthemain object andpurpose ofArticle 15.2
istomake sure thattheother party isaware oftheissues which willberaised attheinterim review
meeting inorder toallow ittoprepare itsrebuttal. Inlight ofthefactthattheEC'swritten request
forreview ofthefindings section only related tofactual aspects, i.e.,thecorrect reflection oftheEC
arguments andthenames ofandreferences toindividual scientific experts, weconsidered thattheUnited
States would notbeunduly prejudiced byallowing theEuropean Communities topresent these factual
points attheinterim review meeting. We, therefore, decided thattheEuropean Communities could
raise these points ontheconditions thatitwould limit itself tofactual issues andtotheparagraph numbers
ithadenumerated initswritten comments. Wenotethatthisdecision corresponds towhat theUnited
States requested initsletter of28May 1997.
7.5 ThePanel metwith theparties on4June 1997 inorder tohear their arguments concerning
theinterim report. Wecarefully reviewed thearguments presented bytheEuropean Communities
andtheUnited States andtheresponses offered byboth sides.
7.6 TheEuropean Communities requested ustofindthatArticles 15.2 and15.3 oftheDSU and
thegeneral principle ofdueprocess prevent thePanel from modifying aspects oftheinterim report
onwhich theparties didnotsubmit comments. However, attheendoftheinterim review meeting
theEuropean Communities appeared tomodify thisrequest byasking thePanel toreview itsfindings
inlight ofthefactual comments made. Weconsidered thatnoprovision intheDSU limits ustoonly
modify those paragraphs commented upon bytheparties. Article 15.3 oftheDSU only provides that
"[t]he findings ofthefinal panel report shall include adiscussion ofthearguments made attheinterim
review stage...".WT/DS26/R/USA
Page 161
7.7 TheEuropean Communities made twotypes ofcomments onthefindings section oftheinterim
report. Thefirstconcerned 20paragraphs inwhich theEuropean Communities isstated tohave argued
oragreed tosomething which, according totheEuropean Communities, does notornotcompletely
reflect theEC'sposition taken during theproceedings. These comments related tothefollowing
paragraphs: 8.105, 8.109, 8.111, 8.112, 8.115, 8.131, 8.175, 8.176, 8.187, 8.190, 8.193, 8.204,
8.205, 8.213, 8.220, 8.224, 8.228, 8.232, 8.243 and8.274. Since these proposed changes concerned
therepresentation oftheEC'sown legal orfactual arguments, weaccepted most ofthem.
7.8 Thesecond typeofcomments made bytheEuropean Communities related toparagraphs where
thephrase "the scientific experts advising thePanel" isused without, according totheEuropean
Communities, citing thenames ofthescientists northeplace where they have made thestatements
thePanel isinvoking. Italsoargued thatfrequently thereference provided does notreflect theviews
ofallthescientists. TheEuropean Communities alsorequested ustoreview theaccuracy ofthefactual
information contained inseveral paragraphs. Wecarefully considered allthefactual comments thus
made and, where weagreed with them, modified those paragraphs accordingly.
7.9 TheEuropean Communities also requested ustoinclude inthefinal report theprocedural
decisions taken bythePanel during thecourse ofitswork. Weadded these decisions inanewSection B
onorganizational issues.
7.10 TheUnited States commented onthesection ofourfindings related tothescope ofthemeasures
indispute. Inresponse, weexpanded ourreasoning inthese paragraphs. Italsorequested thePanel
tomake additional findings onArticles 2.2,2.3and5.6oftheSPSAgreement. Forthereasons set
outinthereport, wedidnotconsider itnecessary toaddress these claims inorder toresolve thematter
inissue inthisdispute.205TheUnited States alsorequested thedeletion ofparagraphs 8.72 to8.77.
Since weconsidered these paragraphs tobevital toourconsideration ofthiscase, werejected this
request. TheUnited States further submitted corrections ofitsown arguments andfactual elements
andsuggested several drafting changes, most ofwhich have been taken intoaccount inourfinal report.
Itargued, forexample, thatourfindings under Article 5.5oftheSPSAgreement with respect tothe
endogenous production ofthehormones, thehormones used fortherapeutic orzootechnical purposes
andthehormones present inother foods, inaccurately ascribe toitsarguments under Article 5.5which
itmade under Articles 2and5.6. This remark isreflected inparagraph 8.171. Nevertheless, we
considered itappropriate, inter alia,fortheoverall structure ofourreport, toaddress these situations
under Article 5.5.
7.11 Both parties also suggested further changes oradditions inrespect oftheinterim report 's
descriptive sections which wetook intoaccount inre-examining thatpartofthereport. Inthiscontext,
theEuropean Communities requested ustoappend thetranscripts ofthejoint meeting with theexperts
advising thePanel tothedescriptive partofthereport, arguing thatmany important statements made
bytheexperts inthese meetings arenotreflected inSection 6oftheinterim report. Inorder toincrease
thetransparency ofourwork andtotake intoaccount most ofthecomments made bytheEuropean
Communities onthedescriptive partoftheinterim report, wedecided toannex thetranscripts ofthe
joint meeting with theexperts of17-18 February 1997 toourfinal report.
205SeeAppellate Body Report on"United States -Measures Affecting Imports ofWoven Wool Shirts andBlouses from
India", adopted on23May 1997, WT/DS33/AB/R, p.19.WT/DS26/R/USA
Page 162
VIII. FINDINGS
A. CLAIMS OFTHE PARTIES
8.1 This dispute arises essentially from thefollowing facts. In1981 theCouncil oftheEuropean
Communities ("EC Council") adopted Directive 81/602/EEC206,inter alia,requiring theECmember
States oftheEuropean Communities toprohibit theadministration tofarm animals ofsubstances having
athyrostatic, oestrogenic, androgenic orgestagenic action. Directive 81/602/EEC further provided
thatpending adoption ofadecision oftheECCouncil ontheadministration tofarm animals forgrowth
promotionpurposes207ofoestradiol-17,testosterone,progesterone,zeranolandtrenbolone208ECmember
States could continue toapply thenational regulations inforce concerning those substances.209In1988
theECCouncil adopted Directive 88/146/EEC210which brought theadministration tofarm animals
forgrowth promotion purposes ofthese fivehormones within thegeneral prohibition imposed by
Directive 81/602/EEC. The1988 Directive alsorequired theprohibition ofimportation from third
countries ofanimals andofmeat from animals towhich substances with thyrostatic, oestrogenic,
androgenic orgestagenic action have been administered.211Two exceptions tothisgeneral banare
providedinDirective88/299/EEC212:(i)theadministrationfortherapeutictreatment213ofoestradiol-17,
testosterone, progesterone andsome oftheir derivatives; and(ii)theadministration forzootechnical
treatment214ofsubstances having anoestrogenic, androgenic orgestagenic action which areauthorized
inaccordancewithECDirectivesonveterinarymedicinalproducts.215On29April1996,theECCouncil
adopted Directive 96/22/EC216(repealing andreplacing Directives 81/602/EEC, 88/146/EEC and
88/299/EEC) which confirms andextends theabove-mentioned prohibitions. This 1996 Directive will
enter intoforce on1July 1997.217
8.2 TheUnited States claims thattheEuropean Communities, bybanning theimportation ofmeat
andmeat products from animals towhich anyofsixspecific hormones have been administered for
purposes ofpromoting thegrowth oftheanimals, hasacted inconsistently with theAgreement onthe
Application ofSanitary andPhytosanitary Measures ("SPS Agreement"), inparticular Articles 2,3
206ECOfficial Journal, L222, 7August 1981, p.32.
207Article 5ofDirective 81/602/EEC uses theterm "forfattening purposes". However, during thePanel proceedings
andinthisreport theterm "for growth promotion purposes" isused.
208Thefivehormones arethesubject ofthisdispute. Asixth hormone indispute, melengestrol acetate orMGA, falls
under thegeneral prohibition ofDirective 81/602/EEC andisaddressed inparagraph 8.4.
209Seepara. 2.2.
210ECOfficial Journal, L70,16March 1988, p.16.
211Seepara. 2.3.
212ECOfficial Journal, L128, 21May 1988, p.36.
213Therapeutic treatment means treatment ofadisease orother health problem.
214ZootechnicaltreatmentforthepurposesoftheECmeasuresindisputemeans,interalia,treatmentforthesynchronization
ofoestrus, termination ofunwanted gestation, theimprovement offertility andthepreparation ofdonors andrecipients for
theimplantation ofembryos (Article 2,paragraph 1(b) ofECDirective 88/299/EEC).
215Seepara. 2.4.
216ECOfficial Journal, L1125, 23May 1996, p.3.
217Seepara. 2.5.WT/DS26/R/USA
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and5;theAgreement onTechnical Barriers toTrade ("TBT Agreement"); andtheGeneral Agreement
onTariffs andTrade 1994 ("GATT"), inparticular Articles IandIII.
8.3 TheEuropean Communities rejects these claims.
8.4 The sixhormones indispute are: oestradiol-17 ,testosterone, progesterone, zeranol and
trenbolone (thefivehormones mentioned above which were brought within thegeneral prohibition
required byDirective 81/602/EEC byDirective 88/146/EEC) andmelengestrol acetate ("MGA"; a
sixth hormone falling under thegeneral prohibition ofDirective 81/602/EEC). Oestradiol-17 isa
natural hormone with oestrogenic action (i.e.,responsible forfemale characteristics); testosterone
isanatural hormone with androgenic action (i.e.,responsible formale characteristics); progesterone
isanatural hormone with gestagenic action (i.e.,responsible formaintaining pregnancy); zeranol
isasynthetic hormone withoestrogenic action (which mimics theaction ofoestradiol-17 );trenbolone
isasynthetic hormone with androgenic action (which mimics theaction oftestosterone); andMGA
isasynthetic hormone with gestagenic action (which mimics theaction ofprogesterone).218Natural
hormones arehormones which areproduced endogenously inanimals andhumans. Synthetic hormones
arehormoneswhichareartificiallyproduced.Oestradiol-17,testosteroneandprogesteronearehereafter
alsoreferred toasthethree natural hormones; zeranol, trenbolone andMGA arehereafter alsoreferred
toasthethree synthetic hormones.
B. ORGANIZATIONAL ISSUES
1. Scientific evidence
8.5 Inthecourse ofthese proceedings, weconsidered several issues related tothegathering and
submission ofscientific evidence. These concerned theappointment ofscientific experts toadvise
thePanel, thedeadline forsubmission ofscientific evidence bytheparties tothedispute andarequest
bytheEuropean Communities toaskspecific national andinternational authorities toprovide thePanel
with scientific studies anddata.
8.6 Article 11.2 oftheSPS Agreement provides thefollowing:
"Inadispute under thisAgreement involving scientific ortechnical issues, apanel
should seek advice from experts chosen bythepanel inconsultation with theparties
tothedispute. Tothisend, thepanel may, when itdeems itappropriate, establish
anadvisory technical experts group ,orconsult therelevant international organizations,
attherequest ofeither party tothedispute oronitsowninitiative" (emphasis added).
Article 13oftheDSU reads asfollows:
"1. Each panel shall have theright toseek information andtechnical advice from
anyindividual orbody which itdeems appropriate ...
2. Panels mayseekinformation from anyrelevant source andmayconsult experts
toobtain their opinion oncertain aspects ofthematter. With respect toafactual issue
concerning ascientific orother technical matter raised byaparty toadispute, apanel
mayrequest anadvisory report inwriting from anexpert review group .Rules forthe
establishment ofsuch agroup anditsprocedures aresetforth inAppendix 4"(emphasis
added).
218Seepara. 2.8.WT/DS26/R/USA
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8.7 Asoutlined above219,wedecided torequest theopinion ofexperts oncertain scientific and
other technical matters raised bytheparties tothisdispute. Wenote thatboth parties tothisdispute
assumed thatinseeking advice from scientific experts, wewould request anadvisory report from an
"expert review group" asprovided forinArticle 13.2 andAppendix 4oftheDSU. Weconsidered,
however, thatneither Article 11.2 oftheSPSAgreement norArticle 13.2 oftheDSU limits ourright
toseek information from individual experts asprovided forinArticle 11.2, firstsentence, oftheSPS
Agreement andArticles 13.1 and13.2, firstsentence, oftheDSU. Forourexamination ofthisdispute,
weconsidereditmoreusefultoleaveopenthepossibilityofreceivingarangeofopinionsfromindividual
experts onspecific scientific andtechnical questions, rather than toestablish anexpert review group
which would have been required toreach aconsensus view onthebasis ofgeneral terms ofreference
given toitbythePanel.
8.8 Wechose thescientific experts inconsultation with theparties tothedispute inaccordance
with Article 11.2 oftheSPSAgreement. Alistofnames ofindividuals expert inthesubject matter
before thePanel wasprovided bytheCodex Commission secretariat aswell asbytheInternational
Agency forResearch onCancer ("IARC"). Theparties were given theopportunity tocomment on
thenames stated inthislistandinparticular tosubmit anycompelling objections theymight have with
regard toanyoftheindividuals appearing onthislist. Theparties were invited tonominate oneexpert
each, notnecessarily from thelistprovided bythePanel. ThePanel then selected three additional
individuals from thelisttaking intoaccount thecomments oftheparties. Wealsosought information
from theCodex Commission secretariat which answered ourquestions inwriting andalsosentanexpert
toouroralhearing with theexperts.220
8.9 Theprocedures weadopted forourconsultation with theexperts andtheviews theyexpressed
aresetoutinparagraphs 6.1andfollowing. Itisofparticular importance thatwemade clear tothe
experts advising thePanel thatwewere notseeking aconsensus position among theexperts butwanted
tohear allviews.221However, wealsopointed outatthejoint meeting with experts that, inorder
togain time, where anexpert agreed with astatement made oranswer provided byanother expert,
theformer expert didnothave totakethefloor.222Any reference made inourfindings to"scientific
experts advising thePanel" (or"experts" or"scientific experts") refers tooneormore ofthefive
individual experts wethusappointed and,asthecasemaybe,theexpert sentbytheCodex Commission
secretariat. This phrase does notrefer tonorincludes thescientists who were partofthedelegations
oftheparties tothisdispute. These arereferred tointhisreport byname, followed bythename of
thedelegation ofwhich they were part.
8.10 With respect tothesubmission ofscientific evidence bytheparties tothisdispute, wedecided
thatthey could submit written material onnew scientific evidence tosupport their arguments byno
later than 8February 1997. Wetook thisdecision inorder toensure thatboth theparties andthe
scientific experts advising thePanel would getanopportunity toexamine thescientific evidence before
the17-18 February joint meeting with theexperts.
8.11 TheEuropean Communities alsorequested thattheUnited States provide thePanel theoriginals
ofthestudies andother relevant dataonwhich itscompetent authorities based thedecision toauthorize
theuseofthehormones atissue. Italsoconsidered thattheoriginals ofthestudies andother data
onwhich the1988 JECFA Report based itsrecommendations should beprovided tothePanel. As
219Seeparas. 6.1ff.
220Theparties 'arguments with respect totheappointment oftheexperts aresetoutinparas. 6.3ff.
221SeeTranscripts ofthejoint meeting with experts of17February 1997, para. 45.
222Ibid.,para. 88.WT/DS26/R/USA
Page 165
farasthestudies anddataused byUSauthorities isconcerned, wedidnotconsider thisinformation
toberelevant toaddress theECmeasures indispute. Similarly, wedidnotconsider itnecessary to
request thestudies anddataonwhich the1988 JECFA Report isbased since itwasourunderstanding
thatboth parties involved inthisdispute participated intheelaboration ofthisreport.
2. Parallel panel requested byCanada
8.12 Inthecourse ofourwork, wealsoconsidered several issues related totheparallel existence
ofthisPanel, requested bytheUnited States, andthepanel requested byCanada. Although different
panels, both panels relate tothesame ECmeasures, were dealt with bythesame panel members and
were assisted bythesame scientific experts. These issues relate totheorganization ofjoint meetings
andtheaccess byparties inoneofthese panel proceedings tomaterials submitted totheother panel.
8.13 Inthisrespect wenote, asageneral guideline, Article 9.3oftheUnderstanding onRules and
Procedures Governing theSettlement ofDisputes ("DSU"), which reads asfollows:
"Ifmore than onepanel isestablished toexamine thecomplaints related tothesame
matter, tothegreatest extent possible thesame persons shall serve aspanelists oneach
oftheseparate panels andthetimetable forthepanel process insuch disputes shall
beharmonized "(emphasis added).
8.14 Prior toourmeeting with scientific experts, wedecided tohold thatmeeting jointly forboth
thisPanel andtheparallel panel requested byCanada. This decision stemmed from thesimilarities
ofthetwocases (thesame ECmeasures areatissue andboth cases aredealt with bythesame panel
members) andourdecision tousethesame scientific experts inboth cases. Inaddition, weconsidered
that, from apractical perspective, there wasaneed toavoid repetition ofarguments and/or questions
atourmeetings withthescientific experts. TheEuropean Communities objected tothisdecision arguing
thatonejoint meeting with theexperts, instead oftwoseparate meetings, waslikely toaffect its
procedural rights ofdefence. Where itmade precise claims ofprejudice toitsrights ofdefence, we
took corrective action.223
8.15 Inview ofourdecision tohold ajoint meeting with experts, wealsodecided togive access
toalloftheinformation submitted under each panel proceeding totheparties intheother panel
proceeding, including theparties 'second written submissions, written versions oforalstatements,
questions raised bythePanel andtheparties ineach case andtheanswers wereceived, aswell asall
scientific documentation submitted bytheparties. Bydoing so,weunderstood that, inthisPanel,
wecould also consider, where appropriate, thematerials submitted before thepanel requested by
Canada.224TheEuropean Communities objected tothisdecision arguing thatitwasmost likely going
toaffect itssubstantive andprocedural rights ofdefence. Itmade, however, nospecific claims of
prejudice. Weconsidered thatproviding allinformation toallparties involved inboth panels would
increase thetransparency ofourwork, without depriving parties oftheir substantive orprocedural
223TheEuropean Communities argued thatajoint meeting with experts deprived itofitsright topresent itslegal and
scientific positions twice (afirsttime before thisPanel andasecond time before thepanel requested byCanada). Inlight
ofthisobjection wedecided thattheEuropean Communities would beallowed toaddress thejoint meeting twice (afirst
time after theUnited States andasecond time after Canada). SeeTranscripts ofthejoint meeting with experts of
17February 1997, paras.1-2.
224This does, ofcourse, notmean that, inthisPanel, theUnited States hasincorporated oragreed with thearguments
submitted byCanada intheparallel panel itrequested orthatwehave todeal, inthisPanel, with thearguments andclaims
submitted byCanada intheother panel. Itonly means that, where weconsidered itappropriate, wewould beabletoinvoke
oraddress, inthisPanel, factual elements, scientific evidence orarguments submitted bytheEuropean Communities orCanada
totheparallel panel requested byCanada.WT/DS26/R/USA
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rights, andisinlinewith theobject andpurpose ofArticle 9.3oftheDSU calling foraharmonization
oftimetables ofboth panels. Onthese grounds werejected theEC'sobjection.
C. GENERAL INTERPRETATIVE ISSUES
1. Scope ofthemeasures indispute
8.16 TheUnited States contests theECbanonimports ofmeat andmeat products from cattle ,treated
with anyofsixspecific hormones (oestradiol-17 ,testosterone, progesterone, zeranol, trenbolone and
MGA) forgrowth promotion purposes. TheUnited States does notchallenge theECbanonimports
ofmeat andmeat products from cattle treated with hormones other than thesixspecified ortreated
with anyhormones forpurposes other than growth promotion.225
8.17 AttheendofthePanel proceedings, theUnited States argued thatitscomplaint wasnotlimited
tomeat andmeat products ofbovine origin (i.e., originating from cattle) butalso extended to,for
example, lamb meat. Inthisregard theUnited States referred toanAnnex toitsfirstsubmission where
itisstated thatzeranol isapproved intheUnited States foruseinlambs. Wenote, however, that,
although technically within theterms ofreference ofthePanel226,atnopoint inthePanel proceedings
didtheUnited States raise specific arguments orsubmit factual orscientific evidence against aban
imposed bytheEuropean Communities ontheuseofhormones infarm animals other than cattle.
Wefurther note that allscientific studies invoked byboth theUnited States andtheEuropean
Communities relate torisks tohuman health orcattle from theingestion oradministration ofhormones;
notrisks toanyother animals. Wefind, therefore, thattheECbaninsofarasitrelates tomeat or
meat products from farm animals other than cattle falls outside thescope ofthisdispute.
8.18 AttheendofthePanel proceedings, theUnited States alsoseemed toargue thatitscomplaint
wasnotlimited tomeat andmeat products butalsoextended toliveanimals.227However, ourterms
ofreference direct ustoexamine "the matter referred totheDSB bytheUnited States in[document
WT/DS26/6, i.e.,therequest fortheestablishment ofapanel bytheUnited States]". Inthatdocument
theUnited States only claimed thatthecontested ECmeasures "adversely affect imports ofmeat and
meat products".228Wetherefore consider thatthematter referred tointhatdocument islimited to
meat andmeat products andthusfindthattheECbanonimports ofliveanimals fallsoutside ourterms
ofreference.
8.19 Finally, wenote thattheEuropean Communities argues thatitsimport banonliveanimals
towhich anyofthesixhormones have been administered, isnecessary fortheprotection ofboth human
andanimal health.229However, theEuropean Communities does notmake thisargument with respect
toitsimport banonmeat ormeat products .Specifically, theEuropean Communities hasnotargued
thatitsimport banonmeat ormeat products isnecessary fortheprotection ofanimal health either
inside oroutside theECterritory. Since theanimal health arguments invoked bytheEuropean
Communities exclusively relate toitsimport banonliveanimals andconsidering thefinding reached
225Seepara. 3.1.
226Therequest fortheestablishment ofapanel bytheUnited States of25April 1996 (WT/DS26/6), refers to"meat and
meat products" without explicit limitation tomeat andmeat products ofbovine origin (seepara. 1.4).
227Seepara. 4.9.
228Seepara. 1.4.
229Seepara. 4.208.WT/DS26/R/USA
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above thattheECbanonimports ofliveanimals treated with hormones does notfallwithin thescope
ofthisdispute, wefindthatwithin thescope ofthisdispute weneed nottakeintoaccount thearguments
made bytheEuropean Communities which relate toanimal health.230
2. Application oftheSPS Agreement, theTBT Agreement andGATT
8.20 TheUnitedStatesinvokesargumentsrelatingtothreedifferentagreements:theSPSAgreement,
theTBTAgreementandGATT. TheEuropeanCommunities,inturn,invokesthesamethreeagreements
initsdefense. Wenext examine which ofthese agreements apply tothepresent dispute.
8.21 With respect totheSPS Agreement, both parties agree thattheECmeasures indispute are
sanitary measures inthesense ofParagraph 1(b) ofAnnex AoftheSPS Agreement.231Paragraph
1(b) ofAnnex Adefines asanitary measure as
"any measure applied toprotect human oranimal lifeorhealth within theterritory
oftheMemberfromrisksarisingfromadditives,contaminants,toxinsordisease-causing
organisms infoods, beverages orfeedstuffs".
Footnote 4toAnnex Aspecifies that"contaminants" include, forthepurposes ofAnnex A,"pesticide
andveterinary drug residues andextraneous matter". Since thesixhormones indispute areveterinary
drugs, theparties agree thatthealleged risks atissue arise from contaminants.
8.22 Weagree with theparties thattheECmeasures indispute are"applied toprotect human ...
lifeorhealth" within theterritory oftheEuropean Communities from risks arising from "contaminants",
namely residues ofsixspecific hormones, infoods (according toparagraph 1(b)ofAnnex A). That
thecontested ECmeasures are,inter alia,"applied toprotect human ...lifeorhealth" canbeinferred
from thepreambles to,andlegislative history of,Directives 81/602/EEC and88/146/EEC.232Since
both parties agree thatthecontested ECmeasures are"sanitary measures", weseenoneed tofurther
examine inthisdispute thedefinition ofmeasures "applied toprotect human ...lifeorhealth".
8.23 Both parties alsoagree that, according toArticle 1.1oftheSPSAgreement, theSPSAgreement
isapplicable tothisdispute.233Article 1.1 provides thattheSPS Agreement
"applies toallsanitary andphytosanitary measures which may, directly orindirectly,
affect international trade".
Weagree with theparties thattheECmeasures "may, directly orindirectly, affect international trade".
Itcannot becontested thatanimport banaffects international trade.
8.24 With respect totheapplication ratione temporis oftheSPS Agreement totheECmeasures
indispute, wenote thattheSPS Agreement entered intoforce on1January 1995 (thedate ofentry
intoforce oftheWTO Agreement ofwhich, according toArticle II:2ofthatAgreement, theSPS
Agreement isanintegral part). The ECmeasures indispute, however, were enacted before 1
230Ourfinding thatanimal health does notfallwithin thescope ofthisdispute does, ofcourse, notmean thatwecannot
takeintoaccount scientific evidence relevant forrisks tohuman lifeorhealth which isderived from studies ortests applied
toanimals.
231Seeparas. 4.7-4.8.
232Seeparas. 2.2-2.3.
233Seeparas. 4.5and4.8.WT/DS26/R/USA
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January 1995 (namely 31July 1981 and7March 1988), thus raising theissue ofwhether the
SPS Agreement applies tothese measures.
8.25 Article 3.2oftheDSU directs ustoclarify theprovisions oftheSPSAgreement "inaccordance
with customary rules ofinterpretation ofpublic international law". According toestablished practice,
thefundamental rules oftreaty interpretation setoutintheVienna Convention ontheLaw ofTreaties
("Vienna Convention") form partofthese customary rules ofinterpretation.234Thegeneral principle
ininternational law, asembodied inArticle 28oftheVienna Convention, isthat"[u]nless adifferent
intention appears from thetreaty orisotherwise established, itsprovisions donotbindaparty inrelation
to...anysituation which ceased toexist before thedate oftheentry intoforce ofthetreaty ..."
(emphasis added). TheECmeasures can, inthiscontext, beconsidered ascontinuing "situations"
which were enacted before theentry intoforce oftheSPSAgreement butwhich didnotcease toexist
after thatdate(contrary tothesituation envisaged inArticle 28). Inlinewith Article 28oftheVienna
Convention, theSPS Agreement should, therefore, inprinciple apply tothese ECmeasures, unless
anintention tothecontrary canbeestablished.235
8.26 Anexamination oftheSPSAgreement reveals nointention tothecontrary. Indeed, several
provisions oftheSPS Agreement confirm thegeneral principle thattheSPSAgreement should also
apply tosanitary measures which were enacted before itsentry intoforce butwhich remain inforce
thereafter. Except forArticle 14which authorizes delays intheapplication ofsome orallofthe
provisions oftheSPS Agreement forleast-developed andother developing countries, notransition
periods areprovided for. ThefactthatArticle 14explicitly provides foratwo-year transition period
fordeveloping countries with respect tosome oftheir existing sanitary andphytosanitary measures,
confirms thattheSPS Agreement generally applies tomeasures enacted before theentry intoforce
oftheSPS Agreement butwhich aremaintained inforce after thatdate. This isalsoconfirmed in
several provisions oftheSPSAgreement which explicitly address situations where Members "maintain"
asanitary orphytosanitary measure, such asArticle 2.2("Members shall ensure thatanysanitary ...
measure ...isbased onscientific principles andisnotmaintained without sufficient scientific evidence
..."), Article 3.3("Members may introduce ormaintain sanitary ...measures ...if..."), Article 5.6
("... when establishing ormaintaining sanitary ...measures ...Members shall ensure that...") and
Article 5.8("... aspecific sanitary ...measure introduced ormaintained byanother Member ...").
8.27 Wefinally note thataccording toArticle XVI:4 oftheWTO Agreement, each Member "shall
ensure theconformity ofitslaws, regulations andadministrative procedures with itsobligations as
provided intheannexed Agreements [including theSPSAgreement]". This provision confirms that
measures which already existed asofthedateofentry intoforce oftheSPSAgreement alsoneed to
beconsistent with therequirements imposed bythatAgreement.
8.28 Thus, wefindthattheSPS Agreement isapplicable tothisdispute.
8.29 Inrespect oftheapplicability oftheTBT Agreement tothisdispute, wenote thatArticle 1.5
oftheTBT Agreement reads asfollows:
234SeeAppellate Body Reports on"United States -Standards forReformulated andConventional Gasoline", adopted
on20May 1996, WT/DS2/AB/R, pp.16-17 and"Japan -Taxes onAlcoholic Beverages", adopted on1November 1996,
WT/DS8/AB/R, pp.10-12.
235Werefer, inthisrespect, totheReports ofthePanel andAppellate Body on"Japan -Taxes onAlcoholic Beverages",
adopted on1November 1996 (WT/DS8/R andWT/DS8/AB/R), where boththePanel andtheAppellate Body applied GATT
(which entered intoforce on1January 1995) totheJapanese Liquor TaxLaw (of1953 andlastamended on1May 1994),
even though thatJapanese measure hadbeen enacted andmost recently been amended before theentry intoforce ofGATT,
ontheimplicit ground thattheJapanese measure remained inforce after thatdate. Thesame reasoning wasapplied inthe
Reports ofthePanel andAppellate Body on"United States -Standards forReformulated andConventional Gasoline", op.
cit.WT/DS26/R/USA
Page 169
"The provisions ofthisAgreement donotapply tosanitary andphytosanitary measures
asdefined inAnnex AoftheAgreement ontheApplication ofSanitary and
Phytosanitary Measures".236
Since themeasures indispute aresanitary measures, wefindthattheTBT Agreement isnotapplicable
tothisdispute.
8.30 Wefinally note thatthisdispute relates totrade ingoods (incasu imports ofmeat andmeat
products) andthatonitsfaceGATT applies.237Inthiscontext, wenote thattheUnited States only
invokes GATT after having addressed theSPSAgreement andthattheEuropean Communities does
notinvoke anyGATT provision other than Article XX(b) asajustification fortheECmeasures in
dispute.
3. Relationship between theSPS Agreement andGATT
8.31 Since boththeSPSAgreement andGATT apply tothisdispute, wenextexamine therelationship
between these twoagreements.
8.32 Thepartiestothedisputepresentdivergingviewswithrespecttowhetherweshouldfirstaddress
GATT ortheSPSAgreement. However, neither oftheparties claims thattherelevant provisions of
theSPSAgreement andGATT areinconflict. Therefore, wedonotneed, asapreliminary matter,
toaddress theGeneral Interpretative Note totheMultilateral Agreements onTrade inGoods which
only applies "[i]n theevent ofconflict between aprovision of[GATT] andaprovision ofanother
Agreement inAnnex 1A[inter alia,theSPS Agreement]".
8.33 TheEuropean Communities makes adistinction between the"substantive" and"procedural"
provisions oftheSPS Agreement. According totheEuropean Communities, thesubstantive provisions
only interpret Article XX(b) ofGATT238,without adding anynewobligations, while theprocedural
provisions contain requirements additional toGATT. Therefore, theEuropean Communities concludes,
the"substantive" provisions oftheSPSAgreement canonly beaddressed ifrecourse ismade toGATT
Article XX(b), i.e.,if,andonly if,aviolation ofanother provision ofGATT isfirstestablished. The
additional "procedural" provisions, ontheother hand, canbeexamined directly andindependently
ofaprior GATT violation.239
8.34 TheUnited States argues thattheSPSAgreement isthelexspecialis forareview ofsanitary
measures andshould, therefore, beaddressed first. TheUnited States claims thattheapplication of
theSPSAgreement does notrequire aprior violation ofGATT since theSPS Agreement isa"free-
236Similarly, butlessexplicitly, Article 1.4oftheSPSAgreement provides that"[n]othing inthisAgreement shall affect
therights ofMembers under theAgreement onTechnical Barriers toTrade with respect tomeasures notwithin thescope
ofthisAgreement".
237With respect totheapplication ratione temporis ofGATT tothisparticular case, thesame reasoning andfindings apply
asthose developed fortheapplication ratione temporis oftheSPSAgreement inparagraphs 8.24 and8.25.
238Article XX(b) ofGATT reads asfollows: "Subject totherequirement thatsuch measures arenotapplied inamanner
which constitute ameans ofarbitrary orunjustifiable discrimination between countries where thesame conditions prevail,
oradisguised restriction oninternational trade, nothing inthisAgreement shall beconstrued toprevent theadoption or
enforcement byanycontracting party ofmeasures: ...(b)necessary toprotect human, animal orplant lifeorhealth".
239Seepara. 4.4.WT/DS26/R/USA
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standing" agreement which applies toallsanitary measures andimposes requirements additional to
those inArticle IIIortheexceptions inArticle XXofGATT.240
8.35 Inexamining therelationship between GATT andtheSPSAgreement, werecall thefundamental
rules oftreaty interpretation setoutintheVienna Convention.241Article 31oftheVienna Convention
prescribes thatatreaty hastobeinterpreted "ingood faith inaccordance with theordinary meaning
tobegiven totheterms ofthetreaty intheir context andinthelight ofitsobject andpurpose".242
8.36 Wefirst consider thewording ofArticle 1.1oftheSPSAgreement which reads asfollows:
"This Agreement applies toallsanitary andphytosanitary measures which may, directly
orindirectly, affect international trade. Such measures shall bedeveloped andapplied
inaccordance with theprovisions ofthisAgreement".
According toArticle 1.1oftheSPS Agreement, tworequirements need tobefulfilled fortheSPS
Agreement toapply: (i)themeasure indispute isasanitary orphytosanitary measure243;and(ii)the
measure indispute may, directly orindirectly, affect international trade.244There arenoadditional
requirements. TheSPSAgreement contains, inparticular, noexplicit requirement ofaprior violation
ofaprovision ofGATT which would govern theapplicability oftheSPS Agreement, asasserted by
theEuropean Communities.
8.37 WefurthernotethatthedistinctionproposedbytheEuropeanCommunitiesbetween"substantive"
and"procedural" provisions oftheSPSAgreement hasnobasis inthetextofthatAgreement andwould,
inanyevent, seem tobedifficult toapply tomost provisions contained therein. Forexample, the
obligation tobase asanitary measure onarisk assessment inaccordance with Article 5ofthe
SPS Agreement includes both substantive andprocedural elements.245
8.38 Moreover, wefind theECclaim thattheSPS Agreement does notimpose "substantive"
obligations additional tothose already contained inArticle XX(b) ofGATT nottobepersuasive. It
isclear thatsome provisions oftheSPSAgreement elaborate onprovisions already contained inGATT,
inparticular Article XX(b). Thefinal preambular paragraph oftheSPSAgreement provides, indeed,
thattheMembers desired "toelaborate rules fortheapplication oftheprovisions ofGATT 1994 which
relate totheuseofsanitary orphytosanitary measures, inparticular theprovisions ofArticle XX(b)".
Examples ofsuch rules are, arguably, some oftheobligations contained inArticle 2ofthe
SPS Agreement. However, onthisbasis alone wecannot conclude thattheSPSAgreement onlyapplies,
asArticle XX(b) ofGATT does, if,andonly if,aprior violation ofaGATT provision hasbeen
established. Many provisions oftheSPS Agreement impose "substantive" obligations which go
240Seepara. 4.5.
241Thelegal basis forthePanel toinvoke theVienna Convention isoutlined above inparagraph 8.25 andfootnote 234.
242According toArticle 32oftheVienna Convention, recourse mayonlybehadtosupplementary means ofinterpretation
"inorder toconfirm themeaning resulting from theapplication ofArticle 31"orincase Article 31leaves themeaning
"ambiguous orobscure" orleads to"aresult which ismanifestly absurd orunreasonable".
243Asdefined inParagraph 1ofAnnex AoftheSPSAgreement, quoted anddiscussed inparas. 8.21 and8.22.
244Seepara. 8.23.
245Seeparas. 8.112 ff.WT/DS26/R/USA
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significantly beyond andareadditional totherequirements forinvocation ofArticle XX(b).246These
obligationsare,interalia,imposedto"furthertheuseofharmonizedsanitaryandphytosanitarymeasures
between Members"247andto"improve thehuman health, animal health andphytosanitary situation
inallMembers".248They arenotimposed, asisthecaseoftheobligations imposed byArticle XX(b)
ofGATT, tojustify aviolation ofanother GATT obligation (such asaviolation ofthenon-discrimination
obligations ofArticles IorIII).
8.39 Wenote inthisrespect thatthegeneral approach adopted inArticle XX(b) ofGATT is
fundamentally different from theapproach adopted intheSPS Agreement. Article XX(b), which is
notlimited tosanitary orphytosanitary measures, provides forageneral exception which canbeinvoked
tojustify anyviolation ofanother GATT provision. TheSPSAgreement, ontheother hand, provides
forspecific obligations tobemetinorder foraMember toenact ormaintain specific types ofmeasures,
namely sanitary andphytosanitary measures.
8.40 Theconclusion thattheSPSAgreement contains obligations which arenotalready imposed
byGATT isconfirmed inArticle 2.4oftheSPS Agreement which provides that"[s]anitary or
phytosanitary measures which conform totherelevant provisions ofthisAgreement shall bepresumed
tobeinaccordance with theobligations oftheMembers under theprovisions ofGATT 1994 which
relate totheuseofsanitary orphytosanitary measures, inparticular theprovisions ofArticle XX(b)".
Indeed, topresume thatonesetofobligations (incasu GATT) ismetbecause another setofobligations
(incasu theSPSAgreement) hasbeen fulfilled, seems toimply thatthelatter setofobligations imposes
atleast asmany as,andprobably more obligations than, theformer. Support forthisconclusion is
alsofoundinArticle3.2oftheSPSAgreementwhichprovidesthat"[s]anitaryorphytosanitarymeasures
whichconformtointernationalstandards,guidelinesorrecommendationsshallbedeemedtobenecessary
toprotect human, animal orplant lifeorhealth, andpresumed tobeconsistent with therelevant
provisions ofthisAgreement andofGATT 1994" (emphasis added). While both agreements may
apply inagiven factual situation, theforegoing provision nonetheless establishes theSPSAgreement
asanagreement which imposes obligations which aredifferent from those imposed byGATT.
8.41 Wetherefore findthat, inaccordance with theordinary meaning tobegiven totheterms of
theSPS Agreement intheir context andinthelight ofitsobject andpurpose (inconformity with
Article 31oftheVienna Convention), there isnorequirement, inanyoftheprovisions oftheSPS
Agreement, thataprior violation ofaGATT provision need beestablished before theSPSAgreement
applies.
8.42 Having reached theconclusion thatwearenotperserequired toaddress GATT claims prior
tothose raised under theSPSAgreement, wemust thendecide which ofthetwoagreements weshould
examine firstinthisparticular dispute. TheSPSAgreement specifically addresses thetypeofmeasure
indispute. Ifwewere toexamine GATT first, wewould inanyevent need torevert tothe
SPS Agreement: ifaviolation ofGATT were found, wewould need toconsider whether Article XX(b)
could beinvoked andwould then necessarily need toexamine theSPS Agreement; if,ontheother
hand, noGATT violation were found, wewould stillneed toexamine theconsistency ofthemeasure
with theSPS Agreement since nowhere isconsistency with GATT presumed tobeconsistency with
theSPS Agreement. Forthese reasons, andinorder toconduct ourconsideration ofthisdispute in
themost efficient manner, weshall first examine theclaims raised under theSPS Agreement.
246One example istheobligation contained inArticle 3.1oftheSPSAgreement which provides that"[t]o harmonize
sanitaryandphytosanitarymeasuresonaswideabasisaspossible,Membersshallbasetheirsanitaryandphytosanitarymeasures
oninternational standards, guidelines orrecommendations, where they exist ...".
247Preambular paragraph 6oftheSPSAgreement.
248Preambular paragraph 2oftheSPSAgreement.WT/DS26/R/USA
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D. THE SPS AGREEMENT
1. Overview oftheprovisions indispute
8.43 TheUnited States claims violations ofArticles 2,3and5oftheSPS Agreement. Article 2
elaborates onthebasic rights andobligations ofMembers under theSPSAgreement. Article 3deals,
more specifically, with theobjective ofharmonization ofsanitary measures onthebasis ofinternational
standards,guidelinesorrecommendations.Article5deals,inturn,withtheobligationofriskassessment
andthedetermination andapplication byMembers oftheir appropriate level ofsanitary protection.
8.44 Article 3.1requires Members tobase their sanitary measures oninternational standards,
guidelines orrecommendations except asotherwise provided forintheSPSAgreement, andinparticular
inArticle 3.3. Wenote, therefore, thateven ifinternational standards may not,intheir own right,
bebindingonMembers,Article3.1requiresMemberstobasetheirsanitarymeasuresonthesestandards.
8.45 According toArticle 3.2sanitary measures which conform tointernational standards, guidelines
orrecommendations arepresumed tobeconsistent with both theSPSAgreement andGATT. Weshall
therefore, asafirst step, examine whether there areinternational standards, guidelines or
recommendations with respect totheECmeasures indispute and, ifso,whether theECmeasures are
based onthese standards, guidelines orrecommendations inaccordance with Article 3.1.
8.46 Ifthere areinternational standards, guidelines orrecommendations and theEuropean
Communities hasnotbased itsmeasures thereon, wewillneed, asasecond step, toexamine whether
theEuropean Communities canjustify itsmeasures under Article 3.3since Article 3.1,which imposes
therequirement tobase sanitary measures oninternational standards explicitly refers toArticle 3.3
asproviding foranexception tothisrequirement.
8.47 Finally, ifthere arenointernational standards, guidelines orrecommendations with respect
totheECmeasures indispute, ortosome ofthem, there would benostandards, guidelines or
recommendations forthese measures tobebased oninlinewith Article 3.1. However, even inthat
casetheconsistency oftheECmeasures indispute with Articles 2and5oftheSPSAgreement would
stillneed tobeexamined.
2. Burden ofproof
8.48 GiventhenatureofdisputesundertheSPSAgreement,whichimposessubstantiveandprocedural
requirements raising various, andinthiscase complex, issues offact, theallocation oftheburden of
proof isofparticular importance. Itinvolves consideration ofthewording, general outline andobject
andpurpose oftheSPSAgreement asawhole. We,therefore, firstexamine thisissue ingeneral before
addressing thespecific burden ofproof foreach oftheprovisions indispute inmore detail below.
8.49 Instating itsclaims under theSPS Agreement, theUnited States seems topresume thatthe
European Communities bears theburden ofproof. TheUnited States argues thattheSPS Agreement,
inter alia,requires theEuropean Communities tobase itssanitary measures onariskassessment and
prohibits theEuropean Communities from maintaining such measures without scientific evidence.
According totheUnited States, theSPSAgreement doesnotallow formeasures tobemaintained without
scientific evidence until such time asscience proves "beyond doubt" thatthere isnorisk(against which
asanitary measure canprotect, forexample, consumers). TheUnited States seems, therefore, to
conclude thatitisuptotheEuropean Communities toprovide evidence thatthere isarisktobeprotectedWT/DS26/R/USA
Page 173
against andthatthere hasbeen ariskassessment. ItisnotuptotheUnited States toprove thatthere
isnoriskorthattheEuropean Communities didnotcarry outariskassessment.249
8.50 TheEuropean Communities argues thattheburden ofproof should restontheparty challenging
theconsistency ofsanitary measures withtheSPSAgreement (incasu theUnited States). TheEuropean
Communities claims, inter alia,thatitisuptotheUnited States toprovide evidence thattheuseof
thehormones indispute forgrowth promotion issafeandwithout risk.
8.51 Inaddressing theburden ofproof under theSPSAgreement, weconsider that, asisthecase
inmost legal proceedings, theinitial burden ofproof rests onthecomplaining party inthesense that
itbears theburden ofpresenting aprima facie case ofinconsistency with theSPSAgreement. Itis,
indeed, fortheparty thatinitiated thedispute settlement proceedings toputforward factual andlegal
arguments inorder tosubstantiate itsclaim that asanitary measure isinconsistent with the
SPS Agreement. Inother words, itisfortheUnited States topresent factual andlegal arguments that,
ifunrebutted, would demonstrate aviolation oftheSPS Agreement. Once such aprima facie case
ismade, however, weconsider that, atleast with respect totheobligations imposed bytheSPS
Agreement thatarerelevant tothiscase, theburden ofproof shifts totheresponding party.250
8.52 Inourview, theallocation ofevidentiary burden under theSPS Agreement totheMember
imposing asanitary orphytosanitary measure flows directly from thewording ofmany oftheprovisions
contained inthatAgreement andinparticular thefirst three words thereof:
"Members shall ensure that..." (e.g. Articles 2.2, 2.3, 5.1 and 5.6 ofthe
SPS Agreement; emphasis added).
8.53 Moreover, thewording ofArticle 5.8(although thisprovision relates more totransparency
thantoanyrequirement oflegal justification) further supports ourreading ofthisassignment ofburden
ofproof totheparty imposing themeasure:
"When aMember hasreason tobelieve thataspecific sanitary orphytosanitary measure
introduced ormaintained byanother Member isconstraining, orhasthepotential to
constrain, itsexports andthemeasure isnotbased ontherelevant international
standards, guidelines orrecommendations, orsuch standards, guidelines or
249Seepara. 4.101.
250Two provisions oftheSPSAgreement do,however, explicitly confer theburden ofproof upon theexporting Member
(i.e.,theMember contesting thesanitary orphytosanitary measure), namely Article 4.1onequivalence andArticle 6.3on
pest- ordisease-free areas orareas oflowpestordisease prevalence. Thefactthatinthese instances theburden ofproof
isexplicitly conferred upon theexporting Member confirms thatunder other SPSprovisions theburden ofproof mayshift
totheMember imposing thesanitary orphytosanitary measure. Wenote, inthisrespect, theReport oftheAppellate Body
on"United States -Measures Affecting Imports ofWoven Wool Shirts andBlouses from India" (adopted on23May 1997,
WT/DS33/AB/R) which addressed theissue ofburden ofproof under theAgreement onTextiles andClothing (the"ATC")
asfollows:
"...aparty claiming aviolation ofaprovision oftheWTO Agreement byanother Member must assert
andprove itsclaim. Inthiscase, India claimed aviolation bytheUnited States ofArticle 6oftheATC.
Weagree with thePanel thatit,therefore, wasuptoIndia toputforward evidence andlegal argument
sufficient todemonstrate thatthetransitional safeguard action bytheUnited States wasinconsistent with
theobligations assumed bytheUnited States under Articles 2and6oftheATC.India didsointhiscase.
And, with India having done so,theonus then shifted totheUnited States tobring forward evidence
andargument todisprove theclaim. This, theUnited States wasnotabletodoand, therefore, thePanel
found thatthetransitional safeguard action bytheUnited States "violated theprovisions ofArticles 2
and6oftheATC" (pp.16-17).WT/DS26/R/USA
Page 174
recommendations donotexist, anexplanation ofthereasons forsuch sanitary or
phytosanitary measure may berequested and shall beprovided bytheMember
maintaining themeasure "(emphasis added).
8.54 Finally, wenote thatthisassignment ofburden ofproof totheparty imposing themeasure
isalsosupported byArticle 3.2which introduces apresumption ofconsistency withtheSPSAgreement
forsanitary measures which conform tointernational standards, guidelines orrecommendations.
Article 3.2states thefollowing:
"Sanitaryorphytosanitarymeasureswhichconformtointernationalstandards,guidelines
orrecommendations shall bedeemed tobenecessary toprotect human, animal orplant
lifeorhealth, andpresumed tobeconsistent with therelevant provisions ofthis
Agreement andofGATT 1994".
Introducing ageneral presumption ofconsistency with anagreement infavour ofaparty (incasu the
party imposing themeasure) intheevent thatcertain conditions aremet, seems, indeed, topresuppose
thattheburden ofproof under thatagreement inprinciple (i.e.,incases where these specific conditions
arenotmet) rests onthatparty.
8.55 Wethus find that, forthepurposes ofthisdispute, theUnited States bears theburden of
presenting aprima facie caseofinconsistency with theSPSAgreement, after which theburden ofproof
shifts totheEuropean Communities todemonstrate thatitsmeasures indispute meet therequirements
imposed bytheSPS Agreement.
3. Article 3.1: sanitary measures based oninternational standards
8.56 Article 3.1oftheSPS Agreement reads asfollows:
"Toharmonize sanitary andphytosanitary measures onaswide abasis aspossible,
Membersshallbasetheirsanitaryandphytosanitarymeasuresoninternationalstandards,
guidelines orrecommendations, where they exist, except asotherwise provided for
inthisAgreement, andinparticular inparagraph 3".
Thefirstquestion wemust address iswhether there exist any"international standards, guidelines or
recommendations" with respect totheadministration ofanyofthesixhormones indispute forgrowth
promotion purposes. Forfood safety, thehealth concern atissue inthisdispute, paragraph 3(a)of
Annex AoftheSPSAgreement defines "international standards, guidelines orrecommendations" as
"thestandards, guidelines andrecommendations established bytheCodex Alimentarius
Commission relating tofood additives, veterinary drug and pesticide residues ,
contaminants, methods ofanalysis andsampling, andcodes andguidelines ofhygienic
practice" (emphasis added).
8.57 Inlinewith Article 3.1,weconsider thatifsuch Codex Alimentarius Commission standards,
guidelines orrecommendations ("Codex standards") exist with respect totheadministration ofany
ofthesixhormones indispute forgrowth promotion purposes, asanitary measure taken byaMember
should either bebased onthese standards orbejustified under Article 3.3oftheSPS Agreement.WT/DS26/R/USA
Page 175
(a) Codex standards
8.58 Within thescope ofthemeasures indispute, wenote thatCodex standards exist forfiveof
thesixhormones atissue (i.e.,forallhormones atissue other than MGA).251Wewillaccordingly
examine thedefinition andscope ofapplication ofthese Codex standards anddetermine whether they
apply totheECmeasures indispute.
8.59 TheCodex Alimentarius Commission ("Codex"), aninternational body ofwhich most WTO
Members (including theUnited States andtheECmember States oftheEuropean Communities) are
members,establishes,interalia,AcceptableDailyIntakes("ADIs"),MaximumResidueLimits("MRLs ")
andother recommendations forveterinary drugs. Itdoes soonthebasis oftheadvice oftheCodex
Committee onResidues ofVeterinary Drugs inFoods andtherecommendations oftheJoint FAO/WHO
Expert Committee onFood Additives ("JECFA"). While Codex iscomposed ofgovernment
representatives ofECmember States, JECFA iscomposed ofindependent scientists. JECFA makes
scientific evaluations andrecommendations; Codex takes thedecision whether ornottoadopt these
recommendations. However, once adopted Codex recommendations are,according totheGeneral
Principles ofCodex, notbinding upon Codex members. They areonly ofanadvisory nature. The
procedures tobefollowed toadopt aCodex recommendation have been outlined above.252
8.60 Thegoal ofJECFA 'sevaluation ofveterinary drugs is
"toestablish safelevels ofintake bysetting Acceptable Daily Intakes (ADIs) andto
develop maximum residue limits when veterinary drugs areused inaccordance with
good veterinary practice" (emphasis added).253
Theterm "good veterinary practice" (aswellastheterm "good animal husbandry practice" often used
inJECFA Reports) isforCodex purposes, according totheCodex expert advising thePanel254,a
synonym forwhat isknown inCodex terminology as"Good Practice intheUseofVeterinary Drugs"
("GPVD"; hereafter alsoreferred toas"good practice"), inturn defined as
"theofficial recommended orauthorized usage including withdrawal periods, approved
bynational authorities, ofveterinary drugs under practical conditions".255
8.61 AnADI setbyCodex is"anestimate byJECFA oftheamount ofaveterinary drug, expressed
onabodyweightbasis,thatcanbeingesteddailyoveralifetimewithoutappreciablehealthrisk(standard
man =60kg)" (emphasis added).256This ADI isderived from theexperimental noobservable effect
level inthemost appropriate animal species, byapplying anappropriate safety factor. ACodex MRL,
ontheother hand, ifimplemented innational law, determines theamount ofresidues which islegally
permitted orrecognized asacceptable infood andisprimarily aregulatory tooltoensure thatintake
does notexceed theADI andthatgood practice isobserved. ACodex MRL isfrequently setatlevels
251Seeparas. 2.20, 2.21 and2.23.
252Seeparas. 2.15-2.16.
253Seepara. 2.14.
254Seepara. 2.19.
255Ibid.
256Seepara. 2.17.WT/DS26/R/USA
Page 176
below (even farbelow) thetheoretical safelevels determined from anADI. Codex MRLs forveterinary
drugs arenormally expressed inµg/kg onafresh weight basis inmeat.257
8.62 With respect tothethree natural hormones indispute, oestradiol-17 ,progesterone and
testosterone (classified byCodex as"veterinary drugs"), similar Codex standards apply. Forallthree
hormones, when used forgrowth promotion purposes, itwasconsidered "unnecessary" toestablish
anADI orMRL. Forallthree hormones thefollowing footnote explained theword "unnecessary":
"Establishing anADI andan[MRL] forahormone thatisproduced endogenously at
variablelevelsinhumanbeingswasconsideredunnecessarybytheCommittee.Residues
resulting from theuseofthissubstance asagrowth promoter inaccordance with good
animal husbandry practice areunlikely topose ahazard tohuman health".258
The32nd JECFA Report of1988259,onwhich theCodex standards arebased, concluded forallthree
natural hormones administered forgrowth promotion purposes thattheresidue levels ofeach ofthese
hormones when found inmeat from animals treated with implants according togood animal husbandry
practice areextremely lowwhen compared with theamounts endogenously produced daily inhuman
beings ornormally present inthedairy products ortissues ofuntreated animals orother foods.
According toJECFA, thepotential toxic effect ofresidues ofthese hormones isdirectly related totheir
hormonal effect. Since theadditional residue levels intreated animals have nohormonal effect, the
Report concluded thatthese residue levels arenotcapable ofexerting anytoxic effect. JECFA further
noted thatthetotal residue levels intreated animals fallwell within thenormal range oflevels found
inuntreated animals ofdifferent types andages. Onthebasis ofthissafety assessment andinview
ofthedifficulty ofdetermining thelevels ofresidues attributable totheuseofthishormone asagrowth
promoter incattle (residues ofendogenous natural hormones inmeat cannot, according toJECFA,
bepractically distinguished from those exogenously administered), JECFA concluded thatitwas
"unnecessary" toestablish anADI orMRL forthese hormones.260
8.63 With respect totwoofthethree synthetic hormones atissue, zeranol andtrenbolone (classified
byCodex as"veterinary drugs"), thefollowing Codex standards apply: anADI of0-0.5 and0-0.02
µg/kg body weight, respectively, andanMRL of2µg/kg -trenbolone inbovine muscle and10µg/kg
inbovine liver.261
8.64 The32nd JECFA Report of1988, onwhich theCodex standard forzeranol isbased, noted
thatzeranol wasshown tobeaweak oestrogen which mimics theaction ofoestradiol-17 .TheReport
concluded thatthetoxic (incasu tumorigenic) effect ofzeranol isassociated with itshormonal (i.e.,
oestrogenic) properties andthatanADI could thusbeestablished onthebasis ofano-hormonal-effect
level. Adopting what itconsidered tobeaconservative approach byusing asabasis studies on
ovariectomized female cynomolgus monkeys (highly sensitive tooestrogenic substances) andusing
asafety factor of100, JECFA setanADI forhuman beings of0-0.5 µg/kg ofbody weight. Fora
70kgperson consuming 500gofmeat daily over anentire lifetime, themaximum permissible orsafe
level ofzeranol residues inmeat would then, according toJECFA, be70µg/kg ofedible tissue.
However, theReport noted thatwhen zeranol isadministered tocattle according totheproposed good
257Seepara. 2.18.
258Seepara. 2.21.
259Seepara. 2.22.
260Ibid.
261Seepara. 2.23.WT/DS26/R/USA
Page 177
practice, themaximum mean residue levels would notexceed 0.2µg/kg inmuscle and10µg/kg in
liver atanytime after implantation (irrespective ofthewithdrawal period respected). These residue
levels obtained onthebasis ofgood practice arethusfarbelow what JECFA determined tobethesafety
level of70µg/kg. However, inorder tosetalevel which isdetectable byusing methods available
forroutine residue analysis, theofficial Codex MRL wasincreased to2µg/kg inmuscle andsetat
10µg/kg inliver.262
8.65 Trenbolone acetate isthechemical form orester used fortheadministration oftrenbolone .
Trenbolone, ortrenbolone acetate ("TBA"), anandrogen which mimics theaction oftestosterone, is
rapidly hydrolysed after administration tocattle, themajor metabolites (i.e., compound intowhich
TBA breaks down bychemical activity when entering thebody) being occurring, inter
alia,inliver, and -trenbolone, present inmuscle.263With respect toTBA, the32nd JECFA Report
of1988 concluded thatitspotential toxic effects only arise asaconsequence ofitshormonal activity
andconcluded that, therefore, anADI could beestablished onthebasis ofano-hormonal-effect level.264
Adopting what itconsidered tobeaconservative approach byusing asabasis studies oncastrated
male rhesus macaque monkeys which arehighly sensitive tocompounds with antigonadotropic activity
andpigswhich areasensitive model forassessing hormonal effects ofTBA andusing asafety factor
of100, JECFA later setanADI forhuman beings of0-0.02 µg/kg ofbody weight (34th JECFA Report
of1989). Themaximum ADI fora60kgperson would thus be1.2µgofTBA residues. JECFA
thensetMRLs for-trenboloneinmuscleand-trenboloneinliverof2µg/kgand10µg/kgrespectively,
based onaverage residue levels inheifers at15-30 days after implantation of300mgTBA, noting
thatconcentrations would even belower attheproposed good practice. According toJECFA, the
MRLs thus obtained onthebasis ofconservative estimates would notexceed theCodex ADI orsafe
level atanytime after implantation ofthedrug (irrespective ofthewithdrawal period respected).
8.66 TheEuropean Communities argues thattheCodex standards outlined above arenotrelevant
tothisdispute. Itargues thatthere arenoCodex standards fortheuseofhormone growth promoters,
only Codex standards formaximum residue levels andthatsince theECmeasures indispute donot
setmaximum residue levels, there exist noCodex standards onwhich theECmeasures need tobe
based. Moreover, theEuropean Communities argues, theCodex standards invoked arelevels of
protection, notmeasures ,andsince there isnoobligation intheSPS Agreement toadopt Codex
recommendedlevelsofprotection,thestandardsinvokedareirrelevantfortheECmeasuresindispute.265
8.67 TheEuropean Communities alsonotes thatthedecision byCodex (ofJuly1995) toformally
adopt thefiveCodex standards atissue wastaken byamajority ofonly 33votes infavour, 29votes
against and7abstentions; avery close vote which isunusual inCodex practice where proposals are
normally adopted byconsensus, indicating thattheissue ofhormone growth promoters hasbeen and
continues tobevery controversial.266
8.68 TheEuropean Communities finally argues thattheprocess which ledtotheadoption ofthe
Codex standards started long before theentry intoforce oftheSPSAgreement andwasonly completed
sixmonths after thatdate. Atthetime thestandards were discussed, Codex members were, therefore,
according totheEuropean Communities, unaware ofthefactthattheCodex standards, which within
262Seepara. 2.24.
263Seepara. 2.25.
264Ibid.
265Seepara. 4.79.
266Seepara. 4.77.WT/DS26/R/USA
Page 178
theCodex system areonly ofanadvisory nature, would inthefuture become "binding" byvirtue of
theSPS Agreement.267TheEuropean Communities seems toconsider thiselement asareason to
disregard these Codex standards inthisdispute.
8.69 Inconsidering these ECarguments, wenote thatArticle 3.1unambiguously prescribes that
"...Members shall base their sanitary ...measures oninternational standards ...where theyexist ..."
(emphasis added). Paragraph 3ofAnnex AoftheSPS Agreement states equally clearly thatthe
international standards mentioned inArticle 3:1are"forfood safety, thestandards ...established by
theCodex Alimentarius Commission relating to...veterinary drug ...residues ..."(emphasis added).
Noother conditions areimposed intheSPS Agreement ontherelevance ofinternational standards
forthepurposes ofArticle 3.Therefore, asapanel making afinding onwhether ornotaMember
hasanobligation tobaseitssanitary measure oninternational standards inaccordance with Article 3.1,
weonly need todetermine whether such international standards exist. Forthese purposes, weneed
notconsider (i)whether thestandards reflect levels ofprotection orsanitary measures orthetypeof
sanitary measure they recommend, or(ii)whether these standards have been adopted byconsensus
orbyawide ornarrow majority, or(iii)whether theperiod during which they have been discussed
orthedate oftheir adoption wasbefore orafter theentry intoforce oftheSPS Agreement.268
8.70 WenotethatthefiveCodex standards outlined above arestandards relating toveterinary drug
residues asrequired inparagraph 3(a)ofAnnex A269andapply exclusively with respect tocattle and
meat andmeat products ofbovine origin andwith respect tofiveofthesixhormones indispute when
these hormones areused forgrowth promotion purposes.270Werecall thescope oftheECmeasures
indispute, inparticular thatthey arelimited totheECbanonimports ofmeat andmeat products of
bovine origin from cattle treated with anyofsixspecific hormones ifthetreatment with anyofthese
substances iscarried outforgrowth promotion purposes.271Wefind, therefore, thatinternational
standards exist with respect totheECmeasures indispute, totheextent they relate tofiveofthesix
hormones atissue (allbutMGA), inthesense ofArticle 3.1andparagraph 3(a)ofAnnex A.We
must next determine whether theECmeasures arebased onthese international standards interms of
Article 3.1.
(b) Sanitary measures based onCodex standards
8.71 TheUnited States argues thattheEuropean Communities ignored thefiveCodex standards
outlined above. Rather thanestablishing anADI orMRL foranyofthese hormones, theUnited States
submits, theEuropean Communities haschosen toprohibit thesaleofmeat from anyanimal towhich
these hormones have been administered forgrowth promotion purposes, whether ornotthere isany
residue ofthese hormones found inthatmeat.272TheEuropean Communities does notsubmit that
267Seepara. 4.78.
268Werecall inthisrespect thattheCodex standards indispute have inanyevent been adopted inJuly1995, i.e.,subsequent
totheentry intoforce oftheSPSAgreement on1January 1995. With respect tothetimeframe fortheapplication ofthe
SPSAgreement ingeneral, werefer toparagraphs 8.24-8.27.
269Seepara. 8.56.
270Seepara. 2.20.
271Seepara. 8.16.
272Seepara. 4.64 and4.67.WT/DS26/R/USA
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itsmeasures arebased ontheCodex standards, butrather argues that, asdiscussed above273,there
arenorelevant Codex standards onwhich itsmeasures indispute need tobebased.
(i) The meaning ofbased on
8.72 TheSPS Agreement does notexplicitly define thewords based onasused inArticle 3.1.
However, Article 3.2,which introduces apresumption ofconsistency with both theSPSAgreement
andGATT forsanitary measures which conform tointernational standards, equates measures based
oninternationalstandardswithmeasureswhichconformtosuchstandards.Article3.3,inturn,explicitly
relates thedefinition ofsanitary measures based oninternational standards tothelevel ofsanitary
protection achieved bythese measures. Article 3.3stipulates theconditions tobemetforaMember
toenact ormaintain certain sanitary measures which arenotbased oninternational standards.274It
applies more specifically tomeasures "which result inahigher level ofsanitary ...protection than
would beachieved bymeasures based ontherelevant international standards" ormeasures "which
result inalevel ofsanitary ...protection different from thatwhich would beachieved bymeasures
based oninternational standards". One ofthedetermining factors indeciding whether ameasure is
based onaninternational standard is,therefore, thelevel ofprotection thatmeasure achieves. According
toArticle 3.3allmeasures which arebased onagiven international standard should inprinciple achieve
thesame level ofsanitary protection. Therefore, ifaninternational standard reflects aspecific level
ofsanitary protection andasanitary measure implies adifferent level, thatmeasure cannot beconsidered
tobebased ontheinternational standard.
8.73 Wefind, therefore, thatforasanitary measure tobebased onaninternational standard in
accordance with Article 3.1,thatmeasure needs toreflect thesame level ofsanitary protection asthe
standard .275Inthisdispute acomparison thusneeds tobemade between thelevel ofprotection reflected
intheECmeasures indispute andthatreflected intheCodex standards foreach ofthefivehormones
atissue.
8.74 Without limiting thepossibilities ofhowalevel ofprotection maybeexpressed foraparticular
substance, weconsider thatinthespecific field ofveterinary drugs (including thesixhormones atissue),
alevel ofprotection canbedirectly linked totheamount ofresidues ofthatdrug allowed either to
beingested byhumans onadaily basis ortobepresent inaparticular food.276Alevel ofprotection
canthus, inter alia,beexpressed bywayofsetting amaximum amount ofresidues allowed fordaily
intake byhumans over alifetime (often defined asacceptable daily intake orADI277)and(or)byway
ofadopting amaximum amount ofresidues allowed tobepresent inaparticular food (often defined
asmaximum residue limit orMRL278).However, thefactthatanADI orMRL canreflect alevel of
protection (without stricto sensu itself being alevel ofprotection), does notexclude, astheEuropean
273Seeparas. 8.66-8.69.
274Article 3.1explicitly refers toArticle 3.3asproviding forexceptions tothegeneral obligation tobasesanitary measures
oninternationalstandards:"...Membersshallbasetheirsanitary...measuresoninternationalstandards...,exceptasotherwise
provided forinthisAgreement, andinparticular inparagraph 3"(emphasis added).
275Werecall, however, that, given theexceptions provided forinArticle 3.3,therequirement that asanitary measure
reflects thesame level ofprotection astherelevant international standard isinnowayabsolute. This requirement isonly
imposed forameasure tobebased onsuch international standard inaccordance with Article 3.1.
276Theconcept of"appropriate" level ofprotection isexamined inparagraph 8.79.
277Seeparas. 8.59 ff.
278Ibid.WT/DS26/R/USA
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Communities hasargued, thatanADI orMRL canalso beasanitary measure inthesense ofthe
SPS Agreement.
(ii) Comparison oflevels ofsanitary protection
8.75 Inthisdispute, twooftheinternational standards applicable, namely theCodex standards with
respect tozeranol andtrenbolone (two synthetic hormones), provide foranADI of0-0.5 and0-0.02
µg/kg ofbody weight, respectively, andanMRL of10µg/kg forbovine liver and2µg/kg forbovine
muscle forzeranol andanMRL of10µg/kg forbovine liver and2µg/kg of-trenbolone
forbovine muscle.279These ADIs andMRLs reflect thelevel ofprotection setbytheCodex standards.280
Todetermine whether theECmeasures indispute with respect tozeranol andtrenbolone arebased
onthese Codex standards, weneed toexamine whether thelevel ofprotection reflected intheEC
measures isthesame asthelevel ofprotection expressed bytheCodex standards.281Since theEC
measures indispute donotallow thepresence ofanyresidues ofthese twohormones inanymeat or
meat product oranyofthese residues tobeingested byhumans (imposing what itcalls a"noresidue"
level), thelevel ofprotection reflected intheECmeasures issignificantly different from thelevel of
protection setbytheCodex standards (a"noresidue" level asopposed toanADI ofmaximum 0.5
and0.02 µg/kg ofbody weight andanMRL of2and10µg/kg for,respectively, bovine muscle and
bovine liver). TheECmeasures indispute, inasfarasthey relate tozeranol andtrenbolone, are,
therefore, notbased onexisting international standards asspecified inArticle 3.1.
8.76 When establishing theother three Codex standards applicable totheECmeasures indispute,
Codex considered it"unnecessary" tosetanADI orMRL forresidues ofoestradiol-17 ,testosterone
andprogesterone(thethreenaturalhormones).282Theamountofresiduesofthesehormonesadministered
forgrowth promotion purposes allowed bythese Codex standards is,therefore, inanyevent higher
thanzero(amaximum level ofsuch residues hasnoteven been prescribed; thislevel ishereafter referred
toasan"unlimited residue level"). TheECmeasures indispute, ontheother hand, donotallow the
presence ofanyresidues ofthese three hormones administered forgrowth promotion purposes (again
imposing what theEuropean Communities calls a"noresidue" level). Thelevel ofprotection reflected
intheECmeasures is,therefore, significantly different from thelevel ofprotection reflected inthe
Codex standards (a"noresidue" level asopposed toanunlimited residue level). TheECmeasures
indispute, insofarasthey relate tooestradiol-17 ,testosterone andprogesterone, are,therefore,
notbased onexisting international standards asspecified inArticle 3.1.
8.77 WethusfindthattheECmeasures indispute (except totheextent they relate tothehormone
MGA) result inadifferent level ofsanitary protection than would beachieved bymeasures based on
therelevant Codex standards andare,therefore, notbased onexisting international standards asspecified
inArticle 3.1.
8.78 Wenextexamine whether theECmeasures with respect tofiveofthesixhormones indispute,
which arenotbased onexisting international standards, otherwise areconsistent with therequirements
oftheSPSAgreement (sections 4and5).Wethen address theECmeasures which relate tothesixth
hormone, MGA, forwhich nointernational standard exists (section 6).
279Seeparas. 8.63-8.65.
280Seepara. 8.74.
281Seepara. 8.73.
282Seepara. 8.62.WT/DS26/R/USA
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4. Article 3.3: sanitary measures notbased oninternational standards
8.79 ThefactthattheECmeasures foroestradiol-17 ,testosterone, progesterone, zeranol and
trenbolonearenotbasedonexistinginternationalstandardsdoesnotnecessarilymeanthatthosemeasures
areinconsistent with therequirements oftheSPS Agreement. Article 3.3reads asfollows:
"Members mayintroduce ormaintain sanitary orphytosanitary measures which result
inahigher level ofsanitary protection than would beachieved bymeasures based on
therelevant international standards, guidelines orrecommendations, ifthere isa
scientific justification, orasaconsequence ofthelevel ofsanitary orphytosanitary
protection aMember determines tobeappropriate inaccordance with therelevant
provisions ofparagraphs 1through 8ofArticle 5.Notwithstanding theabove, all
measures which result inalevel ofsanitary orphytosanitary protection different from
thatwhich would beachieved bymeasures based oninternational standards, guidelines
orrecommendations shall notbeinconsistent with any other provision ofthis
Agreement".
Afootnote toArticle 3.3, first sentence, then specifies:
"For thepurposes ofparagraph 3ofArticle 3,there isascientific justification if,on
thebasis ofanexamination andevaluation ofavailable scientific information in
conformity with therelevant provisions ofthisAgreement, aMember determines that
therelevant international standards, guidelines orrecommendations arenotsufficient
toachieve itsappropriate level ofsanitary orphytosanitary protection".
Theconcept ofan"appropriate level ofsanitary protection" isdefined inparagraph 5ofAnnex Aof
theSPS Agreement as:
"The level ofprotection deemed appropriate bytheMember establishing asanitary
...measure toprotect human, animal orplant lifeorhealth within itsterritory".
ANote tothisparagraph adds thefollowing:
"Many Members otherwise refer tothisconcept asthe'acceptable level ofrisk'".
(a) Requirements forjustification
8.80 Forasanitary measure tobejustified under Article 3.3themeasure needs, firstofall,to"result
inahigher level ofsanitary protection than would beachieved bymeasures based ontherelevant
internationalstandards,guidelinesorrecommendations".Werecallthecomparisonmadeabovebetween
thelevel ofprotection reflected intheECmeasures andthatimplied intheCodex standards foreach
ofthehormones atissue, inparticular thatthelevel reflected intheECmeasures isdifferent from
thatimplied intheCodex standards.283Forpurposes ofouranalysis under Article 3.3, weassume
thattheformer level ishigher thanthelatter, inlinewith thefirstsentence ofArticle 3.3. Inaddition,
thesanitary measure needs tofulfil oneofthefollowing twoconditions:
- there isa"scientific justification" forimposing themeasure, i.e., theMember imposing the
measure hasdetermined "onthebasis ofanexamination andevaluation ofavailable scientific
information inconformity with therelevant provisions of[theSPS] Agreement, ...thatthe
283Seepara. 8.77.WT/DS26/R/USA
Page 182
relevant international standards, guidelines orrecommendations arenotsufficient toachieve
itsappropriate level ofsanitary ...protection" ("the first exception"); or
- themeasure is"aconsequence ofthelevel ofsanitary ...protection aMember determines to
beappropriate inaccordance withtherelevant provisions ofparagraphs 1through 8ofArticle 5"
("the second exception").
However, according tothesecond sentence ofArticle 3.3,even ifoneofthese conditions isfulfilled,
theparty imposing themeasure must stillcomply with theother provisions oftheSPS Agreement.
8.81 Wewillconsider firstwhether either thefirstorthesecond exception outlined above ismet.
Indoing so,wefirstaddress therelationship anddifference between these twoexceptions. TheUnited
States argues thatboth exceptions have thesame effect since both refer toasituation where thebasis
fordeparting from therelevant international standard isthattheinternational standard isnotsufficient
toachieve theMember 'sappropriate level ofprotection.284TheEuropean Communities argues that
thefirst exception isfulfilled when theinternational standard isinadequate, faulty orobsolete from
ascientific point ofview andthat, according tothesecond exception, aMember isinanycaseentitled
tointroduce ormaintain measures which aimatachieving itsappropriate level ofprotection, tobe
determined inaccordance with Article 5oftheSPS Agreement.285
8.82 Wenote thatboth exceptions explicitly refer toother provisions oftheSPSAgreement. The
first exception contains thefollowing reference: "...onthebasis ofanexamination andevaluation
ofavailable scientific information inconformity withtherelevant provisions of[theSPS] Agreement ..."
(emphasis added). Thesecond exception refers to"...therelevant provisions ofparagraphs 1through 8
ofArticle 5"(emphasis added). Article 3.3,second sentence, inturn, explicitly states thateven ifthe
sanitary measure atissue fallsunder oneofthetwoexceptions ofArticle 3.3,firstsentence, thesanitary
measure inquestion stillneeds tobeconsistent with allprovisions oftheSPSAgreement other than
Article 3.
8.83 Wefind, therefore, that, whatever thedifference might bebetween thetwoexceptions, asanitary
measure canonly bejustified under Article 3.3ifitisconsistent with therequirements contained in
Article 5.Ifwewere tofindthattheECmeasures indispute areinconsistent with therequirements
imposed byArticle 5,these measures cannot bejustified under Article 3.3. However, even ifwefind
thattheECmeasures atissue areconsistent with therequirements imposed byArticle 5,thiswillstill
notbesufficient forthese measures tobejustified under Article 3.3since toreach thatconclusion we
alsoneed tofindthattheECmeasures indispute fulfil allprovisions oftheSPS Agreement other than
Articles 3and5(incasu Article 2).
(b) Burden ofproof
8.84 Werecall thefindings made above ontheburden ofproof under theSPS Agreement286,in
particular thatfortheobligations imposed bytheSPS Agreement thatarerelevant tothiscase, the
party contesting asanitary measure (incasu theUnited States) bears theinitial burden ofproof inthat
ithastopresent aprima facie case ofinconsistency with theSPSAgreement, after which theburden
ofproof shifts totheparty imposing themeasure (incasu theEuropean Communities).
284Seepara. 4.91.
285Seepara. 4.90.
286Seeparas. 8.48-8.55.WT/DS26/R/USA
Page 183
8.85 Weconsider thatthisallocation ofburden totheparty imposing asanitary measure is,forthe
reasons setoutabove287,applicable toArticle 3.3andparticularly justified under thefirst sentence
thereof which contains specific requirements tobefulfilled foraMember tojustify asanitary measure
which isnotbased onaninternational standard.
8.86 One purpose oftheSPS Agreement, asexplicitly recognized inthepreamble, istopromote
theuseofinternational standards, guidelines andrecommendations. Tothatend, Article 3.1imposes
anobligation onallMembers tobase their sanitary measures oninternational standards except as
otherwise provided forintheSPSAgreement, andinparticular inArticle 3.3thereof. Inthissense,
Article 3.3provides anexception tothegeneral obligation contained inArticle 3.1. Article 3.2, in
turn, specifies thatthecomplaining party hastheburden ofovercoming apresumption ofconsistency
with theSPS Agreement inthecaseofameasure based oninternational standards. Itthereby suggests
byimplication thatwhen ameasure isnotsobased, theburden isontherespondent toshow thatthe
measure isjustified under theexceptions provided forinArticle 3.3.
8.87 Wefind, therefore, thatonce thecomplaining party provides aprima facie case (i)thatthere
isaninternational standard with respect tothemeasure indispute, and(ii)thatthemeasure indispute
isnotbased onthisstandard, theburden ofproof under Article 3.3shifts tothedefending party.288
8.88 Since inthisdispute wehave already found thatthere exist international standards289andthat
theECmeasures atissue arenotbased onthese standards290,wefindthattheburden ofjustifying the
measures indispute under Article 3.3,andinparticular under thefirstsentence thereof, rests onthe
European Communities.
8.89 Insummary ,insections 3and4wehave found that: (i)there exist international standards,
asdefined inArticle 3.1andparagraph 3(a)ofAnnex AoftheSPS Agreement, with respect tothe
ECmeasures indispute totheextent they relate tofiveofthesixhormones atissue (allbutMGA);
(ii)theECmeasures indispute, inasfarasthey relate tothese fivehormones, arenotbased onthese
international standards, asrequired inArticle 3.1; and(iii)theECmeasures, totheextent they are
notbased onthese international standards, canonly bejustified under Article 3.3ifthese measures
meet, inter alia, therequirements imposed byArticle 5.
8.90 Inthenextsection wewill, therefore, examine whether theECmeasures indispute withrespect
tothefivehormones atissue forwhich international standards exist areconsistent withtherequirements
imposed byArticle 5.
287Seeparas. 8.51-8.54.
288This approach isinlinewithestablished practice under GATT 1947 andGATT 1994 where, forexample, theburden
ofproof tojustify aninconsistency with another GATT provision under Article XXalsorests onthedefending party. See
PanelReporton"Canada-AdministrationoftheForeignInvestmentReviewAct",adoptedon7February1984,BISD30S/140,
p.164, para. 5.20; on"United States -Section 337oftheTariff Actof1930", adopted on7November 1989, BISD 36S/345,
p.393, para.5.27 andon"United States -Standards forReformulated andConventional Gasoline", op.cit.,p.38, para. 6.20.
Inthisrespect, wealsonotethattheReport oftheAppellate Body on"United States -Measures Affecting Imports ofWoven
Wool Shirts andBlouses from India" stated thefollowing withrespect totheburden ofproof under Articles XXandXI:2(c)(i)
ofGATT: "Articles XXandXI:(2)(c)(i) arelimited exceptions from obligations under certain other provisions oftheGATT
1994, notpositive rules establishing obligations inthemselves. They areinthenature ofaffirmative defences. Itisonly
reasonable thattheburden ofestablishing such adefence should restontheparty asserting it"(op.cit.,p.16).
289Seepara. 8.70.
290Seepara. 8.77.WT/DS26/R/USA
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5. Article 5:"Assessment ofRisk andDetermination oftheAppropriate Level of
Sanitary orPhytosanitary Protection"
(a) Risk assessment andrisk management
8.91 Article5oftheSPSAgreementdealsmainly291withtwoseparateaspectsofaMember'sdecision
toenact ormaintain asanitary measure. These twoaspects areseparated intheSPS Agreement, which
provides forspecific rights andobligations inrespect ofeach ofthem.
8.92 Thefirst aspect relates totheexercise ofassessing therisks tohuman, animal orplant life
orhealth against which asanitary measure isintended toprotect. This isreferred tointhe
SPS Agreement asriskassessment .292With respect tofood safety, thepotential adverse effects (if
any) related toaspecific substance areestablished together with theprobability ofoccurrence ofany
such effects.293
8.93 According toArticle 5.1,aMember needs toensure thatitssanitary measures arebased on
anassessment ofrisks. Theobligation tobase asanitary measure onariskassessment maybeviewed
asaspecific application ofthebasic obligations contained inArticle 2.2oftheSPS Agreement which
provides that"Members shall ensure thatanysanitary ...measure isapplied onlytotheextent necessary
toprotect human, animal orplant lifeorhealth, isbased onscientific principles andisnotmaintained
without sufficient scientific evidence ..."(emphasis added). Articles 5.1to5.3sumupfactors aMember
needs totake intoaccount inmaking thisassessment ofrisks.294
8.94 Aswillbeoutlined below295,anassessment ofrisks is,atleast forrisks tohuman lifeorhealth,
ascientific examination ofdataandfactual studies; itisnotapolicy exercise involving social value
judgments made bypolitical bodies.
8.95 Thesecond aspect ofaMember 'sdecision toenact ormaintain asanitary measure relates,
inter alia,tothedetermination andapplication oftheappropriate level ofsanitary protection bythat
Member against therisks tohuman, animal orplant lifeorhealth which have been assessed inaccordance
with Articles 5.1to5.3. This aspect iscommonly referred tobytheparties tothisdispute asanessential
partofriskmanagement .296TheMember wishing toimpose asanitary measure must decide theextent
towhich itcanaccept thepotential adverse effects related toaspecific substance which have been
identified intheriskassessment.
8.96 Articles 5.4to5.6areparticularly relevant totheriskmanagement decision. Article 5.4
establishes theobjective ofminimizing negative trade effects inthedetermination byaMember of
itsappropriate level ofprotection. Article 5.5aims atachieving consistency intheapplication ofthe
291Except forArticle 5.8which hasnotbeen invoked inthisdispute.
292SeethetitleofArticle 5oftheSPSAgreement ("Assessment ofrisk...") andAnnex AoftheSPSAgreement providing
adefinition for"risk assessment".
293Seethedefinition of"risk assessment" contained inparagraph 4ofAnnex AoftheSPSAgreement, discussed below
inpara. 8.98.
294Article 5.7deals with cases where relevant scientific evidence isinsufficient atwhich point aMember may, under
certain conditions, takeprovisional sanitary measures. TheEuropean Communities hasexplicitly stated thatthisprovision
does notapply totheECmeasures indispute.
295Seeparas. 8.98 and8.104-8.107.
296Seeparas. 4.97 and4.101.WT/DS26/R/USA
Page 185
concept ofappropriate level ofprotection. Article 5.6, inturn, provides thatthesanitary measure
which isfinally adopted shall notbemore trade-restrictive than required toachieve theappropriate
level ofprotection oftheMember concerned. Articles 5.4to5.6maybeviewed asspecific applications
ofthebasic obligations provided forinArticle 2.2which, inter alia,states that"Members shall ensure
thatanysanitary orphytosanitary measure isapplied only totheextent necessary toprotect human,
animal orplant lifeorhealth" (emphasis added) andArticle 2.3which provides that"Members shall
ensure thattheir sanitary andphytosanitary measures donotarbitrarily orunjustifiably discriminate
between Members where identical orsimilar conditions prevail ..."andthat"Sanitary andphytosanitary
measures shall notbeapplied inamanner which would constitute adisguised restriction oninternational
trade" (emphasis added).
8.97 Aswillbeoutlined below297,theriskmanagement phase involves non-scientific considerations,
such associal value judgments.
(b) Articles 5.1to5.3: risk assessment
8.98 According toArticle 5.1:
"Members shall ensure thattheir sanitary orphytosanitary measures arebased onan
assessment, asappropriate tothecircumstances, oftherisks tohuman, animal orplant
lifeorhealth, taking intoaccount riskassessment techniques developed bytherelevant
international organizations".
Paragraph 4ofAnnex AoftheSPSAgreement defines "risk assessment" with respect tocontaminants
(including residues ofthehormones atissue) as
"theevaluation ofthepotential foradverse effects onhuman oranimal health arising
from thepresence of...contaminants ...infood, beverages orfeedstuffs" (emphasis
added).
Guided bythewording ofthese provisions, weconsider that, inthisdispute, ariskassessment carried
outinaccordance with theSPSAgreement should (i)identify theadverse effects onhuman health (if
any) arising from thepresence ofthehormones atissue when used asgrowth promoters inmeat or
meat products ,and(ii)ifanysuch adverse effects exist, evaluate thepotential orprobability of
occurrence ofthese effects.
8.99 Article5.1providesingeneralterms,withoutanylimitationintime,that"Membersshallensure
that their sanitary orphytosanitary measures arebased onanassessment, asappropriate tothe
circumstances, oftherisks ...". Itdoes notprevent thatwith respect toasanitary measure enacted
before theentry intoforce oftheSPSAgreement, theriskassessment iscarried outorinvoked after
theentry intoforce ofthatAgreement (andthusafter theenactment ofthesanitary measure inquestion).
However, thefactthatasanitary measure may beenacted before theentry into force oftheSPS
Agreement does notmean that, once theSPSAgreement entered intoforce, there isnoobligation for
theMember inquestion tobase thatmeasure onariskassessment.298Moreover, themore general
obligation contained inArticle 2.2oftheSPSAgreement explicitly provides that"Members shall ensure
thatanysanitary orphytosanitary measure ...isbased onscientific principles andisnotmaintained
without sufficient scientific evidence ..."(emphasis added).
297Seeparas. 8.160 ff.
298Ourreasoning andgeneral finding with respect totheapplication ratione temporis oftheSPSAgreement developed
inparas. 8.24-8.27 alsoapplies toArticle 5.1ofthatAgreement.WT/DS26/R/USA
Page 186
8.100 Wealsorecall ourfinding reached above onthespecific burden ofproof under Article 3.3299,
inparticular thattheburden ofproving thattherequirements imposed byArticle 3.3(inter alia,
consistency with Article 5)aremet, rests with theMember imposing asanitary measure which deviates
from aninternational standard. Since theECmeasures examined inthissection (relating toallhormones
indispute other than MGA) arenotbased onexisting international standards andneed tobejustified
under theexceptions provided forinArticle 3.3,theEuropean Communities hastheburden ofproving
thatitsmeasures arebased onariskassessment inaccordance with Article 5.
8.101 Inthisrespect weconsider attheoutset thatitisfortheEuropean Communities tosubmit
evidence before thePanel thatitsmeasures arebased onariskassessment; itisnotforthePanel itself
toconduct itsownriskassessment onthebasis ofscientific evidence gathered bythePanel orsubmitted
bytheparties during thePanel proceedings.
8.102 Wenext examine: (i)thetechniques andfactors tobetaken intoaccount inariskassessment
inaccordance with Article 5;(ii)whether theEuropean Communities hasdemonstrated theexistence
ofsuch ariskassessment; and(iii)assuming thatsuch riskassessment exists, whether theEuropean
Communities hasdemonstrated thatitsmeasures atissue arebased onthisriskassessment.
(i) Techniques andfactors tobetaken into account
8.103 None oftheparties suggest thatthere are"risk assessment techniques developed bytherelevant
international organizations" inthesense ofArticle 5.1which have tobetaken intoaccount inarisk
assessment forthehormones atissue.300Wenote, however, that, even though noformal decision has
asyetbeen taken byCodex with respect toriskassessment techniques, Codex, andmore particularly
JECFA, hasalong-standing practice with respect totheassessment ofrisks related toveterinary drug
residues (including hormone residues). Thetechniques thus developed have been outlined above.301
WealsonotetheReport oftheJoint FAO/WHO Expert Consultation ontheApplication ofRisk Analysis
toFood Standards Issues convened attherequest ofCodex inMarch 1995. InthisReport "risk
assessment" isdefined asfollows:
"The scientific evaluation ofknown orpotential adverse health effects resulting from
human exposure tofoodborne hazards. Theprocess consists ofthefollowing steps:
(i)hazard identification, (ii)hazard characterization, (iii)exposure assessment, and
(iv)riskcharacterization. Thedefinition includes quantitative riskassessment, which
emphasizes reliance onnumerical expressions ofrisk, andalsoqualitative expressions
ofrisk, aswell asanindication oftheattendant uncertainties" (p.6).302
8.104 Article 5.2provides forthefactors which aMember hastotakeintoaccount intheassessment
ofrisks:
"Intheassessment ofrisks, Members shall take into account available scientific
evidence; relevant processes andproduction methods; relevant inspection, sampling
andtesting methods; prevalence ofspecific diseases orpests; existence ofpest- or
299Seeparas. 8.84-8.88.
300Seepara. 4.113.
301Seeparas. 8.59 ff.
302Arevised version ofthisdefinition hasbeen accepted atthe12thsession oftheCodex Committee onGeneral Principles
held inNovember 1996 andreads asfollows: "Ascientifically based process consisting ofthefollowing steps: (i)hazard
identification, (ii)hazard characterization; (iii)exposure assessment, and(iv)riskcharacterization" (Codex Alimentarius
Commission, CX/GP96/3).WT/DS26/R/USA
Page 187
disease-free areas; relevant ecological andenvironmental conditions; andquarantine
orother treatment".
8.105 None oftheparties involved inthisdispute hasargued thatanyfactors listed inArticle 5.2
other than thefollowing three arerelevant foranassessment ofrisks related tothehormones atissue
inthiscase:
(i) available scientific evidence;
(ii) relevant processes andproduction methods; and
(iii) relevant inspection, sampling andtesting methods.
Inparticular, wenote thatnone oftheparties hasargued thatfactors notlisted inArticle 5.2, such
asconsumer preferences, canbetaken intoaccount inariskassessment inaccordance with Article 5.
8.106 Article 5.3sums uprelevant economic factors tobetaken intoaccount inassessing risks to
animal orplant lifeorhealth. Since thescope ofthisdispute islimited toissues ofhuman lifeor
health303,Article 5.3hasnoapplication tothematter under consideration.
8.107 Wefinally note thattheparties agree that, forthepurposes oftheECmeasures indispute,
ariskassessment inaccordance with Article 5isascientific process aimed atestablishing thescientific
basis forthesanitary measure aMember intends totake.304
(ii) The existence ofarisk assessment
8.108 TheEuropean Communities hasreferred tothefollowing scientific evidence concerning the
fivehormones atissue:305
- the1982 Report oftheECScientific Veterinary Committee, Scientific Committee forAnimal
Nutrition andtheScientific Committee forFood onthebasis oftheReport oftheScientific
Group onAnabolic Agents inAnimal Production306("Lamming Report");
- the1983SymposiumonAnabolicsinAnimalProductionoftheOfficeinternationaldesepizooties
("OIE")307("1983 OIE Symposium");
- the1987 Monographs oftheInternational Agency forResearch onCancer ("IARC") onthe
Evaluation ofCarcinogenic Risks toHumans, Supplement 7308("1987 IARC Monographs");
- the1988 and1989 JECFA Reports309;
303Seepara. 8.19.
304Seeparas. 4.111 and4.123.
305Seepara. 4.28.
306Seepara. 2.28.
307Seeparas. 4.16 and4.132.
308Seepara. 4.129.
309Seeparas. 2.22-2.25.WT/DS26/R/USA
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- the1995 European Communities Scientific Conference onGrowth Promotion inMeat
Production310("1995 ECScientific Conference");
- articles andopinions byindividual scientists relevant totheuseofhormones (three articles
inthejournal Science, onearticle intheInternational Journal ofHealth Service, onereport
inThe Veterinary Record and separate scientific opinions ofDr.H.Adlercreutz,
Dr.E.Cavalieri, Dr.S.S. Epstein, Dr.J.G. Liehr, Dr.M.Metzler, Dr.Perez-Comas and
Dr.A.Pinter, allofwhom were partoftheECdelegation atourjoint meeting with experts).311
8.109 TheEuropean Communities alsoreferred toseveral reports oftheEuropean Parliament (the
Nielsen Report of1981, thefirstCollins Report of1985, thesecond Collins Report of1989 andthe
Pimenta Report of1989) andopinions oftheECEconomic andSocial Committee (of1981 and1984).312
However, werecall thefindings wereached above, inparticular thatriskassessment isascientific
process. Thus, weconsider thatthenon-scientific reports andopinions oftheEuropean Parliament
andtheECEconomic andSocial Committee, which evaluate thescientific andother reports submitted
tothem, arenotpart oftheriskassessment process, butoftheriskmanagement process, further
elaborated below.313
8.110 Wenext consider whether thescientific evidence andattendant evaluation referred tobythe
European Communities constitutes ariskassessment inthesense ofArticle 5.Werecall thatunder
theSPS Agreement ariskassessment should, forthepurposes ofthisdispute, identify theadverse
effects onhuman health arising from thepresence ofthespecific hormones atissue when used asgrowth
promoters inmeat ormeat products and, ifanysuch adverse effects exist, evaluate thepotential or
probabilityofoccurrenceoftheseeffects.314Wefurtherrecallthatariskassessmentshouldbeascientific
examination ofdataandstudies315andthattheSPSAgreement setsoutfactors which need tobetaken
intoaccount inariskassessment.316Wefinally recall thatnoriskassessment techniques, asreferred
toinArticle 5.1, have asyetbeen formally adopted byCodex.317TheAgreement does notfurther
specify therequirements ofwhat constitutes ariskassessment inaccordance with Article 5.
8.111 Wenote thattheEuropean Communities hasinvoked several scientific reports which appear
tomeet these minimum requirements ofariskassessment (inparticular theLamming Report andthe
1988 and1989 JECFA Reports) andthatthescientists advising thePanel seemed toconsider these
310Seepara. 2.33.
311With respect tothescientific evidence referred tobytheEuropean Communities inrelation tothepotential adverse
effects ofthehormones atissue onthehealth orlifeofliveanimals ,werecall ourfindings reached inparagraph 8.19 that
theanimal health arguments invoked bytheEuropean Communities exclusively relate totheECimport banofliveanimals
(which does notfallwithin thescope oftheECmeasures indispute) andthatthese arguments need, therefore, nottobe
taken intoaccount within thescope ofthisdispute.
312Seeparas. 4.21; 4.29; 4.36 and4.40.
313Seeparas. 8.160 ff.
314Seepara. 8.98.
315Seepara. 8.107.
316Seeparas. 8.104 and8.105.
317Seepara. 8.103.WT/DS26/R/USA
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reports, from ascientific andtechnical point ofview, toberiskassessments.318Weshall, therefore,
forthepurposes ofthisdispute, assume thattheEuropean Communities hasmet itsburden of
demonstrating theexistence ofariskassessment carried outinaccordance with Article 5.
(iii) Sanitary measures tobebased onarisk assessment
8.112 Article 5.1requires Members to"ensure thattheir sanitary ...measures ...arebased onan
assessment ...oftherisks tohuman ...lifeorhealth". Itdoes not,however, specify howtodetermine
whether ameasure isbased onariskassessment. Inourview, thisdetermination hasboth aprocedural
andasubstantive aspect.
Procedural requirements
8.113 Notwithstanding thefactthatArticle 5does notcontain specific procedural requirements for
aMember tobase itssanitary measures onariskassessment, weconsider that, according totheordinary
meaning ofthewords based onputintheir context andinlight oftheobject andpurpose ofArticle 5319,
there isaminimum procedural requirement contained inArticle 5.1. Inourview, theMember imposing
asanitary measure needs tosubmit evidence thatatleast itactually tookintoaccount ariskassessment
when itenacted ormaintained itssanitary measure inorder forthatmeasure tobeconsidered asbased
onariskassessment.
8.114 Wenote thatinthisdispute theEuropean Communities, which hastheburden ofproving that
itbased itsmeasures onariskassessment, hasnotprovided anyevidence thatthestudies itreferred
to(insofarastheycanbeconsidered aspartofariskassessment) orthescientific conclusions reached
therein, have actually been taken intoaccount bythecompetent ECinstitutions either when itenacted
these measures (in1981 and1988) oratanylater point intime. Wenote, inthisrespect, thatnone
ofthepreambles totheECmeasures atissue mention anyofthescientific studies referred tobythe
European Communities. These preambles only refer tothenon-scientific reports andopinions ofthe
European Parliament andtheECEconomic andSocial Committee, which cannot beconsidered aspart
ofariskassessment.320
8.115 Inparticular with respect tothearticles andopinions ofindividual scientists onwhich the
European Communities focused ourattention, wenotethattheEuropean Communities hasargued that
some ofthese articles andopinions (inparticular those published in1995 and1996) arewhat itcalled
"new evidence" ofwhich itwasonly informed during thePanel process.321Insofarasthatisthe
case, these articles andopinions cannot forthepurposes ofthisdispute beconsidered aspartofarisk
assessmentonwhichtheEuropeanCommunitiesbaseditsmeasuresunlesstherewouldbesomeevidence
thatthecompetent ECinstitutions actually considered these articles andopinions orreexamined the
potential risks related tothespecific substances atissue inlight ofthese articles andopinions. Inthat
event, theEuropean Communities would then have confirmed orchanged itsearlier conclusions on
thebasis ofsuch consideration orreexamination. According totheterms ofreference given tousas
adispute settlement panel, wehave nomandate toreexamine theriskassessment referred tobythe
318See, ingeneral, answers byexperts toPanel Questions 5and13,paras. 6.51 ff.and6.142-6.147 and, inparticular,
Dr.Arnold atpara. 6.57, Dr.McLean atpara. 6.145 andopinion ofDr.Ritter, Transcripts ofthejointmeeting withexperts
of17February 1997, paras. 20and352.
319Inaccordance with therules oftreaty interpretation contained inArticle 31oftheVienna Convention.
320Seepara. 8.109.
321Seeparas. 4.143-4.148 and4.192. However, later oninthePanel process, theEuropean Communities confirmed
thatmany ofthese articles andopinions constitute evidence which wasalready taken intoaccount intheother studies referred
tobytheEuropean Communities. Insofarasthisiscorrect, seeparas. 8.132 ff.WT/DS26/R/USA
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European Communities inlight ofthis"new evidence", nortomake ourown riskassessment. These
articles andopinions, insofarastheyconstitute "new evidence" gathered bytheEuropean Communities
during thePanel process can, therefore, from aprocedural point ofview, notbeconsidered aspart
ofariskassessment onwhich theEuropean Communities based itsmeasures indispute.322
8.116 Forthese reasons, wefindthattheEuropean Communities hasnotmetitsburden ofproving
thatitmettheminimal procedural requirement contained inArticle 5.1andthat, therefore, theEC
measures indispute areinconsistent with therequirements ofArticle 5.1.
Substantive requirements
8.117 EveniftheEuropeanCommunitieswouldhavefulfilledtheseminimumproceduralrequirements,
there would stillbeaneed toexamine thesubstantive requirements contained inArticle 5.1. From
asubstantive point ofview, weconsider thatinthisdispute weshould, inaccordance with theordinary
meaning ofthewords based onputintheir context andinlight oftheobject andpurpose ofArticle
5323,proceed asfollows todetermine whether theECmeasures atissue arebased onariskassessment:
(i)weneed toidentify thescientific conclusions reached ineachofthestudies referred tobytheEuropean
Communities; (ii)weneed toidentify thescientific conclusion reflected intheECmeasures indispute;
and(iii)weneed todetermine whether thescientific conclusion reflected intheECmeasures canbe
considered asbeing inconformity with anyofthose reached inthestudies referred tobytheEuropean
Communities.
8.118 Forpurposes ofthisanalysis, wefirst address thestudies referred tobytheEuropean
Communities which specifically address oneormore ofthehormones indispute when used forgrowth
promotion purposes before examining thestudies which generally relate tooneormore ofthese
hormones.
1. Scientific conclusions reached inthestudies referred tobytheEuropean Communities
which specifically address oneormore ofthehormones indispute when used forgrowth
promotion purposes
8.119 TheLamming Report came tothefollowing conclusions withrespect tothepotential foradverse
effects onhuman health arising from thepresence inmeat ofresidues ofthehormones indispute
administered forgrowth promotion purposes:
"5.1. TheScientific Working Group isoftheopinion thattheuseofoestradiol-17 ,
testosterone andprogesterone [the three natural hormones indispute] andthose
derivatives which readily yield theparent compound onhydrolysis after absorption
from thesiteofapplication, would notpresent anyharmful effects tothehealth ofthe
consumer when used under theappropriate conditions asgrowth promoters infarm
animals .
5.2. Evaluation ofthedataon'trenbolone 'and'zeranol '[two ofthethree synthetic
hormones indispute] revealed thatsome dataonthehormonal no-effect-level andthe
toxicology ofthese compounds andtheir metabolites arestillmissing.
322These articles andopinions are,from asubstantive point ofview, further addressed inparas. 8.130 ff.
323Inaccordance with therules oftreaty interpretation contained inArticle 31oftheVienna Convention.WT/DS26/R/USA
Page 191
5.3. TheScientificWorkingGroupconsidersitnecessarythatadditionalinformation
beprovided before afinal conclusion canbegiven ontrenbolone andzeranol" (emphasis
added).324
TheScientific Working Group continued itsreview oftrenbolone andzeranol upto1985 butwas
dismantled bytheECCommission justbefore itwastosubmit itsfinal report.
8.120 Some ofthemembers ofthegroup published, intheir personal capacity, theunofficial report
in"The Veterinary Record". Theconclusions reached with respect tothepotential foradverse effects
onhuman health arising from thepresence inmeat ofresidues oftrenbolone andzeranol administered
forgrowth promotion purposes, were thefollowing:
"(1) Wehave examined theextensive dataavailable concerning thetoxicology of
trenbolone andzeranol.
"(2) Webelieve there isadequate evidence from both short term andlong term tests
thatthese compounds andtheir metabolites found asresidues donotshow
significant genotoxic potential.
...
"(5) Thelevels oftrenbolone andzeranol andtheir major metabolites found inedible
tissue, following accepted husbandry practices, aresubstantially below the
hormonally effective doses inanimal testsystems andtherefore donotpresent
aharmful effect tohealth "(emphasis added).325
8.121 With respect tothe1983 OIESymposium ,wenotethatthereport ofthesymposium consists
ofabook with aseries ofarticles byindividual scientists orgroups ofscientists. Noformal scientific
conclusion wasagreed byallparticipants orbytheOIEitself. Thebook contains, however, aforeword
tothearticles which includes thefollowing statement with respect tothepotential foradverse effects
onhuman health arising from thepresence inmeat ofresidues ofthethree natural hormones indispute
administered forgrowth promotion purposes:
"The myth thatallanabolics aredangerous tohuman health isstillvery much alive
inmany countries. Itmust bediscredited. There iscommon agreement withtheproof
presented atthismeeting thattheendogenous anabolics (natural hormones) such as
17-estradiol,progesterone,andtestosterone,whenadministeredasimplantsinanimals,
arenothazardous toman"(emphasis added).
TheEuropean Communities invokes twospecific quotes from individual articles submitted attheOIE
Symposium insupport ofitsmeasures.326However, these quotes, which only stress theinherent
uncertainties ofscientific evidence andtheevolving character ofscience, donotseem toinvalidate
the"common agreement" outlined intheforeword quoted above.
8.122 The1988 JECFA Report came tothefollowing conclusion with respect tothepotential for
adverse effects onhuman health arising from thepresence inmeat ofresidues ofallthree natural
hormones indispute administered forgrowth promotion purposes:
324Seepara. 2.28.
325Seepara. 4.35.
326Seeparas. 4.16 and4.128.WT/DS26/R/USA
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"The Committee therefore concluded thattheamount ofexogenous [oestradiol-17 ,
testosteroneandprogesterone]ingestedinmeatfromtreatedanimalswouldbeincapable
ofexerting ahormonal effect, andtherefore anytoxic effect, inhuman subjects .
The Committee considered anADI unnecessary forahormone that isproduced
endogenously inhuman beings andshows great variation inlevels according toage
andsex. TheCommittee concluded thatresidues arising from theuseof[any ofthe
three natural hormones indispute] asagrowth promoter inaccordance with good
animal husbandry practice areunlikely topose ahazard tohuman health ...
Onthebasis ofitssafety assessment ofresidues of[any ofthethree natural hormones
indispute], andinview ofthedifficulty ofdetermining thelevels ofthishormone as
agrowth promoter incattle, theCommittee concluded thatitwasunnecessary to
establish anAcceptable Residue Level" (emphasis added).327
Asoutlined above328,the1988 and1989 JECFA Reports setADIs andMRLs forzeranol andtrenbolone
(two ofthethree synthetic hormones indispute). JECFA reached theconclusion thattheir toxic effects
arelinked totheir hormonal effects andthat, therefore, ano-hormonal-effect level could beestablished
which would ensure thatresidues uptosuch level aresafe. JECFA alsoconcluded thatthesafety level
orADI itthus adopted would notbeexceeded atanytime after proper implantation (irrespective of
thewithdrawal period respected).
8.123 TheSteering Committee ofthe1995 ECScientific Conference came tothefollowing conclusions
with respect tothepotential foradverse effects onhuman health arising from thepresence inmeat
ofresidues ofthehormones indispute administered forgrowth promotion purposes:
"When used asgrowth promoters, thenaturally occurring gonadal steroid hormones
(oestrogen, testosterone andprogesterone) canincrease thegrowth rate, theproportion
ofleanmeat tofatandthefood-conversion efficiency ofsome species ofanimals ...
while theresidues ofhormone intheresulting meat arewithin thenormal physiological
range ...Totheextent thatimproved food-conversion efficiency reduces excretion
ofnitrogen andphosphorus perunitofmeat production, theenvironmental benefits
(while small) arelikely tobepositive. That isthebasis onwhich theSteering Group
endorses theconclusions ofWorking Group IIthattheconditions defined incountries
where theuseofthese hormones asgrowth promoters ispermitted areareasonable
safeguard ofpublic health .
Several materials similar intheir physiological effects tothenatural sexhormones (such
astrenbolone andzeranol) arealsoused asgrowth promoters inmeat production ...
TheSteering Committee endorses theopinion ofWorking Group IIthatthedefinition
oftheMRL fortrenbolone and itsmetabolites reached byvarious international
committees [inter alia, JECFA] provide reasonable protection ofpublic health "
(emphasis added).329
Therelevant conclusions ofWorking Group IIoftheConference on"Assessment ofHealth Risk",
which specifically address thesafety ofthehormones atissue when used asgrowth promoters, read
asfollows:
327Seepara. 2.22.
328Seeparas. 8.63-8.65.
329Seepara. 2.33.WT/DS26/R/USA
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"Natural sexhormones
Atpresent, there isnoevidence forpossible health risks totheconsumer duetothe
useofnatural sexhormones forgrowth promotion, since:
- Residue levels ofthese substances measured inmeat oftreated animals fall
within thephysiological range observed inmeat ofcomparable untreated
animals.
- Thedaily production ofsexhormones byhumans ismuch higher than the
amounts possibly consumed from meat, even inthemost sensitive humans
(prepubertal children andmenopausal women).
- Duetoanextensive first-pass metabolism, thebioactivity ofingested hormones
islow, thus providing afurther safety margin.
Zeranol andtrenbolone
...
Atthedoses needed forgrowth promotion, residue levels arewell below thelevels
regarded assafe(theMRLs). There are,atpresent, noindications ofapossible human
health riskfrom thelowlevels ofcovalently-bound residues oftrenbolone "(emphasis
added).330
8.124 Ascanbededuced from allconclusions outlined above, none ofthescientific evidence referred
tobytheEuropean Communities which specifically addresses thesafety ofsome orallofthehormones
indispute when used forgrowth promotion, indicates thatanidentifiable riskarises forhuman health
from such useofthese hormones ifgood practice isfollowed. Allofthescientific studies outlined
above came totheconclusion thattheuseofthehormones atissue (allbutMGA, forwhich noevidence
wassubmitted) forgrowth promotion purposes issafe; most ofthese studies adding thatthisconclusion
assumes thatgood practice isfollowed. Wenote thatthisconclusion hasalsobeen confirmed bythe
scientific experts advising thePanel.331
2. Scientific conclusions reached inthestudies referred tobytheEuropean Communities
which generally relate tooneormore ofthehormones indispute
8.125 TheEuropean Communities putsparticular emphasis onthe1987 IARC Monographs andthe
articles andopinions ofindividual scientists outlined above.
330Ibid.
331Seeanswers byexperts toPanel Question 7,paras. 6.93 ff,including theanswers byDr.André (atpara. 6.93) and,
albeitslightlyqualified,Dr.Lucier(atpara.6.95:"Dr.Lucierrespondedthat,tohisknowledge,therewasnopieceofscientific
evidence toindicate thatanyofthesixhormones inquestion hadunequivocally caused adverse effects inhumans when
administered andused properly. However, there wassome information available which raised concern foraslight effect
ontheincidence ofhuman disease"). Inthisrespect, wenoteDr.Lucier 'sstatement that, according tohistentative estimates,
between zeroandoneperson inamillion whoeat500grams ofmeat, treated withoestrogens forgrowth promotion purposes
inaccordance with good practice, perdayover their lifetimes, getcancer (seeTranscripts ofthejoint meeting with experts
of18February 1997, paras. 742and819). This 0-1inamillion riskiscaused bythetotal amount ofoestrogens intreated
meat (theamount ofendogenous oestrogens being highly variable and,according toDr.Lucier, already being carcinogenic),
notbythesmall fraction thereof which isadded forgrowth promotion purposes andwhich isrelevant forthepurposes of
thisdispute. Moreover, thisestimate only represents astatistical range of0to1inamillion, notascientifically identified
risk. Theconcept of"zero risk", towhich thisstatement isclosely related, isfurther dealt with inparas. 8.149 ff.We
note, finally, thatallexperts confirmed thatthere isnoevidence thatparticular ormore significant health problems exist
incountries where thehormones atissue areallowed foradministration asgrowth promoters ascompared tocountries where
such useisprohibited (seeanswers byexperts toPanel Question 9,paras. 6.118-6.122).WT/DS26/R/USA
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8.126 The1987 IARC Monographs ,insofarastheyrelate tohuman health332,contain evidence with
respect tothree general categories ofhormones, namely oestrogens, androgens andprogestins, without
distinguishing thespecific hormones falling within each ofthese categories orthenatural hormones
from thesynthetic hormones.333TheMonographs classify oestrogens asagents which arecarcinogenic
(meaning thatthere issufficient evidence ofcarcinogenicity inhumans); androgens asagents which
areprobably carcinogenic; andprogestins asagents which arepossibly carcinogenic.334
8.127 Wenote thatthescientific evidence included inthese Monographs relates tothecarcinogenic
potential ofentire categories ofhormones orthehormones atissue ingeneral .TheMonographs do
notconsider thecarcinogenic potential ofthese hormones when used specifically forgrowth promotion
purposes orwith respect toresidue levels comparable tothose present after such use.335Moreover,
theMonographs donotspecifically evaluate, asisrequired onthebasis ofparagraph 4ofAnnex A
oftheSPS Agreement336,thepotential foradverse effects arising from thepresence infood (incasu
meat ormeat products) ofresidues ofthehormones indispute orfrom residue levels comparable to
those present infood.
8.128 Wefurther notethat, according tothescientific experts advising thePanel, thedataandstudies
contained inthese Monographs with respect tothecarcinogenic potential ofthehormones indispute
have been fully taken intoaccount inthe1988 and1989 JECFA Reports which, atseveral occasions,
explicitly refer tothese Monographs.337Nowhere dothe1988 and1989 JECFA Reports reject the
conclusions reached inthe1987 IARC Monographs. Onthecontrary, theMonographs constitute part
oftheevidence onwhich theJECFA Reports arebased. JECFA recognized thatallfivehormones
atissue have acarcinogenic potential butconcluded thatthispotential waslinked tothehormonal effect
ofthese hormones.338Since JECFA considered thattheadditional residues ofthethree natural hormones
present intreated meat arenotcapable ofexerting anytoxic effect, itdecided thatitwasunnecessary
tosetADIs orMRLs forthese hormones.339With respect tozeranol andtrenbolone, JECFA identified
ano-hormonal-effect level andadopted, onthatbasis, ADIs andMRLs which, ifrespected, would
ensure thesafeuseofthese hormones.340TheIARC Monographs andJECFA Reports didnot,therefore,
reach contradictory butrather complementary scientific conclusions.
332Inthisrespect, werecall ourfinding thatwithin thescope ofthisdispute weneed nottotakeintoaccount thearguments
made bytheEuropean Communities which relate toanimal health (seepara. 8.19).
333Asoutlined inparas. 2.8and2.9,oestradiol-17 andzeranol areoestrogens; testosterone andtrenbolone areandrogens
andprogesterone isaprogestin.
334Seepara. 4.129.
335Seealsoanswer byDr.Arnold toPanel Question 6,para. 6.83.
336Seepara. 8.98.
337Seeanswers byexperts toPanel Question 5where allexperts confirm thattheJECFA Reports tookintoaccount cancer
risks (para. 6.51 ff.). See,inparticular, statements made byDr.Randell, theCodex expert, atthejointmeeting withexperts
of17February 1997 (Transcripts, paras. 239, 297and436andbyDr.McLean atthejoint meeting with experts of
18February 1997 (Transcripts, para. 823).
338ThelinkmadebyJECFA betweenhormonalandtoxiceffectdoesnotcontradicttheconclusionsintheIARCMonographs;
onthecontrary, since thelatter state thefollowing: "There isabasic incongruity between thehuman dataandtheanimal
carcinogenicity data. Asnoted earlier, however, theeffects ofthese chemicals [inter alia,thegeneral categories towhich
thehormones indispute belong] inhumans appear, atleast inmost cases, tobelinked tothehormonal milieu "(emphasis
added).
339Seepara. 8.62.
340Seeparas. 8.63-8.65.WT/DS26/R/USA
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8.129 Forthese reasons, weconsider thatthe1987 IARC Monographs, insofarasthey canbe
regarded aspartofariskassessment forthespecific hormones atissue when used asgrowth promoters
inthesense ofArticle 5.1, have been taken intoaccount in,anddonotcontradict, theother studies
referred tobytheEuropean Communities (inparticular the1988 and1989 JECFA Reports) which
explicitly conclude thatthespecific useofthese hormones asgrowth promoters inaccordance with
good practice issafe.
8.130 TheEuropean Communities finally invokes several articles andopinions ofindividual scientists .
These articles andopinions dealwith thecarcinogenic orgenotoxic potential ofhormones andcriticize
thescientific methodology orconclusions oftheother studies referred tobytheEuropean Communities.
Asummary ofthecontent ofsome ofthese articles andopinions iscontained inparagraphs 4.131-4.136
and4.180. Thescientific evidence included inthese articles andopinions relates tothecarcinogenic
orgenotoxic potential ofentire categories ofhormones orthehormones atissue ingeneral ;notwhen
used specifically forgrowth promotion purposes orwith respect toresidue levels comparable tothose
presentaftersuchuse.341Moreover,thesearticlesandopinionsdonotspecificallyevaluate,asisrequired
onthebasis ofparagraph 4ofAnnex AoftheSPSAgreement, thepotential foradverse effects arising
from thepresence infood (incasu meat ormeat products) ofresidues ofthehormones indispute or
from residue levels comparable tothose present infood.
8.131 Ofthearticles andopinions invoked, theEuropean Communities hasputmuch emphasis on
theopinion ofDr.Liehr, ascientist with theECdelegation, on"Potential Genotoxicity ofHormones".
Wenotethestatement byDr.Liehr himself thattheevidence hesubmitted isonly based ontests carried
outatelevated doses ofoestrogens andthattherelevance ofthese high dose effects topotential risks
related tothelowlevels ofoestrogens inmeat from growth promoted animals hasnotyetbeen
evaluated.342Moreover, werecall thatthisopinion only applies tooneofthehormones indispute,
namely, oestradiol-17 anddoes notaddress theuseofthishormone asagrowth promoter.
8.132 Wefurther note that, according totheCodex expert advising thePanel, most oftheevidence
contained inthese articles andopinions andthepotential risks addressed therein were already evaluated
andtaken intoaccount inthe1988 and1989 JECFA Reports.343Indeed, intheevent these articles
andopinions should beconsidered asevidence which was, astheEuropean Communities itself argued
attheendofthePanel proceedings, not"new" butwasalready taken intoaccount inthe1988 or1989
JECFA Reports, theLamming Report orthe1995 ECScientific Conference, these articles andopinions
would thennotinvalidate orcontradict thescientific conclusions reached inthese other studies, which
specifically address theuseofthehormones indispute forgrowth promotion purposes, butrather
constitute partoftheevidence onwhich these studies arebased.
8.133 Wealsonotethat, even ifthese articles andopinions could beconsidered asscientific evidence
which ispartofariskassessment forthespecific hormones atissue when used asgrowth promoters
inthesense ofArticle 5.1andwhich wasnotyetconsidered intheother studies invoked bytheEuropean
Communities, thescientific experts advising thePanel were oftheview thatthisevidence, asitstands
today ,does notinvalidate orcontradict thescientific conclusions reached intheother studies invoked
341Seepara. 2.22.
342Seepara. 4.143. Inthisrespect, wealsonote thefollowing statements byDr.Liehr: "...wehave nogenotoxicity
dataatlowlevels" and"...Iagree ...thatatthemoment thisisaninteresting hypothesis andIhave never labelled itmore
than ahypothesis andIalsoagree ...thatmany pieces aremissing ..."(Transcripts ofthejoint meeting with experts of
17February 1997, para. 330). ThefactthatDr, Liehr repeatedly called foramore thorough scientific examination ofthe
risks related tooestrogens andformore data, reveals thatthestudies heprovided tousdonotyetcontain conclusive evidence
ofanidentifiable risk.
343SeeTranscripts ofthejoint meeting with experts of17February 1997, para. 297. Seealsoanswers byexperts to
Panel Question 5,paras. 6.51 ff.WT/DS26/R/USA
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bytheEuropean Communities which specifically relate tothesafety ofthehormones atissue when
used forgrowth promotion purposes:
Dr.McLean:
"Some ofthenew data thathasbeen submitted particularly relies upon invivo and
invitro carcinogenicity testing andalsosome ofthemutagenicity testing butIdonot
believe thatitisanymore significant than thesortofdata thatwasavailable atthe
time theoriginal appraisal wasmade [inthe1988 and1989 JECFA Reports]".344
Dr.Arnold:
"...from mypoint ofview, thesignificant new evidence which hasbeen produced
since thatCommittee [the32nd and34th meetings ofJECFA] didnotinvalidate the
basic conclusions andtherefore Istillamfeeling very comfortable with theconclusions
although Iadmit that alotofnew evidence hasbeen produced bythescientific
community".345
Dr.Ritter:
"The nature ofscientific interpretation isthatlegitimate bona fideknowledgeable
scientists may reach different conclusions from thesame setofdata. ButIthink the
consensus opinion ofthatConference [the1995 ECScientific Conference] wasthat
theweight ofevidence used then continues toprevail now, andthattheassessments
andconclusions drawn thenarestillconsistent with theavailable information now".346
"Iagree thatthere isfurther work thatisindicated. Iagree thatstatements made by
scientists, such asDr.Liehr, willcontinue tocontribute toourunderstanding, butI
alsoagree thatthetotality ofevidence, re-evaluated asrecently asDecember 1995 [by
the1995 ECScientific Conference], suggests thatthewayinwhich these substances
areused andtheresidues which they produce, donotconstitute arisktohuman
health".347
Dr.Lucier:
"There isagroup ofscientists [including DrLiehr, ascientist with theECdelegation]
whoarelooking attheroleofoxidated damage andgenotoxicity ofoestrogens ...But
forthisnarrow purpose thatwearetalking about today, about theinfluence ofthis
onadditional riskfrom oestrogens from eating, consuming meat containing oestrogens
from growth promoted animals, itdoesn 'thave toomuch consequence. ...Iwould
come upwith thesame answer either case; there would benodifference intherisk.
SoIthink inthatrespect whether ornotoestrogen isgenotoxic, haslessconsequence
then what wetalked about uptothispoint intime".348
344Transcripts ofthejoint meeting with experts of17February 1997, para. 4
345Ibid.,para.356.
346Ibid.,para.352.
347Ibid.,para.424.
348Theother scientist advising thePanel, Dr.André didnotexplicitly express hisview onthisissue butdidnotcontest
thestatements made bytheother scientists. Dr.McLean hasfurthermore answered intheaffirmative when asked whether
hebelieved thattheCodex standards arefully adequate toaddress theproblem (Transcripts ofthejoint joint meeting with
experts of17February 1997, para. 9).WT/DS26/R/USA
Page 197
8.134 Forthesereasons,wefindthattheEuropeanCommunitieshasnotdemonstratedthatthescientific
evidence itreferred to,which generally addresses thesafety ofsome orallofthehormones indispute,
would indicate thatanidentifiable riskarises forhuman health from theuseofthese hormones for
growth promotion purposes ifgood practice isfollowed. Inthisrespect werecall thatallscientific
experts advising thePanel confirmed thisconclusion andstated that, asoftoday, noscientific evidence
isavailable which concludes thatanidentifiable riskarises from theuseofanyofthehormones at
issue forgrowth promotion purposes inaccordance with good practice.349
8.135 Thefinding wethusmake does, ofcourse, notexclude thatfuture scientific developments could
require modifications tothescientific conclusions reached inthestudies referred tobytheEuropean
Communities.
3. Scientific conclusion reflected intheECmeasures
8.136 TheEuropean Communities bans theuseforgrowth promotion purposes ofanyofthehormones
indispute, including theuseofthese hormones inaccordance with good practice. During thePanel
proceedings ithasmade clear thatitconsiders anyresidue level ofthese hormones tobeunsafe for
human health, setting itslevel ofprotection ata"zero residue" level. Thescientific conclusion reflected
intheECmeasures indispute isthus thattheuseofthehormones indispute forgrowth promotion
purposes, even inaccordance with good practice350,poses anidentifiable risktohuman health.
4. Theconformity ofthescientific conclusion reflected intheECmeasures with the
scientific conclusions reached inthestudies referred to
8.137 Inourview, thescientific conclusion reflected intheECmeasures indispute, i.e.,thatthe
useofthehormones indispute forgrowth promotion purposes, even inaccordance with good practice,
isnotsafe, does notconform toanyofthescientific conclusions reached intheevidence referred to
bytheEuropean Communities. Alltheevidence referred tobytheEuropean Communities which
specifically relates totheuseofthehormones atissue forgrowth promotion purposes concludes that
theuseofthese hormones asgrowth promoters inaccordance with good practice issafe.351Moreover,
none oftheevidence referred tobytheEuropean Communities which generally deals with oneormore
ofthehormones indispute contradicts thisconclusion.352TheECimport banofmeat andmeat products
from animals treated with anyofthefivehormones atissue forgrowth promotion purposes, allegedly
necessary toprotect human health, insofarasitalsoapplies tomeat andmeat products from animals
treated with anyofthese hormones inaccordance with good practice ,is,therefore, notbased onthe
scientific evidence submitted tothePanel.
8.138 TheEuropean Communities, however, submits thefollowing additional arguments (sections 5
and6).Wenote thatthese arguments have notbeen supported byscientific evidence other than the
evidence examined above. Weconsider itnonetheless appropriate toexamine whether these arguments
demonstrate thattheECmeasures indispute are,from asubstantive point ofview, based onarisk
assessment inaccordance with Article 5.1.
349Seefootnote 331.
350Since, according totheexperts advising thePanel (answers byexperts toPanel Question 3,paras. 6.32 ff),anyuse
ofthehormones indispute willalways leave some residue level, albeit avery small one, theadministration ofthese hormones
inaccordance withgood practice willalsoleave some residue andthusnotachieve theEC"zero residue" level ofprotection.
351Seepara. 8.124.
352Seepara. 8.134.WT/DS26/R/USA
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5. General categories ofrisks invoked bytheEuropean Communities
8.139 TheEuropean Communities argues thatithasbased itsbanontheexistence ofthefollowing
categories ofrisks related tothehormones atissue: (i)risks arising from thenature andmode ofaction
ofthehormones; (ii)risks arising from theaction ofmetabolites; (iii)risks arising from theaction
ofcombinations (orcocktails) ofhormones andfrom multiple exposure ofhumans; (iv)risks arising
from problems related todetection andcontrol ofhormones; (v)risks arising from theadministration
anduseofhormones; and(vi)risks arising from various other parameters, inparticular theinherent
limits toscience.353
8.140 TheUnited States argues thattheEuropean Communities hasnever performed anappropriate
assessment ofthese alleged risks andhas,inanyevent, notrelied on,norputforward, anyassessment
ofthese risks thatcould serve asabasis fortheECban.354
8.141 Werecall thattheEuropean Communities hasnotreferred toanyscientific evidence, other
thanthatexamined above355,inwhich thecategories ofrisks putforward bytheEuropean Communities
have been assessed andthatnone ofthescientific evidence referred tobytheEuropean Communities
reached theconclusion thatanyofthehormones indispute when administered forgrowth promotion
purposes inaccordance with good practice hasanadverse effect onhuman health.356
8.142 Moreover, with respect tothealleged risks related tothenature andmode ofaction ofthe
hormones indispute (including carcinogenicity andlong-term effects) andtheaction ofmetabolites
orcombinations ofandmultiple exposure tothese hormones (i.e.,thefirst three categories ofrisks
invoked bytheEuropean Communities), wenote thestatements ofthescientific experts advising the
Panel thattheavailable datarelating tothese risks have allbeen taken intoaccount bytheJECFA Reports
and/or theLamming Report and/or the1995 ECScientific Conference.357Allthree reports concluded
thatthese risks donotmaterialize ifthehormones indispute areused asgrowth promoters inaccordance
with good practice. TheEuropean Communities hasnotprovided anyevidence tothecontrary. The
ECimport banofmeat andmeat products from animals treated with anyofthefivehormones atissue
forgrowth promotion purposes, insofarasitalsoapplies tomeat andmeat products from animals
treated with anyofthese hormones inaccordance with good practice ,is,therefore, notbased onan
assessment ofthese categories ofrisks.
8.143 Inaddition, with respect tothealleged risks arising from problems related tothedetection,
control, administration anduseofthehormones indispute (i.e.,thefourth andfifth category ofrisks
invoked bytheEuropean Communities), wenote thattheEuropean Communities hasnotreferred to
evidence, other than thatoutlined above358,inwhich anassessment ismade ofthepossible adverse
health effects related tothepotential abuse ofthese specific hormones when used forgrowth promotion
purposes. TheEuropean Communities hasrestricted itself topointing outthecondition contained in
many ofthescientific conclusions mentioned above, namely thatthesafety ofthehormones istoa
353Seepara. 4.126.
354Seepara. 4.110.
355Seeparas. 8.119 ff.
356Seepara. 8.137.
357Seeanswers byexperts toPanel Question 5,paras. 6.51 ff.,inparticular theanswers byDr.Arnold, DrMcLean
andDrRitter andtheopinions ofDr.Randell, paras. 6.166 (see alsoTranscripts ofthejoint meeting with experts of
17February 1997, paras. 239, 297, 374and436andof18February 1997, paras. 730and823).
358Seeparas. 8.119 ff.WT/DS26/R/USA
Page 199
certain extent conditional upon their administration inaccordance with good practice359,without further
providing anassessment ofthepotential adverse effects related tononcompliance with such practice.
8.144 Wefurther note thattheEuropean Communities argues thatifitwere toallow theuseofthe
three natural hormones atissue itwould encounter special problems ininspecting, sampling ortesting
forresidues ofthese hormones inmeat. These problems relate, according totheEuropean Communities,
totheinherent characteristics ofthenatural hormones which make them indistinguishable from natural
hormones present endogenously inmeat orpresent inmeat subsequent totherapeutic orzootechnical
useofthese hormones.360
8.145 Werecall that, inthisdispute, thefactors which canbetaken intoaccount inariskassessment
underArticles5.1and5.2arelimitedto"availablescientificevidence"and"relevantinspection,sampling
andtesting methods".361Totheextent thattheproblems ininspecting (sampling andtesting) natural
hormones would actually pose ariskandcould thus, arguably, betaken intoaccount asariskarising
from "relevant inspection, sampling andtesting methods" inthesense ofArticle 5.1,weconsider that
theEuropean Communities encounters thesame problems ininspecting fornatural hormones under
itscurrent regime. TheECbanofnatural hormones used forgrowth promotion purposes, combined
withitstolerance forthese hormones when usedfortherapeutic orzootechnical purposes orwhen present
endogenously inmeat andother foods, would seem tocause more problems ininspecting forbanned
natural hormones thanaregime where theuseofallnatural hormones would beallowed incombination
with, forexample, amaximum residue ortolerance level forallnatural hormones inanymeat regardless
oftheorigin anduseofthese hormones. Indeed, only under theECcurrent regime does theproblem
ofhow todistinguish between endogenous andadded natural hormones arise; under aregime with
anMRL ortolerance level forallnatural hormones there would benoneed todistinguish endogenous
from added natural hormones.
8.146 With respect tothealleged risks related tothecontrol (or,inother words, theabuse) ofthe
hormones atissue (both natural andsynthetic), wefurther notethateven though aMember would seem
tobeabletotakeintoaccount risks arising from difficulties ofinspecting, sampling ortesting which
arespecific toaparticular substance inaparticular food, the"relevant inspection, sampling andtesting
methods" referred toinArticle 5.2,donotseem tocover thegeneral problem ofcontrol (such asthe
problem ofensuring theobservance ofgood practice) which canexist foranysubstance. Therisks
related tothegeneral problem ofcontrol donotseem tobespecific tothesubstance atissue butto
theeconomic orsocial incidence related toasubstance oritsparticular use(such aseconomic incentives
forabuse). These non-scientific factors should, therefore, notbetaken intoaccount inriskassessment
butinriskmanagement .Moreover, even ifthese factors could betaken intoaccount inariskassessment,
wenotethattheEuropean Communities hasnotprovided convincing evidence thatthecontrol (orthe
prevention ofabuse) ofthehormones indispute ismore difficult than thecontrol ofother veterinary
drugs theuseofwhich itallows. Ithasneither provided evidence thatcontrol would bemore difficult
under aregime where thehormones indispute were allowed under specific conditions than under the
current ECregime where thehormones indispute when used asgrowth promoters arebanned. The
experts advising thePanel made clear thatthepotential forabuse under both regimes would be
comparable, some noting thatabuse would probably occur more frequently under aregime where the
359However, wenote, inthisrespect, thestatements made bysome ofthescientific experts advising thePanel thateven
ifgood practice isnotfollowed theuseofthefivehormones atissue willinmany cases stillbesafe(seeanswers byexperts
toPanel Question 17,paras. 6.172-177, inparticular theanswers byDr.Arnold, Dr.McLean andDr.Ritter andopinions
ofDr.McLean, Dr.Randell andDr.Arnold, Transcripts ofthejointmeeting withexperts of17February 1997, respectively
atparas. 3,26and166). Wealsorecall theconclusions reached byJECFA thattheMRLs (i.e.,thelevels which areset
onthebasis ofgood practice) itestablished forzeranol andtrenbolone arefarhigher thanthesafety levels forthese hormones.
360Seepara. 4.113.
361Seepara. 8.105.WT/DS26/R/USA
Page 200
hormones arebanned compared toone allowing thecontrolled useofprescribed products in
predetermined dosages with well-defined educational programmes, good communication between the
different actors involved andappropriate penalties formisuse.362Inthiscontext, wenote, therefore,
thatbanning theuseofasubstance does notnecessarily offer better protection ofhuman health than
other means ofregulating itsuse.
8.147 Inthisrespect, wefinally note thatforthethree natural hormones indispute, theEuropean
Communities has,forcontrol purposes, adopted MRLs andthereby accepted tolerance levels which
arehigher thanthe"zero residue" level reflected inthemeasures indispute. Insodoing, theEuropean
Communities itself seemingly confirms thescientific conclusions reached inallthescientific evidence
examined above, namely thatresidues ofthese hormones, including when used asgrowth promoters,
aresafebelow acertain level, andcontradicts theconclusion reflected intheECmeasures indispute,
namely thatonly a"zero residue" level ensures theprotection ofECconsumers.
8.148 Forallthereasons outlined above363,wefindthattheECimport banofmeat andmeat products
from animals treated with anyofthefivehormones atissue forgrowth promotion purposes, insofar
asitalso applies tomeat andmeat products from animals treated with anyofthese hormones in
accordance with good practice ,isnotbased onanassessment ofthefourth orfifth category ofrisks
invoked bytheEuropean Communities.
8.149 Inthesixth general category ofrisks invoked bytheEuropean Communities (risks arising from
various other parameters), theEuropean Communities argues thatnone ofthestudies itreferred to
aspartofariskassessment proves beyond doubt orconcludes inanunqualified manner thatthepresence
ofresidues ofthehormones indispute inmeat ormeat products present noriskwhatsoever .The
European Communities refers, inter alia,totheconclusions ofthe1988 JECFA Report which state
thatresidues arising from thehormones atissue used asgrowth promoters areonly unlikely topose
ahazard tohuman health andtothebasic premise ofJECFA recommendations which aimatestablishing
standards which correspond toanoappreciable ornosignificant riskincrease duetotheexposure
tothesubstances inquestion andnottoazero riskincrease. TheEuropean Communities apparently
considers,therefore,thatthisresidualrisk,albeitminuteandnotappreciable,constitutestherisk(derived
from ariskassessment )onwhich theECbanisbased inaccordance with Article 5.1, arguing that,
according toECriskmanagement ,riskother than zero isnotacceptable.364
8.150 TheUnited States argues thatscience cannever prove beyond doubt thatthere isnoriskand
canonly beused todetermine whether there isariskassociated with theuseofaparticular substance;
itcannot eliminate thepossibility thatapotential riskmay befound inthefuture. According tothe
United States, theSPSAgreement does notallow measures tobemaintained without scientific evidence
until such time asscience proves "beyond doubt" thatthere isnorisk.365
8.151 Werecall theconclusions wereached above onburden ofproof, inparticular thattheEuropean
Communities has,with respect toitsmeasures which deviate from international standards, theburden
ofproving theexistence ofariskassessment (and, derived therefrom, anidentifiable risk) onwhich
362See, forexample, answers byDr.André andDr.Ritter toPanel Question 14,paras. 6.149 and6.155 andopinions
ofDr.Arnold, Dr.Lucier andDr.André, Transcripts ofthejoint meeting with experts of17February 1997, paras. 269
and274andof18February 1997, paras. 829and830
363Seeparas. 8.143-8.147.
364Seepara. 4.200.
365Seepara. 4.46.WT/DS26/R/USA
Page 201
theECmeasures indispute arebased. Itisnot,inthisdispute, fortheUnited States toprove that
there isnorisk.
8.152 Wefurther note that, according toscientists advising thePanel, science cannever provide a
certainty, i.e.exclude once andforallthataspecific substance caneverhave adverse health effects.366
8.153 InthisrespectwealsonotethatthesixthcategoryofrisksinvokedbytheEuropeanCommunities
is,asstated bythescientific experts advising thePanel367andadmitted bytheEuropean Communities368,
notidentifiable andthat, therefore, these risks canapriori notbeassessed byscientists (asrequired
inArticle 5.1). Inthissense, these potential risks, which arepresent foranysubstance (also for
substances oruses ofsubstances allowed intheEuropean Communities), areonly theconsequence
ofscience notbeing capable ofassuring thatnorisks willever arise from asubstance.
8.154 Wefinally note thattheECobjective of"zero risk" cannot beachieved inpractice; noteven
under theECbanitself since theEuropean Communities cannot guarantee thatthere isazeroprobability
thatillegal useofthehormones atissue willoccur. Moreover, this"zero risk" objective cannot, as
further examined below369,inanycase beachieved forthethree natural hormones indispute since
theEuropean Communities allows theingestion ofthese same hormones occurring endogenously in
meat andother foods aswell astheuseofthese hormones fortherapeutic orzootechnical purposes.
8.155 TheECbanontheuseofthehormones indispute forgrowth promotion purposes is,therefore,
notbased onanassessment ofthesixth andfinal category ofrisks invoked bytheEuropean
Communities.
8.156 Forthese reasons, wefindthattheECimport banofmeat andmeat products from animals
treated with anyofthefivehormones atissue forgrowth promotion purposes, insofarasitalsoapplies
tomeat andmeat products from animals treated with anyofthese hormones inaccordance with good
practice ,isnotbased onanassessment ofanyofthesixgeneral categories ofrisks invoked bythe
European Communities.
6. Theprecautionary principle
8.157 TheEuropean Communities alsoinvokes theprecautionary principle insupport ofitsclaim
thatitsmeasures indispute arebased onariskassessment. Totheextent thatthisprinciple could be
considered aspartofcustomary international lawandbeused tointerpret Articles 5.1and5.2onthe
assessment ofrisks asacustomary ruleofinterpretation ofpublic international law(asthatphrase
isused inArticle 3.2oftheDSU), weconsider thatthisprinciple would notoverride theexplicit wording
ofArticles 5.1and5.2outlined above, inparticular since theprecautionary principle hasbeen
incorporated andgiven aspecific meaning inArticle 5.7oftheSPSAgreement. Wenote, however,
thattheEuropean Communities hasexplicitly stated inthiscase thatitisnotinvoking Article 5.7.
8.158 Wethusfindthattheprecautionary principle cannot override ourfindings made above, namely
thattheECimport banofmeat andmeat products from animals treated with anyofthefivehormones
366See, forexample, opinions ofDr.Arnold, para. 6.25 andDr.Ritter, para. 6.92. Inthisrespect, wenote thatthe
SPSAgreement explicitly deals with situations where there isscientific uncertainty regarding risks related toasubstance,
inArticle 5.7(discussed inparas. 8.248 ff.),butthattheEuropean Communities hasnotinvoked thisprovision inthiscase.
367Ibid.
368Seepara. 4.197.
369Seeparas. 8.186 ff.WT/DS26/R/USA
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atissue forgrowth promotion purposes, insofarasitalsoapplies tomeat andmeat products from
animals treated with anyofthese hormones inaccordance with good practice ,is,from asubstantive
point ofview, notbased onariskassessment.
8.159 Insummary ,inthissection wehave found that, even assuming thattheEuropean Communities
hasdemonstrated theexistence ofariskassessment inaccordance with Article 5,ithasnotfulfilled
theminimal procedural requirements contained inArticle 5.1tobase itssanitary measures onarisk
assessment. Wehave also found that, even ifitwould have fulfilled these minimal procedural
requirements, theEuropean Communities hasnotmetitsburden ofproving thatitsmeasures indispute,
insofarasthey alsobantheimport ofmeat andmeat products from animals treated with anyofthe
fivehormones atissue forgrowth promotion purposes inaccordance with good practice, are,from
asubstantive point ofview, based onariskassessment. TheECmeasures indispute, insofaras
they relate tofiveofthesixhormones atissue forwhich international standards exist, are,therefore,
inconsistent with therequirements ofArticle 5.1. Thefactthatthese measures arenotbased onexisting
international standards (contrary toArticle 3.1)370cannot, therefore, bejustified under Article 3.3which
includes asoneoftherequirements forjustification, consistency with Article 5.1. TheECmeasures,
insofarasthey relate tofiveofthesixhormones atissue forwhich international standards exist, are,
therefore, alsoinconsistent with therequirements ofArticle 3.1.
(c) Articles 5.4to5.6: risk management
8.160 Werecall thatthere isadistinction between riskassessment which isascientific examination
andriskmanagement which involves social value judgments.371Once therisks have been assessed,
i.e.,once therisks andtheir probability ofoccurrence identified, aMember willneed todecide, on
thebasis ofitsown value judgments, whether itcanaccept these risks. Insodoing aMember sets
its"appropriate level ofsanitary protection". Thedetermination andapplication oftheappropriate
level ofprotection byaMember ispartofriskmanagement.
8.161 Werecall thedefinition of"appropriate level ofsanitary protection", namely:
"The level ofprotection deemed appropriate bytheMember establishing asanitary
...measure toprotect human, animal orplant lifeorhealth ..."(paragraph 5ofAnnex
AoftheSPS Agreement; emphasis added).
Wealsonote thewording ofArticle 5.5, further examined below:
"...intheapplication oftheconcept ofappropriate level ofsanitary ...protection
against risks tohuman lifeorhealth, ortoanimal andplant lifeorhealth, each Member
shall avoid ..."
Guided bythewording ofthese provisions andtheobject andpurposes oftheSPS Agreement, we
consider thatifthere isnoscientific evidence ofanidentifiable risk, there isnobasis onwhich toadopt
ameasure toachieve alevel ofsanitary protection under theSPS Agreement, except asprovided in
Article 5.7. Ifthiswere notthecase, i.e., ifaMember could adopt alevel ofprotection and
implementing sanitary measures even ifitdidnotprovide scientific evidence ofanidentifiable risk,
noeffect would begiven totheobligation contained inArticle 5tobase sanitary measures onan
assessment ofrisks. This approach would undermine thewording andobject andpurpose oftheSPS
Agreement.
370Seepara. 8.77.
371Seeparas. 8.91 ff.WT/DS26/R/USA
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8.162 Wehave found above372thattheEuropean Communities hasnotprovided evidence ofan
identifiable riskrelated tothepresence offiveofthesixhormones atissue forwhich international
standards exist when these hormones areused forgrowth promotion purposes inaccordance with good
practice. Accordingly, theEuropean Communities hasnotestablished theexistence ofanyidentifiable
riskagainst which theECmeasures atissue, insofarasthey alsobantheuseofthefivehormones
when used asgrowth promoters inaccordance with good practice, canprotect human lifeorhealth.
Since weconsidered above373thattheadoption ofasanitary measure presupposes theexistence ofan
identifiable risk(except asprovided inArticle 5.7), itisnotpossible fortheEuropean Communities
tobantheuseofthese hormones asgrowth promoters inaccordance with good practice.
8.163 However,evenifwewouldhavefoundthattheEuropeanCommunitiesmetitsburdenofproving
thatitsmeasures arebased onanassessment ofrisks inaccordance with Articles 5.1and5.2andeven
if,forthatreason, theEuropean Communities could have adopted ameasure toachieve itsappropriate
level ofprotection against these risks, there would stillbeaneed toexamine whether thedetermination
andapplication ofthislevel ofprotection isconsistent with Articles 5.4to5.6. Wewill, therefore,
next examine these provisions.
8.164 Thepartiestothisdisputeseemtoagreethattheestablishmentofan"appropriatelevelofsanitary
protection" byaMember isasovereign act,namely, asthedefinition inparagraph 5ofAnnex Aof
theSPSAgreement provides, thelevel ofprotection "deemed appropriate bytheMember establishing
asanitary ...measure" (emphasis added). Asoutlined above374,wenote, however, thatMembers have
agreed, inexercising their sovereign right tosettheir appropriate levels ofprotection, toobserve the
provisions oftheSPSAgreement, inparticular Articles 5.4and5.5thereof. Furthermore, inchoosing
ameasure toachieve thatappropriate level ofprotection Members have agreed toobserve theprovisions
ofArticles 2,5.1to5.3and5.6.
8.165 Wefinally recall ourfindings reached above onthespecific burden ofproof under Article 3.3.375
Inparticular, wefound thattheburden ofproving thattherequirements imposed byArticle 3.3(inter
alia,consistency with Article 5)aremet, inorder tojustify asanitary measure which deviates from
aninternational standard, rests with theMember imposing thatmeasure. Since theECmeasures
examined inthissection (relating toallhormones indispute other thanMGA) arenotbased onexisting
international standards andneed tobejustified under theexceptions provided forinArticle 3.3,the
European Communities bears theburden ofproving thatthedetermination andapplication ofitslevel
ofprotection isconsistent with Articles 5.4to5.6.
(i) Article 5.4: minimizing trade effects
8.166 Article 5.4provides thefollowing:
"Members should ,when determining theappropriate level ofsanitary orphytosanitary
protection, take into account theobjective ofminimizing negative trade effects"
(emphasis added).
Guided bythewording ofArticle 5.4,inparticular thewords "should" (not"shall") and"objective",
weconsider thatthisprovision oftheSPSAgreement does notimpose anobligation. However, this
372Seepara. 8.137.
373Seepara. 8.161.
374Seeparas. 8.161 ff.
375Seeparas. 8.85 ff.WT/DS26/R/USA
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objectiveofminimizingnegativetradeeffectshasnonethelesstobetakenintoaccountintheinterpretation
ofother provisions oftheSPS Agreement.
(ii) Article 5.5: distinctions inlevels ofprotection
8.167 Article 5.5provides thefollowing:
"With theobjective ofachieving consistency intheapplication oftheconcept of
appropriate level ofsanitary orphytosanitary protection against risks tohuman life
orhealth, ortoanimal andplant lifeorhealth, each Member shall avoid arbitrary
orunjustifiable distinctions inthelevels itconsiders tobeappropriate indifferent
situations, ifsuch distinctions result indiscrimination oradisguised restriction on
international trade .Members shall cooperate intheCommittee, inaccordance with
paragraphs 1,2and3ofArticle 12,todevelop guidelines tofurther thepractical
implementation ofthisprovision. Indeveloping theguidelines, theCommittee shall
take intoaccount allrelevant factors, including theexceptional character ofhuman
health risks towhich people voluntarily expose themselves" (emphasis added).
8.168 Wenote, inthisrespect, thebasic obligations contained inArticle 2.3:
"Members shall ensure thattheir sanitary andphytosanitary measures donotarbitrarily
orunjustifiably discriminate between Members where identical orsimilar conditions
prevail ,including between their own territory andthatofother Members. Sanitary
andphytosanitary measures shall notbeapplied inamanner which would constitute
adisguised restriction oninternational trade "(emphasis added).
Article 2.3deals, ingeneral terms, with sanitary measures which discriminate between Members or
which areapplied inamanner which would constitute adisguised restriction oninternational trade.
Article 5.5,ontheother hand, deals more specifically with distinctions inlevels ofprotection (which
willnormally bereflected inoneormore sanitary measures) which result indiscrimination oradisguised
restriction oninternational trade.
8.169 Weconsider thatthefirstpartofthefirstsentence ofArticle 5.5("With theobjective ofachieving
consistency intheapplication oftheconcept ofappropriate level ofsanitary orphytosanitary protection
against risks tohuman lifeorhealth, ortoanimal andplant lifeorhealth ..."; emphasis added), unlike
thesecond part, does notimpose anobligation upon Members. Consistency isnotimposed asan
obligation butasanobjective which nonetheless hastobetaken intoaccount intheinterpretation of
Article 5.5.
8.170 Wefurther note thattheCommittee onSanitary andPhytosanitary Measures, established by
Article 12oftheSPS Agreement to"provide aregular forum forconsultations", hasbeen given a
mandate byArticle 5.5,second sentence, to"develop guidelines tofurther thepractical implementation
ofthisprovision" and, insodoing, needs to"take intoaccount allrelevant factors, including the
exceptional character ofhuman health risks towhich people voluntarily expose themselves". Nosuch
guidelines have todatebeen developed. However, considering themandatory wording ofthesecond
partofthefirstsentence ofArticle 5.5("each Member shall avoid arbitrary orunjustifiable distinctions
inthelevels itconsiders tobeappropriate indifferent situations ...";emphasis added) andtheexistence
ofthebasic obligations contained inArticle 2.3376,wefindthatthelackofguidelines bytheCommittee
innoway limits thelegally binding nature ofthesecond partofthefirst sentence ofArticle 5.5.
376Seepara. 8.168.WT/DS26/R/USA
Page 205
8.171 TheUnitedStatesarguesthattheEuropeanCommunitiesfailstojustifythefollowingdifferences
inregulatory treatment: (i)abanonnatural andsynthetic hormones when used forgrowth promotion
purposes asopposed tonotsetting anylimit forresidues ofthenatural hormones present endogenously
inuntreated meat andother foods (such asmilk, cabbage, broccoli oreggs) andresidues ofthese
hormones when used fortherapeutic orzootechnical purposes; and(ii)abanonthehormones indispute
whenusedforgrowthpromotionpurposesasopposedtoallowingtheuseoftheveterinarydrugcarbadox
asagrowth promoter inswine production. Only with respect tothelastmentioned difference in
treatment does theUnited States invoke andaddress Article 5.5.377
8.172 TheEuropean Communities rejects these claims, arguing thatitdoes notmake distinctions
initslevels ofprotection fordifferent situations andthat, even ifitwere tomake such distinctions,
thesedistinctionsarejustifiedanddonotresultindiscriminationoradisguisedrestrictiononinternational
trade.378
The three elements contained inArticle 5.5
8.173 WenextexaminetheelementsthatmustbeassessedtodetermineifaMember'ssanitarymeasure
does notconform totherequirements ofthesecond partofthefirstsentence ofArticle 5.5. Therelevant
partofArticle 5.5reads asfollows:
"each Member shall avoid arbitrary orunjustifiable distinctions inthelevels itconsiders
tobeappropriate indifferent situations, ifsuch distinctions result indiscrimination
oradisguised restriction oninternational trade".
8.174 The first element contained inArticle 5.5isthattheMember concerned adopts different
appropriate levels ofsanitary protection in"different situations". The second element isthatthe
distinction inlevels ofprotection forthedifferent situations is"arbitrary orunjustifiable". Thethird
element isthatthedistinction inlevels ofprotection results in"discrimination oradisguised restriction
oninternational trade". Inorder tofindasanitary measure tobeinconsistent with Article 5.5allthree
elements need tobepresent.
8.175 Astothefirstelement ,thewords "different situations" have been interpreted bytheparties
asfollows. TheEuropean Communities argues that"different situations" onlycovers different situations
forthesame residue orfordifferent residues where theadverse health effect isthesame .According
totheEuropean Communities, "different situations" cannot mean thatthesame level ofprotection must
beapplied tosimilar health hazards, whatever their nature orseverity, coming from similar substances.
TheUnited States argues thatthe"different situations" referred toinArticle 5.5ofnecessity must be
comparable situations. Itargues, forexample, thatthepurported health riskfrom carbadox andthe
hormones indispute, when used forgrowth promotion, isinboth instances, cancer inhumans and
that, therefore, thedifferent situations invoked bytheUnited States arecomparable.379
8.176 Wenote thatboth parties indispute agree thatthescope of"different situations" contained
inArticle 5.5includes situations which deal with thesame substance aswell assituations which
involve thesame adverse health effect .Forthisreason, considering thelack ofguidelines bythe
Committee onSanitary andPhytosanitary Measures andwithout further defining orlimiting thescope
of"different situations", wefindthat, forthepurposes ofthisdispute, wecancompare situations where
thesame substance orthesame adverse health effect isinvolved as"different situations" inthesense
377Seepara. 4.220.
378Seepara. 4.218.
379Seepara. 4.220.WT/DS26/R/USA
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ofArticle 5.5. Forthesake ofclarity inthisparticular case, wewillhereafter refer tosuch "different
situations" as"comparable situations" since these situations need tobecompared forthepurposes of
Article 5.5andare,therefore, "comparable".
8.177 Thesecond element contained inArticle 5.5isthatthedistinction inlevels ofprotection for
comparable situations is"arbitrary orunjustifiable".
8.178 TheUnited States argues that, intheabsence ofanyprinciple orcriterion thataccounts for
theselectionofdifferinglevelsofsanitaryprotection,thedistinctioninthelevelsofprotectionisarbitrary
andunjustifiable.380TheEuropean Communities argues thatArticle 5.5clearly states that"arbitrary
orunjustifiable" distinctions aretobeavoided if,andonlyif,theyresult indiscrimination oradisguised
restriction ontrade. Ifthey donotresult indiscrimination oradisguised restriction ontrade, the
European Communities concludes, they arenotprohibited byArticle 5.5.381
8.179 Thethird element contained inArticle 5.5isthatthedistinction inlevel ofprotection results
in"discrimination oradisguised restriction oninternational trade".
8.180 TheUnited States hasnotpresented aclaim with respect totheterm "discrimination"; only
with respect totheterm "disguised restriction oninternational trade". TheUnited States argues that
"adisguised restriction oninternational trade" ispresent inthecontext ofArticle 5.5where aMember
claims alegitimate basis forthedifference inthechosen levels ofprotection being compared, butwhere
instead thediffering levels ofprotection arebeing employed forcommercial reasons torestrict trade.382
TheEuropean Communities argues thatthemeasures indispute donotresult indiscrimination and
thatthefactthatsanitary measures affect imports isnotasufficient reason toclaim thatthey restrict
trade, oreven less, thatthey discriminate.
8.181 Wenote, firstofall,therelation between thisthird element of"discrimination oradisguised
restriction oninternational trade" inArticle 5.5andthebasic obligations contained inArticle 2.3of
theSPS Agreement providing that:
"Members shall ensure thattheir sanitary andphytosanitary measures donotarbitrarily
orunjustifiably discriminate between Members where identical orsimilar conditions
prevail, including between their own territory andthatofother Members. Sanitary
andphytosanitary measures shall notbeapplied inamanner which would constitute
adisguised restriction oninternational trade "(emphasis added).
Wealsonote therelation between these twoprovisions andthelanguage ofthechapeau ofArticle XX
ofGATT which reads asfollows:
"Subject totherequirement thatsuch measures arenotapplied inamanner which would
constitute ameans ofarbitrary orunjustifiable discrimination between thecountries
where thesame conditions prevail, oradisguised restriction oninternational trade ,
nothing inthisAgreement shall beconstrued toprevent theadoption orenforcement
byanycontracting party ofmeasures: ...." (emphasis added).
8.182 With respect tothemeaning of"discrimination" and"adisguised restriction oninternational
trade" werecall theconclusions reached bytheAppellate Body initsReport on"United States -
380Ibid.
381Seepara. 4.218.
382Seepara. 4.221.WT/DS26/R/USA
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Standards forReformulated andConventional Gasoline" where theterms "arbitrary orunjustifiable
discrimination" and"adisguised restriction oninternational trade", contained inthechapeau of
Article XXofGATT, were examined asfollows:
"'Arbitrary discrimination ','unjustifiable discrimination 'and'disguised restriction '
oninternational trade may, accordingly, beread side-by-side; they impart meaning
tooneanother. Itisclear tousthat 'disguised restriction 'includes disguised
discrimination ininternational trade. Itisequally clear thatconcealed orunannounced
restriction ordiscrimination ininternational trade does notexhaust themeaning of
'disguised restriction '.Weconsider that'disguised restriction ',whatever elseitcovers,
mayproperly bereadasembracing restrictions amounting toarbitrary orunjustifiable
discrimination ininternational trade taken under theguise ofameasure formally within
theterms ofanexception listed inArticle XX. Putinasomewhat different manner,
thekinds ofconsiderations pertinent indeciding whether theapplication ofaparticular
measure amounts to'arbitrary orunjustifiable discrimination ',mayalsobetaken into
account indetermining thepresence ofa'disguised restriction 'oninternational trade.
Thefundamental theme istobefound inthepurpose andobject ofavoiding abuse or
illegitimate useoftheexceptions tosubstantive rules available inArticle XX" (original
emphasis).383
8.183 Wefurther recall theAppellate Body Report on"Japan -Taxes onAlcoholic Beverages" where
theAppellate Body found thatforaninternal taxmeasure tobeinconsistent with thesecond sentence
ofArticle III:2 ofGATT, three separate issues must beaddressed soastogive fullmeaning tothe
textandcontext ofthisprovision: (i)theproducts need tobe"directly competitive orsubstitutable";
(ii)they need tobe"not similarly taxed"; and(iii)thedissimilar taxation needs tobe"applied ...so
astoafford protection todomestic production".384TheAppellate Body found thatthepanel haderred
inblurring thedistinction between thesecond andthird issue byequating dissimilar taxation (i.e.,tax
difference above ademinimis level) with theseparate anddistinct requirement ofdemonstrating that
thetaxmeasure "affords protection todomestic production".385TheAppellate Body then concluded
thefollowing:
"Aspreviously stated, afinding that'directly competitive orsubstitutable products '
are'notsimilarly taxed 'isnecessary tofindaviolation ofArticle III:2, second sentence.
Yetthisisnotenough. Thedissimilar taxation must bemore thandeminimis .Itmay
besomuch more thatitwillbeclear from thatvery differential thatthedissimilar
taxation wasapplied "soastoafford protection". Insome cases, thatmaybeenough
toshow aviolation .Inthiscase, thePanel concluded thatitwasenough. Yetinother
cases, there may beother factors thatwillbejustasrelevant ormore relevant to
demonstrating that thedissimilar taxation atissue was applied 'soastoafford
protection '...And, inevery case, acareful, objective analysis, must bedone ofeach
andallrelevant facts andallrelevant circumstances todetermine 'theexistence of
protective taxation '.Although thePanel blurred itslegal reasoning inthisrespect,
383Appellate Body Report on"United States -Standards forReformulated andConventional Gasoline", adopted on20
May 1996, WT/DS2/AB/R, p.25.
384Appellate Body Report on"Japan -Taxes onAlcoholic Beverages", adopted on1November 1996, WT/DS8/AB/R,
p.24.
385Panel Report on"Japan -Taxes onAlcoholic Beverages", adopted on1November 1996, WT/DS8/R, paras. 6.33-34
and7.1(ii).WT/DS26/R/USA
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nevertheless weconclude thatitreasoned correctly thatinthiscase, theLiquor Tax
Law isnotincompliance with Article III:2" (emphasis added).386
8.184 Weconsider thereasoning inboth Appellate Body Reports tobeequally relevant tothe
relationship between thethree elements contained inArticle 5.5. Allthree elements impart meaning
tooneanother. Nevertheless, inorder togive effect toallthree elements contained inArticle 5.5
andgiving fullmeaning tothetextandcontext ofthisprovision, weconsider thatallthree elements
need tobedistinguished andaddressed separately. However, wealsoagree thatinsome cases where
aMemberenacts,forcomparablesituations,sanitarymeasureswhichreflectdifferentlevelsofprotection,
thesignificance ofthedifference inlevels ofprotection combined with thearbitrariness thereof may
besufficient toconclude thatthisdifference inlevels ofprotection "result[s] indiscrimination ora
disguised restriction oninternational trade" inthesense ofArticle 5.5(inlinewith theargument that
themagnitude oftheverydifferential ofadissimilar taxation maybeenough toconclude thatadissimilar
taxation isapplied soastoafford protection, asprovided forinthesecond sentence ofArticle III:2
ofGATT).
8.185 Wenext examine, inlight ofthethree elements ofArticle 5.5outlined above, thedistinctions
inlevels ofsanitary protection allegedly made bytheEuropean Communities which have been invoked
bytheUnited States. Inorder toconduct ourconsideration ofthisdispute under Article 5.5inthe
most efficient manner, wefirstaddress thealleged differences intreatment provided bytheEuropean
Communities forthenatural hormones indispute .Inthisexamination wecompare thetreatment of
these hormones when used asgrowth promoters with both thetreatment ofthese hormones occurring
endogenously inmeat andother foods (such asmilk, cabbage, broccoli oreggs) andwhen used for
therapeutic orzootechnical purposes. Inasecond step, weaddress thealleged differences intreatment
provided bytheEuropean Communities forthenatural hormones indispute asopposed tothatofthe
synthetic hormones atissue .Inathird step, weaddress thealleged differences intreatment provided
bytheEuropean Communities forallhormones indispute (other than MGA) when used asgrowth
promoters asopposed tothatforcarbadox ,anantimicrobial growth promoter.
Natural hormones forgrowth promotion compared to(i)those occurring endogenously
inmeat andother foods, and(ii)those fortherapeutic orzootechnical purposes
1. Comparable situations with different levels ofsanitary protection
8.186 This examination involves acomparison ofthelevels ofprotection forthesame substance ,
namely, respectively, oestradiol-17 ,testosterone andprogesterone, indifferent situations depending
ontheorigin oruseofthatsubstance. Since wehave found above thatwecancompare situations
where thesame substance isinvolved as"different" situations (which werefer toas"comparable"
situations forthepurposes ofthisdispute) inthesense ofArticle 5.5387,wefindthatthetreatment
ofthethree natural hormones indispute when used forgrowth promotion purposes asopposed tothe
treatment ofthese hormones which (i)occur endogenously inmeat andother foods and(ii)which have
been administered fortherapeutic orzootechnical purposes, constitute comparable situations inthe
sense ofArticle 5.5.
8.187 TheEuropean Communities argues thattheorigin ofthese hormones (whether endogenously
producedorexogenouslyadministered)causesthesehormonestobedifferent,claimingthatthehormones
present endogenously inmeat andother foods have formed partofthehuman dietforcenturies. We
note, however, thattheEuropean Communities didnotsubmit anyevidence insupport ofitsclaim
thatthese hormones have different effects. Moreover, allscientific experts advising thePanel have
386Appellate Body Report onJapan -"Taxes onAlcoholic Beverages", adopted on1November 1996, WT/DS8/AB/R,
p.30.
387Seepara. 8.176.WT/DS26/R/USA
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concluded thatresidues ofthethree natural hormones present endogenously inmeat andother foods
oradministered fortherapeutic orzootechnical purposes arequalitatively thesame astheresidues of
these hormones administered forgrowth promotion andthatifanydifferences between these hormones
could exist (e.g., differences inpathways taken ormetabolites), these differences would inanyevent
nothave consequences forthepotential adverse effects ofthese hormones.388Therefore, even ifthese
hormones would notbetotally identical substances, they pose, inanyevent, thesame adverse health
effect andcan,therefore, according toourfinding made above389,beconsidered ascomparable situations
forthepurposes ofArticle 5.5.
8.188 Wenextexamine whether theEuropean Communities hasadopted adifferent level ofprotection
forthese comparable situations.
8.189 With respect tothethree natural hormones administered forgrowth promotion purposes ,the
European Communities argues thatitslevel ofsanitary protection isconcerned only with added
hormones; inother words, theEuropean Communities does notconsider thatitisacceptable toexpose
consumers toanyhormones intheir food over andabove thelevels which occur innature, asanysuch
additional exposure could beahazard tohealth.390
8.190 Theappropriate level ofprotection setbytheEuropean Communities fornatural hormones
present endogenously inmeat andother foods oradministered fortherapeutic orzootechnical purposes
isanunlimited residue level.391Inother words, theEuropean Communities hasnotadopted any
maximum residue level forthese categories ofnatural hormones.392With respect tooestradiol-17
whenusedfortherapeuticorzootechnicalpurposes,thisunlimitedresiduelevelofprotectionhasrecently
been confirmed bytheEuropean Communities when itadopted theconclusions reached inthe1988
JECFA Report andclassified thishormone, when used fortherapeutic orzootechnical purposes, as
asubstance forwhich MRLs areunnecessary.393With respect tothetwoother natural hormones in
dispute, progesterone andtestosterone, when used fortherapeutic orzootechnical purposes, nofinal
decision hasasyetbeen taken bythecompetent ECauthorities.394
8.191 Wethusfindthatthelevel ofprotection adopted bytheEuropean Communities forthethree
natural hormones indispute when used forgrowth promotion andthatadopted forthesame hormones
(i)occurringendogenouslyinmeatandotherfoodsand(ii)usedfortherapeuticorzootechnicalpurposes,
isdifferent ("no residue" level asopposed toanunlimited residue level) andthat, therefore, distinctions
inlevels ofprotection forthese comparable situations exist inthesense ofthefirstelement ofArticle 5.5.
388Seeanswers byexperts toPanel Questions 2and4,paras. 6.22-6.31 and6.40-6.50 andopinions ofallexperts advising
thePanel toanoralquestion asked bytheUSrepresentative atthejointmeeting withexperts of17February 1997, Transcripts,
paras. 77,79,84,85and87.
389Seepara. 8.176.
390Ibid.
391Ibid.
392With respect tohormones administered fortherapeutic treatment, theEuropean Communities argues thatinpractice
noresidues ofthese hormones willbeingested byconsumers because animals undergoing such treatment arenotallowed
tobeslaughtered. However, thefactisthattheEuropean Communities hasdecided thattheadoption ofMRLs forthese
hormone residues isunnecessary andhasthus notsetanyresidue limit (seepara. 8.190 infine).
393Seeanswer byDr.Arnold toPanel Question 5,para. 6.55.
394Ibid., para. 6.56.WT/DS26/R/USA
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2. "Arbitrary orunjustifiable" difference inlevels ofsanitary protection
8.192 Wenext examine whether these twodistinctions inlevels ofprotection are"arbitrary or
unjustifiable". Wefirstaddress thedistinction made between thethree natural hormones when used
asgrowth promoters andthesame hormones occurring endogenously inmeat andother foods. We
thenexamine thedistinction made between thethree natural hormones when used asgrowth promoters
andthesame hormones when used fortherapeutic orzootechnical purposes.
8.193 Natural hormones used asgrowth promoters asopposed tothose occurring endogenously in
meat andother foods. TheEuropean Communities hasnotprovided anyreasons, other than those
addressed above, whyithasadopted adifferent level ofprotection fortheresidues ofthese twocategories
ofnatural hormones. TheEuropean Communities has,inparticular, notprovided anyevidence that
theriskrelated tothenatural hormones used asgrowth promoters isinanywayhigher than therisk
related tonatural endogenous hormones. Wealsorecall thattheexperts advising thePanel concluded
thatboth categories ofhormones (either exogenously administered toanimals orendogenously present
inanimals, meat, other foods orhuman beings) pose thesame potential adverse effects.395
8.194 Inthisrespect wefurther recall theconclusion reached inthe1988 JECFA Report thatthe
total residue level ofnatural hormones inmeat from treated animals (i.e.,thecombination ofnatural
hormonesendogenouslypresentandthoseaddedforgrowthpromotion)fallswellwithinthephysiological
range oflevels found inmeat from untreated animals, which levels vary according tothesexandage
oftheanimal.396Wealsonotethat, according todatasubmitted tothePanel, theresidue level ofnatural
hormones inmany natural products (such aseggs andsoya oil)ismuch higher thanthelevel ofresidues
ofthese hormones administered forgrowth promotion aswellasthetotalresidue level ofthese hormones
intreated meat.397Inthisrespect, wefurther notethatCodex hasalsoestablished MRLs forsubstances
which endogenously occur innatural products.398
8.195 With respect tothepotential difficulties indetecting thepresence ofnatural hormones used
asgrowth promoters, werefer toourconclusions reached above399,namely thatonly under thecurrent
ECregime (aban) does theproblem arise ofhowtodistinguish between endogenous andadded natural
hormones whereas under aregime where onewould allow theuseofthese hormones (with, forexample,
anMRL ortolerance level forallnatural hormones) there would benoneed todistinguish endogenous
from added natural hormones. Wealsonote that, inanyevent, theproblem ofdetection would be
thesame forboth natural hormones used asgrowth promoters andthose occurring endogenously in
395Seepara. 8.187 and, inparticular, thefootnote thereto.
396Seepara. 8.62. Thisconclusion hasnotbeen contested byeither theparties orexperts advising thePanel. Forexample,
according todatasubmitted tothePanel (theaccuracy ofwhich hasnotbeen disputed bytheparties), theresidue level of
testosterone in500grams ofuntreated bullmeat is1,560 nanograms asopposed to35nanograms in500grams ofmeat from
aheifer implanted with testosterone.
397Forexample, according todatasubmitted tothePanel (theaccuracy ofwhich hasnotbeen disputed bytheparties),
theresidue level ofoestradiol-17 equivalents ina50to60grams hen'seggis1,750 nanograms (in10mlofsoybean oil,
20,000 nanograms) asopposed to11.4 nanograms in500grams ofsteer meat implanted withoestradiol-17 and75nanograms
in500grams ofuntreated cowmeat. Inother words, theoestrogen content of1hen'seggisequivalent to76.5 kgofimplanted
steer beef. Inthisrespect, wealsonote thatapre-puberty male child naturally produces 41,000 nanograms ofoestrogens
in24hours, anadult man 136,000 nanograms andapregnant women 20,000,000 nanograms.
398Forexample, MRLs have been adopted byCodex for(naturally occurring) cyanide incassava flour andinGari (a
cassava product).
399Seepara. 8.145.WT/DS26/R/USA
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meat andother foods (since thescientific experts stated thatboth arequalitatively thesame400)and
can, therefore, notjustify adifferent treatment.
8.196 Wefinally note thateven ifsome form ofjustification could bededuced from thearguments
submitted bytheEuropean Communities, such could not,inanyevent, justify sosignificant adifference
inlevels ofprotection between a"noresidue" level fornatural hormones administered forgrowth
promotion andanunlimited residue level fornatural hormones endogenously present inmeat andother
foods.
8.197 WethusfindthattheEuropeanCommunitieshasnotmetitsburdenofprovingthatthedistinction
itmakes inlevels ofprotection forresidues ofthethree natural hormones indispute when administered
forgrowth promotion purposes andresidues ofthesame natural hormones present endogenously in
meat andother foods isjustifiable andthat, therefore, thisparticular distinction inlevels ofprotection
is"arbitrary orunjustifiable" inthesense ofthesecond element contained inArticle 5.5.
8.198 Natural hormones used asgrowth promoters asopposed tothose used fortherapeutic or
zootechnical purposes. TheEuropean Communities argues thattheuseofthenatural hormones for
therapeutic andzootechnical purposes occurs onasmall scale, issubject tovery strict conditions (such
asadministration byaveterinarian andstrict withdrawal periods) andnormally only involves cattle
intended forbreeding, notforslaughter; whereas theuseofthese hormones asgrowth promoters occurs
onamuch larger scale andismore difficult andcostly tocontrol.401These differences inuseandcontrol,
theEuropean Communities argues, ensure thatanyriskrelated tothetherapeutic orzootechnical use
ofthese hormones isprevented andthatinpractice alevel of"noresidue" isachieved, asisthecase
fortheuseofthese hormones asgrowth promoters. Forthese reasons, theEuropean Communities
concludes, thedistinction inlevels ofprotection isjustified.402
8.199 Wenote that, according toscientific experts advising thePanel, zootechnical useofthese
hormones canoccur onalarge scale and atregular intervals, namely each year foroestrus
synchronization ofentire herds.403Moreover, even when these hormones areused fortherapeutic or
zootechnical purposes, allparties andscientific experts advising thePanel agree thatsome residue level,
albeit avery small one, will always remain inthemeat when thetreated animal iseventually
slaughtered.404Therefore, a"noresidue" level cannot inpractice beachieved when these hormones
areused fortherapeutic orzootechnical purposes.
8.200 However, since wehave already concluded thatthedifference inlevels ofprotection imposed
intheEuropean Communities forthethree natural hormones when used forgrowth promotion purposes
asopposed tothose present endogenously inmeat andother foods cannot bejustified, weconsider
itunnecessary todecide whether ornotthedistinction made bytheEuropean Communities between
natural hormones used asgrowth promoters andthose used fortherapeutic orzootechnical purposes
isjustified.
400Seepara. 8.187.
401Seepara. 4.71.
402Seepara. 4.69.
403Seeanswers byexperts toPanel Questions 19and20,paras. 6.183-6.193.
404Ibid. Seealsoopinions ofallexperts advising thePanel onaquestion bytheUSrepresentative atthejoint meeting
with experts of17February 1997, Transcripts, paras. 90,91,93and95andanswers byexperts toPanel Question 3,
paras. 6.32-6.39 andpara. 4.68.WT/DS26/R/USA
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3. Difference which results in"discrimination oradisguised restriction oninternational
trade"
8.201 Wenext examine whether thedifference inlevels ofprotection between residues ofthethree
natural hormones indispute when administered forgrowth promotion purposes andresidues ofthe
same natural hormones present endogenously inmeat andother foods, results indiscrimination ora
disguised restriction oninternational trade within themeaning ofthethird element ofArticle 5.5.405
8.202 Werecalltheconsiderationsmadeaboveontherelationshipbetweenthethreeelementscontained
inArticle 5.5.406Werecall, inparticular, thatinsome cases thesignificance ofthedifference inlevels
ofprotection forcomparable situations combined with thearbitrariness thereof may besufficient to
conclude thatthisdifference inlevels ofprotection results in"discrimination oradisguised restriction
oninternational trade".
8.203 Inthiscase, wenote, firstly, thesignificance ofthedifference inlevels ofprotection forthe
three natural hormones indispute when administered forgrowth promotion purposes andresidues of
thesamehormonespresentendogenouslyinmeatandotherfoods,namelya"noresidue"levelasopposed
toanunlimited residue level. Werecall, secondly, thattheEuropean Communities hasnotprovided
anyplausible justification forthissignificant difference. Wenote, finally, thatthisdifference inlevels
ofprotection results inanimport ban(onmeat andmeat products treated with anyofthethree natural
hormones indispute forgrowth promotion purposes) which restricts international trade. Forthese
reasons, wefindthatthedifference inlevels ofprotection imposed bytheEuropean Communities for
thethree natural hormones indispute when administered forgrowth promotion purposes andthose
present endogenously inmeat andother foods, results in"discrimination oradisguised restriction on
international trade" inthesense ofArticle 5.5.
8.204 Weconsider thatthisfinding isfurther supported bytwoadditional factors. Firstly, werecall
some oftheobjectives (other than theprotection ofhuman health) thattheEuropean Communities
hadinmind when enacting ormaintaining theECbanontheuseofthenatural hormones forgrowth
promotion purposes, asstated inthepreambles oftheECmeasures indispute407andinthereports
oftheEuropean Parliament andtheopinions oftheECEconomic andSocial Committee referred to
bytheEuropeanCommunities408,namelyharmonizingtheregulatoryschemesofthedifferentECMember
405Since wemade nofinding onthejustifiability ofthedifference inlevels ofprotection forthenatural hormones indispute
when administered asgrowth promoters andthose administered fortherapeutic orzootechnical purposes, wedonotaddress,
forthatadditional difference inlevels ofprotection, thethird element ofArticle 5.5.
406Seeparas. 8.182-8.184.
407Such aspreambles 5and6toDirective 88/146/EEC which state, inter alia,thefollowing:
"Whereas theadministration tofarm animals ofcertain substances having ahormonal action isatpresent
regulated indifferent ways intheMember States; ...whereas thisdivergence distorts theconditions of
competition inproducts thatarethesubject ofcommon market organizations andisaserious barrier to
intra-Community trade;
"Whereas these distortions ofcompetition andbarriers totrade must therefore beremoved byensuring
thatallconsumers areabletobuytheproducts inquestion under largely identical conditions ofsupply
andthatthese products correspond totheir anxieties andexpectations inthebestpossible manner; whereas
such acourse ofaction isbound tobring about anincrease inconsumption oftheproduct inquestion".
408Such astheNielsen Report of1981, theCollins Reports of1985 and1989 andthePimenta Report of1989 ofthe
European Parliament andtheopinions oftheECEconomic andSocial Committee of1981 and1984, outlined inparas. 2.28-
2.33. SeealsoJudgment oftheCourt ofJustice oftheEuropean Communities inthecase C-331/88, "The Queen v.The
Minister forAgriculture, Fisheries andFood andtheSecretary ofState forHealth, exparte: Fedesa andOthers", 1990,
ECR I-4023, atp.I-4065, para. 25:"...thematerial made available totheCourt ...shows thatthepossibility ofareduction
(continued...)WT/DS26/R/USA
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States, thereby removing competitive distortions andbarriers tointra-Community trade inbeef, and
bringing about anincrease intheconsumption ofbeef, thereby reducing theinternal beef surpluses
andproviding more favourable treatment todomestic producers.
8.205 Secondly, wenote thatbefore theECbancame intoforce, thepercentage ofanimals treated
with anyofthehormones indispute wassignificantly lower intheEuropean Communities than inthe
United States. Atthattime, according totheEuropean Communities, only four orfiveECmember
States allowed theuseofsome ofthese hormones. Onemember State (theUnited Kingdom) which
hasreplied totheEC'srequest forinformation onthisissue, indicated that"anecdotal evidence suggests
thatgrowth promoting hormones mayhave been used [in]upto40% ofUKcattle prior totheban".409
Ontheother hand, according toatable provided bytheUnited States, anaverage of70percentof
allUScattle were, atthattime, treated with oneormore ofthese hormones.410Bybanning theinternal
saleandimport ofmeat treated withnatural hormones forgrowth promotion purposes (which represents
asignificantly higher proportion ofthetotal USmeat supply than ofthetotal European Communities
meatsupply)butcontinuingtoallowanylevelofresiduesofthesenaturalhormonespresentendogenously
inmeat, theEuropean Communities favoured theconsumption ofdomestic meat and, therefore, de
facto discriminates against USmeat infavour ofECmeat. Inthissense, thedifference inlevels of
protection intheEuropean Communities forresidues ofhormones present endogenously inmeat and
otherfoodsandresiduesofthesamenaturalhormoneswhenadministeredforgrowthpromotionpurposes
could besaidtoresult in"discrimination oradisguised restriction oninternational trade".
8.206 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forresidues ofthethree natural hormones indispute administered for
growth promotion purposes andresidues ofthesame natural hormones present endogenously inmeat
andother foods, inlight ofthethree elements contained inArticle 5.5, andthat, therefore, theEC
measures indispute, insofarasthey relate tothethree natural hormones atissue, areinconsistent
with therequirements imposed inArticle 5.5.
Synthetic hormones forgrowth promotion compared tonatural hormones
8.207 Wenext examine thealleged different treatment provided bytheEuropean Communities for,
ontheonehand, twoofthethree synthetic hormones indispute forwhich international standards exist
(zeranol andtrenbolone)411and, ontheother hand, thenatural hormones indispute occurring
endogenously inmeat andother foods.412
408(...continued)
insurpluses wasindeed taken intoconsideration during theprocess leading totheadoption ofthedirective [incasu, Directive
88/146/EEC] ...".
409Seepara. 4.15, footnote 35.
410Seepara. 4.9, footnote 25.
411Asmentioned above, thehormone MGA, forwhich nointernational standard exists, willbedealt with inaseparate
section inparagraphs 8.250 ff.
412Sincewemadenofindingonthedifferenceinlevelsofprotectionfornaturalhormonesadministeredasgrowthpromoters
andthose administered fortherapeutic orzootechnical purposes (seepara. 8.200), wedonotaddress thealleged difference
inlevels ofprotection forsynthetic hormones administered asgrowth promoters andnatural hormones administered for
therapeutic orzootechnical purposes.WT/DS26/R/USA
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1. Comparable situations with different levels ofsanitary protection
8.208 Inthisexaminationwecomparedifferentsubstances,namely,respectively,zeranolandoestradiol-
17andtrenboloneandtestosterone.Asoutlinedabove413,bothsynthetichormonesatissueareproduced
tomimic oneofthenatural hormones indispute (zeranol mimics oestradiol-17 andtrenbolone mimics
testosterone). However, both parties inthisdispute andtheexperts advising thePanel agree thatthe
situations thus compared involve atleast thesame adverse health effect ,namely carcinogenicity.414
8.209 Since wedecided above thatwecancompare situations where thesame adverse health effect
isinvolved as"different" situations (which werefer toas"comparable" situations forthepurposes
ofthisdispute) inthesense ofArticle 5.5415,wefindthatthetreatment ofzeranol andtrenbolone and
thetreatment ofthenatural hormones indispute which occur endogenously inmeat andother foods,
arecomparable situations inthesense ofthefirst element ofArticle 5.5.
8.210 Wenextexamine whether theEuropean Communities hasadopted different levels ofprotection
forthese comparable situations.
8.211 With respect tozeranol andtrenbolone, theEuropean Communities adopted a"noresidue"
level asitsappropriate level ofprotection.416Asoutlined above417,thelevel ofprotection intheEuropean
Communities forthenatural hormones present endogenously inmeat andother foods isanunlimited
residue level.
8.212 Wethusfindthatthelevels ofprotection adopted bytheEuropean Communities forresidues
ofzeranol andtrenbolone andthatforresidues ofthenatural hormones indispute which occur
endogenously inmeat andother foods aredifferent ("noresidue" level asopposed toanunlimited residue
level) andthat, therefore, adistinction inlevels ofprotection forthese comparable situations exists
inthesense ofthefirst element ofArticle 5.5.
2. "Arbitrary orunjustifiable" difference inlevels ofsanitary protection
8.213 Wenextexamine whether thisdifference inlevels ofprotection is"arbitrary orunjustifiable".
TheEuropean Communities hasnotprovided convincing evidence thatthesynthetic hormones (which
mimic thenatural hormones) areinherently more dangerous than thenatural hormones.418Most of
theevidence referred tobytheEuropean Communities toprove potential risks relates tothenatural
hormones, inparticular oestradiol-17 .419According tothescientists advising thePanel, synthetic
413Seepara. 8.4.
414Seeanswers byexperts toPanel Question 4,paras. 6.38-6.48. SeealsoTranscripts ofjoint meeting with experts of
17February 1997, paras. 342-348.
415Seepara. 8.176.
416Seepara. 4.93.
417Seepara. 8.190.
418Seealsoanswers byexperts toPanel Question 4,paras. 6.40-6.50 andTranscripts ofthejoint meeting with experts
of17February 1997, para. 348, where Dr.Lucier stated thatinhisopinion residues ofsynthetic hormones areofmore
concernthanthoseofnaturalhormonesbecausetherisksrelatedtothenaturalhormonesarealreadythereduetothoseoccurring
endogenouslyinthebody,whereasresiduesofthesynthetichormonesarenewtothebody.Thisdifferencedoesnot,however,
relate totheinherent characteristics ofboth categories ofhormones, buttothefactthatonecategory occurs endogenously
inhumans, whereas theother does not.
419Seeparas. 4.143 and4.145.WT/DS26/R/USA
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hormones canalsobebetter detected andcontrolled thannatural hormones.420Moreover, thefactthat
ADIs andMRLs exist forzeranol andtrenbolone andnotforthenatural hormones does not,according
totheexperts advising thePanel, persemean thatthelatter areinherently safer than theformer since
theinternational standards forboth synthetic andnatural hormones reflect essentially thesame level
ofprotection, namely a"noappreciable risk" level.421Therefore, even ifthere could bevalid reasons
tosubject thenatural hormones toatreatment different from thesynthetic hormones422,theEuropean
Communities hasnotprovided justification forsosignificant adifference inlevels ofprotection as
between a"noresidue" level (forthesynthetic hormones atissue) andanunlimited residue level (for
thenatural hormones endogenously present inmeat andother foods). Werecall, inparticular, that
theEuropean Communities hasnotprovided evidence thattheuseofzeranol ortrenbolone forgrowth
promotion purposes inaccordance with good practice (forexample, theCodex MRLs) isunsafe.423
Inother words, ithasnotsubmitted anyjustification foradopting a"noresidue" level, instead ofthe
Codex MRLs.
8.214 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forzeranol andtrenbolone andthenatural hormones indispute which
occur endogenously inmeat andother foods. Forthese reasons, wefindthatthedifference inlevels
ofprotection thus made bytheEuropean Communities is"arbitrary orunjustifiable" inthesense of
thesecond element contained inArticle 5.5.
3. Difference which results in"discrimination oradisguised restriction oninternational
trade"
8.215 Werecalltheconsiderationsmadeaboveontherelationshipbetweenthethreeelementscontained
inArticle 5.5.424Werecall, inparticular, thatinsome cases thesignificance ofthedifference inlevels
ofprotection forcomparable situations combined with thearbitrariness thereof may besufficient to
conclude thatthisdifference inlevels ofprotection results in"discrimination oradisguised restriction
oninternational trade".
8.216 Inthiscase, wenote, firstly, thesignificance ofthedifference inlevels ofprotection forzeranol
andtrenbolone andthatforthenatural hormones indispute which occur endogenously inmeat and
other foods, namely a"noresidue" level asopposed toanunlimited residue level. Werecall, secondly,
thattheEuropeanCommunitieshasnotprovidedanyplausiblejustificationforthissignificantdifference.
Wenote, finally, thatthisdifference inlevels ofprotection results inanimport ban(onmeat andmeat
products treated with zeranol ortrenbolone) which restricts international trade. Forthese reasons,
wefindthatthedifference inlevels ofprotection imposed bytheEuropean Communities forzeranol
andtrenbolone andthatforthenatural hormones indispute which occur endogenously inmeat and
other foods, results in"discrimination oradisguised restriction oninternational trade" inthesense
ofArticle 5.5.
420Seeanswers byexperts toPanel Question 22,paras. 6.199-6.202.
421See, forexample, opinion ofDr.Randell, para. 6.76. Wealsonote, inthisrespect, theopinion ofDr.Arnold,
para. 6.45: "The potential risks arising from other thanhormonal actions [related tothesynthetic hormones] were qualitatively
different. These risks were assessed during thereview andapproval process, andtheapproved conditions ofuseeliminated
allunacceptable risks".
422See, forexample, theCodex standards which have adopted MRLs forthesynthetic hormones andnotforthenatural
hormones.
423Seepara. 8.15, 137.
424Seeparas. 8.182-8.184.WT/DS26/R/USA
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8.217 Weconsider thatthisfinding isfurther supported bythetwoadditional factors outlined above425,
which areequally valid forthedistinction inlevels ofprotection made bytheEuropean Communities
forzeranol andtrenbolone andthenatural hormones indispute which occur endogenously inmeat
andother foods.
8.218 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forzeranol andtrenbolone andthenatural hormones indispute which
occur endogenously inmeat andother foods, inlight ofthethree elements contained inArticle 5.5,
andthat, therefore, theECmeasures indispute, insofarasthey relate tozeranol andtrenbolone,
areinconsistent with therequirements imposed inArticle 5.5.
The hormones indispute compared tocarbadox
8.219 Wenext examine thealleged different treatment provided bytheEuropean Communities for
fiveofthesixhormones indispute (allbutMGA) when used forgrowth promotion purposes and
carbadox. Werecall thatthisagent isanantimicrobial growth promoter used asafeed additive in
swine production.
1. Comparable situations with different levels ofsanitary protection
8.220 Inthisexamination wecompare different substances .However, both parties inthisdispute
andtheexperts advising thePanel agree thatthesituations thus compared involve thesame adverse
health effect ,namely carcinogenicity.426
8.221 Since wehave found above thatwecancompare situations where thesame adverse health effect
isinvolved as"different" situations (which werefer toas"comparable" situations forthepurposes
ofthisdispute) inthesense ofArticle 5.5427,wefindthatthetreatment ofthefivehormones atissue
when used asgrowth promoters asopposed tothatofcarbadox arecomparable situations inthesense
ofthefirst element ofArticle 5.5.
8.222 Wenextexamine whether theEuropean Communities hasadopted adifferent level ofprotection
forthese comparable situations.
8.223 TheUnited States argues thattheEClevel ofprotection forthehormones atissue when used
forgrowth promotion isdifferent from thatforcarbadox. TheUnited States submits thatwith respect
tothehormones atissue when used forgrowth promotion purposes theEuropean Communities has
suggested thatitsappropriate level ofprotection is"zero risk". With respect tocarbadox, theUnited
States argues thatitisclear from thefactthattheEuropean Communities permits theuseofcarbadox
andthesaleandconsumption ofmeat from animals towhich carbadox hasbeen administered, that
theEuropean Communities ischoosing anappropriate level ofprotection thatislessstringent than
forthehormones involved inthisdispute.428
8.224 Withrespecttothehormonesindisputewhenusedforgrowthpromotionpurposes,theEuropean
Communities adopted a"noresidue" level asitsappropriate level ofprotection.429With respect to
carbadox, theEuropean Communities argues that, even though these substances areallowed, strict
425Seeparas. 8.204 and8.205.
426Seeanswers byexperts toPanel Question 11,paras. 6.128-6.136 andpara. 4.220.
427Seepara. 8.176.
428Seepara. 4.220.
429Seepara. 4.93.WT/DS26/R/USA
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controls, specific characteristics ofthese substances andtheway they areadministered, ensure that
noresidue levels willremain intreated pigs when slaughtered andthat, therefore, intheEuropean
Communities inpractice thesame level ofprotection applies tocarbadox asthelevel adopted forthe
hormones indispute, namely a"noresidue" level.430
8.225 Wenote thattheEuropean Communities allows theuseofcarbadox asagrowth promoter in
pigsandhasnotsetanyMRL forthatsubstance. TheEuropean Communities thus, inprinciple, accepts
anunlimited residue level ofthese substances inpork meat. Moreover, werecall that, contrary to
what theEuropean Communities argues, a"noresidue" level cannot beachieved inpractice when use
ofthesubstance concerned isallowed (even under strict conditions) since there willalways besome
residue level ofthesubstance orametabolite, albeit avery small one, leftinthemeat, even after a
longperiodoftime.431Weconsider,forthesereasons,thattheEuropeanCommunitiescannotreasonably
claim thatitslevel ofprotection forcarbadox isa"noresidue" level.
8.226 WethusfindthatthelevelofprotectionadoptedbytheEuropeanCommunitiesforthehormones
atissue when used forgrowth promotion purposes asopposed tothatadopted forcarbadox isdifferent
(a"noresidue" level asopposed toanunlimited residue level) andthat, therefore, adistinction inthe
levels ofprotection forthese comparable situations exists inthesense ofthefirstelement ofArticle 5.5.
2. "Arbitrary orunjustifiable" difference inlevels ofsanitary protection
8.227 Wenext examine whether thisdistinction inlevels ofprotection is"arbitrary orunjustifiable"
inthesense ofthesecond element ofArticle 5.5.
8.228 TheUnited States argues thattherisks related tocarbadox areatleast asserious asthose related
totheuseofthehormones indispute asgrowth promoters.432Itrefers tothe36th JECFA Report of
1991 which could notsetanADIforcarbadox butdidadopt MRLs foroneofitsmetabolites, asopposed
tothe32nd and34th JECFA Reports of1988 and1989 which onlyadopted ADIs andMRLs forzeranol
andtrenbolone andconsidered MRLs forthethree natural hormones tobeunnecessary. TheUnited
States submits thatnone ofthearguments putforward bytheEuropean Communities justifies astricter
level ofprotection forthehormones indispute (which, according totheUnited States, aresafe) than
thelevel ofprotection forcarbadox (asubstance which, according totheUnited States, maypose serious
risks).433
8.229 TheEuropean Communities claims thatthedistinction inlevels ofprotection isjustified on
thefollowing grounds: (i)carbadox isnotahormone; (ii)carbadox only indirectly actsasagrowth
promoter bycombating thedevelopment ofbacteria andbyaiding theintestinal flora ofpiglets, thereby
alsoexerting preventive therapeutic effects (whereas thehormones directly actasgrowth promoters
andhave nopreventive therapeutic action when used asgrowth promoters); (iii)carbadox isonly
commercially available inprepared feedstuffs (notasinjections orimplants) inpredetermined dosages;
(iv)there arenoalternatives tocarbadox available which have thesame therapeutic action; (v)carbadox
cannot beabused since itonly hasgrowth promotion effects inpiglets uptofour months oldanda
430ECsecond submission tothePanel onECMeasures Concerning Meat andMeat Products (Hormones) -Complaint
byCanada, pp.9-10, paras. 35-36.
431Seeopinions ofallexperts advising thePanel inTranscripts ofthejoint meeting with experts of17February 1997,
paras. 90,91,93and95andanswers toPanel Question 3,paras. 6.32-6.39.
432Seepara. 4.220.
433Seeparas. 4.220 and4.221.WT/DS26/R/USA
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withdrawal period ofatleast 28days isfixed; and(vi)carbadox isused insuch small quantities and
ishardly absorbed thatitleaves practically noresidues atallinmeat destined forhuman consumption.434
8.230 Wenote, firstofall,thattheEuropean Communities hasnotsubmitted scientific evidence in
support ofthese alleged justifications. Wenextexamine thesixarguments putforward bytheEuropean
Communities inlight oftheopinions oftheexperts advising thePanel andthearguments submitted
bytheUnited States.
8.231 With respect tothefirstECargument, i.e.,thefactthatcarbadox isaantimicrobial agent and
notahormone, theEuropean Communities hasnotsubmitted anyreason why thisdifference could
initself justify adifferent regulatory treatment inthelight oftheir potential carcinogenic effect. We
thusfindthatthisargument does notjustify thedistinction inlevels ofprotection forthefivehormones
atissue when used asgrowth promoters andcarbadox.
8.232 TheEuropean Communities next argues thatthefivehormones atissue when used asgrowth
promoters have notherapeutic effect onanimals asopposed tocarbadox which combats thedevelopment
ofbacteria andaidstheintestinal flora ofpiglets. Wenotethat, according toscientific experts advising
thePanel, thehormones atissue when administered asgrowth promoters may alsohave beneficial
effects (such asimproved composition ofthecarcass upon treatment interms ofmore leanmeat and
lessfat).435Moreover, werecall thatthehormones atissue are,effectively, used fortherapeutic purposes
andthatsuch useofthethree natural hormones indispute isallowed intheEuropean Communities.
Forthese reasons, weconsider thatboth thehormones indispute andcarbadox may have therapeutic
effects andthusfindthatthesecond ECargument does notjustify thedistinction inlevels ofprotection
forthefivehormones atissue when used asgrowth promoters andcarbadox.
8.233 With respect tothethird ECargument, i.e.,thefactthatcarbadox isonlycommercially available
inpreparedfeedstuffs(notasinjectionsorimplants)inpredetermineddosagesandis,therefore,allegedly
lessopen forabuse, wenote thatoneofthescientific experts advising thePanel stated thatinjections
orimplants aremore accurate andreliable methods toadminister growth promoters than additives in
feedstuffs (because ofcarry-over risks from treated tountreated feed).436Theexperts alsostated that
additives infeedstuffs pose additional risks inthattheymayharm thepersons handling thefeedstuff.437
Wealsorecall that, according totheexperts advising thePanel, thecommercially available products
containing anyofthefivehormones atissue forimplantation orinjection alsocontain predetermined
dosages ofthese hormones.438Wethusfindthatthethird ECargument does notjustify thedistinction
inlevels ofprotection forthefivehormones atissue when used asgrowth promoters andcarbadox.
8.234 Addressing thefourth ECargument thatthere arenoalternatives tocarbadox available which
have thesame therapeutic action, wenote thatoneoftheexperts advising thePanel stated thatthere
arereadily available alternatives, such asoxytetracycline.439WethusfindthatthisECargument does
434ECsecond submission tothePanel onECMeasures Concerning Meat andMeat Products (Hormones) -Complaint
byCanada, p.9,para. 35.Weconsidered itappropriate toalsoaddress these ECarguments inthisPanel report (forour
reasoning onthisissue seepara. 8.15, 137).
435Seeanswers byexperts toPanel Question 2,paras. 6.22-6.31, inparticular answers byDr.Arnold, Dr.McLean and
Dr.Ritter. Seealsoopinion ofDr.Lucier, Transcripts ofthejoint meeting with experts of18February 1997, para. 742
where hefeels unable, asascientist, tocompare therisks related tothehormones with their potential benefits.
436Seeanswers byexperts toPanel Question 21,paras. 6.194-6.198, inparticular answer byDr.McLean atpara. 6.197.
437Seeanswers byexperts toPanel Question 21,paras. 6.194-6.198, inparticular answers byDr.André andDr.McLean
atparas. 6.194 and6.197.
438Seeanswers byexperts toPanel Question 15,paras. 6.156-6.166.
439Seeopinion ofDr.Arnold, para. 6.130.WT/DS26/R/USA
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notjustify thedistinction inlevels ofprotection forthefivehormones atissue when used asgrowth
promoters andcarbadox.
8.235 Werecall thefifth ECargument, i.e.,thatthepotential forabuse isallegedly smaller for
carbadox thanforthehormones atissue since theformer only exert growth promotion effects inpiglets
uptofourmonths andaresubject toastrict withdrawal period. Wenotethat, according totheexperts
advising thePanel, there isnoguarantee thatthepiglets treated with carbadox willnotbeslaughtered.
Residues ofthissubstance oritsmetabolites may thus enter thefood chain. Wealsonote that, asis
thecase fortheuseofcarbadox intheEuropean Communities, theuseofthehormones atissue as
growth promoters may alsobemade subject tostrict conditions. Wethusconsider thattheEuropean
Communities hasnotsubmitted evidence proving thatcarbadox canbemore easily controlled than
thefivehormones atissue andfind, therefore, thatthefifthECargument does notjustify thedistinction
inlevels ofprotection forthefivehormones atissue when used asgrowth promoters andcarbadox.
8.236 TheEuropean Communities further argues thatcarbadox isused insuch small quantities and
ishardly absorbed sothatitleaves practically noresidues atallinmeat destined forhuman consumption.
Werecall that, according totheexperts advising thePanel, once asubstance hasbeen administered
toananimal there willalways besome residue level ofthissubstance orametabolite left, albeit a
very small one,inthemeat ofthatanimal.440Wefurther notethat, according tothe36th JECFA Report
of1991 which assessed therisks related tocarbadox, notonly carbadox itself (forwhich noADIs could
beestablished) butalsooneofitsmetabolites, quinoxaline-2-carboxylic acid(forwhich anMRL was
adopted) maypresent ahealth risk. Wefinally notethat, according tothescientific experts441,residue
levels ofthehormones atissue willalsorapidly decline after administration toananimal oringestion
byhumans. Forthese reasons, wefindthatthesixth ECargument does notjustify thedistinction in
levels ofprotection forthefivehormones atissue when used asgrowth promoters andcarbadox.
8.237 TheEuropean Communities finally submits thatitauthorizes theuseofabout 10,000 to15,000
veterinary medicinal products andthatthefactthattheUnited States limits itsclaim under Article 5.5
toonlyonesubstance, proves thattheEuropean Communities hasalready achieved aremarkable degree
ofconsistency initslevels ofsanitary protection. TheEuropean Communities alsoinformed thePanel
thattheECCouncil, bydecision of26February 1996, already tookaction onitsowninitiative toreview
carbadox. Weconsider thatthese arguments donotjustify thedistinction which iscurrently stillmade
bytheEuropean Communities inlevels ofprotection forthefivehormones atissue when used asgrowth
promoters andcarbadox. Onthecontrary, these arguments suggest anacknowledgment bytheEuropean
Communities thatthedistinction inlevels ofprotection itcurrently makes may notbejustified and
willbereviewed.
8.238 Fortheabove reasons, wefind thattheEuropean Communities hasnotmetitsburden of
justifying thedistinction itmakes inlevels ofprotection forthefivehormones atissue when used as
growth promoters andcarbadox andthattheEuropean Communities has,apriori ,notmetitsburden
ofjustifying sosignificant adistinction between a"noresidue" level forthehormones atissue when
used asgrowth promoters andanunlimited residue level forcarbadox. Wefind, therefore, thatthe
distinction inlevels ofprotection thusmade bytheEuropean Communities is"arbitrary orunjustifiable"
inthesense ofthesecond element contained inArticle 5.5.
440Seepara. 8.199 and, particularly with respect tocarbadox, opinion ofDr.Lucier, Transcripts ofthejoint meeting
with experts of18February 1997, para. 275.
441See, forexample, opinion ofDr.Lucier, para. 6.37 andDr.Arnold, Transcripts ofthejoint meeting with experts
of17February 1997, para. 91.WT/DS26/R/USA
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3. Difference which results in"discrimination oradisguised restriction oninternational
trade"
8.239 TheUnited States submits thatthedistinction made bytheEuropean Communities inlevels
ofprotection forthehormones atissue when used asgrowth promoters andcarbadox results ina
disguised restriction oninternational trade inthesense ofthethird element contained inArticle 5.5.
According totheUnited States, theEuropean Communities swine industry (where growth promoters
areallowed)isrelativelymoreefficientandmarket-orientedthantheEuropeanCommunitiesbeefindustry
(wheregrowthpromotersarebanned),asectorwhereefficiencyisnotthatimportantbecauseofdomestic
price support measures, import protection andexport subsidies. When banning hormones, theUnited
States concludes, theEuropean Communities clearly wanted toreduce beef supplies, aconcern not
present inthepork sector where theEuropean Communities wanted, onthecontrary, topreserve
competitiveness andmaintain export markets.442
8.240 Werecall thatthethree elements contained inArticle 5.5allimpart meaning tooneanother
andthatinsome cases thesignificance ofthedifference inlevels ofsanitary protection forcomparable
situations combined with thearbitrariness ofthereof, maybesufficient toconclude thatthisdifference
inlevels ofprotection results in"discrimination oradisguised restriction oninternational trade".443
8.241 Inthiscase, wenote, firstly, thesignificance ofthedifference inlevels ofprotection forthe
fivehormones atissue when used asgrowth promoters andcarbadox, namely a"noresidue" level
asopposed toanunlimited residue level. Werecall, secondly, thattheEuropean Communities has
notprovided anyplausible justification forthissignificant difference. Wenote, finally, thatthis
difference inlevels ofprotection results inanimport ban(onmeat andmeat products treated with any
ofthese fivehormones atissue) which restricts international trade. Forthese reasons, wefindthat
thedifference inlevels ofprotection imposed bytheEuropean Communities forthefivehormones
atissuewhenusedasgrowthpromotersandcarbadox,resultsin"discriminationoradisguisedrestriction
oninternational trade" inthesense ofArticle 5.5.
8.242 Weconsider thatthisfinding isfurther supported bythetwoadditional factors outlined above444,
which areequally valid forthedistinction inlevels ofprotection made bytheEuropean Communities
forthefivehormones atissue when used asgrowth promoters andcarbadox.
8.243 Wefinally note thatthere isanother factor which indicates thatthedistinction intreatment
made bytheEuropean Communities forthehormones atissue when used asgrowth promoters and
carbadox results in"discrimination oradisguised restriction oninternational trade". That isthefact
thatthehormones atissue, which arebanned intheEuropean Communities, areused forgrowth
promotioninthebovinemeatsectorwheretheEuropeanCommunitiesseeminglywantstolimitsupplies445
andisarguably lessconcerned with international competitiveness, whereas carbadox, which isallowed
intheEuropean Communities, isused forgrowth promotion inthepork meat sector where theEuropean
Communities hasnodomestic surpluses andwhere international competitiveness isahigher priority.
8.244 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forfiveofthesixhormones atissue (allbutMGA) when used asgrowth
promoters andcarbadox, inlight ofthethree elements contained inArticle 5.5,andthat, therefore,
442Seepara. 4.221.
443Seeparas. 8.182-8.184.
444Seeparas. 8.204 and8.205.
445Seealsopara. 8.204.WT/DS26/R/USA
Page 221
theECmeasures indispute, insofarasthey relate tothese fivehormones indispute, areinconsistent
with therequirements imposed inArticle 5.5.
8.245 Insummary, inthissection wehave found thattheECmeasures indispute, both insofaras
they relate tothetwosynthetic hormones (zeranol andtrenbolone) andthethree natural hormones at
issue forwhich international standards exist, areinconsistent with therequirements contained in
Article 5.5. ThefactthattheECmeasures indispute arenotbased onexisting international standards
(contrary toArticle 3.1) can, forthatreason, notbejustified onthebasis ofArticle 3.3. TheEC
measures, insofarasthey relate tofiveofthesixhormones atissue forwhich international standards
exist, are,therefore, alsoinconsistent with therequirements ofArticle 3.1.
(iii) Article 5.6:measures notmore trade restrictive than required toachieve
theappropriate level ofprotection
8.246 Article 5.6reads asfollows:
"Withoutprejudicetoparagraph2ofArticle3,whenestablishingormaintainingsanitary
orphytosanitary measures toachieve theappropriate level ofsanitary orphytosanitary
protection, Members shall ensure thatsuch measures arenotmore trade-restrictive
thanrequired toachieve their appropriate level ofsanitary orphytosanitary protection,
taking intoaccount technical andeconomic feasibility".
Afootnote toArticle 5.6states thefollowing:
"For purposes ofparagraph 6ofArticle 5,ameasure isnotmore trade-restrictive than
required unless there isanother measure, reasonably available taking into account
technical andeconomic feasibility, thatachieves theappropriate level ofsanitary or
phytosanitary protection andissignificantly lessrestrictive totrade".
8.247 Since wefound above thattheEClevel ofprotection reflected intheECmeasures indispute
hasbeen adopted inviolation ofArticle 5.5,wedonotconsider itnecessary tofurther examine whether
these measures arealso more trade restrictive than required toachieve thatlevel inthesense of
Article 5.6.
(d) Article 5.7: provisional sanitary measures
8.248 Article 5.7reads asfollows:
"Incases where relevant scientific evidence isinsufficient, aMember mayprovisionally
adopt sanitary orphytosanitary measures onthebasis ofavailable pertinent information,
including thatfrom therelevant international organizations aswell asfrom sanitary
orphytosanitary measures applied byother Members. Insuch circumstances, Members
shall seektoobtain theadditional information necessary foramore objective assessment
ofriskandreview thesanitary orphytosanitary measure accordingly within areasonable
period oftime".
8.249 Werecall ourfinding reached above ontherole oftheprecautionary principle inthe
SPS Agreement, inparticular that this principle would notoverride theexplicit wording of
thatAgreement, inter alia,because ithasbeen incorporated inaspecific form inArticle 5.7.446In
thisdispute, theEuropean Communities hasexplicitly stated thatitsmeasures arenotprovisional
measures inthesense ofArticle 5.7. Wedo,therefore, notneed tofurther examine thisprovision.
446Seepara. 8.158.WT/DS26/R/USA
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6. Sanitary measures where nointernational standards exist: melengestrol acetate
("MGA")
8.250 Werecall thatwith respect tothethird synthetic hormone indispute, MGA, nointernational
standard exists.447Asoutlined above, theEuropean Communities is,therefore, notunder anobligation
tobase itssanitary measure inrespect ofthishormone onaninternational standard inaccordance with
Article 3.1.448
8.251 However, even though nointernational standard exists forMGA, theECmeasures indispute
relating toMGA stillneed tocomply with theother provisions oftheSPSAgreement. TheUnited
States hasinvoked violations ofArticles 2and5.Since Article 2provides forbasic rights andobligations
which arefurther specified inArticle 5,wefirstexamine theconsistency oftheECmeasures indispute
relating toMGA with therequirements ofArticle 5.449Theconsistency oftheECmeasures relating
toallhormonesindispute(includingMGA)withtherequirementsofArticle2willbedealtwithbelow.450
(a) Burden ofproof
8.252 Werecall ourfinding reached above onthegeneral burden ofproof under theSPSAgreement451,
inparticular thatfortheobligations imposed bytheSPSAgreement thatarerelevant tothiscase, the
party contesting asanitary measure (incasu theUnited States) bears theburden ofpresenting aprima
facie caseofinconsistency with theSPSAgreement, after which theburden ofproof shifts totheparty
imposing themeasure (incasu theEuropean Communities). Weconsider that, forthereasons mentioned
above452,thisallocation ofevidentiary burden isapplicable totheobligations imposed onMembers
under Article 5.Werecall, inparticular, thewording ofArticle 5.1,especially thefirstthree words
thereof:
"Members shall ensure thattheir sanitary ...measures arebased onanassessment ...ofthe
risks ..."(emphasis added)
andthewording ofthesecond partofthefirst sentence ofArticle 5.5:
"...each Member shall avoid arbitrary orunjustifiable distinctions inthelevels it
considers tobeappropriate indifferent situations, if..."(emphasis added).
Therefore, inthisdispute theUnited States hastopresent aprima facie case thattheECmeasures
indispute relating toMGA areinconsistent with therequirements ofArticle 5,after which theburden
shifts totheEuropean Communities toprove thatithascomplied with these requirements.
447Seepara. 8.70.
448Seeparas. 8.56 ff.
449Weonlyexamine theconsistency oftheECmeasures relating toMGA withtherequirements contained inArticles 5.1
to5.3and5.5. With respect totheother provisions ofArticle 5werefer toourconsiderations setoutinsection 5which
equally apply totheECmeasures relating toMGA.
450Seepara. 8.271.
451Seeparas. 8.48 ff.
452Seeparas. 8.52-8.54.WT/DS26/R/USA
Page 223
(b) Articles 5.1to5.3: risk assessment
8.253 With respect toArticles 5.1to5.3dealing with therequirement ofariskassessment ,theUnited
States argues thattheEuropean Communities hasnotsubmitted anyriskassessment forthehormone
MGA andthattheEuropean Communities has,therefore ,apriori ,notbased itsmeasures with respect
toMGA onanyriskassessment asrequired byArticle 5.1.453TheUnited States further submits that
itsFood andDrug Administration hasfully evaluated thesafety ofMGA andconcluded thattheuse
ofthishormone asagrowth promoter does notpresent arisktohuman health.454Wefindthatthe
United States thusmeets itsburden ofpresenting aprima facie caseofinconsistency with Article 5.1.
8.254 Werecall ourreasoning outlined above ontherequirement oftheexistence ofariskassessment
inaccordance with Articles 5.1to5.3455,inparticular thatwith respect tothefiveother hormones
indispute weassumed thattheEuropean Communities metitsburden ofdemonstrating theexistence
ofariskassessment since itreferred toseveral scientific reports which appear tomeet theminimum
requirements ofariskassessment.
8.255 With respect toMGA, wenote, however, thattheEuropean Communities hasnotsubmitted
anyscientific evidence inwhich thepotential foradverse effects onhuman health ofMGA residues
isevaluated. Moreover, thescientists advising thePanel have atseveral occasions stated thatthey
arenotaware ofanypublicly available scientific study which evaluates thesafety ofMGA456;thestudies
carried outbytheUnited States areproprietary studies which remain confidential.
8.256 TheEuropean Communities argues thattheECmeasures indispute regulate hormones onthe
basis oftheir physiological action, notonthebasis ofindividual substances andthattheadministration
ofanysubstance having anoestrogenic, androgenic orgestagenic action iscovered bytheECban,
including MGA which hasagestagenic action.457
8.257 Wenote, however, thatwith respect toallfiveother hormones indispute, JECFA, Codex
andtheEuropean Communities itself have conducted orinvoked riskassessments foreach individual
substance. Wefurther note thatoneofthebasic principles ofariskassessment appears tobethat
itneeds tobecarried outforeach individual substance.458Aswasstated inthe1995 ECScientific
Conference:
453Seeparas. 4.110-4.112.
454Seepara. 4.131 and4.136.
455Seeparas. 8.108-8.111.
456See, forexample, statements byDr.Ritter andDr.McLean, Transcripts ofthejoint meeting with scientific experts
of17February 1997, paras. 352and354.
457Seepara. 4.93.
458See, forexample, answer byDr.André toPanel Question 13(para. 6.142) andthepractice inJECFA which only
examines specific substances andthis,mostly, when these substances areused forspecific purposes. Inparticular, theJoint
FAO/WHO Expert Consultation onResidues ofVeterinary Drugs inFoods (29October -5November 1984; FAO Food
andNutritionPaperNo.32)recommendedthata"...scientificbodyshouldrelyontheadviceofexpertsinveterinarymedicine,
animal science, toxicology, microbiology, immunology, analytical chemistry andrelated sciences, andestablish criteria for
thesafety ofindividual veterinary drug residues asappropriate, taking intoaccount their public health significance, good
animal husbandry anddrug usepractices, thelikelihood ofresidues andtheavailability ofadequate analytical methodology"
(p.15, emphasis added).WT/DS26/R/USA
Page 224
"Itmust beemphasised thataseparate riskassessment must beconducted oneach
growth promoting substance. Itisnotappropriate toattempt toproduce adetailed
generic riskassessment foraclass ofgrowth promoters".459
8.258 Wethus find thattheEuropean Communities hasnotmetitsburden ofdemonstrating the
existence ofariskassessment with respect toMGA andthat, therefore, theECmeasures indispute,
insofarasthey relate tothehormone MGA, arenotbased onanassessment ofrisks inaccordance
with Article 5.
8.259 Werecall, inthisrespect, thattheEuropean Communities hasexplicitly stated thatArticle 5.7,
which deals with cases where relevant scientific evidence isinsufficient andallows aMember totake
provisional sanitary measures, does notapply tothemeasures indispute, including those relating to
MGA.460
8.260 Wefurther recall ourreasoning andfindings reached above (with respect tothefiveother
hormones indispute) ontheprocedural andsubstantive requirements aMember must satisfy inorder
tobase itssanitary measures onariskassessment inaccordance with Articles 5.1461.Werecall, in
particular, thattheEuropean Communities has, from aprocedural point ofview, notprovided any
evidence thatthestudies itreferred tohave actually been taken intoaccount bythecompetent EC
institutions orarereflected intheECmeasures insuch away thatthese measures could besaidto
bebased onthese studies. Wefurther recall thattheEuropean Communities hasnotmetitsburden
ofproving thatitsmeasures indispute, insofarasthey alsobantheuseofthefivehormones atissue
forgrowth promotion purposes inaccordance with good practice, are,from asubstantive point ofview,
based onariskassessment.
8.261 Thesamereasoningappliesapriori totheECmeasureswithrespecttoMGAsincetheEuropean
Communities hasnotsubmitted anystudy inwhich therisks related toMGA areassessed. Wethus
findthattheEuropean Communities hasnotmetitsburden ofproviding evidence tothePanel that
itsmeasures indispute, insofarasthey relate tothehormone MGA, are,either from aprocedural
orasubstantial point ofview, based onariskassessment andthat, therefore, these measures are
inconsistent with therequirements ofArticle 5.1.
(c) Article 5.5: distinctions inlevels ofprotection
8.262 Even ifwehadfound thattheEuropean Communities metitsburden ofproving thatitsmeasures
relating toMGA arebased onanassessment ofrisks inaccordance with Articles 5.1and5.2andeven
if,forthatreason, theEuropean Communities could have adopted anappropriate level ofprotection
against these risks, there would stillbeaneed toexamine whether thedetermination andapplication
ofthislevel ofprotection isconsistent with Article 5.5.462Inthisrespect, theUnited States argues
thattheEuropean Communities fails tojustify thefollowing differences inregulatory treatment: (i)
abanonMGA when used forgrowth promotion purposes asopposed tonotsetting anylimit forresidues
ofthenatural hormones present endogenously inuntreated meat andother foods (such asmilk, cabbage,
broccoli oreggs) orused fortherapeutic orzootechnical purposes; and(ii)abanonMGA when used
forgrowth promotion purposes asopposed toallowing theuseofcarbadox asagrowth promoter in
swine production. Only with respect tothelastmentioned difference intreatment does theUnited
States explicitly invoke Article 5.5.
4591995 ECScientific Conference Proceedings, p.250.
460Seepara. 8.249.
461Seeparas. 8.112 ff.
462Seepara. 8.163.WT/DS26/R/USA
Page 225
8.263 Werefer toparagraphs 4.209-4.211 forthearguments submitted bytheUnited States with
respect tothese distinctions inlight ofthethree elements contained inArticle 5.5andfindthatthe
United States meets itsburden ofpresenting aprima facie case ofinconsistency with Article 5.5.
(i) MGA forgrowth promotion compared tothenatural hormones occurring
endogenously inmeat andother foods
8.264 Werecall ourreasoning andfindings reached above with respect totheECmeasures indispute
relating tothehormones atissue other than MGA, inparticular ourfinding thattheEuropean
Communities hasnotmetitsburden ofjustifying thedistinction itmakes inlevels ofprotection for
residues ofzeranol andtrenbolone (two ofthesynthetic hormones indispute) andresidues ofthenatural
hormones indispute which occur endogenously inmeat andother foods, inlight ofthethree elements
contained inArticle 5.5, andthat, therefore, theECmeasures indispute, insofarasthey relate to
zeranol andtrenbolone, areinconsistent with therequirements imposed inArticle 5.5.463
8.265 Weconsider thatthisreasoning andthese findings equally apply totheECmeasures indispute
relating toMGA (thethird synthetic hormone indispute). Firstly, theEuropean Communities has
adopted different levels ofprotection (a"noresidue" limit464asopposed toanunlimited residue level)
forcomparable situations, incasusituations posing thesame adverse health effect (i.e.,carcinogenicity),
namely forMGA used asagrowth promoter andthenatural hormones indispute which occur
endogenously inmeat andother foods inthesense ofthefirstelement ofArticle 5.5. Secondly, the
European Communities hasnotsubmitted evidence thatthisdifference inlevels ofprotection isjustified
andhasthus notmetitsburden ofproving thatthisdifference isnot"arbitrary orunjustifiable" in
thesense ofthesecond element ofArticle 5.5. Thirdly, theEuropean Communities hasnotmetits
burden ofrebutting thearguments andevidence submitted bytheUnited States thatthisdifference
inlevels ofprotection results in"discrimination oradisguised restriction oninternational trade" in
thesense ofthethird element ofArticle 5.5.
8.266 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forMGA used asagrowth promoter andthenatural hormones indispute
whichoccurendogenouslyinmeatandotherfoods,inlightofthethreeelementscontainedinArticle5.5,
andthat, therefore, theECmeasures indispute, alsoinsofarasthey relate toMGA, areinconsistent
with therequirements imposed byArticle 5.5.
(ii) MGA forgrowth promotion compared tocarbadox
8.267 Wefurther recall ourreasoning andfindings reached above with respect totheECmeasures
indispute relating tothehormones atissue other thanMGA, inparticular ourfinding thattheEuropean
Communities hasnotmetitsburden ofjustifying thedistinction itmakes inlevels ofprotection for
residues ofthehormones atissue (other than MGA) when used forgrowth promotion purposes and
residues ofcarbadox inlight ofthethree elements contained inArticle 5.5andthat, therefore, the
ECmeasures indispute, insofarasthey relate tothehormones indispute (other than MGA), are
inconsistent with therequirements imposed byArticle 5.5.465
8.268 Weconsider thatthisreasoning andthese findings equally apply totheECmeasures indispute
relating toMGA. Firstly, theEuropean Communities hasadopted different levels ofprotection (a
463Seepara. 8.218.
464Seepara. 4.104.
465Seepara. 8.244.WT/DS26/R/USA
Page 226
"noresidue"limit466asopposedtoanunlimitedresiduelevel)forcomparablesituations,incasusituations
posing thesame adverse health effect (i.e.,carcinogenicity)467,namely forMGA used asagrowth
promoter andcarbadox inthesense ofthefirst element ofArticle 5.5. Secondly, theEuropean
Communities hasnotsubmitted anyevidence thatthisdifference inlevels ofprotection isjustified and
hasthusnotmetitsburden ofproving thatthisdifference isnot"arbitrary orunjustifiable" inthesense
ofthesecond element ofArticle 5.5. Thirdly, theEuropean Communities hasnotmetitsburden of
rebutting thearguments andevidence submitted bytheUnited States thatthisdifference inlevels of
protection results in"discrimination oradisguised restriction oninternational trade" inthesense of
thethird element ofArticle 5.5.
8.269 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forMGA used asagrowth promoter andcarbadox, inlight ofthethree
elements contained inArticle 5.5, andthat, forthisreason, alsotheECmeasures indispute which
relate toMGA areinconsistent with therequirements imposed byArticle 5.5.
8.270 Insummary ,inthissection wehave found thattheECmeasures indispute relating toMGA
areinconsistent with therequirements contained inArticles 5.1and5.5.
7. Article 2:"Basic Rights andObligations"
8.271 Since wehave found thattheECmeasures indispute areinconsistent with therequirements
ofArticles 3and5oftheSPSAgreement andconsidering thatArticles 3and5provide formore specific
rights andobligations than the"basic rights andobligations" setoutinArticle 2,weseenoneed to
further examine whether theECmeasures indispute alsoviolate Article 2.
E. ARTICLES IAND IIIOFGATT
8.272 Since wehave found thattheECmeasures indispute areinconsistent with therequirements
oftheSPS Agreement, weseenoneed tofurther examine whether theECmeasures indispute are
alsoinconsistent with Article IorIIIofGATT.
8.273 Asnoted above inparagraph 8.42, ifwewere tofindaninconsistency with Article IorIII
ofGATT, wewould then need toexamine whether thisinconsistency could bejustified, asargued
bytheEuropean Communities, under Article XX(b) ofGATT andwould thusnecessarily need torevert
totheSPS Agreement under which wehave already found inconsistencies. Since theEuropean
Communities hasnotinvoked anydefence under GATT other than Article XX(b), aninconsistency
with Article IorIIIofGATT would, therefore, inanyevent, notbejustifiable.
466Seepara. 4.104.
467Seepara. 4.108.WT/DS26/R/USA
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F. CONCLUDING REMARKS
8.274 Inorder toavoid anymisunderstanding astothescope andimplications ofthefindings above,
wewould liketostress thatitwasnotourtasktoexamine generally thedesirability ornecessity of
theECCouncil Directives indispute. Theability ofanyMember totake sanitary measures which
donotaffect international trade wasnotatissue inthepresent case. Ourexamination wasconfined
tothose aspects oftheECmeasures thathave been raised bytheUnited States, namely theECimport
banonmeat andmeat products ofbovine origin treated with anyofsixspecific hormones forgrowth
promotion purposes. Itwasfurther limited tothespecific provisions ofGATT andtheSPS Agreement
which have been invoked bytheEuropean Communities insupport ofthisimport ban. That isthe
necessity oftheimport ban, which theEuropean Communities strictly construed asasanitary measure,
fortheprotection ofhuman lifeorhealth. Likewise, theability ofanyMember toenact measures
which areintended toprotect notconsumer health butother consumer concerns wasnotaddressed.
Inthisregard, weareaware thatinsome countries where theuseofgrowth promoting hormones is
permitted inbeef production, voluntary labelling schemes operate whereby beef from animals which
have notreceived such treatment may besolabelled.
IX. CONCLUSIONS
9.1 Inlight ofthefindings above, wereach thefollowing conclusions:
(i) TheEuropean Communities, bymaintaining sanitary measures which arenotbased
onariskassessment, hasacted inconsistently with therequirements contained inArticle 5.1
oftheAgreement ontheApplication ofSanitary andPhytosanitary Measures.
(ii) TheEuropean Communities, byadopting arbitrary orunjustifiable distinctions inthe
levels ofsanitary protection itconsiders tobeappropriate indifferent situations which result
indiscrimination oradisguised restriction oninternational trade, hasacted inconsistently with
therequirements contained inArticle 5.5oftheAgreement ontheApplication ofSanitary and
Phytosanitary Measures.
(iii) TheEuropean Communities, bymaintaining sanitary measures which arenotbased
onexisting international standards without justification under Article 3.3oftheAgreement
ontheApplication ofSanitary andPhytosanitary Measures, hasacted inconsistently with the
requirements contained inArticle 3.1ofthatAgreement.
9.2 Werecommend thattheDispute Settlement Body requests theEuropean Communities tobring
itsmeasures indispute intoconformity with itsobligations under theAgreement ontheApplication
ofSanitary andPhytosanitary Measures.WT/DS26/R/USA
Page 229
ANNEX
PANEL ONEUROPEAN COMMUNITIES -MEASURES CONCERNING MEAT
AND MEAT PRODUCTS (HORMONES) -PANEL ESTABLISHED AT
THE REQUEST OFTHE UNITED STATES
PANEL ONEUROPEAN COMMUNITIES -MEASURES CONCERNING MEAT
AND MEAT PRODUCTS (HORMONES) -PANEL ESTABLISHED AT
THE REQUEST OFCANADA
Transcript oftheJoint Meeting with Experts, held on
17and18February 1997
First day-17February 1997
Chairman
1. Iwould liketowelcome thescientific experts andtheparties tothisexpert meeting. Letme
start byinforming youthattheproceedings ofthismeeting arebeing recorded, therefore, when taking
thefloor, representatives andexperts should please usetheir microphones. Asindicated inmyletter
of7thofFebruary 1997 thePanel decision tojointhetwomeetings with scientific experts stems from
thesimilarities ofthetwocases, asdoes thePanel 'sdecision tousethesame scientific experts inboth
cases andtoinvite Canada andtheUnited States toparticipate onequal footing inthemeetings inboth
cases. Inaddition, there istheconsideration thatfrom apractical perspective there willbeaneed
toavoid therepetition ofarguments andofquestions. Irecall thatastotheproceedings inlegal terms,
thecases arenotformally joined. They arejoined forthissession today andtomorrow asahearing
oftheexperts andthedebate with theexperts. Itend tosaythatthere canonly beonetruth inthis
matter; wecannot have twotruths. That isthephilosophy weshould address atthismeeting andtake
advantage offullmutual information here. Thepurpose ofthismeeting isthattheexperts canexpand
ontheir written briefs andthatourquestions canbeputtothem, views canbechallenged. Iwould
liketotaketheopportunity atthisstage tothank theexperts very deeply thatthey responded insuch
ashort period oftime totherequest ofthepanel. Asyouknow, weareoperating under very stringent
time constraints, wehave toproduce reports with certain delays andthisputs anenormous pressure
notonly onusbutalsoonyou. AndIvery much would liketothank youattheoutset thatyouagreed
mostly towork onthis, Iassume, over Christmas holidays toproduce your substantive reports. These
reports arevery substantive anditisnotamatter ofrepeating them linebylinebutreally tohighlight
themain points andthefocus andalso toputthePanel intoaposition tobefully informed about
controversial issues which may exist here which would allow ustomake alegal assessment here.
2. Ialsowould liketostress thattheproceedings areconfidential. Everything which isbeing
saidinthisroom issubject totherules ofdispute settlement. Soit'sconfidential unless release is
permitted byoneoftheparties. Wehadarequest thismorning from theEuropean Community at
aninformal meeting togrant theopportunity tohave theparties 'experts from ECsidemaking upfront
statements inorder tofully inform theparties andthePanel inthese proceedings ontheir views. The
Panel hasdiscussed thisrequest andhascome totheconclusion thatwewould deny thisopportunity
forthefollowing reasons. This meeting oftwodays wassetupasahearing ofexperts andthepurpose
istohear theexperts andputquestions totheexperts bymaking useofscientific experts within the
delegations. Itisnotthepurpose ofthismeeting tohear newevidence which hasnotbeen submitted
byFebruary 8th. And itisnotthepurpose ofthismeeting tohave formal statements bytheparties,
butjustfrom theexperts. Now, thiswillnotexclude thattheexperts which areonthedelegationsWT/DS26/R/USA
Page 230
oftheparties canspeak tothepoint, thatthey would dosowhen time isgiven tothedelegations and
they areinaposition toexpand ontheir views during these interventions. These interventions will
thenagain give theexperts theopportunity toreact towhat wassaidfrom thedelegations. Inthelight
ofthis, Iwould liketoexplain how wewould liketoproceed today. Wewould firsthave statements
bytheexperts andIwould liketoinvite youtofocus onyour main points, your main arguments, your
main areas where youseetheissues, themain areas ofcontention andalsowhere youseetheproblems
inyour colleagues 'reports. After thestatements, followed bytheexpert oftheCodex, there willbe
discussion within thepanel ofexperts. When thisisconcluded, theUnited States will have the
opportunity toputquestions andtocomment ontheexperts 'views. This willbefollowed bythe
intervention oftheEuropean Community, with thepossibility, asIsaid, tohave statements byyour
ownexperts anditwillthengotoCanada forthesame proceeding. Andsince wehave twoproceedings
heremixed, theECwillagain have anopportunity totakethefloor inthevery end. After thisprocess,
wewould intend togivetheexperts again individually thefloor forafinal statement where theycould
stress their views again andtheir conclusions. ThePanel would then sitintheevening andwewould
then trytofocus onmore specific questions which from alegal point ofview may stillnotbeclear
andinthemeeting oftomorrow afternoon weasaPanel would thencome inwithvery specific questions
totheexperts which westillmayhave toclarify. Sowehave ageneral debate which inthebeginning
hopefully thatwhich willallow ustofocus onthemain issues andtomorrow there might bevery specific
questions here. This does notexclude thattoday theparties mayraise specific questions totheexperts
based ontheir written submissions, based ontheanswers tothequestions here. And Iassume that
delegations areprepared todoso.Mylastpoint isplease trytobeshort andtothepoint inallyour
interventions. Please trytoavoid repetitions, repetitious statements, sothatwecangoalong with the
time. This is,Ithink, theendofmyintroduction. Iwould now liketodeclare open thehearings.
Irepeat thatallthatissaidinthisroom remains confidential under therules ofPanel proceedings and
Iwould propose thefollowing order: Professor McLean, Dr.Arnold, Professor André, Dr.Ritter,
Dr.Lucier andthen Dr.Randell astheCodex expert. Iaminformed thattheslide machine hasnot
been installed, soifsomebody would liketoshow slides itwould have tobedone intheafternoon.
Iapologize forthis. Somay Ithen give thefloor toProfessor McLean.
Dr.McLean
3. Thank youMr.Chairman. Iwillbebrief andhighlight theparts ofmysubmission thatIthink
aremost germane. Inrelation togood practice andgood veterinary andgood animal husbandry practice,
Ithink itisimportant torealize thatthisgood practice isthepractice thatisnegotiated between the
sponsor oftheproduct andtheregistering authorities todefine theconditions under which thecompound
willbeused. Andonce those conditions aredefined, thentheymake uppartoftheregistration approval
andinthatwaythemaximum residue limit canbeestablished. Theother thing thatisimportant with
themaximum residue limit istounderstand thatitisalegal limit andnotahealth limit. Inother words,
theexceeding oftheMRL does notrepresent ahazard tohealth butisrather alimit atwhich the
authorities takeaction. However, Imust saythattoexceed theMRL would notbeseen tobegood
practice. Inrelation tothemeat thatisproduced, toallintents andpurposes, themeat issimilar.
Infactitmay notbepossible totellthedifference between meat produced using growth-promoting
agents andmeat thatisproduced without them. That when welook atthose twohormones forwhich
there isamaximum residue limit, then aminute residue may remain thatcannot bedetected by
commonly-usedregulatorymethods.Ithinkitisimportanttorealizethatthemethodsusedareregulatory
methods rather thansome ofthemore sophisticated methods thatcangotoorders ofmagnitude below
theregulatory method. Ifwewere relying upon those sorts ofmethods then thesurveillance process
would becumbersome andcostly andactually preclude satisfactory surveillance. Oneofthekeys to
theuseofthese sorts ofcompounds istocombine theuseofthecompounds with surveillance toensure
thatgood practice isfollowed andtheMRL isnotexceeded.
4. JECFA haslooked atthese compounds particularly inits1988 meeting andagain in1989 and
itwasatthatpoint thattheADI andMRL wasestablished, orinthecases ofthree naturally-occurring
hormones itwasdeemed thatanMRL wasnotnecessary. These twomeetings were particularlyWT/DS26/R/USA
Page 231
important, because itwasdetermined forthethree naturally-occurring hormones thatthere wasno
way ofshowing thatmeat treated with thehormones oruntreated meat were substantially different
andsotherefore toregulate them byananalytical technique would notbepossible orpractical and
indeed inmany cases thelevels thatwere seen after treatment were extremely small inrelation tothe
naturally-occurring substances. Itisinteresting tonotethatJECFA since 1988 and1989 hasreviewed
anumber ofcompounds onasecond occasion. These compounds have been referred totheJECFA
meetings bysponsors orbyregulatory authorities andgovernments. Butonnooccasion hasthematter
ofthedetermination the'88and'89JECFA meetings inrelation tothefivehormones thatitapproved
been,onnooccasionhasanyorganizationsoughttorevisitthematterofoestradiol17beta,progesterone,
testosterone, trenbolone andzeranol. Ithink itisvery important because onavery significant number
ofoccasions JECFA hasattherequest ofvarious groups revisited thematter ofthetoxicology and/or
theresidues ofproducts orcompounds thatitsetMRL andADIs for.And thattheopportunity exists
andhasexisted since 1988 and1989 torevisit thematters ofthefivehormones under consideration
andthatopportunity hasnotbeen taken. Itisinteresting toseeatthisstage theamount ofmaterial
thatisalleged toshow thatthecompounds should berevisited, thatisbeing produced forthisparticular
meeting yetnoonehastaken theopportunity torefer toJECFA. Yetonnumber ofoccasions, asI
said, theopportunity todothatisbeing taken with other compounds. When JECFA approved the
useofthethree naturally-occurring hormones itaccepted thefactthatindeed welivevirtually ina
seaofhormones. These hormones came from endogenous levels produced inhumans, anditcame
inmaterial thatwetakeininthedieteither from eating meat naturally orfrom eating other material
thatcontains hormonally active substances; things thatarecommonly found inthedietincluding eggs,
soya products, anumber ofplant materials andfungal products such asthose from Fusarium from
which zeranol isderived. Indeed itisvery difficult todetermine exactly where ourhormone burden
comes from butthefacts ofthematter arethathumans areconstantly being exposed tovery significant
levels ofhormones andthattheincidence oftumours associated which arewith hormones inhumans
such as,forexample, thebreast ortheprostate, have notsignificantly increased since thesurveying
hasbeen carried out. When Isaythatwemust takeintoaccount thatthediagnostic technology available
fordiagnosing some ofthese tumours andalsothelevel ofeducation ofthepublic hassubstantially
increased but,ifyoucorrect forthatsortofdataandcorrect itforage, then there hasbeen very little
change. Some ofthenew datathathasbeen submitted particularly relies upon invivoand invitro
carcinogenicity testing andalsosome ofthemutagenicity testing butIdonotbelieve thatitisanymore
significant than thesortofdata thatwasavailable atthetime theoriginal appraisal wasmade.
5. Thehormones inquestion areused inanumber ofcountries andhave been used formany
years andepidemiological datadonotsuggest thatthishashadanuntoward effect onhuman health.
There areanumber ofcompounds thathave been used inveterinary medicine orinassociation with
crops from which wehave seenuntoward effects inhumans, buttheresidues present inthefivehormones
inquestion have notshown anydeleterious effects inhumans thathave been accurately documented.
Many ofthehormones arelipid soluble andtherefore pass intothefatportion ofmilk andthatisa
significant intake forhumans, particularly foryoung children andalsoforadults intheintake ofbutter
andcheese; I'mreferring tothethree naturally-occurring hormones. Thehormones inquestion are
notwell absorbed orally, andindeed theuptake there isextremely small with theexception ofcourse
ofmelengestrol acetate. Aswell, there isdatathatshows thatanything uptoapproaching 80percent
ofsome ofthehormones areactually destroyed upon cooking.
6. Inrelation totheillegal cocktails, inthecountries where thecompounds areregistered then
theuseoftheillegal cocktails isvirtually non-existent. There areregistered products which are
combinations ofzeranol andtrenbolone, oestradiol andprogesterone ortrenbolone ortestosterone and
combinations likethatandtheregistration oftheproducts permits control ofuse. Inrelation tothe
useofthecompounds, theyarepackaged insuch awaythattheyareinaninert matrix andthatmatrix
isinjected intotheanimal, intheear,byspecially developed injection apparatus, andthattherefore
does control theinjection intotheanimal. Incountries where thedrugs arenotregistered andused
illegally then theadministration byanacceptable technique thatcontrols therelease andisremoved
onslaughter, isnotavailable.WT/DS26/R/USA
Page 232
7. Coming back again totheMRL, Istress thatitisalegal limit based ondaily consumption
ofaproduct foralifetime corresponding totheuptake oftheADI, however, itisnotahealth limit
andoccasional consumption isofnoconcern andIthink Iwillstop there Mr.Chairman.
Chairman
8. Thank youvery much, Professor. Could your statement besummarized thatyoubelieve that
thecurrent standards wehave arefully adequate toaddress theproblem?
Dr.McLean
9. Yes, Mr.Chairman, Idobelieve onhaving examined countries where thecompounds have
hadalong history ofuse, having examined thepackages ofdata submitted toJECFA andIthink it
isparticularly important thatpeople thataretalking about these hormones seethefullpackages ofdata
submitted toJECFA bythesponsors. These packages ofmaterial contain theindividual animal data
andaremuch more satisfactory ifoneisgoing topassjudgement thansome ofthematerial intheopen
literature. Where these compounds have been used, then Ibelieve thatevidence shows thatthey are
used responsibly ascompared with countries where theuseisnotpermitted butthey arestillused,
andunder those circumstances Ibelieve thatthere should besome concern butused inaccordance with
theagreed protocols, then Ibelieve thatthey aresafe.
Chairman
10. Thank youvery much foryour statement. Igive thefloor toDr.Arnold.
Dr.Arnold
11. Thank youMr.Chairman. Since Ishare many views expressed byProfessor McLean Iwill
notrepeat arguments putforward byhim. Iwillalsonottrytosummarize mywritten answers which
Ihave submitted induetime. Iwilltrytobevery brief andonly make afewvery general statements
atthistime.
12. Mygeneral view oftheproblem isvery similar towhat hasbeen expressed most recently by
theSteering Committee andaspecialist working party ofascientific conference ongrowth promotion
inmeat production organized bytheEuropean Community. Theexperts which hadbeen invited by
Commissioner Fischler have summarized, andthisisalsomyview, concerning thenatural sexhormones
andIreadfrom their summary: "Atpresent there isnoevidence forpossible health risks totheconsumer
duetotheuseofnatural sexhormones forgrowth promotion since residue levels ofthesubstances
measured inmeat oftreated animals fallwithin thephysiological range observed inmeat ofcomparable
untreated animals. Thedaily production ofsexhormones byhumans ismuch higher thantheamounts
possiblyconsumedfrommeat.Eveninthemostsensitivehumans,pre-pubertalchildrenandmenopausal
women, duetoanextensive firstpass metabolism, thebio-availability ofingested hormones islow,
thus providing afurther safety margin." And onzeranol andtrenbolone thisconference hasstated,
andIshare these views: "Atthedoses needed forgrowth promotion, residue levels arewell below
thelevels regarded assafe, theMRLs. There areatpresent noindications ofapossible human health
riskfrom thelowlevel ofcovalently-bound residues oftrenbolone."
13. This ismyfirstvery general statement. Concerning thenot-disputed carcinogenic properties
ofthese substances, mypersonal views very similar towhat hasmost recently been expressed by
Professor Jonathan Li,whoisaleading expert inthefield ofkidney carcinogenesis. Hehassummarized
onthebasis oftheevidence wehave today: "The inescapable conclusion isthathormones, particularly
oestrogens, arenon-genotoxic carcinogens. This latter term, however, issomewhat misleading since
non-genotoxiccarcinogensbydefinitionultimatelyaffectpermanentgeneticchangesleadingtoneoplastic
transformation. Perhaps amore appropriate term would beepigenotoxic, defined asreferring toanWT/DS26/R/USA
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agent thatisnotinvolved indirect covalent orindirect interactions withgenetic material, butnevertheless
isable toelicit heritable changes byalternative mechanisms." Iaminclined toshare these views.
Ithink alotofconfusion hasemerged inrecent years because atthetime when thepolicies towards
genotoxic carcinogens have been established, genotoxicity hasmeant clear mutagenicity. Inthe
meantime, over thepastdecades, many tests have been developed which picked upvery early end
points ofdamage tothegenome. Justtomention one, single-strand breaks, Icould mention many
others, intheDNA. Now theproblem is,itisclearly agenotoxic effect asingle-strand break observed,
forexample ,invitro.However thisPanel should know thattypically inacellthisevent occurs some
5,000 times perhour andthecapacity torepair such adamage isintheorder of200,000 such events
perhour. Now forexample, Igive only oneexample, Dr.Liehr wasabletodemonstrate such breaks
atextremely highdoses andhewasabletodemonstrate atenpercentincrease itremains tobeconfirmed
thatsuch anevent isofanysignificance invivo. Ihave similar problems with Dr.Metzler 'spaper
who reports about genotoxic potential. Forexample, inhispaper onpage 12,hesays with respect
toagents causing numerical chromosomal abberations (aneuploidy) abiochemical threshold canbe
expected ontheoretical grounds andcanbemeasured ininvitro systems such asculture cells. However,
itisimpossible todetermine thisthreshold inanintact organism invivo,because itisnotknown which
tissue ismost susceptible atwhich stage ofdevelopment andindifferent individuals. Forresidues
infood, exposure occurs forpeople ofallages andvalues ofsusceptibilities. Iagree, firstofall,that
ontheoretical grounds there should beathreshold. Ialsoagree thatwedonotknow where thisthreshold
exactly liesbutwhat weperfectly know isthatthedoses which have provoked such effects aremany
ordersofmagnitudeabovetheconcentrationswearetalkingabouttoday,aminimumof1,000,sometimes
10,000 or100,000 times. There exist many papers andliterature which have demonstrated thatthe
no-effect levels forsuch effects areintheorder ofonemicro-molar orslightly below andthere we
arestillfarabove theconcentrations wearetalking about today. So,myconclusion isalotofevidence
hasbeen puttogether about genotoxicity ofthesubstances, mostly invitro,buttherelevance tothe
invivo situation stillremains unclear. Particular activities have been focused onthemetabolism of
theso-calledcatecholoestrogens.Thisisacategoryofcompoundswhichisknownsinceseveraldecades.
Ihadalready tolearn these structures when Iwasastudent andalsomore than 20years agotheir
metabolic activation hasalready been proposed. However, therealrelevant work hasbeen done in
thepastyears andtheideaisthatthese substances could beactivated inmetabolism toactascarcinogens.
Theproblem which Ihave with thepapers written byDr.Liehr, notonly ontheoccasion ofthisPanel
butIhave very carefully examined, areview article hehaspublished lastyear inAnnual Review of
Pharmacology andToxicology, thatsometimes Ihave theidea thathedoes notclearly discriminate
between what hasbeen done aspure chemical synthesis orintests ininvitro andwhat hasbeen shown
ininvivo situations. Icannot find anyevidence supporting theview thatthemetabolic pathways
elucidated tosometime byinvitro studies areofrelevance ininvivo. So,Ithink alotof
misunderstanding iscreated bythedifferent usesoftheterm "genotoxic carcinogen" asithasevolved
inhistory andasitisused nowadays. Ithink Iwould notliketoaddmuch more atthismoment, but
Iwillbeopen toanswer questions.
Chairman
14. Thank youvery much Dr.Arnold. Doyouhave from thePanel anyquestions atthemoment?
Notnow? Okay. Thank youvery much foryour statement. Now Igivethefloor toProfessor André,
please.
Dr.André
15. Thank you, Mr.Chairman. Iwillbeavery short forthemoment because Ididnotprepare
aspecific assessment. You don'taskbefore, butmaybe youdon'tknow how tomanage thismeeting
today.WT/DS26/R/USA
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Chairman
16. Yes, andIdidn'taskyou, sothatthespeeches willbeshort indeed.
Dr.André
17. Okay, thank you. Soit'sanice surprise. ButIthink alsothatmany things have been said
before andwritten intheanswers tothequestions. Iwould justliketoaddsome comments, personal
comments. Asanexpert Iamhere asaveterinarian first, Iamabiochemist secondly. ButIamnow
working more intheanalytical field ofresidue control ofthese hormones indispute. And when I
received thequestions itlooked thatmany ofthese questions more orlessoutside myfield ofstrict
competence, because Iammore concerned with toxicology aswell aswith some veterinary oranimal
husbandry practices. However, Iaccept toanswer andIdecided atthebeginning towork asastudent
would do,which means looking atfirst atrecent scientific available data andsynthesizing them. I
wasvery impressed todiscover thenumber ofrecent publications, between 1990 andnow, about these
topics ofhormones andspecifically onhormone 'saction inanimal health orabout their toxicology.
Ialsotryalways tostayoutside thepolitical debate andtobestrictly anhonest scientific. About some
points here, Ijustcomment. Forexample, about good animal husbandry practices aswell asgood
veterinary practices, ithasbeen saidjustbefore mytalkthatwhen drugs ingeneral areregistered,
thisregistration iswith some withdrawal periods andrules ofimpairment. Infactproblems, thereal
problem, Ithink, istheproblem ofcontrol, how tobesure thatthese practices arereally respected
andwhat wecansaynow isthatofficial control services areincharge tocontrol these. Butalsothat
now more andmore people themselves, Iwould liketosay, people asveterinarians, asfarmers, as
farmer organizations, aretaking thecontrol andareensuring thatthey willonly useregistered drugs
asitispossible toofficially usethem. About residues andremaining residues, there isaquestion about
thepersistence ofresidues inmeat andanimals. Itisclear thatthisdepends ofanydrug butitsometimes
very surprising todiscover thatwhen youdevelop newsophisticated methods, youobserve thatresidues
arestillremaining avery very very longer time than itiscommonly known. And wehave personal
experiences forcertain drugs, near hormones inthisfield. About toxicity ofthese compounds, and
more precisely carcinogenicity orgenotoxicity, Iwasvery impressed toread many papers about these
compounds, recent scientific papers (and Isent youtheoriginal papers) andjustlooking faston
summaries, conclusions ofthese papers, itseems foreverybody nowclear thattheyhave very dramatic
toxicity andthatmost ofthenatural aswell assynthetic hormones have anaction onDNA assaid
byDr.Arnold. Theproblem isjusttheproblem ofdose response andtheproblem ofthreshold. I
think thatwhen acompound isusually recognized now asgenotoxic, theproblem ofthreshold isnot
ofconcern. And Iwould liketocompare insimple words asif,Mr.Chairman, youwere student,
andIamsorry forthecomparison. Ifyoudrive, forexample, 30,000 miles ayear, youhave a
probability, arisk, tohave anaccident. Ifyoudrive only 1kilometre ayear, youhave alsoaprobability
tohave anaccident. You cannot saythatunder onethousand kilometres orunder athousand miles
ayear, youwill never have anaccident. And thatis,Ithink, thesame thing forthese kind of
compounds. Themore youuse,themore youhave risktohave anaccident. Butyouhave nolimit
under which itispossible tobesure thatyouwillnever have anaccident. Sorry forthecomparison,
ifyouthink itistoosimple, butIthink itissometimes useful. Concerning thevery first problem
ofJECFA andCodex andthese institutions, itisclear thatthejobstheydoisvery useful foreverybody
andthatnobody, noscientist, willthink thatitisabadassessment done bythese organizations. Ijust
have apersonal problem about thedefinition ofdrugs aspublished bytheCodex, forthereason that
drugs inthese definitions involve allfamiliar known drugs butalsophysiological modifiers, asthese
hormones arewhen they areused forgrowth promotion. And tomypersonal opinion, there isvery
bigdifference between adrug, Imean zootechnical andtherapeutical purposes ofthese hormones, and
theuseasgrowth promoter, forthereason thatyoumay admit thatyouhave asmall riskwhen use
adrug because inthiscase, youcannot avoid touseitanditisvery more difficult toadmit thatyou
takeariskwhen using justtomodify. Maybe alsotheconsequence isthatariskassessment forsuch
modifiers must bedone with other rules than theclassical rules fordrugs. This hasbeen saidinthe
previous conference inBrussels in1995. Coming back tothecomparison, youcanadmit thatyouWT/DS26/R/USA
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could have anaccident going tothehospital. Soforthemoment Ithink Iwillstop thespeech. I
apologize tooformyEnglish, which isbad, itisnotmymother tongue. Butwecanlater come back
onmany points, ifyouwish.
Chairman
18. Thank youvery much foryour excellent introduction toyour paper andassessment. May I
now turn toDr.Ritter.
Dr.Ritter
19. Thankyou,Mr.Chairman.Thiscommunicationsystem,Imustcomment,isawonderfuldevice
initself forarbitration asitonly permits oneperson tospeak atatime. Ishould saythatcoming fourth
following three distinguished scientists leaves melittle opportunity toaddanything ofanyconsequence
additionally. Buthaving saidthatofcourse Iwilltaketheopportunity tosayafewthings. Ishould
begin byreally thanking thePanel fortheopportunity tocontribute tothedebate. This isadebate
which hasgone onforsometime now andIsuspect onewhich may continue forsometime yet,and
itisofcourse anextraordinary privilege tobegiven theopportunity tocontribute tothedebate with
myunderstanding oftheissue. So,Iamgrateful forthatunderstanding, forthatopportunity.
20. Iwillattempt tovery quickly addafewpoints tothose thathave already been made bythose
whocame before me. Youknow ofcourse, Mr.Chairman, thatmyself andmythree colleagues were
provided with avery limited period oftime inwhich toprovide comments andsoatleast inmycase
Ihave attempted todosotothebestofmyability within thetime constraints thatwere provided.
There willbeunquestionably information thatsome may citethatIomitted inmycomments andthat
isamatter, Ithink ofpractical necessity rather thananerror, ifyouwish. Informulating myopinions
Ihave, totheextent available tome,attempted touseaslarge aninternational database aspossible.
That iswhyIhave made extensive useof...[data](?) [cassette sidefinished] ...byWHO, byJECFA,
byCodex andinthepublished scientific literature. Ihave notreferred toproprietary data, even to
theextent towhich Imay have haditavailable tome. Ihave, ofcourse, made extensive reference
totheproceedings oftheEuropean Conference onGrowth Promotion fortworeasons. First and
foremost, because Ibelieve thatthatConference which washeld inBrussels inlate1995, represented
theviews ofanoutstanding group ofscientists from theinternational community andbrought some
considerable expertise tothedebate. And secondly, because Ibelieve thatthis1995-96 Conference
was avery important andvery recent updating ofinformation which hadalready been reviewed
internationally byorganizations such asJECFA in1988 andin1989. Socertainly itismyopinion
thatthiswhole issue hasbeen re-evaluated asrecently asearly 1996. And itismyview thatthe
European Conference hasessentially reaffirmed, andindeed I'llgoasfarastosaystrengthened, the
earlier conclusions which were reached byJECFA, andthatisthatinaccordance with operating
procedures thatareprovided fortheuseofthese substances, thattheir usedoes notconstitute arisk
toconsumers offood commodities produced with thehormones atquestion, atleast forfiveofthe
six. ThePanel would beaware thatMGA hasnothadthebenefit ofaninternational review. My
colleague Professor McLean hasalready articulated thefactthatanMRL isnotahealth limit, butrather
aregulatory limit andthatthelimit may well bedifferent indifferent jurisdictions fordifferent
operational reasons, because ofclimate, because ofgeography, because ofusepractice andotherwise.
ButtheADI isaninternational value. And Iwould draw theattention ofthePanel particularly tothe
point thatforthethree natural hormones, itwastheopinion ofJECFA, andindeed theview re-enforced
bytheinternational conference inDecember of1995, thatthese natural hormones donotrequire the
establishment ofanacceptable daily intake, because infacttheir usereflects levels which areentirely
within therange thatonemight expect inanimals thathadnotbeen treated atall.That is,their use
would result inaresidue which would beindistinguishable from animals which hadnever been treated.
Inthecaseofxenobiotic hormones itgoes without saying ofcourse thatthese hormones arenotnatural
bydefinition, andhence anylevel which canbedetected isoutside ofwhat onemight expect inan
animal which hasnothave been treated. Buteven inthatcase, theconclusion thathasbeen drawnWT/DS26/R/USA
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internationally, isthatagain inaccordance withtherecommended useprocedures thatthese levels which
doremain constitute noriskwhatsoever forconsumers oftheproduct.
21. Ishould say,Mr.Chairman, thatthere hasbeen some considerable debate astothepotential
forabuse ofthese products andthehealth risks thatthisabuse mayconstitute. Iwould addmypersonal
conviction thatIdonotbelieve thatthepotential forabuse inanywayspeaks tothesafety ofappropriate
use. Imake thatpoint because thejuxtaposition thatiscreated often inthedebate isthatbecause there
ispotential forabuse ofanything, whether wearetalking about these hormones orwhether weare
talking about motor vehicles orwhether wearetalking about alcohol, Ithink weneed toremember
thatthatpotential hasnoimpact whatsoever ontheappropriate use. Iwould alsosuggest tothePanel
thatbecause thepotential forabuse exists, inmyview, isnotareason toimpute thesafety ofappropriate
use. AndifImaybepermitted todraw avery simplistic example, notunlike theonethatmycolleague
Professor André drew amoment ago, Ihardly think thatwewould beconsidering thebanning ofthe
automobile because some people speed. Itisaquestion ofriskmanagement andnotriskassessment.
And theissue thatIthink wehave todealwith ishow dowecontrol those people who speed sothat
wecanallenjoythebenefitoftheautomobileandsimilarlyhowdoweappropriatelymanagethepotential
forabuse with these hormones rather than imply thatthisabuse somehow oranother makes the
appropriate useunsafe. Ishould addperhaps before Ileave theissue ofabuse justvery quickly that
itisnoteworthy thatincountries where useofthese hormones, thesixhormones inparticular, has
been permitted foravery extended period oftime, andIrefer most notably toCanada andthe
United States, monitoring andcompliance programmes which have been ongoing nowfrom many many
years have consistently demonstrated thatresidue levels areentirely within recommended limits and
thatinstances ofviolative residues, thatisresidues which would indicate abuses taking place, have
almost never been reported. Sothatitseems thatatleast inthose jurisdictions where useislawful,
thepracticality ofabuse hasnever become areality. There are,asIsay,fewandisolated examples
ofviolative residues inthose countries where usehasinfactbeen permitted.
22. Itisperhaps important, Ithink, tobring totheattention ofthePanel thefactthatwehave an
enormously richexperience inthehuman case with these hormones, andIdraw thePanel 'sattention
specifically totheuseofoestrogen, andmost notably oestrogen incombination with progesterone,
asanoralcontraceptive which hasnow been inpractice inthehuman population forperhaps 35to
40years andthatthere have been tensofmillions ifnothundreds ofmillions ofwomen who have
taken these steroids onadaily basis, inmany instances fortheir entire reproductive life, periods of
time thatmayhave ranged from 30to50years. Andthatthese levels have typically reflected anintake
andexposure thatranges somewhere between 20and100micrograms, depending onthepharmaceutical
preparation, onadaily basis fortheentire reproductive cycle ofthehundreds ofmillions ofwomen
inquestion. Itisinteresting tonote thatthese levels arethousands, ifnothundreds ofthousands, of
times greater than thelevels, Mr.Chairman, towhich youorImight beexposed inconsuming meat
which results from theuseofthese hormones inproduction. And although theissue ofbreast cancer
most notably iscertainly oneofconsiderable interest these days, Ithink itisfairtosaythattodate,
there isnocompelling evidence whatsoever todemonstrate thattheuseoforalcontraceptives containing
twoofthevery hormones atissue before thispanel, over atleast anentire generation inhundreds of
millions ofpatients, hasnotresulted inanycompelling evidence tosuggest thattheuseofthese drugs
infactconstitutes anyincreased risktothese women ofcancer whatsoever. Finally, Mr.Chairman,
Iwould only conclude bysaying thatcertainly inthecaseofthenatural hormones, andasIhave already
indicated atleast inthecase oftrenbolone andzeranol forthexenobiotic hormones, Ithink thefive
have allbeen subjected toboth national andinternational reviews which have been re-reviewed, ifyou
like, asrecently asDecember 1995. Itwould certainly bemyview, Iwould certainly share theviews
expressed bothbyJECFA andbythisinternational forum thattheuseofthese compounds, inaccordance
with provisions provided onaregulatory level fortheir useincountries thatinfactpermit theuseof
these products, does notconstitute anincreased riskorharm tothose consumers who consume food
commodities produced with theaidofthese hormones. Thank you, Mr.Chairman.WT/DS26/R/USA
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Chairman
23. Thank youvery much foryour statement. May Iturn now toDr.Lucier.
Dr.Lucier
24. Thank you, Mr.Chairman andIalsothank thePanel forinviting metoparticipate inthisreview.
Mycomments really evolve from myresearch activities inthefield ofreceptor biology. Ihave had
alaboratory activity inthearea ofreceptor biology forover 20years now, andmore recently Ihave
been involved incoordinating anational toxicology programme within theDepartment ofHealth and
Human Services oftheUnited States, thatisresponsible forproviding atoxicological evaluation on
agents ofpublic health concerned whether theybeintheenvironment, intheworkplace, infoodstuffs,
physical agents andsoforth. Ihave alsobeen involved over theyears working with theInternational
Agency onResearch onCancer onanumber oftheir efforts intheir hazard identification, their risk
identification, chemical carcinogens andinparticular those inwhich hormonal activity seems tobe
attheroot ofthepotential carcinogenic activity. Having come last, Iprobably won'tsaytoomany
things thathaven 'tbeen saidbefore, butletmegothrough some ofthekeyissues atleast from my
perspective andthose thatIfeelcomfortable incommenting on.One isthattheresidues thatoccur
from thenatural hormones arecertainly going tobeindistinguishable from those which occur from
thenatural endogenous materials. This isnottrue, ofcourse, forthesynthetics. With appropriate
analytical methods andappropriate residue levels oneiscapable ofdetecting residues ofthesynthetic
materials here inquestion. Ishould alsopoint outthatthehalf-life, thebiological persistence, ofthe
agents inquestion isforthemost partrather short. They donotstick around thebody very long.
Buthaving saidthat, halflifebeing justwhat itsays isthetime inwhich ittakes forhalfthematerial
todisappear. So,ifsomething hasahalflifeofonedayifyoustart outwith tenunits ofit,oneday
later youhave five, twodays later youhave twoandahalfandsoforth. Soeven though several months
may elapse following anexposure toanagent even with arelatively short halflife, afewmolecules
may remain. Thenumber ofmolecules may beremarkably close tozero, probably notdetectable by
analytical methods, butafewmolecules willlikely remain. Ishould alsopoint outinterms ofthe
carcinogenic activity ofthehormones inquestion, wealready know that physiological levels,
naturally-occurring levels ofandrogens andoestrogens arecarcinogenic. One outoftenwomen in
theindustrialized world getsbreast cancer. There iscompelling mechanistic biological information,
human studies andtoxicological studies toshow thatoestrogens areattherootofthis. That their cancer
isamulti-step process butthatoestrogens appear toberesponsible forthemajority ofthecarcinogens
thatareseen inthesite. Sowealready know thatphysiological levels arecarcinogenic. Wealready
know thatearly menarche increases risk, latemenopause increases risk. Weknow thatwhen awoman
loses herovaries andheroestrogen production diminishes, therisktobreast cancer alsodiminishes.
Charles Huggins inhisnoteworthy work back intheearly sixties show thatovariectomy (removal of
theovaries) prevented breast cancer inexperimental animals. Thesame istrueofendometrial cancer.
Weknow from human studies thatendometrial cancer iselevated significantly byexposure tooestrogen
replacement therapy when thisisunopposed byprogesterone. Conjugated oestrogens have been called
aknown human carcinogen bytheInternational Agency forResearch onCancer. DES ofcourse has,
butDES isnotaquestion here andthemechanism bywhich DES produces cancer maynotberelevant
totheissues here. Tamoxifen, ananti-oestrogen inbreasts, produces cancer intheendometrium because
itactslikeanoestrogen intheendometrium, theuterus. Itactslikeananti-oestrogen inthebreast
soitblocks ...chemotherapeutic agent inwomen who have breast cancer andthesizeofthetumours
frequently diminish after thisexposure. Oral contraceptives arealsoaknown human carcinogen but
notbecause ofbreast cancer. They areaknown human carcinogen because ofincreased riskofliver
cancer. Theincreased riskisquite small, butnevertheless there hasbeen aconsistent riskshown across
studies. After having said that, Ineed toaddthatthenumber ofmolecules thatremain following
appropriate useofthese agents isvery small. They arevery small inrelation totheamount of
naturally-occurring oestrogens orandrogens. Sotheaccompanying riskthatwould beassociated by
consuming meat containing residues would beextraordinarily small. Itwould bevery hard onscientific
grounds tosaythattheriskwaszero. Butitislikely tobevery, very small. Itcould bezero. ItWT/DS26/R/USA
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could beashigh asbyestimates asonecancer inamillion people exposed tothem over their lifetime.
Sotherisk, tosum upthose comments, issomewhere between zero andsomewhere around onein
amillion. And thatoneinamillion isavery difficult number topindown. Alotofassumptions
gointoit.What Iwould saywould beaconservative estimate, anupper bound estimate, andIcan
gothrough astohowIcame upwith thatnumber ifthose details arerequired. Acouple ofother points
thatIwould likemake. One isthattheissue ofthreshold really isnotrelevant here. AsIalready
said, theamount ofmaterial thatisadded totheexisting burden isvery very small. Theamount of
naturally-occurring oestrogens andlikely androgens arealready carcinogenic, soyouarealready adding
toacarcinogenic burden. Sotheissue ofthreshold istotally irrelevant tothetoxicological evaluation
ofthese agents. Itmay alsobeirrelevant todistinguish between genotoxic andgenotoxicity, when
onegetsright down toit.Iwould saythatthere isagreat dealofevidence tosupport thenotion that
receptor mediated events, i.e.normal hormone pathways, arethemain reason why hormones and
hormonal agents arecarcinogenic. However, there isabody ofknowledge thatsuggests thatthey do
genotoxic activity, thisgenotoxic activity could possibly contribute tothecarcinogenicity Imean there
areexamples ofsome invivoexperiments thathave shown thisinwhole animals, andIcangoover
those ifrequested. Butmybottom lineisanextensive discussion ofgenotoxicity versus non-genotoxicity
really isn'trelevant tothediscussion andtotheoutcome because wealready know thattheexisting
levels ofhormone arecarcinogenic. The only reason fordistinguishing genotoxicity from non-
genotoxicity inmyunderstanding, anditmay beanaive understanding, istodetermine whether or
nottoapply alinear orathreshold model forriskassessment. Athreshold model would assume that
there isadose below which noeffect could occur. Since wearealready intotheeffect region, again
weareadding anexisting burden byadding anexisting number ofchemicals tothatburden, again
keeping inmind thatthisisavery small addition andmay beremarkably close tozero. Wealso, in
thecourse ofthenational toxicology programme, done carcinogenicity evaluations onapproximately
500agents. Many ofthese agents arecarcinogenic byvirtue oftheir genotoxic activity, many are
carcinogenic byvirtue oftheir non-genotoxic activity. When welooked atthose response relationships
forgenotoxic andnon-genotoxic carcinogens, wecouldn 'tdistinguish onefrom theother. Inother
words, non-genotoxic carcinogens were nomore likely toexhibit linear behaviour thangenotoxic ones.
Soagain thatgoes back tomypoint thatthegenotoxic versus non-genotoxic issue, Idon'tthink that
isarealone. Acouple ofother points tomake. One is,when onelooks atthenatural versus the
synthetic compounds, thesynthetic compounds clearly have hormonal activities, that'swhy they are
used inthesituation. They mayalsohave other kinds ofactivity inaddition tothatbecause molecular
structureisdifferentthanthatforthenaturally-occurringoestrogenssotheremaybedifferentmetabolites,
possibly adifferent spectrum ofadverse effects. Iassume thatwhen onelooks atthetoxicological
datathatisavailable onthese, andnotallofitwasavailable tomebecause some ofitisproprietary,
thattheappropriate studies would bedone todetermine thatother effects arenotoccurring. Effects
thatcould bedetected bysub-chronic 90days studies orthree yearstudies andbyappropriate molecular
screening techniques. Another point regarding thecocktails, thesynergy. There wasarecent paper
indicating possible synergy ofoestrogens inscience, using yeast. Atthispoint, therelevance ofthat
system toeven riskhasnotbeen shown, andthose results have notbeen repeated inhuman cells.
SoIthink theissue ofsynergy, more thanyoumight expect from adding twoweak oestrogens together,
theissue ofadditivity orantagonism, ofoneinhibiting theother, really isanopen question. Inmy
mind, additivity istheappropriate waytoestablish risk. Ishould alsoreiterate again thatcancer is
amulti-step process. Wecandefine thedifferent steps operationally, insome cases, somewhat
mechanistically. Itinvolves DNA damaging steps, creation ofmutation, theability ofcells thatharbour
thismutation toproliferate more rapidly thannormal cells. Itisgenerally thought thatoestrogens act
primarily atthatstepthatstimulates thegrowth rateofgenetically altered cells, cells thatalready harbour
mutation, andthere isawealth ofscientific information andliterature toshow that. Thework by
Dr.Liehr, Dr.Metzler, Dr.Cavalieri andother folks indicate thatthere maybesome genotoxic activity
forthese agents, suggesting thatthey may acttosome extent onthatfirst step, which would bethe
creation ofthatmutation. Soitappears possible thatwithin theframework ofamulti-step model for
cancer, thathormones andthese hormones inquestion byactonmore than onestep. And thelast
point thatIwant tomake iswetalkalotabout thetoxicology ofthese agents, however, itisimportant
topoint outthatoestrogens have been used intherapy foralong time formany purposes. CertainlyWT/DS26/R/USA
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oestrogen replacement therapy isone. There isaconvincing body ofknowledge toshow thatoestrogens
canprevent bone lossinwomen who aresusceptible tothat, soitcanreduce theriskofosteoporosis.
There arealsostudies toshow thatoestrogens candecrease heart disease. Sowhen onestarts looking
atanoverall riskassessment, thesmall amount ofoestrogens thatareadded bytheconsumption of
meat containing these residues, itseems appropriate alsotolook atthewhole balance ofeffects, what
arethebenefits versus risks. And Ithink thatisgoing tobeahard question toanswer. There may
beavery very small riskfrom adding these smaller molecules ,butthere may alsobeasmall benefit.
Idon'tthink wehave thetools inwhich toadequately determine thatriskbenefit ratio, andIthink
that isgoing tobeone ofthedifficulties that thePanel hasincoming togrips with what
recommendations, what decision thatthey make. Letmestop there, andagain Iwillbeglad toadd
more details tomycomments orrespond toquestions asthemeeting ison.
Chairman
25. Thank youvery much foryour introduction. May Igive thefloor toDr.Randell, theCodex
expert.
Dr.Randell (Codex)
26. Thank you, Mr.Chairman. And thank youfortheopportunity ofmeeting with youandyour
fellow Panel members. Andalsofortheopportunity ofmeeting somany oldcolleagues from myJECFA
days; Ihaven 'tseen some ofthem forquite anumber ofyears. JECFA istheFAO-WHO Joint Expert
Committee onFood Additives. Itwasfounded in1955 byFAO andWHO with theintention ofgiving
guidance tothese organizations andtheir member governments onthematter ofchemical substances
added tofood, essentially forwhatever reason. Initsearly days, JECFA established what wasknown
astheADI (Acceptable Daily Intake) concept, initiated infactbyProfessor Rene Truhaut, who isno
longer with us.TheADI concept isbuilt around aconcept ofadding noappreciable riskwhen you
addchemicals tofood. That concept hasbeen with us,asIsay, since thelate1950s andwith very
minor modifications itstands asitstands today. Chemicals thathave been given anADI byJECFA,
orbynational authorities because thesame concept hasbeen adopted bymany national authorities,
anintake lessthan thatADI, over alifetime, produce noappreciable risktotheperson consuming
it.In1960-61, FAO andWHO thenturned their attention topesticide residues andthejoint meetings
onpesticide residues formulated theconcept oftheMaximum Residue Level. This isdifferent tothe
ADI. Maximum Residue Limit wasestablished toensure thatpesticides used infield conditions under
good agricultural practice didwhat they were supposed todoanddiditwithin aframework ofsafety.
IfIcould usearelatively simple explanation oftheMRL inthepesticide context. Ifweapply apesticide
toafield wedoitforcertain reasons, wedoittokillapest. Ifyouapply more than thatthen you
have exceeded what youneed todoandyouhave surplus residue, which isthought tobeanunwise
thing. Ifyouspray lesspesticide onthefield yougettheworst ofboth worlds: yougetthepestand
yougetresidues which youdidn'twant tohave inthefirstplace. Sotoacertain extent themaximum
residue level isameasure ofhowmuch ofthechemical isneeded toachieve theobjective ofpestcontrol
andatthesame time fallswithin theframework ofthesafety analysis. JECFA andJMPR were expert
committees andthey stillareexpert committees. And itwasin1962 thatFAO andWHO formed the
intergovernmental Codex Alimentarius Commission, which wasestablished toprotect thehealth of
consumers andtofacilitate, toremove unnecessary barriers totrade infood products. Thework of
Codex, thework ofJECFA andthework ofJMPR went on,andstillgoes on,with increased interest
from many parties andcertainly alotofincreased interest since theMarrakesh Agreement. Inthe
early 1980s, anumber ofCodex committees began toraise questions, governments atthese committee
meetings, began toraise questions about how dowedealwith theresidues ofthesubstances used for
growth promotion. Itisofinterest tonote thatthese were brought upinthePesticide Residues
Committee,CommitteeonFoodAdditives,CommitteeonMeatHygiene,CommitteeonPoultryProducts.
There wasinfactsome sortofcompetition between theCodex committees astowho wasgoing to
handle thishotpotato. In1984, FAO andWHO convened anexpert consultation toadvise thetwo
organizations onhowtohandle thisparticular problem. Itwasanexpert consultation onprocess ratherWT/DS26/R/USA
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thanonscientific detail. However, theconsultation didcome totheconclusion thatitwasanappropriate
area forCodex towork in;thatthemost significant problem inthefield wasnotthelegitimate use
ofgrowth promoters oranyother veterinary drugs, under good veterinary practice conditions, but
rather theabuse oruncontrolled use; thatitwould beappropriate fortheCodex Commission toestablish
aseparate committee tohandle these matters. And theexpert consultation alsohadthefirst stabat
providing adefinition ofwhat wasmeant byveterinary drugs. Itwastheintention oftheexperts of
thisconsultation, andIwasprivileged tobethesecretary ofthatconsultation, tomake thedefinition
asbroad asonecould possibly imagine andthisiswhy weeven getreferences inthedefinition to
apiculture andbeegrowing. Theexpert consultation resulted intheestablishment ofacommittee by
theCodex Alimentarius forresidues ofveterinary drugs infood, anditalsogave thestimulus forJECFA
tobegin work inthisareainearnest andtoobtain thefirstreally comprehensive datapackages onthe
substances about which wearespeaking today. They were evaluated in1987, andafollow-up evaluation
fortrenbolone acetate in1989. Therecommendations oftheJECFA were intheform ofmaximum
residue limits (MRLs) although ofcourse fortheendogenous hormones therather peculiar statement
thattheMRL wasthatanMRL notnecessary, aninternal tautology which Ithink wearegoing to
have tolivewith forsometime. These MRLs were processed through theCodex system andwere
firstdiscussed atthe19th Codex Alimentarius Commission session in1991, when itwasdecided not
toadopt theMRLs astheycurrently stood. When thecomplementary information ontrenbolone acetate
hadpassed through thesystem, theMRLs were re-presented foradoption at21stsession oftheCodex
Alimentarius Commission, andwere adopted. That isthehistorical level.
27. Onthescientific side, Iwould liketocome back toquestions which youasked theCodex and
Iassume JECFA Secretariat inyour written questions, particularly about therelationship between the
acceptable daily intake andthemaximum residue limit andwhether ornotthese aremeasures ofthe
acceptable risk. Themaximum residue limit isdefinitely notahealth-based limit. Itisalimit established
forthecontrol ofveterinary drugs inactual practice. Thethinking which goes intotheestablishment
ofamaximum residue limit issuch thatthemaximum residue limit willnever leadtoresidues which
would, inanormal ingestion oftheproduct, cause anyconsumer toexceed theacceptable daily intake.
Thereforethereisanupperboundarytothemaximumresiduelimitimposedbytoxicologyconsiderations.
Thelower limit isnormally derived from residue trials inpractice according totheproposed good
veterinary practices intheuseofthese drugs. However, incertainly onecase, inthecaseofzeranol,
thislimit falls sofarbelow notonly thetoxicologically derived limit butiteven falls well below the
limit thatonecandetermine with normal methods ofanalytical chemistry, andtherefore hasbeen
increased totake intoaccount thefactthatifyouaregoing tooperate adecent control programme,
thatisnotgoing tobeoverly expensive, than youhave alimit which iscontrolled bytheanalytical
procedure rather than bytheresidue trials. Theacceptable daily intake itself alsoisnotadirect risk
assessment inthesense thatitprovides astatement ofquantitative risk. TheADI concept states that
there willbenoappreciable riskasaresult ofexposure tothechemicals concerned. This istrueof
within theJECFA andJMPR framework. This istrueoffood additives, residues ofveterinary drugs
andpesticide residues. Iappreciate very much your comment Dr.Lucier thattheriskisprobably
somewhere between zero andoneinamillion (one intentotheminus six), because thisdoes putsome
sortofquantitative framework onthat. ButJECFA hasnever established aquantitative evaluation
ofriskintheapplication oftheADI. Ithink Iwillleave myintroductory comments there ifthatis
satisfactory toyou, butIwould bevery pleased toanswer additional questions ontheevaluations.
Thank you.
Chairman
28. Thank youvery much, Mr.Randell. According toourprocedures, Iwould now liketogive
thefloor totheUnited States delegation forcomments orquestions totheexperts. May Igive you
thefloor, Mr.Brinza?WT/DS26/R/USA
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Mr. Brinza (US)
29. Thank you, Mr.Chairman. First with respect tocomments ontheresponses thatwereceived
from theexperts, wedohave some written comments thatwewould liketomake available toyou
allnow thatwould facilitate usgetting through what Isuspect would bealengthy exercise -itwould
notbevery fruitful tojustread them. Soletmeprovide those toyou. Ithink weshould have enough
copies forthePanel andtheexperts aswellasfortheother delegations. Wethought itwould beuseful
toasksome questions thatwould gotoallfiveoftheexperts. Therepresentative from Codex ofcourse
iswelcome torespond aswell, butweassume thatyouareserving more inyour ex-officio capacity
withrespect totheCodex institutional issues. What wewould liketodowould betoasksome questions
ofallfive, thatIthink would befairly simple questions, justtomake surethatweunderstood theareas
oftheresponses where there wasconsensus since there were different responses -there were insome
cases different wordings -sowejustwant tomake sureweunderstood correctly alltheresponses and
thefoundations forsome ofthose responses.
30. Forexample, with respect tothethree natural hormones -oestradiol 17beta, progesterone
andtestosterone -weassumed thatallfivewould agree thatthese three compounds areallpresent in
themeat-producing animals aswell asinhumans naturally (endogenously produced, Ithink, would
bethebetter way ofexplaining that).
31. Secondly, assuming thatistrue, dotheyalsoagree thatthese three hormones areallnaturally
present inthemeat andthemilk from those animals? Ibelieve wehave heard some oftheexperts
already refer tothatbutitcould beuseful tomake sure thatallthefiveofthem agree with that.
Assumingthereisagreementonthat,whenfoodproductscontainingthenaturallevelsofthesehormones,
inother words levels within thenormal physiological range, dothese hormones have abiological effect
onconsumers? Wehave afewmore likethisandIwilldefer toyouonwhether itisappropriate to
getresponses now onthose andthenwegoonfrom there orwhether youprefer todothem allatonce
inthisparticular series andthen have theresponses. Itmay bedifficult forthem tokeep track ofthe
different questions.
Chairman
32. Iwould propose thatyoudirectly putthequestions tothePanel andenter intoadialogue and
then goonthrough your programme.
Mr. Brinza (US)
33. Thank you, Mr.Chairman. Ifthatistheinstance then, ifIcould askthefiveexperts with
respect toeach ofthose first three questions, Ijustwant tomake sure weunderstood correctly your
responses, firstly arethese three hormones naturally present inthemeat-producing animals andin
humans? Itmay beuseful tojustgoaround thetable starting with Dr.Ritter.
Dr.Ritter
34. Theextent towhich theyarepresented ofcourse asyouwillknow isafunction tosome extent
ofthestatus ofthehuman inquestion andtheage, buttoprovide ageneral answer, Ithink, inmy
view thegeneral answer is"yes", noting thatthere willbesome exceptions invariance onthedegree.
Iunderstand thatthelevels aredifferent butthatthey areallpresent tosome extent.
Dr.McLean
35. Yes. There willbevariations inlevels butthethree naturally-occurring hormones arefound
inboth animals andhumans.WT/DS26/R/USA
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Dr.Arnold
36. Iagree, Mr.Chairman, andweperfectly know thelevels occurring from fetal lifetountil very
lateage.
Dr.André
37. Yes. Thehormones arethesame butitisnotclear ifthemetabolites sometimes could be
different. Forexample, ifyougive anatural hormone as(.?.) tocalves ortoanymeat producing
animals, they canmetabolize andtransform thehormone andinthese conditions thefood intake for
human isnotthesame. You seeanimals have been treated asifthey arenottreated, qualitatively.
Dr.Arnold
38. IfIcould justclarify with Professor André, arewetalking about levels ofthatmagnitude with
respect totheadministration ofanyofthese three forgrowth promotion purposes inaccordance with
good animal husbandry practice?
Dr.André
39. Themetabolic transformation, thebiological transformation, istotally independent ofthelevel.
Itisnotaproblem oflevel. Maybe Idon'tunderstand well your question.
Dr.Arnold
40. Ithought your earlier answer hadbeen thatthere isapossibility thatthese could beadministered
atsuch alevel thatthey cannot bemetabolized bytheanimal. And myquestion was, arethedoses
wearetalking about forgrowth promotion sohigh thatthey would beatalevel thattheanimal cannot
metabolize them.
Chairman
41. There willbenoanswer tothis.
Dr.Lucier
42. Yes, these materials would bepresent atallstages oflife,inboth males andfemales, asmy
colleagues have said, invarying amounts.
Mr. Brinza (US)
43. Then, thenext question was, would thehormones alsobepresent inthemeat oftheanimals
andmilk from those animals? Again recognizing thatthelevels willvary.
Dr.Arnold
44. Mr.Chairman, Ithink there aredifferent pathways ofmetabolism forthese substances. And
certainly athigh levels, itdepends somewhat onthedose which pathway isused, butessentially
metabolism issimilar inanimal andinman. Forexample, incattle the17alpha oestradiol plays a
certain greater rolethaninhuman beings, butthismetabolite islessactive asanoestrogen orpractically
notactive asanoestrogen. Sothere areslight differences.WT/DS26/R/USA
Page 243
Chairman
45. This goes tothefirstquestion. Iamvery gladIcould understand this. Solet'sgotothesecond
question, then. Justasamatter ofprocedure, wedon'tgoforconsensus. Wejusttake andrecord
what theexperts say, butwearenottrying toassess some consensus here.
Mr. Brinza (US)
46. Iunderstand, Mr.Chairman. Itisjustthattotheextent thatwearealltalking from acommon
understanding ofthefacts, then itisuseful forustoperceive that. Yes, thesecond question isthen
willeach ofthese three hormones bepresent inthemeat andthemilk from these animals -theoestradiol
17beta, testosterone andprogesterone.
Dr.Ritter
47. Subject tothesame variances thatIindicated amoment ago, theanswer isyes.
Chairman
48. They willbeinthemilk?
Dr.Ritter
49. Yes, again subject tothesame variances thatwediscussed amoment ago, although thelevels
andtheextent towhich they arepresent andtheratios andsoonandsoforth willbeafunction of
theparticular status oftheanimal inquestion, buttoavoid going intoalengthier response, than is
really necessary inthegeneral case theanswer Mr.Chairman, Ithink would beyes. They would be
present.
Mr. Brinza (US)
50. Mr.Chairman, itmay beuseful aspartofthese questions, tosave some time, wearealso
asking whether thelevels thatwearetalking about would bewithin thenormal physiological range
with respect tothese hormones when they areadministered forgrowth promotion purposes.
Dr.Ritter
51. Toanswer thatquestion, again theanswer isyes. Theposition, certainly thatthethatIhave
offered, Mr.Chairman, isatleast thatwhen these substances areused inaccordance withtheprescribed
useconditions, thelevels thatarepresent areinfactindistinguishable from those which would bepresent
inananimal which hadnotbeen treated atall. Ishould say, toclarify thatjustalittle bitfurther,
there isarange ofconcentrations which iswhat Ihave been attempting toallude tothatonemight
normally detect inuntreated animals. It'snotafinite number, butrather there isadistribution ofvalues
over which onetypically might findthese hormones inanuntreated animal. Thelevels inanimals
thathave been treated falls within therange ofthose numbers thatmight bedetected inanimals that
have otherwise [cassette ended ...]
52. Idon'twant toimpart theimpression thatthere isaprecise number fortestosterone levels,
there isarange ofvalues thatonefinds. Asonemight expect, these arebiological living systems
andthere isadistribution ofvalues, buttreatment results inaresidue level which fallswithin thatrange.WT/DS26/R/USA
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Dr.McLean
53. Mr.Chairman, theanswer isyesandtofacilitate anexplanation, Isuggest thatifyoulook
atAttachment 1ofmysubmission, thenthere areanumber offigures inthere thatrelate toprogesterone
tooestradiol 17beta, andtotestosterone invarious tissues andinparticular theexcretion inthemilk,
andwhen youcome totheother thannaturally-occurring hormones, fortheother hormones trenbolone
andzeranol, because they arelipid soluble, onewould expect them toappear inthetissues andinthe
milk.
Dr.Arnold
54. Chairman, wehave arather complete data base showing us,astheprevious speakers have
already said, there isalarge variability according tophysiological status andthere canbeafactor for
certain hormones upto1,000 andIhave presented thedatainmywritten responses. Therefore Iagree
thatifthesubstances areused according togood veterinary practices, either forgrowth, promotion
orforthetherapeutic uses authorized intheEC,youhave initially aslight difference butatthetime
ofslaughter there isnomeans todiscriminate between treated andnon-treated animals, irrespective
ofwhether forgrowth promotion orfortherapeutic andzootechnical purposes.
Dr.André
55. Yes, both hormones arepresent inmeat andmilk, it'sclear, andthelevel isavery variable
level isclear also. Idon'tagree with Professor Arnold justonthelastpoint, when hesays thatitis
impossible todistinguish between hormones, injected hormones andnatural produced hormones. In
some cases itispossible todistinguish thetwobyphysical means ofisotope relations, butmaybe not
atavery lowlevels, itisvery difficult todo.
Chairman
56. Thank you.
Dr.Lucier
57. Yes, these materials arepresent inmilk atvarying levels. Progesterone ismuch higher than
theother two, asmuch asa100to1,000 times higher, butthey allarepresent.
Chairman
58. Thank you. You wanted toreply.
Dr.Arnold
59. Abroad comment onProfessor André, Itotally agree thisisatheoretical possibility, ifyou
label thehormones withstable isotopes, youcandiscriminate between added hormones andendogenous
hormones, butthishasabsolutely norelevance inpractice.
Dr.André
60. No,Itotally disagree. Iwasspeaking about natural occurring isotopes, C-12, C-13 andits
possible todistinguish inthiscase, some hormones naturally-occurring orinjected, asthey doin
sportsmen. They dothiscurrently insportsmen now fordoping insport andthey candistinguish
endogenous testosterone andinjected testosterone, even ifthecompound isreally thesame, butthe
isotopic composition isnotreally thesame.WT/DS26/R/USA
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Chairman
61. Thank you, Sir. Wetake note ofthetwoviews.
Dr.McLean
62. Ijustwant toaddanother thing. Ithink itisimportant when onelooks atmilk, thatbecause
these hormones arefatsoluble, then theconcentration inthetwocommonly used orcommon articles
ofcommerce, which arecream andmilk, isvery substantially greater. Itissomething oftheorder
ofthree tofourtimes intocream andabout 40times intobutter, andsoIthink onemust takethatinto
account aswell.
Chairman
63. Thank you. Then thenext question wasatthelevels wearetalking about, within thenormal
physiological range, would these residue hormones have abiological effect ontheconsumer?
Dr.Ritter
64. Ithink thattoattempt toanswer thatquestion would really betopre-empt theoutcome ofthis
Panel. Ithink thatisthequestion which thePanel willendeavour toanswer. SoMr.Chairman, with
respect, Ithink theissue thatyoufaceattheendofthese proceedings istoanswer exactly thatquestion.
Atthelevels thatarepresent after theuse,does thisconstitute alevel which mayresult inabiological
activity? Iamgoing to,ifImay Mr.Chairman, modify your question alittle bittotheoneIwould
liketoanswer, rather thantheoneyouasked. Imust sayIfeelsomewhat restrained tomake anattempt
toanswer your question directly forthereasons thatIhave said. Because asIhave indicated, atleast
inmyview, thatinthecaseofthenatural hormones these levels thatarepresent inthemeat oftreated
animals isessentially within therange thatitwould bepresent inthemeat ofuntreated animals, Iwould
suggest thatthequestion becomes moot astowhether ornotthere isbiological activity associated with
these levels ofthehormone. Ithink itisamoot point because thelevel isnogreater orlesser than
itwould beinthemeat ofanuntreated animal. That isaconsumer would beexposed tonolesser
orgreater biological activity asaresult ofthislevel from either atreated animal orfrom anuntreated
animal because both levels areessentially inthesame range. Thank you.
Dr.McLean
65. Mr. Chairman, inrelation tothenaturally-occurring hormones, then itisnotpossible to
differentiate between theeffects ofproduce from treated animals against produce from untreated animals
because essentially they sitinthesame biological range. Inthecase ofthenon-naturally occurring
hormones, inestablishing theADI, then there were very sensitive endpoints derived from studies in
non-humanprimates,andthenthesituationofsensitivemembersofthepopulationwastakenintoaccount
when establishing safety factors. Sothelevels thatonewould getinmeat aresubstantially below those
causing anyeffects inprimates, andthere isareasonably good correlation inhormonal levels in,or
effects ofhormonal levels inprimates against humans. Sotherefore thelevels thatyouwould seein
meat from animals thatwere treated with thetwonon-natural growth promotants would notbecausing
effects inhumans ifthey consume themeat.
Dr.Arnold
66. Mr.Chairman, thethree natural hormones astheyendogenously occur atphysiological levels
certainly have biological effects ofhuman beings. This istheir roleandtheir function. These steroids
areamongst themost successful molecules which have evolved andyoufindthem already invery low
species. Soitisquite clear thatatphysiological levels theyhave important functions andtheyinteract
with many other hormones andtheyactalmost onevery cellinthebody. Now, theadditional amountWT/DS26/R/USA
Page 246
youcould ingest with meat, either from untreated orfrom treated animals according towhat veterinary
practices, cannot modulate thisendogenous activity ofthese hormones because theamounts aretoo
small.
Chairman
67. Itakethatthisisallsubject totheapplication ofgood veterinary practices. Itisalways the
big"if", asIread itinyour paper too,thatistheassumption.
Dr.André
68. Iagree with thatfactandIbelieve with mycolleagues thatwithin thephysiological range as
these hormones have noacute difference biological effects onhuman beings. Butinthephysiological
range theproblem andthequestion istoknow ifwhen youtreat animals orwhether youdon'ttreat
animals youhave thesame mean inthephysiological range. Imean Ibelieve thatifyouonly eatmeat
from treated animals, youwillhave asDieter Arnold said, avery small enhancement ofthemean of
your food hormonal intake andthiswillnotbetransformed inclassical biological effects forhuman
beings. You don'tseeanything, buttheproblem isthatsome other biological effects have notbeen
studied andneed avery very very long time tobestudied. Ithink forexample, aschanges inhuman
fertility orchange insexratio asweknow thissexratio forexample isnowchanging insome countries.
Butwehave norelation between these countries andthefactthatthey banned ornotthese hormones,
thatisnottheproblem now. Butwhat Ionly sayisthatthischange inhuman reproduction forexample,
hasnotbeen studied norrelated tohormonal change ornot,andIhave personally some doubt onthis.
Chairman
69. Thank you, Dr.Lucier.
Dr.Lucier
70. Theshort answer isyes,some biological effect could occur. Ifyouthink about interms of
anormal condition, sayanormal woman would have 30percentofheroestrogen receptors occupied
atsome given point intime. Atthatsame point intime, ifsheisconsuming meat thatcontains an
additional burden ofoestrogens because oftheuseofgrowth promoters, thatreceptor occupancy may
besomething like30.01 or30.001, avery very small increase. This increase would notbedetectable,
noteven close tobeing detectable, byanyexperimental tools thatwehave today. Sotheanswer is
thatabiological effect could beoccurring, ifitisoccurring itwould notbedetectable, andfinally
therelationship between thatbiological effect andatoxic effect, saycancer orbirth defect orsomething
likethis, would beunknown. Butifsuch aneffect wasoccurring itwould beextraordinarily small,
remarkably close tozero.
Chairman
71. Thank you. Dr.Randell would youliketotakethefloor. Now? Aprocedural question or?
OK.
Mr. Christoforou (EC)
72. Mr.Chairman, thank you. During theorganizational meeting wehadthismorning, yousaid
thatwewould review how theprocedure isgoing after awhile andnow itisourfeeling thatitwould
probably beappropriate, after theUnited States hasposed thethree orfourorfivequestions, soprobably
wecanstayhere, andthen Canada willcome upwith thefollow-up questions inthissame area, and
then wetakeupthefloor ourselves, because thatisgoing toolong andwewould likeifpossible to
intervene inthisareaofresidue levels anddistinctions between thethree natural andthethree synthetic.WT/DS26/R/USA
Page 247
Ithink thatitwould bemore appropriate andwillprobably improve thequality ofthedebate andthe
discussion wearehaving here. IftheUnited States cancontinue with oneortwomore questions and
Canada, andthenwecancome inatthisstage withsimilar questions inthisareawhich youarediscussing
now.
Chairman
73. Well mypersonal feeling isthatweareinagood process. Tomeitisvery educational the
wayweproceed andIwould prefer tostick tothemodes wesetoutandyoucancome inwith aquestion
when it'syour time. You canthen alsofocus onthepoints youwant being lessreactive than when
youhave tofollow uptowhat they aredoing. Ithink, it'smyassessment thatit'sefficient andof
course astime goes by,lessandmore specialized question willbecome necessary andwewillfocus
andtarget more down andyouwillbring inother aspects than theother parties. Iwould have a
preference tocontinue theway wearedoing. Igive youthefloor.
Mr. Brinza (US)
74. Thank youMr.Chairman. Thenext question isrelated totheonewewere justasking. I
justwant tomake sure Iunderstood theresponse correctly which is,would theresidues found inthe
meat bechemically identical whether itcame from application forgrowth-promotion purposes versus
endogenously produced versus applied forzootechnical ortherapeutic purposes? Would itbethesame
chemical residue, recognizing thelevels again would bevariable?
Dr.Ritter
75. Ipresume thatyour question isdirected ofcourse tothenatural hormone?
Mr. Brinza (US)
76. Yes.
Dr.Ritter
77. Intheinterest ofexpediency Mr.Chairman, Iwillsayessentially yes. Essentially yes.
Dr.McLean
78. Mr.Chairman, theresidues willbesimilar forzootechnical uses where quite high levels are
used, youcangetspill-over orinhibition ofcertain ofthemetabolic pathways, andinthatwayyou
might getqualitatively similar butquantitatively quite different residue profiles.
Dr.Arnold
79. Thisisalsomyanswer,Mr.Chairman,qualitativelythesamebutquantitativelycouldbeslightly
different depending onthecompound administered, thedose, theroute ofadministration, etc. There
aresome differences.
Chairman
80. Thank you, yesDr.Ritter.WT/DS26/R/USA
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Dr.Ritter
81. Iamsorry Mr.Chairman, justtoclarify, perhaps Imisunderstood thequestion, butwasthe
question directed atforthesame use, thatiswhat ...
Chairman
82. Could yourestate?
Mr. Brinza (US)
83. Yes, thequestion waswould theresidue bechemically thesame whether itwasendogenously
produced, forexample, pick testosterone. Whether itwas endogenously produced testosterone,
testosterone administered forgrowth promotion purposes ortestosterone administered forzootechnical
ortherapeutic purposes.
Dr.Ritter
84. Then ofcourse Icertainly agree with theanswer provided bymycolleagues. Qualitatively
theresidue inmyview would beindistinguishable. Quantitatively, ofcourse, theamount thatcould
bedetected would beafunction oftheamount thatwould have been administered either forgrowth
promotion ortherapeutic uses.
Dr.André
85. Ithink thattheresidues areforthegreatest partoftheresidues thesame, when used forgrowth
promotion natural hormones andforuseastherapeutic zootechnical. Ifdifferences appear itcanbe
inmetabolic profiles, Imean thatwith thelong term effect youinduce some different enzyme panels
andthisenzyme, after along time, canproduce small amounts ofdifferent metabolites aswhen you
arejustusing these hormones onetime. Buttomyknowledge, thisisknown forother compounds
butnotforhormones, buttomyknowledge alsoithasnotbeen studied.
Chairman
86. Thank you, Dr.Lucier.
Dr.Lucier
87. Yes.
Chairman
88. Thank you. Well, ifyouagree youdon'thave totakethefloor, inorder towintime thatis
fine.
Mr. Brinza (US)
89. Thenext question Ithink Dr.Lucier willfinditaneasier time toagree with because Ibelieve
Iunderstood astatement hemade thatgiven theconcept ofhalf-life, thatifyouadminister oneofthese
hormones toananimal, inthiscase Iamtalking ofallsixofthem, youadminister ahormone toan
animal there willbearesidue, even faroutintothefuture, even though itmaybeonly sofewmolecules
itcould notbedetected byanyavailable means thatwehave atourdisposal currently. Ijustwanted
tomake sure Ihadunderstood thatandwhether thatwastheview orwhat Ihadunderstood from the
responses oftheother experts aswell. Please correct meifIhave misstated.WT/DS26/R/USA
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Dr.Lucier
90. Areyouasking mespecifically? That iscorrect afewmolecules would likely remain, not
detectable certainly, butthere isevery likelihood there would beafewofthem leftaround.
Dr.Arnold
91. Mr.Chairman,hormonesadministeredfromexogenoussourceshaveveryshorthalf-livesinitially
after administration, intherange ofminutes. Butthenthehalf-lives becomes longer andlonger because
these hormones gotodifferent compartments inthebody andafter afewhours, thehalf-life isalready
intheorder ofsome 50,100minutes, initially itisintheorder ofsome 10-15 minutes. Soitisvery
difficult topredict forhowlong thelastmolecule willpersist inthebody, butcertainly foravery long
time.
Chairman
92. Thank you.
Dr.McLean
93. Forthesake oftherecord Mr.Chairman, Iagree with Dr.Arnold.
Chairman
94. You nodaswell?
Dr.Ritter
95. Ifyouwould likeacomplete record, Yes.
Chairman
96. Well itisnotnecessary, thank you. Canwegoon?
Mr. Brinza (US)
97. Iwould liketoturnnowtoquestions thathave been raised insome ofthedocuments thathave
been provided toyouallandmake surethatIhadunderstood correctly theresponses insome ofthese
instances. With respect tothestudies thatDr.Liehr hadperformed, Iwant tomake sure thatweare
allunderstanding thatthedose comparisons ofthestudies, thedoses thathewasusing inhisstudy
versus thedoses thatwearetalking about forgrowth promotion purposes. Ijustwant tomake sure
thatweallunderstood thisthesame way, thatthedosage used inDr.Liehr 'sstudy was61micrograms
perdayinthemale Syrian hamster, which weighs approximately 100grams. Letmejustrunthrough
these, thenwecandiscuss thisalittle bit.That would beapproximately 610micrograms perkilogram
perday, ifwearedoing ourmath correctly, andfora60kilogram adult male human thatwould be
equivalent toabout 36.6 milligrams perdayandthatadult male humans produce about 48micrograms
ofoestradiol 17betaperday. Given thatmath then, what Dr.Liehr wasdelivering tothehamsters
inquestion was36,360/48 times more thanthecomparable average daily production rateinadult men,
andthatinturn is15,000 times more than theresidue ofoestradiol inmeat from treated animals.
Ijustwanted tomake sure thatwehadthenumbers there correctly, because then thatwould leadto
result ofadifference between thedose used inthetreatment ofthehamsters andtheresidue in500grams
ofmeat, ofasignificant difference, itwould beequivalent totheoestradiol from 11.5 million 500gram
portions ofmeat being injected intoahuman male every daytobecomparable. Icanrunthrough
those numbers again, Irecognize thatwasrather fast.WT/DS26/R/USA
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Chairman
98. Yes, theCommunity, Mr.Christoforou.
Mr. Christoforou (EC)
99. Ithink itwould beprobably more useful, ifwecangetthewritten version ofthese statements
andthenumbers.
Chairman
100. Well, Iunderstood itsabout hamsterizing humans.
Mr. Christoforou (EC)
101. Yes, indeed, butthere wassome other references toother animals, sowewould likereally
toseesome other products, sowewould appreciate itifwecangetthewritten version with theexact
figures forustohave alook, thank you.
Chairman
102. Yes, Iassume youwant tocome back tothiscomparison later on.Butareyouinaposition
toanswer orwould youpostpone thisneed offigures? Dr.Arnold.
Dr.Arnold
103. Provided thatIcorrectly understood thequestion, Icanperhaps give apreliminary answer.
Ifapellet isadministered tohamsters intheorder ofseveral milligrams 20,50ormore, youcanthink
about 100, 150micrograms which arereleased perday. Therefore some authors insome studies have
simulated thissituation byconstantly infusing similar amounts totheanimals. Sothese areinfact
very high doses which arereleased from such implants.
Chairman
104. Professor McLean.
Dr.McLean
105. Ifit'shelpful Mr.Chairman, Iwould takethesame lineasDr.Arnold. Itisquite clear that
thedose administered tothehamster inapellet wasanumber ofmilligrams, ahamster weighs afew
hundred grams andtoextrapolate from thework inthehamster tothehuman situation Ithink isfairly
dangerous.
Dr.Ritter
106. Mr.Chairman, without double checking allofthecalculations thatwere justgiven tousvis-à-vis
thecomparisons, Ithink thepoint ofmycolleagues Professor McLean andDr.Arnold make isthe
correct one. That isthatthere isorders ofmagnitude difference here, between thedose levels that
were used byProfessor Liehr andthose thatmight result asresidues forexposure inthequestion of
meat. Ithink weneed toremind ourselves thatthefundamental intent here isdifferent. That is
Professor Liehr 'swork andthework ofmany investigators istoproduce aneffect. This speaks to
themost fundamental issue inpharmacology andintoxicology andthatistheconcept ofdose response.
Professor Liehr isvery interested inunderstanding theinduction ofcancer asaresult ofexposure to
these hormones, soofcourse hisprotocol would necessarily bedesigned insuch away, soastoproduceWT/DS26/R/USA
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thedesired effect, inhiscase thetumour. The intent obviously inthecase offood residues,
Mr.Chairman, istoavoid adose level which may constitute ahuman risk, soitwillcome assmall
surprise thatthelevels thatarepresent asresidues infood arethousands orhundreds ofthousands
ormillions oftimes lower thantheywould beinanexperiment which isspecifically designed toinduce
atumour. These twoexperiments, ifyoulike, arecompletely atcross purposes with each other. They
arefrom their very initiation intended toproduce entirely different results. Sotocompare aprotocol
which hasbeen designed toproduce atumour toafood residue theused practice ofwhich issetup
insuch awaysoastominimize thepresence oftheresidue, isinmyview arelatively meaningless
comparison. Thank you.
Dr.Lucier
107. Iamnotinfundamental disagreement with what hasbeen said, butIthink itisimportant to
point outonething, thatphysiological levels ofoestrogen doresult inoxidative damage toDNA and
thishasbeen shown intheratandsothistype ofdamage does occur inphysiological situations in
experimental animals andthisisaparticular form ofdamage toDNA that'sbeen quantified. Sothe
levels thatarenormally circulating inthebody areproducing some ofthese DNA damaging metabolites.
Exactly how itdoes it,isopen toquestion andwith thework ofDr.Liehr which would suggest one
way, other works maysuggest other ways, butIthink itisclear thatthatamount ofdamage isoccurring
andwould occur following asmall dose because itisalready added toanadditional body burden in
which thisisalready occurring. Butagain thatadditional DNA damage would extraordinary small,
again remarkably close tozero.
Chairman
108. Thank you. When you talk about physiological levels, may Itake itthat means
naturally-occurring levels?
Dr.Lucier
109. That isright. Ofcourse these change during thenormal cycling phases ofpeople aswell as
experimental animals, sothere isarange ofvalues thatoccur, butwithin thatnormal range ofvalues
thatyouseeinexperimental animals, which issimilar towhat isseen inpeople aswell.
Chairman
110. Thank you. Any further remarks onthispoint?
Mr. Brinza (US)
111. Sorry, Ijusthadafollow uptothelastintervention. Ijustwant tomake sure Iunderstood.
Isthere evidence thatatthelevels wearetalking about ofresidue inmeat from theuseofthese hormones
forgrowth-promotion purposes inaccordance with good animal husbandry practice, isthere evidence
being putforward ofDNA damage from those levels ofresidue?
Dr.Lucier
112. Letmeanswer thequestion inanother way, perhaps Ihave caused some confusion. Sayyou
alreadyhaveahundredorthousandmoleculesofsomethinginthebody,andthatsomeofthosemolecules
areproducing aDNA damage event. Ifyouaddanother molecule toitthere issome possibility that
thatsame event willoccur because itisthesame molecule. Youwillnotbeabletodistinguish certainly
thatadditional event from theones thatoccurred from thethousand molecules, butyouwon'tbeable
tosay,nonone ofthose events arerelated tothatadditional onemolecule. That iswhat Imeant thatWT/DS26/R/USA
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itwould notbedetectable, very very small, butitwould beimpossible tosaythatthatevent could
notoccur.
Chairman
113. CanIjustfollow upformyunderstanding. Thecomparison between Dr.Liehr 'sprotocols,
inducing cancer ontheonehand using very high doses andontheother hand using very very limited
doses here. Isityour view thatdespite oneusesvery very small doses, there stillmight besome effects?
Dr.Lucier
114. Yes, because youarealready adding toanexisting very large number ofsame molecules, so
justinstead of1,000 molecules youhave 1,001 isirrelevant here.
Chairman
115. And thatiswhy youbasically challenge, ifIamcorrect, thattheconcept ofthresholds...
Dr.Lucier
116. That isexactly right. Ishould alsopoint outthough, tomake itclear from myview, thatI
donotthink ithasbeen demonstrated thatthisparticular mechanism isrelated orproven toberelated
tothecarcinogenicity ofoestrogens. Itisatthispoint aninteresting hypothesis, there some plausibility
toit,butithasnotbeen proven tobeassociated oracause oftumours produced byoestrogen.
Chairman
117. Yes....
Mr. Palecka
118. Thank youvery much, sorry perhaps tointerfere intothediscussion. Justoneprecision: by
adding onemolecule, does itmean thatthere isalinear increase inprobability ofDNA damage or
youthink thatitsprogressive? Does itmean thatitwillperhaps putsomething more oritisjusta
very linear function?
Dr.Lucier
119. Itisalready adding toanexisting burden, ifthatburden thatalready exists isonalinear part
ofadose response curve, thenadding anadditional molecule would create asmall amount ofadditional
damage. Itispossible that that mechanism isalready saturated maximal atthephysiological
concentrations, ifthatisthecase, then thatdamage would notoccur, thisistheopposite situation of
thethreshold.
Chairman
120. Thank you. Any further comments onthis? No,ok. One more.
Mr. Brinza (US)
121. Isaidonemoment please.WT/DS26/R/USA
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Chairman
122. Ohonemoment, Isee.
Mr. Brinza (US)
123. Mr.Chairman, afewmore questions. Ijustdidwant tofollow uponthislastpoint. This
might getabittechnical soImay have toimpose ontheexperts tohelp translate thisintoterms that
areeasily understood bypeople likemyself, who aremore layperson than toxicologist orscientist.
124. Let'smake sure Iunderstood. Ibelieve Iunderstood reference toDNA damage. Ijustwant
tomake clear. IsDNA damage, inother words DNA adducts, always indicative ofagenotoxic effect?
Dr.Lucier
125. No. Doyouwant alonger answer? There isawealth ofscientific evidence toshow thatfor
many carcinogens aDNA adduct stepisessential. Formany ofthepolycyclic aromatic hydrocarbons
forexample, thatoccur ascontaminants andmany industrial processes atpresent inourair,there is
aspecific DNA adduct that'sbeen identified thathasbeen shown toberelated asclose asyoucan
come inacausal sense tothetumours thatresult. Inother cases, some DNA adducts have nomutating
capability, sothere isawide variation. Notalladducts arealike, some have very strong mutating
potential, some have weak mutating potential, others have nomutating potential atall.
Chairman
126. Sorry, would youliketotake thefloor onthispoint?
Dr.Arnold
127. Ithink itcould beinteresting tothePanel tonote thatavery large number ofadducts toDNA
exists atalltimes inallcells ofthebody.
Mr. Brinza (US)
128. Thank you, Iwasabout toinvoke Dr.Arnold 'sname. Iunderstood earlier thatweheard that
asingle strand break inDNA actually occurs something intheorder of5,000 times perhour, Imay
nothave gotten allthiscorrectly, andthatthehuman ability torepair isabout 200,000 events perhour.
Ijustwasgoing toaskDr.Lucier whether theDNA damage thathewasreferring towould fallwithin
therange thatwearereferring tohere, thatDr.Arnold hadreferred toasnormally occurring.
Dr.Lucier
129. Ithink thatthekind ofdamage thatwould result from oxidation, catechol oestrogen formation
of17betaoestradiol, would result, andIamnotahundred percentsure ofthatand, Iamsure Iwill
becorrected when theother folks start asking questions, butIbelieve thatwould besomething called
8-hydroxyguanosine would betheprimary oxidative damage step. You don'tremember that, wewill
notgive youaquiz later, butthisoccurs invery high frequency. Idonothave theexact numbers,
butitdoes occur invery high frequency inthehuman body.
Chairman
130. Thank you.WT/DS26/R/USA
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Dr.Arnold
131. Mr. Chairman, Ididnotwant tosuggest tothePanel thatweshould nottake such effects
seriously. This isthevalue ofthese indicator tests, ofthese early events, thatwegetconscious that
something ishappening toDNA andthatwefurther investigate. Theonly thing Iwanted tosayis
thatsingle-stranded breaks areperseinsufficient evidence, particularly ifobserved invitro andyou
need todofollow upstudies.
Chairman
132. Thank you.
Dr.Lucier
133. Iwould liketoaddonecomment tothat. Ithink thatthatisavery good point. There are
alotofdifferent ways oflooking atgenetic damage andthescience ofchemical carcinogenesis evolves
orprogresses inittybitty little steps andeach piece ofevidence adds tothetotal degree ofevidence
thatachemical isacting through thatpathway. Butsimply having apositive DNA adduct testora
positive cell-transformation testinitself isnotconvincing. What becomes convincing when youhave
awhole body ofknowledge from cellsystems, from experimental systems, invivo,from limited studies
youmay obtain from human samples, andstart putting italltogether andthatadds tothedegree of
compelling nature oftheevidence. Soitisnotlikenow wedonothave it,now wehave it,itsort
ofgoes inastepwise fashion.
Chairman
134. Thank you. Would youliketocontinue Mr.Brinza?
Mr. Brinza (US)
135. Ifthere arenoother comments. Iwanted toaskacouple ofquestions withrespect totheconcept
ofanacceptable daily intake level, which wasexplained Ithought quite well byDr.Randell earlier.
Ijustwould liketomake surethatIunderstood, andfrom theexperts 'responses thatthey were using
theconcept ofanADI inthesame way, which isthatitistheamount ofasubstance thatcanbe
consumed daily byhumans over alifetime without anadverse effect.
Dr.Ritter
136. Yes.
Mr. Brinza (US)
137. Thesilence means theothers were doing itinthesame manner, using thesame manner? In
thatcaseconceptually would itbepossible toestablish anADIforthethree synthetic hormones involved
inthisdispute, trenbolone, zeranol andMGA?
Dr.Ritter
138. Certainly inmyview theanswer isyes.
Dr.McLean
139. Theanswer from mypoint ofview isyes. Iwould justliketoreiterate thattheendpoints
forboth ofthem took intoaccount sensitive subpopulations, sensitive human subpopulations, such asWT/DS26/R/USA
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pre-pubertal children andmenopausal women andalsothattheywere supported bydatagenerated from
studies oradministrations tonon-human primates.
Dr.Arnold
140. Iagree with theprevious speakers.
Chairman
141. Could perhaps Dr.Randell explain why wedonothave ADIs onthese hormones. Why were
they notestablished?
Dr.Randell (Codex)
142. Thedifference between thethree natural hormones andthexenobiotic hormones Ithink has
been discussed earlier today. Firstly, forthexenobiotic hormones itisrelatively simple application
oftheADI concept andtheADI paradigm ifyouwish toestablish ADIs forthese substances. For
theendogenous hormones, theJECFA looked attheavailable information, found thatbecause these
were produced inman andthatthelevels ofingestion were several magnitudes lessthan endogenous
production, then itwasunnecessary tosetanADI. Onthebasis thattheendpoint would achieve the
same result, thatthere would benoadditional risktothehumans.
Chairman
143. Onthenecessity, isthatview shared bytheother experts? Dr.Arnold?
Dr.Arnold
144. Mr.Chairman, itmight beinteresting tothePanel thatintheECwehave reviewed thethree
natural hormones independently from JECFA. Atleast aresult ofonesuch evaluation hasbeen
published intheOfficial Journal. Wehave setanMRL notnecessary foroestradiol twoyears ago
forthetherapeutic uses andthewhole evidence hasbeen reviewed bytheCommittee forVeterinary
Medicinal Products andtheEuropean Medicine Evaluation Agency. Since these arejustnine lines,
maybe Icanread theconclusions oftheECCommittees anditslegally binding now, published inthe
Official Journal. "The conclusions oftheFAO/WHO Expert Committee onFood Additives, JECFA,
thatnoADI andMRLs foroestradiol willneed tobeestablished, isadopted. Neck andplasma residue
levels after treatment with oestradiol benzoate andoestradiol valerate have shown tobewithin
physiological limits. Although itislikely thattissue residues levels willalsobewithin physiological
limits, thiscannot beguaranteed given theresults with oestradiol-hexahydrobenzoate. Stillcompared
tothelowesthumanproductionrateofoestradiolpre-pubertalboys,6microgramsperday,andcompared
totheamount ofoestradiol inother foodstuffs thatarepartofthehuman diet, theamount ofexogenous
oestradiol thathumans willbeexposed through ingestion oftissue from treated animals isbiologically
insignificant andwillbeincapable ofexerting hormonal effect inhuman beings." Soitisabout the
same lineofevidence andofarguments puttogether bytheECCommittee, than hasbeen previously
done byJECFA.
Chairman
145. Thank you. Isthisreference inyour paper?
Dr.Arnold
146. Yes, itis.WT/DS26/R/USA
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Chairman
147. Thank you.
Dr.Arnold
148. And ifyouwant Icangive youacopy ofthatCouncil Regulation.
Chairman
149. Please Dr.Randell.
Dr.Randell (Codex)
150. Iwould justliketostate thatanacceptable daily intake isanumerical estimate ofwhat might
becalled anoeffect level inhumans, with built insafety factors. However, inthebroad range of
substances thatJECFA hasevaluated over anumber ofyears, ithasonmany occasions notallocated
anumerical ADI. Thereason fordoing thisisthatcertain substances areessentially safetoingest
atanylevel andinthese cases JECFA willgive anADI which itcalls "not specified". Itdoes not
specify theacceptable daily intake. Very common safefood additives such asascorbic acid, vitamin C,
fallintothisgroup. Onthese three substances were theonly three substances inwhich JECFA has
used theexpression "notnecessary". Inthisparticular caseJECFA feltthatitwasnotnecessary because
oftheoverwhelming endogenous production byhumans ofthese substances andthattosetanADI
would notachieve anyadditional improvement inunderstanding ofthesafety ofthese substances in
humans. So"notnecessary" wasbasically anevaluation ofwhat JECFA wastrying toachieve ingeneral
interms oftrying toprotect health ofconsumers.
Chairman
151. Thank you. Further comments onthisorwould youliketogoon?
Mr. Brinza (US)
152. Thank youMr.Chairman. Ibelieve thatIhave understood previously Dr.Randell andwould
liketomake sureandconfirm, thatintheinstance ofthetwosynthetics thatwere reviewed byJECFA,
ontrenbolone andzeranol, thattheADI wassetusing themethodology thatyoudescribed ingeneral
foranADI. That ADI hasthesame meaning forthose twoasitdoes forother substances.
Dr.Randell (Codex)
153. TheADI forthezeranol andthetrenbolone wasestablished onthebasis ofano-effect level
being identified intestanimals. Inthese twoparticular cases, theno-effect level which JECFA selected
wasthenohormonal effect level forboth substances.
Mr. Brinza (US)
154. Thank you. IfIcould turntoasubject thatwastouched onbyoneoftheexperts earlier today,
Iwilljustmake sureIunderstood correctly. With respect totheparticular implantation offiveofthese
hormones under discussion, what factors, ifany, make theearasasiteofimplantation favourable
foruseover other sites ofimplantation?
Chairman
155. Would youliketotake thefloor?WT/DS26/R/USA
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Dr.Ritter
156. Isuppose, following theorder thatwenow seem tohave set,Mr.Chairman.
Chairman
157. Well itisunfair thatyouhave totake it,justfeelfreewhen youwant toanswer.
Dr.Ritter
158. Ithink theprimary impetus, Mr.Chairman, fortheselection oftheearisbecause itisatissue
which isnotnormally used toenter thefood supply, soitmakes identification ofthesource ofthe
material very easy. Idonotwant tosayensures, butitgoes some veryconsiderable distance toensuring,
thatinjection siteresidues, which understandably could bemuch higher than normal tissue residue
levels, areextremely unlikely toenter thefood supply. Itismyunderstanding thatthatistheprimary
motivation forselecting asitewhich willnever enter thefood supply.
Dr.McLean
159. And oneadditional advantage ofusing theear,itisvery easy topalpate apellet oranimplant
under theskin oftheear,whereas ifitissubcutaneously onthebody then youwould never findit.
Sothatisasecond wayofidentifying treated animals. Infactforsome other treatments with hormones,
butnotthese ones, itisactually possible toremove theimplant from theear.
Mr. Brinza (US)
160. IfIcould justfollow uponthat, Iunderstood areference earlier thatinfacttheimplants come
with adevice which isspecially designed toimplant thepellet intheear. Ibelieve Ihave understood
thereference thatthatdevice would notbesuitable forimplanting itthrough thehide, forexample.
Ijustwant tomake sure Ihave understood thatcorrectly.
Dr.McLean
161. Iwould bealittle bitunwilling toextend itthatfar.Itisjustthatthe"gun" used toadminister
theimplants issuch thatitmakes administration convenient, easy andaccurate, inthatthepellets or
theimplants aregenerally inacartridge anditrotates around alittle bitlikeasixshooter andsoit
isaconvenient, easy andaccurate way toadminister theprescribed dose.
Mr. Brinza (US)
162. Thank you. IfIcould thenaskwhether there isanyspecific evidence thattheexperts areaware
ofevidence thatusing adose ofhormone greater thanthatapproved forgrowth promotion would lead
toaproportionately greater response infeed efficiency.
Dr.McLean
163. Generally not. When thesponsor suggests thedose, then thedose thatthey suggest willgive
theoptimum response andsotherefore, within limits, there isnoneed, noreturn inadministering more
thanissuggested. Thesecond thing is,however, most regulatory authorities, including JECFA, require
thatdatasetting residues does takeintoaccount dose rates thatareinexcess ofwhat isnormally used,
generally twice atleast andsometimes more, sothattheeffect ofoverdosing, ifyoulike, orvariations
inuptake, canbeseen.WT/DS26/R/USA
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Mr. Brinza (US)
164. Thank youandthen ifIcould justfollow on,Iamsorry didyou...?
Dr.Ritter
165. Iwasonly going toadd, Mr.Chairman, thatIthink Dr.Randell inhisopening comments
articulated inmyview very very clearly, thenature ofthebalance thatonetries tostrike inestablishing
anADI andanacceptable usepractice. Ithink, inmyview, hemade thepoint very very well, that
tousetoolittle achieves nothing. That isonedoes notobtain thedesired effect butatthesame time
results inaresidue. Todotoomuch, tousetoomuch, goes beyond what onecananticipate interms
ofaneffect. Sothatthecorrect istheonewhich isultimately recommended andthatisavalue which
willoptimize thebalance between thereturn, thebenefit ifyouandtheresidue. That isthelevel to
which wearereferring.
Dr.Arnold
166. Mr.Chairman, inthedevelopment byindustry ofthese pellets andanother devices, they have
been optimized with respect tothedose. However thisdoes notnecessarily prevent some farmers
tousemore implants, forexample. Butthisagain does notnecessarily cause higher residue levels
inthecarcass. There aresome examples thatIhave shown inmywritten response, where theuse
ofuptosiximplants didnotnecessarily have theeffect thattheresidue levels intheremaining carcass
were significantly higher. Soitisaquestion youcannot easily answer, youhave toanswer onacase-by-
case basis. Ontheother side, itisquite clear thatifyouinject twice theamount directly, thatthen
alllevels increase inplasma andintissues, notnecessarily inalinear way, buttheyincrease significantly,
ifyoudouble thedose, forexample byinjection. That isthedifference between aslow release device
andadirect injection. Ontheother hand thelong term release ofhigh doses may have influences
onthepattern ofhormone excretion intheanimal 'sbody andthisistheintention ofusing such
compounds.
Chairman
167. Thank youvery much. May Ijustmake, ohsorry, yes, please.
Dr.André
168. Justonecomment onthispoint. Itisnotsoevident thatadouble dose, even atthesame time,
willgive abetter response. Butwhat weobserved alotofyears agoinourcountry, when these
hormones were allowed byimplants intheear,isthatfarmers tried toputanother ofthesame doses
butlater. They donotwait thewithdrawal period andthey inject another onemaybe atthehalfof
thetheoretical withdrawal period, andtheyhadbenefit todothis, clearly, because theeffect wasmore
longer atthetime. Consequently itisclear alsothatrespecting thestrict withdrawal period attheend,
theresidue level washigher. Doyouunderstand?
Chairman
169. Yes. Myquestion would be,doyouthink thiswastypical forEuropean situation oristhat
aphenomenon which isobserved world-wide?
Dr.André
170. Itisnotascientific question, butthen, well Ithink really itisnottypical foranycountries.
Itisaproblem offarmer, ofrespect with regulation andofbenefits thattheyhave. Icanreturn through
thesame question, doyouthink people drive faster than allowed inanycountry orinanother one?WT/DS26/R/USA
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Itisaproblem ofrespect ofregulation, only. Butitisclear thatitwasthesame situation atthattime
inFrance asitisnowinUS,forexample. Because oneimplant wasallowed intheearwithawithdrawal
period, itisquite thesame situation itwasjust10years ago. That situation seems tobethesame,
Ithink.
Chairman
171. Thank you. Would youliketocomment onthispoint?
Dr.McLean
172. Ijustwould liketomake acomment. Generally, ofcourse, forzeranol andtrenbolone the
useofexcess would beorcould bepicked upiftheMRL wasexceeded, andsotherefore there would
beapenalty iftheMRL wasexceeded. And sotherefore, farmers knowing thatyoucananalyze for
quite accurately, orscreen forandconfirm, thepresence ofzeranol ortrenbolone arenotgoing to
dothat. And theother interesting thing isthatincountries where theuseofthese compounds is
permitted andthere aregood educational campaigns forfarmers astothecorrect useandthereasons
whyyoushould notexceed theprescribed dose, andthepenalties thatexist ifyoudo,theresults from
residues surveys show thatbyandlarge there isnoexceeding oftheMRL. However inthose countries
where theuseisnotcontrolled andthatisnofarmer education campaign anddifficult toapply apenalty,
then weknow thattheMRL issignificantly exceeded. Sooneoftheimportant factors oflegalizing
these compounds istobeabletoconduct aneducation campaign andtobeabletoputinplace monitoring
campaigns toseethattheMRL isnotexceeded.
Chairman
173. Thank you. Dr.Arnold.
Dr.Arnold
174. Mr.Chairman, inJECFA weuseaterm called theoretical maximum daily intake. That means
wemultiply arbitrarily high consumption figures with MRL figures, tocalculate what could happen
intheworse casescenario. Ifyouassume allanimals aretreated, allareattheMRL andunder these
conditions about fivepercentoftheADI isused with zeranol andtrenbolone. Itwasvery interesting
formetoseethatinthedocumentation ofthe32nd JECFA there wasanexample ofvery bigabuse.
Itwasintentionally done thisstudy, andItellyouwhat people haddone. They hadadministered a
dose more than100times higher thantherecommended dose. They have administered itintravenously,
insixdoses over three days, soreally itisascenario youcannot more exaggerate. Under these
conditions thetheoretic maximum daily intake wasincreased byafactor ofthree, sothatwewere in
theorder of15-16 percentoftheADI. This ismycomment, toshow thepotential consequences of
misuse orabuse ofthese substances. Wehave some data, andthisdatahadbeen available tothis32nd
JECFA.
Chairman
175. Thank youvery much. Wearepastoneo'clock andIwonder, doyouintend tocontinue with
thequestions forsome time, Isuppose.
Mr. Brinza (US)
176. Well, Mr.Chairman, actually Iwasabout tosay,looking attheclock, thatitmight beofsome
relief toyouandthePanel andothers thatweonly have oneortwomore questions, relatively short
ones ...WT/DS26/R/USA
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Chairman
177. Ifwecould finish theUSquestions andthen wewould break. Would youagree tothator
would youneed abreak? Well, yes. Ifyouagree whydon'twefinish your questions andthenbreak.
Thank you.
Mr. Brinza (US)
178. Justaquick follow upIbelieve totheanswer wereceived earlier. Isthere anyevidence that
implantation oftheapproved implants atasiteother thantheearwould leadtogreater feedefficiency?
Inother words, isthere anyreason toimplant itsomewhere elsetogetabetter effect?
Dr.McLean
179. Ithink thegeneral consensus would bethatproviding itsubcutaneously, probably not.
Mr. Brinza (US)
180. Onefurther question, there areseveral hormonal compounds thatareused forasoestrus control
intheEuropean Union andamong these aremedroxy progesterone acetate andallyltrenbolone and
another compound methyl testosterone isalsoused forsexreversal inaquaculture, weunderstand.
Thequestion, though, iswhether these compounds arechemically related tothesynthetic hormones
used forgrowth promotion inanimals.
Dr.Ritter
181. Mr.Chairman, Iliketheuseoftheword related because itprovides onewith enormous scope.
Ofcourse they arerelated. They arestructure-related andthey have activity andfunction which is
similar tothehormones thatwearediscussing hereatissue. Butofcourse there arenotable differences
aswell, sothey are"related", Ithink isagood word touse.
Dr.Lucier
182. Yes, Iwould agree with thatcomment thatchemically they aredifferent. Intotal, butthey
very have conserved parts ofthemolecule andthey perform orstimulate cells inmuch thesame way.
Nevertheless, since their parts arealittle bitdifferent, they willbemetabolised different soyouwill
have some different breakdown products, youwillhave different, they may gotodifferent parts of
thebody, preferentially because ofthose differences inthemolecule. Sothey willactpretty much
thesame way once they getintoatissue, buttheamount thatgetsintoatissue might bequite abit
different, oritsbiological persistence inatissue orcellmight bequite abitdifferent.
Chairman
183. Thank you. Dr.Arnold.
Dr.Arnold
184. Two substances named bytheUSdelegation arecertainly chemically related andalsowhat
concerns themechanism ofaction, there aregreat similarities. Nevertheless, allyltrenbolone isnot
useful forgrowth promotion, ithasnoanabolic properties andtherefore there isanexemption inthe
ECdirectives concerning thissubstance.WT/DS26/R/USA
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Chairman
185. Thank you.
Dr.McLean
186. Generally Iaminagreement, except Ithink wealsoshould note thatmethyl testosterone is
more active orally than testosterone andIthink allyltrenbolone isactive orally aswell. ButIthink
weshould note thattheoralactivity ofthose twocompounds ishigher than theoralactivity ofthe
chemically related compounds. That istheonly point Imake.
Chairman
187. Thank you. Yes, Professor Arnold.
Dr.Arnold
188. Iagree with what hasbeen saidabout therelation between hormones they arerelated. Itis
agood word. Butwehave justtocompare what iscomparable. When wespeak about these hormones
wehave tospeak only about thetherapeutic andzootechnical uses ofthehormone inquestion andnot
about growth promotion. Itisvery different, because they areused punctually (?)onanyindividual
orgroups, well defined, ofanimals soitisvery different. Itisnotthesame use.
Mr. Brinza (US)
189. Thank youMr.Chairman. Ijustwant tothank alloftheexperts fortheir assistance andthank
thePanel fortheir patience.
Chairman
190. Thank youvery much. This brings ustotheendofthismorning 'ssession. Ihave the
impression thatthelearning ratethismorning wasmuch higher than itusually isinthese rooms and
Iwasvery impressed. About timing, could wecontinue atthree o'clock with thequestions bythe
European Community? Could wedoitthree o'clock sharp, otherwise wemay runintonight. Do
youhave aprocedural point, Mr.Christoforou?
Mr. Christoforou (EC)
191. When would weexpect thedocument bytheUSonthese quantities ofmicrograms?
Chairman
192. Could youarrange tohand them over
Mr. Brinza (US)
193. Mr.Chairman, wedonothave copies with usbutwecancertainly provide thattoyouwhen
wereconvene.
Chairman
194. Thank youvery much. Themeeting isadjourned.WT/DS26/R/USA
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Mr. Christoforou (EC)
Mr.Chairman andMembers ofthePanel, Ladies andGentlemen, Experts advising thePanel
195. Ithink itisthenormal practice toallow thisdelegation topresent itself, ifyouplease excuse
me,because there aresomany scientists from somany places. Ithink fiveminutes orthree minutes
presentation byallthedelegation might behelpful asthese scientists willbeintervening inthisdebate.
Since theECdelegation isknown tothePanel, itisthenormal composition ofthedelegation, Iwould
only request scientists which areadvising theEuropean Community inthiscasetopresent themselves
very briefly towards onwhat they have been until now.
196. Iwillstart then with Doctor Liehr onmyleft-hand sideplease.
Dr.Joachim Liehr (EC)
197. Mr.Chairman, myname isDr.Joachim Liehr andIamachemist andhave worked forthe
last17years onthemechanism ofoestrogen-induced tumours. This mechanism Ihave concentrated
on,thegenotoxicity studies, because everybody knew atthetime when Istarted these studies that
oestrogens arehormones andmany people accepted thefactthathormonal agents actashormones and
itwasatthesame time clear thatoestrogens arecomplete carcinogens. There arequite anumber of
animal model systems where oestrogens arecomplete carcinogens without anyother agents. Soin
order toexamine thiscarcinogenicity effect, complete carcinogenicity effect, Iwanted toknow can
oestrogens alsoactasgenotoxins inaddition to,notseparate of,butinaddition to,thehormonal effects
thattheynormally exert. This hasresulted inanumber ofpositive genotoxicity effects notjustinvitro
butalsomany ofthem invivo andquite adifferent class, many different classes ofgenotoxicity, so
thatwecantalkinthewords ofDr.Lucier ofcompelling evidence thatthere isgenotoxicity by
oestrogens.
Dr.Ercole Cavalieri (EC) oftheCancer Institute University ofNebraska Medical School
198. Iamherebecause alsoIhave done from adifferent approach what Dr.Liehr hastried toattempt.
When Istarted myresearch inchemical carcinogenicity Ihave astrong feeling thatoestrogen isthe
origin ofmany human cancers, andittook more than25years toresolve theproblem. Mr.Chairman,
thathappened because inorder tounderstand how oestrogen induced cancer, could initiate cancer,
wehave studied alarge class ofmoderate compounds called polycyclic aromatic hydrocarbons which
induce cancers andarepresent, many ofthem, inourenvironment, from thecombustion oforganic
material likegasoline, etc. These compounds have been anexcellent model forunderstanding how
oestrogen induced cancer andwearenowatthepoint inwhich wecansaythatoestrogens areinitiating
cancer andbytheso-called receptor-mediated process incancer andproduce cancer. Therefore my
point incontention isthatsince they initiate cancer forpeople thatthey donothave theprotective
mechanismthatnormallyeverybodyshouldhave,evenaminimaldosethatcanimbalanceourequilibrium
could beafactor ininducing cancer tohumans. Iwould bevery glad toexpress thisinamore visual
way with theslides later during these procedures ifIcan.
Dr.JimBridges (EC) from theUniversity ofSurrey inGuildford
199. Iamprofessor oftoxicology andIsitontheScientific Committee onAnimal Nutrition for
theEUandtheUKVeterinary Products Committee. Myinterest ismechanisms oftoxicity andtheir
useinriskassessment.WT/DS26/R/USA
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Dr.ManfredMetzler(EC)-ProfessorofFoodChemistryandToxicologyattheUniversityofKarlsruhe
inGermany
200. Ihave been trained asachemist andworked infield ofbiochemical toxicology formore than
20years. Mymajor interests over theyears have been thebiochemical mechanisms ofoestrogen and
hormonal carcinogenicity andmore recently wehave focused onthechromosomal effect ofoestrogens
ascarcinogens, which wethink isanimportant aspect ofhormonal carcinogenesis.
Dr.Alan Pinter (EC)
201. Iamapathologist bytraining andIhave been involved inmutagenesis oestrogen and
carcinogenesis forthelast15to20years. Now IamattheNational Institute ofPublic Health in
Budapest, Hungary. Thank you.
Dr.Samuel Epstein (EC)
202. Iamapathologist bybackground. Ihave worked forsome three tofourdecades inproblems
ofcarcinogenesis andtoalesser extent inmutagenesis. Mymajor interests areinpublic health and
preventive medicine. Ofrelevance inthisconnection Iwasakeyadvisor totheUnited States Congress
intheearly 70sinrelation toaseries ofactions leading totheeventual banning ofDES, having analysed
DES residuedatawhichweobtainedfromavarietyofsourcesincludingFDAandUSDA.Mytestimony
wascritical tothebanning oftheuseofDES asananabolic.
Dr.Reiner Stephany (EC)
203. Iamachemist and25years involved inresidue analysis ofanabolic agents, alltypes ofanalysis,
research, development, regulatory, forensic, whatsoever. Thelastyears Iamfocused onthequestion
ofthereliability ofanalysis, forwhat purpose andforwhat price. Iamemployed with theDutch
National Institute ofPublic Health andtheEnvironment andinvolved inECgroups andCodex groups
andsoon.
Dr.Adolfo Pérez-Comas (EC)
204. Iamapediatric endocrinologist, Associate Professor ofPediatrics Endocrinology inthe
University ofPonce inPuerto Rico andprior with theUniversity ofPuerto Rico Medical Science
Campus. Iamalsoanadvisor fortheCentre forDisease Control andforNIA, National Institute of
Health, onthearea ofdiabetes. Iamanadvisor ondiabetes andtechnology forHEW intheUnited
States.
Mr. Christoforou (EC)
205. Asyouseethere isonescientist missing andthisisDr.Adlercreutz, whounfortunately could
notjoinustoday buthewillbewith ustomorrow. Heinformed methathewould only liketomake
avery short statement, lessthan fiveminutes, when heisintheroom andbewilling toreply to
statements andquestions since hispaper hasbeen reviewed andcriticized both bytheUnited States
andCanada. Mr.Chairman, while Ihave thefloor onemore procedural issue isthattheUnited States
hasargued against thesubmission ofanyevidence, new evidence inthiscase. Wehave heard that
thismorning inthePreparatory Meeting, andyetwehave seentoday afairly long document circulating
commenting onthereplies ofthescientists. According totherules oftheDSU, thisdocument should
notcirculate unless itisread out. TheCommunity would agree thatitiscirculated ifwearegiven
thechance toprovide asimilar document within avery short time-limit. This document iscirculated
soIdonotknow thestatus ofthisdocument. Ifitistoremain, Ihave noobjection, butitstays with
thefiles ofthePanel, butwearegiven thechance ofthree days maximum orfour toprovide similarWT/DS26/R/USA
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documents inthisrespect. Ithink thatwould beaccording totherules oftheDispute Settlement
Understanding.
Chairman
206. Mr.Christoforou, would yougive ustherulewhich prescribes thatevery document hasto
beread out?
Mr. Christoforou (EC)
207. Mr.Chairman, theruleisthatevery time wemeet yousayplease give thewritten version
ofyour oralstatement otherwise youcannot filedocuments with thePanel. Ifyouprovide alimited
interpretation tothatpractice Icanprovide documents without reading them. ButIremember the
argument wasmade bytheUnited States inoursecond substantive meeting where they would like
thatweread literally thedocuments thatwewere submitting. This istheruleandastandard practice,
anditisthesubmissions intheannex giving thetable ofthedispute settlement, itisthewritten version
oftheoralstatements willbeprovided. Itisintheannex oftheDSU. Icanprovide youwith the
exact provision.
Chairman
208. Wedoinvite, wehave invited youinfact, tosubmit your comments inwriting, butthiswould
notmean thatyouhave toread them outbecause Iusually encourage people tosummarize what they
hand ininwriting instead ofreading itout. Ithink itshould notbeaproblem ofyouhaving such
adocument submitted within ashort period oftime -three days -okay.
Mr. Christoforou (EC)
209. Thank you. Mr.Chairman, wehave heard carefully thesummarizing thatwasmade bythe
distinguished experts advising ofthePanel inthiscaseandwewould liketotackle anumber ofresponses
thatwere given tofirsttheir initial presentation andthen thewaytheUnited States andanumber of
thequestions posed bytheUnited States.
210. Thefirstquestion would relate towhat wediscussed thismorning inthisroom. Physiological
levels ofresidues ofthese hormones inthehuman body. Ofcourse thisrelates tothethree natural
hormones only which occur naturally, itdoes notrelate tothediscussion onthesynthetic xenobiotic
hormones. Itisalsofrequently referred tointheJEFCA report of1988, where sometimes reference
ismade thattheresidues, forexample, ofoestradiol, would beincreased from twotofive-fold but
thiswasstillconsidered tobewithin thephysiological normal physiological levels. Inthiscase and
inthisrespect Ihave Dr.Epstein whowould liketomake atwo-minute explanation thenaskaparticular
question andIthink, Iunderstand from theSecretariat, apaper iscirculating thatgives theexact
calculations ofthose so-called physiological levels. This isimportant inourview because welater
linkthistothemost sensitive partofthepopulation -theso-called pre-pubertal boys, andthevalues
thatthey have given fordaily 24-hours concentration ofoestradiol, because thisisanimportant issue
inourview. SoIwillgive thefloor toDr.Epstein please.
Dr.Epstein (EC)
211. Thank you. Ifirstofallwould liketothank theChairman ofthePanel forallowing methis
opportunity toaddress youbriefly. Before Icommence mybrief statement Ihave justbeen reminded
thatIneglected togive youmyprofessional affiliations, which isProfessor ofEnvironmental and
Occupational Medicine attheSchool ofPublic Health inChicago.WT/DS26/R/USA
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212. TheJEFCA document andpreceding documents clearly give theimpression thatresidues of
natural anabolics fallwithin thenormal physiological ranges asindicated previously. There isalso
aclear statement thatlevels inmuscle arenormal. There isalsothestatement thatlevels inpre-pubertal
boys areabout sixmicrograms aday,which isroughly athousand times theresidue levels ofoestradiol.
213. Iwouldnowliketocommentonthesestatementsandpointoutthattheyappeartobeinconsistent
with industry datawhich Ibelieve areavailable andhave been available toJEFCA andother bodies.
Letuslook firstofallatthedataforSynovex Swhich isoestradiol andprogesterone andwhen you
examine levels ofoestradiol inliver youfindthey increase six-fold, inkidney nine-fold, inmuscle
twelve-fold andinfattwenty-three fold. Sothatdoesn 'tappear tobeentirely consistent with what
weheard thismorning: namely thatmuscle levels arenotincreased when infacttheyincreased twelve-
foldandatwenty-three foldexcess forfathardly appears tobetrivial. Now these relate ofcourse
justtothelevels oftheparent oestradiol, andnotofcourse itsmetabolites, sotherefore thisrepresents
anunderestimate ofthetruehormonal residues inthemeat.
214. Turning now tothequestion ofthefactor ofsixmicrograms adaybeing athousand times the
residue levels ofoestradiol forpre-pubertal boys: thispre-pubertal data, however, does notrelate
tochildren andenfants from theageof0to8.Now based onIARC documentation, volume 21,1979,
page 42to46,youcanmake thevery simple calculations showing what arethelevels ofoestradiol
production daily forchildren ofthis ageand itturns outthat thelevels range from 0.16 to
0.8micrograms aday. Sowearenow shifting thelevels inpre-pubertal boys from sixmicrograms
to0.16. This isimportant fortworeasons: first ofallthefigure ofsixisclearly misleading and
secondly ourlevel ofconcern isvery much greater forinfants andyoung children andchildren under
theageofeight, because there isabundant dataonthemuch higher level ofsensitivity tocarcinogens
ofyoung children than toadults. Soforthese tworeasons, Ithink itisimportant tofocus onthis.
Infactthemathematics clearly show thatthemargin ofsafety, theso-called margin ofsafety orthe
excess over background levels, isnotathousand-fold butsayforfatitiseight-fold, lessthan anorder
ofmagnitude. Itranges from eight to40,lessthan anorder ofmagnitude atthelower level. Sothese
aresome very fundamental distinctions andmisapprehensions onthese conceptions which Iwould like
tofocus on.
215. Allthisrelates purely tothelegal application. Theapplication conformance with standard
recommended good husbandry practice. IfImay turnforthemoment totheillegal, Ishould liketo
preface mycomments ontheillegal byquoting from areference thatDr.Ritter kindly provided us
with; namely thereference toTruhaut in1985 who stated thattheunlawful useoftheanabolics can
result inresidues 300-fold inexcess oftheestablished tolerances. Irepeat, theunlawful usecanresult
inresidues 300-fold inexcess oftheestablished tolerances. Ihave notreviewed theoriginal paper
ofDr.Truhaut butIrelyonDr.Ritter 'sreference toitandthestatement -thequotation -hemakes
from it.
216. Thesecond point inthisconnection Ishould make iswhen wearetalking about illegal or
misplaced implants, wearenottalking about anoccasional liberation byanirresponsible farmer. We
aretalking about twothings: firstofallabout common practice asIwillprove inamoment. Secondly
wearetalking about asituation inwhich toallintents andpurposes there isnoreasonable orpracticable
way ofmonitoring whether ornotillegal practice iscommon ornot. Irefer youtoa1986 USDA
survey ofsome 32major feedlots intheUnited States where halfthecattle were found tohave misplaced
implants. Irepeat, wearenotdealing with anoccasional abberation ofanirresponsible farmer. We
aredealing with acommon place situation inwhich there isnowayofmonitoring, ofresidue analysis,
ofpractical residue analysis, sohow canweeven begin todiscuss concepts ofADI ifwedonothave
theslightest level, slightest idea, ofthekind ofresidues. Wealready know thatwhen administered,
when thehormones areadministered inaccordance with recommended practice, thelevels areway
inexcess ofwhat yougentlemen have been ledtobelieve. Butwhen itcomes tothemisplaced implants
wehave twosetsofproblems. Oneyouhave theproblem attheimplant siteinwhich itcould beargued
thatinfactinspectors regularly check every piece ofthemeat andifthey findanimplant they wouldWT/DS26/R/USA
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cutoutthataffected piece ofmeat anddiscard it.Itisquestionable whether infactthathappens and
ourfriends from USDA may perhaps bewilling togive ustheassurance thatevery portion ofevery
animal slaughtered isinspected formisplaced implants. Butfarmore tothepoint thefactiswhen
youimplant, putanimplant intheavascular, thenon-vascular subcutaneous tissue under theskin of
theear,therateofabsorption isextremely low, butwhen youimplant itinmuscle which ishighly
vascular, youcanhave amuch higher rateofabsorption. Now Ihave searched theliterature as
thoroughly asIcould andcannot findanyreference oranydataatalllevels ofhormones ofoestradiol
atsites atadistance from theimplant site. Thebasic knowledge ofpharmacology could make itvery
clear thatwhen youimplant ahormone oranyagent inahighly vascular tissue thenitsrates ofabsorption
would bemany-fold higher, whether it'soneorder ofmagnitude, twoorders ofmagnitude, three orders
ofmagnitude -Idonothave theslightest idea, butIdoknow thatmisplaced implants arenotuncommon
andIdoknow from theindustry data thatthelevels oftheresidues, areway inexcess ofwhat you
have been ledtobelieve.
Mr. Christoforou (EC)
217. Iwould likenow toraise twoquestions, after thestatement ofDr.Epstein, andtoallour
scientists advising thePanel. Ifitiscorrect aswehave been making thecalculations, andthedocument
iscirculating,aboutthelevelofoestradiolinpre-pubertalboys,whichisnotsixmicrogramsper24hours
butitiseight-fold lessthanthephysiological levels, thenIwould request thescientists togiveustheir
view: Isthisreally arisk, anadditional oranincreased riskofthese residues causing therisks we
have been discussing here among other things carcinogenicity, tothistype ofsensitive partofhuman
population? This isthefirst question, thank you.
Chairman
218. Thank you. May Iinvite youjusttocomment generally onDoctor Epstein 'sthesis, because
wewould liketohave your reaction onthis? Who would liketotakethefloor? Doctor Ritter, please.
Dr.Ritter
219. Thank youMr.Chairman. Ioffer to,Ifoolishly offer toleadonly because Ithink Iwould
liketoclarify forthePanel aspecific reference thatDr.Epstein made tomysubmission with regard
totheTruhaut reference. Itiscorrect indeed thatIcited thisreference, butIwould submit tothePanel
thatthereference hasbeen somewhat misquoted. Asapoint ofclarity, Dr.Epstein didcorrectly note
thatIrefer tothepossibility ofthe300-fold excess inresidues with oestradiol.
220. ButifImay, Mr.Chairman, andIwillprovide specific reference tothePanel andtotheEU,
Ihave brought italong willme. Buttoputintoproper context what theauthors have saidexactly
isthat"when 50milligrams ofoestradiol inanoil-injectable preparation isadministered intra-muscularly
intheneck ofavealcalfthree weeks prior toslaughter" andthen they goontotalkabout thisillegal
practice, "the levels ofresidues inthevicinity oftheinjection sitemay be300-times greater".
221. This isapivotal issue, Mr.Chairman, because infactthere isnotaninjection atissue forthe
proper use. Sothisparticular three-fold increase inresidues refers toamultiple ofabuses, ifyoulike.
Itwould beatthewrong siteandusing thewrong method ofadministration. The300-fold increase
inpotential residue does notrefer tothenormal use. This refers toanextraordinarily abnormal use.
Thesame authors inreferring tothatvery conclusion thatthey have drawn then goontosayintheir
conclusion: "Itisourbelief thatneither 17beta oestradiol norzeranol, poses anytoxicity problem
when used asananabolic inanimal production. Itiswidely agreed thatintheinstance ofhormonally
mediated toxicological effects including carcinogenesis, atolerance level canbeset". They finally
conclude "even intheinstances inwhich misuse mayhave occurred, itisvirtually impossible tovisualize
anyhazard tohumans ingesting meat from animals treated with zeranol". These aretheir words, not
mine.WT/DS26/R/USA
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222. Imake thispoint ofclarity because Ididnotwant thePanel leftwith theimpression thatthis
300-fold increase towhich Ireferred issomething thatcould beanticipated, ifyoulike, under normal
circumstances, andindeed astheauthors suggest itisnotlikely thatonecould anticipate iteven under
abnormal conditions ofabuse. Itsimply demonstrates than onecancreate ascenario where atthe
injection site, which would notbeapplicable innormal growth promoting uses, itcanbeinexcess.
Chairman
223. Who would liketospeak tothequestion submitted bytheCommunity?
Dr.McLean
224. Justtomake acomment about thereaction totheimplant ifitisplaced intheearcompared
with inthemuscle. Ofcourse inthose vascular tissues likethemuscle then yougetquite anactive
tissue reaction and indeed you gettheimplant walled off. One ofthefeatures ofinjections
subcutaneously intheearisthatyoudonotgetthemassive reaction atthesiteanditisspecifically
designed, andalltheresidue studies arecarried out,with theimplant injected intheear. Theaim
ofinjecting itthere istogetprolonged andslow release atlowlevels over aperiod oftime; sothat
isspecifically designed tobethatway.
Chairman
225. Thank you. Could youoffer anycomments onthetable wewere given andinparticular the
impact onthepre-pubertal situation? You donothave tospeak. Letmeknow. Yesplease Doctor.
Dr.Arnold
226. Chairman, there isoneproblem when thisinformation comes soquickly, ittakes some time
tolook attheevidence. Theonly thing Icandoatthemoment istoconfirm thatthese figures really
stand intheIARC report involume 21.Itisimportant tonote thatthese values differ tremendously
according tothesource. SoIcan'tsayfrom where thislevel ofsixmicrograms came. This Idonot
know currently, butIhave some tables from some textbooks ofendocrinology with meshowing that
there isatremendous range andifyouread carefully thetextinwhich IARC explains theway how
theyhave estimated, theymake quite clear thatthisisanestimate andthatthevariability canbeenormous
andtheygiveexamples ofindividual goods where there wasavery large range ofdata. Sothefigures
areokay, butyoucannot insist andsaythisistheone.
Dr.Ritter
227. Thank youMr.Chairman. Ioffer only twopoints forconsideration bythePanel. Ithink
asDr.Arnold hasalready noted weareresponding somewhat onthefly,even though yousuggested
thatweneed notfeelanyobligations todoso.
228. Inthetable wehave been provided, Mr.Chairman, theintake factors thathave been calculated
arebased onapproximate level ofexposure to500grams ofmeat. This table hasbeen calculated on
thebasis ofpre-pubertal boys under eight years ofage. Iwould suggest toyouMr.Chairman that
itisnotlikely thatachild oftwoorthree willconsume 500grams ofmeat aday. This calculation
isbased ondaily intake ina500gram sample offood, every dayforhisentire life. Iwould submit
toyouMr. Chairman thatasamember oftheJEFCA process now forsome years, Ifeelthatthe
500gram estimate isanover-exaggeration even inthecase ofadults. ButIthink topresume in
calculating therisks thatachild under eight years ofagewillconsume 500grams ofmeat every day,
respectfully Sir,Ithink itissomewhat ofanexaggeration.WT/DS26/R/USA
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229. Theother point thatIwould bring toyour attention andagain Iapologize forresponding on
thefly,isIthink thepoint thatDr.Arnold hasalready elaborated onandthatisthatthenumbers that
youseebefore youarepresented as,how shall Iputthis, asifthey were rigid when infacthormone
levels, either present asresidues ornormally circulating endogenous levels, youwould normally be
accustomed toseeing them asarange. These donothave rigid values. Ifyoulook, forexample,
atthe,letustakethemost extreme example ofthetable before you, ifyoutakealook atfat,the23-fold
excess factor isofcourse assuming thatthefive-year oldorthefour-year oldorthetwo-year oldhas
consumed 500grams ofmeat. Ithink ifthatcalculation were redone with amore realistic figure the
23-fold excess might infactbereduced toatwo-fold excess. Butinaddition tothat, Iwould suggest
toyouMr.Chairman thatthetestvalue of41.4 microgram isavalue from arange ifyoulikeand
thattherange isvery broadly distributed. Similarly the1.82 intheuntreated control isextracted from
arange. Depending onwhere intherange these twovalues fall,respectively, mayimpart theimpression
thatitishigh orlow, when infactwhat weshould bedoing when talking about ranges isjustthat,
weshould beexpressing arange rather than arigid point estimate.
Dr.Lucier
230. Thank you. Many ofthenumbers aresimilar tothenumbers thatIputtogether inpreparation
forthemeeting -certainly therange ofoestrogen production perdayinyoung boys andgirls isabout
what isreported here from thatIARC publication, therange of0.4to0.2micrograms perday. This
isabout 140times, from myestimates, higher than theamount obtained from eating ifoneofthese
young boys orgirls ate500grams ofmeat containing themaximum level permissible. Inaddition,
ifyoulooked atapre-menopausal woman interms ofoestrogen thatwould beabout 200times that
iswhat isnormally seen inayoung boyorgirl, sothatratio instead ofoneover 140becomes one
in28,000. Soeating thatamount ofmeat perdayforapre-menopausal woman would addonemolecule
forevery 28,000 shewould normally have inherbody, andItakethepoint thatthisisapoint estimate
andofcourse thatisanaverage estimate forthewomen, notencompassing therange thatDr.Ritter
justdescribed which isinfacttrue. Butatleast apoint estimate itwould beonemolecule perevery
28,000 normally present inawoman 'sbody. Inaddition, probably only about tenpercent ofthat
isgoing tobeabsorbed because itisdegraded inthestomach, soyoucanaddanother factor often
onthatsoitbecomes oneover 1,400 oroneover 280,000 fortheyoung boys orgirls andthe
pre-menopausal woman, respectively. Butsome ofthese numbers arevery consistent with thenumbers
thatIhave had-justused differently.
Dr.McLean
231. Mr.Chairman, ifIcould make twocomments following onfrom mycolleague. Theother
thing isthatdepending onthemode ofcooking wecanloseupto80percentofthese steroid hormones
inthecooking process andnotterribly many people eatrawmeat.
232. Themain point Iwould liketomake wastoaddress thematter ofmisplaced implants and
violations ofadministration. Inmycountry andintheUnited States, butparticularly inmycountry,
wehave targeted inresidue surveys trenbolone andzeranol, very specifically looking forviolations,
andinfacttoallintents andpurposes violations donotoccur. Now thismeans thateven ifthere is
misuse, andthatisdifficult toprove, wearestillnotgetting residues thatexceed theMRL. Iwould
suggest thatasimilar situation exists with thenaturally-occurring hormones, where itisnotpossible
todetermine whether aviolation hasoccurred ornotbecause thelevels thatyoufindinthecarcass
sitwithin thenormal range. ButIthink thatyoucantakesome comfort intheresidue surveys ofzeranol
andtrenbolone which show toallintents andpurposes violative residues notpresent.
Chairman
233. Arethere anyfurther comments from thePanel? May IaskProfessor Epstein tocomment
briefly onwhat wassaid?WT/DS26/R/USA
Page 269
Dr.Epstein (EC)
234. Unfortunately American (you may gather from myaccent thatIamnotAmerican) butone
ofthethings thathasimpressed about American boys istheir appetite for"Whoppers" andfor
hamburgers. Itisnotatalluncommon forachild ofseven oreight tohave ahamburger atlunch and
a"Whopper" atlunch andanother oneintheevening, andthatisroughly 500grams. That isthefirst
point.
235. Thesecond point iswearereally dealing with asituation inwhich wehave provided thePanel
with datawhich areentirely inconsistent with dataprovided tothem previously byJECFA. Onecan
trytoexplain thisaway invarious ways andmeans butthedata arefundamentally different andthe
pre-pubertal levels inpre-pubertal boys areclearly themargin ofsafety islessthan oneorder of
magnitude. Again, letmealsoemphasize thatinfluence hasbeen made thatmisplaced implants are
theexception rather than therule. Irepeat, in1986 asurvey ofUSDA feedlots showed thatsome
32major feedlots orfeedlots bytheUSDA, showed misplaced implants inhalfofthem.
236. Myfinal point isthatintheabsence ofroutine monitoring chemical analysis wedonothave
theslightest idea, wehave noinformation atall,astowhether wehave 100percentmisplaced implants,
tenpercent misplaced implants oranynumber atall.
Mr. Christoforou (EC)
237. Imeant toaskaspecific question, thisquestion ofpotential misuse, forthescientists 'reply,
butiftheywant tocome inearlier thatisfinewith usaswell. Because inourview thequestion about
thepre-pubertal boys hasnothing todowith misuse. Wearetalking about proper useofthese implants
andinthatcase theJECFA Report said, andthecalculation wasbased onthe6micrograms per24
hours andtheysaidtheresidue thatwould result is1,000-fold whereas inthiscaseweseeitiseight-fold
lessthanisthephysiological level. This issue hastobedisconnected from thepotential increased risks
from misuse onwhich Iwillcome tolater. Wearetalking about proper useofthese implants and
what isthesensitive partofthepopulation which may beaffected bythis. Thank you.
Chairman
238. AsIunderstood there were twolines ofargument butthescientific datawasforregular use.
Igive youthefloor. Iamsorry Ihave togive thefloor firsttoDoctor Randell, Ithink hewasfirst.
Dr.Randell (Codex)
239. Thank youMr.Chairman. Iwould justliketodispel theimpression given thatthedata in
thetable justpresented tous,which isentitled Symtex NADA 9-576 1983 Synovex Steers, wasnot
available toJECFA. Those dataareinfactabbreviated datafrom Table 6oftheJECFA evaluation
of1987 published in1988. Itisonelineinonetable ofthedatawhich JECFA considered andIwould
point outthattheJECFA alsoexamined thevariations inthedata, thatistheJECFA data contains
theranges ofeach ofthese datapoints aswell. Sothedatawhich have been presented here aretaken
inisolation from alarger setofdata which JECFA considered. Thank you.
Dr.Arnold
240. Mr.Chairman, inthemeantime Ihave found thetables Ihave produced inpreparation oftoday 's
meeting. Iused abrand new textbook ofendocrinology andmetabolism published in1995. What
youcaneasily seefrom these tables thatinfactthere isatremendous range ofvalues. Sofirstofall,
whether itistwoorsix,itisthesame order ofmagnitude. Then oneneeds toknow whether itisan
average, amean oramedium; there canbeatremendous difference because therange andIhave
allthefigures from foetal life,allstages ofpuberty andadult life,therange sometimes isa250-foldWT/DS26/R/USA
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oreven greater andtherefore youcanfully explain thedifference iftwopeople take thesame data
andonescientist takes themean andtheother takes themedium andtherefore what Idid-Iputtogether
themean, theminimum andthemaximum andhere youcanseethatforsome ofthese hormones there
isjusta500-fold range. This hasbeen puttogether from allsources available inamost recent 2,500
page textbook onthissubject. Ifyouwant thefullreference isgiven andIcanleave itforyou. It
wasmypersonal preparation butifitisofvalue tothePanel, youmay have it.Itisnotincluded in
mystatement. Ididitafter.
Chairman
241. Could itbegiven tothePanel andwewould hand italsototheparties.
Mr. Christoforou (EC)
242. Mr.Chairman, wewould begrateful ofcourse tohave alook intothose. Atleast Icanexplain
oursources. Oursources, andIthink there might have been again amisunderstanding, itisonpage 19
oftheJECFA Report, where itisstated andIquote "even inpre-pubertal boys theamount ofoestradiol
17betaproduced daily (6.5micrograms) isa1,000 times theamount derived from ingestion of5grams
oftreated meat." Wedidnotlook intothetables referred tobyDr.Randell, welooked intothetext
where thisisacitation. Then wetried tofindoutwhat thecitation wasanditturned outthatitwas
anarticle published in1974.
243. Ourdata, which youseefrom thispaper wecirculated, came from theIARC volume andthey
arebased onamore recent article byBrown andTolle, 1987. Sothisisourbasis ofcalculation and
wewould ofcourse appreciate thatthere areother calculations made thatwould show adifferent
calculation. Butwealsotakethepoints thatmay bearranged andthere may bevariations butweall
based ourselves onwhat itisinthepublication oftheInternational Agency forResearch ofCancer.
244. Mr.Chairman, Icannow proceed with posing theother questions. Iwould liketorequest
because some ofmyscientists would liketohave aprecise, ifpossible, reference onwhat Dr.McLean
issaying, thatupon cooking about halfofthese aredestroyed andwedonotknow ofanysuch reference
inanyacademic reviews. Ithink itwillbeuseful ifwecangetthereference sothatwecancontrol
thisbutwedonothave thistype ofinformation andIwould appreciate areference tothat.
245. Mynextquestion islinked tothemisuse because thisisaslightly different issue. Dr.Epstein
hasmade thereference tothemisuse thatthishasbeen reported intheUnited States. Wehave also
made thereference tothismisuse inoursubmissions. Iwillremind only with anumber offigures
here andourexports andthen Iwillraise thequestion.
246. Forexample, wehave examined thenational plans, theannual control plans intheUnited States
anditwould appear thatbetween 1972 and1994 there wasnocontrol ontrenbolone. There wasnever
anycontrol onprogesterone. There wasnever anycontrol ontestosterone. Onoestradiol itwaschecked
only fortheyears 1987 to1990. MGA waschecked only fortheyears 1978 to1983. then itwas
discontinued, andstarted again in1987 to1990 andthen discontinued andthen in1993 only.
247. Forzeranol itwastested fortheyears 1973 to1974. Again thenin1977 andin1985 to1989.
This hasbeen referred tothePanel itisparagraph 57ofoursecond written submission ofthe
United States Panel. Wehave alsocalculated onthebasis ofthesamples thatareexamined annually
intheUnited States that, forexample, intheyear 1993 there were checked only 39,128 samples.
Onmaking thecalculations what does thisnumber represent interms oftotal livestock production the
United States tells usthisisonly 0.005 percent. Ilinkthen these factual statements andIalsonote
thatintheyear 1993 there were only 22samples ofMGA forMGA tested, 22samples only andthere
wasoneviolation. Ifweextrapolate thisforthefurther amount oflivestock thatenter thefood chain,
thatcanamount to4.5percent oftests positive.WT/DS26/R/USA
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248. Thequestion isbecause Dr.McLean alsosaidthere isnoincentive forthefarmers tomisuse
because there willbepenalties ifthey arecaught. Inlight ofthis, andIcancitesimilar numbers for
Canada, theyareinparagraph 11ofoursecond written submission, ifyouwould likeIcanmake similar
references. Inlight ofthis0.005 percent-check -doyoureally think itis?-thethreat ofpenalties
itisarealdissuasive instrument sothatfarmers willnotmisuse those implants, because those implants
arevery cheap apparently andthey may speed thegrowth rateandwehave heard thismorning that
they may beanadditional injection ofanimplant before thewithdrawal period hasexpired. Sohow
credible really isthisdisincentive onfarmers tomisuse inview ofthepotential advantages ofeither
misusing oradding more implants. Thank you.
Chairman
249. Would youliketocomment this?
Dr.McLean
250. AsfarasIcanMr.Chairman. Theresidue surveys thatarecarried outintheUnited States,
Icannot comment precisely onthenumbers, buttheviolation rateoffivepercentissignificantly less
than theviolation ratethatwasbeing quoted before of50percent, sothere isavariation andIthink
thattheUnited States delegation could throw light onthelevels ofviolation.
251. Thesecond thing isthattheresidue misuse thatwewere talking about wasin1986. Iwould
suggest nowthatwith theadvent ofpellets andpelleting administration devices thenitismyimpression
thattheimplant administration totheearhave improved quite dramatically.
252. Inanswer tothequestion about cooking, Iwasfairly careful tosaythatsteroids ingeneral
there could bedestruction ofupto80percent. Myfigures come from asubmission made onanother
steroid forregistration andasIsaidIwasvery careful tosayitwasupto80percent andIwould
suspect thatthedestruction ofsteroids bycooking would besimilar across therange.
Chairman
253. Thank youvery much. Any other comments onthisquestion? Doctor Arnold?
Dr.Arnold
254. Mr.Chairman, Icannot speak onthedetails ofAmerican residue surveillance plans. What
could perhaps help, maybe other people have thatinformation, what istheresult ofEuropean residue
control onimports. Ihave seen that, forexample, France does alotofwork inthisfield, butasfar
asIknow, Isawmore than 1,000 samples in1995 butnopositive.
Chairman
255. Thank you. Iwould liketostaywith thisresidue controls andaskwhat isthesituation inthe
European Community operating under theban? Youneed tohave controls asmuch aswhen youallow
it,buthow isitdone, doyouhave figures onthis? Does anyother delegation have figures onthis?
Mr. Christoforou (EC)
256. Mr.Chairman, itisinoursubmission brought fortheUnited States andCanada andthishas
notbeen disputed asfarasIknow andIshould know because Iamalways inallmeetings present.
There aresamples tested every year, there areabout 200,000 samples ofanimals tested intheEuropean
Community. This iswhat isthelevel oftesting intheEuropean Community.WT/DS26/R/USA
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257. Wealsohave provided thereply tothequestion byCanada concerning thenatural hormones
andwesaidwetestannually 59,000 ofblood toverify thelevels forthenatural hormones. These
arethefigures wehave already given tothePanel andIhave sofarnocomments onthis. Butthis
isourofficial figures.
Dr.Arnold
258. Mr.Chairman, since Iamalsofrom theEuropean Community Imayslightly correct thisfigure.
This isthetotal number ofsamples forallresidues andnotforhormones. Forhormones thenumber
with allfood animals andallsubstances altogether isintheorder of20,000 andalmost halfofthat
figure comes from onecountry.
Mr. Christoforou (EC)
259. Mr.Chairman,forthenaturalhormoneswehaveverifiedeachindividualcheckdoneinresponse
tothequestion byCanada forthatwearesure. Forthenatural hormones theblood samples tested
are59,000. Forthetotal number ofchecks done itisindeed 200,000 samples ofanimals tested. We
arenotgoing toverify howmuch ofthis,ourunderstanding isvery much higher than20,000 mentioned
byDr.Arnold. Iwillclarify thisforthetotal hormones, butfortheblood residues, forthenatural
hormones checked lastyear, itwas59,000.
Chairman
260. Doyouhave anyindications ofpercentage inherds? What thatwould mean?
Mr. Christoforou (EC)
261. Mr.Chairman, weneed tounderstand alsothatthenatural hormones arenotallowed tobe
used intheECforgrowth promotion. Thechecks aredone because only oneofthose natural hormone,
oestradiol, isallowed tobeused fortherapeutic orzootechnical reasons. Sotheinformation isthere
isnoexcess butIdonothave theexact figure ifthere wasanyviolation orifthere isanyphysiological
level forthenatural hormones. Wedonothave anyfigure ofviolation intheCommunity because
they arenotused andthey cannot detect high violations inthose 59,000 wechecked lastyear.
Dr.Ritter
262. Thank youMr.Chairman. Ioffer justabrief commentary. Iofcourse willnotendeavour
tospeak fortheUnited States orforCanada with regard tohow many samples they have sampled but
Ithink itisimportant torecognize thatthenumber ofsamples thatonetakes andmeasures canbe
somewhat misleading. 20,000 may appear tobelarger than 5,000 forexample, buttheintent ofany
monitoring programme isthedevelopment ofaprogramme thathasthestatistical confidence necessary
todetect violations totheextent thatthecompound isused, ifinfactresidue levels which areoutof
compliance arepresent. Iwould besurprised thateither theCanadian ortheUSscheme hasnot
considered thatstatistical design inthemonitoring programme.
263. Ithink theissue ofhow many samples were measured canreally besomewhat misleading.
Ithink themore relevant question is-isthemonitoring programme statistically confident andisit
abletodetect ineither country, orintheEuropean Community forthatmatter, isitabletodowhat
itisintended todo? And generally speaking most monitoring programmes areintended todetect a
fivepercent violation rate95percent ofthetime. Thenumber ofsamples thatarerequired todo
thatwillvary from country tocountry andfrom commodity tocommodity because itisafunction of
theusepractice. Imake thispoint only because Ithink itwould berelatively fruitless togetintoa
debate astowhether ornot20,000 islarger than 5,000. Itclearly is.Butthatquite frankly, Ido
notthink, istherelevant issue.WT/DS26/R/USA
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264. Iwould just add one other commentary perhaps onthat. The Council forthe
European Community hasjustmade reference tothefactthatthere maybesomewhat lessthanarigorous
programme forsome oftheanabolics because thecompounds arenotused andhence ofcourse, one
would notexpect todetect them. Buttheinternational experience with clenbuterol, forexample, which
isnotpermitted foruseasananabolic, isthatitiswidely used andabused particularly inEurope,
with very realcases ofadverse effects inhumans, insome cases Ithink death, resulting from theuse
ofaanabolic, clenbuterol, inthiscase, which most certainly isprohibited foruse. Sothefactthat
itisnotpermitted, Ithink asyoureferenced yourself amoment agoMr.Chairman, certainly isnot
evidence thatitisnotused. Todraw some confidence from thefactthatitmay notbeapproved for
thatuseandtherefore should notbepresent Ithink iseuphoria.
Dr.André
265. Idonotwish togooninthese disputes ofanumber ofsamples because itisaregulatory
problem, itisnotarealscientific one. ButIjustwould liketoinvite youtoobserve what isdone
with thesample, because youcanmanage alotofsamples foroneortwohormones andyoucanhave
samples for30ormore hormones, andinthese cases theefficiency ofthecontrol isvery different.
266. Tomyknowledge, inFrance aswell asinmost countries inEurope now, wedeveloped very
nice multi-residue control programmes. Itmeans thatforonesample wecheck sometimes for30
anabolics, different anabolic steroids, andinthiscaseitshows thatwediscover sometimes black-market
compounds. Itisnotthateverybody knows it.
267. Butmyquestion istoknow when ourcolleagues saythatintheir country they donotobserve
misuse ofhormones, myquestion would bewhat hormones areyouchecking for?Ifitisonlytrenbolone
zeranol they canbesure thatthere isnomisuse ofthese hormones -these twoorthree hormones -
inthatthey have nohigher residue levels than allowed asMRL. Buttomyknowledge Idonotthink
thatallthese hormones areassayed inthese countries aswell aswedouptonow, sothey cannot say
thatthey have nomisuse ofother xenobiotics.
Chairman
268. Thank you. May Ijustfollow uponequestion. Iknow thisisnotastrictly scientific question
butyouhave extensive experience inthis. Doyouconsider thecontrol tobemore efficient, more
feasible, under asystem which allows andrestricts orunder asystem which attheoutset prohibits
andtries tofindthose who stepover thelaw. Justfrom your assessment, from your background and
experience: Iknow youhave notextensively discussed thisinyour papers because itisnotascientific
question, butIthink from thelegal point ofview ithassome relevance. Would youliketospeak on
that?
Dr.Arnold
269. Iamalittle bitreluctant because thisiscertainly subject tospeculation. Iwould assume, and
Iexpressed thisinmypaper, Iwould assume acertain competition between legal products andillegal
substances. Iwould assume thatasignificant number offarmers would uselegal products because
they areefficient andnottooexpensive, buttosaythiswould result innomisuse Ithink would be
pure speculation.
270. IfImay justaddonemore sentence tothesampling andresidue control. Itisinfactvery
important toconsider theimportance ofmulti-residue methods andalsowhether theprogramme is
based onrandom sampling, statistically-based sampling oronsuspicion. IntheEC,forexample, we
have atleast these twoaspects: random sampling andsampling ofsuspected animals, plus control
ofimports.WT/DS26/R/USA
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271. Ifwelook attherandom sampling, thenthesituation isnotsobadexcept forcertain substances
incertain countries. Butifwelookatthesuspect sampling, thenwefindallsubstances including zeranol
andtrenbolone from ourdomestic production. Theonly areawhere Ifeelthateven under conditions
ofrandom sampling wehave some problems iswith vealcalves andthenatural hormones. Ifwelook
attheplasma levels, there wehave sometimes insome countries some problems with ahigh incidence
ofviolating levels. Buthere asascientist, Imust say,distribution ofphysiological levels andoflevels
resultingfrommisuseareoverlappingtosuchanextentthatthismayjustbeacoursebecausethedecision
limits have been inappropriately defined toseparate thetwopopulations.
Dr.André
272. May Iaddsomething toDieter Arnold 'spresentation? Wehave alsotheopportunity, more
than random samples andsuspected samples, togoonfarm andtocheck formisuse during breeding
ofanimals andnotonly atslaughter house andthisissometimes very efficient tool.
273. AsIsaidthismorning, inFrance we,concerning theoperation, wehadfouryears, orfiveyears,
Idonotremember, during when these hormones were allowed andafter thislong period during which
these hormones were banned andreally Iwasincharge ofcontrol during thistwodifferent periods
Icanconfirm thateven ifinmycountry hormones were allowed, themisuse ofother hormones, the
black market wasalsopresent based ontheideathatwhen youallow something youhave anofficial
label andpeople have anofficial label andcanhave treated animals, butthen tryalways togive more
andmore andtogive different compounds tohave more results andwenever observed differences
intheblack market when thehormones were allowed orafter. Itwassoimportant.
Dr.Lucier
274. IfIcanoffer myspeculation onthis. Myfeeling would bethattheviolations probably would
occur more frequently incases where itwasbanned ifyouarecomparing ittoacontrolled useinwhich
there waswell-defined educational programmes, very good communication efforts andappropriately
stiffpenalties formisuse. Ifallofthose things were inplace with thecontrol programme, myguess
isthatyouwould have fewer violations inthatcase-ifitwasavery systematic approach forcontrolling
them thatadequately addressed those andalsovery stiffpenalties forviolations.
Chairman
275. Canwegoonwith your questions andcomments?
Mr. Christoforou (EC)
276. Mr.Chairman, Ithink oneofourexperts would liketomake avery short statement onthe
issue ofcooking -thepercentage ofthenatural hormones destroyed during cooking -Ithink hemight
have acouple ofwords tosay, then Iwillproceed tothenext question. Thank you.
Dr.Stephany (EC)
277. First ofallIassume thatwearetalking about cooking andIdonothave toaddanything to
that. Ionly have questions. Ivery recently didaliterature research onbehaviour ofveterinary drugs
ingeneral during thepreparation inthekitchen -sothatiswhat Icallcooking: frying, braising, etc.
Icould notfindanydataonsteroids butwhat Ifound onother types ofveterinary drugs ingeneral,
ranging from very oldwork with diethylstilboestrol tomore recent work.
278. Thegeneral pattern isthatmost ofthese residues arequite stable. Some arelost, notbecause
they aredestroyed, butthey arecooked outofthetissue when they arefatsoluble andsoon,soif
youdonotusethedrippings youwilllosesomething. That isthegeneral pattern. SoIamvery muchWT/DS26/R/USA
Page 275
surprised about thestatement ofDr.McLean (sic) thatupto80percentor80percentofthese residues
willbedestroyed. Iwould bevery interested inhaving areference orthedata ofthat. That ismy
remark, soitismore ofaquestion.
Chairman
279. Thank youvery much. Would thePanel liketocomment ontheeffects ofcooking?
Dr.McLean
280. Mr.Chairman, Imade thecomment anditwasinrelation toasubmission thatwasmade about
asteroid thatiscommercial inconfidence andbefore IleftIapproached themanufacturer orthesponsor
andatthisstage they arestilltrying togetclearance formetorelease theinformation. Icansayno
more andvery carefully Imust saythatthecooking methods vary -they involve braising, boiling and
thefigures varied quite considerably. Icansaynomore.
Chairman
281. Arethere anyother data oncooking available ornotnow?
Mr. Christoforou (EC)
282. Mr.Chairman, since wehave such awide range ofexpertise present here, Ithink, Dr.Liehr
hasdone some research himself andwould liketosayafewwords onthisparticular point oncooking.
Dr.Liehr (EC)
283. Notoncooking itself, buttheprocess ofheating. Ihave done chemistry, chemical work,
chemical preparations ofoestrogens which involved heating these oestrogens to120-140 degrees and
wefoundnoevidencefordecompositioninvariousorganicsolvents.Oestrogensarequitestableproducts
andIcannot imagine an80percentdestruction ofthese compounds under cooking procedures. Thank
youMr.Chairman.
Dr.Randell (Codex)
284. Thank youMr.Chairman. Thediscussion puzzles mebecause there isnothing intheJECFA
orCodex evaluation thattakes intoaccount possible reduction factors asaresult ofcooking. Infact
theJECFA Codex figures would beapplicable tothose people, who forsome reason oftheir own,
aterawmeat, rawkidneys, rawliver andraweggs.
Chairman
285. Soyouaresaying thatbasically youwould assume that100percentisstillinthefood which
isbeing prepared andeaten bypeople.
Dr.McLean
286. Itwasmethatintroduced itandIthink thattheimportant thing torealize isthattheevaluations
thatnormally occur through, sayforexample, theJECFA process, dolook attheworst case andthe
worst case isthatyougetthefullload anditisabenefit ifprocessing removes some ofit.WT/DS26/R/USA
Page 276
Dr.Arnold
287. Ithink thatwhat Dr.Liehr hassaidisabsolutely correct. Thesteroid hormones aresostable
youfindthem inpetrol, inmineral oil,they survive even theconditions under which these products
have been formed. Mr.McLean wasnotspeaking about steroids, hewasmeaning another substance.
Dr.Lucier
288. Yes, Ithink thatisabsolutely correct. There isnoreason tothink thattheywould beextensively
destroyed. Theonly wayyouwould getridofthem, Ithink wasmentioned earlier, isingetting rid
ofthedrippings which would contain many ofthesteroids justbyextracting them outbecause they
aresofatsoluble.
Chairman
289. When theartificial hormones areused andadded towhat isnaturally there onstock arethey
going tostayinthatway intheenvironmental situation given their stability?
Dr.Lucier
290. Yes, they should stayinthesame form. Through thecooking process youmean?
Chairman
291. No,justwhen they arereleased andthey arenotdestroyed bycooking orother ways andyou
saidtheywould even befound inpetrol. Myquestion iswhether theamount ofhormones ontheglobe
arejustincreasing byadding artificial hormones.
Dr.Lucier
292. Most ofthesteroids themselves once inthebiota andsubjected toliving organisms ontheplanet,
those organisms would tend todegrade most ofthesteroids. They have some ofthesame abilities
todeactivate them aspeople have sothebiota itself iscapable ofdegrading them, soyouwould not
getagradual accumulation ofthese intheenvironment asyouwould forsaysome ofthemore persistent
organochlorine compounds such asthePCBs andDDEs andthese kind ofthings which aremuch more
resistant tothiskind ofdegradation. You would notgetthatsame kind ofbio-accumulation with the
steroids.
Dr.McLean
293. IfIcould addtoitcholesterol, which isthebasic nucleus upon which thesteroids arebased,
isextensively oxidized oncooking, andinfactitisthought thatitisoxidized cholesterol which isthe
contributing factor toheart disease rather than cholesterol perse.Iwould suggest thattocompare
anenvironment where asteroid isaninorganic solvent, which weknow protects thenon-extraction
compared with thecooking environment which contains water, oxygen andanumber ofother salts
andother compounds would beindeed theideal environment fordestroying compounds. SoIdonot
want toexplore itanyfurther -Ithink thejuryisstillout,butIamnotsurethatthesteroid hormones
inthecooking environment arequite asstable aspeople would believe.
Dr.Ritter
294. Mr.Chairman, Idonotknow ifyouwish anyfurther comment onthistable thatwasrecently
circulated butIhave justtaken amoment now. Iamalittle slower perhaps than most andIneed a
moment toabsorb theinformation andtrytocome toterms with it,butasIlook atthese numbersWT/DS26/R/USA
Page 277
now andunder No.2-thisSyntex data -Iamnotentirely sure what thisisintended torepresent.
Iamleftwith theimpression thatthese numbers arederived from usedatawhich hasnowithdrawal
period whatsoever, because when Ilook atthefood standards programme -theresidue levels -which
Ithink weallreferenced inoursubmissions, andIlook onpage 9ofthat, Inote that, forexample,
with withdrawal periods ofaslittle as24hours, following implantation with 24milligrams of
oestradiol 17betacontrol-released implants andwithdrawal periods aslittle as24hours, residue levels
were infactidentical tothecontrol -theywere nothigher atall.Ifoneincreases thatwithdrawal period,
infactthescenario continues -withdrawal periods inthisparticular study were measured upto72hours,
which isstillavery short withdrawal period andcertainly much shorter than what isrecommended
intheactual usepractice, theresidue levels fortheE2areidentical foralltissues totheir respective
control. They arenot23-fold higher, they areprecisely thesame number. SoIamnotsure Iknow
what thebasis forthese numbers areatall,orwhat theexperimental conditions are, which are
represented inthistable.
295. Would Ibecorrect inassuming thatthistable does notrepresent orreflect anywithdrawal
period whatsoever?
Chairman
296. CanIgive thefloor toDoctor Randell andthen Professor Epstein.
Dr.Randell (Codex)
297. Ifyoutake thevolume ofNutrition Paper 41which istheresidue studies ortheevaluation
oftheresidue studies done byJECFA atits32nd Session, youwillfindonpage 11inTable 6the
numbers thatareinthispiece ofpaper justhanded tous.They arethenumbers associated with the
study done at15-day withdrawal period. TheJECFA table, asIsaidearlier, puts these numbers in
context bygiving ranges ofthedatathatwere presented. Imight point outthatofallofthestudies,
andofallofthewithdrawal periods looked atbyJECFA andreported inthisparticular volume, Ithink
thisisabout thehighest setofnumbers thatyoucould select outofthisgroup ofdata. However, they
have tobeseen within theoverall context, Mr.Chairman, ofallofthestudies thatJECFA looked
atwhen itdiditsevaluation andthese data presented toustoday arenotnew data; they were data
thatwaspartofthepackage evaluated byJECFA.
Dr.Epstein (EC)
298. Iamgladtohave theopportunity ofexplaining thistable further. Ifyourefer toTable 2under
thecolumn marked "test" itsays 15D -thisisfor15days. Asyouknow when itcomes toimplants
intheUS, there areimplants relied ontwooccasions: oneonentry intothefeedlot andtheother
half-way through thefeedlot period, butthisisasample taken at15days andIshould simply saythat
Isimply picked thisoutofawide range ofNADAs which Ihave andthisisbynomeans atypical.
Forinstance Ihave another NADA forSynovex Hreferring totestosterone where levels infactwere
30-fold times. Soifyoureally would liketohave adetailed analysis ofalltheNADAs ofwhich I
have afairsample, Iamsureyoucould getthem allfrom Syntex, Upjohn andalltheother companies
anddocomparable simple calculations. This isbynomeans aselected sample, butjustoneIhappened
topick outandIcanassure youthatthere aremany others thatshow similar high ranges andtheone
onSynovex Hisanother example: 30-fold increase infat.
Dr.Ritter
299. Mr.Chairman, forgive me,Idonotreally want totakeupagreat dealmore time with this
residue issue butitisperhaps animportant one. IfIrefer tothesame page, page 11,ofthesame
document, theresidue document thatDr.Randell referred toamoment ago, weshould perhaps make
thisspecific table available toanyone sothatweareallspeaking from thesame piece ofpaper.WT/DS26/R/USA
Page 278
300. Table 5specifically refers toresidue results inmuscle, liver, kidney andfatfrom both treated
andcontrolled animals following a63-day withdrawal period after theadministration ofa24milligram
implant ofoestradiol 17betain12bulls weighing approximately 850lbs. Inthatparticular study and
reported hereinTable 5,thefatvalues bywayofexample arebarely twice what theyareinthecontrol -
not23times asisreported inTable 2thatDr.Epstein haspresented.
301. Ithink thepoint thatDr.Randell wasattempting tomake isavery important one. That is
thatthese values represented inTable 2,while theyareofcourse taken from datathathasbeen presented
insome context, they are,inmyview, atoneextreme. That isIrefer toTable 5,forexample, on
page 11,these values arebarely twice, andinfactwhen onelooks atthestatistical range ofthevalues
reported here, onemight even argue thatthere issome significant degree ofoverlap between thecontrol
andthetreated values.
302. Ihave ofcourse made thepoint because itrefers specifically tomysubmission with regard
toTable 3inthefootnote -Truhaut etal1985 states thatunlawful usecanresult inresidue levels from
300-fold inexcess ofestablished tolerance limits. Ihave ofcourse made thepoint, Mr.Chairman,
butIthink thismisrepresents somewhat thecontext oftheremark made bythese authors.
Chairman
303. Areyousaying Dr.Ritter thattaking atestafter 15days isunusual? That would never be
thenormal ordinary slaughter date from which itwould come intothefood chain?
Dr.Ritter
304. Thewithdrawal period ismore typically intherange of60days andwhat Iamsaying isthat
witha63-day withdrawal period reported hereinTable 5theresidue levels, utilizing withdrawal periods
which ismore consistent withtypical usepractice, thecomparison between thetreated andthecontrolled
isvery much narrower than a23-fold range asisreported here. Itisbarely twice.
Dr.Epstein (EC)
305. Ithink thesituation hasbeen forsome time theFDA allows aseparate implant half-way through
thefeedlot period. So63days infactwould represent thetime when theinitial pellet fortheinitial
implant istailing off. So15days isamuch clearer indication oflevels intheanimal than 63days
atwhich time levels have tailed offandfurthermore, asIsaidbefore, youhave second implants. So
at63days now youwould have theinitial residue from theinitial implant when theanimal enters the
feedlot, plusasecond round ofextra hormone added at50days. Soinfactyour 63-day period would
beequivalent to13days after thesecond implant.
Mr. Christoforou (EC)
306. Mr.Chairman, thetable thathasbeen circulated anddiscussed contains twoelements: one
istheonewearediscussing now, theother element wasthelevel inpre-pubertal boys andsince we
arenow alllooking attheJECFA Report inpage 15forpre-pubertal boys thevalue 6micrograms
per24hours adayisgiven. That iswhat alsowhat wecontest strongly because thisisbased ondata
of1974 andourcalculations areonthebasis oftheInstitute forResearch ofCancer which aremore
recent, butthisvalue isincorrect. There areanumber ofthings onthispage aswell which Ihope
willbeclarified inthiscase.WT/DS26/R/USA
Page 279
Dr.Lucier
307. Areyousaying thatthenumbers thatyoubelieve arecorrect are0.4totwomicrograms per
dayasopposed tothesix. Ibelieve thatthe0.4totwoprobably ismore inlinewith reality. Ibelieve
youarecorrect onthat.
Chairman
308. Could yourepeat thatagain andjustelaborate ontheimpact?
Dr.Lucier
309. Theimpact isifyouuseanumber -sayonemicrogram perdaythattheyoung boys orgirls
produce -andifyoucompare thatnumber totheamount thatisingested from 500grams ofbeefyou
willhave aratio ofabout 140above that. Inother words, theboys aremaking 140times more than
what they areingesting, justfrom their natural bodies. Ifyouuseanumber ofsix,then thatwillbe
sixtimes higher than that, andthey would bemaking 840times what they areingesting inthatmeat.
Soitmeans thatthesafety factor would change from 140to840. Isthatcorrect?
Mr. Christoforou (EC)
310. Ifthere isnoargument Icancontinue ..
Dr.McLean
311. CanIjustraise thepoint, Mr.Chairman, Ithink itmight beimportant -Iamnotabsolutely
sure thatthefigures inTable 6forthecontrols areactually correct. Isuspect thatthey areoutby
oneorder ofmagnitude alltheway through because wearetalking, forexample, ofmuscle at.84
whereas most oftheother control muscles inalloftheother tables aresomewhere around thesix,
seven, eight mark. Liver is.91whereas most oftheothers are8,10,16. Iwould draw ittoyour
attention, without being abletogoanyfurther, Isuspect thatthecontrol values inthatfirstbitofthe
table foroestradiol areinfactoutbyafactor often. They differ very significantly from allofthe
other controlled data andthatwould notbebeyond therealms ofpossibility.
Chairman
312. Ithink weshould goonwith remarks andquestions.
Mr. Christoforou (EC)
313. First thisinformation toDr.Arnold. Itseems thatthenumber ofsamples tested isvery close
to2,000,000 samples peryearforthehormones. Butthisisourownfigures. Forexample inGermany
205,000 checks were made forinhibitor substances fortheyear 1995. Thenumber isreally very high.
Fortheyear 1995 wechecked, asIsaid, 69,000 forblood forthenatural hormones. That shows that
thetotal number ofthechecks made fortheother hormones ismuch higher anditisconfirmed that
itisthisfigure thatwascited at200,000 samples forhormones iscorrect.
314. Thenext question relates tosince now hasbeen clarified what isthelevel ofwhat wewould
consider tobenormal physiological levels, especially inthearea ofthesensitive population thatis
pre-pubertal boys. Then wewould intervene intheareaofthreshold andwhether itisreally appropriate
inthatcase andindeed itseems intheJECFA Report, thatthe1,000 foldasitsaidhigher than what
itisinthenormal so-called, butisnow contested. Inthatcase byfixing theDAI andbysuggesting
andrecommending themaximum residue limit, inthiscase, they didnotrecommend because they
thought theJECFA Report may fallwithin thephysiological level, butthatisnotcorrect; thesecondWT/DS26/R/USA
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reason wasthatthey cannot control andcheck. Inthatcase, andalsothisislinked with theargument
made about theexisting physiological levels arealready dangerous; thatwassuggested byoneofthe
five experts here. Dr.Liehr would liketointervene inthatcase with respect tothreshold and
genotoxicity andhewillhave three questions toaskinthatrespect.
Dr.Liehr (EC)
315. Iwould liketostart outwith genotoxicity since thiswasalready earlier brought upbyseveral
oftheexperts because, asyouremember Mr.Chairman, itwassaidthatthegenotoxicity wastested
largely only invitro attoohigh doses andthatthedatawere irrelevant. When Istarted outthestudies
intheearly 80s,thegeneral consensus wasthatoestrogens, which hadbeen known atthattime already
tobecarcinogenic inseveral animal models, thatoestrogens were carcinogens byamechanism involving
solely receptor mediator pathways. Inother words thatoestrogens acted only thewayhormones act
asweunderstand it.
316. Istarted outwith these genotoxicity tests athigher doses because indeed, aspointed outby
Dr.Ritter, theaimwastoestablish whether anygenotoxicity could befound inthemeantime many
other laboratories andmany other researchers participated andcontributed inthisandthere areseveral
ormultiple classes ofgenotoxicity established foroestradiol -thenatural hormone. And justto...
[tape ends]
317. Single strand breaks, Dr.Arnold, hasbeen determined byusinvivo andnotinvitro asyou
asserted thismorning. Ithasbeen determined byDr.Nater andAbul HajinMinnesota incells in
culture, inbreast cancer cells inculture, 8-hydroxy radical DNA damage toguanine bases(?) hasbeen
established byusinvitro andinvivochromosomal abberations have been established byDr.KarlBarret
invitro andalsoinvivo,byDr.Jonathan Liwhom youcited thismorning Dr.Arnold. Furthermore,
DNA adductshavebeendeterminedandestablishedinvitrobyDr.Cavalieri,whocancertainlyelaborate
onthislater onthan, invivo.Wehave alsodetermined invivoDNA adducts bylipid pro-oxidation
products thataregenerated byoestrogen administration. Sothere isawhole variety ofdifferent types
ofDNA damage ofgenotoxicity established foroestrogen andIwould submit toyouMr.Chairman
thatthiswhole variety ofDNA damage constitutes what Dr.Lucier thismorning called compelling
evidence forgenotoxicity ofoestrogens. Now theJECFA report in1988 considered forgenotoxicity
tests mainly bacterial assays. This isanassay testcalled theAmes Test anditiswell known andwell
established thatoestrogens arenotmutagenic intheAmes test. This isabacterial testsystem where
many carcinogens have been tested formutagenic activity. Now when Dr.Ames introduced thistest
inthe70s, anumber ofcarcinogens were tested andahigh correlation between mutagenicity and
carcinogenicitywasestablished.Andsowhenoestrogensweretestedandwerefoundnottobemutagenic
itwasgenerally assumed there isnomutagenicity andthere isnogenotoxicity. However, aswehave
beentestingintheAmestestthousandsandthousandsofcompounds,carcinogens,ithasbeendetermined
thattheAmes testisactually avery poor predictor forcarcinogenic activity. Themutagenicity test
thatIreported toyouforoestrogen bymyself andbyother laboratories have allbeen done inmammalian
systems andIsubmit toyou, Mr.Chairman, thatthese mammalian genotoxicity tests aremuch more
important than theAmes testthathasbeen done inbacterial testsystems, wearequite different from
bacteria. Now there isanother point thatIwould liketobring upthatisvery important. This DNA
damage byitself might ormight notbehighly significant. These tests were done atelevated doses
andtheimpression wasgiven toyouthismorning thattesting genotoxicity atelevated doses washighly
unusual andwasaskewing ofthescientific evidence andMr.Chairman thisisnotthecase. Because
carcinogens areroutinely tested, initially atelevated doses andwhen carcinogenicity isfound thenpeople
testatlower andlower doses tofindoutwhether thisisstillthecase. Thesame istrueforgenotoxicity
initially asitistested athigher doses andthen later onlower andlower doses aretested. And these
tests have only begun, wehave determined genotoxicity atelevated doses, Iagree. They need tobe
tested atmuch lower doses todetermine ifatthelevels thatarefound inbeef, genotoxicity exists and
Isubmit toyouthattheparties thatdiscuss thiscasemight want tofund such studies because itisdifficult
toobtain funding forthistype ofwork.WT/DS26/R/USA
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318. Oneadditional point Iwould liketomake, wehave demonstrated earlier onorpostulated earlier
on,thatoestrogens arecarcinogens byacombined pathway -both their hormonal action which is
stimulating celldivision andgenotoxicity. Now thisisanimportant factthatoestrogens canhave both
these qualities orboth these characteristics, because acellwhich hasbeen damaged genetically can
thenatthesame time bestimulated todivide andthisrepresents afixation ofthemutation mechanism.
And these things need tobeexplored inthefuture further, butthepreliminary evidence exists that
such possibilities exist. Atthemoment allwehave isthegenotoxicity dataatelevated doses, yethow
canweestablish thatat"physiological levels" these carcinogens present noriskwhen oestrogens in
linewith many other carcinogens aregenotoxic atelevated doses andwehave notdetermined how
lowalevel issafe. SoIwould liketoendwith aquote. Dr.Arnold hasquoted Dr.Jonathan Liand
Iwould liketoendwith aquote from Dr.Karl Barrett, acolleague ofDr.Lucier attheNational Institute
ofHealthinNorthCarolinaandthatquotecomesfromtheJournalofEnvironmentalHealthPerspective's
review article ofDr.Barrett 'sinvolume 100, pages 9-20 1993. Dr.Barrett states that"Itcanbe
concluded thatthere issignificant evidence thatcertain oestrogens canalsocause genetic alterations
byamechanism notinvolving theclassical oestrogen receptor, [inother words, thephysiological
hormonal pathway] andthathormonal carcinogenesis ismost likely aresult oftheinterplay ofboth
genetic andepigenetic factors", exactly what Ihave been arguing. Sobased onthis, Iwould liketo
conclude thatitisdifficult toestablish thatlowdoses arenotgenotoxic when these experiments have
notbeen done.
Chairman
319. Thank youvery much. May IaskthePanel tocomment onwhat wassaidandtotelluswhether
they believe thisissomewhat far-fetched orwhether there isreason tobelieve thatthere isapotential
thatsuch effects could occur within theADI levels which have been defined. Dr.Ritter?
Dr.Ritter
320. Thank youMr.Chairman. Iwillattempt tobegin perhaps. Ithink Dr.Liehr makes thepoint
thatwhen referring tothestudies attheelevated concentrations andhequite correctly points outthat
these arehigh concentration compared towhat onemight expect interms ofexposure tofood residues.
Ithink heisquite correctly inorder thattherelevance ofthese high dose effects toactual human risk
remains tobeevaluated.
Chairman
321. Butheisnottalking about high doses now. Hesubmits thatfuture trials have totake them
down andthatthere isreason tobelieve thattheriskexists andnow Iwould liketoknow what your
reaction isonthepotential ofhaving theriskwithin theaccepted levels because thisseems tobea
new series oftrials.
Dr.Ritter
322. Iwould offer only twovery simplistic views, Mr.Chairman, inthatregard. Thefirstisto
refer tothearguments thatwere advanced thismorning byDr.Lucier, andthatisthatatthevery low
levels thatwearetalking about interms offood residue exposure, thecontribution ofthatresidue to
thealready existing biological load thatwenormally carry inourbodies, Ithink thattheexample that
Dr.Lucier used wasasifweareadding oneadditional molecule, inoneinstance hereferred toevery
28,000 thatarepresent. Idonotthink anybody canreasonably assure youthatthepresence ofthese
residues albeit atlowlevels constitutes zero risk, infactIamnoteven sure thatisafairquestion to
ask,scientifically itwould beimpossible toevertesttoacertainty. ButIthink thepoint thatDr.Lucier
attempted tomake isthatifthese lowlevels doconstitute arisk, they constitute ariskofamagnitude
which approaches zero. This istheorder ofthemagnitude ofriskthatwearetalking about forthese
very lowlevels andtheexample thathereferred toasIsayisthatitmay constitute oneadditionalWT/DS26/R/USA
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putative molecule inthepresence of28,000 others. Additionally though, Iwould remind thepanel
andinfactIthink theargument ismade inoneoftheCanadian submissions, thatparticularly inthe
caseofoestradiol, wehave what Ibelieve aresome very relevant human experience, never mind trying
tomodel from bacterial ormammalian genotoxic systems orfrom animal studies forthatmatter. We
have apopulation literally ofhundreds ofmillions ofwomen who have taken these compounds, as
Imentioned thismorning, inmany cases forperiods of25to35years. Inspite ofthatexposure study
ifyoulikewhich hasnow gone onforaperiod inexcess ofageneration andpopulations which would
certainly belarge enough todetect anincrease incancer riskifitwere associated with these compounds,
Ithink thatitisfairtosaythatwhile there hasbeen reports inliterature reporting orpurporting to
report such anincrease from time totime, thattheweight ofevidence with regard toincreased cancer
riskinassociation with theuseofsteroid oralcontraceptives isthattheydonotconstitute anincreased
risk. Thebesttestimony ofthatconclusion which Ihave justdrawn isthefactthattheir usecontinues
largely unabated, inspite ofthefactthatallofthiswork hasgone onnow for,I'llsay35years with
regard totheriskoftheuseoforalcontraceptives inwomen throughout theentire world. There has
certainly notbeen anyrestriction onprescribing thismedication forwomen, there certainly hasnot
been areduction inuse,infactifanything, andIdon'thave thenumbers infront ofme,butIthink
useingeneral hassomewhat increased over aperiod ofyears. And thisisanexperiment conducted
intheultimate species. Thank you
Chairman
323. Thank you, Dr.Arnold.
Dr.Arnold
324. Mr.Chairman,thismorningandobviouslythisafternoonIwillnotmakeanyattempttochallenge
theexcellent quality ofDr.Liehr 'swork, thisisnotmyproblem, heisdoing excellent work andhe
should continue doing thiswork because these areinteresting possible pathways heistrying toelucidate.
What myproblem wasthismorning andstillisthatIfeelthatthere arestilltoomany missing links.
Forexample, ifyouwould saycatechol oestrogens orthe16-hydroxyestrone whatever theybindinvivo
toDNA, OKthatwould bestrong evidence. Butinyour very excellent review article inAnnual Review
ofPharmacology andToxicology oflastyear, youwrite, yourself, youwrite thatyouwere unable
toconfirm these data invivo.You sayyouthatitcould notbedemonstrate invivo using thepost-
labelling techniques. Soforthemoment atleast, Ithink weexclude this. Iamalsonotatallopposing
theideatofurther investigate theprobable pathway ofcreating reactive oxygen species, butsince you
were referring tothework ofNater, Ihave seen there thatthey forexample sayinoneoftheir
publicationsinChemicalResearchandToxicology,whilethereactiveoxygentheoryinoestrogeninduced
DNA damage isareasonable one, there isnodirect evidence utilizing oestrogen quinones andthe
physiological conditions thatsupport thishypothesis andsoon.SoIseethere arestillsome missing
links orgaps intheevidence. Also ifIhave correctly understood Dr.Cavalieri 'swork, butwewill
later hear from himself, hehassynthesized these quinones andhehassynthesized with more orless
chemical methods thepossible adducts andthisisquite aninteresting piece ofinformation because
now wehave reference substances forfurther research. And Iseeinyour paper which youhave for
example published inChemical Research andToxicology lastyear, thatyouwere saying inconclusion
theadductsdescribedhereprovideinsightintothetypeofDNA damagepossiblewhencatecholoestrogen
quinones aregenerated invitro andinvivoandwillbeused instudies designed toelucidate thestructure
ofoestrogen adducts inbiological systems. Soagain Ihave thefeeling thatitisquite attractive and
ifIlook atthese substances with theeyes ofthechemist, Iwould immediately agree with chemical
methods youcanproduce allthese things. Thequestion tomeisdoes itoccur inliving cells, atwhat
concentrations, what aretheenzymes involved, what isthecompartmentalization ofthese enzymes,
etc.etc. Insome ofyour papers, Dr.Liehr, youwere talking about indirect DNA adducts, Iamnot
sure whether Ihave correctly understood these papers, butmight itbethatthese were adducts of
malondialdehyde resulting from stimulation oflipid peroxidation? What doyouthink ofthemechanism
ofstimulation oflipid peroxidation byoestrogens? Sothisisjustasmall number ofquestions IhaveWT/DS26/R/USA
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andIreiterate itisnotthepurpose ofmystatement tocriticize inanywaythequality ofDr.Liehr 's
excellent work, butIfeelthere aremany gaps intheevidence. Ican'texclude asascientist thatat
theendsomebody youwillshow thatoestrogens canactdirectly onthegene, nobody canexclude.
Forthemoment Idon'tseethattheevidence, theconvincing evidence. Thank you, Mr.Chairman.
Chairman
325. Dr.Lucier.
Dr.Lucier
326. Yesjustafewcomments onDr.Liehr 'scomments. Oneisontheability ofnon-genotoxic
materials tocause cancer. Wehave analyzed atanational toxicology programme 500bioassays and
approximately onethird ofthem thatturn outtobepositive arenegative inthesalmonella testfor
mutagenicity. Sothatstatement iscorrect. There aremany carcinogens inanimals systems thatdo
notcause mutations, sothisstatement iscorrect, andthatisabout one-third oftheones thatwehave
tested, the500. Theother points thatIwant tomake, onerelates tothereceptor mediated response
versus thegenotoxic response. Thereceptor mediated response being theoneinwhich anoestrogen
binds theoestrogen receptor andstimulates thegrowth, thedivision ofcells thatalready contain a
mutation. There isagreat deal ofevidence inthescientific literature thatsupports thatasacritical
event intheability ofhormones tocause cancer. SoIthink that, andDr.Liehr saysthatthatisclearly
animportant aspect ofhormonal carcinogenesis. Inaddition heisproposing thatgenotoxic events
may alsobefacilitating thecarcinogenic process ofhormones. Iwould saytheevidence, although
notweak isnotasstrong inthatcase asitistothereceptor mediated pathway. That does notmean
thatitisnotoccurring andnotplaying arole, butisnotascompelling atthispoint intime asthe
evidence isforthereceptor mediated pathways. Butifsayifitisanimportant event, Ithink Dr.Ritter
gave myexample, 28,000 molecules ofoestrogen being naturally produced tothebody forevery one
thatwasintroduced bymeat containing thegrowth promoting agents. Once thebody sees those
molecules, itdoesn 'tdifferentiate, itisn'tthatthere istheonefrom thegrowth promoted animals,
ittreats all28,001 asidentical sothechance ofthatonemolecule being converted toagenotoxic molecule
isequal tothatofanyother molecule ofoestrogen thatthebody produced. Soitjustgetsthrown into
themixandIthink thatmay beanimportant point toconsider. Soeven though itwould beunusual
foranevent tooccur inthatonemolecule, itispossible, andwesaidearlier wecan'truleoutthat
notoccurring, even though itwouldn 'tcontribute much because thenumber ofmolecules aresosmall
relative towhat isnaturally occurring. Theother point with breast cancer andoralcontraceptives that
wasmade, there hasbeen anumber ofstudies looking atbreast cancer, Idon'tknow howmany maybe
15orsoandsome ofthem show anincrease, some ofthem don'tshow anincrease. Ifyouaddthem
allupyoudon'tknow what tomake ofit.Ifyouaddthem allupyougetabout a15to20percent
increase inbreast cancer inwomen who useoralcontraceptives butthisnotstatistically significant.
Sothatmay justbeoccurring bychance. Epidemiology studies arevery insensitive inpicking upthe
changes intumour incidence especially when thetumour incidence occurs invery high frequency.
Since oneoutoftenwomen getbreast cancer, atenpercentincrease orfivepercentincrease ortwoper
cent increase issignificant interms ofthenumber ofcases, butthiscould never bepicked upby
epidemiologystudies,theyaresimplynotsensitiveenough.Itisnotlikethecasewithdiethylstilboestrol,
wehadavery raretumour soitwasvery easy topick itup.Thevaginal adenocarcinoma infemale
offspring who hadbeen exposed atthatageandduring their gestations, sothatgenerally occurred in
lowfrequency andwasvery easy topick up.Changes andincidences ofbreast cancer arevery very
hard topick upfrom epidemiology studies.WT/DS26/R/USA
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Chairman
327. Thank youvery much. Wewould propose maybe weclose thedebate atthispoint andwe
would briefly have abreak maybe for10,15minutes. Iwasinformed thatthecoffee barcloses at
5:30, so...youmake itandthenwewillcontinue perhaps until 7:00 which istheusual time. ........
Well, during theUruguay Round itwaseven later! Buthow shall weproceed, would youliketo
comment onthisquestion?
Mr. Christoforou (EC)
328. Somehow Ithink Dr.Liehr would liketomake acomment andthen Dr.Cavalieri and
Dr.Epstein would liketointervene onthisparticular point.
Chairman
329. OK, sowehave three interventions briefly. Thank you.
Dr.Liehr (EC)
330. First ofallMr.Chairman, considering thecomments ofDr.Ritter, yousaidthatyouquoted
thiscase ofoneadditional molecule over 28,000 andthatthisconstitutes avery lowriskandthatthe
riskisapproaching zero atthese lowlevels. Iwould liketosubmit toyouMr.Chairman thisispure
speculation, wehave nogenotoxicity dataatlowdoses. This isexactly thepoint thatIammaking.
Theexperts make statements thatthey cannot back upwith data, anduntil wehave dataIwould like
tofirst seethiscarcinogen oestrogen tested fully before large populations arebeing exposed tothis.
Secondly, Iagree concerning Dr.Arnold, Iagree with youthatatthemoment thisisaninteresting
hypothesis andIhave never labelled itmore than ahypothesis andIalsoagree with youthatmany
pieces aremissing butthisisexactly ourpoint. Ithink thatinfaceofasubstance which where there
aremany troubling aspects, weshould proceed carefully andweshould proceed inavery measured
waybefore westorm inandpermit theexposure ofwide populations until these troubling questions
have been clarified. Concerning theindirect DNA adducts andthestimulation oflipid peroxidation,
Mr. Chairman isoneaspect, anon-genotoxic aspect ofaction offreeradicals incells induced by
oestrogen metabolites. Thestimulation oflipid peroxidation nevertheless isvery important because
itre-routesoraltersmetabolism,includingmetabolismofoestrogen,andpermitstheformationofreactive
metabolites atmuch much higher levels. Sothey areprocesses thataresetintomotion andthen feed
onthemselves which have really insufficiently been examined andwehave really only started toscratch
atthesurface. Iagree with youbutnevertheless they aretroubling aspects thatreally need tobe
examined inmore detail. Concerning Dr.Lucier 'scomments, thatinthedebate ofreceptor mediated
responses versus genotoxic responses, thegenotoxic hypothesis maynotbeascompelling atthemoment,
again intheabsence ofdataIdon'tknow whether wecanmake such ajudgement orstatement atthe
moment. Itispossible thatgenotoxicity iselicited only intherelatively rareinstances, butlet'splease
notforget atthispoint wearedealing alsowith ahormone andsowhen ahormone stimulates cell
proliferation andamutation getsfixed, Mr.Chairman, Iagree with Dr.Lucier thatbecause webreath
oxygen andbecause weareexposed toawide range ofgenotoxic substances thisisaprocess thatis
occurring onadaily basis within allofus.However, andDr.Lucier made anargument thatthese
oestrogens would provide anincremental increase thatissosmall thatitisnegligible however, since
oestrogens arealsohormones, thehormonal stimulation ofcelldivision thenmaywellfixthemutation
andinduce tumours. Soatthemoment intheabsence ofmore data Idon'tseehow wecanarrive
atasafepassage foroestrogens.
Dr.Cavalieri (EC)
331. Iwould liketocomment inanswering Dr.Arnold that, Ithank himforhaving acknowledged
justthetipoftheiceberg ofalloftheproblem. Sopractically what hehasrecognized isthattheseWT/DS26/R/USA
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metabolites oftheoestrogen canreact with partofthenucleic acidandthishasbeen very vital increating
thestandard compounds thatnow wehave demonstrated invitro andinvivo,asyoucanseeinmy
report thatIhave submitted toyou. Thebasic principle, Dr.Arnold, onwhich thatitisvery difficult
todemonstrate thegenotoxicity ofoestrogens hasbeen there because wedidn'tknow what achemical
carcinogen is.That hasbeen thebigproblem andweknow now what achemical carcinogen issince
twoyears andthisisthebasic paper thatnow hasbeen published in1995 intheProceedings ofthe
National Academy ofScience. Achemical carcinogen isacompound, andwehave demonstrated that
forthepolycyclical aromatic hydrocarbon thatishuge class ofcarcinogen andcanbeextended to
compounds likeaflatoxin etc., isacompound thatproduces inexcess what wecallapurinicides. It
means thatittakes outoftheDNA twobases. Oneiscalled adenine andtheother oneiscalled guanine
andthisprocess issorichinthesense thatitissohigh compared tothenormal depurination thatwe
have everyday. You know thatacarcinogen becomes carcinogenic, itinitiates cancer, when these
processes ofrepair ofthese apurinicides isnotanymore longer possible. Byadding thisbasic knowledge
onaromatic hydra-carbon, wehave found outthesame formation ofapurinicide byaspecific metabolite
oftheoestrogen thatiscalled 4-catechol oestrogen quinone. These they bind totheDNA forming
anamount ofapurinicide. These wehave demonstrated thatinvitro andyoucanseefrom thereport
andinvivobyinjecting thecatechol onthemammary gland oftheratandfinding outthiskind ofatom.
Wethink asDr.Lucier hasmentioned inthemorning thattheadducts thattheyform apurinicide inside
theyarethemostmutagenicadducts,thattheyareconsistentwiththedefinitionofachemicalcarcinogen.
This istheinitiating event iscancer andIthink andInotonly think, Iamsure because ofuniqueness
ofthese phenomena offorming these depurinating carbons thatoestrogen they aretheorigin ofbreast
cancer asDr.Liehr andother they already have very strong compelling evidence forprostrate cancer
andforother human cancers. Therefore, Ireally think themajor problem thatwehave inourlifetime
isthatwehave theoestrogen. When theoestrogens areplaced correctly, youknow inthenormal
human being they areplaced correctly, they arevery well controlled, they areallbeneficial, butif
something goes wrong inthecontrol because wehave allprotective mechanisms inorder nottogo
onthewrong place. Butifthisprotective mechanism forsome orforsome reasons orforcomplex
theydon'twork, these oestrogens canbecome chemical carcinogens andinitiating theseries ofevents
thatlead tocancer. What inhormonal carcinogen isbeing studied andwhat thedata thathere are
based thesame data asyoucallit,ADI etc., isbased only onthehormonal effect ofthereceptor
mediated process. Theinitiating defect canoccur inanon-protected person, inaperson very likely
thatwhen heis30hasbreast cancer because thisprotective mechanism they don'twork, andthiscan
come with avery minute amount ofoestrogen. You know because theprotective mechanism they
arenotthere toimpede thatthewrong pathway occurs. This wrong pathway isthemetabolism of
oestradiol tocatechol oestrogens. These twoexist, twokinds ofcatechol oestrogens. Themost abundant
ingeneral iscalled 2-catechol oestrogen isnotdangerous, itdoesn 'tproduce cancer. Theother one
thatiscalled 4-catechol oestrogen ifoxidized further toquinone caninduce cancer andthatisthething
thatwehave totakeintoaccount. Unfortunately, orfortunately, thisresearch isonthemaking now
butisgoing tobeanymoment outandthereason thatweworked onadifferent paradigm ofother
peoplecreatestheproblemincommunicatingheretodayandcommunicatingingeneralwiththescientific
community. Butyouknow, Ithink thatallhuman endeavours work ondifferent paradigm andata
certain moment theonethatthey count they have tobeconsidered. Thank youforthepossibility.
Chairman
332. Thank youvery much, Professor Epstein please.
Dr.Epstein (EC)
333. Apart from thefascinating technical details ofthegenotoxicity, Ithink thatmammalian
genotoxicity datawhich wehave been talking about forthelasthalfhour, Ithink thattheimportance
is,really relates tothefundamental factthatintheFAO/WHO andJECFA documents thebasis for
classification ofoestradiol asepigenetic waslargely derived onthenegative Ames test,negative bacterial
tester andbecause ofthisADIs, theconcept ofADI andthresholds crept into thewhole oftheWT/DS26/R/USA
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documentation because youcanhave thresholds forepigenetic carcinogens. Now Iwould submit that
theevidence forthatistosaytheleast shaky andit'shigh time thattheFAO/WHO documents reflected
thegrowing body ofdataonmammalian genotoxicity. Even atthetime oftheJECFA document, there
wasabody ofdataonthiswhich wasinnowayreflected, Ithink that'sthefirstpoint Iwould make.
Secondly, letmemention three ofthemost potent known human carcinogens: benzene, asbestos and
arsenic, foralong time these were classified asepigenetic because they were negative intheAmes
test, butsubsequent work over thelastdecade orsohasshown themammalian genotoxins. Infact
inoneofthem, aDr.Legator, acolleague ofDr.Liehr hastitrated thelevels with mammalian
genotoxicity tests andshown genotoxic effects atthelowest level possible, 40parts perB,which isn't
very much higher than when yougotoagarage andfillyour carwith gasoline andstand next toit
andsniff it,you'llgetit.Soinfact, intheoneortwoinstances where genotoxicity hasbeen titrated
down, wefindnoeffect levels similarly towhat weknow from ourvastknowledge ofradiation biology
onlinear dose responses. Over andabove that, inview ofthefactthatthenegative Ames testwas
used toestablish theconcept ofthresholds, Ishould point outthatthere arevarious other issues that
have tobetaken intoaccount when youwant toconsider setting thresholds. One isthequestion in
thiscontextoftheinterrelationshipofthefactthatyougivetwodifferentanabolicstogether,twodifferent
hormones together, likeoestrogen andprogesterone which weknow have additive orsynergistic effects.
Itignores thesynergism between thehormones andbetween pesticide residues, which some ofwhich
arecarcinogenic andsome ofwhich oestrogenic. Italsoignores thehigh factofthesensitivity of
children. Nowhere intheJECFA document isthere anyreference tothehigh sensitivity ofinfants
andchildren. Furthermore, tosaythatacompound hasathreshold itputstheonus onthose thatsay
ittoproduce bioassay datatoconfirm that. Intheabsence ofbioassay data youcan'tsaythere isa
threshold ifyouhaven 'ttitrated itdown andfound anoeffect level. Letmemove very briefly on
totwoother issues, namely, thedifferentiation between thehormonal andtheproliferate effects of
oestrogens andthecarcinogenic effect. Agreat dealhasbeen made ofthefactthatthecarcinogenic
effects oftheoestradiol isdirectly related tothehormonal things. Iwould suggest thatweshould re-
think that. Forinstance, oestrogens increase theincidence ofsalivary cancer, thyroid cancer andmelanin
cells cancer ormelanotic cells inhumans andinfactother oestrogen receptors, Idon'tknow. Are
these tissues reproductive? Certainly not. Arethey proliferative? No. Sothewhole concept of
hormonal, ofcarcinogenesis being duetohormonal proliferative effect needs very very careful
re-examination. Coming back totheoralcontraceptive, Iwould agree withDr.Lucier thatitisdifficult
todoepidemiological studies when youaredealing with arelatively common cancer. However, I
should point outtohim, thatintheOctober issue ofContraception, there wasananalysis ofevery
single study done onthecarcinogenic effects ofcontraceptives, oralcontraceptives, inrelation tobreast
cancer. Over 60studies were analyzed andmetoanalysis anddetail every single possible permutation
andcombination wasstudied. And with duerespect andcontrary toDr.Lucier, what wasfound was
asfollows: thatwhen youfocus onadolescents orwomen starting totakeoralcontraceptives at15,
16,17which isnotuncommon now, andtaking itforprolonged periods oftimes, there wasahighly
significant increase inrates ofbreast cancer, avery highly significant increase, thisisthelargest
compilation ofstudies everanalyzed. Letmeendupbymaking onecomment onreproductive cancers.
Dr.McLean thismorning made some comment totheeffect thatthere hasn'tbeen anyincrease in
reproductive cancers. With duerespect Sir,thisisquite contrary tothefact. Let'stake first what
testicular cancer. Testicular cancer intheUnited States based onNational Cancer Institute andSEER
datashow somewhere intheregion ofabout 150percentexcess thanagestandardized datafrom 1950
tonow, andwhen youconcentrate onanagegroup of28to35,thefigure comes 280percent, nearly
athreefold increase intesticular cancer inthatperiod oftime, number one. Number two, breast cancer.
Tosuggest thattheincrease inbreast cancer rateisduetoimproved detection mammography islargely
incorrect andtheevidence forthisisasfollows: intheUnited Kingdom, large scale mammography
hasonly relatively recently started. We'veseen thesame rateofincrease intheUnited Kingdom as
weseeintheUnited States. IntheUnited States large scale mammograph started inabout 1981 and
82.Ifyoulook atthedatafrom 1950 to1981, youfindthattherateofincrease inbreast cancer is
perhaps thesame oralittle bitgreater then thatfrom 1982 onwards. Asfarasprostate cancer, so
inother words, tosuggest thatthere hasn'tbeen anymajor increase inreproductive cancers isentirely
contrary toanestablished database from theNational Cancer Institute andSurveillance EpidemiologyWT/DS26/R/USA
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andEndResult Programme. Asfarasprostrate isconcerned, there isnoquestion thatthere hasbeen
asignificant increase inprostrate cancer. However, Iwould agree thatacertain amount ofthisisdue
toover-diagnosis andparticularly with thePSA testandother things, soonecannot exclude thatthere
isanelement intheincreased incidence ofprostrate cancer duetoover-detection. However, there
isalsoanincrease inmortality rateandmortality ratecan'tbeanexpression ofimproved early diagnosis.
Sothepoints thathave been made, thatthere arenodatawhatsoever relating oestrogens andhuman
cancer,exogenousoestrogensandhumancancer,iscontrarytoaverysubstantialbodyofepidemiological
data, which inthetime available tomeandI'vehadtosummarize terribly briefly andterribly hardly.
Thank youSir.
Chairman
334. Thank youvery much. Well Ithink wewillbriefly break here soyoucanstillmake itand
wewould inform thecafeteria thatthere willbeaqueue. Could weresume at5:45, 6:00 please,
themeeting isadjourned.
Chairman
335. Over toDr.Lucier tocomment briefly onwhat wassaidbefore thebreak. I'djustliketo
indicate theintention ofthePanel. Weintend toconclude with thepartoftheEuropean Communities
asaresponse totheUnited States forthissession, because tomorrow wecannot have ameeting in
themorning, because theexperts arenotavailable duetoother commitments. ButIwould liketo
assure thatwestart at2:00 with thestatements andquestions bytheCanadian delegation sothatwe
have enough time forthisround andthen thefinal comments bytheECandthen theexperts. SoI
would liketourge theexperts ontheECdelegation tohave inmind thatweshould finish bytonight
with their presentations which isnow being scheduled inthisfirstblock here andIhope thiscanbe
done by7:00-7:15 soplease keep thisinmind. Okay thank you. Dr.Lucier, canIgiveyouthefloor
inresponse tothestatements bytheECexperts before thebreak.
Dr.Lucier
336. Thank you, Mr.Chairman. Ijustwanted tomake afewcomments regarding Dr.Epstein 's
presentation. One regarding thepresence oftheoestrogen receptor invarious tissues ofthebody.
Hehadmade thepoint thatthere were oestrogen caused tumours innumerous sites. Itisalsotrue
thatoestrogen receptors arefound inevery tissue ofthebody, sothere isnoreason tothink that
oestrogen action isn'toccurring through anormal receptor mediated pathway. That doesn 'tmean
genotoxic events aren'talsooccurring, butit'sclear thatclassical receptor mediated events would be
occurring aswell. Theother point relates totheincreased incidences ofsome tumours occurring in
various countries intheworld. Regarding testicular cancer, Ithink thatit'sprobably truethatthere
isarealincrease intesticular cancer andthisincrease appears tobepredominant inyoung men which
isespecially disturbing. Why thisisoccurring, noonereally knows, butasapublic health person
itisvery disturbing. There isnoreason however tothink thatthishastobeassociated with oestrogen,
there arealotofother kinds ofthings thatcould becausing that, sothere isnotadirect linktoit,
although thatincrease isinfactarealone. Regarding breast cancer, thatisalsolikely increasing.
However, onecan'tnecessarily attribute thattoexposure toexogenous external oestrogens. There
areseveral studies intheliterature which suggest thatordemonstrate thatexposure togenotoxic agents
during thetime thatawoman isateenager causes adramatic increase inbreast cancer. This wasshown
inatomicbombsurvivorsfromJapan.Thosewomenwhosurvivedtheatomicbomb,whowereteenagers
atthetime, hadvery elevated riskofbreast cancer later inlife, women who survived who were in
their 20sor30shadnoincrease inriskandthere isvery plausible biology forthiswhich Iwon'tgo
into. It'salsobeen shown now inthree publications thatwomen whostart smoking asteenagers have
ahigher increase inbreast cancer later inlife, whereas ifthey start smoking later, they donot. So
there arealotofreasons why exposure togenotoxic agents could beaccounting fortheriseinbreast
cancer rates thatareseen throughout theworld. Soweneed tobecognisant ofother factors andnotWT/DS26/R/USA
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justblame theexogenous oestrogens foreverything. Regarding theoralcontraceptive issue, Ithink
Dr.Epstein isprobably right thatthere would beanincrease inbreast cancer riskforwomen who
start taking thepillvery young because thatextends theperiod oftime inwhich they areexposed to
high levels ofoestrogen andthisisaknown riskfactor forbreast cancer. Thesame exposures alittle
bitlater probably wouldn 'thave anincrease, sowhen youaverage everything outtogether youdon't
getastatistically significant increase inbreast cancer from oralcontraceptives. Idon'tthink thatanyone
ischallenging thefactthatoestrogens arecarcinogenic, IARC isclassified conjugated oestrogens as
aknown human carcinogen, they have classified oralcontraceptives asan...[tape ends]
...carcinogen based onanincrease ofliver cancer notontheincrease inbreast cancer. They have
alsoclassified tamoxifen asaknown human carcinogen because ofitsoestrogenic activity intheuterus.
Idon'tthink thatanyone isdisputing thatfactthatoestrogens docause cancer.
Chairman
337. Thank you.
Dr.McLean
338. Justbywayofexplanation, Ididnotmean tomislead andIcanseehow thatappeared. Iwas
talking inthecontext oftumours relating totheuseofhormones asgrowth promotants, andIjustmake
oneobservation thattheincrease intumours occurs inthose countries where theuseofgrowth promotant
isnotwidespread andtheincrease began before thehormonal growth promotants received widespread
use. Butitwasinthecontext ofthehormonal growth promotants rather than anincrease incancer
persethat Imeant toconvey, andifImisled then Iapologise.
Chairman
339. Thank you. Mr.Christoforou canIcome back toyou. OhDr.Arnold, youwanted tospeak
aswell, sorry.
Dr.Arnold
340. Justashort remark, Mr.Chairman. Dr.Liehr andDr.Cavalieri have proposed interesting
mechanisms how oestrogens could induce cancer bygenotoxic mechanisms. ThePanel should know
thatother well-known people working with other models came todifferent views. Forexample, I
mentioned Dr.Schulte-Hermann who isawell-known expert inrodent liver carcinogenesis. Hesays
forthehormones toexert their action, there must besome pre-neoplastic lesions already present in
theanimals, andalthough hisevidence isalsonotcomplete, hehasquite alotofdatasupporting his
ideas. Heforexample hasshown thattheincidence oftumours after oestrogen treatment depends on
theageoftheanimals atthetimetheystartthetreatment. Andhehasdeveloped experimental techniques
toreduce thenumber ofpre-neoplastic lesions byrestricting thediet, andhecould show thatunder
these conditions theincidence oftumour formation waslower when hestarted with oldanimals he
keptontherestricted dietandthenadministered oestrogens. Sothere issome evidence inother models
thatperhaps there isnoneed thatoestrogens arecomplete carcinogens butthefirst stepcould bean
unknown initiation, theformation ofpre-neoplastic lesions andtheninaddition thehormone promotes
thefurther development. Thank you.
Chairman
341. Thank youvery much. Canwegotoyour next comment andquestion?WT/DS26/R/USA
Page 289
Mr. Christoforou (EC)
342. Wehave been addressing until now, thepotential atleast genotoxic effects ofthenatural
hormones. Butthree ofthehormones indispute inthiscase also aresynthetic. They don'toccur
naturally bytheother animals. Sowewould likealsotoaddress thepotential genotoxic andcarcinogenic
effects ofthesynthetic hormones. Iwould give thefloor with your permission toDr.Metzler who
hasproduced apaper andwho willafter thisshort presentation conclude byframing aquestion tothe
scientists. Thank you.
Dr.Metzler (EC)
343. Thank youMr. Chairman. Although thesynthetic oestrogens orIwould rather callthem
xenobiotic oestrogens andandrogens, trenbolone andzeranol have been farlessthoroughly studied
interms oftheir genotoxicity, they have most been subject toroutine toxicological testing which is
difficult topick upthegenotoxicity ofhormonal carcinogens. Nevertheless, there issome evidence
thatthese xenobiotic hormones alsoaregenotoxic andI'djustbriefly summarize theevidence. There
aredatafrom three different laboratories showing thatthere isDNA binding atalowbutsignificant
amount ordegree with acovalent index ofabout 10.There isinduction ofchromosomal damage in
mammalian cells bytrenbolone andother bythenon-hormonally active isomer diethyl trenbolone and
there isevidence forcelltransformation invitro indifferent laboratories. Forzeranol there isalso
evidence forDNA binding with asimilar covalent binding index andforclosely related compounds,
zeralenone there isrecent evidence ofDNA adducts invivoinmice indifferent organs. Soalthough
there arenotmany studies available, thefewstudies indicate thatthere isalsogenotoxic potential for
these xenobiotic hormones andIwould liketofinish thisbrief presentation byaddressing aquestion
toDr.Lucier. Dr.Lucier hasindicated thatforthenatural hormones itdoes notmake much sense
orhecalled itirrelevant todiscriminate between genotoxic andnon-genotoxic compounds. How would
youview thisissue forthexenobiotic compounds?
Dr.Lucier
344. Before Ianswer, youhave toanswer oneofmine before Ianswer your question Manfred.
What is,attheriskofgetting tootechnical, what istheevidence fortheDNA adduct formation for
zeralenone orzeranol? Isthissimple binding ofradioactivity toaDNA fraction orhasaltered nucleoside
isolated andcharacterized?
Dr.Metzler (EC)
345. Forzeralenone orthemicrotoxin, orthemicro-oestrogen Ishould probably say,there hasbeen
arecent study with thepost-labelling assay indicating invivo inmice both inthekidney andinthe
liver alevel ofadducts, ofvarious adducts asshown bythepost-labelling assay atthelevel ofabout
1,000 nucleitides, modified nucleitides per10(?) nucleitides. Soit'ssuch aspining ofdiscrete adducts
thatshown forzeralenone. Nosuch study hasbeen done forzeranol tomyknowledge, forthegrowth
promotant.
Dr.Lucier
346. One other quick question. Isitpossible thatP-30 post-labelling which doesn 'tcharacterize
anindividual adduct, isitpossible thatthatisjustarising because achange inself-proliferation rates
because when acelldivides, ofcourse, itloses itsDNA adduct, orifitdoesn 'tdivide itkeeps its
adducts. Soameasurement oftheendogenously occurring adducts could leadtoanalteration inthe
apparent number butnotberelated tothezeranol itself. Inother words, sothatadduct hasn'tbeen
characterized it'sjustbeen seen asaspot onaTLC plate?WT/DS26/R/USA
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Dr.Metzler (EC)
347. Well these adducts have been seen asspots butthere were controls onuntreated animals of
course andthere were also species differences likeinrats. None ofthese adducts were seen with
zeralenone, they were only seen inmice. Sothere isaspecies difference which alsoisinfavour of
realadduct.
Dr.Lucier
348. Sorry Mr.Chairman forthatdigression, butIneeded thatinformation toanswer Dr.Metzler 's
question. Theadducts thatmayarise from synthetic materials arelikely different andofmore concern
thantheones, interms ofariskassessment, thantheones thatarise from thenaturally-occurring ones,
because wealready know thatthere isagiven body burden ofthenaturally-occurring oestrogens.
Sowhether DNA adduct formation isoccurring orwhether itscellreplication youarejustadding a
very small amount toanexisting burden, whether itbegenotoxic orwhether itbenon-genotoxic so
thatmechanism isirrelevant asManfred said forthenaturally-occurring oestrogens. That isnot
necessarily trueforthesynthetic materials andinfactanadduct orDNA damage hasbeen characterized
andidentified thismay bestarting outfrom ground zero. Wehave nokind ofdamage likethatis
currently inthebody, sothere theissue ofathreshold versus linear models becomes much more
important interms ofahazard identification. Sothatinfactanadduct hasbeen characterized and
Iwould probably sayatthispoint thedataissuggestive ofthat. That aDNA adduct isoccurring that's
related tothezeranol itself orzeralenone, butnotconvincing because thatadduct hasnotbeen identified
interms ofthealtered nucleoside. Inother words itcould bejustbealtering theoccurrence of
naturally-occurring adducts isapossibility. Although thedatetheDr.Metzler hasbriefly presented
issuggestive thatsuch anadduct independent ofthenaturally-occurring adducts isinfactbeing formed.
Chairman
349. Thank youvery much.
Mr. Christoforou (EC)
350. Mr.Chairman, Ithink wehave reviewed thepotential totoxic andcarcinogenic effects ofnow
allthesubstances inquestion. Thenext question isrelated totheresponse thedistinguished experts
gave tothequestion whether theJECFA report of1987 and1988 istaken intoaccount thistype of
evidence which youhave been hearing thisafternoon. Asyoualready noticed, thisevidence hasstarted
appearing quite late, Iwould rather putitroughly, mid1980s anditisgrowing very fastinthisarea.
Thescientists have replied thatallthese aspects ofgenotoxicity, synergistic effect, long-term exposure
tothese substances have indeed been taken intoaccount intheJECFA report. Butthere were very
strong differences inmyviews. Forexample Dr.Ritter would saythatthey have notaddressed
mutagenicity forallhormones, they have notaddressed definitive studies forgenotoxicity or
carcinogenicity ofcombinations although thisisthepreferred method foruse. Theother scientist,
Dr.Arnold forexample, would saythatgenotoxicity andcarcinogenicity have been examined and
Dr.André would saythatsynergistic effects have notbeen taken intoaccount. Iwould appreciate
ifallthescientists could summarize once again whether thissynergistic effect, thelong-term exposure
andthepotential effects orincreased effect from theuseofcombinations have indeed been taken into
account intheJECFA report. And ifthey have notbeen taken intoeffect what istheconsequences
ofthat? Dowehave toreview thatreport now inview ofthatevidence? Dr.Ritter hassaidthere
isnocompelling evidence thatweneed toreview ittoday. Inhiswritten reply hesaidtheweight
ofevidence would notappear tosuggest thatthere isno,thatthey aregenotoxic andcarcinogenic.
Sothere aresome variations andslight nuances intheexpression. SoIwould appreciate ifwecan
come back onthisissue byhearing thefiveexperts onthis.WT/DS26/R/USA
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Chairman
351. Didyougetthequestion andcould you, who would liketostart? Dr.Ritter.
Dr.Ritter
352. ThankyouMr.Chairman.InthewrittencommentswhichIofferedwithregardtothexenobiotic
hormones, Ithink thatitwillbeevident toallthatMGA forexample, hasnotbeen subjected toaJECFA
evaluation. AsIindicated earlier onintheday,myassessments were drawn primarily, letmegofurther,
they were drawn entirely from information which waspublished intheopen literature andobviously
dominated byJECFA reports andother ones. Itisclear thatMGA hasnotbeen subjected tosuch
anevaluation andconsequently, Ihave noinformation other than ofaproprietary nature which Idid
notuse,from these evaluations tooffer anypublic opinion onMGA. Insofarasthecarcinogenicity
testing ofthecombinations areconcerned itwillalsobeevident toanyreader oftheJECFA reports,
thattheassessmentsandconclusionsofferedthereinarebasedonthesinglecompoundthatwereevaluated
bytheCommittee anditwasinthatcontext thatIoffered those views. When Iconcluded thatthere
isnocompelling evidence tosuggest thatthese compounds should beimmediately re-evaluated, itwas
onthebasis again ofmyunderstanding notonly ofthehistorical reviews which have been carried out
byJECFAandotherorganizations,butindeedhowmuchmorerecentreviews,includingthosepublished
asaresult oftheEuropean Conference onGrowth Promotion inlate1995, early 1996, andindeed
onthebasis ofthestatements presented byourcolleagues heretoday, Dr.Liehr, Dr.Metzler andothers.
Ithink asDr.Liehr indicated, thework which hehascarried outrecently thework which others made
outrecently, thework which others have presented recently, suggest thatthere arecircumstances under
which adverse effects may bedemonstrated inassociation with themultitude ofthese compounds.
ButIthink thescientists inmyview have quite correctly noted thattheir relevance tothedoses atwhich
thisdebate focuses isunknown, andI'msimply suggesting thatthatisnotinmyview necessarily a
reason toargue thatitshould therefore beimmediately redone. Inother words, letmeputitanother
way, ifMr.Chairman, anorganization likeJECFA orindeed anational regulatory authority, were
toimmediately conclude thatevery evaluation thatithadcarried outshould always besubject toan
immediate re-evaluation atanytime thatareport indicating thatthere arecircumstances under which
anadverse condition canbedemonstrated with aparticular compound, thenIwould respectfully submit
wewillalways bere-evaluating everything thatwehadever done. Because work goes on,notonly
onthese hormones butindeed onevery substance thatwecanthink of.Butasscientists, Ithink we
arecompelled tolook atthetotality oftheevidence asit'savailable. Ithink thattotality ofevidence,
certainly recognizing theinformation thathasbeen presented here today aswell asthehistorical
information, suggest tomethattheassessments thatwere provided thencontinue toassure areasonable
degree ofsafety toconsumers ofthese commodities. AsIsaythisisnotonly myopinion butinfact
itwastheconclusion ofaconference held very recently andsponsored bytheEuropean Commission
onexactly thisissue. That these compound when used inaccordance with accepted practice, Ishould
perhaps useaphrase thatwehave allbeen using, good veterinary practice, good practice intheuse
ofveterinary drugs, whichever acronym youwould liketouse. Ithink thishasbeen theconsensus
view ofthisConference ifyoulike. Iusetheword consensus because clearly inanyscientific endeavour
ofthissortonecanquite properly andrealistically anticipate thatthere willbeadivergence ofopinion.
Thenature ofscientific interpretation isthatlegitimate bona fideknowledgeable scientists may reach
different conclusions from thesame setofdata. ButIthink theconsensus opinion ofthatConference
Mr.Chairman, wasthattheweight ofevidence used then continues toprevail now, andthatthe
assessments andconclusions drawn thenarestillconsistent with theavailable information now. Ithink
asDr.Arnold hasindicated, thisinnowayisintended tocastanydoubt orvalidity onthework which
others such asDr.Liehr have performed. Andcertainly thissortofwork should continue, andIdon't
think anybody canassure youthatinsome time down theroad, thatitwillnotrequire ordictate that
there beare-evaluation. Butaswesithere inthisroom today, Icontinue tobeofaview thatthose
assessments served thecommunity well then, theinternational community, andthey continue todo
sonow. And thatthere hasnotbeen compelling evidence thathasbeen provided tosuggest thatthose
assessments have been inserious error.WT/DS26/R/USA
Page 292
Chairman
353. Thank youvery much. Professor McLean.
Dr.McLean
354. Thank Mr.Chairman. I'llbebrief. I'dliketohighlight thefactthatinmysubmission Imade
nocomment about melengestrol acetate because there hasn'tbeen alarge amount ofdata package
available forevaluation andsoIrestricted mycomments totheother fivehormones. Theonly other
comment Iwould make thatifanynational body orgroup believe thatthetime forre-evaluation of
some ofthehormones previously evaluated byJECFA wasupon us,then Iwould invite them tomake
anapproach toJECFA ashasbeen done onanumber ofoccasions with thenumber ofcompound of
varying chemical classes. Itisinteresting thatifthisinformation thathasconcerned some hasbeen
socompelling, toaskwhy anapproach toJECFA hasnotbeen made.
Chairman
355. Thank youvery much. Dr.Arnold.
Dr.Arnold
356. Thank youChairman. Concerning thetable Ihave presented inmywritten contribution, I
justwanted tofacilitate thework ofthisPanel sothatyoudon'tneed toread allthese documents and
soIsummarize thekind ofinformation, Iwassaying information pertaining totheeffects have been
considered bythestudy, it'sonpage 9.Ihave notstated thatIfeltthatallthisevidence wascomplete
atthattime, Iexplicitly mentioned thatsome datahadbeen completed only atthe34th meeting ofthe
Committee. This wasonly tofacilitate thediscussion. What concerns thesixsubstances, Imade no
statement onmelengestrol acetate because Ihaven 'tseen thedata. Theonly statement Imade was
ontheavailability ofanalytical methods because thisissomething Iknow, butotherwise Ihave limited
mystatements onthefiveendogenous hormones. Ididhowever saythatfrom mypoint ofview, the
significant newevidence which hasbeen produced since thatCommittee didnotinvalidate thebasic
conclusions andtherefore Istillamfeeling very comfortable with theconclusions although Iadmit
thatalotofnew evidence hasbeen produced bythescientific community. Coming tothequestion
ofcombinations thesynergistic andantagonistic effects ofwhatever, Ihadsome difficulties tounderstand
thisquestion because every time ifweadminister fixed combination toanimals orhumans, it'squite
clear andinallcountries participating inthisdispute there aremechanisms thatthese fixed combinations
areevaluated. ButIdidn'tunderstand thesignificance ofthese questions when wearetalking about
theresidue levels because atthose concentrations, allthese substances occur simultaneously inhuman
beings ofallsexes allages andit'squite obvious thatthese substances have both synergistic or
antagonisticeffectsinlivinganimalsincludinghumanbeings.Thisistheirnormalphysiologicalfunction
andtheycansynergize inonetissue inonecellwith respect tooneeffect andtheycanantagonize each
other. Therefore Ihaddifficulties ifthese substances enter theinternal pools ofthehormones they
areimmediately confronted with allkinds ofhormones, soIdidn'tunderstand what thequestion meant
attheresidue level. Atpharmacological levels ofcourse they aretested inallstates ifthey are
administered asfixed combinations.
Chairman
357. Could youProfessor Epstein precise thequestion?
Dr.Epstein (EC)
358. Iamsorry thatmypoint thatIraised wassoobscure. Iwould have thought thatifyouadd
twocarcinogens toananimal ortoahuman, youstand theriskofinteractions ofonekind oranother.WT/DS26/R/USA
Page 293
There aredatashowing thatarepositive interactive effects whether theybeadditive orsynergistic such
asthose between oestrogen andprogesterone. With oestrogen andprogesterone together, produce
afargreater increase inmammary cancers inrodents than doeither separately. Sothatisclear what
onemeans bysynergism. I'munaware ofanyevidence ofantagonistic, anyexperimental evidence
ofantagonistic effects ofanyanabolics andwould behappy ifyoucould refer metotheappropriate
citations.
Dr.Arnold
359. Iagree with Dr.Epstein thatthere areexamples ofsynergistic effects butIcould listanumber
ofsituations where these hormones counteract. I'mnotprepared atthemoment togive yousuch
references butI'msure Icandoittomorrow.
Chairman
360. Dr.Lucier.
Dr.Lucier
361. Probably thebestexample istheonethatyoujustcited; oestrogen andprogesterone inwhich
oestrogen unopposed byprogesterone causes anincrease inuterine cancer. Ifprogesterone isgiven
atthesame time thenthateffect isblocked. Sowhere asoestrogen andprogesterone seem tosynergize
each other interms ofbreast cancer risk, they actually antagonize each other foruterine cancer risk.
Soitjustpoints tothefactthat'svery difficult tofully appreciate thecomplexity oftrying toestimate
synergistic responses, additive responses orantagonistic responses. Even thesame twohormones in
different tissues willdoexactly theopposite, onesynergize, theother antagonize.
Chairman
362. Thank youvery much. CanIgive youthefloor?
Dr.André
363. Wewillspeak about thesixhormones andnotofMGA, itisclear wearejustspeaking about
theother ones. Ithink thatconcerning thisquestion when JECFA hasconsidered these hormones,
they have been considered asdrugs, asclassical drugs andforthisreason, allthedata concerning
toxicological assays hasbeen asked tocompanies andevaluated byvery well scientific expert groups.
ButIthink they have notbeen evaluated asforthereviews forgrowth promoters, Imean with avery
large scale use. Ithink interference between thislarge scale useofhormones andtheother drugs used
also inanimal breeding hasnever been studied, anditsclear thattheuseofhormones hasbeen
demonstrated tolonger some withdrawal period andelimination rates ofother drugs. Theprobability
tohave interference between twodrugs when they areused fortherapeutic useisvery small because
youhave noopportunity tohave atthesame time twodifferent illnesses andtwodrugs atthesame
time. Butwhen youareusing such compounds inlarge scale ashormones, then youhave ahigher
probability toseeonthesame animal atthesame time theuseofthese hormones anduseofanother
drug. And Ithink inthisparticular case ofgrowth promoting substances, theassay hastobedone.
Andconcerning thenewscientific evidence wearespeaking about very recent datafrom thismorning
altogether andIwould justmake tworemarks thatmany ofthese dataconcerning mode ofmechanism
ofaction carcinogenicity andother arerecent datafrom '90tonowandmost ofthem have been published
during 1995 and1996, thetwolastyears. Sothiscould alsoexplain insome ways thatmany ofthese
data, recent datahave notbeen taken intobytheECConference in'95because thebibliography and
theinvestigation hasbeen done forthisConference uptothebeginning of'95andnotmore recently.WT/DS26/R/USA
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Chairman
364. CanIgive youthefloor?
Mr. Christoforou (EC)
365. Mr.Chairman, Dr.Liehr would liketomake acomment onthesynergistic effects andthen
Dr.Bridges would liketointervene ontheso-called 1995 ECScientific Conference what was.......
during thatConference. Then ifyouallow meIwillsummarize once again what wassaidImay be
making probably slightly legal butdirectly related question towhat istheJECFA standards inthis
caseandwhat isthelegal context inwhich wearelitigating inthiscase. Ithink thatwillbeimportant
forourscientists. Thank you.
Dr.Liehr (EC)
366. Mr.Chairman, concerning thesynergism ofhormones, Iagree with Dr.Lucier who stated
thatthecombination ofoestrogen plusprogestin inhibits uterine tumour formation whereas itappears
toenhance mammary tumour formation. Itcertainly does soinanimals andtheepidemiological evidence
inhumans isalsoquite strong. Inthiscontext, Ithink itisvery important forallofustorealise that
when several hormones arecombined andgiven asacombination thatthebalance ofhormones within
thebody, theregulation byvarious hormones appears tobealtered orinfluenced inways thatwehave
notsufficiently taken intoaccount. Ifforinstance progestin inhibits uterine tumour formation then
andenhances mammary tumour formation, then itisobvious thatcirculating within allofusare
hormones inaquite well-defined balance andashumans proceed through life, through stages, the
endocrine regulation isquite well balanced. Once combinations ofhormones areadded thisbalance
isbeing destroyed andIthink anobvious example ofhow this, effects, synergistic effects canarise,
isthefactthatthemetabolism ofoestrogen isclearly orhasclearly been shown tobeinhibited by
progestins. Socombinations ofhormones they easily alter thebalance between these, between
endogenous hormone levels andforthemany synthetic progestins, Idon'tknow towhat extent this
isknown. Anumber ofsynthetic progestins have been examined butcertainly notallofthem. Thank
youMr.Chairman.
Chairman
367. Thank youvery much.
Mr. Christoforou (EC)
368. Mr.Chairman before giving thefloor toDr.Bridges, Iwould liketoclarify onepoint and
Dr.Stephany will intervene justafterwards. Dr.Ritter hassaid, JECFA evaluated only single
compounds, single substances. From what weknow inthemarket, theimplants, there isonly one
implant thatisonesubstance only marketed. Alltheothers areimplant ofcompounds ofsimilar
substances andIthink Dr.Stephany would liketosayacouple ofwords about this. Soinfact, what
itisadministered totheanimals inthiscase, they arenosingle substances except one. Themajority
ofalltherestoftheimplants areseveral compounds together. That Ithink Dr.Stephany would like
tosayacouple ofwords onthis.
Chairman
369. Yes? Dr.Ritter please.WT/DS26/R/USA
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Dr.Ritter
370. Idon'twant topre-empt thecomments, butinaddressing theissue ofcombinations, I'mnot
sureifyouaredealing with theissue ofanimal safety, whopresumably would beatgreatest riskfrom
thecombination, ifthecombination wastoproduce synergistic effects? Because I'mleftwith the
impression, perhaps these comments willbeaddressed, thatinterms ofhuman safety, theissue isthe
exposure tothelevels which arepresent asfood residues, which indeed arepresent incombination
with hundreds ofother substances, notonly these twoalone. SoI'mnotsure ifthecomments are
intended tobemore relevant totheissue ofsafety inthecow, ortotheissue ofsafety tohumans who
consume commodities from which theresidues mayindeed bepresent incombination butatvery much
reduced levels andagain inpresent incombination notonly forthetwosteroids inquestion, butindeed
present incombination with hundreds ofother residues ofboth natural andexogenous origin.
Mr. Christoforou (EC)
371. Thank you, thank youvery much indeed. Because there isoneaspect which isnotpractically
discussed inthisroom buthasbeen argued inthesubmissions oftheparties, especially insubmissions
oftheEuropean Community. This case concerns both thefacts onhuman beings ofcourse, butalso
onanimals, andwedidnotelaborate because theeffects ontheanimals areeven more obvious than
what theeffects areofthisresidue forhuman beings. ButDr.Stephany willalsogiven yousome
information onanimal health alsointhiscase, thatistheprostate ofanimals thatareaffected. Our
question isnotonlythepotential effects oftheanimals butalsothepotential effects ofthose combinations
forhuman beings. And thelinkthatwasmade, hasbeen explained, issince theimplants which are
used onthemarket, apart from onetheothers arecompounds ofseveral substances, thisislinked to
ourquestion, what arethepossible synergistic effects ofthiscombination? Hasthisbeen studied by
theJECFA Report? That wastheaimorthepoint thatwewere trying tomake. ButIgive thefloor
first toDr.Stephany then willcome back toDr.Bridges. Thank you.
Dr.Stephany (EC)
372. Thank youMr.Chairman. First ofallIhave tomake onevery small correction, oftheimplants
thatareonthemarket, there aretwohaving asingle active component butonly onehaving oestradiol
andtheother oneiszeranol. Sothere aretwo, oneisoestradiol thebrand name isCompudose and
theother onecontains zeranol, xenobiotic andthename isRalgro. Allothers asfarasIamaware
arecombinations ofhaving atleast onexenobiotic hormonal active compound init.What surprises
mealittle isthatwealways talkabout, thattheimplants contain compounds thatareidentical tothe
natural ones. That'ssimply nottruebecause theimplants contain either thenatural ones inchemical
different form likeanester likeoestradiol benzoate andorthetestosterone asatestosterone propionate.
And atleast testosterone propionate what isxenobiotic circulates freely inthebody asisknown from
clinical chemical studies, andI'mnotaware ofanyresidue studies oftestosterone propionate assuch
anditiscertainly nottruethatalltestosterone propionate oralloestradiol benzoate only willhydrolyse
andwillyield thenatural identical hormones. SoIthink that'sonething andcoming orresponding
totheremarks ofDr.Ritter, ifyouhave twohormonal active components inyour implants youwill
have twoatleast twohormonal active residues. Sotheconsumer willinhisfood have, inbetween
awealthofotherthings,Ifullyagree,theprobabilityofbeingservedwithtwohormonalactivehormones
orresidues atthesame time, atleast twodifferent ones. Well what'snext? Ohtheremark onanimal
health, it'sonly asmall remark. Some recent research intheNetherlands with, picking upoldresearch,
weknow thatifyoutreat bull-calves with oestrogenic compounds thenatleast afeworgans willchange
liketheprostate andwith some new technology based onhisto-chemical itsanew thing, wefound
thatatleast thiseffect ismuch more extended thanwehave found previously. Whether thatwilleffect
thehealth oftheanimal assuch, Icanhardly sayespecially forcalves only having afulllifeofhalf
ayear. Butatleast it'sanother signal thatalotofthings change inthebody oftheanimal, besides
thatmore meat isproduced. Andalsothat'sanitemthatistouched intheEuropean Conference, ranging
from animal health toanimal welfare, butthat'scompletely another thing. Ithink that'sitfortheWT/DS26/R/USA
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moment, andonce again Ithink themost important thing isthattheimplants donotcontain inmost
cases natural identical compounds.
Chairman
373. Thank youcould. I'msorry Imissed before Dr.Randell hewanted tointervene. May Igive
youthefloor?
Dr.Randell (Codex)
374. Thank youMr.Chairman. Iwould notlikethePanel togoaway with theidea thatJECFA
didnotevaluate theresidues present inanimals from these mixed implants. Themonographs which
were prepared byJECFA atthe32nd session clearly indicate thattrials were done onmixed implants
aswell asonsingle substances implants andexactly thesortofmixtures thatwehave justheard, that
is,oestradiol together with testosterone; oestradiol together with progesterone; oestradiol benzoate
together with testosterone propionate andalsooestradiol with trenbolone acetate under theoestradiol
evaluations. These were known toJECFA atthetime andthepharmacokinetics ofthese substances
asthey were gradually metabolized andexcreted bytheanimals were studied bytheexperts atthat
time. Thank you.
Chairman
375. Sorry, Dr.Arnold.
Dr.Arnold
376. Thank youMr.Chairman. Dr.Stephany isabsolutely right thattheesters areadministered.
However, thisisalsothecaseintheEuropean Union. Ifthese substances arelegally used fortherapeutic
purposes because, andIthink heretherules areentirely right, itisrecognized thattheesters arereadily
hydrolyzed toyield thesubstances. Therefore itdoesn 'tmake agreat difference ifwehave talked
about oestradiol, testosterone andprogesterone because these esters areinfactreadily hydrolyzed.
Thereason why theesters areused isthatthefreesubstances aremore slowly released because we
discussed thisearlier today. Theplasma half-life issoshort. However, inorder togive youanidea
how ineffective these substances stillare,when testosterone propionate wasused inearlier times as
androgen substitution therapy, itwasnecessary toinject 25mg.every dayintra-muscularly, soalthough
heisfrom anacademic viewpoint entirely right, Ithink wecancontinue discussing theeffects ofthe
freesubstances. Thank you.
Chairman
377. Thank youvery much. Igive thefloor back totheCommunity.
Dr.Bridges (EC)
378. Chairman, I'djustliketoclarify thenature oftheDecember 1995 Conference because several
speakers have referred toitasifitwasanup-to-date comprehensive riskassessment onsteroids. It
wasn 'treally ofthatnature atall,ithadnearly 400participants, which isapretty difficult wayofgoing
about riskassessment. Itwascovering three areas, development ofnewgrowth promoters generally,
riskassessment across arange ofgrowth promoters andthen monitoring andsurveillance. Sothere
wasn 'tandthewaythepapers were identified wasthatwehadasmall organizing committee whochose
thespeakers. Now intheir wisdom orotherwise, they chose nottohave anybody who wasinvolved
ingenotoxicity andsoasaconsequence, andIwasaplenary speaker forriskassessment soIremember
thebrief well, asaconsequence thisissue ofgenotoxicity wasnotaddressed atallbytheconference
andtherefore theconclusions oftheConference didnottakeitintoaccount. Soitisn'tandwasneverWT/DS26/R/USA
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intendedtobeacomprehensiveriskassessmentanditdidn'treallyconsideranyothermechanismbecause
ofthewaythespeakers were selected other thanjusttolook atthehormonal mechanism andhow that
may berelated tocancer.
Chairman
379. CanIaskyou, thefactthatyoudidnotinvite speakers, wasthatanindication thatthiswas
notpartofthemainstream thinking atthetime, or?
Dr.Bridges (EC)
380. Chairman, Iwasn 'tamember oftheorganizing committee butthey were clearly very wise
because they chose measaplenary speaker soIcouldn 'targue with them. Ithink really thethinking
wasthatthey wanted tofollow uptotheso-called Lamming Report, andtheLamming Report had
concentrated very much onhormones acting ashormones orhormonal mechanism. SoIthink the
natural assumption wasthattheywould getanupdate onthose sortofissues rather thanlook atbroader
issues andI'vetaken theopportunity totalktomembers oftheorganizing committee recently toconfirm
thatthatwastheir view.
Chairman
381. Butcould itbesaidthatifthiswould beorganized today theywould probably takeadifferent
approach? Isthat, Imean these issues we'rediscussing have they moved intothedebate?
Dr.Bridges (EC)
382. I'msureChairman thatifwewere organizing thesame conference today, genotoxicity issues
would loom very large inthediscussion andI'msure Iwould have hadtorefer toitparticularly in
mypaper.
Chairman
383. Thank youvery much. Dr.Arnold.
Dr.Arnold
384. Thank youMr.Chairman. Itotally agree with youthatthisConference hasnotproduced the
slightest element ofriskassessment, Itotally agree withyou. ButIhave recognized thatsome important
information hasbeen disseminated including your own very important keylecture, butIwanted to
underline thisConference hasnotproduced theslightest element ofriskassessment.
Chairman
385. Thank youvery much. Dr.Ritter please.
Dr.Ritter
386. Thank youMr.Chairman. Ithink itmaybeuseful, anumber ofushave referred tothereport,
Ihave thereport with mewhich Ibrought attheriskofgreat personal injury totransport it...[tape
ends]
Mr. Christoforou (EC)
387. Itisaddressed, particularly forDr.Ritter, Dr.McLean, Dr.Arnold andofcourse, Dr.Randell.WT/DS26/R/USA
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Chairman
388. Thank youvery much. Could Istart with youDr.Randell because theprocedural questions
areaddressed toJECFA.
Dr.Randell (Codex)
389. Thank you, Mr.Chairman.
390. First I'dliketosaythattheJECFA Secretariat, ofwhich Ihadthehonour tobeapartfor
aperiod ofmycareer, would feelvery disturbed ifthey were aware thatdata were available tothe
scientific community thatwere notavailable toJECFA, orwere notbeing proposed tobeavailable
toJECFA, inamanner thatwould render JECFA 'sadvice toFAO andWHO member countries, either
obsolete orinappropriate.
391. Therefore, mycomment earlier, wasreally tomaintain, what Ibelieve tobethestanding
excellence ofJECFA 'sevaluations inallofthefields thatJECFA deals with, inorder that, wecould
perhaps encourage those scientists thathave these data toassemble them andbring them toJECFA
forreview. Itwasmeant asapositive, notanegative, statement.
392. Afewminor corrections tothehistory which we'vejustheard. Thevote which took place,
inwhich thehormones were failed tobeadopted bytheCodex Commission, wasin1991, not1992.
393. Thefour principles concerning theroleofscience inCodex decision-making, andtheextent
towhich other factors aretaken intoaccount, wasnever discussed, asfarasIamaware, byJECFA.
Itwasnotprocessed through theJECFA system. Itisentirely aCodex matter and, therefore, entirely
operated bythemember governments ofCodex andnotbytheexperts inJECFA.
394. LetmeputtheJECFA material intoperspective. JECFA provides advice toFAO andWHO
andthrough them tothemembers ofthose twoorganizations andalso totheCodex Alimentarius
Commission.
395. The Codex Alimentarius Commission has, asamatter ofprocedure, taken theJECFA
recommendations inavariety ofareas andplugged them intotheeight-step elaboration system and
theresult ofthis, inmost cases, isaconsensus adoption ofthese points ofview which arethenavailable
forcountries toapply, ifthey feelthatthey wish to.They arenotobliged tounder theCodex rules.
396. There have been anynumber ofemergency re-evaluations inJECFA which have been initiated
inCodex andwhich have found themselves reflected inCodex opinion.
397. Astothedirect question ifthere isonethathasoccurred inthenine-month period since the
entry intoforce oftheUruguay Round Agreements, I'dhave tocheck thatinbutIcan'tthink ofone.
Themost recent onewhich hassimilar import would bethedecision ofJECFA towithdraw previous
evaluation inregard topotassium bromate, asaflour-treatment agent, andthesubsequent withdrawal
byCodex ofallapproved uses ofpotassium bromate inflour, primarily because potassium bromate
residues remain intheflour atthetime ofingestion bythehuman consumer, andpotassium bromate
isacarcinogen.
398. Themaximum residue limits arenotexclusively concerned with trade. They areconcerned
with thecontrol ofgood agricultural orgood veterinary practice andthey areapplied intrade. To
bequite practical about it,it'sdefinitely beneficial totrade ifcountries have thesame numerical values
formaximum residue limits, oratleast ifyouareexporting aproduct, thelevel atwhich youare
exporting islower than thelimit applied byyour importer.WT/DS26/R/USA
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399. However, themaximum residue level should reflect thegood agricultural, orgood veterinary
practice, onyour territory andnotbelinked exclusively totrade considerations.
400. Iwould takeumbrage atthepoint thattheMRL isatrade-derived figure. Itis,infact, afigure
derived from good veterinary orgood agricultural practice.
Chairman
401. CanIaskyoutogointothequestion which wasputforward?
Dr.Ritter
402. Very quickly, Ithink theprinciple thatwasbeing elaborated, thephilosophy ismore popularly
referred toastheprecautionary principle.
403. Astowhat isthemost appropriate action inthefaceofthekind ofinformation, forexample,
thathasbeen presented today, Itake thatreally tobethework ofthePanel, andsoIwillmake no
attempt toanswer thatquestion.
404. Ithink itgoes well beyond thejurisdiction thatI'vebeen provided here tocomment.
405. Iwill, very quickly, comment on,ifyoulike, theageoftheassessment andI'vealready made
comments onthisanumber oftimes, butitperhaps bears repeating.
406. Ithink itisincorrect andIwould respectfully submit thatitismisleading tosuggest that
1988/1989 isthelasttime thatthisissue onthesafety ofthehormones, inquestion, hasbeen examined.
407. I'vealready mentioned thatcertainly inmyview, thisissue, without going intoalengthy debate
astowhether ornotthestrict definition ofriskassessment wasmade bytheEuropean Conference,
Ithink itgoes without question thattheissue ofthesafety ofthehormones, inthegeneral sense, was
most certainly re-evaluated inDecember 1995, which isalittle more than oneyear ago.
408. Indeed, anumber ofpeople who arehere today were active participants atthatconference.
409. Imust saythatIdisagree with theview that1989 isthelasttime thatthisissue wasformally
evaluated onaninternational level. Ithink that'sincorrect andIthink it'smisleading.
410. More specifically, ontheissue ofriskassessment, whatever thatmeans. Wecould spend the
restoftheevening debating whether ornotriskassessment have, orhave not,formally been discussed
bytheConference.
411. Iwould refer thePanel toaspecific section entitled, Risk Assessment, onpage 3ofthe
Conference Report, anditfallsunder thegeneral section oftheReport entitled Report andConclusions
oftheSteering Committee, specific section entitled, Risk Assessment.
412. Although theConference wasconcerned withmany technical matters, itisinevitable thatgeneral
interest should have centred ontheriskassessment ofdifferent classes ofboth promoting substances,
thesubject ofdiscussions ofWorking Group 2.
413. Then Iwould refer, Mr.Chairman, thePanel toanumber ofspecific papers which Iwould
respectfully submit, dealt with very much with theissue ofriskassessment. Irefer toWorkshop No.2
onpages 245-401 andIwould refer specifically toanumber ofpapers, including theonepresented
byProfessor Bridges, butalso including papers presented byDr.Miller from theUnited States,
Dr.Hoffmann from Germany, andsoonandsoforth.WT/DS26/R/USA
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414. IfIrefer, justbywayofexample, nottogiveparticular preference toanyoneofthese papers,
tothepaper presented byDr.Miller from theUSFDA atthatConference, sheconcluded, atthattime,
"hormonalgrowthpromotingagentsincludeavarietyofcompoundwhichverymarkedlyinpharmacology
andbiochemistry" soonandsoforth.
415. "When these animal drug products areused according tolabel directions, theedible tissues
from treated animals, aresafeforallconsumers."
416. Iwould respectfully submit, Mr. Chairman, thatthatisvery much anassessment ofrisk,
regardless ofwhether ornotwecancome toaformal definition ofwhat constitutes ariskassessment.
It'scertainly myview thatthisismost definitely theelement ofriskassessment. Itstrikes theheart
ofwhat ariskassessment is,because after alltheproduct ofariskassessment, isthestatement ofsafety
tothetarget population. That'swhy wecarry outriskassessments. It'snotmerely amathematical
exercise.
417. Iwould suggest tothePanel thatthere areanumber ofpapers here thatdealvery much with
theissue ofrisktohuman populations, resulting from theuseofthese compounds, andthattheconsensus
ofthisWorkshop wasthattheuseofthese compounds, asrecently reviewed asDecember of1995,
does notconstitute anyrisk.
Dr.André
418. May Iaddsome comments forthePanel? Itcanalso seeinthesame paper, page 378,
conference.
419. Iwillread what itsays:
"New quantitative riskassessment models areneeded forthesafety evaluation ofchemicals
with toxic actions, likegeneral carcinogen."
420. It'sinthesame paper soit'snotpossible toextract something when youdon'textract allthe
information.
Dr.Ritter
421. Ididn'tintend tomislead. Imean obviously I'mnotgoing toread intotherecord theentire
Conference Report itisavailable.
422. There isnoquestion thatanumber ofdeficiencies, interms ofourstate ofknowledge, as
identified throughout thereport, butthose efficiencies, those deficiencies were weighed intheconclusion
which thePanel hasreached. They weren 'tweighed byme.Buttheconclusions oftheWorking Group
wasthatthepresent state ofknowledge issufficient todemonstrate thesafety, intheir view, ofthe
useofthese chemicals incontemporary times.
423. Ithink itwould besilly foranyscientist topresume thatthedaywillever come, onthisissue
oronanyother, where wecould sayweknow enough andthatthere isnoneed todoanyfurther work.
Ihave never been associated with ascientific issue where Ihave ever heard ascientist say, there is
noneed todoanyfurther work onthistopic, weknow allthatweneed toknow.
424. Iagree thatthere isfurther work thatisindicated. Iagree thatstatements made byscientists,
such asDr.Liehr willcontinue tocontribute toourunderstanding, butIalsoagree thatthetotality
ofevidence re-evaluated, asrecently asDecember 1995, suggests thatthewayinwhich these substances
areused andtheresidues which they produce, donotconstitute arisktohuman health.WT/DS26/R/USA
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425. Idon'tfindthose statements tobecontradictory atall.
Chairman
426. Dr.Lucier.
Dr.Lucier
427. MyquestionmayshowacertainamountofnaivetybutdidJECFAdocumentorthe1995meeting
address theissue ofcarcinogen riskassessment, inanykind ofway?
428. Itseemed tomeliketheriskwasbased onthehormonal activity oftheagents, inprimates.
Chairman
429. Wediscussed thatbriefly before. Would youliketogive your views onthis.
Dr.Ritter
430. Ithink only tosaythatunless wewere tospend agreat dealoftime strictly defining what we
mean bythephrase "risk assessment" wecould continue togoaround thiscircle, Ithink, allnight.
Thepoint thatIwastrying tomake that, intheopinion ofthescientists thatwere gathered atthe
Conference, itwastheir collective wisdom, forwhatever reasons theyconsidered. Ithink, asProfessor
Bridges hasalready quite correctly indicated thatitdidnotinclude extensive examination ofsome of
theevidence which waspresented today. Butforallthetotality ofreasons thatthey considered, at
thattime, they came toconclusions which have already been made clear. Onemay raise thequestion
iftheywere redoing ittomorrow, would theycome tothesame conclusion? Ithink thisisspeculation.
Onecould raise thequestion, iftheywere doing itagain ayearfrom now, would theycome toadifferent
conclusion? Idon'tknow.
Dr.Lucier
431. Were theacceptable levels, ortheacceptable daily intakes, were theyderived, primarily, from
thetests ofhormonal activity innon-human primates? Isthatcorrect?
Dr.Ritter
432. No,Idon'tthink that'scorrect. Ithink there were extensive carcinogenicity data thatwere
available totheJECFA Committee. These data have been described, theassessments provided, at
least inthecase oftwoofthexenobiotic hormones. Tothebestofmyrecollection, monographs on
thethree natural hormones arenotavailable, buttheyareavailable forthetwosynthetics, andcertainly
theywere based onchronic toxicity carcinogenicity studies thathadbeen conducted inavery classical,
NTP kind ofmethodology.
433. No,thenaturals were evaluated, what Iindicated, tothebestofmyknowledge, monographs
arenotavailable onthenaturals. Butdatawasevaluated bytheCommittee, onwhich they drew their
conclusions, Ihave notbeen privy tothatdata. Butthen again, Ihave tobecandid, Ihave notre-
evaluated thecarcinogenicity dataforanyofthese compounds, inorder toprepare thissession. This
would have been neither practical orarguably even necessary. Iwould never pretend tosuggest that
Ihave greater wisdom inthisarea than thecollective wisdom oftheJECFA Panel.
Chairman
434. Dr.Randell, please.WT/DS26/R/USA
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Dr.Randell (Codex)
435. Mr.Chairman, justperhaps toclarify thatpoint.
436. Inthecaseofzeranol, forexample, theJECFA Committee didevaluate carcinogenicity studies,
inratsandinmice, andsoforth, buttheconclusion thatJECFA came tointhissubstance andinthe
other substances, thatthecarcinogenicity was linked with thehormonal effect, andtherefore the
establishment ofthe"nohormonal effect" level wasthepoint atwhich theevaluation hinged, ithinged
around thatpoint.
437. This iswhy thenew data, which we'rehearing about today, isofinterest because itwould
supplement thatevaluation andhelp usconsiderably. However, theinformation which wasavailable
toJECFA definitely didinclude carcinogenicity studies forallofthesubstances concerned.
Chairman
438. I'mlooking atmywatch. It'sabout 7.30. Could youcome toaclose fortoday?
Mr. Christoforou (EC)
439. Mr.Chairman, Iwillcome toaclose onthisparticular point, ifyouallow me.
440. Iwillread from what theresponse ofDr.Ritter wastoQuestion No.5,because thatiswhat
wearediscussing now.
441. Iquote page 12ofhisreply toQuestion 5,attheendofthefirst bigparagraph:
442. Forprogesterone:
"The report wassilent ontheresults ofmutagenicity studies which were available tothe
Committee forreview."
Fortestosterone:
"Results from mutagenicity studies, although available totheCommittee, were notdescribed
inthereport."
Forthesynergy:
"The issue ofpotential synergy hasbeen addressed, atleast inpart, through thecontext of
biochemical studies, directed attheeffect ofexcretion ofhormone combinations when compared
tosingle hormones alone."
This isonpage 14.
"Itis,however, clear, thatdefinitive studies relating togenotoxicity orcarcinogenicity of
hormone combinations have notbeen carried outeven though thisisfrequently thepreferred method
ofuse."
443. I'mslightly puzzled bythepositive terms inwhich Dr.Ritter isnow phrasing hisreplies for
thereview ofthe,intheJECFA report. Allissues wehave been discussing here now about the
genotoxicity, notonly duetothehormonal effects, ashasbeen rightly pointed byDr.Lucier butall
theother possible sources ofrisks wehave identified.WT/DS26/R/USA
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444. Atleast thewayIunderstand hisreplies isthatthese studies have notbeen carried out. They
might have been available butthey have notbeen reported inthereport. Wedon'tknow ifthey were
realstudies.
445. HewasnotpartoftheJECFA committee, inthatparticular case. SoIdon'tknow where he
hasgotthisinformation. Whereas Dr.McLean waspartofthisreport andalsohemight have aninterest
toexplain touswhether thishasbeen done. From thereports wehave infront ofus,Dr.Arnold
hasprovided atable, where there aresome black holes where things which have notbeen examined.
Iseethere is,atleast some, contradiction between what ourscientists aresaying onthisparticular
issue. Ifonereads theentire report ofJECFA, itisclear thatonly thehormonal effects ofthose
substances have been studied forthepotential carcinogenic effect. Sowhat istheexact scientific basis
onwhich Dr.Ritter ismaking these comments?
446. One more comment.
447. Ithink Dr.André, because hewaspartoftheOrganizing Committee ofthe1995 Conference,
hehas,inmyview, direct inside information onhowthisconference wasorganized. TheCommunity
only funded theConference andleftthescientists entirely toaddress some issues.
448. Inthereport ofDr.Ritter, itisfrequently referred toastheECConference. ItisnottheEC
Conference. Itisaconference funded, butnomore than that. Itwasentirely lefttotheSteering
Committee who toinvite andwhat todiscuss inthisconference.
Chairman
449. Iwould propose thatwehave afinal round onthisquestion andthenwewillclose themeeting
fortoday, andIwould give theopportunity torespond tothescientific experts.
450. Maybe Dr.Ritter would speak attheend.
451. I'llstart with Dr.McLean.
Dr.McLean
452. Ithoroughly concur with thecomments ofDr.Randell. Wewere trying toputapositive view
ontheavailability ofJECFA, ifpeople wanted totake thatopportunity, rather than forcing people
todoit.
453. Inrelation tothemutagenicity data forthenaturally-occurring substances, themutagenicity
data thatwasreviewed isreferenced inthereport, ineach case, andsotherefore, notsomuch that
iswassilent butitreferred tomutagenicity data thatwasintheopen literature. So,inthecase of
progesterone, testosterone andoestradiol 17beta, there were anumber ofpublished documents that
theCommittee didlook at,andthey arereferenced inthereport.
Chairman
454. Dr.Arnold.
Dr.Arnold
455. Mr.Chairman, Ihave twopoints.WT/DS26/R/USA
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456. Thefirstpoint isIhave difficulty understanding howitcould happen, butthelegally competent
authorities oftheEEC, ontheadvice ofthecompetent advisory scientific body, have established no
MRL foroestradiol andthishappened twoyears ago.
457. The public summary report states, inter alia,"The conclusion oftheFAO/WHO Expert
Committee onFood Additives, JECFA, thatnoADI andMRL foroestradiol need tobeestablished,
asadopted." And then alltheother things Imentioned thismorning, thisiswhat Ihave difficulty
inunderstanding, thishappened in1994. And thisRegulation hasbeen implemented, ithaspassed
alltheECinstitutions andtheresult hasbeen published intheOfficial Journal. Irefer tothisinmy
answers tothequestion ofthePanel.
458. Mysecond point isIwasrapporteur oftheCodex forfiveconsecutive years. That means
Ihadjointly, with thesecretaries ofthetwoagencies oftheUnited Nations andwith theUSSecretariat
oftheCommittee, toprepare thereport. Iwasinareally difficult situation because it'struethatthe
ECobjected tomove these MRLs tothenext stepintheprocedure, butwithout raising anyhealth
issues. So,Iwasreally introuble andyoucanfindtheresult inthereport. Ifinally gotawritten
statement andthearguments youwillfindthere are,inter alia,theECisopposing because they have
specific legislation prohibiting theuseandtheECconsumer doesn 'twish toreceive meat from animals
treated.
459. These were thearguments, soI'malittle disappointed thatthese questions have notbeen raised
earlier, firstofall,inearlier years during theCodex discussions. Itcould have happened, forexample,
torefer thewhole matter back toJECFA with new health arguments forre-evaluation, atthattime,
butthisproposal wasnotmade.
460. And thatsecondly, twoyears agoithappened thatwecame tothesame conclusions bythe
competent authorities oftheECregarding oestradiol. Progesterone hasalsobeen finished butnotyet
published intheOfficial Journal, andtestosterone isstillunder evaluation.
Chairman
461. Ithink wewillreserve thisfortomorrow.
462. I'dliketoconclude andifanybody ofyouwould liketospeak?
Dr.André
463. Justtosayalittle more about thisConference because Ihave been asked todoso.
464. It'sclear thattheEChasjustasked fourexperts toorganize thisConference: SirJohn Maddocks
istheHead Director oftheNature Review, ascientific paper, anIrish colleague, Bergen colleagues
andmyself.
465. Icanwitness thatwewere very, very freeofourtoourchoices, interms ofselecting scientific
people. And weorganized thiswith afirstgroup oftwopeople forthethree Work Shops, andthey
proposed thatweinvite scientific people andweagreed, onthebasis ofthepublication andthefamous
ofthese people.
466. But, Ithink, andIpersonally regret now thatwedidn'ttake enough care with thescientific
publication. Idiscovered thismorning alotofpublications onthistopic andsome ofthem were available
andthescientific were alsoavailable, andmaybe wehave notdone ourbest. Wehave done ourbest
butmaybe itwasnotgood enough, andthatwillexplain alsothemissing ofsome information inthis
Conference.WT/DS26/R/USA
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467. Onthelastpoint,Iwouldliketosaythattheconclusionsareareflectionofacommondiscussion,
anditisnotacomplete reflection ofthemajority ofpeople. Itisnotatotal opinion ofthemembers
oftheCommittee anditcannot betaken intoaccount assomething coming from anofficial body.
Ourobjective wasjusttoputsome light, some knowledge, onthese hormones inorder toinform
politicians preparing newregulations andnomore. Itisnotthesame thing astoestablish anofficial
MRL. Theresponsibility wasnotexactly thesame order.
Chairman
468. Dr.Lucier.
Dr.Lucier
469. I'mjustsurprised inreading through thisreport that, given thefactthatoestradiol isaknown
human carcinogen, thatanADI wasconsidered unnecessary forit.There isatolerance butnotan
ADI, ifI'mreading thereport correctly.
Chairman
470. What page?
Dr.Lucier
471. 19.
Chairman
472. TheJECFA Report. This wasthe1988 JECFA Report. Isthatcorrect?
Dr.Lucier
473. Inthemiddle ofpage 19itsaidtheCommittee considered anADI unnecessary forahormone
thatisproduced endogenously inhuman beings andshows great variation andlevel according toage
andsex.
Dr.McLean
474. Thedifficulty thatJECFA hadofsetting anyADI wastheproblem oftheincrease thatone
sawupon treatment, against abackground ofvery large levels thatoccurred naturally. Andsotherefore
itmeant thatthesetting oftheADI really wasn 'tpossible, because thetreatment altered thelevels by
such asmall amount when compared withtheendogenous levels incattle tomake anyADImeaningless,
andthatwasthedifficulty wehad.
475. Iwould suggest, today, thatisnotpossible toregulate theuseofthethree naturally-occurring
hormones bythesetting ofanADI because youcan'ttellthedifference between treated animals and
untreated animals, byamethod thatissuitable forregulatory purposes.
476. It'sapractical consideration, arealandpractical consideration. Idon'tquarrel with what you
say, butinpractise there 'snoway ofregulating it.WT/DS26/R/USA
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Dr.Lucier
477. Butifoneknew, which wedoknow, what aregiven body burden inthecattle would beproduced
bytheuseofgrowth promoters, wecancertainly estimate various eating habits ofpeople, what they
would take intheir body from those agents thatwere exogenously administered.
478. Onecould come upwith reasonable estimates onthatandestablish anADI. Inmymind, that
could bedone. From mycomments thismorning, Idon'targue with your point thatit'savery small
number ofmolecules, onein28,000 Icame upwith inmycalculations, nottaking intoaccount the
factthatitispoorly absorbed andthatwould make itonein280,000.
479. Butnevertheless, some sortofanassessment should have been made, inmymind, ofwhat
thatriskwas, aslowasitis.I'mnotsaying thattheriskishigh butIbelieve theriskisextraordinarily
loworzero. That'snotmypoint. Iamjustsurprised thatthatexercise wasnotdone.
Chairman
480. Ifmore points onthisaretobediscussed, Iwould liketodiscuss them tomorrow because I
think wearealittle tired.
481. Would youliketomake statements tonight?
482. Iapologise forthelength ofthemeeting butithasbeen, inmyview, very informative and
Iwould liketothank theexperts andalsothedelegations fortheir support.
483. Asagreed, wewillmeet tomorrow at2o'clock, hopefully sharp, andwewillopen discussions
with thestatements andquestions bytheCanadian Delegation.
484. Thank youvery much andgood night.
485. Themeeting isclosed.
Second day-18February 1997
Chairman
486. Asannounced yesterday, weshall proceed inthefollowing manner. WewillgofirsttoCanada
fortheir comments andquestions totheexperts. Wewillthenturnagain totheEuropean Communities
andIwould urge theCommunity tolimit their interventions totheutmost necessary inorder tosave
time. Wewillseehow much time canbeallocated when theCanadians have made their statements
andquestions andthen there willbefinal questions from thePanel totheexperts andthen thefinal
statements bytheexperts intheend. Ihave tobeabletoconclude thismeeting byaround 6o'clock.
Iamnotabletosaywhether wewillbeabletodoso.Itdepends onyouandIaminyour hands to
alarge extent.
Mr. Christoforou (EC)
487. Wewould really doourbesttorespect what youhave indicated, butourdelegation hasaserious
problem inthesense thattheplanes oftwoofourscientists areleaving at6o'clock andweconsider
their testimony andtheir presentation very important. Itisjustarequest andwehope wehave the
understanding ofthePanel inthisroom. Ifitispossible by4o'clock, Canada does notfinish, Ido
notknow how many questions they have, ifwecanstopforawhile they canmake their presentationsWT/DS26/R/USA
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andifthere areanyquestions oranswers andthen they could probably beabletotaketheir taxis and
gettotheairport intime. That istherequest.
Chairman
488. Thank youvery much. Ithink wewillseewhere wearewith Canada at4o'clock.
Mr. Brinza (US)
489. Mr. Chairman, aprocedural question. Last night wehadleftthatthePanel wasgoing to
deliberate onourquestion about thefollow-up submission. That wasrequested bytheEuropeans and
Iwondered ifthePanel hadcome toaconclusion with respect tothematter wehadraised lastnight.
Itisimportant, inpart, because asweunderstand, theprocedure thatwasjustdescribed, there would
benomore opportunity forcomments byeither Canada ortheUnited States after theCanadians have
finished their questions today (and obviously wefinished ourquestions yesterday), andthere area
number ofpoints thathave been made thatIthink itwould beappropriate togive usanopportunity
torespond to.
Chairman
490. Thank youvery much. Iintended totakethisupattheendofthemeeting butsince youraise
itIcangivetheanswer ofthePanel. Wehave looked intothequestion andbased upon thetextwhich
wascommunicated on3February bytheSecretariat totheParties, which Iwillread inasecond, we
reviewed thedecision Imade yesterday andwewillnotaccept anyex-post submissions from theParties.
TheUnited States hassubmitted some materials, youhave submitted some materials yesterday which
wetook onthefile,butwewillnottakeonanymore written materials after thisday. Thetextreads
"Please findattached theresponses offour ofthefivescientific experts responses toPanel questions.
Professor Arnold requested afewmore days tosubmit these responses. [They came later on.] The
Parties areinformed thattheir comments tothese questions atthe17-18 February meeting withscientific
experts should bemade available, asiscustomary with theParties 'oralstatements atpanel meetings,
inthewritten form andifpossible ondiskette totheSecretariat". Sothismeans thatweexpected these
comments bytoday andIthink wewillconclude theproceedings based onthisletter. Soifyouhave
additional materials, please hand them inbytheendofthismeeting.
Mr. Christoforou (EC)
491. Mr.Chairman, thepractice though isthatweareallowed tosubmit adocument atleast the
next dayafter theoralpresentation. This hasalways been thecase. Weareadjusting thetextwhile
wearespeaking andIhave been doing thatforsomany years anditisalways thenext dayweare
allowed tosubmit inwriting theoralpresentation. Itisvery restricted thistime-limit oftoday. Iwould
appreciate itiftomorrow there isalsoachance forustosubmit adocument. Thank you.
Chairman
492. Ithink theproblem isthatthenweneed tohave another goonrebuttals. AndIthink westick
tothishere forthemoment because thishasbeen ahearing ofexperts byapanel andwedorecord
ontape andwilltranscribe everything which isbeing saidatthismeeting soIdonotthink thatwe
would need another written statement onthesideofyour part.
Mr. Christoforou (EC)
493. Mr.Chairman,ifyouapplythisrulethentheentiretextwhichisinthetextthattheUnitedStates
hascirculated hasnotbeen read outorally. Then Iwould have unfortunately torequest youtoexcludeWT/DS26/R/USA
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allthose parts ofthedocuments which have notbeen read out. Ireally regret thatinthispartofthe
document there aresomany things which have notbeen saidyesterday.
Chairman
494. Ithink itwasnotrequired thatthisberead outbecause itsays thatthecomments onthese
questions should bemade available totheSecretariat. Itisnotexactly thesame proceeding inmy
view asintheordinary firstandsecond substantive meetings here. Idohope thatyouareabletoprovide
some ofthematerials asitwasdone yesterday, today -thestatements bytheexperts andsoon.
Mr. Thompson (Canada)
495. Thank youMr.Chairman. IfIamgoing togetstarted before my4o'clock deadline then I
hadbestgetquicker with thefinger onthebutton.
496. Ithadbeen Canada 'soriginal intention tocomment quite briefly ontheexperts 'answers to
thePanel 'squestions. Primarily bynoting inpoint form some seven areas where theexperts were
ingeneral consensus andthen toputwhat wehoped were afewfocused questions. Westillintend
todothat, however some oftheevents ofyesterday require some broader comments onCanada 's
understanding ofthepurpose ofthismeeting andtherulings thatyoumade onhowwewere toproceed.
497. Wecame here prepared tocomment onandexplore thePanel ofExperts 'answers toyour
questions andabide byyour ruling thatnonewevidence would beintroduced after 8February. Ibelieve,
Mr.Chairman, thatyouwillrecall thepurpose ofthatruling wasintended toprovide allparticipants
with anequal opportunity toreview relevant material inadvance sothatinformed commentary could
bemade.
498. Yesterday weallhadtheprivilege tohear some oftheworld 'sleading experts comment and
debate theproperties andcharacteristics ofthesubstances inissue. Some highly technical andcomplex
issues were discussed with clarity andprecision. Unfortunately andunfairly, inCanada 'ssubmission,
wewere sometimes deflected from thatvery high level ofdebate bytheintroduction ofnewmaterial,
some ofwhich wasapparently presented outofcontext andinaselective way. ThePanel 'sexperts
were asked tomake extemporaneous replies onmatters they hadnothadanopportunity toconsider
inadvance. This sometimes ledtoprolonged discussion clarifying facts onmatters ofmarginal
importance totheissues thisPanel must decide.
499. Anexample, nobetter orworse thanmany Icould choose, isDr.Epstein 'stable onoestradiol
residues ineight-year olds, which ultimately ledtothesomewhat surprising assertion that two
quarter-pounders or110gram whoppers were theequivalent of500grams ofmeat. IfIcould be
permitted apun, thatwasarealwhopper! With respect, itisimportant torefocus theissues these
experts arehere tohelp elucidate.
500. Thecomplaint before thisPanel concerns ameasure oftheECwhich bans theimportation
ofbeeforanyofthesixhormones, alone orincombination, thathave been used forgrowth promotion
purposes inthefaceofproperly established international standards ofsafeuse.
501. OnegoaloftheSPS Agreement istofurther theuseofharmonized sanitary measures between
Members soastoprotect health butnotunnecessarily interfere with trade. TheAgreement permits
aMember todepart from these standards forcertain prescribed circumstances. Therelevant onefor
theissue concerning thePanel 'sexperts, andtheonly oneinmysubmission, isascientific justification.
Dr.Randell hasspoken eloquently ofthehigh standards ofJECFA andCodex andthesubject matter
thatwastaken intoaccount inestablishing thestandards ofboth thenatural andsynthetic hormones
andthevery conservative assumptions adopted toensure safety through theuseofADIs andMRLsWT/DS26/R/USA
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where required. Itisclear thatthese organizations aretobecommended fortheir work andnurtured
rather than criticized.
502. Wehave learned thatstudies have been conducted formore than 12years totryandprove
ahypothesis thatoestrogen isgenotoxic. Many ofthese studies were known toandconsidered by
JECFA. Dr.Liehr, inoneofhisstudies, hasinjected comparatively massive doses ofoestrogen in
amale Syrian hamster inanexperiment designed toproduce tumours. Thequantities areabout twice
thedose given tocattle. Dr.Lucier, asIunderstood him, agreed thatinlight ofthisevidence there
wasarisk, butheputsthatriskatalevel somewhere between zero, aconcept which cannot beachieved
inabsolute terms, andafactor sosmall thatitcannot bemeasured.
503. Thequestion forthisPanel isthisinmysubmission: isthatariskthatjustifies departing from
aninternational standard inlight ofitsimpact ontrade andtheobjects oftheAgreement. One way
oftesting that, Mr.Chairman, isbycomparing other ECsanitary measures where there aresimilar
orgreater risks. Canada willpose some questions ontheissues ofconsistency orlackofitintheEC's
handling ofthese andother veterinary drugs.
504. Before turning tothose questions Iwould liketoreview what Canada submits arethepoints
ofconsensus between thePanel 'sexperts: (1)good animal husbandry practice isabroad term
encompassinggoodherdhealth,managementpracticesandincludesgoodpracticeintheuseofveterinary
drugs; (2)intheevent thatgood practice intheuseofveterinary drugs isnotfollowed, higher residue
levels may result.
505. However, given thefactthattheMRL wasderived from anADI where alarge safety margin
hasbeen applied, such anevent isunlikely tocause anadverse health effect; (3)consumers arenot
able todistinguish themeat ofananimal treated with growth-promoting hormones andthemeat of
anuntreated animal; (4)observing withdrawal times forthehormones does notguarantee zero residues
inmeat. Noresidues detected does notimply thatthere arenoresidues present inmeat asthey may
bepresent atlevels thatarebelow detection; (5)following treatment with thenatural hormones, for
either therapeutic, zootechnical orgrowth-promoting reasons, hormone levels willfalltothose normally
associated with untreated animals. There arenodifferences between theresidues ofnatural hormones
thatareendogenous totheanimal andtheresidues ofthesame hormones administered exogenously
totheanimal. Extensive datarelating togenotoxicity andcarcinogenicity were available totheJECFA
andwere considered bytheCommittee. TheCommittee concluded thatthefivecompounds evaluated
arenotgenotoxic carcinogens; and(6)growth hormones have been used inanimal husbandry formany
years; insome cases upto40years andthere arenohuman epidemiological datathatsuggests ahazard.
Adverse health effects have notbeen observed inthose countries using growth hormones.
506. Ihave justoneother point Iwanted toraise briefly, notforpurpose ofresolution butrather
toalert thePanel toanadditional concern that Canada has. Ithasbecome apparent that the
European Communities intend topresent aslide demonstration atsome time thisafternoon. Ihave
notseen thatdemonstration andIdonotknow thecontents ofit,butIamconcerned thatitmay well
befresh evidence which would beintroduced after theFebruary deadline thePanel hassetandIam
alsoadvised bysome people who claim tohave seen these slides thatitisoflittle scientific assistance
andmaywellbeinflammatory. Ifandwhen theECchooses topresent thatslideshow Iwould hopefully
have anopportunity todiscuss whether itisappropriate ornot.
507. IfImay Iwould liketoturn tomyquestions.
508. Dr.Arnold, onpages 10to12ofyour written answers youdescribed theevaluations conducted
bytheECforoestradiol andprogesterone pursuant toRegulation 2377/90. Asaresult oftheevaluation
oestradiol hasbeen putintoAnnex 2ofthatRegulation andprogesterone ispending Iunderstand.
Could youdescribe thesignificance ofputting these substances inAnnex 2andcould youcontrastWT/DS26/R/USA
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itwith thesignificance ofputting asubstance intheaccompanying Annex 4andperhaps describe some
ofthesubstances thatareinAnnex 4?
Dr.Arnold
509. Ishould perhaps spend thefirstminute describing theworking relationships between JECFA
Codex andthecompetent bodies oftheCommunity because Ithink then youwould better understand
how thishappened.
510. Wehave setupintheCommunity aworking party obliged topropose maximum residue limits
forresidues ofveterinary drugs in1984. Westarted atthebeginning without having atruelegal basis
soitwasabigadvantage when Regulation 2377/90 became effective on1January 1992. Ifyoulook,
forexample, attheOfficial Journal, ormaybe atVolume 6oftheRules Governing Medicinal Products
intheEuropean Community, youwillseeawhole volume devoted tothisissue. You willseethe
regulation, youwillseeguidelines, what therequirements arefortheevaluation andyouwillseean
annex tothatregulation with alistofstudies required inorder toscientifically evaluate thesubstances.
This listisabsolutely identical with thelistofJECFA requirements because ithaspractically been
copied from JECFA.
511. IwastheChairman ofthisSafety Group atthiscritical time formore than three years and
washelping drafting these rules andregulations atthattime. This wasalsoaninteresting time because
JECFA hadjuststarted doing reviews andwequickly realized thatthiscould beofgreat help tous
intheEuropean Community.
512. IfIlook back atthetime between 1984 and1988-90 wehadnotachieved tosetanyMRL
because itisreally atedious procedure, andassoon aswewere able tocooperate with JECFA and
Codex andharmonized ourprocedures with asystem, wealsoharmonized with theFood andDrug
Administration wehadregular meetings theECCommission andvarious experts with theFood and
Drug Administration, there wasanexponential growth. Ifyoucheck thelistofMRLs wehave so
faradopted itisquite aconsiderable list. Butyouwillfindtheexposure limits, theADI, arealmost
every time identical, those proposed byJECFA with those used intheEC. There areslight differences
intheMRLs andthiscanbereadily explained because veterinary practices arenotthesame inall
countries.
513. Coming tothehormones, when JECFA hasproposed MRLs andADIs forhormones itwas
impossible todiscuss thisissue inthisSafety Group andintheCommittee ofVeterinary Medicinal
Products because itiswellknown thatwehave hadalready atthattime thespecific agricultural policies
andthespecific rules. Therefore itwassurprising tome,andItoldyouyesterday, thatsixyears after
JECFA haddiscussed these substances, aCommittee oftheECcame tothesame conclusions thatthe
JECFA position isadopted andtheyalsofeltitwasunnecessary tosetanamount inADI foroestradiol
andwasunnecessary tosetanMRL andthishasbeen signed bythecompetent authorities ofDGIII,
ofDGVI, ithasbeen published intheOfficial Journal. Andthisdemonstrates that, scientifically spoken,
what JECFA produces, what theJECFA Codex system produces, even iftheresults have notbeen
officially accepted intheCodex procedure they areused everyday andtothebenefit oftheconsumer
protection inEurope.
514. Iwanted tosaythisatlength because otherwise youcould have theimpression thatwefeel
very uncomfortable with JECFA. Infacttheopposite istrue.
515. Coming back more specifically toyour question Annex 2ismeant forsubstances which no
MRL isneeded. Igiveyoumaybe twoexamples. Ifyouusesometimes alocal anaesthetic onahorse
itmight benecessary tosetawithdrawal time butthisisaridiculous problem inview ofsetting MRLs
forconsumer safety inacommunity liketheEC. This could beacandidate forsuch asubstance, or
ifthesubstance absolutely harmless after theevaluation hadbeen done. Theusual procedure isthatWT/DS26/R/USA
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thecompany hastoapply forinclusion inAnnex 2andtheyhave tosubmit scientific evidence. Harmless
substances,mainlyharmlesssubstances,forwhichthereisnoneedtosetanMRL, forexample,elements
which endogenously occur inthebody. Itisarather long listandthey areputintoAnnex 2.
516. InAnnex 4itisalittle bitmore difficult. Originally thisAnnex hadbeen developed toinclude
substances forwhich itisimpossible todevelop anyconditions ofsafe use. This means forreal
hazardoussubstances,thiswastheoriginalmeaning.Butwhatthenoccurredthatlaterwehadsubstances
forwhich there were indications thatthey could behazardous andgaps inourknowledge missing
information. Since these were alloutofpatent substances andsince nosponsor applied toprolong
thepresence ofthese substances onthemarket inorder tobeabletodevelop themissing data, some
ofthese substances have alsobeen included inAnnex 4.That means wefindthere substances forwhich
itisquite sure thatthey arehazardous under allcircumstances andother substances forwhich there
isastrong indication thatthey might behazardous andnosponsor could beidentified who iswilling
toproduce themissing data. Maybe thisisenough forthemoment from mypoint ofview.
Mr. Thompson (Canada)
517. Mysecond question isalsodrawn from some ofthematerial inDr.Arnold 'sanswers. By
wayofprelude Icanletyouknow itisacompound question andthere willbesome follow-ups that
come with it.
518. Inyour answer toquestion 2.2onpage 5ofyour written answers there isatable thatdescribes
theuses ofnature identical hormones andtheir esters intheEuropean Communities. Myfirstseries
ofcompound questions are: How arethese substances used? Why arethey used for
oestrus-synchronization andwhen used forsynchronizing oestrus, aretheanimals treated because they
aresick orforazootechnical purpose? This question may also venture into theexpertise of
Professor McLean.
Dr.Arnold
519. Icannot satisfactorily answer allyour questions andsub-questions. Iwanted toshow only
afewexamples ofsubstances forwhich Iabsolutely know thattheyareused. Thelistmight belonger
because alistofsubstances which areincompliance with ourrules intheEChasbeen setupearly
ontheadvice bytheCommittee forVeterinary Medicinal Products, there aremore substances onthe
market. Iamnotaveterinarian soIcannot really tellyouwhether thisisjustified tousethese substances
forthispurpose. What Iwanted toshow youwashow similar some ofthese substances arewhich
areused ontheonesideforgrowth promotion andontheother sidefortherapeutic andzootechnical
purposes, butthere arealsodifferences intheesters, andbased onthistable Ideveloped myanswer
sothese were justexamples andIcanasanon-veterinarian notjustify their usebutIamsure they
areused inaccordance with thedirectives intheEC.
Mr. Thompson (Canada)
520. Iwonder ifProfessor McLean oroneoftheother experts canassist mewith thatinformation?
Dr.McLean
521. Thank youMr.Chairman. Oestrus-synchronization isacommonly-used animal husbandry
practice. You synchronize thereproductive activity ofyour herd foravariety ofpurposes; itmay
relate totheavailability offeed, itmight relate totheavailability ofmarkets, etc. Itisarelatively
common animal husbandry practice.WT/DS26/R/USA
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Mr. Thompson (Canada)
522. After usewould residues ofthese administered substances bepresent inmeat andmilk ofthe
treated animal?
Chairman
523. Iwould suggest thatalloftheexperts may takethefloor ifthey wish todoso.Who would
liketogofirst?
Dr.McLean
524. Yes, theresidues would beinmeat ormilk iftheanimal wasslaughtered. Itisinteresting
thatoestrus-synchronization thatisoften used indairy cattle inavariety ofproduction circumstances
andtheresidues would beinmilk.
Mr. Thompson (Canada)
525. IfIcould continue with thattable andsome oftheinformation onit.Iwonder ifanyofthe
experts who feelconfident could help mewith theuseofthese various esters intheECformulations.
What arethechemical differences between theesters andwhy aredifferent esters used andisthere
anycomparison ofpersistence inthebody ofthese various esters?
Dr.McLean
526. Theesters aregenerally used toalter therateofuptake ofthedrug from either theinjection
siteorifitisinsome sortofintravaginal device forexample, although generally notthere, italters
therateofuptake. Butwhat generally happens isthattheoestradiol ester isactually metabolized either
atthesiteofinjection intheblood orinthetissue andthebond between theactive substance, the
oestradiol, andtheside chain towhich itisbound isreadily broken andtheactive constituent
oestradiol 17beta, ortestosterone initsvarious forms, istheactive constituent.
527. There canbeunder some circumstances small quantities oftheester appearing intheblood
andthatispicked upbyanalysis. Butthose levels aresmall andnoconsideration when itcomes to
looking atthetoxicity because, forexample, ifthere were esters inthemeat andsomeone ingested
thatmeat thentheenzymes ofthegastrointestinal tract ofhumans thatdigests normal food readily cleave
theester bond.
Chairman
528. Mr.Thompson, justforthebenefit ofthePanel, would youanticipate todraw some conclusions
from these statements? Iamnotinaposition todosomyself.
Mr. Thompson (Canada)
529. Ithoughtthatwasthepurposeoftomorrow'smeetingwhenIwouldbepresentingoralargument.
Butthegeneral purpose ofthese lines ofquestions andafewothers thatIhave istotryanddemonstrate
thattheEuropean Communities usesome ofthese hormones either alone orincombination for
zootechnical purposes such asinincreasing therateofproduction insheep andcattle. Notwithstanding
thatother alternative means maybeavailable theycontinue tousethese substances forthese purposes.
What Iwould bearguing tomorrow inalikemanner isthatNorth America andother places usegrowth
hormones.WT/DS26/R/USA
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Dr.André
530. Mr. Chairman, Ithink there isavery bigdifference between theuseofsuch drugs for
therapeutical orzootechnical purposes. Invery precisely defined animals, asProfessor McLean said,
andtheuseofthesame hormones orsimilar hormones inlarge scale forgrowth promotion. Noscientist
hassaidthatitisabadthing tousethese hormones fortherapeutical use. Theproblem isforgrowth
promotion onlarge scales onalltheanimals, itisnotthesame thing asisbeing discussed now.
Chairman
531. Isittruethatfortherapeutical reasons thisisdone under prescription byassistance ofthe
veterinarian, while thegrowth promotion isnotdone so?CanIaskthisjustformyclarification to
oneoftheexperts?
Dr.André
532. InEurope itisdone under veterinarian control. Directly byveterinarians insome countries
orunder veterinarian control byprescription inother countries. Forgrowth promotion wehave no
experience.
Mr. Thompson (Canada)
533. Perhaps Icould continue with some oftheother parts ofmyquestion anditmaybecome clearer
astothereasons Iamasking this. Myunderstanding isthatitisnotsomuch therapeutic uses as
zootechnical uses inorder toincrease theproduction ofsheep andcattle sothattheir gestation periods
arereduced andhappen more frequently.
534. Can theexperts help mewith whether there areany synthetic hormones used inthe
European Communities forsynchronization ofoestrus such asmedroxy progesterone acetate or
allyltrenbolone, orwhether oestradiol iscombined with progesterone insome ofthese proceedings?
Dr.Arnold
535. Iwould liketoaskmycolleagues toassist me. What concerns allyltrenbolone there isan
exemption inthedirectives. This substance canbeused because, asIsaidyesterday, itisnotsuited
forgrowth promotion. Although thename issuggestive, itdoes nothave theproperties oftrenbolone.
Allyltrenbolone istotally different from trenbolone with respect tothebiological facts. Sothisisthe
first partofmyquestion.
536. Thenext partIamnotsosure. Iknow thattheEuropean Medicines Evaluation Agency and
theCVMP hasjustfinished anevaluation ofmedroxy progesterone acetate under myrecommendation
andthisdoes notfitintomypicture ofwhat islegal intheEC. Maybe you, François,youknow?
Dr.André
537. No,Ihave noinformation ofthisregulatory point butinanycase thiscompound isused for
zootechnical purposes andnotforgrowth promotion. Itwillnever beevaluated byECOrganization
asgrowth promoters. Itisavery different thing. Wearespeaking about things thatarenotofconcern
with growth promotion here.
Dr.Arnold
538. Myproblem isthatitissynthetic anditdoesn 'tyield thenatural hormone upon hydrolysis.
That ismypoint. Itiscertainly notsuitable forgrowth promotion.WT/DS26/R/USA
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Dr.McLean
539. Medroxy progesterone acetate issometimes included intoanintravaginal device along thelines
ofthesecond lineontable 2.2ofDr.Arnold 'ssubmission. Itisused inanumber ofcountries.
540. IfImight justaddforthesakeofclarification, whilst these substances forzootechnical purposes
areused inindividual animals, itisnotunusual insome practices forasignificant portion oftheherd
tobetreated over thelifeofareproductive season, ifIcould putitthatway.
541. Inother words, whilst individual animals aretreated youmight get10or15or20,Iamnot
fully familiar with theproduction procedures ofEU, oftheherd treated over onepartoftheyear that
isassociated with thebreeding season.
Dr.André
542. Mr.Chairman, maybeyouarenotvery familiar withthereproduction control infarm animals.
Inthiscase, may Iexplain toyouthatthemedroxy progesterone acetate isincluded inasponge and
thesponge isputintothevagina ofthesheep with asmall cord. During aperiod between 10days,
15days, twoweeks ormaybe alittle more butitisnotaproblem. Then thesponge ispulled outwith
asmall cord andthen after thistreatment theanimal comes intooestrus andisthen inseminated and
becoming pregnant inmost cases. Only onepercent failtobepregnant andthismaybe could bea
problem forthese animals, butusually people tryagain anditisnotreally aproblem. Itisnotaproblem
ofresidue ofsynthetic hormones because these animals arebred tohave sheep andthey willstaya
long time inthefarm. They willnotbeslaughtered after such treatment. Itisnottheobjective. It
isvery different totreating animals forgrowth promotion andtoslaughter them attheend. Itshould
bevery clear inyour mind.
Chairman
543. Isthisastepofpreventive medicine oristhisatreatment foranimals who have difficulties
toconceive?
Dr.André
544. Itisjustaso-called zootechnical practice. That means itismore easy forthefarmer tohave
allthefemales atthesame dateonoestrus andtoinseminate them atthesame time andthen tohave
products atthesame time. Itismore convenient formanagement ofanimals. Nomore.
Chairman
545. Butitisastandard procedure which isapplied tohealthy animals?
Dr.André
546. Itisfamiliar procedure. Itisapplied insheep mainly. More insheep Ithink than incows.
Mr. Thompson (Canada)
547. Can Iunderstand youtosay, Professor André, thatfarmers didittotheir whole herds ata
single time inorder toassist conception occurring atthesame time?WT/DS26/R/USA
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Dr.André
548. Ifyour question istoknow iftheycanbuythisproduct freely, theanswer isno.This product
isalways under veterinary control.
Mr. Thompson (Canada)
549. Ihadnotasked thatquestion. May Iproceed with mynext question Mr.Chairman?
550. Again Ihave asomewhat compound question. Inanswer toquestion 30ofthePanel concerning
thepotentialadverseeffectsonhumanhealthfromresiduesofcarbadox,monesin,olaquindox,avoparcin,
benzylpenicillin andcarazolol, ivermectin andorganophosphorus compounds, some oftheexperts noted
thatwhen used correctly, theresidues from approved veterinary drugs should notproduce adverse
effects inthehuman population.
551. Inquestion 17ofthePanel theexperts were asked toconsider theimplications forhuman health
ofresidues from themisplaced implants orimproper administration ofthesixhormones indispute.
And Iwonder iftheexperts could extend their analysis andcomment inrespect totheresidues ofthe
veterinary drugs Iread outandlisted inquestion 30,astowhat aresome oftheimplications forhuman
health when theyaremisused inasimilar waydescribed inquestion 17?Forexample, could theexperts
explain what adverse health effects may result ifahypersensitive person ingests meat ormilk from
ananimal thatwastreated with benzylpenicillin, when therequired withdrawal period hasnotbeen
observed andtheresidues from benzylpenicillin insuch meat ormilk exceeds prescribed MRLs, as
anexample.
Dr.Arnold
552. Maybe Icanpartly cover thisquestion. Iamalittle bitreluctant tocompare thehormones
with carbadox because both substances have been regulated, orproposals have been made byJECFA
concerning these substances, thatinboth cases ifgood practises areobserved there isnoappreciable
risk. SoIcould saytheyareequally safeifgood veterinary practices areobserved. Because although
carbadox itself isagenotoxic carcinogen, itissoquickly metabolized thatifgood practices areobserved
neither carbadox noritsmain carcinogenic metabolite ispresent asaresidue. Only aninnocent
metabolite quinoxaline carboxylic acid, which hasbeen extensively tested including carcinogenicity,
andthisisthecompound onwhich theMRL hasbeen proposed.
553. Ifsomebody does notrespect thewithdrawal time there might beanincrease inthisinnocent
metabolite, butthecloser youcome totheadministration there isanincreasing riskthatthecarcinogenic
compound itself oritsmetabolite ispresent. Forexample, atzero time ofwithdrawal itisobvious
thatitwould bepresent andthatnow youhave adifferent quality ofriskandhow doyoucompare
this? IfIamalittle bitreluctant andImust insist thatitistheaimofourprocedures, tocheck whether
conditions ofusecanbeproposed which iffollowed guarantee thatthere isnoappreciable risk. And
ifthepossible riskisqualitative innature howdoyouprepare this? This isthefirstpartofmylengthy
answer.
554. Concerning benzylpenicillin, Ihadlooked carefully atbenzylpenicillin, Iwasconsultant to
WHO atthetime benzylpenicillin hadbeen evaluated. What isinteresting toseeisthatabout 15per
centoftheworld population, some figures arehigher, other figures arelower, aresensitized against
benzylpenicillin. Butwehave carefully looked atallthereported cases. Only avery small number
ofcases onecandiscuss between fiveandtenbutinnowaymore than ten,have been observed over
themany years ofuse. Billions ofdoses administered ofbenzylpenicillin tohuman individuals causing
sensitization butfewcases where residues were thecause ofanallergic reaction. Thelevels proposed
byJECFA ofbenzyl penicillin aresolowthatinthewhole literature youfindonly three cases where
alower level hascaused aneffect inahuman being. Thedairy industry needs these lowlevels tooWT/DS26/R/USA
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because themost sensitive population inthiscase arethestarter cultures used foryogurt production,
forexample. They aremuch more sensitive than human beings. Sothehuman consumer benefits
from thisthatthemixcannot beused forfood processing purposes ifitcontains highlevels ofpenicillin.
Chairman
555. Thank youDr.Lucier.
Dr.Lucier
556. Ihave acouple ofquestions, before Iattempt toanswer thequestion. Socarbadox does produce
tumours inthelong term bioassays inrodents, isthatcorrect? And arethere multi-sites more than
onesiteofcancer intheanimals?
Mr. Thompson (Canada)
557. Idon'tknow ifI'mqualified toanswer thatquestion. Iunderstand thatit's11outof12sites;
perhaps Man SenYong cananswer thequestion forus?
Dr.Man SenYong (Canada)
558. Well, actually Ithink theJECFA hasdone theconcrete evaluation ofthetoxicology ofcarbadox,
including thegenotoxicity andcarcinogenicity. Somaybe Iwould have theJECFA persons toanswer
forthat.
Dr.Lucier
559. Letmeaskoneother question while youarelooking thatup. How are, inrelation to
Dr.Arnold 'sanswer, carbadox residues ever found inproducts consumed bypeople? And ifsoare
theMRLs exceeded from time totime?
Dr.McLean
560. AnMRL wasnotsetforcarbadox andnorwasADI specified. And it'spermitted foruse
providing with asensitive regulatory method you cannot detect residues. It'sametabolite
desoxycarbadox that'scarcinogenic. It'sashort-term intermediate metabolite between carbadox and
quinoxaline compound. And also quinoxaline-2-carboxylic acid, theend-metabolite, there were
carcinogenicity studies onthataswell astheintermediate desoxycarbadox. Soyouhave theparent
compounddesoxycarbadoxandthefinalmetabolite.It'sacompoundthat'susedwidelyinsomecountries
including theEUandtherecommendation ofJECFA wasthattheycould notontheevidence presented
state anADI oranMRL forgenotoxic carcinogenic.
Dr.Lucier
561. Soresidues arenever detected Iguess ofcarbadox?
Dr.Arnold
562. Ifthewithdrawaltimeisobservedwewillnotevenfinditquinoxalinicacidwithroutinemethods.
However, with more sophisticated methods youcanshow thatupto70days after treatment this
metabolite persists.WT/DS26/R/USA
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Chairman
563. CanIbriefly justformyclarification now askthePanel whether they consider itpossible to
compare theuseofthehormones wearetalking about andthesubstances wewere justdiscussing,
youwere reluctant todoso.Could Ihave theviews oftheothers whether thisiscoming intoacategory
where wecould really start comparing theuse.
Dr.McLean
564. Iwilltryandshed some light onitMr.Chairman. When anADI setforacompound, providing
thatADIisnotexceeded, thentheriskassociated withconsumption ofproduce containing thecompound
inquestion uptotheADI isessentially zero. Now Iusetheword essentially toputting emphasis on
thefactthatzero riskisnotanobtainable figure. However, ifyouexceed theADI, then thenature
oftheriskvaries from compound tocompound. Forexample, ifyouseriously exceeded theintake
ofcertain compounds, thendepending onthistoxicological profile, youmaycause some quite serious
effects. However, many oftheADIs aresetonarelatively minor change such asabody weight change
andchange inanorgan weight, some minor variations insome constituents ofblood. Sotherefore
toexceed theADI inthatcase would notbeasserious. And sowhat wedoiswedetermine alevel
where there isnoobserved effect inthetestanimal systems, thenweapply asafety factor andbydoing
thatyouessentially reduce theriskofconsuming anamount equal totheADIonadaily basis forlifetime
tozero. However, once youbegin toexceed thatADI youintroduce risk. Therateatwhich thatrisk
comes in,ifIcanputitthatway, andtheintensity ofthatriskvaries from compound tocompound,
depending onthattoxicological endpoint which made thenoeffect level upon which youderived the
ADI. You'vegotafurther question Iguess?
Chairman
565. Dr.Lucier, onthiscomparison question.
Dr.Lucier
566. That'swhere Iwastrying togetsome information sothatIcould determine whether ornot
such acomparison could bemade, interms ofatleast carcinogenic risk. Ithink thatwhat Dr.McLean
wastalking about wasnotessentially acarcinogenic riskthatwasahormonal activity risk. Sothey
aretwodifferent things, twodifferent methods toestablish risk, butIwasjusttrying todetermine
with theinformation available ifitwould bepossible tocompare thecarcinogenic riskatresidues that
might benormally encountered versus theresidues thatmight benormally encountered from thesix
hormones inquestion.
Dr.Ritter
567. Buttheissue Mr.Chairman, Ithink asanumber ofpeople have already attempted toexplain,
isthatatpermitted residue levels, none ofthese compounds constitute arisk. That'sthenature of
theprocess ofestablishing anADI andsubsequently aMRL. Itpresumes thatthere canbelifetime
dietary exposure, every dayofyour life,andthatcontinuous dietary consumption willpose, forlack
ofabetter term I'llsayessentially noriskatall.Thequestion thatyouareasking infactiswhat if
thatresidue level isexceeded? Itgoes beyond what'sbeen specified intheregulation, orinternationally,
andIthink theattempt that'sbeing made bywayofexplanation isthatitwould bepotentially misleading
tosuggest toyouthatthese risks canbecompared, because theADIs thatwe'vereferred torepeatedly
arebased onentirely different endpoints. They canrange from something relatively innocuous, in
which case ifanADI isexceeded theconsequence would berelatively trivial. And they canonthe
other hand extend tosuch issues ascarcinogenicity, inwhich caseitwould bepotentially avery serious
consequence. Sotocompare thetwo, simply because theyboth have anADI, presumes thatthatADI
hasbeen established onasimilar endpoint. Which isalmost never thecase.WT/DS26/R/USA
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Chairman
568. Would youthink thatthefactthattheuseabove theADI levels varies greatly alsoinduces
thepossibility tohave them regulated differently?
Dr.Ritter
569. Ithink thenature, having been involved intheprocess ofsetting ADIs both nationally inmy
ownjurisdiction andparticipating intheprocess onaninternational scale, oneisleftwiththeimpression
thatthenature oftheprocess issuch thatthere isasignificant margin built intotheprocess, thatin
factwillhave theeffect ofcompensating forthatinanycase. Ibriefly alluded tosome ofthose
yesterday. Forexample theassumption is,oneoftheassumptions wediscussed yesterday, isthe
consumption of500grams ofmeat perday. Imean Ithink wecanallprobably agree thatinfirst
principles that'sanoverestimate. And sotheriskhasprobably been exaggerated inthecalculation.
That youwillconsume thatriskevery dayofyour lifeandsoonandsoforth. SoIthink collectively
astoxicologistsinvolvedinthatkindofaprocess,wehavetheimpressionthatMRLs thataretemporarily
exceeded, occasionally exceeded, infrequently exceeded, arenotlikely toresult inasignificant health
consequence,becausethecalculationhasalreadybuiltinsomuchovercompensation,thattheseoccasional
transgressions arenotlikely toproduce anadverse effect. That'stheinherent nature ofthecalculation
itself.
Chairman
570. Isthisaview shared bythePanel?
Dr.Lucier
571. I'mstillsearching forananswer tohelp me. Irecognize thatthecarcinogenic riskofthese
agents isvery low. Within thatrange ofzerotovery low, ifIcould getinformation Icould saywhether
ornottherisks were comparable forcancer. Now thisisthegenotoxic carcinogen, oneaccepts an
ADI isestablished notonthebasis ofcarcinogenicity forgenotoxic carcinogens itsonthebasis of
something else.
Dr.Ritter
572. Inthecase ofcarbadox Ithink Dr.Lucier, what hasbeen explained isthatthere isnoADI
andthere isnoMRL, because itwastheconsensus ofthePanel thatreviewed thematerial thatasa
genotoxic carcinogen wewere unable toestablish what would popularly bereferred toasanacceptable
intake. Theacceptable intake isnothing.
Dr.McLean
573. Wewould notnormally seteven anendpoint based oncarcinogenicity, because generally
carcinogenicity occurs atmuch higher doses than wewould setano-effect level. Iftheno-effect level
wasbased oncarcinogenicity, wewould look atthecompound andalter safety factors andother things,
oragain wemight notpermit it.And sointhisprocess, inmanaging therisks through theADI, the
aimisreally tomake surethatyoudon'tendupwith carcinogens, asaresult atleast ofanimal toxicity
studies, inthefood chain.
Chairman
574. Perhaps, Dr.Lucier, youmentioned twodifferent methods ofdetermining risks. Onewould
beforhormonal action andtheother forcarcinogenic effect. Itseems tomethatwehave anestablished
method forthefirstoneandthesecond oneissomewhat newtothefield here. Could youelaborateWT/DS26/R/USA
Page 319
alittle bitonthesecond method andhow youseetheimplications inthatparticular field here, in
particular when wetalkabout whether these substances canbecompared orbetreated alike andso
on.
Dr.Lucier
575. IfIsawthetumour dataforcarbadox, Icould establish alevel atwhich acertain proportion
oftheanimals gottumours, andasbestIcould, Icould extrapolate down intothevery lowlevel risks
what people might beexposed to.There would have tobesome residues leftofcarbadox, justmaybe
notdetectable, there have tobesome residues left. And Icould compare thatcarcinogenic riskto
thatfrom oestradiol oranyofthese other hormones inquestion. Now, that'sacomparative riskof
carcinogenicity thecomparative potency inwhat people ingest from 500grams ofmeat aday. Sothat
would beadirect comparison. Iwould have toassume what carbadox levels exist andthatwaswhy
Iwaswondering how often they aredetected infactinmeat samples, ifever, andwhat thelimits of
detection would be.Then Icould take, youknow, something below thelimits ofdetection ofwhat
people areexposed toanddothecalculation onarough estimate with considerable uncertainty but
atleast toseeifthecarcinogenic potency isinthesame ballpark ornot. That'sallthatI'mafter.
Chairman
576. Issuch data available ornot? May Iasktheexperts?
Dr.Arnold
577. Ihave never seen positive results andIseeresidue monitoring data since many years. But
ithasnotbeen intensively monitored ontheother side, thatistheother difficulty. ButIcould perhaps
saythatatleast intheCommunity itisonly used inpiglets uptoamaximum ageof4months, soit's
quite realistic thatthewithdrawal times areobserved andthen there isnocarcinogenic residue inthe
tissues, justmaybe atrace ofthisinnocent metabolite.
Dr.Lucier
578. Iwon'tbelabour thisanymore after thisonepoint. Ifapparently there istumour data that
issummarized, ifIcould look atthatsometime during theafternoon I'lldomylittle calculations.
Myintuition tells methattherisks aregoing tobesimilar, carcinogenic risks.
Mr. Thompson (Canada)
579. I'madvised thatthere may beresidue datafordesoxycarbadox, butperhaps ifIcould restate
thequestion. Ithink wearenotcoming directly with what Iwasgetting at,wehave heard statements
and,Ithink Dr.Ritter wasdrawing attention tothefactthatwhen JECFA andCodex review andapprove
things andsetstandards itisassumed thatthere isnoriskassociated with anyofthese substances, any
ofthesixhormones atissue, orcarbadox, orcarazolol orthebenzylpenicillin. Theexperts hadbeen
asked tospeculate ifthestandard administration procedures areabused inrespect tohormones and
proper procedures arenotfollowed, isthere apossibility ofacarcinogenic effect. Andwehave heard
thatinrespect ofsome ofthehormones theanswer was, while close tozero risk, yes. And I'vebeen
asking inrespect tosomething likecarbadox, which hasalsobeen described asgenotoxic carcinogenic,
where anMRL andanADI cannot besetbecause ofit,ifwetake thehypothetical situation where
ithasbeen abused, administration hasnotbeen properly followed, canwedraw thesame conclusions?
Ortoputthematter another way, isthere arational reason todistinguish between permitting substances
which aregenotoxic carcinogenic islikecarbadox andpermit their use, while imposing atotal ban
onhormones which aresaidtohave norisk, verging onzero aswell?WT/DS26/R/USA
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Chairman
580. Who would likethefloor?
Dr.Arnold
581. Since youareasking fordata, maybe fortherecord Icould tellyouwhat wehave seenatJECFA
when pigs were treated with carbadox. The residue level ofthis, Icallitinnocent metabolite,
quinoxaline carboxylic acid was18.9 micrograms perkilogram at30days withdrawal; was 5.5
micrograms perkilogram at45days, 1.3microgram perkilogram at70days withdrawal.
Chairman
582. This goes totheprevious question. Would youcome back onthefigures here?
Dr.Lucier
583. Iactually dohave thetumour data. Carbadox isapretty potent carcinogen interms ofmultisites.
Sotheanswer toyour question isyesifimproperly used andthere were residues itwould pose a
carcinogenic risk.
Mr. Thompson (Canada)
584. And justbefore weleave thatperhaps Icould askDr.McLean toexpand onhisanswer to
question 11where hediscusses organophosphorus compounds andthehealth effects there. Perhaps
Icould askhimtocomment oncarazolol which Iunderstand isused fortransporting pigsimmediately
prior toslaughter andthecomparative withdrawal periods, andwhether there areanyrisks associated
with theuseofthatdrug.
Dr.McLean
585. Inrelation totheorganophosphorus compounds, theyarequite powerful neurotoxins inhumans
andinanimals, andareused generally tokillinsects although there areother uses forthem such as
removing foliage from certain crops. There aretwoproblems with them, oneisdelayed nerve damage
andthatisgenerally aresult ofdirect exposure ofoperators andthelike. However, under some
circumstances residues incrops inexcess oftheno-effect level have caused problems, acute problems
oforganophosphorus poisoning. And some ofthem arecarcinogenic andsotherefore safety factors
toremove thecarcinogenic hazard intheappraisal, that'sbeen taken intoaccount although, generally,
thesafety limits arebased onacute effects thatthepoisoning effects thatyousee. Butthey have been
associated with poisoning associated with exceeding theMRL. Inrelation tocarazolol, carazolol does
have aneffect oflowering blood pressure andheart rate, it'srelated tothedrugs commonly used in
human tocontrol blood pressure andheart rate. Itisalsoused toprevent aspecific form ofstress
inpigs during slaughter. And ofcourse pigs aresentfrom thefarm directly toslaughter generally
andifyouaregoing tohave aneffective treatment forthestress associated with transport, then you
have totreat them justbefore transport sothatthedrug iseffective during thetransport process. And
there hasbeen concern thatifpeople were toingest carazolol atthesiteofinjection then they may
getadose which could have effects onheart rateandblood pressure. Thesensitive human population
thatwastaken intoaccount inthisassessment arethose people already under treatment with thisgroup
ofagents forthecontrol ofblood pressure andassociated cardiovascular disorders, andifonewas
tosuperimpose adose ofcarazolol ontopoftheexisting medication then there could beaproblem.
Sothese twocompounds invarious ways, iftheADI isexceeded cancause difficulties.WT/DS26/R/USA
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Mr. Thompson (Canada)
586. Justaquick follow up. Aretheorganic phosphates ever used inanimal production?
Dr.McLean
587. Theyarecommonlyusedinanimalproductiontokeepundercontrolinsectsonanimals,relatively
widely used.
Mr. Thompson (Canada)
588. Yesterday theEuropean Communities quoted fingers, sorry figures, onthenumber oftests
they doforresidues ofhormonal substances. Weunderstand thatProfessor André 'sexpertise isin
theresidue testing. Henoted that theEChasdeveloped multi-residue tests. And Iwonder,
Professor André, could youdescribe what substances theEuropean Communities testforandcomment
onhow many ofthese tests come back positive andforwhat substances?
Dr.André
589. Icangive yousome comments inthefield ofmycompetence, thatmeans onhormones, on
thyrostatic compounds andonbeta agonist compounds. Concerning thefirst partofyour question
Icannot give youacomplete list,sotoday ofallthexenobiotic compounds which arelooked forin
arealmulti-residue analysis, butyoucanimagine thattheyinclude progesterone, nandrolone, oestradiol
andmanyothers,usually30differentcompoundsarelookedsystematicallyfor.Concerningthethyrostat
they arejustabout 6compounds usually, small compounds, andthey areallofthesame groups and
derivatives ofuroside compounds, true-uroside compounds. Andconcerning betaagonists theclassical
research includes now something astendifferent compounds from clenbuterol anditsgroup, Imean
manbuterol andothers andsalbuterol aswell asractopamine andmany others. Allthese compounds
have been banned inECandwearelooking forpotential misuse ofthese compounds. Thelevel of
detection ofthisresearch isvery important toconsider anditsalways below 2ppb. andsometimes
reach more sensitive levels assome 10or20ppb's.forlooking atresidues inmeat specifically.
Concerning thesecond partofyour question, interms ofpercentage ofpositive results Icannot answer
thisquestion asascientific people andthenumbers Icangive toyouwould bewrong numbers for
different reasons. Thereason ispersonally Iamincharge ofanofficial national laboratory andIhave
more positive thanusual because Iconfirm results ofother laboratories. This question hastobeasked
toofficial bodies ormaybe toourrepresentative ofofficial Community reference laboratories butnot
tome.
Mr. Thompson (Canada)
590. Iunderstand Dr.Arnold might beaware ofresults oftesting ofresidues ofhormonal substances
intheECandinparticular astudy ortesting done inBelgium. Could youhelpuswith thatDr.Arnold?
Dr.Arnold
591. Ithink FrançoisAndré made agood suggestion since theresults oftheresidue testing inthe
EUaregiven toallreference laboratories. It'sagood suggestion thatmaybe someone from these
laboratories answer thequestion. Ontheother hand Ialsoseethese results onaregular basis and
I,what Icansayissomething thatIhave already saidyesterday, wehave todiscriminate between
random sampling which gives youamore relevant picture andsampling ofsuspect animals. And I
saidyesterday already andIwould liketoconfirm this, ifwetaketheresults ofrandom sampling it's
notsobadthepicture. Inthemajority ofthemember States youfindnothing. There aresome member
States, Iwould notname themember States, butthere aresome member States where inveal calf
there seem toexist problems, mainly with thenatural hormones. Ifwegotosuspect sampling thenWT/DS26/R/USA
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thepicture istotally different, then wehave member States where wefindtrenbolone, zeranol, where
wefindprotestosterone, sometimes justafewsamples, sometimes ahigher amount. Butthishigher
figure isnotrepresentative forthesituation because thisthen sometimes arefollow upanalysis, so
Ihope Imade clear what mypoint is.Based onrandom sampling thesituation seems toberelatively
okay, with theexception ofveal calves insome countries. Based onsuspect sampling, wefindall
30things sometimes insome samples.
Dr.André
592. May Iaddjustashort complement tothese twocommunications. First ofall,itsclear that
allthecompounds Ispeak about arenotlooked forinanyother countries asinEC. And when we
discover some misuse ofsuch compounds, usually andquite systematically Ithink, themeat isnot
delivered tohuman consumption.
Mr. Thompson (Canada)
593. Yesterday weheard quite abitofdiscussion concerning hormone levels andIwould liketo
clarify withtheexperts what isaphysiological range andhowthatrange isdetermined andwhat controls
thatrange. Inparticular Ibelieve Dr.Liehr cautioned usthatpermitting theuseofgrowth-promoting
hormones inmeat might upset thebalance ofhormones inahuman ingesting themeat. Cantheexperts
describe what thebalance ofhormones inthebody is;isitfixed ordoes itchange onadaily orweekly
basis? And ifhormones areadded directly toahuman, what effect does thishave onthathormonal
balance? Perhaps some comparisons between theubiquitous 500grams ofmeat andacouple ofeggs
oraglass ofmilk which arealsoingested onaregular basis would beauseful comparison.
Dr.André
594. Concerning thebalance ofhormones weneed tomaybe aweek fordiscussion toexplain what
isnowknown about theinter-relations between hormones andthecomplex feed-backs phenomena and
soon.Justtohave anideaoftheeffect ofinjection ofhormones tohuman beings, it'swell known
Ithink thatbody-builders orsportsmen who areusing hormones asanabolizing agents, with higher
doses asusually used ingrowth promotion it'sclear, butthese people have always later very many
problems interms ofreproduction andsterility itsclear. That isoneidea toillustrate what cana
hormone doinhuman beings.
Dr.Lucier
595. Iagree with what Dr.André said. Thehormonal situation inyour body ischanging aswe
speak. It'schanging inmybody, yougetnervous your glucocorticoids goup,thatdoes other things
toyou, sothey areconstantly changing, inconstant state offlux. How each ofthehormones regulate
each other isnotanentirely known fact, infactitsnotreally known atall,except thatthattype of
balancedoesoccur.There'stremendousinter-actions,crosstalkaswecallit,betweendifferenthormonal
systems. When thisisdisrupted there canbeawhole cascade ofevents which could result inchanges
inbiology andpotentially adverse effects. After having saidthat, theamount thatonewould takein
from sayifwecome back totheexample of17beta oestradiol ineating 500grams ofmeat aday,
youbasically takeinonemolecule ofoestrogen ifyouwere awomen toevery 280,000 inyour body.
Sothechances thatthatwould cause anendocrine disruption isprobably very very slight, remarkably
close tozero. Ifyouareaman your levels would beone-fifth thatsoitwould beonemolecule to
every 50,000 molecules orsomething likethis,sothechance thatthatwould cause initself anendocrine
disrupting event isofcourse highly unlikely. There 'snodoubt thatit'scausing endocrine disruption
intheanimals thatarereceiving it,that'swhy they grow because their hormone system isdisrupted
andmodified andthebalance ischanged. It'saquestion ofamount.WT/DS26/R/USA
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Dr.McLean
596. Justbyway ofillustration ofthevariation, ifpeople want toturn totheattachment ofmy
submission, youwillseetheenormous ranges inpregnant cattle, orincattle ofprogesterone, oestradiol
andtestosterone; theranges andthevariations e.g.inpregnant cattle inmuscle forexample, thelevels
are10,000 nanograms perkilogram plusorminus 6,600. Enormous variations. And Ithink thatjust
reflects theindividual animals andsoit'sterribly difficult totiethisdown absolutely andprecisely.
Chairman
597. Imean avery popular comparison alluded to,theegg, theamount ofhormones youeatwith
aneggandthen it'scompared towhat youeatwhen youhave anintake ofhormone treated meat.
Isthatacomparison which canbedone andcould youelaborate onthis?
Dr.Ritter
598. Well I'mthinking wecould andinfactanumber ofresponses contain thatdirect comparison.
Thesteroid levels would becontained inaglass ofmilk, forexample. Thesteroid levels thatwould
becontained inafeeding ofbreast milk toanew-born infant would bethousands oftimes higher than
what onemight expect inasteak orahamburger. Butifyouwould likeamore precise number I'm
justgoing to.
Chairman
599. Itisjustwhether onecanmake these comparisons, whether they aresound.
Dr.Ritter
600. Ithink what I'mintimating Mr.Chairman, isthatonereally can'tbecause theyareindifferent
worlds...
Chairman
601. ...You can't...
Dr.Ritter
602. Letmeputitanother way. One canphysically make those comparisons, thenumbers are
available. Butthere isnobasis forcomparison. Thesteroid levels associated with aglass ofmilk
orhuman breast milk oranynumber offoods would bemany many many times greater...
Chairman
603. ...Yes, butthese arethesame steroids?
Dr.Ritter
604. Exactly thesame. Wearetalking orders ofmagnitude difference interms ofthedimension
vis-a-vis thelevels ofexposure from ahamburger resulting from ananimal thathasbeen treated, when
compared toaglass ofmilk thatyoumight have from ananimal that'snever been treated atall.WT/DS26/R/USA
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Dr.Arnold
605. Mycolleagues have limited their statements totheidentical molecules. Ifwewould addto
those identical molecules other naturally-occurring hormones infood which have adifferent potency
maybe lesspotent, buthave oestrogenic action forexample, thenwewould discover thatinmany kinds
ofnatural food including plant origin wefindsuch activity. Thesteroids andtheir derivatives, asI
saidyesterday, were very successful inevolution. So,even ifyougodown tomolluscs toseaurchins,
youfindthese substances, youcan'tescape eating these substances, orsimilar substances with related
biological potential every day. So,there isnowayeven ifyoudecide tocastrate yourself, inaddition
tostarve todeath, toescape these hormones.
Dr.Ritter
606. Mycolleague Professor McLean points outthatinthesecond submission oftheUnited States
(28October 1996) thatsortofcomparative table, Ihave personally notverified each oneofthese
numbers, butthatsortofcomparative table isinfactispresented onpage 4.Theintake ofoestrogen
oroestrogenic equivalents ranges from tensofthousands inthecase ofsoya beans; thecase ofin
anegg,youreferred toaneggas17,015 nanograms, andwhen wearelooking atanoestradiol implanted
steer, levels thathave been estimated aresomewhere intheorder of11nanograms. Aglass ofmilk
might represent 75nanograms inthistable, cabbage 24,000 nanograms. Iemphasize thatthese are
oestrogen equivalents because insome cases itisoestrogen directly, inother cases these willbewhat
issometimes referred toasphyto-oestrogen which arecompounds which arenotquite oestradiol but
areknown tohave anactivity thatiswhat wesometimes refer toasanoestrogen mimic, it'sanoestrogen
want-to-be. Zeranol isinfactproduced forexactly thatpurpose. Itisnotoestradiol directly, butit
isclearly, itisproduced asaresult ofafungus, butithasanaction which issosimilar tooestradiol
although thepotency issomewhat different, thatwecallitanoestrogen.
Mr. Thompson (Canada)
607. Justtofollow uponthatalittle bit,asisobvious toevery oneI'mnotascientist andsimple
examples help me. Someone hassuggested anexample fordealing with physiology istocompare it
toathermostat inahouse where there isarange oftemperature thatiscontained andwithin thatrange
arenormal things thatoccur, andthetemperature mayvary upanddown butthat'sanormal occurrence.
Andwhen onedrinks milk oreatseggs orconsumes cabbage there willbeanincrease within thatnormal
physiological range. One ofthethings Iwanted tofollow upon,andperhaps Dr.Lucier canhelp,
ashedrew thecomparison with the500grams oftreated beef ofonemolecule from 28,000, by
comparison areyouabletohelp uswith how many molecules per28,000 wemight findwith aglass
ofmilk inapre-pubertal boy, theglass ofmilk forbreakfast?
Dr.Lucier
608. Justsayyoung boy! tosave further embarrassment!
609. Now thenumbers formilk Ihave arealittle bitdifferent. Ihave them for17betaoestradiol
andtheyarealittle bithigher thanwhat youseeinmuscle tissue, Ihave nowaytoknow, since Ihaven 't
done themeasurement myself, which numbers areaccurate. These things ashasbeen stated before,
arepresent inmilk andvirtually everything weeat,oestrogen. So,yougetanoestrogen loadinaddition
toyourendogenousoestrogenfromanumberofdifferentsources.Notonlythenatural17betaoestradiol
from what youeatbutalsofrom thephyto-oestrogens andthefungal oestrogens thatwere already talked
about. There 'saconsiderable amount ofphyto-oestrogens insoya products especially soya oil. So
weareexposed toalotofdifferent kinds ofoestrogens justfrom day-to-day living thatareexogenous,
notproduced byourown body. Itwould bevery difficult formetototal them allupandthat'sone
ofmyactual research interests totryanddothattoseewhat thebody burden oestrogen thatweencounter
from day-to-day living from exogenous sources, togetsome idea what theriskofvarious kinds ofWT/DS26/R/USA
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disease might bebecause ofthose exogenous sources. SoIcannot giveyouavery good answer except
tosaythiswould only be,theamount onereceived from eating 500grams ofmeat, would berelatively
small compared totheother sources ofexogenous oestrogen onereceives.
Dr.André
610. Mr.ChairmanmayIgiveyouanotherexampleofhormoneinteractions,inrelationtothequantity
ofhormones inorder justtoillustrate what hasbeen saidpreviously. Wehave known hormone the
name iscortisone which hasvarious properties andanti-inflammation properties. Andwehave always
asecretion inside ofthese compounds. When youhave, forexample, anacute inflammatory process
thephysician willgiveyouahigh dosage ofexogenous orsimilar compounds ascortisone, forexample.
And thenyour ownsecretion willdecrease dramatically inplace oftheexogenous compound butafter
thismaybe aweek later youwillnomore need the....... [tape ends]
611. Forachronic skindisease youwilltakevery, very small doses ofthesame compound, cortisol
orcortisone oranother one, andyour own secretions willdecrease very, very slowly. Butifyoutake
these very small compounds asdrugs during months, andthen when youwillstop, youwillnever
recover your own secretions. Itwillhave stopped definitely.
612. That'sthedifference between anoccasional useandapermanent use.
Chairman
613. What willbetheconclusion?
Dr.André
614. Wecannot compare thefood intake ofdrugs orhormones inmeat occasionally, orthe
consumption ofapregnant cow, beefforexample, which cangiveyoualotofhormones andthesmall
amount ofhormone food intake forallthepopulation during months andyears. Itistwovery different
things.
Dr.McLean
615. IfIcould give youanother example, asamale contraceptive agent, male humans aregiven
testosterone,whichbyfeedbackmechanism,inhibitstheproductionofsperm.Thisformofcontraception
inhuman males isbeing trialed atthemoment. Inother words, youaregiving extra testosterone and
thepituitary gland sends amessage down thatthere istoomuch testosterone andshuts offthenatural
production, butatthesame time, itshuts offsome ofthehormones associated with sperm production,
andrenders theindividual temporarily sterile. And ofcourse once youremove thetestosterone being
administered tothemale, then itallcomes back tonormal. That istherapy thatisundergoing trial,
atthemoment, inanumber ofcountries oftheworld.
Chairman
616. CouldIjustcomeinwithonequestionwhichpuzzlesme?Whenweseethesenaturally-occurring
high exposures inmilk oreggs, how does thatrelate tothecancer research weheard yesterday? Is
theriskthatisbeing assessed today where wehave seen some thesis onit,isthatequally valid for
thisnaturally-occurring intakes every dayoristhere something special when wetalkabout growth
promoters? Could Dr.Lucier perhaps elaborate?WT/DS26/R/USA
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Dr.Lucier
617. Letmedothebest Icanonthat. Ifyoustart outwith apre-menopausal woman andher
oestrogen level which ofcourse isvery high, thisresults byatumour-promoting mechanism, andI
don'tthink Ineed togointothatatthispoint, inabout onewoman getting cancer inevery ten. So,
outofevery tenwomen intheir lifetimes, oneofthem willgetcancer. And that'sprimarily the
consequence ofhernaturally-occurring oestrogens. And that'sthepoint, andI'vemade alotof
comparisons throughout thismeeting.
618. Ifyoulook atthebeef, eating 500grams ofbeef, youwould getonemolecule forevery 28,000,
thepre-menopausal woman normally has, andonecould estimate acancer riskbased onthat.
619. Ifonesays then from other sources, besides beef, there isahundred molecules, andI'mjust
pulling thatnumber outoftheair,butsayit'sahundred, andthat'sprobably aconservative estimate.
Then, thatwould contribute ahundred molecules andsothecancer riskfrom allother sources of
exogenous oestrogens would beahundred times thatwhat itisinbeef, from agrowth promoted animal.
620. Sotheriskwould bevery, very small. Eating meat from agrowth promoted animal would
onlyrepresent asmall fraction ofthetotal cancer burden caused byexogenous oestrogens, notnormally
produced bythebody. Again, it'simpossible togive aprecise number forthereasons Isaid, because
there isavastnumber ofenvironmental oestrogens outintheenvironment andweonly know about
afewofthem. Wecertainly don'tknow about allofthem.
621. Ithink myconclusion would bebased ontheassumption thatalltheoestrogens areacting alike,
that they allinteract with theoestrogen receptor andstimulate thesame battery ofgenes asa
naturally-occurring 17betaoestradiol. That'scertainly trueforthemore potent oestrogens, some of
thefungal oestrogens, some ofthephyto-oestrogens, these kinds ofthings. They activate thesame
kind ofgenes sothere isareasonable scientific foundation, formyconclusion, although there issome
uncertainty init.
Chairman
622. Mr.Thompson.
Mr. Thompson (Canada)
623. Professor André, there areacouple ofquestions Ihave concerning some ofyour answers to
thePanel andIamhoping youcanclarify them forme,inparticular, your answer toQuestion 2.
You state inpart:
"On theother hand, ifthephysico-chemical ororganoleptic criteria areconcerned bythis
question, andthequestion ofmeat quality canbediscussed, significant alteration ofeating
quality, Lowman etal,andsignificant lossoftenderness, Gerkin 1995, ofmeat produced with
various implants have actually been reported."
624. When wegotothesource ofLowman, thestatement does notseem tobesupported. Icould
read from page 48oftheLowman Report. Itsays:
"With regard tothecomposition ofthecarcass andthemeat, itwasapparent thattheuseof
thehormone implants affected areduction inthepercentage ofcarcass fat,anincrease inthe
percentage lean andamarginal decrease ineating quality..."
asopposed toasignificant alteration, asmentioned inyour quote. Itgoes on:WT/DS26/R/USA
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"...andanincrease intheproportion ofsaleable meat forboth heifers andsteers."
625. Inrespect oftheGerkin Article, where youhave indicated theGerkin article identifies a
significant lossoftenderness, atpage 3323 oftheGerkin Article, theauthor states:
"Results ofthepresent study suggest thattheuseofsingle implants containing oestradiol, TBA
orthecombination ofoestradiol andTBA, hadlittle appreciable effect ondeposition of
intramuscular fatoronbeef tenderness."
626. Canyouhelp mewith how these articles support your statement?
Dr.André
627. It'sclear thatIhave notinvented thisassertion andthatthey arealsoinside. When yousee
only Lowman abstract, inthelastsentence. Itsays:
"...with marginal reduced eating quality."
That means thatthere isasmall reduction ofeating quality butthere isone.
628. Ifyoudiscuss about thedifference between significant andmarginally, marginally canbe
significant, statistically! Sorry, butstatistically, itcanbesmall, butsignificant!
Mr. Thompson (Canada)
629. Ialsohadaquestion about Question 6A.
630. This isdealing with whether there isanymore recent scientific evidence available with respect
totheeffects onhuman oranimal health oftheuseofthesixhormones indispute, especially when
used forgrowth promotion purposes, other than theevidence already taken intoaccount byCodex.
And youstate asfollows:
"Concerning human health, there isadiscussion onthedecrease ofhuman sperm counts"
andyouciteNimrod andBenson:
"An apparent increase oftheincidences ofhormonally mediated diseases likebreast cancer
andendometriosis andthedecrease inthemale/female ratio which arethought tobedueto
oestrogens intheenvironment. Whether theuseofhormones forgrowth promotion is
contributing tothisornot,cannot bescientifically proven, atthepresent time."
631. When Ilook atthesource, namely Nimrod andBenson, itappears thattheconclusion that
sperm counts have declined, isinfactcontroversial. And theonly reported decrease inhuman sperm
count refers tocounts ofmeninParis, over thepast20years, which iswithin theEuropean Community
andunlikely tobedirectly related toeating hormone-treated beef.
632. Can youhelp mewith thecorrelation between thedecrease insperm andthesexhormones
atissue forgrowth promotion here? This question isaddressed toDr.André.
Dr.Lucier
633. Thesperm count issue iscontroversial. Some people feelthatsperm counts intheindustrialized
world aregoing down, other people feelthattheyarenot. Andthere isalotofmethodological issues,
without going intothedetails, thatarecreating thecontroversy.WT/DS26/R/USA
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634. Thedecreased sperm count hasbeen reported inmore thanonepublication, however, butthat
hasnotremoved thecontroversy inthislegitimate scientific debate. Itisnotonly men inParis. For
example, men inCalifornia only have halfthesperm asmen inNew York. I'mnotsure why! The
men inNew York arevery proud.
635. Itisavery acontroversial issue. There aredata from experimental animals thatshow that
neonatal exposure tooestrogenically active agents does cause adecrease insperm count, later inlife,
inthemale offspring, andthere areplausible biological mechanisms forthat.
636. Butagain, thequestion ofwhether ornot,theamount received, Ithink itishighly questionable
thattheamount received ineating beeffrom hormone treated animals would benecessary toproduce
that.
Dr.Ritter
637. Tocontribute something perhaps tothedebate here, Ithink mycolleague, Dr.Lucier puts
itquite accurately. TheFrench datathatwasreferred toamoment ago,waspublished byPierre Roget,
Ibelieve in1992, intheBritish Medical Journal. Itwasthefirstofsubsequent reports thatwere to
come popularizing theissue ofdeclining sperm counts. There were subsequently significant
methodological issues identified inthatreport, nottheleast ofwhich were thatmany ofthese subjects
originated from infertility clinics orsperm banks! Consequently, Ithink itwaswidely recognized that
thismayhave been aninappropriate sample tousetoexamine declining sperm counts, orforthatmatter,
anything related tosperm.
638. Ithink Dr.Lucier puts itquite accurately, when hesays thatthisisvery much anemerging
area andIthink thebestthing orthemost accurate thing thatonecansay,isnothing atall,because
onecanfindasmany reports infavour ofadeclining sperm story, asonecanfindopposed toit.As
amatter offact, theNew York datathatDr.Lucier referred toamoment ago, wasrecently reported
byHarry Fish, who declared New York men tohave thehighest sperm counts intheUnited States,
butnohigher than New York men have been forthelast25years.
639. Thepoint thatDr.Fish wasattempting tomake isthatitwould beinappropriate tocompare
New York menwith Californian men, butrather youhave tocompare New York menwith New York
men, California menwith California men, because there canbemany variables thataffect sperm count
within ageographic region. Ithink thatthepoint thathewastrying tomake isthatitisinappropriate
tocompare across wide geographic regions, thebottom linebeing thatitiscertainly anemerging area,
butoneabout which theonly certainty iscomplete uncertainty!
Chairman
640. Would youliketotake thefloor?
Dr.André
641. Iread thispaper onemonth agoandIcannot findexactly thesentence butIamsure tofind
before thisevening something sointhispaper. Ithink youread italso, sowecanagree attheend
ofthissession thatthere issomething.
642. You cannot saythatthesperm elaboration isnotunder hormonal control, that'sclear. And
youcannot alsosaythatsome alkylphenol ethoxylates have avery dramatic effect onsperm elaboration
inmen andthatthese compounds have alsosome oestrogenic effects. That'sclear ornot?WT/DS26/R/USA
Page 329
Dr.Ritter
643. With respect, I'mnotsure itisquite asclear asperhaps youfeelitis.Thenonyphenol and
other ethoxylated compounds, Idon'twant togetintoasidedebate here, butthere areanumber of
authors whohave published reports indicating thatwhen compared toE2,interms oftheir oestrogenic
potency, they are10,000 times lesspotent. That order ofmagnitude. Infact, oneauthor suggested
thatifwewere tocallnonyphenol oestrogenic, there would befewsubstances thatwould notbe
considered oestrogenic, onthesame scale.
644. ButIthink toputitmore correctly, intoperspective, Ithink asDr.Lucier indicated, there
have been dramatic increases inbreast cancer which appear togobeyond those increases thatcansimply
beattributed totheintroduction ofmammography, particularly intheindustrialized world. There have
been increases inprostatic cancer, theorigin ofwhich seems tobeatleast inthefirstinstance, related
insome significant measure totheintroduction ofprostatic specific anogen. Forthose menintheroom
who areover 40,you'llknow theexperience very well.
645. Theinterest inapotential roleoftheenvironment inbreast cancer, Ithink, stems from the
fact, thatwhen weaddupalloftheknown riskfactors forbreast cancer, weinclude theageoffirst
pregnancy, thenumber ofsuccessful pregnancies, thenumber oflactations, theduration ofthose
lactations, allofthose things thatweknow areimportant riskfactors inbreast cancer. Wecan'taccount
forallofit,andconsequently there hasbeen aninterest inthescientific community tolook forother
things thatmay beinfluencing thedisease.
646. Ithink itwillbesome time. Certainly, Idoubt very much inmylifetime, where wewillbe
abletodemonstrate aclear definitive roleforaspecific environmental substance. Thework isjustified
because itisthedisease thathassuch enormous proportions thatasmall contribution hasanenormous
impact. IntheUnited States andCanada, toputitintoperspective foryou, there isanewcasediagnosed
approximately every 29minutes. Soyoudon'tneed tomake abigdenttohave ahuge impact. Ithink
thework isentirely justified, butforthose who arelooking forquick fixes, it'sgoing toberelatively
unrewarding. Theanswer isn'taround thecorner.
Chairman
647. It'saround 4o'clock. How long areyouplanning toproceed orshall wemake aninception
with theCommunity presentation. What would yousuggest?
Mr. Thompson (Canada)
648. Mr.Chairman, notwithstanding theslow start, ifyou'llpermit me,I'lltake30seconds tothank
thescientists fortheir very helpful andconcise answers andturnthephone over toMr.Christoforou
by4o'clock, ashewished.
Chairman
649. Thank youvery much foryour understanding.
650. May Igive thefloor totheEuropean Communities, Mr.Christoforou.
Mr. Christoforou (EC)
651. Iwould liketothank theDelegate ofCanada forhisunderstanding, inthisparticular case.WT/DS26/R/USA
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652. Before proceeding, Iwould liketoremind youthatwehave formally requested through the
Panel, Dr.Ritter, thepaper ofDr.Truhaut andwewould appreciate ifwecanreceive acopy ofthis
paper forourscientists tohave alook atthis.
653. Thespeaker who willbeleaving very shortly isDr.Adolfo Pérez-Comas from Puerto Rico,
who hasbeen investigating thepossibility ortheexplanation ofawide-scale premature sexual
development inPuerto Rico formore than about 20-25 years.
654. Iunderstood there were some problems raised bytheDelegate ofCanada whether these
projections willbemade. Icanonly announce there are,Ithink, 11or12slides. Some ofthem are
graphs showing theincrease ordecrease according towhich dietisfollowed, andthey areonly slides
which show what exactly wearetalking about. Ihave viewed myself these slides andwhat they are.
Most ofthem aredocuments andcharts ofestimations andthere areonly twoslides with theeffects
onchildren, pre-pubertal girls, what itisabout.
655. Iwould givethefloor ifourcolleague from Canada orprobably theUnited States, would like
tomake acomment.
Chairman
656. Mr.Brinza.
Mr. Brinza (US)
657. Asmycolleague from Canada hadindicated earlier, weshare similar concerns withtheproposed
presentation. Itsounded from thedescription Ijustheard, thatwearetalking about apresentation
ofnewscientific evidence, notapresentation designed tofallwithin thepurpose ofthismeeting, today,
which istotalkabout theresponses tothe28questions ofthefiveexperts, andtherefore wedon't
seehow thisisappropriate, atthispoint intime.
Chairman
658. It'shard totalkabout something youdon'tknow. Thequestion iswhether thiscomes inas
newevidence orwhether itsupports what hasbeen submitted bythedate. Asapractical matter, this
material canbeintroduced tomorrow, atanyrate. Youcould dothisinthesecond substantive meeting.
And from thatperspective, justavery pragmatic point ofview, Ithink it'ssimpler ifit'sdone here.
Mr. Thompson (Canada)
659. Areyousaying it'spossible tointroduce evidence ofthesecond oralmeeting tomorrow?
Chairman
660. I'mafraid Ierred. Lawyers areoften known asbeing champions forprocedures. Butthe
very good lawyers areinterested inthetruth andsosometimes they subject procedures tothefinding
ofthetruth, butthisdoes notalter thefactthat, yes, wecannotintroduce new evidence.
661. Whether it'sdone today ortomorrow. Itwould really depend onwhether it'swithin therealm
ofwhat hasbeen submitted by8February.
Mr. Christoforou (EC)
662. The United States hascirculated previously adocument which was notsubmitted bythe
8February. The issue about theincidence inPuerto Rico hasbeen argued bytheEuropeanWT/DS26/R/USA
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Communities, both inthesubmissions concerning theUnited States extensively, andinthefirstand
second submission forCanada.
663. Theissue hasbeen touched. Itwaswithin thetime-limits. Itisnotnew evidence. Itisan
elaboration ofwhat isalready inthesubmissions.
664. Icould nothave theslides soIcould send them before the7th. That iswhat so-called the
newevidence, theslides, butIhave here alsothedocuments which Iwould request their circulation.
Ifyoudon'tallow theslides, sowecancirculate thedocuments andhave alook atthem, butyouwill
miss the"nice" pictures ofgirls under theageof8with exactly what wearetalking about. This is
notanew document. They arewell aware oftheissue. Wehave debated thisduring thesecond
substantive meeting. TheUnited States hassubmitted documents about thiscase. They arealsoannexed
here sowedon'treally takejustoneview. Thedocuments submitted bytheUnited States, areinthis
document. Icancirculate thedocument ifyouwish andtheslides arethere. There 'snonewevidence
inthiscase.
665. Both ofthedelegations were aware when wediscussed forthefirst time on7January.
Chairman
666. Yes, Mr.Thompson.
Mr. Thompson (Canada)
667. IfIcould respond, Iamnot,noristheCanadian Delegation afraid ofthetruth. Butasan
experienced lawyer Iknow that, justasinscience, there areagreat many truths. And what Iam
concerned about, Mr. Christoforou hasraised what occurred on7January. You willrecall thatI
specifically asked Mr.Christoforou toidentify theexperts heproposed tocallsothatwewould have
anopportunity ofpreparing ourselves todeal with whatever evidence they hadtopresent. Hehas
never, until yesterday, indicated thatthisevidence wasgoing tobecalled orwho thisperson was.
668. Asamatter ofsubstantive fairness, irrespective ofprocedure, itisunfair topermit someone
topresent onesideofanissue thatmaybecontroversial andinflammatory without aproper opportunity
ofhaving evidence thatmay gotoanother point ofview.
Chairman
669. Mr.Brinza.
Mr. Brinza (US)
670. Iwould alsopoint outthatwhether they areslides ordocuments, ifthepoint istogoback
toissues orpoints thatwere raised inprevious submissions andmaking another presentation here,
thatisnotthepurpose oftoday 'smeeting. That would make thisanother substantive Panel meeting.
That isnotwhat wearehere for. TheCommunity hadplenty ofopportunities inourPanel process
topresent thisandtheysaidthatthey already have. There isnoreason togothrough thisagain today.
Wearenottalking about being afraid ofthetruth, butaslawyers, those procedures, Iliketothink
aredesigned tohelptomake surethatthetruth isbrought outandhaving breaches inthose procedures
isnotaway toensure afairness andafairairing ofthefacts.
Chairman
671. Mr.Christoforou.WT/DS26/R/USA
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Mr. Christoforou (EC)
672. Mr. Chairman, from what Iheard, they both don'tdeny thattheissue oftheincidence in
Puerto Rico hasbeen discussed extensively inthesubmissions. This istrue. IseeQuestion No.7
ofthePanel totheExperts saying isthere anyevidence andscientific evidence available which
demonstrates thatthepotential foradverse effects onhuman health arise andwhether there isany
evidence tothateffect.
673. Aswedidyesterday, Icould have Dr.Pérez explain orally, astheother scientists did,since
theissue hasalready been touched before. Ifyouindeed insist thatthese slides arenotprojected, at
least, there isaquestion totheexperts andweareallowed tomake comments.
674. Aswedidyesterday, wecanelaborate fiveminutes andthenanswer thequestion. Isthatreally
outside what istheunderstanding oftoday 'smeeting? Youhave been circulating documents yesterday
andwecancirculate those documents, aswell. There isaspecific question ofthePanel onthisissue.
Soasweagreed yesterday, hemay make thispresentation tenminutes orally andhave noprojections.
675. Mr.Chairman, Iwould forcefully really object tothattypeofprocedure which isapplied only
unilaterally, inthiscase, I'mafraid. These issues andfacts should beexplained inthepresentations
andthere isaquestion which wewould liketocomment onandprovide areply andaskaquestion.
Chairman
676. AsIsaid, itisdifficult totalkabout something youhaven 'tseen, sologically wehave tosee
itbefore wecanmake aruling. ButIdon'twant tospend toomuch time onthese procedural questions
andIwould invite youtomake thepresentation. Then theparties would have anopportunity tocomment
onthis, ifthey want to,theUnited States andCanada. Sothefairness ispreserved.
677. ThePanel would perhaps reserve it'sright tosubmit oneortheother question totheexperts.
Somay Iaskyoutogoahead with thepresentation?
Mr. Christoforou (EC)
678. What should Iunderstand bypresentation. Should Imake itmyself?
Chairman
679. No,no. Your expert, please.
Dr.Adolfo Pérez-Comas (EC)
680. Thank youMr.Chairman. Good afternoon ladies andgentlemen, members ofthePanel.
681. Myname isAdolfo Pérez-Comas. Iamapediatric endocrinologist andclinical geneticist,
fully trained under United States 'standards andcertified inendocrinology andmedical genetics under
United States 'standards andanadvisor totheCentre forDisease Control andtheNational Institute
ofHealth intheUnited States inthearea ofmyspecialty, participating atdifferent ongoing steering
committees, both attheCDC andNIH. Iamalsoanassociate professor ofpediatrics atthePonce
Medical School andpreviously attheMayaguez Medical Centre andtheUniversity ofPuerto Rico
Medical Science campus.
682. Wearegoing topresent toyoutoday accurately documented data collected inPuerto Rico
thathasbeen published inprime medical journals, such astheLancet, theNew England Journal of
Medicine, theJournal ofPediatrics andtheAmerican Journal oftheDiseases ofChildren, aswell asWT/DS26/R/USA
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inthePuerto Rican Medical Association Medical Bulletin thatisacertified journal inindex medicals,
andallofthese journals arepeer-reviewed byleading scientists inthefield, intheUnited States and
intheworld.
683. Iwillcondense here the50-year history ofPuerto Rican exposure tohormones with 28years
inthepractice ofpediatric endocrinology with 14slides presenting anomalous sexual development
inmycountry.
684. Imight also addthatPuerto Rico isthesecond-largest producer, atthemoment, oforal
contraceptives andhasbeen exposed forover 40years tooralanti-conceptives because theywere tested
inPuerto Rico prior toitscommercial disposition intheworld.
685. Original studies were carried outintheisland ofPuerto Rico inthelate50s.
686. Theaspect considered today hasbeen presented atguest lectures intheUnited States, Canada,
Spain, Cuba, Venezuela andtheDominican Republic. This isasummary ofthepatients wehave seen
under ourcare, dating back to1969, uptotheyear 1985 andpartof1986, where most ofthestudies
carried outbytheCDC were done atthesame time. Wearenotincluding recent data. Wearejust
going back tothedate when thedata collected bytheCDC wastaken on.
687. Thisisayear-and-a-halfoldfemalechildthatpresentsanomaloussexualdevelopment,categorized
aspremature telarche, because shehasisolated breast development, thatisnotnormal forachild eighteen
months old. Breast development should appear normally inourpopulation after eight years ofage.
Ifyouhave pubic hairorlaxial hair, thatshould notappear before theageofnine years, andifyou
have premature menses ormenarche, itshould notbepresent inanybody before tenyears ofage.
Anyone ofthose conditions thatappear before those ages, isnotnormal. Itmaybesecondary tothese
differentprocessesortumoursintheorganismoritmaybesecondarytoexogenoushormonesindifferent
areas thatcanbepresent.
688. This isaten-year oldgirlwho presented breast tissue atseven years, who presented pubic
hairatanormal age,attenyears, who presented menarche atanormal ageoftenyears, butwho also
presentedpolycysticovaries,ahighlyelevatedserumtotaloestrogenforherageandextremelydeveloped
breasts, thatIclassify asvirginal hyperphacial ofthebreast, acondition thatwasnotpreviously
associated with premature telarche orwith increased serum total oestrogen.
689. This isanother aspect oftheproblem weareseeing inPuerto Rico. Wehave severe cases
andwehave mild cases anditaffects children ofanyageanditaffects males, itaffects females and
itdoesn'taffectonlyPuertoRicans.Itaffectscontinentals,NorthAmericanslivingintheisland,German
people living intheisland, people from Latin America living intheisland. Once they getthere, some
ofthem suffer from these problems.
690. Inthepatients wehave studied uptothatdate, wemeasured, inasignificant number ofthem,
thelevel ofoestrogen. And wemeasured specifically thatserum total oestrogen thatwere carried on
under thesame standards ofDr.Arnold presented yesterday, inthetable with thenormal value as
specified andthisprocedure was carried onindifferent United States 'research andcommercial
laboratories, Biosign, Intersign, Project Clinical Laboratory inmainland United States andnotinPuerto
Rico.
691. Approximately 85percentofthose male patients whowere tested and86percentofthefemales
thatwere tested, presented high oestrogen levels. Iamspeaking of522patients hereandIamspeaking
here of146males with ahigh oestrogen level. Iamnotspeaking of30patients, ofnine patients or
of15patients. These areasignificant number ofpatients who presented high oestrogen levels.WT/DS26/R/USA
Page 334
692. When westarted studying these clinical cases intheearly 70swefound anincreased sizeof
theuteri. Atthatmoment wedidn'thave available sonographic studies, laparoptomies insome children
wehave toinvestigate what happened intheovaries. Theuterus wasfound enlarged insome ofthem
with thepresent ovarian cysts. When westarted having available pelvic sonogram, thisstudy was
alsodone inasignificant number ofpatients whocanafford topayforit.Outof447pelvic sonogram
studies, infemales with anomalous sexual development, 276ofthem presented abnormal pelvic
sonograms, enlarged uteri, polycystic ovaries, thesame thatcanbeseeninoestrus, inanimal husbandry.
693. 62percentofthose girls presented ovarian stimulation syndrome. When westudied thebone
cage, wefound thatin26percentofourpatients, thebone agewasaccelerated. This implicates that
theexcess ofhormones thatwaspresent inthese children have been ofmore prolonged duration because
itwasaccelerating thebone ageofourchildren. This data hasbeen published intheNew England
Journal ofMedicine, hasbeen published inthejournals Ihave mentioned previously, andcanbe
corroborated byanyone.
694. Wewere searching forthepossible cause ofthisinourisland. Welooked forexogenous causes
because thecondition didn'tfitwhat itshould beinanormal endocrine situation.
695. Asapediatric endocrinologist, Ishould seeone, twoorthree patients with abnormal sexual
development inayear. Once upon atime Iwasseeing fourorfiveaweek andsome days Iwasseeing
three orfour, inthesame day, new cases.
696. Wefound in1982 thatthediethylstilboestrol wasbeing soldover thecounter inPuerto Rico,
thiswasdone inonelocal agricultural store inPuerto Rico. That Ralgro orZeranol wasalsobeing
soldover thecounter atthattime. DES wasbanned intheUnited States atthattime andPuerto Rico
hasthesame rules andregulations astheUnited States, andduetothat, westarted suspecting that
something wasinthefeeding ourchildren were getting andwestarted agroup ofourpatients ona
diet. Wemodified thedietwith limited ingestion ofmeat, poultry, milk andeggs. Inaperiod offour
tosixmonths, themales thatwere onadiet, 60outof103, 58percent ofthem presented apartial
remission ofthecondition. Theabnormal hormones intheblood started going down, thebreast tissue
thatwaspresent started todiminish, those thathadpubic hairshowed nodifference, itdidnotincrease,
butitdidn'tdisappear.
697. Inthefemales, weobserved more atthesame period oftime, 51percentreduction with the
dietandapartial remission andeven atotal remission ofthesymptoms wehave observed before.
AsIpointed outpreviously they have been published bythatdate. 11percent ofthefemales and
sixpercentofthemales onnodiet, alsohadaremission, buttheremission presented inayear and
ahalftotwoyears. Inanobvious period during which thedietmayhave changed byitself ingrowing
children. This confirmed indirectly thatwewere dealing with some kind ofexogenous contamination.
There were notcases oftrueprecocious puberty byendogenous origin.
698. This remission ispresented hereregarding thedifferent agesin1969, 1970, 1972, 1973. There
wasvery small remission because wehadnotintroduced thediet. When weintroduced thediet
modifications andafter there wasabigpublic awareness intheisland when thissituation appeared
inonepatientintheTimemagazineoftheUnitedStates,theremissionstartedincreasing.Noteverybody
remitted butasignificant number ofthem didsowith themodification indiet.
699. TheFDA didsome screening studies andthisisacopy ofoneofthose studies, where apoultry
from Bonito Puerto Rico andapoultry from Royal Brothers Processing inMississippi were found in
thisscreening study aspositive foroestrogenic substances. Posteriorly ithadbeen reported thatthese
were negative inthenext studies thatwere performed bytheFederal agencies.
700. Dr.Carmen Saenz whohasbeen working inthisareawith me,whoatthesame time presented
apublication inthesame bulletin ofLancet asIdid,Ipresented a272page andhepresented 350ofWT/DS26/R/USA
Page 335
thesame condition. Shemeasured percentage ofzeranol through alaboratory inParis byDr.Morfine
where fiveoutofsixpatients thatwere sotested revealed levels ofwhat appeared tobezeranol, by
thattime orazeranol-like substance, confirming indirectly thesuspect wehad.
701. Wehave nowascreening testpositive foroestrogens andatest,possibly positive, forzeranol.
702. In1986, Dr.Fred E.Titulowel(?), another collaborator from theCDC, published anarticle
onanepidemiological study done inourpatients inPuerto Rico. 50ofmypatients, 60ofthepatients
ofDr.Saenz andapproximately 20more patients from theUniversity Pediatric hospital inSt.Juan.
703. Initially, wewere toldthatthisstudy didn'treveal anyrelation towhat wewere seeing related
toexogenous hormones, butifyoulook indetail intheconclusions ofthisstudy, thisstudy reflects
apositive andstatistical association between premature telarche andtheconsumption ofsoya-based
formula, which hasbeen widely known foralong time, various meat products andamaternal history
ofovarian cysts.
704. Obviously themother iseating thesame food asthechild andthefamily. With theclinical
experience wehave with thedietandwith thepresumption ofthelaboratory study, wemust conclude
thatwearestrongly thinking thatanexogenous thing ishappening inPuerto Rico andisstrongly
suggestive ofanexogenous contamination bythese substances.
705. Last week, on2February, thegovernor ofPuerto Rico under theprogramme oftelarche, that
istheonly onethatexists intheworld made some declaration totheSanJuan Star, thatisthelocal
press. Thenumber ofchildren with signs ofearly sexual development nearly doubled inthepastsix
years according tofigures released byasurvey byoneoftheisland 'stopexperts onthiscondition.
Thestatistics adds fueltoconjecture thatPuerto Rico hasthehighest incidence ofpremature sexual
development intheworld. There isnoother place intheworld with asimilar situation said
Carlos Bourdony who runs theHealth Department 'sPremature Telarche andSexual Development
Programme.
706. Astudy tobepublished intheApril issue ofPediatrics, theOfficial Journal oftheAmerican
Association ofPediatrics suggests thatgirls seen inpediatric office practice aredeveloping pubertal
characteristics atyounger ages than suggested instandard pediatric text books andbyearlier
United States 'studies. Early sexual development hasbeen monitored inPuerto Rico since 1988 when
thelocal health department setuparegister, theonly oneofthiskind intheworld, according to
Dr.Bourdony. Todate, 6,115 cases ofchildren with premature sexual development have been
documented bythePuerto Rican Department ofHealth.
Chairman
707. Could Iaskyoutocome toaclose. You have onemore minute.
Dr.Adolfo Pérez-Comas (EC)
708. This figure isnearly double. The3,162 cases documented between 1969 and1991 anddo
notinclude the4,500 patients evaluated byDr.Saenz andmyself. This includes thepatients evaluated
bytheother 11endocrinologists. [Tape ends]
...studies .....performed bytheUSDA Department ofAgriculture found nosignificant ortrace level
ofgrowth andenhancing hormone inthelivestock specimen, according toBourdony. Butintheabsence
ofconclusive research, wecan'tsaythisfactor hasbeen completely eliminated, asisstated by
Dr.Carlos Bourdony, theHead ofthisTelarche Programme oftheDepartment ofHealth inPuerto
Rico. Thank youvery much, Mr.Chairman.WT/DS26/R/USA
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Chairman
709. Thank youvery much Professor foryour very interesting presentation. Thematter wasraised,
reference wasmade inearlier proceedings totheCosta Rica studies. Wewillassess towhat extent
new evidence wassubmitted here, inparticular, Irefer toanApril study which seems tobenew to
usandthePanel willreserve itsrights toregard ordisregard theevidence submitted inthelight of
thistesthere. Iwould nevertheless asIindicated briefly, give theopportunities toCanada andthe
United States tocomment onthis. And Icansummarize ofcourse myimpression thatnothing has
been saidabout therealcauses which may have ledthissituation anditwould take very elaborate
discussions togointothishere.
Mr. Thompson (Canada)
710. Thank youMr.Chairman. That would bemyimmediate reaction aswell, asIamunsure how
anyofthismaterial relates totheissues thatthePanel must decide. IfIwastobeputting questions,
Iwould beinterested toknow what tests methodology wasused forzeranol, were theresults confirmed,
andwhat ismeant byazeranol-like substance?
Chairman
711. Thank youvery much, Mr.Brinza.
Mr. Brinza (US)
712. Thank you, Mr. Chairman, onemoment please. Iwould liketohave some ofourexperts
comment onthisvery briefly. Dr.Miller who ishere with usisfamiliar with thissituation, asare
some ofourother experts aswell.
Chairman
713. Thank youvery much.
Dr.Margaret Miller (US)
714. IamDr.Margaret Miller, Centre forVeterinary Medicine, FDA, andIwould liketosaythat
these types ofhealth effects arevery disturbing totheAgency andweexpended alarge amount of
research dollars andenergy, asdidourcolleagues attheUSDA, investigating thissituation. And as
aresult ofthatactivity weconcluded thatthissituation isnotduetothehormones present inmeat
from animals treated with approved products used forgrowth promotion.
Mr. Brinza (US)
715. And thisisDr.Richard Ellis who isalsofamiliar with thissituation.
Dr.Richard Ellis (US)
716. Thank you, Mr.Chairman. Ihadaresponsibility forcoordinating oursampling programme
during thatspecial study. Infactweactually conducted three studies, over theperiods ofwhich were
referenced bythispresentation. Thethird study which weconducted wasbyfarthemost extensive
oneandwelooked atapproximately 700samples thatwere collected from beef animals, piganimals
andpoultry. Welooked atboth domestic production from slaughter plants, from imported product
atinspection sites, andalsoproduct collected atlocal markets. And asDr.Miller said, inallofour
studies, wedidnotfindthepresence ofanyzeranol, DES orrelated products inourstudy. Butin
asmuch aswedidnothave methodologies foralltheproducts thatwewould have liked tohave lookedWT/DS26/R/USA
Page 337
at,weeven submitted aportion ofthose samples forbioassays byFDA. And wehadnegative results
onthose bioassays ofsamples submitted toFDA forthatpurpose. Ifitwould beworthwhile tothe
Chairman, when wegoback toWashington Iwould beglad tosend youcopies ofthose documents
tosupport mystatements. Thank youMr.Chairman.
Chairman
717. Thank youvery much. May Iaskwhether oneofthemembers oftheexperts would liketo
take thefloor onthispresentation here? Yes, Professor McLean.
Dr.McLean
718. Ijustwould liketomake twocomments. First ofall,Ireally donotseewhat thishastodo
withtheissue ofusing hormonal growth promoters inaccordance withgood animal husbandry practice.
And justacomment, theuseoftheword "zeranol-like" would suggest tomethatthere iswidespread
contamination offood material with Fusarium fungi, fortheFusarium fungus which produces zeranol
anditsrelated compounds, sothatmight give some indication astowhat onemight look forifone
islooking atacontaminant. AndIwould draw attention tothePanel thatzeranol wasactually discovered
because Fusarium contamination ofpigfeed, asIremember it,produced signs ofoestrogen responses
inpigs, asIremember it.Itwasfrom there thattheresearch work identified thatitwasaproduct
offungal metabolism bytheFusarium species andonitwent there. SoIwould suggest thatthe
Puerto Ricans might liketoinvest some money onwidespread looking ofwhere theFusarium is,what
species itisandwhat itisproducing. ButIdonotbelieve thatthishasanyrelevance totoday 'shearing.
Dr.Lucier
719. Excuse me,ifIcould addabittothat. Itisknown thatzeralenone andzeranol-like substances
produced from Fusarium doproduce hyper-oestrogenism inswine andincattle, which itfedmouldy
corn thatcontains high levels ofthis, andlikewise itcancause neonatal problems, butthese areusually
massive amounts. Butthen Ithink there have been some Indian tribes intheUSwho have eaten large
amounts ofmouldy corn inwhich there wasoestrogenic responses which areadverse aswell. Sothere
isinformation intheliterature astosuggest thathigh levels ofthese, cancause adverse effects, ina
number ofdifferent ways. Theamounts thatarepresent ingrowth promoted animals, however, have
been very, very much lower than thisandwould notproduce those kinds ofchanges thatthey were
reported here. Although itispossible zeralenone substances from mouldy corn andother products could
doit.
Chairman
720. Thank youvery much. Canweclose thediscussion onthispresentation. Mr.Christoforou?
Mr. Christoforou (EC)
721. Mr.Chairman, ifyouwillallow uswewould suggest thatthispresentation isabout 90per
centareproduction ofthedocument thattheUnited States hascirculated during thesecond oralmeeting
wehadhere on11November. Asrightly Dr.Pérez hassaid, there aresome uncertainties about the
actual cause, buthehasprovided some insights, some information onthepotential possible explanations.
Inthearticle which theUnited States hasamended totheir submission during thesecond meeting of
thePanel, thatwas theofficial explanation given bytheUnited States andwhat wedidisthat
Dr.Stephany hasgone today through thearticle provided bytheUnited States asanexplanation of
thesituation inPuerto Rico. Hewould liketomake atwo-minute statement about theanalytical methods
used, inthatarticle provided bytheUnited States inthiscase.WT/DS26/R/USA
Page 338
Chairman
722. Isitabsolutely necessary? Because westillhave alisthere ofquestions which arevery much
tothepoint here andwedonotwant to,butIdoappeal toyouandurge youtoselfrestraint justto
really submit issues which arepertinent. Thank you.
Dr.Stephany (EC)
723. Thank youMr.Chairman. Some material hasbeen disclosed tomeyesterday andtonight.
Iamnotquite sure whether thatisthedocument Dr.Christoforou spoke about, sohave Itomake
thatrestriction, butbasically itisnotessential. Ihadthepleasure in1983 according tomyrecollection,
thatDr.Alice came tomylaboratory andwediscussed thewhole case. Atthattime wehadsuperior
technologies available forhandling these problems, unfortunately samples never showed upandfor
methecase wasclosed andonly yesterday Isawsome details. Iwillnotgointoanydetails but
summarizing what Ihave seen, Iwasverymuch surprised about thesmall amount ofpotential substances
thathave been checked orcould beseen bythetechniques used atthattime. That what especially
inthefield ofthezeranol-like compounds, Idonotthink thatIhave anycriticism basically, butsome
oftheso-called bioassays andreceptor-assays Ithink Ihave severe criticism thatpotentially strong
oestrogens have slipped through thesystem, notbeing detected. Sostating itvery shortly thatnothing
hasbeen seen soitcould notcome from xenobiotic oestrogens, maybe thatisalittle bittoostrong.
ButDr.Miller summarized thatthisdidnotcome from thecompounds thatareintheregular implants
orthose implants thatonce have been regular, likediethylstilboestrol. SoIdon'twant togointoany
details, Ionly offer once again after allthose years tocooperate, toclarify thisvery intriguing affair
inPuerto Rico. Butwhatever thecause is,itisavery serious problem, andIlearned from mycolleague
thattheproblem hasnotstopped, elsewhere intheworld alsosimilar problems areshowing up.That
iswhat Ihave tosay.
Chairman
724. Thank youvery much. Mr.Christoforou youmay continue.
Mr. Christoforou (EC)
725. Thank youMr.Chairman andthank youvery much indeed. Both theUSandtheCanadian
delegation ofthisparticular issue, which wasofserious concern totheCommunity because wehave
been making thisargument since thevery beginning. With your permission then, ournext scientist
who willbeleaving isDr.Adlercreutz. Hehasalready provided thepaper within thetime-limits.
Forthispaper theUnited States have already made comments andIwould state thatDr.Adlercreutz
willtouch only upon onewhich wethink important andrelevant issue inthiscase. Iwillgive the
floor toDr.Adlercreutz.
Dr.Adlercreutz (EC)
726. Iwasasked tosaysomething about thepossibility ofcarrying over anabolic steroids tohumans
after eating meat. Ihave brought with meoneofthearticles, andtheother because Icame yesterday
from theUSA, Icould notrecover thesecond one. Butinessence itissothatwecannever besure
thatthefarmers really usethesubstances they arelegally asked touse. Inthisarticle written by
Demetrios Esgotas andTom Tuten from theDepartment ofPathology andLaboratory Medicine Emory
University School ofMedicine inAtlanta. Noexcuse me. Itwas Debruyckere, Sagher and
Van Peteghem andthisisfrom theNetherlands, inGhent, Belgium, excuse meyes[passage unclear].
Ireceived thisyesterday. Inanycasethey state here, inthiscountry Iknow thattheyarevery careful
with their testing ofthemeat andthey tested in1990-1991 608injection sites. And they found that
over 60percentcontain atleast oneillegal anabolic agent. And Ihave avery long experience inthe
doping field andIwould saythatIamoftheopinion thatitisimpossible thatgood veterinary practiceWT/DS26/R/USA
Page 339
isused because there issome bigeconomical benefits ofgetting ahigh gross. SoIwould liketoask
theAmerican delegates andCanadians also, whether anysuch study hasbeen done intheUnited States,
testing really how much illegal anabolic steroids areused. Infactthere aretwoarticles, onewhich
Icouldn 'tyetgetbutIwaspresent atthemeeting when itwaspresented, andthey found inpeople
whowere notsportsmen andnottaking partinanysuch activities which would need anabolic steroids,
they hadfound onecasewith nandrolone metabolized inurine which must have come from thefood,
because there wasnoother possibilities. And then they didthisstudy here andfound inthecontrol
group onesubject who hadclostebol which isanabolic steroid intheurine, despite thatthere wasno
possibility thatthisperson hadtaken anydrugs. Then they added alittle bitofthisdrug tomeat and
fedittosome people andfound thattheycould detect bydoping tests these compounds. Andweknow
from thedoping field thatforexample, nandrolone injected intohumans canbedetected four tosix
months after theyhave been given. So,inmyopinion itisavery serious thing ifsportsmen arecaught
andgetting doping positive samples, ifthey eatmeat. And theriskaswell isrelatively high, because
now itisnecessary forevery doping laboratory tohave high resolution apparatus, soitmight bethat
they candetect even after sixmonths, sovery small residues inmeat. Imean I'msure thatifyou
testthings inmeat andyougetnegative results youcanstillfindthese compounds inurine, absolutely
sure,becausetheurinemethodsareextremelysensitiveandthemeatmethodsarenotsosensitivebecause
itisdifficult toextract these compounds. SoIwould liketoaskwhether thisistaken intoconsideration,
thatthefarmers don'tfollow therules andthatthisisinfactvery comparable tothesports field?
Chairman
727. Thank youverymuch. According toourrules these questions maybesubmitted totheMembers
ofthePanel andmay Iinvite youtocomment onwhat Dr.Adlercreutz. saidandIalsorefer tothe
paper which wascirculated, theevaluation ofthe32nd report ofJoint FAO/WHO Expert Committee
inFood Additives andthediscussion ofProfessors Liehr 'sreport. Have youbeen abletoread this?
Butifnot,could youcomment onthethesis thatDr.Adlercreutz issubmitting.
Dr.McLean
728. Pigsandhorses naturally produce 19nortestosterone andwefindthatderivative oftestosterone
intheir tissues andinurine. They canalso, using thesame enzymic pathway, produce 19norsteroid
derivatives ofanabolic steroids, which ispermitted innormal therapy inhorses forcertain disorders.
And soitmay well bepossible thatthehuman athletes have eaten pigorhorse meat which could be
thesource of19nortestosterone, oreven may have eaten horse meat from horses which have been
treated 19norsteroids. Andsotherefore itdoes notsurprise methesorts ofresults thatDr.Adlercreutz
hasreported areso.
Dr.Arnold
729. Itseems toconfirm what Ihave saidyesterday andtoday andwhat Ihave alsosaidinmywritten
answers. There isasignificant black market inEurope andinsome countries itismore important
than inothers. SoIperfectly know that, specifically inBelgium, along listofillegal substances are
regularly found. Theauthorities spend alotoftime andmoney toanalyze many samples. ButIdo
notseewhat therelevance iseither thelegal useforgrowth promotion orfortherapeutic purposes.
Imean, onboth sides oftheocean, wehave strict rules andweseeanexample thatononesideof
theocean these rules areviolated.
Dr.Randell (Codex)
730. The1984 FAO/WHO expert consultation certainly pointed outtheopinion oftheexperts at
thattime thattheillegal useofveterinary drugs created afargreater potential public health problem
than theregulated useforgrowth promotion. Ithink thatthatfinding in1984 probably stillstands.
Iwould liketopoint outtwotexts adopted bytheCodex Alimentarius Commission, andImight addWT/DS26/R/USA
Page 340
adopted onthebasis ofconsensus, bytheCodex Alimentarius Commission. The recommended
International Code ofPractice fortheControl anduseofVeterinary Drugs andtheCodex Guidelines
fortheEstablishment ofaRegulatory Programme fortheControl ofVeterinary Drug Residues inFood.
Both ofthese texts exist toguide governments inestablishing control practices andincontrolling
veterinary drug residues. Togodeeply intothesecond oneofthose texts, itdoes getintoalotof
sampling statistics andunfortunately sampling statistics tend toshow thatunless youarewilling to
essentially send allofyour food supply tothetestlaboratory, andtherefore starve todeath, youare
notreally going tofindwhat itisyouwant tofindatvery, very lowlevels. Sosporadic cases such
aswehave heard could probably exist even within theframework ofaproperly regulated control
programme.
Mr. Christoforou (EC)
731. Before Igivethefloor again toDr.Adlercreutz Iwould liketosaysomething, something which
probably might have escaped thepoint which wewere trying tomake. Thepoint wearetrying to
make isnotonly from illegal use, itisalsoaswehave heard yesterday from Dr.Lucier, thatthere
isaprobability even from theuseaccording tothegood agricultural veterinary practice. Itmay be
anincrease atwhat wecould call,butwedonotknow what exactly itisthenormal physiological levels.
Ifthey areallowed tobeused, asitisintheUnited States andCanada, there isapossibility they may
be,more possibility thatthese increases may befound. And thepoint Dr.Adlercreutz wastrying to
make isitmay have repercussions notonly ontrade issues, these questions, butmay affect legitimate
sports activities because suddenly people bysimply eating meat may bediscovered tohave increased
quantities ofthose residues which theywilldisqualify them from thegames without them having done
anything wrong. That isthepoint Dr.Adlercreutz wastrying tomake.
Dr.Adlercreutz (EC)
732. This isinfactoneofthepoints. Intheother paper, Iamwell aware that19norsteroid
metabolites occur incertain animals andsoitwould bepossible naturally andtheoretically thatthese
people have been eating, Idonotthink horse meat ashorse meat isnoteaten much inEurope, itmay
bepigmeat. Butinfactthere hasnotbeen shown thateating thiskind ofmeat youcangetthese
metabolites inhuman urine. Buthere inthispaper infacttheclostebol isnotfound inanyanimal
andhere they found onecase with clostebol inthecontrol group sothere isvery little chance thatit
came from anyother source than thediet. Butwhat Iwould alsoliketopoint outisthatwhich Ialso
pointed outinmyreport, isthatweknow very little about theeffects ofthissteroid inthebrain. And
Ihave personal experience alsowith regard tothebehaviour ofathletes both before andafter taking
anabolic steroids. And weknow now because thisneuro steroids inthebrain occur invery very low
concentrations andyouneed very small things tochange thelevels ofnormal steroids inthebrain.
They arereally atvery lowlevels active. Soifyouthink thatyouconsume meat containing lowlevels
ofanabolic steroids every day, they willbetransferred viatheblood brain barrier andtheoretically
could interfere inthebrain. And Ihave been involved inpolice cases andinsevere depression cases
after taking anabolic steroids andnaturally thedoses have been high. Butnow knowing thework by
Etienne Emile Beaulieu inFrance which shows thatthese arevery lowamounts which areneeded to
change, forexample, animpression ofanimal ofanother animal, canchange their levels very little,
butsignificantly. Soitispossible thatlowlevels ofsynthetic steroids canaffect ourbrain long term
andvery little isknown about thatandIhave notbeen abletofindanystudies showing how high the
concentrations of,forexample, anabolic steroids, areinthebrain after intake. Idonothave anysuch
material, butIamalittle bitreluctant because ofthisphysiological observations made recently inrecent
years.
Chairman
733. Mr.Christoforou, howlong would youintend togo?Wewant toreserve some time forfinal
questions bythePanel which areimportant tous.WT/DS26/R/USA
Page 341
Mr. Christoforou (EC)
734. Mr.Chairman, Ithink itmaytakemeprobably until quarter tosix.Itwilldepend onthereplies
Iwillbegetting from thequestions ofcourse, butabout quarter tosixorsixo'clock, butIhave a
number ofquestions andIwillcutalotofthem, butitwilltake mereally some time.
Chairman
735. Ihave afeeling thatabreak would dogood tothismeeting. Wewould resume, ifyouagree,
inquarter ofanhour, buttrytocutitdown totheessentials. Thank you.
Chairman
736. Iwould liketogive thefloor totheEuropean Community forcontinued intervention.
Mr. Christoforou (EC)
737. Mr.Chairman, yesterday weleftthediscussion atthepoint where wewere discussing theissue
why JECFA hasnotfixed anacceptable daily intake forthethree natural hormones. And there was
anargument going between, asIunderstood, Dr.Lucier andDr.McLean, whether thatwasfirstof
allfeasible tobedone andthen ifitwasfeasible, why itwasnotdone inthatcase. This isalready
with therecord ofthePanel atthispoint, butIwould liketorecall andthencome back with theprecise
question.
738. We have already explained inour second written submission tothePanel that the
European Community does apply maximum residue limits andtests, asIsaidyesterday, 59,000 in
serum forthethree natural hormones. They arethevalues given hereonpage 16ofoursecond written
submission. Exactly thesame, theUnited States hasalready said intheletter thatwassent tothe
European Community in1987, andwehave quoted these values inthefootnote thatwehave submitted
inthesecond written submission totheUnited States Panel.
739. Forexample, theUnited States hasfixed foroestradiol 120ppt,forprogesterone 3ppband
fortestosterone 640ppt. These arepublicly known andhave been communicated totheEuropean
Community asbeing thevalues thatshould notbeexceeded: thetolerances, thethresholds. Butthen
theUnited States hasreplied thatalthough reliable research methods areavailable fordistinguishing
these levels from background, aregulatory method isnotrequired because under conditions ofuse
theactual increases intheendogenous steroids arefar,farbelow permitted concentrations. Sofor
thatreason they donotinclude them intheir annual control plan.
740. Mr.Chairman, linked tothatissue istheexplanations were given byDr.Lucier onthefact
thatprobably thealready existing physiological levels arecarcinogenic ofthethree natural hormones,
inthiscase itwasoestrogens. TheCommunity hassubmitted evidence, which wasnotdiscredited
asfarasIknow, showing thattheincrease oftheriskwasprobably two-fold from those residues and
nottwotofive-fold asitisstated foroestradiol intheJECFA Report of1988. Wehave alsosubmitted
evidence about theincreased risks forthepre-pubertal boys -thecalculation waswrong.
741. Thetwoissues thenlinked together andmyindirect question toDr.Lucier would be,according
tohisown estimation thatitmay beoneinonemillion theriskofadditional riskfrom theresidues
ofthose natural hormones which, forexample, ifwetake the total population ofthe
European Community mayleadtoabout 300-350 potential cancers intheEuropean Community. And
ontheother sideweput,thisisalsointherecord, thatthemaximum economic potential benefit for
thefarmers oftheuseofthese hormones ranges between minimum 30andmaximum 80dollars -that
iswhat itisintheliterature. How would youreevaluate theresponse thatisitreally from therisk
assessment, theriskmanagement point ofview, isitreally worth while taking intoaccount thepotentialWT/DS26/R/USA
Page 342
benefits oftheuseofthathormone inview oftherisks thatarealready there, asyousaidfortheexisting
levels, andifyouwould take ourlevels thatitiseven higher. Would youreally, asascientist who
isinvolved intheissue ofriskassessment andprobably management ofthatrisk, how would youlike
toexpress yourself ontheregulatory authority andhow youwould take thatinto account when
legislating?
Dr.Lucier
742. Risk assessment ishard enough, now youaregoing toaskmeabout riskmanagement too?
Iamreally notinaposition toevaluate benefits versus risk. What Iknow ishow hormones andother
agents cause cancer andhowtotranslate thatinformation intoasgood ascience-based riskassessment
asispossible. Ireally have essentially noexpertise interms ofquantifying benefits interms ofwhat
thebenefit might beeconomically orwhat itmight besocially, politically, whatever. Ihave no
experience inthatsoIamreluctant todothat. Iappreciate your point andIthink itisnotatrivial
point, butIamreally notinaposition togive aninformed answer tothequestion. Myestimates are,
andthere isalotofvariability inthese kinds ofestimates, butgenerally anupperbound estimate of
theriskofbreast cancer, andInarrowed ittothatparticular areabecause Ishould think thatiswhere
thedataisstrongest, would beabout onecancer inclose toamillion ofpeople exposed tothatbyeating
500grams ofmeat perdayover their lifetimes. SoIfeelrelatively comfortable with thatnumber,
recognizing alltheuncertainties thatareassociated with anykind ofextrapolated riskassessment and
Iwish Icould give youananswer interms ofhow thatrelates topotential benefits, Idon'tknow.
Oneinamillion isnotavery high number ofcourse -itisavery lownumber, butforthatoneperson
who does getcancer itisasignificant risktothem, soonecannever underestimate that, butasmuch
asIwould liketoanswer your question about thebenefits partIreally donothave abasis onwhich
todoit.
Dr.Ritter
743. Icannot offer anything with regard tobenefit, butIthink there isanimportant point of
clarification here. Intheestimates thatDr.Lucier presented yesterday, Ithink what youhave done
istaken theoneinamillion thathetalked about andmultiplied itbythepopulation inEurope and
from thatprojected ananticipated increase of350cancers. Ithink youshould notethatoneinamillion
istheupperbound. Thenumber could bezero too. Theoneinamillion represents, inDr.Lucier 's
opinion, thehighest probable risk, notthelikely probably risk. Butinriskassessment wetalkabout
anupperbound, thatis,thehighest riskthatwecancontemplate from amathematically derived model
issomewhere inthatrange. Butitwould beincorrect andcertainly misleading, andweseethisall
thetime inriskassessment, touseasingle number because thenature ofmathematically derived risk
assessment isthatthey provide arange ofvalues rather than asingle value. Ithink thatwasthepoint
thatDoctor Lucier wastrying tomake; thattheriskprobably falls somewhere between zero andone,
anditwould beincorrect tociteeither zero oronebecause themethodology simply does nothave
thedegree ofcertainty thatallows youtociteanumber, whichever oneitis,withthatdegree ofprecision
-itisarange.
Dr.Arnold
744. Iwanted tomake twocomments onwhat youhave justsaidinyour recent contribution. One
thing isimportant, Ithink, forthePanel toknow. Ifyoudesign thestatistical sampling plan, itis
very important what isthepopulation tobesampled, what istheareaandIknow atleast theAmerican
delegation cancorrect meifIamwrong, butIspent many hours with their experts attheFood and
Drug Administration. Atthatyear, USDA, thebasis isanational residue plan. Itcovers allofthe
United States andyoucannot directly compare thisfigure with thefigure oftheEuropean Community
because theplans oftheEuropean Community have tocomply with certain concepts, butthese are
plans fortheindividual member States. Sotheminimum number required tohave acertain statistical
certainty, ifyoutake afigure from theUnited States, andwant tocompare ittotheEC, youhaveWT/DS26/R/USA
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tomultiply with thenumber ofmember States; soyoucannot directly compare these figures. Atleast
forGermany Iknow thatyour figures arewrong, butIwould alsobewilling toprovide youwith the
ECdocument showing thatyour figure iswrong. Ihave noexplanation, maybe youcombine allresidue
testing, butforthehormones definitely your figure iswrong. Ihave thepaper with meandIamwilling
either togive youthedocument orthereference number: they arewrong. SointheEC,Ididnot
have thetime tosum upallsamples, butitseems tobeintherange of20,000 to25,000. And asI
saidyesterday, halfofthesamples aretaken inonecountry sothere areremaining maybe 15,000 or
12,000 fortherestofthemember States. And ifyouthen prepare thiswith thefigures ofthe
United States, itisroughly anequivalent programme. That ismyconclusion.
745. The second point Iwanted tomake: Iagreed thatintheIARC Report therange ofthis
production, daily production, isbetween 0.4and2.Itstands inthatReport. Butnobody hassaid
thatthefigure used byJECFA comes from thisReport. Iwasabletotrace itback toapaper given
byDoctor Farber andDoctor Arcos from theFood andDrug Administration in1983 attheOIEmeeting.
Icould notgofurther back, soIamnotsure from where thedatacomes, butIcansaythey definitely
donotcome from theIARC Report. Itried toexplain how such small differences could happen if
youhave avery bigrange andonegroup decides tousethemean andtheother decides tousethe
median, then youhave already thisdiscrepancy. From mypoint ofview, itisinthesame order of
magnitude andweshould notspend alotoftime tosaywho isright orwho iswrong. This figure
definitely does notcome from theIARC Report.
Mr. Christoforou (EC)
746. Mr.Chairman, Iamafraid Iwillneed toinsist onthisandIwilltake thetime from other
valuable questions butwedidgoback, Dr.Arnold, ourselves onthisissue. Asyourightly tosay
intheReport oftheInternational Office forEpizootics, thearticle byFabre andArkas, they citethe
article byArgus Engler(?) of1974. And ifyoulook atfootnote 39oftheJECFA Report they cite
exactly thesame article. Soboth theFabre andtheOIE Report, both theJECFA Report, relies on
thesame reference which is6micrograms per24hours. Whereas theIARC Report of1987 isbased
onthevalues ofBrown which aremore recent andwhich wehave discussed yesterday -they arenot
6micrograms per24hours. Wedidthatresearch soIcanshow youthedocuments ifyouwish. It
iswrong theconclusions youdraw.
Dr.Arnold
747. Ihave saidthefigure doesn 'tcome from IARC andyouhave confirmed. Which isthebetter
figure?
Mr. Christoforou (EC)
748. Well, inourview, weusethefigures theIARC which aremore recent. These figures are
alsodiscussed intheissues ofBrown andthey arenotapproved. That istheconclusion wecandraw.
They were coinciding with thefigures ofwhich Dr.Lucier wasaware aswell. ButIwould also, if
wehadthetime Mr.Chairman, liketogointothecomparison ofthenumber ofsamples because we
definitely disagree onthisissue with Dr.Arnold, butthatwilldeprive meagain ofvaluable time which
Iwould notliketodo.Weformally disagree, wehave theprotocols here, forserum wehave checked
59,000 only forthethree natural hormones oftheEuropean Community andforthetotal number of
hormones checked intheEuropean Community thetotal amount isjustabout 200,000 samples.
749. Mr.Chairman, Iwould liketocome back again onthisissue oftheriskthatwasdiscussed
between Dr.Lucier andversion intheplace ofDr.Ritter. Thereason forwhich Ipose thisquestion
isbecause thedelegate ofCanada hasmade theshort statement starting thediscussion andhesaid"Is
thislittle riskenough tojustify thedeparture from therestrictions oninternational trade" andofcourse
thisisrelated both toriskassessment andriskmanagement andtheeffects ofthat. Wehave probablyWT/DS26/R/USA
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different views what themagnitude oftheriskis.Butthese arethevalues wearecomparing here.
This riskisinvoluntary fortheconsumers. Weare,ofcourse, aware thatmaybe zero toonethousand,
onemillion, butitisaninvoluntary riskformillions ofpeople. Thequestion asascientist, ifyou
were, youprobably don'twant tocontinue thediscussion, butIwassimply trying tolinkthistothe
ADI which JECFA refused tosetinthiscase, although Dr.Lucier would sayitisfeasible tofixone,
wedoit,theUnited States does it,butthey donotapply it,whereas wedoapply it,even ifthethree
natural hormones oftheCommunity areonly allowed fortherapeutic use. Thenatural hormones are
notallowed tobeused forgrowth promotion, stillwecheck forthelevels ofthose 59,000, asIsaid,
intheEuropean Community. This isaninvoluntary risk. Why should theconsumers take such a
risk, probably itslow, butitisthere arisk.
750. Thesecond question ofcourse andIwilllinkthistowhat IsaidtoDr.Arnold thatrelates
totherapeutic use. Hehasmentioned twice theevaluation made bytheInstitute, theagency inLondon
ofoestradiol which isalready published asaregulation andofprogesterone which isonitsway. But
Dr.Arnold didnotmention probably alltheconditions which areimposed fortheuseofthese oestradiol
astherapeutic instrument. Weknow thattheyhave tobeadministered byaveterinary ifitistherapeutic
use,weknow theanimal hastoberegistered andidentified andweknow these animals donotgointo
thefood chain because they arenotslaughtered. Wehave provided evidence tothePanel thatthis
percentage isnotmore than one, andwehave more evidence which willprovide tothePanel from
other member States which have notreplied bytheendofJanuary which indeed demonstrates that
therateisnotover onepercent. These animals might have been treated, aswassaidbyDr.André,
once fortherapeutic orzootechnical treatment. Butthere isinatime-lapse between thetreatment and
when wedecide forthatonepercent toslaughter itandtosend ittothefood chain.
Chairman
751. May Iaskyoujusttosubmit succinct questions totheexperts andnottoplead. Ithink this
isnotthehour toplead. Youhave another goonpleading tomorrow, butjustplease dosubmit questions
andmake thebestuseofthisvery, very little time westillhave available thisday. Theexperts are
flying home andthen they aregone andweonly have correspondence, andIhave awhole listof
questions which aresustained andIwillcome inwiththese questions at6o'clock andthatismydecision.
Mr. Christoforou (EC)
752. Theprecise question is,therapeutic treatment, weknow what itis-theword explains it-would
youthink because oftheneed tohave theanimals treated fortherapeutic purposes, anextrapolation
canbemade ofthatandallow theuseofthese hormones forgrowth promotion. Isthisacomparable
example? Isitcomparable tosaythatbecause they areused fortherapeutic purposes they should also
beallowed tousefor. Is,inother words, thepotential risktoconsumers thesame from oneandthe
other situation ifyoutake intoaccount theconditions under which thetherapeutic useisallowed to
theCommunity? This isinparticular toDr.McLean andtoDr.André.
Dr.McLean
753. Theonly reply thatIcanmake isthatyouhave made much oftheillegal useofhormones
ortheabuse oftheuseofhormones andso,therefore, onewould suggest thatveterinarians aregoing
tobenobetter ornoworse than therestofthepopulation. Iwould remind youthatitisoften the
casewhere theveterinarian leaves thematerial behind foradministration bythefarmer forlatertreatment
andsothatisapossibility -Icansaynomore.
Mr. Christoforou (EC)
754. Weareallsometimes inourlifeillandwemayneed treatment byadoctor. Areyousuggesting
thateven thattypeoftreatment should notbemade because Isometimes have tobetreated fortherapeuticWT/DS26/R/USA
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orzootechnical reasons. Either way, what wecallzootechnical fortheanimals, ifawoman cannot
getpregnant shewould have togotoadoctor forthattreatment tobemade. Itiscomparable, itis
justonce, aswesaid, itisdone. Doyoureally think thisisareason enough initself toextrapolate
andallow theuseofthehormones asgrowth promoters? That istheissue. Weallgetill,butfrom
thatwhat istheconclusion oneshould draw?
Dr.McLean
755. Itisvery difficult toanswer thatquestion ifyouareasking metoextrapolate Iwould suggest
toyouthatgiven thepotential formisuse andthesmall amount ofmeat thatmight beeaten bythe
average person intheEUfrom imported meat then theriskwould bejustabout thesame.
Mr. Christoforou (EC)
756. Thesecond question relates totheargument wehave been discussing about. Wegetincreased
values ofallthese natural hormones from anumber ofsources. Oneofourexperts hascalled thesea
ofoestrogens which areexisting inourdaily lifeandIwould liketogive thefloor toDr.Liehr to
make acouple ofcomments andthen probably askoneprecise question.
Dr.Liehr (EC)
757. Mr.Chairman, yesterday weheard Dr.McLean talkabout andIquote him"We liveinasea
ofhormones andthathormones areinourdiet" andhealsosaidthatitisdifficult todetermine where
ourhormone burden comes from. Also today there were references early onindiscussion about the
various hormones thatweareexposed to.
758. Iwould liketobring toyour attention animportant distinction here. Oestradiol, testosterone
andprogesterone arehormones thatarecirculating within allofusandcarefully controlling endocrine
functions within allofus.Theproduction ofthese hormones within mammalian systems, including
humans,areverycarefullycontrolled,thedispositionisverycarefullycontrolledbecausethesehormones
very carefully controlled reproductive function andavariety ofother functions thatIcannot goand
donotwant togointohere. Atelevated levels such hormones may beharmful -wearetalking about
breast cancer riskandalsoDr.McLean thismorning talked about extra testosterone shutting offsperm
production andlowering male fertility. Many compounds, including phyto-oestrogens forinstance,
insoyaproducts,haveoestrogenicactivitybutthereisavastdifferencebetweenhormonesinmammalian
systems andcompounds with oestrogenic activity such asforinstance inphyto-oestrogens. Differences
arethatthey aredifferent compounds with different activities -oestrogenic activities ofmany ofthese
compounds are1,000 to10,000-fold lower than thatofthemammalian hormones. There isreally
avastdifference between acompound thathasoestrogenic activity andtheactual hormone. Some
ofthese compounds have also been shown tobeoestrogenic andothers areanti-oestrogenic. As
Dr.Lucier saidalittle bitearlier on,thisisavery active areaofresearch andIknow heisinvolved
inthis,nevertheless, itisobvious alsothatonbalance between oestrogenic andanti-oestrogenic activity
itmaybebeneficial andmuch ofthisisnotknown atthispoint. What isclear though isthatacompound
with much, much lower oestrogenic activity than anatural hormone introduced intoasystem with
oestradiol insuch asystem, such aphyto-oestrogen may actually beanti-oestrogenic, oractinan
anti-oestrogenic manner, because itcompetes fortheoestrogen receptor. Anindication ofthisisthe
lowbreast cancer riskinpopulations where high soya bean diets areconsumed. Sotoimply thatthe
administrationofthemammalianhormoneatlowlevelsislikeapplyinganantibioticoraphyto-oestrogen
isreally inadmissible. These aredifferent compounds, theyhave different spectrums ofactivities and
they should beweighed ontheir own benefits.WT/DS26/R/USA
Page 346
Mr. Christoforou (EC)
759. Isthere notadifference between thehormones inmammals andphyto-oestrogens indiet, in
physical, chemical andhealth effects? Isthere adifference between these three?
Dr.Ritter
760. Imay beable tomake thisshort. This answer isyes. There aredifferences.
Chairman
761. Could youperhaps saywhy?
Dr.Ritter
762. Well, Ithink, ashasbeen quite correctly pointed out,there aredifferences inbinding capacity,
there aredifferences instructure, there aredifferences infunction. Clearly aphyto-oestrogen was
never invented tohave aphysiological function inamammal. SoIagree with everything you'vesaid
except thattheydonotcontribute much totheoverall risk. That partIamlesscertain about thanyou.
That they aredifferent intheir structure, thatthey were clearly developed through evolution tohave
afundamentally different purpose, Ithink itisaninescapable truth. Butthatthey donotcontribute
torisk, Iwillnotengage youinadebate now, about breast cancer statistics incountries where soya
bean intake forexample ishigh, except tosaythatitisnotquite asclear asyoupresent it.ButIthink
theshort answer, without labouring itinthelimited time available, isofcourse there aredifferences
inthese different categories ofoestrogens.
Dr.Lucier
763. Iwillquickly addtothat. Iagree with what youhave saidaswell. There aredifferent binding
proteins anddifferent receptors that arenow being discovered fordifferent agents. There isa
beta-receptor thathasjustbeen discovered andsoforth andthisisadifferent binding spectra than the
receptor that we'veallcome toknow andlove. The interaction issue isavery complex one.
Nevertheless there isalotofinformation inthepublished literature oncellsystems andin-vivo systems
thatcertain mixtures ofexogenous hormones doproduce stimulatory responses thatarecharacteristically
oestrogenic. Sointotal these things areproducing anoestrogenic response. Exactly themagnitude
oftheoestrogenic response ishighly uncertain.
Mr. Christoforou (EC)
764. Thenext question relates towhat thelawyers among ourselves calltheissue ofconsistency
andinthatcaseitwasdiscussed byreferring toanumber ofsubstances. Iwilltouch only thesubstance
ofcarbadox. Thediscussion waslively butwedidnotexplain theconditions under which carbadox
isallowed tobeadministered intheEuropean Community. Carbadox does notactasadirect growth
promoter asthenormal hormones wearethinking about. These growth-promoting effects areonly
because itcombats thebacteria andithelps theintestinal flora andindoing thatithelps thegrowth
oftheanimal. Thehormone does notexert anyother action apart helping thegrowth promotion of
theanimal. And there arenoother readily available substances onthemarket which candothesame
thing. Itisadministered only topiglets andthere isa28-day obligatory withdrawal period. From
thatdiscussion andbecause theCommunity allows theuseofcarbadox under theconditions andeven
stricter conditions than those recommended byCodex. Iwasleftwith theimpression thatprobably
because theCommunity allows theuseofcarbadox, should itallow alsotheuseofhormones, because
attheendthetwotypes ofsubstances forthesame risktohuman health, thatiscarcinogenicity. What
should betheparadigm? Because weprohibit thehormones should wealsoprohibit carbadox orbecause
weallow carbadox wealsoshould allow thehormones? This isanimportant question. AndasIsaid,WT/DS26/R/USA
Page 347
wedorespect exactly theconditions ofJECFA asthey arerecommended. There isnoriskbecause
wehave been doing allthesamples andthechecking andthere isnoreported case ofexcess. Sodo
youthink, andIaddress thistoDoctor Lucier because attheendthequestion ofwhat areweexactly
comparing wascritical. Doyouthink thiscomparison isreally meaningful andshould itbetaken into
account intheglobal riskassessment ofthehormones inthiscase?
Chairman
765. Ithink thequestion should belimited tothescientific distinction oftheagents andnotthepolicy
options which youinvoked aswell, ifyouagree?
Dr.Lucier
766. Ihadn'theard thatpartofthequestion anyway, Mr.Chairman. Iunderstand what youare
saying thatcarbadox isnotused asagrowth promoter, itisused asananti-microbial agent, soits
purpose, itsuse,ismuch different than forthehormones inquestion. Ontheother hand, itis,and
Ionly sawthecarcinogenicity data onittoday andmynext-door-neighbour hasgone andleftwith
it,soIcannot refer toitagain, butitwasafairly potent carcinogen -itwasacarcinogen atmulti-sites,
atdoses wellbelow themaximum tolerated dose anditisgenotoxic, soitisnotanagent thatyouwant
toexpose alotofpeople to.That ismyonly point. SoIthink strict attention needs tobegiven to
theavoidance ofresidue levels ofcarbadox given theavailability ofthatcancer data.
Chairman
767. IfIamcorrect, theagent works assisting theflora anditisnotreally having hormonal effect.
Would youconsider thistobeacritical distinction between thetwoagents ornot?
Dr.Lucier
768. Itdepends, itisadistinction, they areused fordifferences purposes. Idonotknow how to
sayitbeyond that. Thepurposes arevastly different. Nevertheless, they areboth present andboth
may have their own risk. Theriskofcarbadox, ifresidues arepresent, arelikely greater than that
ofsome ofthehormones inquestion.
Dr.McLean
769. Ithink itwould beuseful forthePanel toknow thatthere isanother drug related tocarbadox
-olaquindox, andwhilst JECFA hasreviewed it,ithasnotsetMRLs andADIs because thedatapackage
isincomplete. Butnotwithstanding Ibelieve itisused intheEUanditisjustaseffective, ithasa
mode ofaction thatissimilar, inother words, interfering ormodifying themicrobial population and
sotherefore itisanalternative anditisjustaseffective andofcourse there areother anti-microbial
agents thatareused inanumber ofother countries asgrowth promotants thataresubstitutes forboth
olaquindox andcarbadox, such asthetetracyclines asanexample.
Chairman
770. Butcantheagent becompared with thehormonal agents orisit...
Dr.Ritter
771. Areyouasking thequestion thatyouareasking when youaskabout thedifference being
important between carbadox, forexample, areyouasking thedifference inrisks tohuman health?WT/DS26/R/USA
Page 348
Chairman
772. Theproblem isthatlegally theagreement requires consistent policies. One argument goes
thatyouallow thisagent butyoudonotallow theother oneandofcourse youcanmake thisargument
ifthese arecomparable agents. Itisimportant forustoknow whether from thescientific point of
view youcancompare these agents andputthem onthesame level, knowing thattheoneaffects the
hormonal household andtheother onethemicrobiological situation inthestomach. Socanwecompare
thetwoandputthem onthesame level andaskforthesame policy under theagreement oristhat
acompletely different story. Carbadox andtheother oneisolaquindox.
Dr.Ritter
773. Thehour islateandIamgoing togooutonalimb andeven though anumber ofushave
consistently saidduring thedaythatwefeeluncomfortable with drawing comparisons, ifitwould assist
thePanel, carbadox isagenotoxic carcinogen. Ithink there arefewpeople inthisroom who would
disagree with thatconclusion. There isvery much debate, some ofwhich youhave heard inthelast
dayortwo, astowhether ornotthehormones areindeed genotoxic carcinogens. Toputthisinto
perspective, within thetoxicological community, wewould attach greater concern toacompound which
wasagenotoxic carcinogen than wewould toonethathasbeen referred tointhelastcouple ofdays
asepigenetic. Carbadox issuch agenotoxic carcinogen. Ipersonally would beinclined tosaythat
theevidence foroestradiol, forexample, being agenotoxic carcinogen, isweak, whereas inthecase
ofcarbadox itisdefinitive andifonehadtoputonaranking scale where youwould attach greater
concern orgreater importance, Ithink most ofusinthescientific community would argue thatwe
would probably have aheightened level ofconcern forgenotoxic carcinogens thanwewould forsome
other class. Idonotknow ifthatassists.
Chairman
774. Yes, itdoes. Would youliketospeak onthatpoint?
Dr.Arnold
775. Dr.McLean mentioned olaquindox -itisalsoused intheEC. Itisinthesame annex tothe
feed additives directives. Itischemically similar tocarbadox butthere areinteresting differences.
Olaquindox isgenotoxic inavery large number oftests, butinthecarcinogenic studies, which were
available toJECFA, itdidnotshow carcinogenicity. There wasnoincrease ineither benign ormalign
tumours. That isastrange finding, butitisreally genotoxic andIwould sayinmore than tentest
systems. Thesubstances used intheECasgrowth promoters could replace carbadox theoretically,
unfortunately theresidue situation isnotclear. Wehave nomarker residue, wearenotable toset
anMRL, sowehave nomeans tocontrol theuseofthissubstance. Buttheoretically itcould replace
carbadox anditisinthesame annex tothedirective.
Dr.Lucier
776. Inrelation tothatpoint andthepoint thatDr.Ritter made, Idonotgetsoconcerned about
thedistinction between genotoxic andnon-genotoxic. There aregenotoxic non-carcinogens andthere
arenon-genotoxic carcinogens. What Iprefer tolook atisthestrength ofthecarcinogenic response -
what sites areaffected, what number ofsites, whether itoccurs inmultiple species, orinmultiple
organs. SoIlooked atthecarbadox carcinogenicity dataIwasimpressed forthenumber ofsites that
were affected where tumours appeared, themagnitude oftheresponse, they were very high over a
background andthey occurred inmore than onedose; suggesting thismight beasensitive effect.
Ontopofthatisgenotoxic. Butmyconcern wasnotsomuch forthegenotoxicity, itwasthefact
thatthetumour response wasavery strong oneforcarbadox.WT/DS26/R/USA
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Dr.McLean
777. Onepoint thatisgermane, inmycountry carbadox isbanned andisbanned onoccupational
health andsafety grounds -inother words, wehave more concern with those thathave tomixitin
with thefeedandfeedtothepigs, thanwedototheconsumers oftheproduct andsoitisanoccupational
health hazard.
Dr.André
778. Iamnotaspecialist ofcarbadox butIamhappy tohearthis, because Iunderstood thismorning
orthisafternoon, thatcarbadox isacarcinogenic compound, butitisnotaproblem touseitbecause
itisimmediately andvery fasttransformed inaninnocent metabolite. Therealriskisforfarmers
andformanufacturers -itisnotformeat orforpigsormeat containing carbadox, meat cannot contain
carbadox residue, itisokay. Justtoclarify.
Mr. Christoforou (EC)
779. Itisunfortunate thatthisisgoing tobethefinal andprobably your final decision onthisissue.
Ifitisindeed final question itisregrettable because wedohave many questions. Then Iwould only
comment onthatDr.Ritter saidoestrogens areweak carcinogens -thatisthestatement Iheard -weak
genotoxic, could youplease restate?
Dr.Ritter
780. What Isaidwasthattheavailable evidence inthecaseofcarbadox intheexample Iwasdrawing
isthatcarbadox wasgenotoxic inavariety oftestsystems. Thedataisoutlined inthe1989 JECFA
Report. What Isaidwasthatthegenotoxicity ofoestrogens isstillopen tosome speculation. That
iswhat Isaid.
Mr. Christoforou (EC)
781. Ithought weheard theword "weak". Butifitisso,wehave already, anditispublished,
thattheIARC, theInstitute onCancer Research, hasclassified oestrogens ingroup 1,which isgenotoxic
andcarcinogenic.
Dr.Ritter
782. Iamgoing topresume thatyouaredirecting thatquestion tome. Ithink weareconfusing
apples andoranges. That oestrogens have thepotential tobehuman carcinogens isabsolutely true.
Idonotthink there isanybody who would argue with thatwho isallfamiliar with thediscipline.
IthinkDr.Lucierexplainedthatyesterday.Thereisnoquestionthatweknowthatcirculatingoestrogens
inawoman 'sbody have aprofound impact onherriskforbreast cancer. This isofnoquestion
whatsoever. What wehave been discussing here forthelastcouple ofdays iswhether thelevels that
arepresent asaresult oftheuseofthese products ingrowth promotion aresufficient toconstitute a
meaningful risk, andwedefine meaningful asbeing somewhere intherange ofoneinamillion. This
hasbeen thenature ofthediscussion forthelastdayortwo. Notthatatsome dose oestrogens are
capable ofcausing cancer. IfIhave imparted theimpression thatsomehow oranother Idoubted that,
letmecorrect it.Tobeclear, oestrogens arehuman carcinogens. Inever meant toimpart anyother
impression. ButIhave alsoindicated thatinmyview theoestrogens present atthelevels thatwould
bepresent asresidues asaresult oftheir useasgrowth promotion constitute, inmyopinion, no
significant riskatalltothehuman population.WT/DS26/R/USA
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Chairman
783. This now brings ustothelaststage ofthishearing andIamsorry wehave toadvance and
Iwould really justliketogetusthrough these questions asrapidly aspossible. Wehave prepared
anumberofso-calledadditionalquestionswhichwerecirculatedwiththePanelandalsowithdelegations.
What Iwould intend todoistotouch upon them orally andthen seeintheendwhether itmight be
feasible tomaybe have them done inwriting inorder tobefully accurate. ButIwould liketohave
theopportunity ofdiscussing them orally since youarehere.
784. Thefirstquestion really addresses apoint wehave nottouched upon, which isthedifference
inhealth risks ofthenatural andartificial hormones. Isthere adifference intheriskofusing natural
hormones ortheartificial hormones? Inother words, canthey legally beclassified inthesame group
ordoyouseethere ground fordistinguishing these agents?
Chairman
785. Justtotake thefloor asitcomes andthen wehave agood debate.
Dr.Lucier
786. Letgivemeastabatthat. Notthatwehave ananswer toallthequestions, butforthenatural
hormones wehave agreat wealth ofinformation about how they work indifferent cells andtissues
ofthebody. This isinthepublished literature. Weknow alotabout, asyouhave heard, about how
theygoabout producing cancer aswellasother adverse health effects. Weknow lessabout thesynthetic
materials. Now thesynthetic materials aredesigned tomimic thenatural hormones. Sotheywillhave
onesetoftheir biological properties, willbevery similar tothose forthenaturally-occurring hormones,
thatistheability tointeract with thereceptor system andstimulate thesame kind of,sayoestrogen
ortestosteroneresponsivesystemsthatthenaturally-occurringonesdo.Butinaddition,thecomplicating
factor isthattheir structure isdifferent. Sotheymaypotentially have biological properties inaddition
tothehormonal properties. And thatiswhere anylevel ofconcern would come in.Now togetany
ofthese synthetic materials registered foruse,they have togothrough thesignificant testing protocol
todetermine whether notthey cause cancer orproduce other kinds ofeffects. That information is
notavailable from theregulatory agencies because itisproprietary. Somuch lessofitisinthe
peer-reviewed published literatures. Youdon'thave asmuch information inpeer-reviewed published
literature forthesynthetics asyoudoforthenaturally-occurring ones.
Chairman
787. Thank youvery much. Anyother views? Addition? Itakeitifthere issilence thatyouagree?
Otherwise youwould justoppose orclarify.
Dr.Arnold
788. Itisadifficult question. Ilargely agree, butifforexample, Itake themolecular structure
andlook atthings, Dr.Liehr hasalready described andDr.Cavalieri andImust saythispotential
isnotassociated tosuch extent with zeranol. Sodepending onwhat youarelooking, youcould come
totheideathatsynthetic hormones aresafer than thenatural andifyoulook atother things youcould
come toanother conclusion andthatistheproblem.
Chairman
789. Soyouwould agree weknow less, youknow about them than thenormal ...WT/DS26/R/USA
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Dr.Arnold
790. Weknow lessabout thesynthetic butthey might besafer than thenatural.
Dr.André
791. Ashort point. Ithink thefactthatCodex didnotestablish MRLs forthethree naturals in
comparison with theothers isnever mind thattheyaresafer ornot. Theproblem isthatCodex establish
noMRL forthese natural hormones onthebasis first, thatthey arenatural, andapriori, thatifthey
arenatural, they arelesstoxic, Ithink, may be.And they arethought so.And thesecond reason
isthattheresidue level hasbeen demonstrated tobewithin thephysiological range. Andtaking account
these twofacts, they decided nottofixMRL butnotonsafety basis.
Chairman
792. Thank youvery much. Yes.
Dr.McLean
793. Very quickly, theevaluation process, theformal evaluation process ofveterinary drugs is
designed toreach apoint where youeffectively reduce therisktozero. Now inthecase ofthe
naturally-occurring hormones, itwasbelieved thattheadditional amount thatwould come from ingested
food would notcontribute totheoverall burden inasignificant wayandsothatriskwaszero. Inthe
caseofzeranol andtrenbolone, thenanacceptable daily intake wasset,andagain, providing thatwasn 't
exceeded, theriskwasessentially zero. Andthesecond point Iwould liketoaddthatthetwosynthetic
hormones have been subjected toaformal toxicological evaluation process designed tobring outthe
toxicity. And sotherefore, insome ways, those processes, which arecomplete forzeranol andfor
trenbolone, areidentifying thetoxic hazard andbringing itout. Andwhilst Iaccept thefactthestudies
arenotpublished intheopen literature. Themonographs thatJECFA prepares areopen literature
andthere areahundred orsopages ofmaterial relating nottoeach ofthem, toboth ofthem, andthat
isavailable forperusal andscrutiny. They arealso included inthatmaterial, itisfrom theopen
literature, although thatisnotlarge. And so,thatisthecouple ofadditional points Iwould liketo
make, Mr.Chairman.
Chairman
794. Thank youvery much. Ithink wedon'thave toaddress questions 2and3because, wehad
anextensive discussion hereoncarbadox andolaquindox, justaminute ago. Iliketoturntoquestion 4.
Arethere anyqualitative chemical orother differences between thethree natural hormones indispute
inthehuman being, depending onwhether these hormones arebeing endogenously produced bythat
human being; secondly areadded tothehuman being because ofconsumption offood endogenously
containingthesehormones,orthree,ofmeattreatedwiththesehormonesforgrowthpromotionpurposes
orfour, ofmeat treated with these hormones fortherapeutic purposes? Doanyofthese chemicals,
orother differences, ifany, pose anadditional risktohuman health? And ifProfessor André could
elaborate onhisthesis onthenatural hormones added tohuman beings having different metabolites.
Dr.André
795. Very quickly. When natural hormones areadministered toanimals firstasesters, asimplants
orbyinjection, they don'tfollow inthebody same route astheendogenous ones. Because the
endogenous ones aresecreted inonegland, circulate andaremetabolized inanother partofthebody.
Sotheycannot beexactly compared. There aresmall differences intheanimal. Sothatthese animals
might produce different metabolites with same hormones injected asthey could dowith their own
hormones. Forexample, theycould produce various proportions inconjugate forms. AssulphosteroidsWT/DS26/R/USA
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instead ofglucurono steroids, forexample. After this, inthemeat, youmay have different varieties
ofmetabolites. When human beings areeating these metabolites, theyareeating different compounds
from natural hormones astheir own endogenous natural hormones. Following myexample, itcould
bethathuman beings absorb some sulphosteroids andithasbeen saidthisafter thatanewinformation
appear now ontheroleofsulphosteroids inthehuman brain. Sothatyoucannot exactly assimilate
thenatural oestradiol, progesterone andtestosterone ofhuman beings withhormones theyareconsuming
infood. Ihope tobeclear enough.
Chairman
796. Would youliketotalkonthisquestion?
Dr.Ritter
797. Nottoprecipitate alengthy debate, buttosimply present analternative, ifyoulike. Tothe
bestofmyknowledge andagain thatinformation waspublished intheEuropean Conference onGrowth
Promotion, aswell. Tothebestofmyknowledge, ifthestructure ofthehormone thatisifweare
talking about thesame hormone which isproduced endogenously orexogenously, ifintroduced
exogenously, theyenter theidentical pathway. Andfrom thatmoment intimetheyareindistinguishable
tothebody. And IsayIcanprovide thePanel with published references which support thatview.
Chairman
798. Butisitfairtosaythatthere aretwodifferent views inscience?
Dr.Ritter
799. Ithink itisfairtosaythatthere areprobably 30. Asmany...
Chairman
800. Asauthors?
Dr.Ritter
801. You know thestory ofthetwo-handed scientists: ontheonehand andontheother. Lawyers
areoften looking forone-handed scientists.
Dr.Lucier
802. There isprobably some small differences intheexact pattern ofmetabolites orbreak down
products resulting from aslightly different route ofexposure. This might beexpected because ofthe
waytheymove through thebody. Idon'tthink there would bequalitative differences inthemetabolites.
There might besmall differences inthepattern ofmetabolites. SoIthink that'swhat Dr.André was
saying. Idon'tbelieve thatthisdifference inpattern ofmetabolites would betoxicologically significant.
Chairman
803. Thank you. Would you...WT/DS26/R/USA
Page 353
Dr.McLean
804. Ijustwanttoconcurwiththatview.Therecouldbesmallqualitativeandquantitativedifferences
butthere would benoeffect onhuman health duetothose small differences, within thebiological
variations, sotospeak.
Dr.André
805. Ontheopposite, youcannot besure thatthey have not.
Chairman
806. That'snotanappropriate scientific method!
Dr.McLean
807. JustallIamreally saying isthatIaccept thefactthatthere arequalitative andquantitative
differences. Ibelieve thatdemonstrate anysignificant effect would notbepossible anditisunlikely
thatitwould bethere.
Chairman
808. Ijustwant tosay,youdon'thave toagree. Iamnotputting adealtogether. Thequestion 5
isbasically justaquestion ofclarification about thenotion ofnormal physiological range. Ifyoucould
comment onthisquestion, whether itdoes relate totherange inhuman beings orinanimals? Then
thelatter partofthequestion, theimpact onthethreshold approach really goes over intoquestion 6,
which then Iwould liketoaddress toDr.Lucier.
Dr.Lucier
809. Thepoint thatIwastrying tomake is,andthishasbeen saidnow, Ithink, many times and
nooneseems todisagree with it,thattheamount ofhormones naturally circulating inthebody are
infactcarcinogenic. There isawealth ofinformation inthescientific literature, both experimental
aswell ashuman studies, todocument this. Now when anadditional molecule comes intothebody
adding tothatburden, itwillnotbedistinguished from those other hundred thousand molecules you
puthere inthequestion. Instead ofonehundred thousand molecules of17betaoestradiol circulating
there willbe100,001 andthebiological systems won'tdistinguish thatonefrom theother hundred
thousand. Sointhatsense theissue ofthreshold isirrelevant, since wearealready dealing with the
carcinogenic dose. Weknow thatifathreshold exists, ithasalready been exceeded. Soadding that
additional molecule would addasmall increment torisk. Avery small increment ofrisk, because
thebody won'tdistinguish thatmolecule from anyoftheother naturally-occurring ones. Andtherisk
assessment thatItalked about isreally based onthese relative proportions ofmolecules, recognizing
thatthethreshold ifoneexists, ithasalready been exceeded. And thatwasthebasis ofmyargument
thatthethreshold issue wasirrelevant here. Because even ifitdidexist, ithasalready been exceeded,
bythewoman 'snaturally-occurring hormones.
Chairman
810. What isofinterest tothePanel isreally what does thismean fortheentire concept ofthe
threshold under which themaximum residue levels andtheADI. From your point ofview, ifyou
take thistotheend, would thismake thisapproach redundant? This iscontained inquestion 6and
Ithink itisaconceptually very interesting point. You know, isthisachallenge tothethesis thatif
wecandefine these levels what wedobelow issafeandeven what wedoabove itisprobably safe
foralong time.WT/DS26/R/USA
Page 354
Dr.Lucier
811. Any acceptable daily intake willnotguarantee zero risk.
Chairman
812. Soyouwould challenge thatbelow itwecantalkabout asafety ...
Dr.Lucier
813. Inother words anyadditional incremental increase beyond wealready have, itwould be
reasonable toassume thatanadditional riskiscreated. Soanacceptable daily intake could notbe
established thatwould guarantee zero riskfortheoestrogens. Because wealready know, again, that
weareatthecarcinogenic levels, sotheassumption isthatanadditional molecule addupvery, very
small incremental increase inrisktothat.
Chairman
814. ButIamcorrect tounderstand thatthemainstream, thetraditional understanding, isthatif
weoperate within these limits, wearesafe.
Dr.Lucier
815. Well, what thatconcept wasdeveloped forwaslooking atmolecules which wenormally do
nothave present inourbodies. Soforsome types ofcarcinogenicity youcanestablish adose below
which youarereasonably confident thatnoeffect canoccur. And that'swhat athreshold is.Incases
youhave inaddition toanalready endogenously acting mechanism andweknow wehave ithere, the
issue ofthreshold isreally anirrelevant one. One may setanacceptable daily intake asapolicy.
Butthatpolicy does notguarantee zero risk.
Dr.McLean
816. Thedifficulty with thehormones inmeat, thenaturally-occurring ones isthattheyarealready
there inmeat. And sothevery actofeating meat adds more hormones. And sotherefore thatisa
risk. And perhaps onewould therefore, ifyouwant toeliminate thatrisk, youwouldn 'teatmeat.
Buttheargument Ithink iswhether theextra amount produced ortaken inbywhat isalready there
normally plus thesmall increment duetothetreatment, isasignificant extra risk. And with normal
chemicals when wesetanADI, theyarenotnormally inproduce. Andsotherefore, youcansaywell
it'snotthere andyoucanhave thatsmall increase andthey arenotnaturally occurring. Soit'seasy
tosetanADI. Butwith thecase ofthehormones, they arenaturally there already andit'sdifficult
tomeasure what theADI is,because thelevels ofincrease arequite small inrelation towhat isalready
there inmany cases. Imean ifyoulook atprogesterone inthenormal cycling cowandtheamount
thatyouaddisvery, very small inrelation tothetotal. Soit'snotapractical consideration andIthink
that'swhere wearehaving thedifficulty. Notbetween thecolleagues, buttheconcept ofmanaging
risk.
Mr. Palecka
817. Thank youvery much, Mr.Chairman. Perhaps justtobeonehundred percent sure ...It
means thatlooking atthisproblem quite likely. Ifthere arecabbage eaters oreggs eaters, who may
perhaps addsome more molecules than oneincase ofeating thehormone meat, itmeans thatthey
may theoretically through alinear increase beexposed ...more tosaydangerous orthreats, then for
example, those who eathormone containing meat. There aredifferent diets, forexample, youknow.
Such as"cabbage eaters" or"eggs eaters", that'swhat Ihadmind.WT/DS26/R/USA
Page 355
Dr.McLean
818. Orthose thatdrink milk ...You arejustadding totheoestrogen burden. And whether you
takeitinmeat with thatlittle bitextra added from growth promotion which isdifficult todetect because
itsitsinarising andfalling normal level andifyoutakeasample ofmeat outthere, from thebutcher
andbring itin,youcannot really saywhether thatmeat hasbeen treated ornot. Because thedifference
thatyouaddisburied inthenormal range. Therefore, when youeatit,youaddthatlittle bit. Now
incase ofeggs orparticularly, butter andcheese, forexample, thathave gotalotoffatinthem, then
youtakethose hormones inanywayandtheyarequite high when youcompare them onaweight basis
with meat, particularly with treated meat.
Dr.Lucier
819. Putitadifferent way. Forevery million women alive intheUnited States, Canada, Europe
today, about a110,000 ofthose women willgetbreast cancer. This isobviously atremendous public
health issue. Ofthose 110,000 women getbreast cancer, maybe several thousand ofthem arerelated
tothetotal intake ofexogenous oestrogens from every source, including eggs, meat, phyto-oestrogens,
fungal oestrogens, thewhole body burden ofexogenous oestrogens. Andbymyestimates oneofthose
110,000wouldcomefromeatingmeatcontainingoestrogensasagrowthpromoter,ifusedasprescribed.
Does thathelp?
Chairman
820. Thank you. Could Ifollow uponthis. Inthelight ofthis, doyouconsider theMRLs for
thesynthetic hormones adequate?
Dr.Lucier
821. From myreading oftheinformation thatIhave seen theMRLs arederived bylooking at
hormonal responses inmonkeys. Andthere isaseries ofmeasurements theonegoes about todetermine
those hormonal responses. Ithink inanycase thatwearetalking about carcinogenicity datahasnot
been used except theMRL. Ithink thathasbeen basically ahormone derived response. Ithink in
thecase oftrenbolone, there wasweak carcinogenic response. And again correct meifIamwrong,
andthatwasessentially disregarded inestablishing theADI. Inthecaseofzeranol, itthinks itwasn 't
really considered atall,there wasaweak carcinogenic response thattobeduetothehormonal activity
oftheagent. After having saidthat, weheard from Dr.Metzler yesterday thatthere isaDNA adduct
which isofzeralenone, which isastructural analogue ofzeranol inthemetabolic chain ofit.Now
thatDNA adduct ispartofthezeralenone bound covalently toDNA, andforsome chemicals thisis
anearly stepinthecarcinogenic response andanearly stepinagenotoxic response thatinitial binding
covalently toDNA, sowhen thecellreplicates thatadduct isfixed intothe[?]orcellular mutation.
Ifthemutation occurs inacritical target gene, itcould goontoproduce cancer. Andthat'sthewhole
concept behind theideathatgenotoxic carcinogens need tobeclosely regulated. Now zeranol isnegative
intestforgenetic activity thatlook attheability toproduce mutations. Yetthisadduct hasbeen
discovered, apparently, andthere issome questions about exactly what itisanadduct of.Ithasn't
shown tobeclearly related tothezeralenone. SoIdon'tknow, with a100percentcertainty ofthese
acceptable MRLs arecorrect. ButIseenoreason tostrongly dispute them atthispoint interms of
thezeranol. Theonewith trenbolone causes mealittle bitmore concern. Trenbolone ispositive in
celltransformation assays, inother words, itiscapable oftransforming cells. Ithink there arecouple
ofstudies thathave shown that. And that'sindicative of,itisawaythatpeople screen forpotential
carcinogens, when they seethisresponse itraises asortofaredflag togoonandlook forthe
carcinogenic activity ofacompound thatdoes this. Sothatraises anissue with thecarcinogenicity
studies thatIguess were conducted bythecompany who requested thatthisbeused. Now asI
understand, thecarcinogenic studies were essentially negative. That there were small increases inliver
tumours. Isthatcorrect? Ithink there were small increases inliver tumours thatwere seen. IthinkWT/DS26/R/USA
Page 356
theissue oftrenbolone should belooked atperhaps alittle more closely fortheMRL, inmymind.
Iammore comfortable with theoneforzeranol. It'salong-winded answer without being much of
ananswer, butittries togive mybasis forsome concern ononepartandlittle concern ontheother.
Chairman
822. Thank youvery much. CanIaskaquestion which actually comes intothefirstquestion, but
itisrelated here. Dothestudies considered byJECFA evaluate carcinogenic effect ofthehormones
atissue? Was thistaken intoaccount bythestudies which JECFA considered?
Dr.McLean
823. Yes, they were. JECFA actually looked attrenbolone acetate ontwooccasions because it
requested additional information. Iwillsaythatthecelltransformation assays under some circumstances
were equivocal, they weren 'taccepted byallasbeing positive. Ofcourse thecarcinogenicity was
investigated thoroughly andonbalance Ifeelthatthiscompound, thiscompound isbeing pretty much
looked ataswell asanycompound andindeed forsome ofstudies weaskforelectron microscopy
rather than normal microscopy todetermine certain endpoints. And ofcourse thenoeffect levels
arebased onfairly innocuous changes inmonkeys andtheyarevery low, andthen ontopofthatthere
arefurther safety factors forspecies, inter- andintra-species variation. Soyouhave gotthatchain
built in.
824. IfIcould addjustonething, when wewere talking about theincreased incidence ofbreast
cancer ofone, Ithink, itwasin150,000. That'sIthink, according toyour calculations, amaximum
ofone. [Yes.] Soitcould beanywhere between essentially zero andoneandIthink it'simportant
toappreciate thatdifference. And thatcomes back tothepoint thatmycolleague, Dr.Ritter made
thatwhen wearelooking atriskassessment, because it'samathematical consideration, wehave arange
anditliessomewhere between essentially zero andone.
Chairman
825. Thank youvery much. Would youliketotalktothispoint.
Dr.Lucier
826. That'scorrect, between zero andoneandIshould alsoremember tosaythat, when Isayone,
Iwasjusttrying tomake thepoint toputincomparison with theother oestrogens. Ihave looked at
some ofthatdata, though withthecelltransformation assays andIdon'tfinditequivocal. It'sassociated
with increased production ofoncogenes intheSyrian hamster embryo cells, therasandmyconcogenes,
which areanexpression ofthose critical target genes incarcinogenesis. And theresult seems tobe
realone.
Dr.McLean
827. Iwasmaking thepoint thatsome ofthestudies were equivocal andsome arenot.
Chairman
828. I'dliketoleave question 7totheendandmove ontoquestion 8.Wehave thesituation of
abanorprohibition with qualifications andifIamcorrect thatDr.André contended thattheabuse
willoccurinsimilardegreesinsituationswhereonebansthehormonesindisputeasopposedtosituations
where allows these hormones under certain conditions. Isthere anydataavailable inthisrespect which
could support your thesis?WT/DS26/R/USA
Page 357
Dr.André
829. Theresult, asIsaidyesterday Ithink, inFrance weknew thetwosituations andthesame
hormones were allowed between 84and89. SoIdon'tknow really ifthedataareavailable. They
areinmyGovernment andofficial bodies andmaybe itispossible togetrealdata inarchive from
thatdate. ButIcanjustgive some witnesses onthis. Forexample, during theauthorization ofthese
hormones, fiveyears ofauthorization, wefound some positive results, positive results ismisuse, of
theDES. And theDES misuse haddisappeared intheearly seventies. Soitwasacoming back of
DES misuse during thisperiod. Asecond factisthatithasbeen said. Ispeak forFrance, notfor
other countries, okay?, thatinFrance, thebanhasbeen followed bythemisuse ofnew class of
hormones, so-called beta agonist. And it'sclear thatwediscovered themisuse ofbeta agonist just
after theofficial ban. Butinfactwhen now, with themethods wehave, when welook infeedsamples
taken during theperiod where thehormones were authorized, wefindalsoclenbuterol orbetaagonists.
Somyidea isthattheauthorization, legalization, ofthese compounds hadnoeffect, realeffect on
some black market andthemisuse ofhormones.
830. Thesecond partofyour question isconcerned with thecontrol. And toknow ifthecontrol
iseasier under regime, with abanornot,Iwould justanswer thatit'sclearly easier technically for
allthexenobiotics. Because ifyouhave notanyxenobiotics allowed each time youfindoneit'sclearly
amisuse. Andit'salsotechnically more easy because youhave justtohave qualitative survey, Imean,
youhave tocheck inyour sample meat, urine, feeds, whatsoever, youhave justtolook ifthecompound
ispresent. And then yousay,yesit'spresent. Soyouhave aqualitative analysis. When hormones
areallowed, then it'sthesame thing fordrugs, andsoyouareobliged todoaquantitative analysis,
more complicated analysis tocompare with thetolerance, with theMRL andsotechnically it'smore
easy. Butit'ssmall differences, anylaboratory know how todothetwojobs.
Chairman
831. Thank youvery much. Mynext question related tothistoallthePanel members. Isthere
afundamental difference ...[Iamsorry.]
Dr.Arnold
832. Mr.Chairman, Iwould liketoaddfewsentences. Sometimes abanmakes lifeofanalytical
chemists easier. Butnotalways andthere isnoeasy answer tothatquestion. Igiveyoutwoexamples.
Oestradiol 17-B, isused asbenzoate illegally andaccording tolegal authorizations fortherapeutic
purposes. Onaroutine basis, theonly waytodetect thesubstance, currently, istodetect aninjection
site. Although Iknow thatmany people arestarting being able todetect theester. Buteven ifyou
detect theester somewhere, notattheinjection site, then it'sstillthequestion, wasitillegal orhas
itbeen legally used? Soit'snotsoeasy. And most results have been obtained ifpeople hadfound
theinjection siteandifthey were able then togoback tothefarm andlook. Ifsomebody misuses
these substances, then henever uses itonanindividual animal basis. Then youtrace back andyou
see,there aremany animals treated thesame wayandthen youaresure, itwasillegal. So,it'salot
ofeffort andcosts alotofmoney tocontrol this.
Chairman
833. CanIfollow up.Asalayman, Iassume thatifthepractice isillegal andyouwant toapply
thedrug, youcan'tusetheearmark, because itistooobvious. Sowhat youdois,youmake massive
injections inthemuscle. And ifwetake theevidence thatthere hasbeen about, wasit20,000 cattle
controlled, thisisasmall percentage ofallcattle controlled. And ifyouhappen tobetheconsumer
ofgetting thatmuscle, isn'tthere ariskthatyouhave enormous intake? Imean, istheriskgreater
under abanthan when it'scontrolled? This isthemain argument andIwould liketojustaddthis
oneandIhave twomore elements which should gowith it.Weshould alsoconsider thecontrol ofWT/DS26/R/USA
Page 358
imports under thetwothings. And thefinal point is,isthere afundamental difference between
controlling hormones than from other veterinary drugs andsubstances used. Does itallow a
fundamentally different approach than what wehave inother areas?
Dr.Arnold
834. Mr. Chairman, theusefortherapeutic uses isbyinjection. This istheonly way which is
permitted. Sotheillegal people, theydoitbyinjection andtrytohide theinjection site. Soyouhave
injection inboth thecases. This makes thething sodifficult.
Chairman
835. Butyoucantrace it,because itisused bytheveterinarian onthetherapeutic side.
Dr.Arnold
836. You canaskthefarmer toshow hisprescription, forexample. Soyouhave todoalotof
effort. Simply byanalytical means it'svery difficult toanswer thequestion whether ithasbeen used
legally orillegally.
Dr.André
837. Yes, inshort, concerning thecontrol ofhormones andother drugs, Ithink theproblem isthe
same. Because wehave alsotocheck forbanned compounds aschloramphenicol andtheproblem
isthesame tocontrol forchloramphenicol asfortrenbolone ornandrolone. It'snotreally different,
Ithink. Thecontrol ofimported meat, theproblem isthatitisimported meat. Itisnotaliveanimal
andit'sclear also, everybody, every scientist, analytical man cansaythatit'smore easy towork on
feed, towork onurine, astowork onmeat. Soit'smore difficult. It'snotimpossible. Butit'smore
difficult. And concerning your third short question, theoccasional consumption ofthemeat with an
injection site. Thisishighly improbable. Because, formany reasons: firstofall,these injected solutions
aremainly oilsolutions ofbenzoate, oestradiol andother compounds. Sothebutcher islooking for
what itis.Heiscutting anditisvery improbable thataninjection sitecanbeeaten. Even ifitis,
letmeremind youthatitisanoccasional consumption. Itwillnever be,youhave noopportunity
toeateach dayaninjection site. Itwould beanexceptional thing andmaybe youwill beinformed
bythenews ofthatvery strange thing.
Chairman
838. Thenextpoint isrelating tothelabelling. Youhadawritten question onlabelling, theanswers
were fairly short inmost cases. Andwewould liketoback uponthisone. There aretwoapproaches.
You could have voluntary labelling basically ofmeat which hasnotbeen treated, what wecallgreen
labels, andyoucanhave mandatory labelling oftreated meat, which hastobeenforced. Reading this
question, doyouthink labelling would beafeasible approach? Ifnot,inwhat ways would thislabelling
procedure differ from thecontrols already carried outbytheECtoensure thatimported meat hasnot
been treated with hormones atall?Isthefactthatonecannot distinguish between treated anduntreated
meat sufficient reason nottolabel meat? What isthedifference between labelling already carried out
today, even with respect tomeat, such asthismeat isBSE-free orAmerican meat, orFrench meat,
andlabelling forpurposes astowhether meat isorisnottreated with hormones? Imean thelabelling
isamajor policy today inmaking orleaving decision toconsumers. Most reactions were negative
except yours, Dr.Lucier. And weneed toknow little bitmore why youthink thisisnotadoable
way. Now, butwell that'sananswer yes. Butmaybe, youhave scientific reasons toowhich itis
notdoable.WT/DS26/R/USA
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Dr.McLean
839. Imean, anything ispossible, Mr.Chairman. It'sjustthecost. Butifyoulook attherealities
oflabelling meat, especially when theliveanimal isacommodity, it'sbought andsold andtraded.
Then what youmean byuntreated, ifyoumean never ever treated inthelifetime, then yougotolook
atthecalf, yougottolook atasitchanges hands, once ortwice itmoves intoafeedlot. Soyouhave
gotachain ofidentification, youreally need apassport with each animal, towhich each owner attests
thathasnever treated andtheir passport goes onwith ...
Chairman
840. Itcould beanother earmark.
Dr.Lucier
841. It'sapractical problem. Theother difficulty iswith thenaturally-occurring substances, how
doyoureally determine whether ithasbeen treated ornot,except forthepresence ofthepellet in
theear. Because analytically youcan'ttellwhether ithasbeen treated. And there isanother problem
with zeranol. Insome countries, Fusarium which produces thezeranol-like components contaminates
pasture andfeed. And there arecountries intheEC, Ibelieve, where when itcomes totaking the
farmer tocourt forexample, itisimpossible really toprove beyond allreasonable doubts thatparticular
animal didn'ttakeinafairburden ofthezeranol-like substances thathave leftsome residue. Sothere
arepractical problems across theboard. And Imade thepoint, andIknow thatit'sunrelated butone
hastolook atthecostofthisagainst thebenefit. And thebenefit islargely psychological, butthe
costisenormous. Andwhen youlook forexample, there 'stheexample thatIgave with theoutbreaks
ofE.colifood poisoning thatisoccurring allaround theworld, where there arehundreds ofpeople
getting illandanumber ofthem dying, onewonders whether oneisbetter tospend thedollar on
rectifying thisproblem than putting itintosomething thatcanconfers apsychological advantage to
theperson eating themeat. Asimple practical problem.
Chairman
842. Thank you.
Dr.Lucier
843. Mywritten comment wasprobably anaive oneinmany respects. ButIthink oneought
nevertheless toconsider whether theprimary source caninfactbelabelled. Obviously there isalot
ofspin-off meat products thatwillbedeveloped anditwillbevery difficult totrace those andlabel
each ofthose. ButIthink itneeds tobelooked atastowhether theprimary source canbelabelled
such asthisanimal hasbeen treated withagrowth promoting agent forthepurpose ofgrowth promotion.
Ithink itcould benarrowed down tothatandperhaps benotquite socostly asiffull-blown labelling
procedures were putintoeffect. Ithink ifthat'sallpossible anditisnotgoing tobreak thebank,
Ithink itreally needs tobeconsidered. Imean, after allifthepublic isconcerned about these issues,
thepublic hasaright toknow, ifatallpossible.
Chairman
844. Thank youvery much.
Dr.Ritter
845. Intrying toprepare awritten response tothis, Mr.Chairman, infactIcited inanumber of
references who understand thistopic much better than I.ButIsuppose thequestion thatIaskmyselfWT/DS26/R/USA
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iswhat would betheobjective ofthelabelling. Because Ithink thathelps todefine thestrategy. We're
accustomed around theworld tolabelling products where aninformed decision isauseful thing to
offer. Ifyouwant tosmoke, these arethepotential consequences. Orthere aremany therapeutic
drugs, notnecessarily veterinary medicines, buthuman medicine, which may raise theriskofbirth
defects, andwelabel them, because theymay confer enormous benefits topatients. ButIwasunclear
when thequestion wasraised. Toturnitaround, ifitwere theview ofthePanel thattheuseofthese
agents does notconstitute ariskthathastobedealt with, then Iaskmyself what'stheobjective.
Chairman
846. Well, Iamrecalling asubmission which wasintheEC'ssubmission tohigh USGovernment
officials explaining thehormone treatment andwhen hewasasked privately what type ofmeat doyou
prefer, hesaid, ifIcanafford itIbuynon-hormone treated beef. And Ithink that'sthesortofchoice
people would want tomake. Ithink wemake these choices every time, particularly now attheage
ofBSE. Youfindonthecardinarestaurant, USbeef, beefimported from theUnited States andthat's
another label, andthat'salabel inthemeat sector, andsothatlabel somehow works, Ihope itdoes.
Dr.Ritter
847. Well, then, Iwould beinclined tothink, ifthat'sthecase toprovide those who wish tomake
achoice, theopportunity tomake one. And ifit'snotamatter ofhelping aconsumer decide onthe
basis of....[cassette ended.]
848. Ithink ofsome ofthesupermarkets particularly intheUnited States, South West inCalifornia
where there hasbeen awhole culture offranchises that'sdeveloped around assuring theconsumer that
it'spesticide freeorthisresidue free, andmyview onthatisallpower tothem, ifyoucancreate a
market niche foryourself byoffering aconsumer something which theywant butwhich maynotprovide
anydirect benefit. ButIunderstood thequestion toasked inthecontext ofaregulatory imposition,
andinthatcontext Iasked myself what'stheobjective. Because ifitdoesn 'thelp theconsumer make
an"informed" decision, andIusetheword informed toimply nottheknowledge thathasbeen treated,
butrather information which canmaterially affect thedecision, then Ihave toaskmyself ifonecan
justify thecostandeverything elsethatgoes with itwhen onecould simply allow themarket-place
toaccommodate it.Idon'thave thatview ifit'saquestion ofrisk, ifwe'retalking about adrug that
may induce abirth defect andaphysician hastomake adecision onbehalf ofhispatient, than Ithink
labelling isvery appropriate. Very appropriate fortobacco, although Ihave other views about tobacco.
Ithink there isamore appropriate way todeal with tobacco than labelling. SoI'mnotinanyway
trying tosuggest thatconsumers should notbegiven thechoice. Butifthechoice asIsayisbased
onpreference andnotscience, then myposition would bethatIletthemarket prevail. And weknow
from worldwide experience, IcitetheUSasanexample butthere aremany others, thatindeed there
willbeentrepreneurs who willgrow uptofillthatniche. AndIthink thatifthey candothatandtake
advantage ofthatsortofasituation, itisthehallmark offreeenterprise.
Chairman
849. Thank youvery much. I'mtrying towrap up,there isonequestion Istillhave toaddress,
atechnical one. Theexperts have notaddressed (this isNo.10). Theexperts have notaddressed
thehormone MGA. Hasanyriskassessment been carried outwith respect tothishormone? Does
thishormoneposedifferenthealthriskthantheothertwosynthetichormones?Doyouhaveanyevidence
onthis? It'squestion 10here onthepaper, thelastquestion.WT/DS26/R/USA
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Dr.McLean
850. Iguess allIcansayMr.Chairman isthatIhave nothadtheopportunity tolook atapackage
ofdata, contemporary data, thatiscomplete, andsotherefore I'munable tocomment andImade that
comment atthebeginning.
Dr.André
851. Justacomment, onemajor riskforthese hormones istheriskassociated with management
ofanhormone, anactive hormone imported directly inthefeedonthefarm. That'sarealriskIthink.
Inthishormone isvery different from theothers, butnomore comment onthis.
Dr.Lucier
852. Well I'mnotsaddled with thesame amount ofinformation mycolleagues aresoit'sdifficult
formetomake acomment because oflack ofinformation. There issome, there isareport thatit
produces anequivocal increase inmammary tumours, along-term study andthatit'savery potent
progestational agent. Theinformation thatIcould getisthatit'sabout 30times more potent than
progesterone andorally active soit'sanextraordinarily potent progestant. Sothatraises some concerns
toxicology justforthatreason. ButIhaven 'tseen thetoxicology studies thatapparently areavailable
butIwould have some concern based onthese twopieces ofinformation.
Chairman
853. Would itbepossible togetthisinformation forthePanel oristhistoodifficult?
Dr.Ritter
854. No,buttheissue Mr.Chairman, isthatinthecase offiveofthesix,Ithink theview that
you'veheard from allofusparticipating, notnecessarily agreeing, butthatthere hasbeen asubstantial
amount ofinformation onwhich wehave based ouropinion. Inanumber ofcases wehave arrived
atdifferent opinions, butwehave allagreed thatthere hasbeen asubstantial amount ofinformation.
Inthecase ofMGA because ithasnotbeen subjected toaninternational review thus far,aJECFA
review, andbecause information submitted insupport ofthese sorts ofpetitions tonational regulatory
authorities isgenerally proprietary, Ithink none ofuswould have hadthebenefit ofthedepth ofthe
review thatwould beavailable fortheother five. SoIthink thatthecautionary notethatyouarehearing,
atleast from Dr.Arnold, Professor McLean andmyself, isthatthemost accurate thing wecould say
isthatwesimply don'tknow. Imean thatnotonewayortheother butthatIonmyown, would not
venture aguess onewayortheother because Ihave notseen onepercentoftheinformation onMGA
thatI'vebeen able toexamine fortheothers.
Chairman
855. Thank youvery much. I'dliketocome tothefinal tour detable onthesideoftheexperts
andI'dliketolinkthistoquestion seven here, Ithink thatthiswillbeatheart ofthe,alsoofthelegal
issues tobediscussed inthiscase. Dr.Liehr hasprovided touswhat iscalled thenewevidence on
thepotential genotoxicity ofthehormones. Other experts have questioned therelevance ofthisevidence.
Iwould liketohave your personal views onwhat istherelevance ofthisnewevidence forveterinary
drugs other thanthehormones atissue, such ascarbadox, andfortheuseofnatural hormones, especially
oestrogens, fortherapeutical purposes. Ifthisnewevidence would beareason tobanhormones added
forgrowth promotion, would italsobeareason tobanallother usesofthese hormones ortobanother
veterinary drugs? And perhaps before youaddress this, wearenotvery clear onthePanel onyour
fundamental views towhat extent oneshould, ascientist should orshould notconsider when heconsider
theriskforhormone residues, towhat extent heshould really takeintoaccount thegenotoxic effects.WT/DS26/R/USA
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There seems tobedifferent, slightly different views. Butifyoucould state again your position on
thegenotoxic effects andthen perhaps follow thisup.How would youadvise thePanel totakeinto
account thisnewevidence which hasbeen presented particularly yesterday tous.Maybe we'llstart
with Dr.Ritter andthen gothrough thePanel.
Dr.Ritter
856. Justvery quickly, Iwon'ttakemuch time Mr.Chairman. Ithink, I'mreminded thatDr.Liehr
mayhave captured thereference point onthisinformation thathepresented better perhaps thananyone
else. When hesuggested himself yesterday, Ithink quite correctly, thatinorder toestablish thedirect
relevance ofhispreliminary findings, hewasseeking additional research funding. Ithink hesaidthat
theparties tothedispute would have made abetter investment, iftheywould have funded himtoexamine
therelevance ofthese findings atthelowlevels which arebeing present, than they have expended in
coming tothishearing. Iamparaphrasing alittle bit,butIthink thatwasthegistofhiscomments.
Ithink hehasputitbetter than anyone else. Ithink thefindings areinteresting buthehimself Ithink
hassuggested thatthey arenotintheform orofthenature where they canbedirectly applicable to
thenature ofthedeliberations here. Thenature ofscientific investigation isthatitgoes forward. And
ifwewere tomeet again inayear, Idare sayyouwould belooking atevidence which youdidn'thave
available today. Imentioned toyouyesterday Mr.Chairman, thatIknow ofnoscientist who has
ever saidonanyissue, because wearealllooking forfunding, Iknow enough, please don'tprovide
anymore money onthisissue. Iknow I'venever done it.SoIthink justvery quickly inthecontext
oftherelevance, thatwould bemyview, it'sinteresting, butIliketheway Dr.Liehr phrased it.
857. Interms oftherelevance inalarger sphere toother veterinary drugs, again Ithink theonly
waytoanswer thatquestion istoapply thesame technology toother drugs. Itisconceivable thatif
oneapplied thenew methodology thatweheard described yesterday toarange ofother veterinary
drugs, pesticides, other food contaminants, thatitmight raise thevery same degree ofconcern that
itseems tohave generated inthisdebate over thelastcouple ofdays. Idon'tknow theanswer because
ithasn'tbeen done. Butifyou'dliketoprovide thefunding Mr.Chairman ....And finally Ithink
ontheissue ofcarbadox specifically, ifIread thistobethethird issue ifyoulike, Ithink inthecase
ofcarbadox there isalready general agreement thatitisagenotoxic agent, sotosubject thatspecific
example tofurther investigation, Ithink would contribute little toourknowledge because wehave
already concluded thatitiscapable ofthistype ofaction. Subjected tofurther studies would only
confirm what wehave already allagreed on. SoI'mnotlooking formore funding onthatone.
Chairman
858. Thank youvery much. Professor McLean.
Dr.McLean
859. YesMr.Chairman, thewaythatIreaditwasthatDr.Liehr wasputting forward aninteresting,
along with anumber ofother people, were looking atthemechanism ofcarcinogenesis ifIcould put
itthatwayandtherefore genotoxicity wasimportant. That hehadahypothesis, hehadmade aseries
ofobservations andhewastesting thathypothesis andthatmay ormay notbesignificant, when it's
finally worked itswaythrough, tothisparticular group ofhormones. Dr.Arnold didpoint outthat
there were other hypothesis being tested with similar sorts, atthisstage, ofstrength, ifyoulike. And
sotherefore Ithink inrelation tothenewevidence, thejuryisreally stilloutanduntil thehypothesis
firms up,ifIcould putitthatway, then there islittle wecando.And itwould beunfortunate ifthe
hypothesis didn'tstand upandother hypothesis came forward andwere tested andshown tobeeffective
ifthey dothatwe'dmade amistake there. Inrelation toother veterinary drugs, many ofthem are
carcinogenic inanimals. Justtoname afew, dimetridazole, metronidazole which iswidely used in
humans isquite carcinogenic inanimals, yetitisstillused, thesulphonamides arequite carcinogenic
inrodent carcinogenicity tests, carbadox, weknow iscarcinogenic andthat'stoname four. And toWT/DS26/R/USA
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gothatnext step, wedon'thave themechanism oftoxicity inallofthecases. And wecould develop
ahypothesis andtestitandthenwemight arrive attheprecise mechanism. SoIthink wehave asimilar
situation with other veterinary drugs although, with thehormones, theydohave avery serious human
health effect inproducing forexample breast cancer andsowe'reputting alotofmoney inthearea
towork thatthrough. Because itisanimportant human health activity andIwould support continuing
research with theother drugs, they don'tassume thatimportance andsowedon'tputthemoney in.
Chairman
860. Thank youvery much. Dr.Arnold
Dr.Arnold
861. Idon'twant toaddvery much because Ilargely agree with thetwoprevious speakers. But
should ithappen that, forexample, oestradiol would beidentified asgenotoxic carcinogenic andshould
thisthen cause abanofthissubstances forgrowth promotion, Iwould sayfrom theviewpoint ofa
consumer, Icould thennotunderstand itsuseforzootechnical purposes Forexample, thenoneshould
doresearch toreplace thisanduseother substances which could beavailable forthesame purpose.
And alsoIwould saythen thesubstance should berestricted inveterinary therapy toamore narrow
definition oftherapeutic use. Wehave avery broad, asaconsumer, Icannot agree with thisbroad
definition oftherapeutic uses. And itwould have severe consequences inhuman medicine because
then itwould bevery difficult tojustify theuseofthissubstance inoestrogen replacement therapy,
forexample, fortheprevention ortreatment ofosteoporosis where millions ofwomen take one
microgram, intheorder ofonemicrogram ofmicronized andbio-available amounts ofoestradiol every
day. Soitwould have severe consequences inmany areas.
Chairman
862. Professor André.
Dr.André
863. Yes, Ithink thatDr.Liehr gives usnewresults inthemode ofaction ofthese oestrogens in
their carcinogenic effects, butheisnotalone togive these results. Wehave many different ways to
understand howtheyact.Thedifference hereisitacomplete theory which seems very understandable
andtherelation between oestrogens andDNA seems tobemore identified thatitwasearlier, forthis
it'sclear. ButIthink thatifweadmit thatthese hormones aregenotoxic, it'stwovery different things
tobanthem asgrowth promoters, asIsaidyesterday, inalarge scale forallpopulations anditisvery
different fortheir useastotherapeutic use. It'sthesame difference asItried toexplain with my
example. Astherapeutic use,they areused inoneanimal foronetime andusually forreproduction
purposes, soit'sacompletely different thing. Sothey canbebanned forgrowth promotion andthey
canbeused fordrugs. ButIagree with Dieter Arnold onthefactthatthere issome problems inthe
definition ofwhat istherapeutic useandalsohow toevaluate really adrug fortherapeutic use,asis
done classically foryears now bydifferent committees, andtheuseofcompounds forother purposes
thanreally therapeutic use. And inthiscase, tomyopinion, theevaluation hastobemaybe different.
Chairman
864. Thank youvery much. Dr.Lucier.
Dr.Lucier
865. Mycomments willbeabitdifferent. Ithink thework thatDr.Liehr isdoing, Ithink it's
important topoint out,ashehas,isthatit'snotjusthimself. There isagroup ofscientists who areWT/DS26/R/USA
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looking attheroleofoxidative damage andgenotoxicity ofoestrogens, himself andseveral other folks
throughout theworld. AndIthink thisactivity isvery important toourunderstanding ofhowoestrogens
andhow hormones may cause cancer. SoI'mastrong supporter thatkind ofwork, Iactually have
acouple ofpublications initmyself. Butforthisnarrow purpose thatwearetalking about today,
about theinfluence ofthisonadditional riskfrom oestrogens from eating, consuming meat containing
oestrogens from growth promoted animals, itdoesn 'thave toomuch consequence. IfIdidacalculation
ofriskasI'vedone, thisoneinamillion thing how thathasbeen much discussed, Iwould come up
with thesame calculation whether ornotoestradiol wasgenotoxic. That would bear noinfluence on
thecarcinogenic riskastheassumption iswearealready onalinear partofthecurve interms ofamount
ofoestrogen, themagnitude ofoestrogen andthemagnitude ofresponse, sayforbreast cancer. Iwould
come upwith thesame answer either case; there would benodifference intherisk. SoIthink in
thatrespect whether ornotoestrogen isgenotoxic, haslessconsequence then what wetalked about
uptothispoint intime.
Chairman
866. Well thank youvery much foryour final statements. This brings ustotheendofthisexpert
hearing, Icome toprocedures, which brings ustotheendofthistwo-day meeting. Inmyview, the
combination both ofyour excellent papers, andIknow youtook pains towrite them inaway that
thenormal person canread it,together with your oralpresentations andthequestions andcomments
ontheparties, Ithink have exceedingly helped toinform thePanel onthescientific side. Asidewhich
isvery difficult andvery complicated. Itisalmost ascomplicated astheprocedural one, butnotas
much. Sothank youvery much foryour tremendous effort andalsotheeffort youputinsuch ashort
timetoassist thePanel which isoperating under these verystrict rules. Thank youalsotothedelegations
forassisting inthese proceedings. Thank youinparticular alsoforthescientists who satwith theEC
delegation andcame here topresent their views andtheir convictions andinform usaswell.
867. Sothisbrings ustothefinal procedural point. With aview tothemeeting tomorrow, which
isthesecond substantive meeting, thePanel hasreflected andinthelight ofthefactthatthishasbeen
ajoint meeting today andwehaddifficulties tomake decisions about what isnew evidence, what is
anew argument, andsoon,andalsoinlight ofthefactthatallthepapers have been exchanged in
thetwoproceedings, thePanel hastaken adecision tocome back toitsright which itreserved before
andwedecided toinvite theUnited States delegation toattend themeeting tomorrow. Doyouhave
anyother points onprocedure?
Mr. Brinza (US)
868. Mr.Chairman, youanticipated correctly thequestion Iwasgoing toask, thank you
Chairman
869. Professor André
Dr.André
870. Justonbehalf ofmycolleague experts, Iwould liketothank youfortheexcellent level of
thisdebate, duemainly toanexcellent chairmanship.
Chairman
871. Thank youvery much. Sothemeeting isclosed, good night. I'msorry, ...Mr.Christoforou,
youwanted thefloor.WT/DS26/R/USA
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Mr. Christoforou (EC)
872. YesMr.Chairman. Iwould alsoliketothank theexperts, anditisnotusual procedure but
wewould appreciate ifitispossible togetthetyped version ofwhat wasdiscussed here today. Iknow
itisnotusual, butIthink itwould bevery useful ifwecangetthediscussions today typed andcirculated
totheparties.
Chairman
873. Yes, thisisunderway, butitwillofcourse take some time. Butthiswillbedone yes.
Mr. Thompson (Canada)
874. Itoowould liketothank again theexperts forparticipating, Iwaswondering what time we
arereconvening tomorrow andisitinthisroom.
Chairman
875. Thank youvery much, themeeting willbea10:00 inthisroom here. Sothemeeting isclosed.