WORLD TRADE ORGANIZATION

WT/DS320/R/Add.3 31 March 2008

(08-0901)

Original: English

UNITED STATES CONTINUED SUSPENSION OF OBLIGATIONS IN THE EC HORMONES DISPUTE Report of the Panel
Addendum This addendum contains Anne ! to the "e#ort o$ the %anel to &e $ound in document 'T()*320("+ The other anne es can &e $ound in the $ollo,ing addenda: Anne Anne Anne Anne Anne Anne A: .: ): E: 1: 3: Add+1 Add+2 Add+/ Add+0 Add+2 Add+4

'T()*320("(Add+3 %age !-1 ANNEX C REPLIES OF THE PARTIES TO QUESTIONS POSED BY THE PANEL AND OTHER PARTIES AFTER THE SECOND SUBSTANTI E MEETING AND COMMENTS BY THE PARTIES ON THE OTHER PARTIES! REPLIES C"#$%#$& "e#lies o$ the Euro#ean !ommunities to 5uestions #osed &6 the %anel a$ter the second su&stanti7e meeting (18 Octo&er 2002) !omments &6 the Euro#ean !ommunities on the re#lies o$ the 8nited *tates and !anada to 5uestions #osed &6 the %anel and other #arties a$ter the second su&stanti7e meeting (31 Octo&er 2002) "e#lies o$ the 8nited *tates to 5uestions #osed &6 the %anel a$ter the second su&stanti7e meeting (18 Octo&er 2002) "e#lies o$ the 8nited *tates to 5uestions #osed &6 the Euro#ean !ommunities a$ter the second su&stanti7e meeting (18 Octo&er 2002) !omments &6 the 8nited *tates on the re#lies o$ the Euro#ean !ommunities to 5uestions #osed &6 the %anel a$ter the second su&stanti7e meeting (31 Octo&er 2002) P'(% !-2 !-2/

Anne !-1 Anne !-2

Anne !-3 Anne !-/

!-/0 !-/4

Anne !-0

!-00

'T()*320("(Add+3 %age !-2 ANNEX C) REPLIES OF THE EUROPEAN COMMUNITIES TO QUESTIONS POSED BY THE PANEL AFTER THE SECOND SUBSTANTI E MEETING (18 Octo&er 2002) Q*%&$+"#& $" ',, -'.$+%& Q). W+$/ .%0%.%#1% $" $/% &$'$%2%#$ 34 $/% E*."-%'# C"22*#+$+%&5 inter alia +# -'.'. )2 "0 $/% EC .%-,4 $" Q*%&$+"# 3 "0 $/% U#+$%d S$'$%&5 d" $/% -'.$+%& 1"#&+d%. $/'$ ' P'#%, +& %#$+$,%d $" 'dd.%&& 6&4&$%2+1 1,'+2&6 ". +&&*%& .%,'$%d $" 6&4&$%2+1 "3,+('$+"#&6 '#d5 +0 &"5 $" 7/'$ %8$%#$9 1+ .6 9s6stemic claims9 and 9s6stemic o&ligations9 the Euro#ean !ommunities is re$erring to o&ligations contained in the )*8 that are related to the 'TO dis#ute settlement mechanism as a s6stem: are #rocedural in nature and inde#endent o$ su&stanti7e o&ligations contained in other 'TO agreements+ A $ailure to &ring a case under Article 21+0 is a 7iolation o$ a #rocedural o&ligation: irres#ecti7e o$ ,hat the underl6ing disagreement on the 5uestion o$ com#liance is a&out+ E5uall6: $rom the Euro#ean !ommunities; #oint o$ 7ie,: the continued a##lication o$ sanctions in the $ace o$ #resumed com#liance and in the a&sence o$ a com#liance re7ie, constitutes a 7iolation o$ a #rocedural nature: irres#ecti7e o$ the su&stanti7e re5uirements o$ actual com#liance+ 2+ The %anel is not onl6 entitled: &ut has an o&ligation to rule on claims o$ 7iolation o$ such o&ligations under the )*8: ,hich ha7e &een #ro#erl6 made &6 the Euro#ean !ommunities in this dis#ute+ The Euro#ean !ommunities $urther notes that se7eral %anels in the #ast ha7e alread6 ruled on Article 23 claims+1 Q2. W+$/ .%0%.%#1% $" $/% US .%3*$$',5 -'.'. 2:5 d" $/% -'.$+%& 1"#&+d%. $/'$ ' 2%'&*.% $/'$ d"%& #"$ 1"2-,4 7+$/ $/% .%;*+.%2%#$& "0 A.$+1,% <.: SPS 7"*,d '*$"2'$+1',,4 3% +# 3.%'1/ "0 A.$+1,% 2.2 SPS5 ". A.$+1,% <.) SPS5 ". 3"$/9 3+ <n the Euro#ean !ommunities; 7ie, this 5uestion ma6 &e &ased on a misunderstanding o$ the #oint made in #ara+ 24 o$ the 8* "e&uttal *u&mission+ The 8nited *tates is not arguing that a $ailure to meet the re5uirements o$ Article 0+4 automaticall6 results in a 7iolation o$ Articles 2+2 and(or 0+1+ "ather the 8* is arguing that a measure has to satis$6 the o&ligations under Articles 2+2 and 0+1 i$ the conditions o$ Article 0+4 do not a##l6+ /+ <ndeed: assuming that a $ailure to meet the re5uirements o$ Article 0+4 ,ould automaticall6 lead to a 7iolation o$ Articles 2+2: 0+1 or &oth: ,ould lead to a&surd results+ %icture a measure that is &ased on a ris= assessment ,ithin the meaning o$ Article 0+1+ That measure ,ould not $ul$il the conditions o$ Article 0+4: as it is not #ro7isional in nature: is not &ased on 9a7aila&le #ertinent in$ormation:9 has not &een $ollo,ed u# through $urther research etc+ >e7ertheless: the measure is o$ course #er$ectl6 in com#liance &oth ,ith Articles 2+2 and 0+1+ 0+ At the same time: there is no dou&t that i$ a measure that ,as thought to $ul$il the re5uirements o$ Article 2+2+ and 0+1-0+2 is $ound a %anel not to do so: it should &e considered ,hether it $ul$ils the re5uirements o$ Article 0+4: in 7ie, o$ the lo,er amount o$ #ertinent scienti$ic e7idence and the greater role ,hich scienti$ic uncertainties #la6 in the ado#tion o$ an Article 0+4 measure+ As the Euro#ean !ommunities has argued in its re#l6 to ?uestion 22 o$ the %anel: Article 0+4 is a s#ecial

*ee onl6 US Certain EC Products: US Section 301@ EC Vessels (9*hi#&uilding *u&sidies9)+

'T()*320("(Add+3 %age !-3 regime in relation to Article 0+1+ <t a##lies to #ro7isional measures ado#ted in the $ace o$ insu$$icient scienti$ic e7idence and is in that sense also identi$ied as lex specialis to Article 2+2+ Q3. W/%# '#d /"7 7'& %'1/ "0 $/% 0",,"7+#( d"1*2%#$& 2'd% '='+,'3,% $" C'#'d' '#d $/% U#+$%d S$'$%&9 P,%'&% '#&7%. +#d%-%#d%#$,4 0". %'1/ "0 $/% d"1*2%#$& 2%#$+"#%d 3%,"7> ?+@ ?++@ ?+++@ ?+=@ )AAA O-+#+"#B 2000 O-+#+"#B 2002 O-+#+"#B %'1/ "0 $/% 6): &$*d+%&6.

2+ The Euro#ean !ommunities has re#lied to this 5uestion in detail in its re#l6 to ?uestion 12 o$ the %anel (see #aras+ 49$$) and in #aras+ 111$$ o$ its *econd 'ritten *u&mission+ 4+ The 1999 O#inion ,as ado#ted on 30 A#ril 1999 and #ut on the internet almost immediatel6 therea$ter: and ,as transmitted to the 8* and !anada+ <n &ilateral contacts: &oth 8* and !anadian counter#arts ,ere made a,are o$ this $act+ As e #lained in #ara+ 92 o$ its Oral *tatement at the $irst su&stanti7e meeting as ,ell as in #ara+ 112 o$ its *econd 'ritten *u&mission: a meeting &et,een E! and 8* scientists ,as arranged in 'ashington in Aune 1999 to discuss the results o$ the 1999 O#inion+ >o such meeting too= #lace: ho,e7er: &et,een !anadian and E! scientists: as none ,as re5uested &6 !anada+ 8+ The 2000 O#inion ,as ado#ted on 3 Ma6 2000 and #ut on the internet 7er6 shortl6 therea$ter+ <n in$ormal &ilateral contacts: &oth 8* and !anadian counter#arts ,ere also made a,are o$ this $act+ 9+ On 3 >o7em&er 2000 the E! dra$t legislation ,as noti$ied to the *%* !ommittee (3(*%*(>(EE!(102)+ The noti$ication (re7ised 7ersion su&mitted on 14 >o7em&er 2000: see 3(*%*(>(EE!(102("e7+1): in #oint 12: re$ers &oth to the 1999 and the 2000 O#inion and #ro7ides the internet lin= ,here the O#inions can &e accessed+ !anada su&mitted its comments on this noti$ication in )ecem&er 2000 (see E!-E hi&it 2/) in ,hich it stated that !anadian o$$icials at Bealth !anada had re7ie,ed the O#inions: so clearl6 !anada must ha7e had access to them+ 10+ The 2002 *!C%B;s third assessment had &een long announced &e$ore it ,as actuall6 carried out+ The Euro#ean !ommunities had made #u&lic the $act that it had launched 14 studies: the results o$ ,hich ,ould &e re7ie,ed in time+ 2 The 2002 O#inion: ,hose sole #ur#ose ,as to re7ie, all the a7aila&le e7idence and in #articular the results o$ the 14 studies: ,as ado#ted on 10 A#ril 2002 and #ut on the internet shortl6 therea$ter+ <n &ilateral contacts: &oth 8* and !anadian counter#arts ,ere made a,are o$ this $act and actuall6 ha7e ne7er com#lained that the6 had not recei7ed it+ 11+ The #reliminar6 $indings $rom 14 scienti$ic studies had alread6 &een ta=en into account in the 1999 *!C%B o#inion: as the6 ,ere a7aila&le at the time+ The $inal results $rom the studies ,ere ta=en into account and ,ere cited and re$erenced in the 2002 O#inion (#age 28)+ At the time o$ the ado#tion o$ the 2002 O#inion: onl6 one stud6 had not 6et &een #u&lished (that is E hi&it E!-29): ,hilst one stud6 ,as $rom the start not meant $or #u&lication (E hi&it E!-4): as it contained the sam#les o$ meat collected $rom the 8* su#ermar=ets that ,as sent $or anal6sis in the Euro#ean la&oratories+ Also one other stud6 (E hi&it E!-30) ,as #artl6 #u&lished in Dange <+3+: )a en&erger A+: Me6er B+B+: "aE#ert-)e Me6ts E+: *=a==e&ae= >+E+: Ceeramachaneni )+>+: "elated Articles: Din=s A&stract ?uantitati7e assessment o$ $oetal e #osure to tren&olone acetate: Feranol and melengestrol acetate: $ollo,ing maternal dosing in ra&&its+ Geno&iotica+ 2002 Aug@ 32 (8):2/1-01+ .ut in 7ie, o$ the &readth o$ its research it continued in colla&oration ,ith 8* scientists a$ter 2002+ <t a##ears that its $inal results ha7e not &een #u&lished 6et+ <t should also &e clari$ied that
2

>ot least in !ode : see $or e am#le 11th session o$ the !!"C)1+

'T()*320("(Add+3 %age !-/ E hi&it E!-10 ,as #u&lished in AM%B<* 2001: 7ol+ 109: #+ 89-90: and it is contained also in E hi&it E!-20: at #ages */22-/32+ <t should $urther &e mentioned that some o$ the scienti$ic e #eriments in 7ie, o$ their &readth ha7e gi7en rise to more than one #u&lication (see list su&mitted &6 E! as E hi&it E!-4 through /2: see also re#l6 to ?uestion 12)+ <t $ollo,s that all o$ the studies: e ce#t t,o: ,here #u&lished and thus ,ere #u&licl6 a7aila&le at or &e$ore the 2002 *!C%B O#inion+ Moreo7er: E hi&it E!-20: ,hich is the result o$ an international scienti$ic con$erence o$ Ma6 2001 to ,hich man6 8* scientists including $rom the 8* 1)A had #artici#ated: #u&lished again a 7er6 large num&er o$ the 14 studies+ The6 ,ere thus accessi&le to the de$ending #arties &e$ore 2002+ 12+ As mentioned in #ara+ 9/ o$ the *econd 'ritten *u&mission: !anada: according to its o,n statements made on the internet: carried out an 9intensi7e re7ie,9 o$ the 14 studies (&ased on the re$erence list as anne ed to 2002 O#inion): onl6 the conclusion o$ ,hich is re#orted on the internet (see $ootnote 44 at #ara+ 9/ $or internet address)+ QC. H'& $/% E*."-%'# C"22*#+$+%& '&&%&&%d +# ' &4&$%2'$+1 2'##%. $/% %8+&$%#1% '#d ,%=%, "0 .+&D& 0."2 0'+,*.% $" "3&%.=% (""d =%$%.+#'.4 -.'1$+1%& 7+$/ .%&-%1$ $" $/% 'd2+#+&$.'$+"# "0 "%&$.'d+", ):E '& ' (."7$/ -."2"$+#( /".2"#% $" 1'$$,%5 +# -'.$+1*,'. +# $/% U#+$%d S$'$%&! '#d C'#'d'!& 2'.D%$&9 I0 &"5 -,%'&% +#d+1'$% 7/%.% $/+& '&&%&&2%#$ +& $" 3% 0"*#d +# $/% %=+d%#1% -."=+d%d $" $/% P'#%,. 13+ Hes: the Euro#ean !ommunities has indeed assessed in a 7er6 s6stematic manner &oth the e istence and the le7el o$ ris=s $rom $ailure to o&ser7e 3C% in the administration not onl6 o$ oestradiol-14I &ut also o$ the other $i7e hormones ,hen used $or gro,th #romotion: in #articular in the 8* and !anada+ Although it is not clear ,hat the %anel means &6 9s6stematic manner9: the Euro#ean !ommunities has #er$ormed this assessment as s6stematic as it can &e and: in an6 case: in accordance to the indications contained in the 1998 A##ellate .od6 re#ort in the Hormones case (at #ara+ 204)+ There the A##ellate .od6 has said that 9s6stematic anal6sis9 ,ould entail to in7estigate and e7aluate 9the actual #ro&lems that ha7e arisen at the &orders o$ the Euro#ean !ommunities or ,ithin the 8nited *tates: !anada and other countries e #orting meat and meat #roducts to the Euro#ean !ommunities9+ The Euro#ean !ommunities has alread6 e #lained the e7idence and assessment it has made in some detail ,ith its re#l6 o$ 3 Octo&er 2000 to ,ritten 5uestions no 14: 24 and 31 $rom the %anel+ 1/+ More s#eci$icall6 a regards the %8+&$%#1% "0 .+&D: the Euro#ean !ommunities has alread6 re$erred to the rele7ant e7idence ,ith its re#l6 o$ 3 Octo&er 2000 to 5uestion 14 (#ara+ 89) and 5uestion 24 (at #ara+ 10/)+ The e7idence is contained in E hi&its E!-11: 12: 12: 14: 18: 3/: /4: 01.: 02: almost all o$ ,hich ,ere also #u&lished in E hi&it E!-20 (in the $orm o$ a &oo=)+ This e7idence has clearl6 identi$ied and characterised the haFard resulting $rom the im#lants that are $reel6 a7aila&le in the 8* and the !anadian mar=et+ Moreo7er: #lease note that most o$ the e #erts ha7e con$irmed (e+g+ )r+ .oisseau) that i$ 3C% is not o&ser7ed the A)<s and the M"Ds #ro#osed &6 !ode &ecome useless+ The e #eriments descri&ed in the E hi&its mentioned a&o7e ,ere carried ,ith hormonal im#lants that are actuall6 licensed $or use in the 8* and !anada and considered &oth their recommended use and situations o$ a&use and(or misuse+ 3 10+ As regards the ,%=%, "0 $/% .+&D: the Euro#ean !ommunities has underta=en s#eci$ic studies to e7aluate the e #osure assessment $rom situations resulting $rom .%', '& 7%,, '& %8-%.+2%#$', situations o$ a&use and(or misuse in the mar=ets o$ &oth de$ending mem&ers+ Thus: it carried out s#eci$ic 7eterinar6 ins#ections in the 8* (E hi&it E!-24) and !anada (E hi&it E!-28): ,ith the agreement o$ these countries: and has made a s#eci$ic calculation o$ the le7el o$ the ris= $or im#orts coming $rom &oth countries in E hi&it E!-43+ This assessment o$ ris= is not &ased on theoretical or
*ince oestradiol-14I is #resent in almost all o$ the licensed im#lants in the 8* and !anada: it is o&7ious that the e7idence mentioned in the a&o7e EG E hi&its has also e amined oestradiol-14I+
3

'T()*320("(Add+3 %age !-0 h6#othetical assum#tions (as the 8* and !anada ,rongl6 contend): &ut on e am#les $rom realistic conditions o$ use: ta=ing into account &-%1+0+15 .%', '#d *#d+&-*$%d instances o$ a&use and(or misuse that ha7e occurred &oth in the 8* (see: e+g+: E hi&its E!-03: 24: 29 and 92) /: and in !anada (see: e+g+: E hi&its E!-03: 28 and 40)+ <n addition: the le7el o$ ris= ,as $urther assessed in a s#eci$ic stud6 that im#orted in the E! hormone-$ree and hormone-treated meat sold in the su#ermar=ets in the 8* (see E hi&it E!-03): and this ,as $urther com#ared ,ith the situation in the E! (see: e+g+: E hi&it E!-/9)+ The Euro#ean !ommunities su&mits that a more s6stematic assessment o$ realistic conditions o$ a&use and(or misuse cannot &e carried out: and the e7idence sho,ed le7els o$ e #osure that e ceeded the A)<s esta&lished &6 !ode : ta=ing into account the most recent detection methods and the le7els o$ endogenous #roduction &6 #re-#u&ertal children+ More im#ortantl6: the e7idence sho,s &e6ond dou&t that the situations o$ a&use(or misuse occurring in the 8* and !anadian mar=et are not e ce#tional nor occasional+ 12+ <t should $inall6 &e stressed that all these #ieces o$ e7idence ,ere assessed in the 1999 O#inion (section 3+3: #ages 30-32) and the 2002 O#inion (#ages 10-12) o$ the *!C%B and ha7e &een ta=en into account &6 the ris= manager $or the ado#tion o$ )irecti7e 2003(4/(E!+ <t is note,orth6 that the de$ending mem&ers ha7e not reall6 contested this e7idence: other than to argue &asicall6 that the E! used 9unrealistic misuse scenarios9 (see: e+g+: !anada;s 2 nd oral statement o$ 2-3 Octo&er 2002: at #ara+ 4/@ and the 8* oral statement o$ 2 Octo&er 2002: at #ara+ 20)+ <t is amaFing that the 8* $or the $irst time tries to minimiFe the health ris=s $rom 9e tra-la&el use9 and sale $reel6 o7er the counter (ibid+: at #ara+ 21): ,hich are contradicted &6 the statements &6 the 8* 1*<*+ 0 E5uall6 sur#rising is no, the attem#t &6 the 8* to do,n#la6 the im#ortance o$ a&use and(or misuse ( ibid+: at #ara+ 22) arguing that there can &e no 100J assurance+ The 8* argues ( ibid+: at #ara+ 2/) that 9no $ood sa$et6 s6stem is sa$e9: im#l6ing that the other 'TO mem&ers are o&liged to acce#t the $ailures o$ the 8* s6stem des#ite the ris= to human health in the im#orting countr6 ,hich this =ind o$ $ailures ,ill ine7ita&l6 ha7e: as the e #erts ha7e e #lained ( e.g. )r+ .oisseau and )r+ )e .ra&ander)+ Moreo7er: the 8* does not e #lain ,h6 the statements &6 the 8* 1*<* that 9 is concerned a&out the ,ides#read: illegal use o$ drug im#lants in 6oung cal7es that ,as disco7ered in 200/9: and that 91*<* learned that the use o$ gro,th #romoting im#lants ,as a ,ides#read #ractice ,ithin the 7eal industr69 (and the so man6 other e am#les cited in E hi&it E!-43) should not &e gi7en the a##ro#riate ,eight &6 the E! in its ris= assessment+ Q<. I# +$& 1"22%#$& "# 1"22%#$& "0 $/% U#+$%d S$'$%& '#d C'#'d' "# %8-%.$& .%-,+%& $" $/% P'#%, ;*%&$+"#& ?+# -'.$+1*,'. Q*%&$+"# )3@5 $/% E*."-%'# C"22*#+$+%& +#d+1'$%& $/'$ "%&$.'d+", ):E 2+(/$ 3% ' 67%'D (%#"$"8+#6 ?-'.'. CC@. A$ 7/'$ d"&%& +& (%#"$"8+1+$4 "3&%.='3,% in vivo9 H"7 '.% $/%&% d"&%& 1"2-'.'3,% $" $/"&% 0"*#d +# 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ (."7$/ -."2"$+#( /".2"#%&9 H"7 7"*,d $/+& '&&%.$+"# '00%1$ $/% +d%#$+0+1'$+"# "0 'd=%.&% %00%1$& '#d $/% %=',*'$+"# "0 -"$%#$+', "11*..%#1% "0 $/%&% %00%1$& 0."2 1"#&*2-$+"# "0 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ "%&$.'d+", ):E 0". (."7$/ -."2"$+"# -*.-"&%&9

/ *ee E hi&it E!-102 ,hich states: inter alia: that the 8* 1ood *a$et6 and <ns#ection *er7ices (1*<*) 9is concerned a&out the ,ides#read: illegal use o$ drug im#lants in 6oung cal7es that ,as disco7ered in 200/9+ 0 *ee a&o7e E hi&it E!-102 ,hich states: inter alia: that the 8* 1ood *a$et6 and <ns#ection *er7ices (1*<*) 9is concerned a&out the ,ides#read: illegal use o$ drug im#lants in 6oung cal7es that ,as disco7ered in 200/9+ The same e hi&it also states that 91*<* learned that the use o$ gro,th #romoting im#lants ,as a ,ides#read #ractice ,ithin the 7eal industr6+ Bo,e7er: the 1ood and )rug Administration has not a##ro7ed gro,th #romotion im#lants $or use in $ood animals #resented $or slaughter as 7eal and considers their use to &e a 7iolation o$ the 1ederal 1ood: )rug: and !osmetic Act9+ This e am#le and so man6 other that ha7e &een identi$ied demonstrate that: contrar6 to ,hat the 8* has &een arguing &e$ore the %anel: a&use and(or misuse is a 9,ides#read #ractice in the 8* 7eal industr69+ <ndeed: it cannot &e other,ise as long as these im#lants are a7aila&le $reel6 o7er the counter in &oth de$ending countries: and the manu$acturers recommend multi#le im#lanting ,ith com&inations o$ these hormones $or $aster gro,th o$ the animals+

'T()*320("(Add+3 %age !-2 14+ The 5uestion concerns essentiall6 ,hether oestradiol-14I is mutagen in vivo: and: i$ so: at ,hat dose+ The 1999 *!C%B O#inion cites one stud6 o$ mutagenicit6 in 7i7o (at #+ /1)+ 'ith its re#l6 to %anel;s ?uestion no 13 to the e #erts: the Euro#ean !ommunities has also #ro7ided $urther more recent - re$erences to in vivo studies+ 18+ The stud6 &6 Cavalieri et al+ (2002) (E hi&it 120) re#orted that e #osure o$ rats $or 20 ,ee=s (1/0 da6s) to oestradiol $rom *ilastic ca#sules: ,hich is a method to release lo, amounts o$ a com#ound o7er #rolonged time #eriods: led to a statisticall6 signi$icant increase in mutagenesis in the inguinal mammar6 $at #ads+ A dose o$ 0 milligram o$ estradiol ,as used: ,hich at $irst sight seems 7er6 high+ The #recise amount released &6 the ca#sules used in the !a7alieri et al+ stud6 ,as not determined+2 Assuming that the 0 milligrams ,ere com#letel6 released ,ithin 1/0 da6s (,hich usuall6 is not the case &ecause the dose is designed high enough to secure that the dail6 e #osure is still the same on the last da6): a rather conser7ati7e estimate &ased on the #u&lished $indings ,ould &e a&out 1 microgram #er da6 oestradiol release $rom the ca#sules containing 0 mg oestradiol used &6 !a7alieri: and $or a 330 g rat: this ,ould &e a&out a 3 microgram #er =ilogram #er da6 dose o$ oestradiol (3000 ng ( =g (da6)+ This ,ould mean that the M)) (Ma imum )ail6 )ose) o$ estradiol in this rat stud6 ,as at ma imum a&out 30 micrograms 4 or a&out 0+1 micromole or a&out 200 micrograms #er =ilogram &od6 ,eight+8 19+ <$ the dail6 #roduction rates in #re-#u&ertal children: according to the original 7alues $rom the Klein assa6 ,ere ta=en into account (0+0/ Lg(da6): the A)< esta&lished &6 AE!1A (&ased on the 7er6 high rates o$ endogenous #roduction o$ #re-#u&ertal children o$ 2+0 Lg(da6): ma6 &e e ceeded at most around 1-2 $old: &ut not &6 orders o$ magnitude or 9massi7el69 higher: as the de$ending #arties ha7e argued+ Moreo7er: the6 are still much less than the doses o$ten used in to icological studies o$ chemicals: ,here the lo,est doses could &e 2-3 orders o$ magnitude larger than the doses e #erienced &6 human consumers+ 20+ <ndeed: AE!1A has determined that the ma imum oestrogen deri7ed $rom hormone-treated &ee$ is 8/ ng( #erson ( da6 that ,ould &e $or a 20 =g adult 1+/ ng(=g(da6+ .ut $or a 20 =g child: the amount ,ould &e /+2 ng(=g(da6+ <$ so: this ,ould mean that oestradiol had a mutagenic e$$ect at a

>ormall6 such silastic tu&es are made to ensure an e7en release o7er a long time and to do that there must &e a lot le$t at the end o$ the e #eriment (other,ise the dose ,ould decrease during the e #eriment)+ On a dail6 &asis this ,ould &e: 9total amount o$ estradiol in im#lant9 - 9le$t o7er at end o$ e #eriment9 ( 9da6s o$ e #osure9+ *ince there are 7alues $or ho, much is le$t in the hormonal-im#lants used in cattle at slaughter and gi7en that it is the same #rinci#le as silastic tu&es in rodents: the J-le$t-o7er could &e com#ara&le+ <$ so the released amount in the rodents could &e calculated+ 'e understand that the underl6ing stud6 ,hich ,ill #ro7ide these data is a&out to &e #u&lished: %+!+ Mailander: A+D+ MeFa: *+ Biggin&otham and )+ !ha=ra7arti: <nduction o$ A+T to 3+! mutations &6 erroneous re#air o$ de#urinated )>A $ollo,ing estrogen treatment o$ the mammar6 gland o$ A!< rats: A+ *teroid .iochem+ Mol+ .iol+: at the >o7em&er issue: 2002+ Moreo7er: as )r+ 3utten#lan has &een ,or=ing ,ith the same scientists in that stud6: so the %anel ma6 ,ish to as= him to clari$6 this in$ormation+ 4 This estimate is li=el6 to &e on the high side at the end o$ the stud6 at ,hich #oint a&out /0J o$ the initial dose usuall6 remains in the silastic ca#sule+ 8 Bo,e7er: $rom other e #eriments using similar silastic ca#sules the dose o$ oestradiol released $rom these ca#sules ,as re#orted+ 1rom an article #u&lished &6 E,ing et al+ in 1949 ,ho used the same *ilastic ca#sules (O) 3+18 mm: <) 1+98 mm) used in the !a7alieri et al+ 2002 stud6: the re#orted release rate $or oestradiol ,as 2+/ micrograms ( cm (da6: and according to another #a#er &6 'ang and 'ong (1998): this ,ould &e i$ there ,as 20 mg o$ oestradiol #ac=ed into a 1-cm ca#sule+ *ee E,ing: D+D+: "+A+ 3ors=i: "+A+ *&ordone: A+C+ T6ler: !+ )esEardins and .+ "o&aire (1949): Testosterone-estradiol $illed #ol6dimeth6lsilo ane su&dermal im#lants: e$$ect on $ertilit6 and masculine se ual and aggressi7e &eha7ior o$ male rats+ .iol "e#rod 21(/): 42042@ and 'ang: H+M+ and H+!+ 'ong (1998)+ *e hormone-induced #rostatic carcinogenesis in the no&le rat: the role o$ insulin-li=e gro,th $actor-< (<31-<) and 7ascular endothelial gro,th $actor (CE31) in the de7elo#ment o$ #rostate cancer+ %rostate 30(3): 120-44+

'T()*320("(Add+3 %age !-4 dose #otentiall6 ,ithin the 1000-$old sa$et6 margin esta&lished $rom a DOAED: &ased on the assum#tion o$ a threshold $or this e$$ect N 21+ 'ith res#ect to the other in 7i7o studies mentioned: the Euro#ean !ommunities ,ould li=e to clari$6 the $ollo,ing+ The stud6 in *E>!A" mice sho,ing mutagenicit6 o$ the 3:/-5uinone o$ E2 (the #utati7e mutagenic meta&olite) used a dose o$ 200 nanomoled: ,hich is a&out 20 microgram+ Again: ,e do not =no, $or sure ho, this relates to the dail6 amount o$ E2 in the mouse: &ut an educated guess is that the dose o$ 20 microgram is #ro&a&l6 one or at the most t,o orders o$ magnitudes a&o7e the endogenous #roduction: and cannot &e considered as huge dose either+ As $or the stud6 on the mutagenicit6 in the mammar6 gland o$ A!< mice is so $ar a7aila&le as an a&stract onl6: so there is no much in$ormation a7aila&le+ 22+ 1inall6: the stud6 sho,ing the $ormation o$ the t6#ical )>A adducts o$ E2-3:/-5uinone in human &reast tissue (E! E hi&it 118) did not administer an6 e ogenous E2+ *o the adducts are $ormed &6 the meta&olites o$ the endogenousl6 #roduced E2 alone+ 23+ <n conclusion: it is 7er6 im#ortant to understand that the issue o$ the dose administered is not 7er6 crucial $or the in vivo genoto icit6 in the case o$ oestradiol-14I: and that the de$ending #arties ha7e &een tr6ing to con$use the de&ate on the &asis o$ unscienti$ic and sim#listic allegations+ <ndeed: $rom the #re7ious comments it a##ears that the doses used to elicite in 7i7o mutagenicit6 are not massi7el6 high+ ?uite the o##osite: the6 seem to $all ,ithin the sa$et6 margin esta&lished &6 AE!1A: ,hich means that the residues in meat $rom hormone-treated meat are also ca#a&le o$ #roducing this ad7erse e$$ect+ Moreo7er: there are man6 scientists toda6 ,ho rightl6 &elie7e that setting A)<s and M"Ds ,ould not &e used $or )>A-reacti7e su&stances ,hich are &oth genoto ic and carcinogenic &ecause 9it is assumed that there is no e #osure ,ithout an6 #otential ris=: i+e+ it is suggested that e #osure to e7en a single molecule could #roduce )>A damage9+ 9 Q*%&$+"#& $" $/% E*."-%'# C"22*#+$+%&> QF. S/"*,d $/% P'#%, '(.%% 7+$/ $/% E*."-%'# C"22*#+$+%&! 2'+# 1,'+2 $/'$ $/% U#+$%d S$'$%& '#d C'#'d' /'=% 3.%'1/%d A.$+1,% 23 "0 DSU .%'d $"(%$/%. 7+$/ A.$+1,%& 2).< '#d 22.G5 7/'$ 7"*,d 3% $/% 1"#&%;*%#1%& "0 &*1/ ' 1"#1,*&+"# 0". $/% U#+$%d S$'$%& '#d C'#'d'9 M".% -'.$+1*,'.,45 7"*,d $/% U#+$%d S$'$%& '#d C'#'d'> ?'@ 3% %8-%1$%d $" 7+$/d.'7 $/% &*&-%#&+"#& "0 1"#1%&&+"#& ". "$/%. "3,+('$+"#& ". &*&-%#d $/%+. '--,+1'$+"#9 ?3@ ?1@ 3% %8-%1$%d $" +#+$+'$% '# A.$+1,% 2).< -."1%d*.% '('+#&$ $/% EC9 ". 7"*,d $/%4 3% %8-%1$%d $" d" 3"$/9

?P,%'&% #"$% $/'$ $/% P'#%, +& 0*,,4 '7'.% "0 +$& "3,+('$+"#& *#d%. A.$+1,% )A DSU@ 2/+ As e #lained in #aras+ 43 et se5+ ('T()*320) as ,ell as in #aras+ 41 et se5+ ('T()*321) o$ its $irst ,ritten su&mission as ,ell as in #aras+ 9/ ('T()*320) and #ara+ 92 ('T()*321) the Euro#ean !ommunities; #osition is that !anada and the 8nited *tates are at least under an o&ligation to do eit er (a) or (&)+ Bo,e7er: the Euro#ean !ommunities considers that it ,ould &e a##ro#riate i$ the 8nited *tates and !anada did (c)+

9 *ee *+ !arlo" et al+: "is= assessment o$ su&stances that are &oth genoto ic and carcinogenic - "e#ort o$ an <nternational !on$erence organised &6 E1*A and 'BO ,ith su##ort o$ OD*< Euro#e: 1ood and !hemical To icolog6: // (2002) 1232-1200: at #age 1234: a7aila&le on line at ,,,+sciencedirect+com+

'T()*320("(Add+3 %age !-8 20+ <n the a&sence o$ such a resolution to this dis#ute: ho,e7er: there can &e no dou&t that the 8nited *tates and !anada are under an o&ligation to ,ithdra, the sus#ension o$ concessions o$ other o&ligations or sus#end their a##lication: i$ the6 do not initiate a 21+0 #roceeding+ 22+ E5uall6: there can &e no dou&t that the6 are under an o&ligation to initiate a 21+0 #roceeding i$ the6 continue to disagree on the com#liance o$ the E! im#lementation measure (mani$esting this disagreement through the continued a##lication o$ the sus#ension o$ concessions)+ 24+ <n the case o$ a continued disagreement: as e #lained else,here: the Euro#ean !ommunities is $urthermore o$ the 7ie, that it ,ould &e a##ro#riate $or the 8nited *tates and !anada to &oth sus#end the a##lication o$ the sus#ension o$ concessions and initiate 21+0 #roceedings+ This is ,hat the Euro#ean !ommunities has done in the #SC case+ 28+ O$ course and ideall6: a$ter the thorough de&ates at the e #ert meeting: the 8nited *tates and !anada are $ree to a&andon their disagreement and acce#t the Euro#ean !ommunities im#lementation measure as com#liant+ Thus: the6 ,ould cease the a##lication o$ the sus#ension o$ concessions and there ,ould &e no need $or a 21+0 #roceeding+ Q:. I& $/% P'#%, 1"..%1$ +# *#d%.&$'#d+#( $/'$ $/% E*."-%'# C"22*#+$+%& -*.&*%& $7" d+00%.%#$ 62'$$%.&6 3%0".% $/% P'#%,> ?'@ "#% .%('.d+#( $/% U#+$%d S$'$%&! '#d C'#'d'!& *#+,'$%.', d%$%.2+#'$+"#& "0 =+",'$+"# 34 $/% E*."-%'# C"22*#+$+%& 0*.$/%. $" +$& #"$+0+1'$+"# "0 D+.%1$+=% 2003/:C/ECB '#d ?3@ "#% .%('.d+#( $/% 2'+#$%#'#1% "0 .%$',+'$+"#& 34 $/% U#+$%d S$'$%& '#d C'#'d' d%&-+$% '1$*', 1"2-,+'#1%B $/% ,'$$%. 3%+#( 1"#d+$+"#', *-"# $/% P'#%, .%H%1$+#( $/% EC 1,'+2& *#d%. $/% 0".2%.9 29+ 30+ )*.: The Euro#ean !ommunities is not sure to $ull6 understand the meaning o$ this 5uestion+ <t seems a##ro#riate to $irst recall the A##ellate .od6;s de$inition o$ the 9matter9 &e$ore the OtPhe ;matter re$erred to the )*.; +++ consists o$ t,o elements: the s#eci$ic measures at issue and the legal basis o$ t e complaint (or the claims)+10 31+ On the &asis o$ this de$inition: there is one single matter here and that is the matter as re$erred to in the Euro#ean !ommunities; re5uest $or esta&lishment o$ a %anel+ The re5uest descri&es se7eral measures and a num&er o$ di$$erent claims+ These claims are $urther de7elo#ed in the Euro#ean !ommunities; 1irst 'ritten *u&mission and certain o$ these claims ha7e &een made unconditionall6 ,hile others are conditional+ 1or the sa=e o$ clarit6: these unconditional and conditional claims are set out in t,o di$$erent #arts: #art one addressing claims &ased on Article 23 read together ,ith Article 21+0 and ,ith Article 22+8: #art t,o addressing a direct 7iolation o$ Article 22+8+ The second #art is conditional u#on a negati7e $inding on the $irst #art+ 32+ The a&o7e descri#tion o$ t,o su##osedl6 di$$erent 9matters9 does not re$lect the $act o$ a single matter as Eust descri&ed: nor is it accurate in itsel$: the issue o$ a unilateral determination also relates to the maintenance o$ retaliation as e7idenced through the claim &ased on Article 23 read together ,ith Article 22+8+
10

A. "e#ort %uatemala Cement &: at #ara+ 42+

'T()*320("(Add+3 %age !-9 33+ 1urthermore: the Euro#ean !ommunities has not generall6 argued that the 9noti$ication9 as such is the e7ent that triggers the issue o$ a unilateral determination (see also #ara+ // o$ its Oral *tatement at 1irst Bearing)+ <n the s#eci$ic circumstances o$ this case: it seems clear that &oth the 8nited *tates and !anada ha7e made such a unilateral determination immediatel6 $ollo,ing the noti$ication+ 1urthermore: as e #lained in #ara+ 32 o$ its "e&uttal *u&mission the Euro#ean !ommunities sees merit in the argument that the time $actor ma6 &e rele7ant ,hen $or assessing ,hen a 9determination9 has &een made+ QG. T/% P'#%, *#d%.&$'#d& $/'$ $/% E*."-%'# C"22*#+$+%& +#+$+'$%d .+&D '&&%&&2%#$& 7+$/ .%&-%1$ $" ',, &+8 /".2"#%& '$ +&&*% ?&%%5 %.(.5 D+.%1$+=% 2003/:C/EC5 $/+.d +#$."d*1$".4 -'.'(.'-/@. ?'@ C"*,d $/% E*."-%'# C"22*#+$+%& 1"#0+.25 7+$/ .%&-%1$ $" "%&$.'d+", ):E '#d +# ,+(/$ "0 +$& &$'$%2%#$ +# -'.'. )A2 "0 +$& .%3*$$', '#d +$& 1"22%#$& "# Q*%&$+"# )C "0 $/% P'#%, $" $/% %8-%.$&5 7/%$/%.> ?+@ +$ -."1%%d%d $/."*(/ $/% 0"*. &$%-& "0 .+&D '&&%&&2%#$ +d%#$+0+%d 34 C"d%8B ". ?++@ 1"*,d /'=% -."1%%d%d $/."*(/ $/% 0"*. &$%-& 3*$ d%1+d%d #"$ $" d" &" +# ,+(/$ "0 +$& 0+#d+#(& "# (%#"$"8+1+$4 "0 "%&$.'d+", ):E9 ?3@ C"*,d $/% E*."-%'# C"22*#+$+%& 1"#0+.25 7+$/ .%&-%1$ $" %'1/ "0 $/% "$/%. 0+=% /".2"#%& '$ +&&*%5 '$ 7/'$ &$'(%?&@ "0 +$& .+&D '&&%&&2%#$ +$ 1"#&+d%.%d $/'$ .%,%='#$ &1+%#$+0+1 %=+d%#1% 7'& +#&*00+1+%#$ '#d d%1+d%d $" -."=+&+"#',,4 3'# $/% +2-".$'$+"# "0 2%'$ $.%'$%d 7+$/ $/"&% /".2"#%& "# $/% 3'&+& "0 '='+,'3,% -%.$+#%#$ +#0".2'$+"#. 3/+ Ad ?'@. The Euro#ean !ommunities con$irms its comments on the ?uestion 1/ o$ the %anel to the e #erts+ As regards the statement in #ara+ 192 o$ its "e&uttal *u&mission: the Euro#ean !ommunities is grate$ul to the %anel $or #ointing out the error and o7ersight+ The error is dou&le &ecause: $irst: the ste#s o$ a ris= assessment as de$ined &6 !ode are $our (not three) and: second: the terminolog6 used in #ara+ 192 to descri&e the $irst three o$ them is not correct either (see $ollo,ing #ara+ 193 ,here the #ro#er terminolog6 is used $or the $irst three ste#s)+ The ,ords used in #ara+ 192 is an isolated o7ersight and does not re$lect the #osition ,hich the Euro#ean !ommunities has e #ressed in so man6 other #laces in its ,ritten su&missions and the oral hearing+ <ndeed: ,ith its re#l6 o$ 3 Octo&er 2000 to 'ritten ?uestion >o 2/ $rom the %anel: in #articular #aragra#hs 1/0-1/3: the Euro#ean !ommunities has #ro#erl6 descri&ed the $our ste#s o$ a ris= assessment and the reasons $or ,hich it thin=s it has com#lied ,ith them in this case+ *ee also #aragra#hs 1/0-102 o$ its re#l6 o$ 3 Octo&er to 'ritten ?uestion >o 20 $rom the %anel+ Moreo7er: a care$ul e amination o$ the 1999 O#inion sho,s &e6ond dou&t that the Euro#ean !ommunities has com#leted the $our ste#s: al&eit it made a 5ualitati7e e #osure assessment $or the reasons e #lained therein+ 30+ Ad ?'@5 ?+@ '#d ?++@. The Euro#ean !ommunities has said and re#eats that it has #er$ormed the $our ste#s in its ris= assessment $or all these hormones+ As regards the third ste# (e #osure assessment): it #er$ormed &oth a 5uantitati7e estimation and a 5ualitati7e assessment+ 11 The de$ending #arties argue that the third ste# (e #osure assessment) is not #ro#erl6 #er$ormed: &ecause the6 contest the data used $or the 5uantitati7e assessment (the6 contest the Klein assa6: the &ioa7aila&ilit6 rate: the rate o$ endogenous #roduction &6 #re-#u&ertal children: etc+): and the6 also argue that the 5ualitati7e assessment lac=s scienti$ic rigour (8*)+ The de$ending #arties ma6 disagree:
<ne7ita&l6: there$ore: the $ourth ste# ,as glo&all6 5ualitati7e+ *ee the 1999 *!C%B o#inion: #ages 29-43 and the re#lies to 5uestions 1: 2 and 3: at #ages 4/-44+
11

'T()*320("(Add+3 %age !-10 &ut the6 cannot credi&l6 argue that the Euro#ean !ommunities has not com#leted the $our ste#s o$ the ris= assessment+ 32+ F". "%&$.'d+",I):E: section /+1+0: #are 32-39: o$ the 1999 O#inion is entitled 9assessment o$ e cess e #osure to oestrogens $rom consum#tion o$ hormone-treated &ee$9 and it e #lained ,h6 the AE!1A A)< and the 8* acce#ta&le le7els are e ceeded+ This is a 5uantitati7e estimation and is meant to address the assum#tion o$ AE!1A and o$ the 8* that oestradiol-14I acts onl6 through rece#tormediated mechanism+ <t concluded that: OTPhe 1)As acce#ta&le dail6 inta=e (102 ng(#erson(da6: see a&o7e) could e ceed the dail6 #roduction rate o$ oestradiol &6 1:400 $old (o$ #re-#u&ertal children)+ 'hile there is some e #erimental e7idence in su##ort o$ the currentl6 used &lood le7els o$ oestradiol &eing 100 $old too high (Klein et al+: 199/): the other assum#tions used in coming to this conclusion ma6 &e too conser7ati7e+ Thus: i$ a&sor#tion is reduced to 10J and the M!" $or children is onl6 1(2 that o$ adults: the 1)A acce#ta&le dail6 inta=e could still &e 80 $old too high+ 34+ <n other ,ords: the 1999 O#inion has made a 5uantitati7e estimate o$ the e #osure assessment using the latest in$ormation and data a7aila&le and also assumed 10J &ioa7aila&ilit6: e7en i$ this lo, rate is scienti$icall6 5uestiona&le+ Het: e7en under such estimation: it concluded that the 8* acce#ta&le dail6 inta=e 9could still &e 80 $old too high9 (and: conse5uentl6: also AE!1A;s A)< o$ 0+00 ng(=g(&,(da6 ,ould &e e ceeded)+ Accordingl6: the Euro#ean !ommunities $ails to see ,h6 this is not the &est #ossi&le 5uantitati7e estimate o$ the e #osure assessment: ta=ing into account the latest scienti$ic in$ormation+ 38+ .ut the 1999 O#inion then goes on and contains sections /+1+2 to /+1+8: #ages 39-/3: ,hich anal6sed the other mechanism &6 ,hich oestradiol-14I is &elie7ed to act: i+e+ &6 direct genoto icit6+ An e #osure assessment is again #er$ormed: &ut this time o$ a 5ualitati7e nature: ,here it states that: 9OTPhese )>A-damaging e$$ects indicate that no threshold e ists $or the ris= $rom oestrogen meta&olites9 (at #age /1)+ <t also states that: 9>o data are currentl6 a7aila&le on the e$$ects o$ e ogenous lo,-dose oestrogens+ Bo,e7er: genoto ic e$$ects inde#endent $rom the #resence o$ hormonal rece#tors ha7e &een recognised $or meta&olites o$ certain oestrogens: as indicated a&o7e+9 (at #age /2)+ <t also states on the same #age that: 9 These results indicate that induction o$ mammar6 tumors relies on the #resence o$ E 2: &ut not that o$ the maEor oestrogen rece#tor: suggesting a genoto ic role o$ E2 in the induction o$ these mammar6 tumors+9 <t also arri7ed at a 5ualitati7e conclusion as $ollo,s: &n conclusion' ,hereas it is clear that e ogenous oestrogens: #resent in oral contrace#ti7es or used in hormonal re#lacement thera#6 in ,omen: are res#onsi&le $or an increased ris= o$ endometrial cancer and to lesser e tent some increased ris= o$ &reast cancer: there is no direct e7idence on the conse5uences o$ the contri&ution o$ e ogenous 14-oestradiol originating $rom the consum#tion o$ treated meat+ Het ,e =no, $rom the data deri7ed $rom human #o#ulations ,ithin the ranges o$ #h6siological 7alues o$ hormones in &lood: that high le7els are associated ,ith an increased ris= o$ &reast cancer+ Also =no,n are the carcinogenic e$$ects o$ 14 oestradiol in e #erimental animals as ,ell as the deleterious e$$ects in #re- and #erinatal de7elo#ment (see section 2)+ 1inall6: in consideration o$ the recent data on the $ormation o$ genoto ic meta&olites o$ oestradiol: suggesting that 14Q-oestradiol acts as com#lete carcinogen: &6 e erting tumour initiating and #romoting e$$ects: it has to &e concluded: that no 5uantitati7e estimate o$ the ris= related to residues in meat could &e #resented+

'T()*320("(Add+3 %age !-11 39+ Ad ?3@. The Euro#ean !ommunities #er$ormed $or the other 0+=% /".2"#%& the same ris= assessment as that $or oestradiol-14I+ <ndeed: a care$ul loo= at the 1999 *!C%B O#inion: con$irms that all $our ste#s ,ere com#leted in the same ,a6 as $or oestradiol-14I+ 'hilst com#leting the $our ste#s: the *!C%B O#inions o$ 1999: 2000 and 2002: ha7e ta=en care (unli=e AE!1A;s assessments) to #oint to the numerous ne, scienti$ic e7idence: to the serious ga#s in our =no,ledge and the scienti$ic uncertainties surrounding man6 im#ortant as#ects+ <t ,as the o7erall state o$ the $ile $or each o$ these $i7e hormones: and $or each s#eci$ic as#ect re5uired $or the $our ste#s o$ the ris= assessment: ,hich led the *!C%B to come to the o7erall conclusion that it ,as not #ossi&le to com#lete the ris= assessment: in the sense o$ Article 0+1 SPS (greement+ /0+ <n addition: as $or oestradiol-14I: the *!C%B #er$ormed an assessment o$ e #osure assessment under realistic conditions o$ use o$ these hormones: ta=ing into account misuse and #otential a&use+ /1+ On the &asis o$ these o#inions the com#etent ris= manager decided to a##l6 Article 0+4 o$ the SPS (greement+ <n #articular: recital no 4 o$ the #ream&le to the )irecti7e 2003(4/ e #lains that: 9 As regards the other $i7e hormones (testosterone: #rogesterone: tren&olone acetate: Feranol and melengstrol acetate): the *!C%B assessment is that: in s#ite o$ the indi7idual to icological and e#idemiological data a7aila&le: ,hich ,here ta=en into account: the current state o$ =no,ledge does not ma=e it #ossi&le to gi7e a 5uantitati7e estimate o$ the ris= to consumers9+ <n other ,ords: the Euro#ean !ommunities &ased its measure on all the a7aila&le #ertinent in$ormation $or each o$ the $our ste#s o$ the ris= assessment ,hich it had #er$ormed+ QA. C'# $/% E*."-%'# C"22*#+$+%& %8-,'+# $/% 2%'#+#( +$ (+=%& $" $/% $%.2 62%.% d"*3$6 +# -'.'. )G) "0 $/% EC &%1"#d &*32+&&+"# ?US 1'&%@9 /2+ The use o$ the terms 9mere dou&t9 (in #ara+ 181 o$ the E! "e&uttal *u&mission) is made there in order to distinguish a situation ,here the a7aila&le rele7ant e7idence is su$$icient $rom the situation ,here the #ertinent e7idence is insu$$icient+ The term 9mere dou&t9 does not mean an6 =ind o$ dou&t &ut dou&t that is scienti$icall6 esta&lished: in other ,ords in &oth cases the 9su$$icienc69 or 9insu$$icienc69 o$ the rele7ant e7idence should &e scienti$icall6 esta&lished+ <ndeed: mere dou&t could &e $ound to &e su$$icient to ta=e a measure in cases o$ su&stances or ris=s that are ne, or ha7e not &een e7aluated &e$ore+ 1or e am#le: ,hen in 1992 the Euro#ean !ommunities too= drastic measures against .*E the a7aila&le rele7ant scienti$ic e7idence ,as 7er6-7er6 meagre and the #rohi&ition ,as &ased essentiall6 on dou&ts and #ossi&le associations+ /3+ !on7ersel6: in situations ,here the su&stances ha7e &een e7aluated &e$ore: the dou&t should &e serious: as the last sentence o$ #ara+ 181 states+ T6#icall6: reasona&l6 serious dou&ts ma6 e ist ,hen the #ertinent a7aila&le e7idence is contradictor6: inconclusi7e or incom#lete+ This is related not onl6 to the 5uantit6 o$ the a7aila&le e7idence: &ut $re5uentl6 to the 5ualit6 o$ the #ertinent e7idence+ *erious dou&ts ma6 a##ear or de7elo# $or the $irst time a&out the sa$et6 o$ a su&stance ,hich is alread6 authorised on the &asis o$ de7elo#ments in scienti$ic research+ The di$$icult6 $or the ris= assessment and ris= management is to decide ,hen the #ertinent e7idence mo7es $rom a situation o$ &eing #re7iousl6 thought to &e 9su$$icient9 into a situation that is no, $ound to &e 9insu$$icient9 $or the #ur#oses o$ assessing ris= in a ,a6 that does not com#romise the chosen le7el o$ #rotection+ The $ormal re5uirement o$ ha7ing to conduct a ris= assessment is not a #ro&lem: &ecause a ris= assessment (,ith all $our ste#s in a 5uantitati7e or 5ualitati7e manner) is nearl6 al,a6s #ossi&le to #er$orm+ The #ro&lem is ,hen the ne, e7idence #oints to credi&le scienti$ic uncertainties: incom#leteness o$ the data or contradictor6 $indings+ That is ,h6 all legal s6stems that aim to #rotect e$$ecti7el6 human: animal or #lant li$e and health #ro7ide that: in such situations: 5ualitati7e assessment is acce#ta&le $or some o$ the $our ste#s in the ris= assessment+ As Article 0+4 o$ the SPS (greement states: mem&ers ma6 ado#t measures 9on the &asis o$ a7aila&le #ertinent in$ormation9 and should see= to o&tain the additional in$ormation necessar6 9$or a more o&Eecti7e assessment o$ the ris=9+

'T()*320("(Add+3 %age !-12 //+ The Euro#ean !ommunities has gi7en the e am#le o$ !ar&ado (at #aras+ 100-102): ,here AE!1A ,aited $or a #eriod o$ a&out 10 6ears in order to mo7e $rom a situation o$ su$$icient e7idence to authorise !ar&ado (in 1991) to a situation o$ su$$icient e7idence to #rohi&it !ar&ado (2003)+ The 5uestion is ,ho is to &ear the res#onsi&ilit6 $or the ad7erse e$$ects on human health during the #eriod o$ ten 6ears that la#sed in &et,eenR An inter#retation o$ Article 0+4 that does not allo, ta=ing into account credi&le scienti$ic de7elo#ments and scienti$ic uncertaint6 that 5uestion #re7iousl6 held scienti$ic 7ie,s is not correct+ This #oint is 5uite di$$erent $rom the #oint that science al,a6s de7elo#s+ To guard against #otential a&uses: as e #lained a&o7e: the ne, e7idence should not &e ar&itrar612 &ut credi&le and should sho, that there is genuine scienti$ic disagreement identi$ied in a ris= assessment+ This =ind o$ scienti$ic uncertaint6 should &e acce#ta&le under Article 0+4 o$ the SPS (greement: i$ the right o$ mem&ers to choose their a##ro#riate le7el o$ #rotection is to &e #reser7ed+ <ndeed: Article 2+2 o$ the SPS (greement re5uires a measure to &e &ased on scienti$ic #rinci#les and not maintained ,ithout su$$icient scienti$ic e7idence+ .ut Article 2+2 does not la6 do,n such re5uirements $or #ro7isional measures: &ecause it states 9e ce#t as #ro7ided $or in #aragra#h 4 o$ Article 09+ Q)0. T/% E*."-%'# C"22*#+$+%& &-%1+0+%& $/'$ 6+$ /'& +&&*%d ' #%7 1',, 0". &1+%#$+0+1 d'$' '#d .%&%'.1/ 0."2 2002 "#7'.d&5 "# &*3&$'#1%& 7+$/ /".2"#', '1$+=+$4 7/+1/ 2'4 3% *&%d 0". (."7$/ -."2"$+"# -*.-"&%& +# 3"=+#% 2%'$6. C"*,d $/% E*."-%'# C"22*#+$+%& &-%1+04 7/'$ +#0".2'$+"# +$ /'& '1$*',,4 .%;*%&$%d9 W/%# d"%& +$ %8-%1$ $" .%1%+=% +$9 /0+ The Euro#ean !ommunities has re$erred to this call $or scienti$ic data in %ara+ 22/ o$ its "e#lies to the %anel;s ?uestions a$ter the $irst su&stanti7e hearing and in %ara+ 129 o$ its *econd 'ritten *u&mission+ A lin= to the OA #u&lication on the internet has &een #ro7ided each time+ 1or ease o$ re$erence the Euro#ean !ommunities attaches the #u&lic call no, as E hi&it E!-128+ As can &e seen $rom the document: the in$ormation re5uested ,as an6 scienti$ic e7idence ($rom 2002 on,ards) on su&stances ,ith hormonal acti7it6 ,hich ma6 &e used legall6 in Third !ountries $or gro,th #romotion #ur#oses in &o7ine meat ha7ing oestrogenic: androgenic or gestagenic action since the )ast *evie" o$ t e (ssessment o$ *is+s to Human Healt $rom Hormone *esidues in !ovine ,eat and ,eat Products o$ the *!C%B in 2002 $ollo,ing the criteria outlined under item 3+ /2+ 8nder item 3 cited a&o7e it is s#eci$ied: inter alia: that: E1*A encourages the su&mission o$ #eer-re7ie,ed data(#u&lications (not Eust the re$erence) as the most rele7ant and relia&le documents+ /4+ 1i7e #a#ers ha7e &een su&mitted $ollo,ing the call+ E1*A is currentl6 re7ie,ing these $i7e #a#ers together ,ith the $inal 7ersion o$ the 8K 3rou# re#ort (see &elo, ?uestion 1/) as it has &een #u&lished in Aul6 2002+ An assessment is e #ected $or A#ril 2004+ Q)). W/'$ +& 2%'#$ 34 #" 6'dd+$+=% .+&D69 6'dd+$+=%6.
12

P,%'&% %8-,'+# $" 7/+1/ 6.+&D&6 $/%&% '.%

<t should &e noted that the A##ellate .od6 had $ound in its 1994 Hormones re#ort (at #aras+ 2//-2/0) that the old E! )irecti7e ,as not im#osed $or ar&itrar6 or discriminator6 #rotectionist reasons: contrar6 to the arguments o$ the de$ending #arties at that time and the $indings o$ the 1994 hormones #anel+ Moreo7er: none o$ the #arties has argued in the #resent #roceedings that the ne, E! measure is is &ased on ar&itrar6 or discriminator6 e7idence+ All o$ the %anel;s e #erts ha7e con$irmed that the di$$erent 7ie,s held &6 the de$ending #arties and AE!1A: on the one hand: and the E!: on the other: are &ased on legitimate and genuine scienti$ic disagreement+

'T()*320("(Add+3 %age !-13 /8+ <t is scienti$icall6 not dis#uted (in this case e7en &6 the de$ending #arties) that li$e-time e #osure o$ humans to the le7els o$ endogenous #roduction o$ oestrogen (and in #articular to oestradiol-14I and its meta&olites) and: most li=el6: to the other t,o natural hormones (testosterone and #rogesterone) are su$$icient to cause and(or #romote cancer in some indi7iduals+ This is $re5uentl6 called ris= o$ cancer $rom &ac=ground (endogenous) e #osure+ This =ind o$ e #osure (and the attenti7e ris= o$ cancer) 1'##"$ 3% '="+d%d+ /9+ .ut humans are e #osed dail6 to 7aria&le le7els o$ residues o$ these hormones: in #articular estrogen (including oestradiol-14I and its meta&olites): $rom man6 e ogenous sources ,here these hormones naturall6 occur: such as mil=: eggs: &roccoli: so6a &eans: etc+ <n scienti$ic literature it is seriousl6 dis#uted ,hether the estrogenic acti7it6 o$ residues in #lants is the same: &oth as regards the mode o$ action and #otenc6: ,hen consumed &6 humans+ 13 <t is ne7ertheless not dis#uted that human e #osure to such residues adds some more &urden to the &ac=ground le7els+ <t is thus e #ected that this addition ma6 increase the ris= o$ cancer+ <t is im#ortant to note: ho,e7er: that this =ind o$ human e #osure to le7els o$ residues occurring in natural $oods (e ogenous e #osure) 1'##"$ 3% '="+d%d: unless the consum#tion o$ such natural $oods is reduced or #rohi&ited+ .ut as the A##ellate .od6 has e #lained in its 1998 Hormones re#ort (at #ara+ 221): this =ind o$ #rohi&ition is not #ossi&le as it ,ould re5uire such a com#rehensi7e and massi7e go7ernmental inter7ention in nature and in the ordinar6 li7es o$ #eo#le as to reduce the com#arison itsel$ 9to an a&surdit69+ <ndeed: it ,ould re5uire changing human diet and ha&its that ha7e &een #racticed $or centuries &6 human &eings+ 00+ The conce#t o$ 9additi7e9 ris= re$ers to e #osure ,hich is $urther added on humans $rom the le7els o$ residues in meat $rom animals treated ,ith these hormones $or gro,th #romotion+ The ris= o$ cancer1/ $rom this =ind o$ e #osure to residues $rom hormone-treated meat is 9added9 to the cancer ris= $rom the e isting (endogenous) e #osure through the &ac=ground le7els o$ hormones and through the e #osure to (e ogenous) sources as contained in non-treated natural $ood+ <t is not dis#uted (see: e+g+: the 2002 8* "e#ort on !arcinogenesis) that 97eterinar6 use o$ steroidal estrogens to #romote gro,th and treat illness can increase estrogens in tissues o$ $ood-#roducing animals to a&o7e their normal le7els9: in general su&stantiall6 higher than the normal (endogenousl6 #roduced) le7els+ 10 There$ore: it should &e stressed that: unli=e $or the other t,o sources o$ e #osure: e #osure to residues $rom hormone-treated meat +& '="+d'3,% &ecause these hormones are chemical su&stances that are deli&eratel6 added in meat+ *ee also the re#l6 to ?uestion 13 &elo, $or the regulator6 im#lications $rom these di$$erent sources o$ e #osure+ 01+ The ris= o$ cancer $rom the consum#tion o$ residues in hormone-treated meat are 9additi7e9 (to ris= o$ cancer $rom the t,o other sources o$ e #osure): irres#ecti7e o$ ,hether these hormones are genoto ic carcinogens or onl6 #romote cancer through rece#tor-mediated mechanisms+ <ndeed: i$ the6 cause cancer &6 direct genoto ic action: the addition o$ such e #osure increases the li=elihood o$ the ad7erse e$$ect to occur+ <$ the6 act onl6 through rece#tor-mediated mechanism: the ris= $rom such e #osure ,ill &e again 9additi7e9: ,hen the6 cause the #resumed threshold to &e e ceeded+ The ris=
*ee: e+g+: E hi&it E!-30: ,hich is a #ioneering stud6 in this area: o$ ,hich neither the de$ending mem&ers nor AE!1A ,ere a,are ,hen the6 e7aluated these hormones+ 1/ 1or reasons o$ con7enience: onl6 the #otential ris= o$ cancer is mentioned here: although the 1999 o#inion o$ the *!C%B has identi$ied a num&er o$ other #ossi&le ad7erse e$$ects on humans $rom e #osure to e ogenous hormonal residues: in #articular $rom hormone-treated meat+ 10 The 1999 *!C%B contains data on the higher residue le7el in treated animals ,ith these hormones (as com#ared to untreated animals)+ *ee ta&les 2 ($or oestradiol-14I): 0 ($or testosterone) and 4 ($or #rogesterone)+ *ince the other three s6nthetic hormones are not #roduced endogenousl6: their residues ,ill al,a6s &e additional+ The 1999 *!C%B o#inion is &ased on recent studies: see: e+g+: E hi&it E!-11 (concerning melengestrol acetate sho,ing that the 8* tolerance le7els ,ill &e e ceeded a$ter administration o$ 1+0 mg(da6: that is according to the recommended dosage o$ use in the 8*)+ *ee also E hi&its E!-1/: 12: 14: 18: /4: 00: 03 and 48: ,hich #ro7ide the most recent measurements o$ residues in meat $rom animals treated ,ith these hormones $or animal gro,th #romotion according to 3C% and in situations o$ a&use+
13

'T()*320("(Add+3 %age !-1/ assessment o$ the Euro#ean !ommunities has esta&lished that oestradiol-14I is a #ro7en genoto ic carcinogen and that the other t,o natural hormones (testosterone and #rogesterone) are also sus#ected to &e genoto ic+ Moreo7er: the ris= assessment o$ the Euro#ean !ommunities has also demonstrated that the A)<s recommended &6 AE!1A $or all these hormones ,ill &e e ceeded under realistic conditions o$ use o$ these hormones in the 8* and !anada+ The6 ,ill also &e e ceeded in an6 case i$ the more recent data on the endogenous #roduction o$ the natural hormones &6 #re-#u&ertal children is ta=en into account+ Q)2. A )AAA R%-".$ "0 $/% C"22+$$%% 0". %$%.+#'.4 M%d+1+#', P."d*1$& "0 $/% E*."-%'# C"22*#+$+%& .%0%.& $" $/% ,"7 3+"'='+,'3+,+$4 "0 "%&$.'d+", ):E. H"7 +& $/+& 0+#d+#( .%1"#1+,%d 7+$/ .%0%.%#1%& $" 3+"'='+,'3+,+$4 +# $/% SC PH O-+#+"#9 ?-,%'&% .%0%. $" 1"22%#$& 34 $/% -'.$+%& "# $/% P'#%,!& Q*%&$+"# C3 $" %8-%.$&@ 02+ The 1999 re#ort o$ the !ommittee $or Ceterinar6 Medicinal %roducts (!CM%) (see E hi&it !)A-0) states: as regards oestradiol-14 -: the $ollo,ing: 9the &ioa7aila&ilit6 o$ 14I-oestradiol esters a$ter oral administration is lo, (3J as unchanged 14I-oestradiol): &ut might &e higher i$ estron: an estrogenic acti7e meta&olite: is included9 (at #+ 2)+ 03+ 1irst: it should &e noted that the 1999 !CM% re#ort does not cite an6 s#eci$ic ne, literature in su##ort o$ this statement+ <ndeed: o$ the scienti$ic literature cited on #ages 1/ - 14 o$ that re#ort: there a##ears to &e no #a#er or stud6 s#eci$icall6 relating to measuring &ioa7aila&ilit6 o$ oestradiol14I+ !onse5uentl6: the !CM% o#inion must &e sim#l6 re#roducing on this #oint the AE!1A e7aluations o$ 1988 and 1999 $or oestradiol-14I: and is not &ased on ne, scienti$ic e7idence+ 0/+ *econdl6: it is im#ortant to note that the last sentence $rom the a&o7e 5uoted 1999 !CM% re#ort states that: 9S &ut might &e higher i$ estron: an estrogenic acti7e meta&olite: is included9+ <ndeed: the AE!1A re#orts and: &6 e tension the 1999 !CM% o#inion: ha7e considered onl6 some o$ the residues o$ oestradiol-14I in meat@ in #articular: the6 ha7e not considered the li#oidal ($att6 acid) esters nor estrone residues+ This is im#ortant &ecause li#oidal esters 9re#resent a&out /0J o$ the total oestradiol-14I esters in $at meat sho,n in the meta&olic stud69: and the6 are 9a&out ten$old more acti7e on uterotro#hic assa6 than oestradiol-14I ,hen gi7en orall69 (see E hi&it E!-01A: #age 18)+ The t,o scienti$ic studies &6 the Euro#ean !ommunities (E hi&it E!-01A: and E hi&it E!-01!: at #age 32) concluded that the residues o$ li#oidal esters and o$ oestrone ha7e not &een considered so $ar &6 an6 ris= assessment =no,n at the time (either &6 the de$ending mem&ers or the 1988 and 1999 AE!1A assessments) and that it is im#erati7e that the6 are ta=en into account in the calculation o$ &ioa7aila&ilit6 and the #harmaco=inetics (see also E hi&its E!-9 and E!-114: &oth con$irming these $indings)+ <t $ollo,s that the 1999 !CM% re#ort: ,hich is &ased on the old AE!1A e7aluations on &ioa7aila&ilit6: can no longer &e considered relia&le+ !on7ersel6: the $indings on &ioa7aila&ilit6 &6 the *!C%B in 1999 and 2002 are more accurate &ecause the6 are &ased on more recent and #ertinent scienti$ic in$ormation+ 00+ Moreo7er: the Euro#ean !ommunities has commented in detail on the comments made &6 the de$ending mem&ers on the %anel;s ?uestion /3 to e #erts and maintains entirel6 the comments it su&mitted on 12 Aul6 2002 (at #aragra#hs 100-10/)+ 'ith its comments the Euro#ean !ommunities has tried to e #lain ,h6 the data on &ioa7aila&ilit6 used &6 the de$ending #arties and AE!1A are most li=el6 to &e ,rong $or t,o reasons: 1) as Eust &eing e #lained a&o7e: &ecause the6 do not ta=e into account all the rele7ant residues in hormone-treated meat@ and 2) &ecause their estimate that &ioa7aila&ilit6 o$ oestradiol-14I is T10J is in itsel$ not correct: $or the reasons e #lained in the E!;s comments o$ 12 Aul6 2002 (at #aras+ 100-10/)+ 02+ !anada;s comments o$ 12 Aul6 2002 (at #ara+ 93) do not hel# de7elo# the de&ate $urther &ecause !anada seems to es#ouse the argument o$ )r+ .oo&is a&out the A)< re#resenting a 9&ioa7aila&ilit6 adEusted9 does+ .ut e7en i$ the arguments o$ )r+ .oo&is ,ere correct ( .uod non):

'T()*320("(Add+3 %age !-10 determining ,ith accurac6 the le7el o$ &ioa7aila&ilit6 is 7er6 im#ortant - instead o$ #roceeding ,ith mere assum#tions as does AE!1A - i$ ,e ta=e into account the much lo,er endogenous #roduction rates &6 #re-#u&ertal children in the calculation o$ the A)< and that multi#le im#lanting o$ animals ,ith these hormones is recommended &6 the manu$acturers and currentl6 #racticed in the 8* and !anada+ 04+ The comments o$ the 8* o$ 12 Aul6 2002 (at #aras+ 12/-128: as ,ell as at #aras+ 119-120 thereo$) are con$using and misleading+ The 8* comment (at #ara+ 12/) that 9the )ampit stud6 7er6 clearl6 indicates that: to o7ercome the lo, &ioa7aila&ilit6 o$ estradiol 14I: 7er6 large amounts o$ the hormone must &e administered orall6 to achie7e a thera#eutic e$$ect9 is ,rong+ 08+ The )ampit et al. #a#er o$ 2002 (see E hi&it E!-99) states that: 9The mini-dose o$ estrogen used here is &ased on an attem#t to re#lace #re#u&ertal estrogen le7els+ <t is much lo,er than the lo, dose estrogen em#lo6ed $or gro,th acceleration in girls ,ith Turner s6ndrome+ .ased on the relati7e estrogenic acti7it6 o$ conEugated estrogen and ethin6l E2 and a mean #atient ,eight o$ 20 =g: it ,as calculated that the mini-dose is 12- to 28-$old ,ea=er than the usual lo, dose o$ 100 ng(=g ethin6l E2 gi7en $or gro,th acceleration+9 (at #age 289: $ootnotes omitted)+ 12 !ontrar6 to ,hat the 8* argues: there$ore: the 2002 )ampit et al. #a#er states that 7er6 lo, doses su$$ice to o&ser7e &iological action in #re-#u&ertal children: ,hich must mean that &ioa7aila&ilit6 o$ oestradiol-14I at those 7er6 lo, doses cannot &e insigni$icant+ 09+ More im#ortantl6: ho,e7er: the 8* comments (in #ara+ 12/) that 97er6 high doses are re5uired to elicit the desired thera#eutic e$$ect9 is misleading &ecause such high doses are not administered (at least not onl6) in order to elicit the desired thera#eutic e$$ect &ut in order to elicit it ;*+1D,4: other,ise the treatment ,ill not &e thera#eutic+ There$ore: $rom the high doses used $or thera#eutic treatment: it does not $ollo, (as the 8* argues) that such doses are necessar6 &ecause o$ the lo, &ioa7aila&ilit6 o$ oestradiol-14I+ 20+ 1inall6: the other 8* comments o$ 12 Aul6 2002 (at #aragra#hs 120-128) do not hel# us de7elo# the de&ate $urther: as the 8* misinter#rets the E! arguments and the o#inion o$ )r+ 3utten#lan+ Moreo7er: the 8* comment in #ara+ 128 is con$using: &ecause all the scientists con$irmed that the &ioa7aila&ilit6 o$ the three s6nthetic hormones (tren&olone acetate: Feranol and melengestrol acetate) is not =no,n+ 'hether AE!1A assumed 100J &ioa7aila&ilit6 $or these s6nthetic hormones is another issue: as e #lained a&o7e: and this is not the #oint the E! ,as ma=ing ,hen arguing that the &ioa7aila&ilit6 o$ the three natural hormones &6 the de$ending #arties and in the AE!1A e7aluations has &een underestimated+ Q)3. I# +$& 1"22%#$& "# .%-,+%& "0 %8-%.$& $" P'#%, Q*%&$+"# )A ?-'.'.:<@ C'#'d' '&&%.$& $/'$ ' .%1%#$ O-+#+"# "0 $/% E*."-%'# F""d S'0%$4 A(%#14 ?EFSA@ .%1"(#+J%& $/.%&/",d& 0". (%#"$"8+1 &*3&$'#1%&. P,%'&% %,'3".'$%. 21+ The Euro#ean !ommunities $ails to understand ,h6 !anada made the re$erence to the o#inion o$ E1*A o$ 18 Octo&er 2000 (see also e hi&it !)A-/2): &ecause that document does not su##ort !anada;s claim+ 22+ <t should $irst &e noted that !anada does not 5uote in its entiret6 the #aragra#h in 5uestion $rom the E1*A;s o#inion (cited at #ara+ 40 o$ !anada;s su&mission)+ The #aragra#h in 5uestion reads as $ollo,s:

12 <ncidentall6: the 2002 Dam#it et al+ #a#er cites ,ith a##ro7al the calculations o$ endogenous #roduction rates o$ #re-#u&ertal children estimated &6 the Klein et al+ assa6: ,hich the Dam#it #a#er e #licitl6 characterises 9as the landmar= re#ort &6 Klein et al+9 (at #+ 289)+

'T()*320("(Add+3 %age !-12 The *cienti$ic !ommittee concludes that &ased on the current understanding o$ cancer &iolog6 there are le7els o$ e #osure to su&stances ,hich are &oth genoto ic and carcinogenic &elo, ,hich cancer incidence is not increased (&iological thresholds in dose-res#onse): /"7%=%.5 #*2%.+1', =',*%& 0". &*1/ ,%=%,& "0 %8-"&*.% 1'##"$ 3% +d%#$+0+%d "# &1+%#$+0+1 (."*#d& '$ $/% -.%&%#$ $+2%. (the highlighted #hrase ,as le$t out &6 !anada)+ 23+ More im#ortantl6: ho,e7er: the o#inion o$ E1*A has clari$ied 7er6 clearl6 that the #ur#ose $or ,hich it ,as #ro7ided is di$$erent $rom the one mentioned &6 !anada+ The E1*A o#inion states that the margin o$ e #osure a##roach is $or 9cases ,here su&stances that are &oth genoto ic and carcinogenic ha7e &een $ound in $ood: irres#ecti7e o$ their origin: and ,here there is a need $or guidance on the #ossi&le ris=s to those ,ho are: or ha7e &een: e #osed9 (at #age 21)+ This means that this a##roach a##lies onl6 $or su&stances that "11*. ". d%=%,"- #'$*.',,4 in $ood or the en7ironment (e+g+ the a$lato ins in dried $ood or the naturall6 occurring oestrogens in &roccoli or in eggs: etc+)+ 14 This is e #lained at #age 0 o$ E1*A;s O#inion ,hich states: 8ndesira&le su&stances occur in $ood ($or e am#le as an inherent natural constituent in the $ood #lant or as contaminant through their #resence in the en7ironment: through $ungal contamination or through #re#aration #rocesses)+ The general need to minimise e #osure to such su&stances: ,hen the6 are demonstrated to #resent a carcinogenic and genoto ic haFard: is e #ressed in the ADA"A (as lo, as reasona&l6 achie7a&le) #rinci#le+ The o#inion o$ the *cienti$ic !ommittee addresses a##roaches &e6ond the ADA"A #rinci#le allo,ing a le7el o$ #otenc6 assessment o$ s#eci$ic su&stances ,hich are #resent in $ood and ,hich are &oth genoto ic and carcinogenic+ *uch an a##roach ,ill not su&stitute $or minimising e #osure to all such su&stances+ <t ,ill ensure that: ,here resources are limited: the highest #riorit6 is gi7en $irst to those su&stances ,hich #resent the greatest ris= $or humans+ 18 2/+ .ut acce#ta&le margins o$ e #osure do not a##l6 $or chemical su&stances (li=e the si gro,th hormones) ,hich are intended to &e d%,+3%.'$%,4 added (i+e+ administered e ogenousl6) to $ood+ Authorisations $or such chemical su&stances to &e added deli&eratel6 to $ood: $eed or the en7ironment are not granted+ !anada has a##arentl6 not read the other rele7ant #arts o$ E1*A;s O#inion ,hich e #lain this as $ollo,s: The *cienti$ic !ommittee is o$ the o#inion that in #rinci#le su&stances ,hich are &oth genoto ic and carcinogenic should not &e deli&eratel6 added to $oods or used earlier in the $ood chain i$ the6 lea7e residues ,hich are &oth genoto ic and carcinogenic in $ood+ (at #ages 0 and 21)+ 20+ The reason $or ,hich the E1*A o#inion came to this conclusion is that:

14 *ee: e+g+: !ommission "egulation (E!) >o 1020(98 (O+A+ D 201: 14+4+98: #+ /3) ,hich has sought to eliminate or reduce e #osure $rom a$lato ins in dried $ood or in mil= on the $ollo,ing grounds: 9'hereas a$lato ins: in #articular a$lato in .1: are genoto ic carcinogenic su&stances@ ,hereas $or su&stances o$ this t6#e there is no threshold &elo, ,hich no harm$ul e$$ect is o&ser7ed@ ,hereas no admissi&le dail6 inta=e can there$ore &e set@ ,hereas current scienti$ic and technical =no,ledge and im#ro7ements in #roduction and storage techni5ues do not #re7ent the de7elo#ment o$ these moulds and conse5uentl6 do not ena&le the #resence o$ the a$lato ins in $ood to &e eliminated entirel6@ ,hereas it is: there$ore: ad7isa&le to set limits as lo, as #ossi&le9 (see 0th recital o$ the #ream&le)+ 18 <ndeed: the E! has a consistent record o$ ta=ing the measures necessar6 to reduce or eliminate ris=s $rom the naturall6 occurring genoto ic and carcinogenic agents+ *ee: e+g+: !ouncil "egulation (EE!) 310(93 la6ing do,n !ommunit6 #rocedures $or contaminants in $ood (O+A+ D 34: 13+2+1993: #+1): ,hich has &een amended se7eral times and most recentl6 &6 !ommission "egulation (E!) /22(2001: O+A+ D 44: 12+3+2001: #+ 1+

'T()*320("(Add+3 %age !-14 1or genoto ic su&stances ,hich interact ,ith )>A: directl6 or a$ter meta&olic trans$ormation (direct-acting genoto ic chemicals): the a&sence o$ a threshold in their mechanism o$ action is generall6 assumed: i+e+ there is no dose ,ithout a #otential e$$ect+ (at #age 0) 22+ The Euro#ean !ommunities ta=es this o##ortunit6 to stress that it has a consistent and coherent record o$ #rohi&iting chemical su&stances that are &oth genoto ic and carcinogenic ,hen a##lications $or authorisation in order to &e deli&eratel6 added to $ood: $eed or the en7ironment are made+ <t has #rohi&ited a num&er o$ chemical su&stances once e #eriments on animals ha7e sho,n that the6 are genoto ic carcinogens or the6 ,ere sus#ected o$ ha7ing such #ro#erties: $or instance: the ,ithdra,al o$ the authorisations $or !ar&ado and Ola5uindo in 1998: 19 ,ell &e$ore AE!1A and !anada did so@ the ,ithdra,al o$ the authorisation $or the coccidiostat >i$ursol in 2002@ 20 the ,ithdra,al o$ the authorisation $or a num&er o$ $la7ouring su&stances: such as meth6leugenol and estragol in 2002@21 #ro#6l /-h6dro 6&enFoate and #entane-2:/dione in 2000@22 and acetamide in 2002+23

24+ The Euro#ean !ommunities ,ould li=e to address another related error in the re#l6 o$ )r+ .oo&is to ,ritten 5uestion >o 11 o$ the %anel: ,here he made re$erence to the #esticide daminoFide (a sus#ected genoto ic carcinogen) and im#lied that 9there ma6 &e =inetic or d6namic $actors indicating that although theoreticall6 there ,as no e #osure ,ith Fero ris=: in #ractice the ris= ,ould &e minimal and there$ore acce#ta&le9+ The statement &6 )r+ .oo&is is misleading: ho,e7er: &ecause the administration o$ daminoFide has not &een a##ro7ed $or edi&le cro#s &ut onl6 $or #"#I %d+3,% #lants ($lo,ers): something he does not e #lain+ 2/ 28+ <n conclusion: there$ore: a distinction should &e made &et,een genoto ic carcinogens that are occurring or de7elo#ing naturall6 in $ood (e+g+ nitrate: a$lato ins: &roccoli: so6a&eans: and eggs) and the chemical su&stances that are intended to &e added deli&eratel6 to $ood (e+g+ car&ado : the si hormones $or animal gro,th #romotion: etc)+ 1or the $ormer: there is not much that can &e done other than ta=e measures to reduce or eliminate the ris= to the e tent #ossi&le+ 1or the latter: ho,e7er: re$usal to authorise their use is an e$$ecti7e means o$ #re7enting their addition to $ood: so as to achie7e the chosen le7el o$ #rotection+ The Euro#ean !ommunities ho#es this ,ill clari$6 that there is no &asis in the con$using argument o$ the de$ending #arties that: since human &eings are e #osed to estrogens $rom so man6 sources (endogenous animal and human #roduction and e ogenous inta=e $rom natural $oods): the small addition $rom the residues in hormone-treated meat ,ould #ose no ris=+ The Euro#ean !ommunities contests the sim#listic logic o$ this unscienti$ic argument &6 the de$ending #arties that: un$ortunatel6: has $ound its ,a6 also in the e7aluations o$ AE!1A+ 29+ The Euro#ean !ommunities can there$ore con$irm that it a##lies consistentl6 a #olic6 on ris= anal6sis that #rohi&its the authorisation o$ chemical su&stances ,hich are sus#ected or #ro7en to &e genoto ic carcinogens ,hen the6 are intended to &e added deli&eratel6 to $ood+ This is in order to achie7e its le7el o$ health #rotection o$ no (a7oida&le) ris=: that is a le7el o$ #rotection that does not
*ee !ommission "egulation (E!) >o 2488(98: OA >o D 3/4: 23+12+1998: #+ 31-32+ *ee !ouncil "egulation (E!) >o 1402(2002: OA >o D 220: 3+10+2002: #+ 1+ 21 !ommission )ecision 2002(113(E! o$ 23+1+2002: OA >o D /9: 20+2+2002: #+1+ 22 !ommission )ecision 2000(389(E! o$ 18+0+2000: OA >o D 128: 21+0+2000: #+ 43+ 23 !ommission )ecision 2002(202(E! o$ 24+0+2002: OA >o D 91: 29+3+2002: #+ /8+ 2/ *ee !ommission )irecti7e 2000(03(E! o$ 12+9+00: OA >o D 2/1: 14+9+2000: #+ 01: at #age 00: #oint 100+
20 19

'T()*320("(Add+3 %age !-18 allo, an6 unnecessar6 addition $rom e #osure to genoto ic chemical su&stances that are intended to &e added deli&eratel6 to $ood+ The ris= $rom residues in hormone-treated meat is such an a7oida&le ris=: and this is ,hat the Euro#ean !ommunities aimed to achie7e ,hen it ado#ted the )irecti7e 2003(4/(E!+ Q)C. H'& $/% d.'0$ '&&%&&2%#$ "0 $/% UK G."*- ?.%0%..%d $" +# -'.'.)G: "0 $/% E*."-%'# C"22*#+$+%&! .%3*$$', &*32+&&+"#@ ',.%'d4 3%%# '&&%&&%d 34 EFSA ". "$/%. .%,%='#$ +#&$+$*$+"#&9 I0 &"5 7/'$ '.% $/% 1"#1,*&+"#&9 40+ As mentioned in its re#l6 to ?uestion 12 a&o7e: the 8K 3rou# ado#ted the $inal 7ersion o$ its re#ort in Aune 2002+20 E1*A is currentl6 re7ie,ing this re#ort+ An assessment is e #ected $or A#ril 2004+ 41+ A mere reading o$ the re#ort;s conclusions and recommendations: ho,e7er: alread6 sho,s that the 8K 3rou# has considera&l6 changed its assessment since the last assessment it had carried out in 1999 (to ,hich the *!C%B reacted ,ith its 2000 O#inion)+ <ndeed: ,hile the 1999 8K assessment ma=ed a num&er o$ &old 9no e7idence9 conclusions: $or e am#le on mutagenic(genoto ic acti7it6 or threshold considerations: the 2002 8K re#ort contains conclusions ,hich are 7er6 nuanced and #ut hea76 em#hasis on the $act that the scienti$ic data are incom#lete and that man6 uncertainties remain and need to &e studied+ The Euro#ean !ommunities recalls that ,hen )irecti7e 2003(4/(E! ,as ado#ted &6 the Euro#ean %arliament and !ouncil: the 8nited Kingdom did not 7ote against the )irecti7e+ 42+ Thus: on mutagenic(genoto ic acti7it6: the re#ort no, re$ers to the 9,eight o$ a7aila&le e7idence O,hichP suggests that li=el6 le7els o$ human e #osure to hormonall6-acti7e su&stances in meat $rom treated animals ,ould not &e su$$icient to induce an6 measura&le &iological e$$ect9 and goes on to state that 9s#eci$icall6: it is 7er6 unli=el6 that the #resence o$ 14I-oestradiol and its meta&olites in meat $rom treated animals ,ould signi$icantl6 increase the ris= o$ ad7erse e$$ects in consumers+9 That conclusion is &ased on a num&er o$ im#ortant 95uali$ications and reser7ations9 including the assum#tion that there is a 9correct9 or 9recommended9 use o$ the e ogenous hormonal su&stances and the reser7ation that all scienti$ic data relate to single su&stances onl6 and not to their com&ined use+ 43+ A&sence o$ in$ormation and scienti$ic uncertaint6 is also the reason ,h6 not all o$ the conclusions ,ere su##orted &6 all mem&ers o$ the 8K 3rou# (note that the #ress release s#ea=s o$ t,o dissenting o#inions)+ <ndeed: the $ollo,ing is stated under 95uali$ications and reser7ations9: the 'or=ing 3rou# had to decide ,hat to do in the a&sence o$ in$ormation or ,here there ,as uncertaint6 o$ inter#retation o$ in$ormation+ One Mem&er e #ressed the 7ie, that $or the su&stances under consideration: there ,as a large element of uncertainty, so the precautionary principle should become the primary consideration. The many uncertainties associated with the current lack of knowledge could be addressed by further research where this was both feasible and affordable. The Working Group was unanimous that all uncertainties must be made clear, especially those that were considered crucial in the risk assessment process. 4/+ The re#ort states clearl6 that 9there are im#ortant ga#s in the e7idence &ase that #reclude #roducing de$initi7e ris= assessments $or 14I-oestradiol or the other $i7e hormonall6-acti7e su&stances9+ (at #oint 2 o$ the e ecuti7e summar6)+ <t is signi$icant to note that the re#ort $urther states (at #oint 2) that:
20

%ress release o$ 0 Aul6 2002 and re#ort a7aila&le at htt#:((,,,+7#c+go7+u=(+

'T()*320("(Add+3 %age !-19 >ot all data ga#s are e5uall6 im#ortant $or the #ur#oses o$ ris= assessment and the 'or=ing 3rou# highlighted a num&er that could im#ro7e $uture ris= assessments+ As an e am#le: it ,ould &e hel#$ul i$ the !CM% and AE!1A could ma=e a7aila&le data on #harmaco=inetics and meta&olism o$ assessed com#ounds that ,ere su##lied in manu$acturers; dossiers+ This o#enness and trans#arenc6 ,ould allo, greater #u&lic scrutin6 o$ the $acts and con$idence in the haFard and ris= assessments #roduced+ 40+ <ndeed: this is ,hat the Euro#ean !ommunities has &een arguing: namel6 that the !CM% and the AE!1A e7aluation ,ould ha7e to &e o#ened to trans#arent #rocedures and #ro7ide the old e7idence on ,hich their assessments ,ere &ased in order to ena&le an o&Eecti7e and trans#arent ree7aluation o$ these su&stances+ Moreo7er: the 8K re#ort;s conclusions end ,ith a list o$ things that 9need to &e esta&lished in order to im#ro7e $uture ris= assessments+9 <t is ,orth 5uoting some o$ the im#ortant ga#s that are listed in #oints 4 to 9 o$ the e ecuti7e summar6: as it ta=es u# man6 o$ the #oints on ,hich the Euro#ean !ommunities has argued that there is scienti$ic uncertaint6: the #recise relationshi# &et,een the #otential use o$ gro,th-#romoters and concentrations of residues in meat le7els o$ e #osure in consumers dose-res#onse relationshi#s $or the e$$ect o$ hormonall6 acti7e su&stances (and their meta&olites) in e #erimental animals and humans the &ioa7aila&ilit6: meta&olism and #ossi&le &ioaccumulation o$ li#oidal esters o$ oestrogen $ollo,ing ingestion o$ meat $rom im#lanted cattle the #ossi&le s6nergistic e$$ects o$ coc=tails o$ hormonal su&stances a 7alidated techni5ue to detect and assign lo, residual concentrations o$ oestradiol in the $inished edi&le #roducts to natural sources or im#lant residues+

Q)<. W/'$ &$%-& /'& $/% E*."-%'# C"22*#+$+%& $'D%# $" .%;*%&$ .%I%=',*'$+"# "0 $/% %8+&$+#( +#$%.#'$+"#', &$'#d'.d& 0". $/% 0+=% /".2"#%&5 '11".d+#( $" $/% -."1%d*.%& "0 LECFA ". C"d%89 P,%'&% -."=+d% d"1*2%#$'$+"#. 42+ 1irst: it is ,orth reca#itulating ,hat the Euro#ean !ommunities did (as descri&ed at #ara+ 92 et se.. ('T()*320): #aras+ 49 et se.. ('T()*321) o$ its *econd 'ritten *u&mission)+ The Euro#ean !ommunities in$ormed !ode and the AE!1A *ecretariat in Ma6 1998 that it ,as carr6ing out ne, ris= assessments on the si hormonal su&stances in 5uestion and that it had launched a series o$ s#eci$ic studies+22 44+ 8#on learning that AE!1A: on its o,n initiati7e: has decided to re-e7aluate the three natural hormones: the Euro#ean !ommunities: &6 letter o$ 31 Aul6 1998 to !ode and letter o$ 24 >o7em&er 1998 to AE!1A re5uested that this re-e7aluation &e #ost#oned until the results o$ the studies commissioned ha7e come in+24 An indicati7e list o$ the 14 studies ,as attached to the letter+ Bo,e7er: &oth !ode and AE!1A declined to heed to this re5uest: ,ithout an6 7alid reason+ 28 At the 11th session o$ the !!"C)1 in late Aune 1999: the Euro#ean !ommunities re-iterated its re5uest: to no a7ail+ 29
*ee re$erence to letter o$ 4 Ma6 1998 in E!-E hi&it 23 - >o 13: letter to Mr+ Orriss: !hie$ o$ Aoint 1AO('BO 1ood *tandard %rogramme: dated 31 Aul6 1998+ 24 *ee E! E hi&it 23 - >o 13 and >o 1/ (letter o$ re#l6 to letter sent on 24 >o7em&er)+ 28 *ee E! E hi&it 23 - >o 1/ (letter $rom Mr+ Berman: AE!1A *ecretariat: dated 23 )ecem&er 1998)
22

'T()*320("(Add+3 %age !-20 48+ *econd: according to AE!1A;s #rocedural rules there are $i7e ,a6s o$ #lacing 7eterinar6 drugs on the agenda $or (re-)e7aluation+30 These are the $ollo,ing31: ). C"d%8 1"22+$$%%&

The !ode !ommittee on "esidues o$ Ceterinar6 )rugs in 1oods (!!"C)1) re$ers su&stances to AE!1A &ased on #riorities that it esta&lishes using criteria that it has de7elo#ed that are in accord ,ith acce#ted #rocedures o$ the !ode Alimentarius !ommission+ 2. FAO '#d WHO M%23%. S$'$%&

1AO and 'BO Mem&er *tates ma6 re5uest the inclusion o$ 7eterinar6 drugs on the agenda o$ AE!1A through a direct re5uest to the 1AO and 'BO *ecretariats+ *uch a re5uest must &e accom#anied &6 a commitment to #ro7ide the necessar6 data 2-4 months &e$ore the meeting+ 3. S-"#&".&

1or 7eterinar6 drugs not #re7iousl6 e7aluated &6 AE!1A: an industr6 s#onsor ma6 $or,ard a re5uest $or e7aluation through the go7ernment o$ a Mem&er *tate to !!"C)1: ,ith a commitment to #ro7ide the rele7ant data+ "e5uests $or the ree7aluation o$ a 7eterinar6 drug that has &een re7ie,ed &6 AE!1A #re7iousl6 ma6 &e $or,arded directl6 to the AE!1A *ecretariat+ As ,ith all other su&stances on the agenda: the Aoint *ecretariat includes the su&stance in the call $or data $or the meeting to ensure that all interested #arties ha7e the o##ortunit6 to su&mit data+ C. LECFA S%1.%$'.+'$

The AE!1A secretariat ma6 #lace a 7eterinar6 drug on the agenda $or re-e7aluation e7en though no outside re5uest has &een recei7ed+ <. LECFA +$&%,0

The !ommittee o$ten esta&lishes a tem#orar6 A)< or recommends tem#orar6 M"Ds: ,ith a re5uest $or $urther data &6 a certain time+ These 7eterinar6 drugs: ,hich ha7e the highest #riorit6 $or e7aluation: are #laced on the agenda o$ the a##ro#riate meeting &6 the Aoint *ecretariat+ 49+ The $irst listed here is the 9#riorit6 list9 #rocedure descri&ed &6 )r+ M6agishima at the e #ert meeting+ The Euro#ean !ommunities has: since the e7ents descri&ed a&o7e: not made a $ormal re5uest to ha7e an6 o$ the si hormonal su&stances in 5uestion #ut on the #riorit6 list+ As e #lained at the hearing: ho,e7er: the Euro#ean !ommunities ma6 do so once the ne, ris= anal6sis #rinci#les on residues in 7eterinar6 drugs ha7e &een ado#ted+ 32

*ee #ara+ 120 o$ the "e#ort o$ the Ele7enth *ession o$ the !ode !ommittee on "esidues o$ Ceterinar6 )rugs in 1oods (AD<>O"M 99(31): a7aila&le at htt#:((,,,+code alimentarius+net(,e&(archi7es+Es#R6earU99+ 30 >ote that t,o sets o$ #rocedural guidelines go7ern AE!1A;s ,or=: one issued &6 the 'BO and one issued &6 the 1AO+ The $ormer is a7aila&le at htt#:((,,,+,ho+int(i#cs($ood(Eec$a(#roceduralVguidelines J20Vdrugs+#d$: the latter at $t#:(($t#+$ao+org(es(esn(Eec$a(2002-09-2/VCetV)rugsV%rocV3uidelines&+#d$+ 31 <n res#ect o$ the $i7e ,a6s o$ ha7ing a su&stance (re-)e7aluated: the t,o a&o7ementioned sets o$ guidelines are identical+ The te t re#roduced a&o7e is the Anne 1 o$ the res#ecti7e guidelines+

29

'T()*320("(Add+3 %age !-21 80+ >ote: ho,e7er: that this $irst ,a6: contrar6 #erha#s to ,hat ma6 ha7e trans#ired at the e #ert meeting: is not the onl6 #ossi&ilit6 $or a Mem&er to re5uest e7aluation o$ a su&stance through AE!1A+ <ndeed: as can &e seen $rom the a&o7e #oint 2: there is also the #ossi&ilit6 $or a Mem&er to directl6 re5uest such e7aluation $rom either 1AO or 'BO+ 'hat the Euro#ean !ommunities has done as descri&ed a&o7e can &e su&sumed under this second ,a6 o$ re5uesting (re-)e7aluation o$ su&stances+ As seen a&o7e: the Euro#ean !ommunities turned directl6 to 1AO (the E! ,as onl6 a mem&er o$ 1AO - not !ode Alimentarius - at that time) to in$orm it o$ the ne, ongoing ris= assessments on all si su&stances and to re5uest the #ost#onement o$ the im#ending re-e7aluation o$ the three natural hormones until a$ter the results o$ the 14 studies ,ould &e a7aila&le+ O&7iousl6: this im#lies a commitment to ma=e the results o$ these ris= assessments and 14 studies a7aila&le to AE!1A+ E5uall6 o&7iousl6: this a7enue &ecame o&solete ,ith AE!1A;s re$usal to #ost#one $or a #eriod o$ 2-3 6ears the re-e7aluation o$ the three natural hormones+ 81+ >ote: $urthermore: that under the a&o7e rules (#oint /): the AE!1A *ecretariat can also decide on the (re-) e7aluation o$ a su&stance on its o,n initiati7e+ This is ,hat the AE!1A *ecretariat has indeed done ,ith regard to the three natural hormones+ >ote $inall6: that ,hen #er$orming an e7aluation: the tem#orar6 ad7isor (i+e+ a mem&er o$ the AE!1A secretariat #ut in charge o$ #re#aring ,or=ing #a#ers on the su&stance in 5uestion on the &asis o$ a7aila&le data) is as=ed to #er$orm a literature search on the su&stance in 5uestion+ 33 <n light o$ these $acts: it is clear that AE!1A has had e7er6 o##ortunit6: a$ter the Euro#ean !ommunities; re#eated raising o$ the issue o$ the ne, ris= assessments: to #ost#one the 1999 ris= assessment and to #lace again these hormones $or e7aluation a$ter 2002+ 82+ Moreo7er: the )elegation o$ the Euro#ean !ommunit6 re$erring to its ,ritten comments contained in !G("C)1 02(12(4: Add+1: stated that the M3A ,as e7aluated &6 AE!1A as gro,th #romoters and that such use o$ hormones ,ith estrogenic: androgenic or gestagenic action ,as #rohi&ited in the Euro#ean 8nion+ The #rohi&ition ,as #ermanent $or Oestradiol 14&eta and #ro7isional $or the other hormonal su&stances+ The 2002 re7ie, o$ the *cienti$ic !ommittee on Ceterinar6 Measures (*!CB%) relating to %u&lic Bealth considered the re#ort on M3A #re#ared &6 the 0/th meeting o$ AE!1A and o&ser7ed that it #ro7ides a com#rehensi7e re7ie, o$ the #harmaco=inetic(to ico=inetic #arameters and to icological #ro#erties o$ M3A in 7arious s#ecies+ The )elegation argued: ho,e7er: that no original data ,ere #resented in the re7ie, and the maEorit6 o$ re$erences ,ere re#orts that had not &een #u&lished in the #eer-re7ie,ed scienti$ic literature+ There$ore: $or M3A: concerns remained that e cess inta=e o$ hormone residues and their meta&olites: endocrine: de7elo#mental: immunological: neuro&iological: immunoto ic: genoto ic and carcinogenic e$$ects could &e en7isaged: in #articular $or susce#ti&le ris= grou#s+ 1or these reasons: the Euro#ean !ommunities could not su##ort the ado#tion o$ the M"Ds #ro#osed &6 the 22 th AE!1A+ This #osition ,as su##orted &6 t,o other delegations+ 83+ The $ollo,ing ,ere the E! ,ritten comments on the matter deli7ered in time &e$ore the meeting and su&mitted to e7er6&od6 in !G("C)1 02(12(4: Add+1:

%ro#osed )ra$t "is= Anal6sis %rinci#les a##lied &6 the !ode !ommittee on "esidues o$ Ceterinar6 )rugs in 1ood ($or inclusion in the !ode %rocedural Manual): A##endi C<<< o$ AD<>O"M 02(29(31 (re#ort o$ 12th !!"C)1) A7aila&le at htt#:((,,,+code alimentarius+net(,e&(archi7es+Es#RlangUenP+ As e #lained at the hearing: the ne, %aragra#hs 19 and $ollo,ing o$ these #rinci#les #ro7ide the !!"C)1 as the ris= manager ,ith much more concrete #ossi&ilities to gi7e s#eci$ic instructions to AE!1A on ,hich as#ects to co7er in its ris= assessment+ 3i7en that the E! ris= assessments on the si su&stances in 5uestion raise man6 issues ,hich ha7e so $ar not &een addressed &6 AE!1A: it is o&7ious that the Euro#ean !ommunities ,ould ,ant AE!1A to &e instructed to s#eci$icall6 address these issues+ 33 .oth the 'BO and the 1AO guidelines underline the im#ortance o$ this literature search: see 'BO guidelines: #age 2 in &old: see 1AO guidelines: #oint 0+2+

32

'T()*320("(Add+3 %age !-22 M%,%#(%&$.", '1%$'$%> The su&stance ,as e7aluated &6 AE!1A $or use as gro,th #romoters+ *uch use o$ hormones ,ith estrogenic: androgenic or gestagenic action is #rohi&ited in the Euro#ean 8nion+ This #ro7ision is #ermanent $or oestradiol 14. and #ro7isional $or the other hormonal su&stances+ <t is also in line ,ith Article 0+4 o$ the *%* Agreement+ <t a##lies ,hile the !ommunit6 see=s more com#lete scienti$ic in$ormation+ The Euro#ean !ommission (&6 means o$ the *cienti$ic !ommittee on Ceterinar6 Measures relating to %u&lic Bealth - *!C%B: and no, the Euro#ean 1ood *a$et6 Authorit6 - E1*A) re7ie,s regularl6 an6 additional scienti$ic data $rom all #ossi&le sources that is #u&licl6 a7aila&le+ This entails continuing to re7ie,: as done in 2000 and 2002: the a7aila&ilit6 o$ scienti$ic #u&lications and e7aluation re#orts+ The 2002 re7ie, o$ the *cienti$ic !ommittee on Ceterinar6 Measures relating to %u&lic Bealth considered the re#ort on melengestrol acetate #re#ared &6 the 0/th meeting o$ AE!1A and o&ser7ed that it #ro7ides a com#rehensi7e re7ie, o$ the #harmaco=inetic(to ico=inetic #arameters (adsor#tion: distri&ution: meta&olism and e cretion) and to icological #ro#erties o$ M3A in 7arious s#ecies+ <t criticised: ho,e7er: that no original data are #resented in this re7ie, and the maEorit6 o$ the re$erences are to re#orts that ha7e not &een #u&lished in the #eer-re7ie,ed scienti$ic literature+ The 0/th AE!1A re#ort itsel$ states that 9 ,ost o$ t e studies "ere conducted be$ore 1/0/ according to t e standards in existence at t at time and "ere not carried out in compliance "it %)P9 (#age 20: 3rd #aragra#h o$ 0/th AE!1A "e#ort) and the 22nd AE!1A #resented onl6 ne, in$ormation regarding the structure and acti7it6 o$ the meta&olites o$ M3A (#age 22 o$ 22nd AE!1A "e#ort)+ The E8 scienti$ic committee considered more recent in7estigations and summarised (see #age 14 to o$ the *!C%B re#ort o$ 20022)+ %reliminar6 data cited in this re#ort: indicated that the meta&olism o$ M3A is more com#le that #re7iousl6 assumed: &ut $urther e #eriments should 7eri$6 the s#eci$ic meta&olite #attern in target animal s#ecies as ,ell as man@ demonstrated that M3A has a 7er6 strong #otential to &ind to &o7ine #rogesterone rece#tors: although these data need $urther 7eri$ication@ suggested that in utero or #re- and #eri#u&ertal e #osure to hormones (including animal e7idence on s6nthetic #roducts) ma6 a$$ect #u&ertal de7elo#ment and e#idemiological studies ,ith o##osite se ed t,ins indicate that #renatal e #osure to hormones ma6 &e lin=ed to adult cancer ris=@ sho,ed that ne,er e #eriments clearl6 identi$6 a ris= $or e cessi7e e #osure o$ consumers to residues $rom mis#laced or o$$-la&el used im#lants and incorrect dose regimes+ <n these cases: le7els o$ oestradiol and its meta&olites in muscle: $at: li7er and =idne6 $rom hormone treated cattle ma6 &e 2-$old u# to se7eral hundred $olds higher as com#ared to untreated meat+ The le7el o$ increase de#ends on the treatment regime and the actual hormone le7els in the im#lants used+

There$ore $or melengestrol acetate concerns remain that &6 e cess inta=e o$ hormone residues and their meta&olites: endocrine: de7elo#mental: immunological: neuro&iological: immunoto ic: genoto ic and carcinogenic e$$ects could &e en7isaged: in #articular $or susce#ti&le ris= grou#s #ersist+ The Euro#ean !ommunit6 can there$ore not su##ort the ado#tion o$ the #ro#osal $or ma imum residue limits $or this su&stance+ The ne t re7ision o$ its scienti$ic o#inion &6 E1*A is to &e #resented

'T()*320("(Add+3 %age !-23 later in 2002+ There has &een a res#ecti7e call $or data at: htt#:((,,,+e$sa+eu+int(inde Vde+html+ The Euro#ean !ommunit6 suggests that this su&stance is sent &ac= to AE!1A $or re-e7aluation in the light o$ the latest in$ormation #ro7ided in the 2002 and the e #ected 2002 ris= assessments &6 the scienti$ic committees o$ the Euro#ean !ommunit6+ Q)F. P,%'&% %8-,'+# $/% .%'&"# 0". $/% d+00%.%#1%& 3%$7%%# $/% 6,+&$ "0 $/% ): &$*d+%&6 $/'$ 7'& '--%#d%d $" $/% 2002 O-+#+"# '#d $/% "#% $/'$ 7'& -."=+d%d $" $/% P'#%,. ?-,%'&% &%% -'.'(.'-/ 20 "0 $/% U#+$%d S$'$%&! R%3*$$', S*32+&&+"# '#d +$& T'3,% )@ 8/+ As e #lained a&o7e under ?uestion 3: ,hen the 2002 O#inion ,as issued all e ce#t t,o o$ the studies had alread6 &een #u&lished+ )i$$erences in the t,o lists are mainl6 the result o$ $urther #u&lications o$ #artial as#ects o$ the studies+ The Euro#ean !ommunities is anne ing as E hi&it E!-129 a commented 7ersion (trac= changes) o$ the 8* Ta&le 1 re$erred to in the a&o7e 5uestion+ <t sets out in detail ,here and ,hen the di$$erent studies ha7e &een #u&lished+

'T()*320("(Add+3 %age !-2/ ANNEX CI2 COMMENTS BY THE EUROPEAN COMMUNITIES ON THE REPLIES OF THE UNITED STATES AND CANADA TO QUESTIONS POSED BY THE PANEL AND OTHER PARTIES AFTER THE SECOND SUBSTANTI E MEETING (31 Octo&er 2002) P'#%, Q*%&$+"#& $" ',, -'.$+%&> Q). W+$/ .%0%.%#1% $" $/% &$'$%2%#$ 34 $/% E*."-%'# C"22*#+$+%&5 inter alia +# -'.'. )2 "0 $/% EC .%-,4 $" Q*%&$+"# 3 "0 $/% U#+$%d S$'$%&5 d" $/% -'.$+%& 1"#&+d%. $/'$ ' P'#%, +& %#$+$,%d $" 'dd.%&& 6&4&$%2+1 1,'+2&6 ". +&&*%& .%,'$%d $" 6&4&$%2+1 "3,+('$+"#&6 '#d5 +0 &"5 $" 7/'$ %8$%#$9 1+ There does not seem to &e a disagreement among the #arties as to the su&stance o$ this 5uestion: all agree that the %anel has the tas= o$ ruling on the claims that the Euro#ean !ommunities has made under Article 23 o$ the )*8 irres#ecti7e o$ ,hether one ,ants to call them 9s6stemic9 or not+ 2+ O&7iousl6: the #arties; 7ie,s di$$er on the 5uestion o$ ho, $ar the o&ligations contained in Article 23 go+ !anada reiterates its 7ie, that it is the E! and not !anada that is acting unilaterall6 &6 #roclaiming com#liance+ <n its res#onse: !anada;s also o7erloo=s one o$ the central E! claims in this dis#ute: namel6 the &reach o$ Article 23 that lies in the $act that the 8* and !anada $ailed to ha7e recourse to the )*8 to see= redress o$ a 7iolation: and instead unilaterall6 determined that the E! continued to &e in &reach o$ 'TO o&ligations+ The 8*: ,hile &eing #olemic: does not &other to e #lain its 7ie, on the e tent o$ these o&ligations+ <t merel6 dismisses the Euro#ean !ommunities; reading as an attem#t 9to see the )*8 redra$ted: at least $or #ur#oses o$ this dis#ute+9 3+ 1act is: ho,e7er: that this %anel has the tas= o$ a##l6ing Article 23 to the situation at hand: A Mem&er: in good $aith: #resents its com#liance measure and ne7ertheless has to su$$er continued a##lication o$ sanctions: &ecause the other side denies that com#liance has &een achie7ed and re$uses to initiate the dis#ute settlement #roceedings $oreseen in Article 21+0+ <t is the $irst time that this situation arises in the dis#ute settlement s6stem+ <s it a situation that the )*8 does not addressR >either side in this dis#ute sa6s so+ The #arties merel6 ha7e di$$ering 7ie,s on ho, to inter#ret Article 23 and Articles 21+0 and 22+8 ,hen a##lied to this situation+ /+ 1or some o$ the #arties in7ol7ed in this dis#ute: these 7ie,s: not sur#risingl6: are related to #ositions ta=en in the current )*8 re7ie,: in !anada;s case since rather recentl6 (see E!;s res#onse to %anel 5uestion >o+ 2/)3/+ <ndeed: not sur#risingl6: the current )*8 re7ie,: amongst other issues: addresses this one: in order to #recisel6 sol7e - through negotiation - the e isting di7ergence o$ 7ie,s on ho, the )*8 should &e a##lied in this situation+ This is a not uncommon #henomenon in the 'TO s6stem: The correct inter#retation o$ o&ligations is su&Eect to disagreement among mem&ers and there is an initiati7e to settle that disagreement through #olitical consensus+ 30 *uch initiati7es are not al,a6s cro,ned &6 success or - as the #resent case sho,s - do not reach a result in time to address a gi7en situation ,hen it arises+ The o&ligations - dis#uted as their content ma6 &e - do: ho,e7er: e ist+ Thus: in the a&sence o$ an e #licit clari$ication o$ the e isting o&ligations &6 the collecti7e Mem&ershi# itsel$: it is $or the dis#ute settlement &odies to discharge their dut6 to a##l6 and inter#ret
*ee #aras+ 200 et se5+ o$ the E! "e#lies to %anel;s ?uestions a$ter 1irst *u&stanti7e Bearing: erroneousl6 called ?uestion 20+ 30 Another e am#le is the role o$ multilateral en7ironmental agreements in the inter#retation and a##lication o$ the 'TO agreements+ 9Meroing9 methodolog6 ma6 ser7e as a $urther e am#le+
3/

'T()*320("(Add+3 %age !-20 the rules that e ist toda6+ E7en i$ there ,ere a #ros#ect o$ a conclusion o$ the )*8 negotiations in the 7er6 near $uture: there is in no e7ent a non li.uet o#tion o$ sa6ing 9,e ,ill ,ait $or the outcome o$ the negotiations+9 Q2. W+$/ .%0%.%#1% $" $/% US .%3*$$',5 -'.'. 2:5 d" $/% -'.$+%& 1"#&+d%. $/'$ ' 2%'&*.% $/'$ d"%& #"$ 1"2-,4 7+$/ $/% .%;*+.%2%#$& "0 A.$+1,% <.: SPS 7"*,d '*$"2'$+1',,4 3% +# 3.%'1/ "0 A.$+1,% 2.2 SPS5 ". A.$+1,% <.) SPS5 ". 3"$/9 0+ There seems to &e agreement among the #arties on the #oint that there is no automatic &reach o$ Articles 2+2 and 0+1: i$ a measure does not com#l6 ,ith the re5uirements o$ Article 0+4+ <ndeed: the legalit6 o$ a measure &ased on Article 0+4 can &e determined inde#endentl6 o$ the re5uirements o$ Articles 2+2+ and 0+1: since Article 0+4 is an e ce#tion to &oth o$ them+ This is &ecause: in addition to the comments made at #aras+ 3-0 o$ the E!;s re#lies o$ 18 Octo&er 2002: it is necessar6 to ta=e into account the reasons $or ,hich: in a gi7en situation: all the re5uirements o$ Article 0+4 *%* are $ound not to ha7e &een com#lied ,ith+ <t should &e noted that the &asic o&ligation under Article 2+2 *%* is to &ase the measure on su$$icient scienti$ic e7idence+ The #er$ormance o$ a ris= assessment: in the sense o$ Article 0+1-0+2: is one ,a6 o$ #ro7iding such #roo$+ Bo,e7er: as the e #erts ha7e argued in the case o$ #rohi&iting to&acco smo=ing: it ,as not necessar6 to #er$orm a ris= assessment in the sense o$ Article 0+1 &e$ore ta=ing a measure in the light o$ the o7erall scienti$ic e7idence a7aila&le+ 2+ The Euro#ean !ommunities ,ould: ho,e7er: agree ,ith the 8* and !anada that in the #resent cases the recommendations and rulings o$ the )*. had identi$ied a &reach o$ Article 0+1 ,hich the E! com#liance measure needs to address+ .ut no such &reach e ists an6 longer: i$ either o$ the $ollo,ing t,o situations a##lies: the measure is no, &ased on a ris= assessment and there$ore consistent ,ith Article 0+1@ or the measure is &ased on Article 0+4 &ecause the rele7ant scienti$ic e7idence is not su$$icient to carr6 out a $ull ris= assessment in the sense o$ Article 0+1 *%*+32 Bo,e7er: the Euro#ean !ommunities disagrees ,ith the 8* comment (at #ara+ 0 o$ its re#l6 o$ 18 Octo&er 2002) that 9the E! does not claim to ha7e #er$ormed a ris= assessment consistent ,ith Article 0+19+ This is not true+ The E! has #er$ormed such a ris= assessment $or oestradiol-14 I+ Moreo7er: the E! has #er$ormed such a ris= assessment also $or the other $i7e hormones+ <n the #er$ormance o$ such a ris= assessment: ho,e7er: the E! has come to the conclusion that $or the $i7e hormones it ,as not #ossi&le to com#lete the ris= assessment &ecause the rele7ant scienti$ic e7idence ,as insu$$icient on a num&er o$ im#ortant issues and #oints that are clearl6 identi$ied and e #lained in the ris= assessment+ That is ,h6 the E! had to &ase its measure $or the $i7e hormones on Article 0+4 *%*: until 9the additional in$ormation necessar6 $or a more "3H%1$+=% assessment o$ ris=9 &ecomes a7aila&le+ 4+ The &asic error in the 8*;s and !anada;s reasoning stems $rom their narro, (&lac= or ,hite $ashion) inter#retation o$ the term 9insu$$icient9: &6 em#lo6ing de$ault #resum#tions: sa$et6 $actors: and the ,eight o$ e7idence a##roach: the6 eliminate an6 9insu$$icienc69 that comes $rom incom#lete or contradictor6 e7idence or $rom di7ergent or minorit6 scienti$ic 7ie,s+ Their a##roach 7ie,s as #redominantl6: i$ not e clusi7el6: 5uantitati7e the conce#t o$ 9insu$$icient9 e7idence+ This is: ho,e7er: contrar6 to the $indings &6 the A##ellate .od6 ,hich has stated that: 9Article 0+1 does not re5uire that the ris= assessment must necessaril6 em&od6 onl6 the 7ie, o$ a maEorit6 o$ the rele7ant scienti$ic communit6+ <n some cases: the 7er6 e istence o$ di7ergent 7ie,s #resented &6 5uali$ied scientists ,ho ha7e in7estigated the #articular issue at hand ma6 indicate a state o$ scienti$ic uncertaint6+ *ometimes the di7ergence ma6 indicate a roughl6 e5ual &alance o$ scienti$ic o#inion: ,hich ma6 itsel$ &e a $orm o$ scienti$ic uncertaint6+ <n most cases: res#onsi&le and
As is alread6 =no,n $rom #re7ious su&missions the #arties disagree on the nature o$ Article 0+4+ This does in #rinci#le not a$$ect the a&o7e statement+
32

'T()*320("(Add+3 %age !-22 re#resentati7e go7ernments tend to &ase their legislati7e and administrati7e measures on 9mainstream9 scienti$ic o#inion+ <n other cases: e5uall6 res#onsi&le and re#resentati7e go7ernments ma6 act in good $aith on the &asis o$ ,hat: at a gi7en time: ma6 &e a di7ergent o#inion coming $rom 5uali$ied and res#ected sources+ .6 itsel$: this does not necessaril6 signal the a&sence o$ a reasona&le relationshi# &et,een the *%* measure and the ris= assessment: es#eciall6 ,here the ris= in7ol7ed is li$e-threatening in character and is #ercei7ed to constitute a clear and imminent threat to #u&lic health and sa$et6+ )etermination o$ the #resence or a&sence o$ that relationshi# can onl6 &e done on a case-to-case &asis: a$ter account is ta=en o$ all considerations rationall6 &earing u#on the issue o$ #otential ad7erse health e$$ects+9 (at #ara+ 19/ o$ its re#ort in Bormones): and that: 9Thirdl6: a #anel charged ,ith determining: $or instance: ,hether 9su$$icient scienti$ic e7idence9 e ists to ,arrant the maintenance &6 a Mem&er o$ a #articular *%* measure ma6: o$ course: and should: &ear in mind that res#onsi&le: re#resentati7e go7ernments commonl6 act $rom #ers#ecti7es o$ #rudence and #recaution ,here ris=s o$ irre7ersi&le: e+g+ li$e-terminating: damage to human health are concerned+9 (at #ara+ 12/ o$ its re#ort in Bormones) 8+ <t $ollo,s $rom the a&o7e that a measure ,ould &e in con$ormit6 ,ith Article 0+1 i$ acted in good $aith and on the &asis o$ ,hat ma6 &e a di7ergent o#inion coming $rom 5uali$ied and res#ected sources+ As the A##ellate .od6 has said: such a measure ,ould not necessaril6 signal the a&sence o$ a reasona&le relationshi# ,ith the ris= assessment: in the sense o$ Article 0+1+ *%*+ ( $ortiori' there$ore: a good $aith measure that is &ased not on the mainstream &ut on di7ergent scienti$ic o#inions ,ould also &e in con$ormit6 ,ith Article 0+4 *%*+ Q3. W/%# '#d /"7 7'& %'1/ "0 $/% 0",,"7+#( d"1*2%#$& 2'd% '='+,'3,% $" C'#'d' '#d $/% U#+$%d S$'$%&9 P,%'&% '#&7%. +#d%-%#d%#$,4 0". %'1/ "0 $/% d"1*2%#$& 2%#$+"#%d 3%,"7> ?+@ )AAA O-+#+"#B ?++@ 2000 O-+#+"#B ?+++@ 2002 O-+#+"#B ?+=@ %'1/ "0 $/% 6): &$*d+%&6. 9+ The Euro#ean !ommunities considers that it has: in its re#lies to ?uestion 3 and 12 and on man6 instances #re7iousl6: demonstrated in am#le detail not onl6 that all three O#inions and the 14 studies (e ce#t t,o o$ them) ,ere #u&licl6 a7aila&le: &ut also that there ,as a continuous discussion a&out them ,ith the de$ending #arties on the &ilateral and on the multilateral le7el throughout these 6ears+ An6 suggestion that a Mem&er ,as le$t in the dar= a&out the #rogress and the results o$ the ne, ris= assessment or that it ,as not in the #ossession o$ the 14 studies is not onl6 &aseless &ut &orders on &ad $aith+ 10+ The 8* $urther argues (at #aras+ 4-10 o$ its re#l6 o$ 18 Octo&er 2002) that the E! had to re5uest $rom the 8* $or the 2000 and 2002 ris= assessments 9a discussion or a con$erence on the scienti$ic under#innings o$ the E!;s &an9: as it did $or the 1999 ris= assessment+ .ut there is no #ro7ision in an6 o$ the 'TO Agreements rele7ant to this dis#ute that ,ould #lace such a &urden on the E!+34 ?uite the o##osite: the im#ortant #oint is ,hether the 8* could ha7e had access to the rele7ant e7idence under#inning the E! ris= assessment: i$ it had so ,ished+ <ndeed: a&out this there is
34 The $act that the scientists $rom &oth sides met in Aul6 1999 and discussed the $irst ris= assessment ,as &ecause o$ the good ,ill o$ the E!: not &ecause o$ an6 #articular o&ligation on the E! under the 'TO Agreements a##lica&le in this case+

'T()*320("(Add+3 %age !-24 no dou&t since the 1999: 2000 and 2002 ris= assessments and all the underl6ing e7idence on ,hich the6 are &ased ,ere #u&lished in #eer-re7ie,ed Eournals and ,here thus accessi&le to the 8*+ This contrasts shar#l6 ,ith the #ersistent re$usal &6 the 8* and !anada (and also o$ AE!1A) to ma=e a7aila&le the underl6ing scienti$ic studies u#on ,hich the6 claim to ha7e &ased their ris= assessments+ 11+ The &urden: there$ore: ,as on the 8* to su&mit an6 o&ser7ations and comments: i$ it had so ,ished+ The 8* $ailed to react e7en a$ter the dra$t and the $inall6 ado#ted E! measure ,as $ormall6 noti$ied to the 'TO in accordance ,ith the *%* Agreement+ 38 The )ecem&er 200/ re5uest &6 the 8* is a &elated attem#t to camou$lage its lac= o$ due diligence and &ad $aith $or the resolution o$ this dis#ute+ QC. H'& $/% E*."-%'# C"22*#+$+%& '&&%&&%d +# ' &4&$%2'$+1 2'##%. $/% %8+&$%#1% '#d ,%=%, "0 .+&D& 0."2 0'+,*.% $" "3&%.=% (""d =%$%.+#'.4 -.'1$+1%& 7+$/ .%&-%1$ $" $/% 'd2+#+&$.'$+"# "0 "%&$.'d+", ):E '& ' (."7$/ -."2"$+#( /".2"#% $" 1'$$,%5 +# -'.$+1*,'. +# $/% U#+$%d S$'$%&! '#d C'#'d'!& 2'.D%$&9 I0 &"5 -,%'&% +#d+1'$% 7/%.% $/+& '&&%&&2%#$ +& $" 3% 0"*#d +# $/% %=+d%#1% -."=+d%d $" $/% P'#%,. 12+ The E! disagrees ,ith the 8* comment that 9the E! has not e7en seriousl6 argued in the course o$ these #roceedings that it has done so9 (at #ara+ 11 o$ its re#l6 o$ 18 Octo&er 2002)+ 13+ The 8* resorts again to its $a7ourite tactic in arguing that the E! #resented onl6 9unrealistic misuse scenarios9 and that the e7idence is 9#urel6 s#eculati7e and unsu##orted9: ,ithout engaging in an6 serious discussion a&out the e7idence that is #resented to the %anel+ Thus: the 8* does not mention nor discuss the $ollo,ing: 1/+ <n E hi&it E!-43 the $ollo,ing undis#uted instances o$ misuse or a&use are clearl6 mentioned: At #ara+ 10: 9<n 1982: the 8*)A;s 1ood *a$et6 and <ns#ection *er7ice (1*<*) re#orted a ,ides#read misuse o$ hormone im#lants in the 8*A+9 At #ara+ 12: 9Euro#ean !ommission ins#ection mission to !anada in 1998 re#orted that the o$$icial la&orator6 o$ the !anadian 1ood <ns#ection Agenc6 (!1<A) in *as=atoon had recentl6 detected increased residue le7els o$ &eta-tren&olone in nec= muscles o$ 7eal cal7es: e ceeding the 9administrati7e action le7el9 o$ 2 ##& in muscle+ The re#orted le7els o$ u# to 12 Lg(=g in muscle cannot &e achie7ed &6 im#lanting in the ear onl6 in accordance ,ith 3C%+9 ($ootnotes omitted) 39 At #ara+ 14: 9<t should also &e noted that neither the 8* nor the !anadian meat ins#ection regulations #ro7ide $or regular chec=s o$ the carcasses $or mis#laced im#lants at slaughter+ >either the 8* nor !anadian authorities o$$er an6 other ade5uate in$ormation ,hich ,ould allo, the Euro#ean !ommunit6 authorities to 7eri$6 the magnitude and $re5uenc6 o$ mis#lacement o$ im#lants+9 ($ootnotes omitted)

The 8* argues (at #ara+ 9 o$ its re#l6 o$ 8 Octo&er 2002) that instead o$ e7idence 9the E! res#onse contained internet lin=s $or the 2000 "e7ie, and the 2002 O#inion9+ The im#ortant #oint to note: ho,e7er: is that the 8* has a##arentl6 ne7er tried to access the internet lin=s #ro7ided &6 the E!: &ecause had it done so it ,ould ha7e had access to all the re$erences and materials on ,hich the E! &ased its ris= assessments+ 39 The E! Mission re#orts resulting $rom ins#ections carried out in !anada and the 8* are #ro7ided in E hi&its E!-24 and 28+

38

'T()*320("(Add+3 %age !-28 At #ara+ 22: 9 <m#lanting strategies commonl6 a##lied in toda6;s &ee$ #roduction include not onl6 re-im#lanting as a rule: resulting in the #resence o$ se7eral im#lants #er animal: &ut also a shortening o$ inter7als &et,een the last a##lication o$ an im#lant and the slaughter o$ the animal+ There is no legall6 #rescri&ed ,ithdra,al time $or an6 o$ the a##ro7ed im#lants in the 8*A and !anada+ Ta&le 3 gi7es an o7er7ie, o$ im#lanting strategies currentl6 a##lied in &ee$ #roduction: recommended 9re-im#lant ,indo,s9: i.e. o#timum re-im#lant times: and calculated 9o#timum #a6out #eriods9: i.e. the time during ,hich an im#lant releases gro,th #romoter a&o7e an e$$ecti7e gro,th stimulating le7el+ 1or ma imum &ene$it: $armers and animal #roducers are ad7ised to =ee# the le7el o$ im#lant gro,th #romotant a&o7e the e$$ecti7e gro,th stimulating le7el until slaughtering+9 ($ootnotes omitted) At #ara+ 31: 9<n the 8*A and !anada 7eterinar6 #rescri#tion is not com#ulsor6 $or a##ro7ed hormonal gro,th #romoters+ *u#er7ision &6 a 7eterinarian is not re5uired either+ To the contrar6: in &oth countries hormonal gro,th #romoters are $reel6 a7aila&le in the o7er-the-counter sale as ,ell as in sel$-ser7ice at agricultural retail stores and e7en &6 mail+9 ($ootnotes omitted) At #ara+ 32: 9Bormonal gro,th #romoters are not a##ro7ed $or use in 7eal cal7es in !anada and the 8*A+ There is ne7ertheless clear e7idence that di$$erent hormones are &eing used in 7eal cal7es in &oth countries+ A Euro#ean !ommission ins#ection mission to !anada in 1998: intended to e7aluate the !anadian residue control s6stem: re#orted that the !1<A had recentl6 #er$ormed t,o s#ecial sur7e6s to e7aluate the #ossi&le misuse o$ tren&olone in 7eal cal7es+ The sur7e6s ,ere carried out in com#ressed time #eriods using random sam#les and #roduced the $ollo,ing results: The $irst sur7e6 co7ered the #eriod &et,een Aune and Aul6 1994 and #roduced 91 #ositi7e out o$ 281 li7er sam#les ta=en (32+4J)+ The second sur7e6 co7ered the #eriod $rom A#ril 1994 through Aanuar6 1998 and #roduced 80 #ositi7e out o$ 210 li7er sam#les ta=en (/0J)+9 ($ootnotes omitted) At #ara+ 33: 9The !anadian 1ood and )rug Act and "egulations do not de$ine clearl6 e tra-la&el or o$$-la&el use+ The !anadian authorities acce#t: ho,e7er: that a $armer ma6 use authoriFed hormone im#lants in 7eal cal7es on condition that residues in li7er and muscle com#l6 ,ith the so-called 9administrati7e action le7els9 esta&lished $or &o7ine tissues+ <n other ,ords: the !anadian authorities tolerate the o$$-la&el use o$ hormone im#lants &6 $armers $or gro,th #romotion #ur#oses and do not en$orce the la&el instructions+9 ($ootnotes omitted) At #ara+ 3/: 9<n the case o$ the 8*A: t,o Euro#ean !ommission ins#ection missions in 1989 and 1990 had alread6 re7ealed that hormone im#lants are also used in 7eal cal7es+ The Euro#ean !ommission ins#ectors themsel7es $ound im#lants in the ears o$ t,o out o$ ten 7eal cal7es the6 e amined@ ho,e7er: no su&se5uent action ,as ta=en &6 the national authorities+ 1urthermore in a letter $rom the !enter $or Ceterinar6 Medicine o$ the 1ood and )rug Administration (1)A) to the American Ceal Association o$ 29 )ecem&er 1989 the 1)A e #resses its concern a&out the misuse o$ hormone im#lants in $ormula-$ed 7eal+9 ($ootnotes omitted) At #ara+ 30: 9The most recent results o$ a stud6: ,hich ,as commissioned &6 the Euro#ean !ommission as #art o$ its com#lementar6 to icological ris= assessment o$ hormonal gro,th #romoters and ,hich ,as intended to determine the amount o$ hormone residues in 8* meat and o$$al: con$irms the o$$-la&el use o$ hormonal gro,th #romoters in the 8*A+ 1irst: although no hormonal gro,th #romoter is

'T()*320("(Add+3 %age !-29 a##ro7ed $or 7eal cal7es: residues o$ tren&olone acetate and Feranol ,ere $ound &oth in cal$ li7er $rom the 8* domestic mar=et and in cal$ sam#les $rom 8* meat consignments sam#led at the &order ins#ection #oints o$ the E8+ *econd: although melengestrol acetate (M3A) is onl6 a##ro7ed $or use in hei$ers: a su&stantial num&er o$ the meat sam#les that tested #ositi7e $or M3A residues ,ere su&se5uentl6 identi$ied &6 )>A gender identi$ication to stem $rom male animals+9 ($ootnotes omitted)/0 At #ara+ 39: 9A $urther 7iolation o$ 3C% related to o$$-la&el use o$ hormonal gro,th #romoters ,as re#orted $rom !anada+ The registration re5uirements $or the use o$ melengestrol acetate (M3A): a gro,th #romoter incor#orated in the $eed $or hei$ers: sti#ulate that: 9,%( must not be $ed to ei$ers treated "it ot er ormonal drugs. 9 >e7ertheless: during the 7isit o$ a Euro#ean !ommission ins#ection team in 1998 to a !anadian $eedlot: the $eedlot o#erator declared that until recentl6 his hei$ers ,ere treated simultaneousl6 ,ith *6no7e W: an a##ro7ed im#lant containing testosterone and estradiol: and ,ith M3A+9 ($ootnotes omitted) At #ara+ 04: 9E7idence on the e istence o$ a &lac= mar=et $or 7eterinar6 drugs and gro,th #romoters in the 8*A and in !anada can &e in$erred $rom #u&lications o$ the 1)A;s !enter $or Ceterinar6 Medicine+ These #u&lications re7eal that o7er the #ast 6ears there has &een a large-scale smuggling o$ illegal animal drugs: e+g+ clen&uterol: $rom !anada into the 8*A+9 ($ootnotes omitted) At #aras+ 20 and 28: 9<n the 8*A a threshold le7el: utilisa&le $or residue control #rogrammes: has &een esta&lished $or onl6 one o$ these si hormones: that is a tolerance le7el $or melengestrol acetate+ The other so-called 9 sa$e concentrations $or total residues in edible tissues9 esta&lished $or tren&olone acetate and Feranol and the so-called 9increments9 esta&lished $or the three endogenous hormones are not suita&le $or a residue e7aluation &6 routinel6 #er$ormed e aminations+9 and 9<t can: there$ore: &e concluded that in the 8*A onl6 the tolerance limit $or melengestrol acetate is a##ro#riate to &e used in a residue control #rogramme+9 ($ootnotes omitted) At #aras+ 40: 41 and 43: 940+ )es#ite clear #ro7isions in the 1ood and )rug Act and "egulations on the general Fero tolerance ,ith certain ,ell-de$ined e em#tions: the !anadian authorities ha7e ado#ted so-called 9administrati7e action le7els9 $or certain su&stances: including tren&olone: Feranol and melengestrol acetate: not listed in the 1ood and )rug "egulations+ <t has to &e stressed that the a##lication o$ the 9administrati7e action le7els9 is not consistent ,ith the !anadian 1ood and )rug Act+ Although the 9administrati7e action le7els9 are identical ,ith the M"Ds esta&lished &6 !ode it can &e concluded that the !anadian authorities ha7e not ado#ted legall6 en$orcea&le threshold le7els $or the three a##ro7ed s6nthetic hormones+9: and that: 941+ <t has to &e noted that these 9administrati7e action le7els9 are a##lied also to 7eal cal7es: although the hormones in 5uestion are not authorised $or this categor6 o$ &o7ine animals+9: and that: 943+ <t $ollo,s that the 8*A and !anada: ,ith the e ce#tion $or melengestrol acetate in the 8*A: either lac= en$orcea&le residue limits or cannot or do not en$orce the ones the6 ha7e+9 ($ootnotes omitted) At #ara+ 81: 9These $indings ha7e no, &een con$irmed &6 the #ro7isional results o$ the 1999 s#eci$ic Euro#ean !ommission stud6 on residue control o$ meat and li7er im#orted $rom the 8*A under the Bormone 1ree !attle %rogramme (B1!
The recent stud6 in 5uestion is E hi&it E!-03+

/0

'T()*320("(Add+3 %age !-30 %rogramme)+ The a7aila&le #reliminar6 results o$ this stud6: &ased on 8* meat and li7er sam#les collected at the &order ins#ection #osts o$ the E8: sho, that : 9 &n total it is concluded $rom t is stud1 t at t e H#C Programme is not e$$ectivel1 controlled b1 t e responsible US aut orities. #rom t e residue $indings t e misuse o$ t e US approved xenobiotic 2 ormones3 trenbolone' 4eranol and ,%( in t is H#C Programme is s o"n in at least 156 o$ t e samples. 7o de$initive conclusions can be dra"n $rom t is stud1 about t e misuse in t e H#C Programme o$ t e US approved ormones 8109:estradiol' testosterone or progesterone. Ho"ever' $or estradiol t e misuse is indicated $or at least one sample. 7o evidence as been $ound so $ar t at in t e H#C Programme ot er 2 ormones3 are used t an t ose approved in t e US(. H#C violative products "ere exported to t e European Union b1 3 out o$ ; di$$erent US( meat sellers sampled in t is stud1.9 9($ootnotes omitted) At #ara+ 90: 9<t must &e underlined that there are no s#eci$ic regulations in the 8*)A !ode o$ 1ederal "egulations on dis#osal #rocedures $or im#lantation sites: e+g+ $or im#lants in the ears+9 ($ootnotes omitted)

10+ 1urther concrete e7idence that misuses or a&uses are not e ce#tional occurrences in the 8* and !anada is #ro7ided at the $ollo,ing E hi&its: E hi&it E!-29: ,here in 200/ 3uidance $or <ndustr6: the 8* 1)A stated that 9use o$ una##ro7ed hormone im#lants in non-ruminating 7eal cal7es has occurred+9 E5uall6: E hi&it E!-40 $or !anada+ E hi&its E!-92 and 103: ,hich although concern the unauthorised hormone )E* in 1999-2000: do sho, that a &lac= mar=et also e ists in the 8* $or these hormones as ,ell as $or other hormonal su&stances+ Moreo7er: E hi&it E!-29 contains se7eral e am#les o$ misuse and &lac= mar=et acti7ities in the 8*+ E hi&it E!-102: ,hich states: inter alia: that the 8* 1ood *a$et6 and <ns#ection *er7ices (1*<*) 9is concerned a&out the ,ides#read: illegal use o$ drug im#lants in 6oung cal7es that ,as disco7ered in 200/9+ The same e hi&it also states that 91*<* learned that the use o$ gro,th #romoting im#lants ,as a ,ides#read #ractice ,ithin the 7eal industr6+ Bo,e7er: the 1ood and )rug Administration has not a##ro7ed gro,th #romotion im#lants $or use in $ood animals #resented $or slaughter as 7eal and considers their use to &e a 7iolation o$ the 1ederal 1ood: )rug: and !osmetic Act9+ This e am#le demonstrates that: contrar6 to ,hat the 8* has &een arguing &e$ore the %anel: a&use and(or misuse is a 9,ides#read #ractice in the 8* 7eal industr69+

12+ <t is: there$ore: im#erati7e that the 8*: instead o$ a7oiding the discussion &6 arguing that the E! has &ased its e7idence on unrealistic or h6#othetical e am#les: to engage $or once in a real discussion on the su&stance o$ the concrete e7idence #ro7ided &6 the E!+ 14+ The 8* comment (at #ara+ 13 o$ its re#l6 o$ 18 Octo&er 2002) and E hi&it 8*-28 con$irm the E! $indings+ E hi&it 8*- 28 con$irms that the author o$ the >e&3uidance (8ni7ersit6 o$ >e&ras=a) on re-im#lanting ,as himsel$ con$used and #er#le ed &6 the #ossi&le inter#retation o$ the >e&3uidance: as so man6 less-educated $armers ,ould undou&tedl6 ha7e &een $or so man6 6ears that the6 ha7e &een $ollo,ing it+ Be ne7ertheless agreed to #ro#ose to ma=e re7isions to it: &ut he still insisted that the corrections 9should not &e inter#reted as a change in our recommendations+9

'T()*320("(Add+3 %age !-31 18+ 1urthermore: it is im#ortant to note that the >e&3uidance is not the onl6 e am#le o$ concrete e7idence that recommends multi#le re-im#lanting+ E hi&it E!-14 e #lains on #age 0/ (,ith $urther citation o$ at least si scienti$ic #u&lications) that 9the manu$acturers; instructions #ro7ided ,ith the #re#arations: $or instance: do not contain an6 e #licit ,arning against multi#le a##lication+ E7en in the scienti$ic literature: re#eated or multi#le treatment o$ di$$erent com&ined #re#arations is o$ten recommended to achie7e o#timal results (/-9)9+ The 8* has not re#lied nor has it e7er contested the e7idence contained in these scienti$ic #u&lications+ 19+ The same a##lies to !anada;s comments+ E hi&it E!-14 states on #age 0/ (,ith concrete re$erence to scienti$ic literature) that: 9Misuse o$ tren&olone acetate in cal7es ,as re#orted in !anada (10)+ According to that stud6: in 1992(94: 1/J o$ 303 tested 7eal li7er sam#les contained more than 2 ng tren&olone-14a(g: and 0J e7en more than 10 ng(g9+ 20+ The 8* argues (at #aras+ 12 and 10 o$ its re#l6 o$ 18 Octo&er 2002) that the E! has $ailed to #ro7ide an6 e7idence that 7iolati7e residue le7els ,ould result e ce#t in the most e treme o7erdosing+ This is not correct+ The 1999 *!C%B o#inion contains Ta&le 2 on #age 30: ,hich sho,s as regards oestradiol-14I that the le7el o$ residues concentration in la,$ull6 treated animals according to 3C% e ceeds &6 se7eral times the le7el o$ concentrations o&ser7ed in untreated animals+ /1 Moreo7er: the stud6 &6 "+ *te#han6 2001 (AM%<* 109: 304-3/2) (see E hi&it E!-20: at #age *304) $ound that 2%'$ 0."2 $/% .%(*,'. US 2'.D%$ 1"#$'+#& "# '=%.'(% :.< $+2%& 2".% %&$."(%#& $/'# 2%'$ 0."2 *#$.%'$%d '#+2',&+ <$ the more recent data concerning the endogenous #roduction &6 #re-#u&ertal children are ta=en into account: such treatment according to 3C% alread6 leads to the A)< &eing e ceeded+ <t goes ,ithout sa6ing that multi#le im#lanting: ,hich necessaril6 leads to higher concentration o$ residues: ,ould ine7ita&l6 e ceed e7en $urther the recommended A)<s &6 AE!1A+ /2 21+ !ontrar6 to the 8* statements (at #ara+ 1/-10): &oth )r+ .oisseau and )r+ )e .ra&ander (to 5uestions /0: /2: /8) ha7e con$irmed that i$ 3C% is not res#ected: the A)<s and M"Ds &ecome useless and ris=s to human health are li=el6 to occur+ /3 8nli=e the 8* argument (and the re#l6 o$ )r+ .oo&is to 5uestion /8): the E! has #er$ormed a 5ualitati7e assessment and a 5uantitati7e assessment (to the e tent #ossi&le) o$ e #osure to residues in meat $rom animals treated not in accordance ,ith 3C%: e7en i$ a 5ualitati7e assessment alone ,ould ha7e &een su$$icient (see section 3+3: #ages 30-32 o$ the 1999 *!C%B: and E hi&it E!-43)+ Q<. I# +$& 1"22%#$& "# 1"22%#$& "0 $/% U#+$%d S$'$%& '#d C'#'d' "# %8-%.$& .%-,+%& $" $/% P'#%, ;*%&$+"#& ?+# -'.$+1*,'. Q*%&$+"# )3@5 $/% E*."-%'# C"22*#+$+%& +#d+1'$%& $/'$ "%&$.'d+", ):E 2+(/$ 3% ' 67%'D (%#"$"8+#6 ?-'.'. CC@. A$ 7/'$ d"&%& +& (%#"$"8+1+$4 "3&%.='3,% in vivo9 H"7 '.% $/%&% d"&%& 1"2-'.'3,% $" $/"&% 0"*#d +# 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ (."7$/ -."2"$+#( /".2"#%&9 H"7 7"*,d $/+& '&&%.$+"# '00%1$ $/% +d%#$+0+1'$+"# "0 'd=%.&% %00%1$& '#d $/% %=',*'$+"# "0 -"$%#$+', "11*..%#1% "0 $/%&% %00%1$& 0."2 1"#&*2-$+"# "0 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ "%&$.'d+", ):E 0". (."7$/ -."2"$+"# -*.-"&%&9 22+ The E! contests the 8* argument (at #ara+ 12) that the E! has #resented 9Eust one stud69 ,hich addresses genoto icit6 o$ estradiol-14I in vivo+ The 1999 *!C%B contains alread6 re$erence to one such stud6 (at #age /1: section /+1+4)+ The E! #ro7ided $our more studies ,hich discuss genoto icit6 in vivo on di$$erent animal tissues: see E hi&its E!-/8: 118: 121 and 120+ As regards E hi&it E!-120: the E! notes that the 8* has made incorrect assum#tions (at #aras+ 14-18) that are inconsistent ,ith the data #ro7ided &6 the E!: &ased on a su&stantial literature #u&lished o7er the last
The 1999 *!C%B o#inion contains similar e7idence $or the other natural hormones+ Another error o$ the 8* is to com#are the le7el o$ residues resulting $rom treatment according to 3C% ,ith the le7el o$ circulating oestradiol-14I in #regnant co,s+ This is ,rong &ecause in the E! #regnant co,s are not slaughtered $or human consum#tion+ /3 Moreo7er: des#ite the 8* argument to the contrar6: )r+ .oisseau stated (re#l6 to 5uestion 00) that $armers ha7e 9a tem#tation to use these hormones in a ,a6 di$$erent $rom the a##ro7ed ones+9
/2 /1

'T()*320("(Add+3 %age !-32 3 decades regarding the use o$ *ilastic ca#sules to administer hormones to e #erimental animals and ,omen+ The im#lant in *ilastic ca#sules $or ,omen ,as mar=eted as &eing e$$ecti7e $or u# to 0 6ears due to slo, release o$ the steroid ,hen it is #ac=ed into a ca#sule+ As the E! #ointed out: the dail6 release rate $rom a *ilastic ca#sule used in the Cavalieri et al. stud6 containing a total o$ 0 mg oestradiol: that is intended $or long-term studies and stead6-state release o7er a long #eriod o$ time: is a&out 1 microgram(=g(da6+ !learl6: the 8* assum#tion that the entire amount o$ oesttradiol-14I in the ca#sule (0 mg) is released each da6 cannot &e correct+ Another issue is that the 8* res#onse assigned a ,eight to rats o$ 200 mg: ,hich is the ,eight o$ a 7er6 6oung rat: and ,ould not &e the ,eight o$ a 2-4 months old rat &6 the end o$ a stud6: in ,hich the oestradiol-14I ,as administered to adult rats $or 1/0 da6s: as ,as done in the Cavalieri et al. stud6+ <n this regard: the E! estimate o$ a ,eight o$ 330 g is 7er6 conser7ati7e+ *ince the dose #er da6 is e #ressed relati7e to &od6 ,eight: &6 assuming an unrealisticall6 lo, &od6 ,eight: the 8* is attem#ting to ma=e it a##ear that the dail6 administered dose is higher than it reall6 is+ 'hen this is ta=en together ,ith the in7alid 8* assum#tion that a *ilastic ca#sule releases the entire amount loaded into it each da6 (,hich ,ould re5uire it &eing re$illed each da6): it is clear that the 8* calculations o$ the oestradiol-14I doses that result in mutagenesis are #ro$oundl6 $la,ed+ As the E! has e #lained ,ith its re#l6 o$ 18 Octo&er 2002: the mutagenic e$$ect in E hi&it E!-120 ,as &rought a&out at a dose ,hich is #otentiall6 ,ithin the 1000$old sa$et6 margin esta&lished $rom the lo,est o&ser7ed ad7erse e$$ect le7el (DOAED) on ,hich AE!1A;s A)< is &ased+// There$ore: the dose at ,hich in vivo genoto icit6 ,as o&ser7ed ,as not 9astronomicall6 higher9: nor 9e #onentiall6 greater9: nor 9massi7e9: as the 8* (and !anada) has ,rongl6 argued+ ?uite the o##osite: it is #"$ /+(/%. than the dose normall6 used in e #eriments $or the a##ro7al o$ chemical su&stances internationall6+ P'#%, Q*%&$+"#& $" $/% U#+$%d S$'$%& '#d C'#'d'> Q)G. W"*,d 4"* 1"#&+d%. $/'$5 0". $/% -*.-"&% "0 $/% DSU5 D+.%1$+=% 2003/:C/EC &/"*,d 3% =+%7%d '& ' #%7 2%'&*.% ". '& $/% 1"#$+#*'$+"# "0 $/% -.%=+"*& 2%'&*.% 0"*#d $" 3% +#1"#&+&$%#$ 7+$/ $/% WTO A(.%%2%#$5 &+#1% +$ &$+,, +2-"&%& ' 3'#9 23+ There can &e no dou&t that $ollo,ing the )*.;s rulings and recommendations a measure has &een ta=en &6 the E! to com#l6 ,ith+ 1or the #ur#oses o$ the )*8: there$ore: there e ists a ne, measure+ 2/+ 1irst: )irecti7e 2003(4/(E! un5uestiona&l6 is a ne, measure in that it came out o$ an entirel6 ne, legislati7e #rocess: in7ol7ing &oth the Euro#ean %arliament and the !ouncil o$ the Euro#ean 8nion as legislature+ *econd: the measure is &6 no means identical to the #re7ious measure+ <t $or the $irst time enacts a #ro7isional &an ,ith regard to all su&stances &ut oestradiol-14I: $urther restricts use $or thera#eutic and Footechnical #ur#oses and a&olishes all other e em#tions+ Third: and most im#ortantl6: the ne, )irecti7e is o&7iousl6 &ased on a ris= assessment ta=ing into account the most recent scienti$ic e7idence a7aila&le+ 20+ 'hether this ne, measure success$ull6 im#lements the rulings and recommendations o$ the )*. is a di$$erent 5uestion+ .oth !anada and the 8nited *tates seem to argue that it is the onl6 5uestion that matters $or the #ur#oses o$ assessing ,hether the6 are entitled to continue the sus#ension o$ concessions+ <n the Euro#ean !ommunities; 7ie, it is not+ <n the #resence o$ an o&7iousl6 ne, measure that has &een ado#ted in a trans#arent and good $aith e$$ort to im#lement the
The 8* attem#ts (at $ootnote 13 o$ its re#l6 o$ 18 Octo&er 2002) to diminish the im#ortance o$ the in vivo studies #er$ormed ,ith catechol meta&olites and re$ers to an alleged statement o$ )r+ MetFler: ,hich he has not made+ The im#ortant #oint a&out catechol meta&olites in treated meat is to note ,hat )r+ 3utten#lan has said (,ith his re#l6 to 5uestion 14): namel6 that the small amount o$ catechol meta&olites detected in meat $rom treated animals is e #lained &6 the $act that 9cattle do not e$$icientl6 meta&oliFe estradiol to catechols9: and that 9the lac= o$ catechols in meat does not im#l6 that meat $rom estrogen-treated cattle is ,ithout ris= $or genoto icit69+
//

'T()*320("(Add+3 %age !-33 )*. rulings and recommendations: Article 23 )*8 triggers an o&ligation on the original com#laining #arties to assess that ne, measure: to &ring a 21+0 #roceeding i$ the6 ta=e the 7ie, that the measure does not achie7e com#liance (and) or (to sus#end) to cease the sus#ension o$ concessions+ The latter o&ligation results $rom the $act that there is no multilateral determination that the ne, measure 7iolates or continues to 7iolate 'TO o&ligations+ <t $ollo,s that the &urden is on the 8* and !anada in the $irst #lace to demonstrate that the E! has not sol7ed the nulli$ication or im#airment through the ne, measure once noti$ied to the 'TO+ <ndeed: ha7ing $ollo,ed an o#en and trans#arent #rocedure $or the ela&oration and ado#tion o$ the ne, measure: ha7ing noti$ied it in accordance ,ith the #ro7isions o$ the 'TO(*%* Agreements: and ha7ing gi7en the de$ending mem&ers the o##ortunit6 to su&mit their comments all along: it is reasona&le to argue that the &urden is on them to esta&lish that the ne, E! measure does not sol7e the nulli$ication or im#airment+ An6 other inter#retation ,ould &e unreasona&le and ,ould go against the o&Eect: #ur#ose and structure o$ the 'TO Agreements &ecause it ,ould ena&le recalcitrant 'TO mem&ers to unla,$ull6 a$$ect international trade almost inde$initel6+ P'#%, Q*%&$+"#& $" $/% U#+$%d S$'$%&> Q)A. D"%& $/% U#+$%d S$'$%& '.(*% ' =+",'$+"# "0 A.$+1,% <.2 '#d "0 A.$+1,% <.F SPS9 I# "$/%. 7".d&5 d" 4"* %8-%1$ $/% P'#%, $" +&&*% 0+#d+#(& .%('.d+#( $/% 1"2-,+'#1% "0 D+.%1$+=% 2003/:C/EC 7+$/ $/"&% -."=+&+"#&9 W/'$ +& $/% -*.-"&% "0 $/% .%0%.%#1% $" A.$+1,% 2.2 SPS +# -'.'. 2: "0 $/% US .%3*$$', &*32+&&+"#9 22+ The Euro#ean !ommunities ta=es note o$ the 8nited *tates; re#l6 that the %anel ,ould &e re5uired to loo= onl6 at Articles 3+3: 0+1 (including an e amination o$ Article 0+2) and 0+4+ 24+ Moreo7er: as the E! has e #lained a&o7e ,ith its comments on the 8* re#l6 to 5uestion 2: the 8* is ,rong to argue that the E! has not &ased its measure on a ris= assessment ,ithin the meaning o$ Article 0+1 and 0+2 *%*+ The E! did conduct such a ris= assessment not onl6 $or oestradiol-14I &ut also $or the other $i7e hormones+ .ut $or the reasons e #lained se7eral times to the %anel: it could not com#lete the ris= assessment $or the $i7e hormones &ecause o$ the insu$$icienc6 o$ the rele7ant in$ormation and the im#ortant ga#s in our scienti$ic =no,ledge+ That is ,h6 it had to &ase its measure on Article 0+4 *%*+ <t should &e noted that Article 0+1 *%* #ro7ides that the measure is &ased on an assessment 9as a##ro#riate to the circumstances9: and Article 0+4 states that a more 9o&Eecti7e9 assessment o$ ris= ,ould &e #er$ormed once the missing #ertinent in$ormation is o&tained+ Q20. C"*,d $/% U#+$%d S$'$%& 1,'.+04 7/%$/%. +$& '.(*2%#$& .%('.d+#( ' =+",'$+"# "0 A.$+1,% 3.3 SPS '--,4 "#,4 +# .%,'$+"# $" $/% d%0+#+$+=% 3'# "# "%&$.'d+", ):E ". 7/%$/%. $/%4 '--,4 ',&" +# .%,'$+"# $" $/% -."=+&+"#', 3'# +2-"&%d "# $/% "$/%. 0+=% /".2"#%&9 28+ The Euro#ean !ommunities ,ould li=e to recall ,hat it has understood to &e the 8nited *tates re#resentati7e;s statement at the second su&stanti7e hearing+ Mme OroFco had as=ed ,hich !ode Alimentarius standards the 8nited *tates ,as rel6ing on $or the #ur#oses o$ its Article 3+3 claim+ <n re#l6 to this 5uestion the 8nited *tates re#resentati7e re$erred onl6 to the standards ado#ted $or testosterone: #rogesterone: Feranol and tren&olone acetate+ >o mention ,as made o$ the standard $or oestradiol-14I+ 29+ Moreo7er: the 8* states (at #aras+ 24-28) a num&er o$ times that it has demonstrated that the E! has $ailed to #ro7ide a scienti$ic Eusti$ication+ The E! does not agree that the 8* has managed to discharge its &urden o$ #roo$+

'T()*320("(Add+3 %age !-3/ EC Q*%&$+"#& $" U#+$%d S$'$%& '#d C'#'d'> Q). P,%'&% %8-,'+#5 +0 -"&&+3,% +# d%$'+,5 7/'$ D+#d "0 &1+%#$+0+1 %=+d%#1% "# %8-"&*.%I '&&%&&2%#$ 0."2 .%&+d*%& +# 2%'$ $.%'$%d 7+$/ $/% &+8 /".2"#%& 0". '#+2', (."7$/ -."2"$+"# 7'& *&%d 34 $/% U#+$%d S$'$%& '#d C'#'d' 7/%# $/%&% &*3&$'#1%& 7%.% '*$/".+&%d9 W'& $/+& %8-"&*.% '&&%&&2%#$ ' ;*'#$+$'$+=% "#%9 P,%'&% -."=+d% 1"#1.%$% .%0%.%#1% $" &$*d+%& *&%d +# 4"*. %8-"&*.% '&&%&&2%#$ '#d5 +0 -"&&+3,%5 $" $/"&% "0 LECFA 0". $/% &+8 /".2"#%& +# ;*%&$+"# ?+# 1'&% 4"* D#"7 $/% .%0%.%#1%&@. 30+ The 8* states (at #ara+ 3 o$ its 18 Octo&er 2002 re#l6) that the 8* 1)A 9re5uired the s#onsors to conduct e tensi7e residue studies9+ These residues studies ha7e ne7er &een #u&lished and the E! has ne7er &een gi7en a co#6 $ro re7ie,: ,hereas the 8* has had access to the more recent (same or similar) studies conducted &6 the E!+ 31+ The 8* re#l6 (at #ara+ 0) con$irms that the 8* 1)A did #"$ esta&lish an A)< $or the three natural hormones+ Most im#ortantl6: it also con$irms that no e tensi7e to icological testing in e #erimental animals has &een #er$ormed+ <n other ,ords: it con$irms that the 8* has not #er$ormed the $ull &atter6 o$ to icological testing in order to decide ,hether these hormones are carcinogenic and(or genoto ic+ <t also con$irms that the 9#ermitted increased dail6 e #osures9 set &6 the 8* 1)A are &ased on the assum#tion - and no more than an assum#tion - that 9the amounts o$ these hormones #resent in edi&le tissues o$ treated cattle ,ere $ound to &e 7er6 small relati7e to the endogenous #roduction in humans9+ <n other ,ords: the 8* admits that it has not carried out the =ind o$ 5uantitati7e e #osure assessment o$ residues in hormone-treated meat: ,hich it no, accuses the E! $or not ha7ing #er$ormed+ The realit6: there$ore: is that the 8* 9 permitted increased dail1 exposures9 are &ased on sim#listic and scienti$icall6 unsound e tra#olations and assum#tions: not on sound scienti$ic e #eriments+ 32+ The 8* re$ers (at #ara+ 2 o$ its re#l6 o$ 18 Octo&er 2002) to the 9e #osure assessment conducted &6 AE!1A9: thus again admitting im#licitl6 that it has itsel$ not conducted such an e #osure assessment $rom residues in hormone-treated meat+ Bo,e7er: as the E! has e #lained se7eral times to the %anel: AE!1A has not conducted such an e #osure assessment either+ 'hat AE!1A has done so $ar ,as to re7ie, the old residues de#letion studies $rom the 1940s #ro7ided to it con$identiall6 &6 the 8* #harmaceutical industr6 (see e+g+ E hi&its !A>-14 $or the three natural hormones and the similar studies $or the other three s6nthetic hormones) and esta&lished the A)< on the &asis o$ assum#tions: e tra#olations and sa$et6 $actors+ .ut the E! has also #er$ormed and made a7aila&le to the #u&lic residues de#letion studies $or all these hormones similar to those used &6 AE!1A+ Moreo7er: the E! has in addition made an e #osure assessment: ,hich )r+ 3utten#lan e #lained in his re#l6 to 5uestions 02 and 00: as $ollo,s: 9calculations are #resented (E! re&uttal: #ara+ 122) that suggest that e7en ,ith lo, #ercentages o$ &ioa7aila&ilit6 o$ estrogen: the le7els in meat could result in &ioa7aila&le estrogen e ceeding the dail6 #roduction rate o$ oestradiol in #re#u&ertal children9+ The 8* re#l6 sho,s that it has not done so+ 33+ 1inall6: the 8* and !anada;s re#lies cannot hide &ehind the argument that AE!1A has #er$ormed a 5uantitati7e e #osure assessment: &ecause the data claimed to &e used &6 AE!1A are the same data o$ the 1940s #ro7ided &6 the #harmaceutical industr6 during the authorisation #rocedure in the 8*+ Q2. P,%'&% +#d+1'$%5 +0 -"&&+3,% +# d%$'+,5 7/%$/%. 4"*. .+&D '&&%&&2%#$&5 '#d +0 4"* D#"7 $/"&% "0 LECFA5 "0 $/% &+8 /".2"#%& +# ;*%&$+"# 0". '#+2', (."7$/ -."2"$+"# /'=% '$$%2-$%d $" 1',1*,'$% $/% .+&D $" /*2'#& 0."2 $/% 'dd+$+"#', %8-"&*.% .%&*,$+#( 0."2 $/% .%&+d*%& +# /".2"#%I$.%'$%d 2%'$ 7/%# *&%d '11".d+#( $" G P '#d 7/%# G P +& #"$ .%&-%1$%d. W'& +$ ' ;*'#$+$'$+=% %8-"&*.% '&&%&&2%#$9 I0 &"5 -,%'&% -."=+d% $/% -.%1+&% .%0%.%#1% $" $/% d'$'. ?P,%'&% #"$% $/'$ 7% '.% #"$ .%0%..+#( /%.% $" .%&+d*%Id%-,%$+"# &$*d+%& 1"#$'+#%d +# CAN E8/+3+$I):5

'T()*320("(Add+3 %age !-30 &+#1% $/% EC /'& ',&" 1"#d*1$%d &*1/ .%&+d*%& d%-,%$+"# &$*d+%& 0". +$& )AAAI2002 .+&D '&&%&&2%#$&@. 3/+ The 8* re#l6 (at #aras+ 4-12) con$irms once again: as e #lained a&o7e: that the 8* has not attem#ted to calculate itsel$ the ris= to humans $rom the additional e #osure to residues $rom hormone-treated meat+ <t re$ers to the AE!1A monogra#hs: ,hich do not contain an e #osure assessment: ,hich is not di$$erent $rom that #er$ormed &6 the E!: ,ith the nota&le di$$erence that the E!;s assessment is &ased on more recent: #u&licl6 a7aila&le and #eer-re7ie,ed scienti$ic data+ 30+ The same comment a##lies to the re#l6 o$ !anada+ !anada $orgets that e #osure to &ac=ground (endogenous) le7els alone o$ the natural hormones has alread6 $ound to cause cancer in humans and ina##ro#riatel6 assumes: li=e AE!1A: that the additional e #osure $rom the residues in meat ,ould not increase the ris=+ !anada: li=e the 8*: $orgets that the E! has demonstrated (see: e+g+: the stud6 &6 "+ *te#han6 2001: AM%<* 109: 304-3/2: E hi&it E!-20) that meat $rom the regular 8* mar=et contains on a7erage 4+0 times more estrogens than meat $rom untreated animals and that: e7en ,ithout misuse: the A)<s esta&lished &6 AE!1A ,ill &e e ceeded i$ the most recent 7alues o$ endogenous #roduction &6 #re-#u&ertal children is ta=en into account+ Q3. T/% EC *#d%.&$'#d& $/'$ &"2% "0 $/% %8-%.$& ?D.&. G*$$%#-,'#5 S+--%, '#d C"(,+'#"@ /'=% &$'$%d $/'$ +$ +& #"$ -"&&+3,% $" d%$%.2+#% 7+$/ '11*.'14 $/% d"&%I.%&-"#&% 1*.=% '$ $/% =%.4 ,"7 ,%=%,& "0 %8-"&*.% 0."2 $/%&% /".2"#%& +# (%#%.', '#d 7/%# *&%d 0". '#+2', (."7$/ -."2"$+"#. D" 4"* '(.%% 7+$/ $/%&% &$'$%2%#$&9 I0 #"$5 1"*,d 4"* -,%'&% -."=+d% $/% -.%1+&% .%0%.%#1%& $" &1+%#$+0+1 &$*d+%& 7/%.% $/+& /'& 3%%# d"#%9 W/'$ 7"*,d 3% $/% +2-,+1'$+"#& "0 $/+& +2-"&&+3+,+$4 0". $/% #%%d $" -%.0".2 ' ;*'#$+$'$+=% ". ;*',+$'$+=% %8-"&*.% '&&%&&2%#$ 0". $/%&% /".2"#%& 7/%# *&%d 0". '#+2', (."7$/ -."2"$+"#9 32+ The E! notes $irst that the 8* does not correctl6 re#resent (at #ara+ 1/ o$ its re#l6) the statement &6 )r+ 3utten#lan at the meeting o$ the %anel ,ith the e #erts+ <n that meeting: )r+ 3utten#lan stated (as did three other scientists) that: in his 7ie,: there ,ill &e a ris= (,hich ,ill &e not Fero &ut a small one) caused $rom the residues in meat $rom animals treated ,ith these hormones $or gro,th #romotion+ The same a##lies to the comment &6 !anada (at #ara+ 9 o$ its re#l6)+ 34+ 1urthermore: the 8* gi7es credit to the statement &6 )r+ .oo&is that the 9carcinogenic e$$ects a##ear to &e a conse5uence o$ its endocrine acti7it69: ,hen the 8* admits that no long-term carcinogenicit6 studies ha7e &een #er$ormed ,hen it a##ro7ed these hormones $or gro,th #romotion+ 38+ 1urthermore: !anada argues (at #ara+ 10 o$ its re#l6) that the statements &6 )r+ *i##el and )r+ !ogliano 9must 6ield to the e #ert ad7ice o$ those ,ho are 5uali$ied to e7aluate actual carcinogenic #otential at lo, doses9+ Bo,e7er: !anada $orgets that &oth )r+ .oisseau and )r+ .oo&is are the same #ersons ,ho ha7e #artici#ated in the ela&oration o$ the AE!1A re#ort and: moreo7er: )r+ .oisseau admitted that he has ne7er carried an6 to icological e #eriment ,ith these hormones himsel$+ QC. I0 4"* 7%.% $" '(.%% $/'$ &1+%#$+&$& 1'##"$ d%0+#% $/% d"&%I.%&-"#&% 1*.=% '& %8-,'+#%d +# $/% -.%=+"*& ;*%&$+"#5 7"*,d $/+& &$'$% "0 &1+%#$+0+1 D#"7,%d(% 3% d%0+#%d '& 6&1+%#$+0+1 *#1%.$'+#$46 +# $/+& '.%'9 I0 #"$5 -,%'&% %8-,'+#. 39+ The 8* re#l6 (at #aras+ 10-12) is another distraction &6 re$erring to 9theoretical ris=9: ,hen the scientists agreed that the dose-res#onse cur7e at lo, dose in the case o$ these hormones cannot &e de$ined+ Moreo7er: gi7en that in the calculations o$ the 8* and AE!1A the e istence o$ a threshold &elo, ,hich ad7erse e$$ect is alleged not to occur is a &asic assum#tion: the E! 5uestion does not #ertain to a theoretical ris= &ut to a 7er6 real and undis#uted one+ The 8* and !anada (li=e AE!1A) ha7e not managed to e #lain ho, is it #ossi&le to esta&lish a no hormonal e$$ect le7el ,hen the

'T()*320("(Add+3 %age !-32 scientists ignore the real dose-res#onse cur7e o$ these su&stances ,hen used $or gro,th #romotion #ur#oses+ /0+ <n addition: !anada #laces (at #ara+ 12) on the same side )rs+ .oo&is: .oisseau and 3utten#lan: ,hen the latter clearl6 stated in the hearing that the ris= $rom residues in hormone-treated meat is small (&ut not Fero) and )r+ .oissaeu admitted that he has no s#eci$ic =no,ledge as he has ne7er carried an6 e #eriment ,ith these hormones+ Q<. C"*,d 4"* -,%'&% %8-,'+# 7/'$ +& 4"*. -"&+$+"# "# $/% %8+&$%#1% ". #"# %8+&$%#1% "0 '# +#$%.#'$+"#', &$'#d'.d 0". MGA 0". $/% -*.-"&%& "0 A.$+1,%& 25 3 '#d < "0 $/% SPS A(.%%2%#$ +# $/%&% d+&-*$%&9 /1+ !anada argues that 9other agencies and health authorities ha7e conducted similar assessments and ha7e come to the same conclusion9: &ut $ails to mention ,hich are these other agencies and authorities nor does it #ro7ide co#6 o$ their assessments+ <$ !anada im#lies that these other authorities are the agencies o$ the 8* and !anada: the E! ,ould &e 7er6 ha##6 to recei7e co#6 o$ their assessments and the underl6ing studies on ,hich the6 are &ased $or re7ie,+ <ndeed: the E! urges !anada to su&mit such assessments: i$ the6 reall6 e ist: to the %anel $or re7ie,+ EC Q*%&$+"#& $" $/% U#+$%d S$'$%&> Q). T/% 2002 US R%-".$ "# C'.1+#"(%#%&+& ?E8/+3+$ ECI)0)@ &$'$%& +#$%. ',+' $/'$> 6=%$%.+#'.4 *&% "0 &$%."+d', %&$."(%#& ?$" -."2"$% (."7$/ '#d $.%'$ +,,#%&&%&@ 1'# +#1.%'&% %&$."(%#& +# $+&&*%& "0 0""d -."d*1+#( '#+2',& $" '3"=% $/%+. #".2', ,%=%,&6 ?-.G@. H"7 d" 4"* .%1"#1+,% $/+& 7+$/ 4"*. -."-"&+$+"# +# -'.'. <) "0 4"*. F+.&$ W.+$$%# S*32+&&+"#9 /2+ The E! notes that the 8* is selecti7el6 5uoting $igures $or di$$erent (male or $emale) animals and at di$$erent #h6siological state (#regnant or not) is order to sustain its claim that the residues are ,ithin the range o$ naturall6 o&ser7ed le7els+ Bo,e7er: the 8* does not discuss the other e7idence #resented &6 the E! sho,ing that 2%'$ 0."2 $/% .%(*,'. US 2'.D%$ contains on a7erage 4+0 times more estrogens than meat $rom untreated animals (see E hi&it E!-20: at #age 304: and the ta&les 2: 0 and 4 o$ the 1999 *!C%B o#inion)+ 1urthermore: the 8* =ee#s com#aring the residues $rom treated animals ,ith the le7els o$ residues in #regnant cattle: ,hen the E! has e #lained to the %anel that such #regnant cattle are #racticall6 not slaughtered $or human consum#tion in the E!+ /0 %regnant co,s: there$ore: are not the a##ro#riate com#arator+ Q2. W/'$ 7'& $/% .%'&"# $" 1"#1,*d% 0". $/% 0+.&$ $+2% +# $/% 2002 US R%-".$ "# C'.1+#"(%#%&+& $/'$ %&$."(%#& ?+#1,*d+#( "%&$.'d+",I):E@ '.% 1'.1+#"(%#+1 #"$ "#,4 34 .%1%-$".I 2%d+'$%d %00%1$& 3*$ $/'$ +# 'dd+$+"# $/%.% '.% -"&&+3,4 34 d+.%1$ '#d +#d+.%1$ (%#"$"8+1 2"d% "0 '1$+"#9 W'& +$ 3%1'*&% "0 #%7 d%=%,"-2%#$& +# &1+%#$+0+1 .%&%'.1/ $/'$ 3%1'2% '='+,'3,% '0$%. )AAA9 /3+ The E! considers that the 8* re#l6 (at #ara+ 22 and $ootnote 1/) con$irms that oestradiol-14I has mo7ed $rom 9reasona&l6 antici#ated to &e human carcinogen9 in 1980 to &e listed $or the $irst time in 2002 as 9=no,n to &e a human carcinogen9+ Moreo7er: the 2002 8* "o! lin=s $or the $irst time the ris= o$ cancer to residues in meat $rom animals treated ,ith this hormone $or gro,th
<n an6 case: the 8* argument is also $actuall6 not entirel6 correct &ecause T'3,% 2 o$ the 1999 *!C%B o#inion (at #age 30) #ro7ides data sho,ing that the concentration o$ E2 (oestradiol-14 I) residues in muscle o$ treated hei$ers (30 da6s) according to 3C% are slightl6 higher (33+2 ng(=g) than the 7alues $or untreated #regnant hei$ers (32+4 ng(=g)+ The same a##lies to $at tissue: 82+4 ng(=g in treated hei$ers com#ared to42+0 ng(=g in untreated #regnant hei$ers: ,hilst the 7alues $or =idne6 are not su&stantiall6 di$$erent+ Moreo7er: the E! has sho,n that misuse or a&use o$ these hormones leads ine7ita&l6 to much higher concentration o$ residues in treated meat+
/0

'T()*320("(Add+3 %age !-34 #romotion+ The 8* claims (at #aras+ 23-2/) that the 2002 8* "o! is not e7idence o$ a ris= $rom meat $rom cattle treated ,ith estradiol $or gro,th #romotion+ Bo,e7er: the 8* cannot ma=e this claim &ecause it has not #er$ormed the necessar6 e #eriments '0$%. the 2002 "o! has declared oestradiol14I a #ro7en human carcinogen &6 direct genoto ic action+ All the assessment ,hich the 8* claims to ha7e #er$ormed $or these hormones $or gro,th #romotion date $rom the 1940s+ !on7ersel6: as the re#lies o$ )r+ !ogliano and )r+ 3utten#lan to %anel 5uestion 22 ha7e esta&lished: the data used &6 the E! to esta&lish such an association are 9at least consistent ,ith a #ossi&le e$$ect o$ hormones on &reast and #rostate cancer9+ There$ore: the 8* has $ailed to #ro7ide &etter e7idence to the one used &6 the E!+ Q3. T/% 2002 US R%-".$ "# C'.1+#"(%#%&+& &$'$%& +#$%. ',+' $/'$> 6T/% R"C d"%& #"$ -.%&%#$ ;*'#$+$'$+=% '&&%&&2%#$& "0 $/% .+&D& "0 1'#1%. '&&"1+'$%d 7+$/ $/%&% &*3&$'#1%&. T/*& ,+&$+#( "0 &*3&$'#1%& +# $/% R"C "#,4 +#d+1'$%& ' -"$%#$+', /'J'.d '#d d"%& #"$ %&$'3,+&/ $/% %8-"&*.% 1"#d+$+"#& $/'$ 7"*,d -"&% 1'#1%. .+&D& $" +#d+=+d*',& +# $/%+. d'+,4 ,+=%&. S*1/ 0".2', .+&D '&&%&&2%#$& '.% $/% .%&-"#&+3+,+$4 "0 $/% '--."-.+'$% 0%d%.',5 &$'$%5 '#d ,"1', /%',$/ .%(*,'$".4 '#d .%&%'.1/ '(%#1+%&.6 I0 &"5 /'=% $/% 1"2-%$%#$ US '*$/".+$+%& 2'd% $/% ;*'#$+$'$+=% '&&%&&2%#$ "0 $/% .+&D& "0 1'#1%. -"&%d 34 $/% .%&+d*%& "0 &+8 /".2"#%& +# 2%'$ 0."2 '#+2', $.%'$%d 0". (."7$/ -."2"$+"#9 I0 #"$5 7/%# '.% 4"* ("+#( $" d" +$9 //+ The E! notes that the 8* has care$ull6 a7oided (at #ara+ 20) to re#l6 to this crucial 5uestion+ Bo#e$ull6 the %anel ,ill &e a&le to dra,: to the e tent #ossi&le: the necessar6 in$erences+ /0+ The 8* statement (at #ara+ 22) ina##ro#riatel6 do,n#la6s the im#ortance o$ e7idence coming $rom e#idemiological studies+ <n an6 case: the 2002 8* "o! is not &ased onl6 on e#idemiological e7idence: &ut also on the re#orted results $rom to icological and carcinogenicit6 studies: as is the #a#er &6 %ro$essors Diehr and Hager mentioned therein to demonstrate direct genoto icit6+ /2+ that: The 8* $or the $irst time admits (at #ara+ 24) ,hat the E! has al,a6s &een arguing: namel6 9assessment o$ the ris=s to human health associated ,ith the use o$ se steroids in $ood-#roducing animals #resents uni5ue challenges due to the $act that e #osure to the com#ound occurs against a &ac=ground le7el o$ endogenous #roduction in all segments o$ the #o#ulation9+ /4+ As the E! mentioned a&o7e ,ith its comments on the 8* re#l6 to 5uestion 1 $rom the E!: the 8* has not conducted e tensi7e to icological testing: as should ha7e done: and &ased its 9#ermitted increased e #osure9 on #ure assum#tions and sim#listic e tra#olations+ <ndeed: the 8* assumed that residues in hormone-treated meat ,ould add 7er6 little to the endogenous #roduction &6 humans+ .ut the 8* assum#tion ignores the $act that e #osure to &ac=ground (endogenous) le7els o$ oestrogens alread6 causes cancer in humans and an6 $urther addition to such e #osure $rom e ogenous sources is going ine7ita&le to increase the li=elihood o$ causing cancer+ This is all the more so since the scientists do not =no, ,hat is the dose-res#onse cur7e $rom lo, e #osure to these hormones in order to esta&lish a sa$e threshold+ QC. T/% 2002 US R%-".$ "# C'.1+#"(%#%&+& &$'$%& +#$%. ',+' $/'$> 6E&$+2'$+#( $/% %8$%#$ $" 7/+1/ ,+&$+#( ' &*3&$'#1% +# $/% R"C -."$%1$& -*3,+1 /%',$/ +& -%./'-& $/% 2"&$ d+00+1*,$ $'&D +# -.%-'.+#( $/% R"C. T/% 1'.1+#"(%#+1 .+&D ?+.%.5 $/% -."3'3+,+$4 "0 d%=%,"-+#( 1'#1%.@ d%-%#d& "# 2'#4 $/+#(&5 +#1,*d+#( $/% +#$%#&+$45 ."*$%5 '#d d*.'$+"# "0 %8-"&*.% $" ' 1'.1+#"(%#. P%"-,% 2'4 .%&-"#d d+00%.%#$,4 $" &+2+,'. %8-"&*.%&5 d%-%#d+#( "# $/%+. '(%5 &%85 #*$.+$+"#', &$'$*&5 "=%.',, /%',$/5 (%#%$+1&5 '#d 2'#4 "$/%. 0'1$".&. O#,4 +# ' 0%7 +#&$'#1%& 1'# .+&D 0". 1'#1%. 3% %&$+2'$%d 7+$/ 1"2-,%$% 1"#0+d%#1%5 '#d $/%&% %&$+2'$+"#& .%;*+.% &$*d+%& "0 ,"#(I$%.2 /*2'# %8-"&*.%& '#d 1'#1%. +#1+d%#1% +# .%&$.+1$%d %#=+."#2%#$&5 7/+1/ .'.%,4 '.% '='+,'3,%.6 D%&-+$%

'T()*320("(Add+3 %age !-38 $/+& .%1"(#+$+"# "0 $/% d+00+1*,$+%&5 1"*,d 4"* -,%'&% %8-,'+# +0 4"* /'=% #%=%.$/%,%&& -%.0".2%d $/% ,"#(I$%.2 /*2'# %8-"&*.%& $" $/% .%&+d*%& "0 $/%&% /".2"#%& +# $.%'$%dI2%'$ +# ".d%. $" ;*'#$+04 +0 $/%4 -"&% ' .+&D $" /*2'# /%',$/9 D" 4"* D#"7 +0 LECFA /'& -%.0".2%d &*1/ ' &-%1+0+1 ;*'#$+$'$+=% d"&%I.%&-"#&% '&&%&&2%#$9 /8+ The E! argues that the a&o7e-mentioned 5uotation $rom the 2002 8* "o! con$irms its arguments that a 5uantitati7e e #osure assessment is not reall6 #ossi&le and the 8* (and !anadian) criticism in this regard is un$ounded+ Q<. I# .%,'$+"# $" -'.'. G "0 $/% US &$'$%2%#$ "0 3 O1$"3%. -,%'&% %8-,'+# +0 4"* /'=% #"7 2'd% ' d%$%.2+#'$+"#9 I0 #"$5 7/'$ d"%& +$ 2%'# 63%+#( +# $/% -."1%&& "0 .%=+%7+#(9 W/'$ '.% 4"* d"+#( %8'1$,49 S+#1% $/% EC!& .+&D '&&%&&2%#$ d'$%& "0 )AAA ?'#d .%=+%7%d '#d 1"#0+.2%d +# 2000 '#d 2002@5 /"7 ,"#( +& 4"*. .%=+%7 -."1%&& ("+#( $" $'D%9 I& $/%.% '#4 +#0".2'$+"# $/'$ $/% US +& #"7 2+&&+#(9 I& $/%.% '#4 2%1/'#+&2 34 7/+1/ $/% US 7+,, 1"2-,%$% +$& .%=+%7 7+$/+# ' .%'&"#'3,% -%.+"d "0 $+2% #"79 /9+ The E! considers that the 8* re#l6 con$irms that it has not 6et com#leted its re7ie, and: a##arentl6: is not li=el6 to com#lete it an6 time soon+ QF. T/% US &$'$%d $/'$ $/% .+&D '&&%&&2%#$& -%.0".2%d 34 LECFA 2*&$ 3% -.%&*2%d $" 3% +# 1"2-,+'#1% 7+$/ A.$+1,% <.). "0 $/% SPS A(.%%2%#$. B*$ $/% .+&D '&&%&&2%#$& -%.0".2%d 34 LECFA 0". $/%&% /".2"#%& 0". '#+2', (."7$/ -."2"$%.& d" #"$ 1"#$'+# $/% D+#d "0 ;*'#$+$'$+=% ". ;*',+$'$+=% %8-"&*.% '&&%&&2%#$ $/'$ C'#'d' '#d $/% US 1.+$+1+&% $/% EC 0". #"$ /'=+#( d"#%. N%=%.$/%,%&&5 $/% US '#d C'#'d' '--%'. $" '&&*2% $/'$ LECFA!& '&&%&&2%#$& '.% 1"#&+&$%#$ 7+$/ A.$+1,% <.). SPS. P,%'&% %8-,'+# 7/4 *#d%. $/%&% 1+.1*2&$'#1%& 7"*,d $/% EC!& .+&D '&&%&&2%#$ 3% +#1"#&+&$%#$ 7+$/ A.$+1,% <.). "0 $/% SPS A(.%%2%#$. 00+ The E! notes that the 8* #ro7ides a general re#l6 ,ithout an6 arguments nor s#eci$ic re$erence to the documents sho,ing that AE!1A did the =ind o$ e #osure assessment ,hich the 8* accuses no, the E! $or not ha7ing #er$ormed+ As the E! has e #lained se7eral times (see: e+g+: E! Oral statement o$ 3 Octo&er 2002: at #aras+ /-0): the =ind o$ 5uantitati7e e #osure assessment: claimed to ha7e &een done &6 the de$ending mem&ers: cannot &e #er$ormed+ EC Q*%&$+"#& $" C'#'d'> Q). I# .%,'$+"# $" 4"*. %8'2-,% 0". $/% "%&$."(%# ,%=%, +# -.%(#'#$ 7"2%# ?-'.'. <3 "0 4"*. O.', S$'$%2%#$@ 1"*,d 4"* -,%'&% 1"22%#$ "# E8/+3+$ ECI<F 7/%.% $/%.% +& %=+d%#1% $/'$ in utero %8-"&*.% $" "%&$.'d+", /'& (+=%# .+&% $" ' #*23%. "0 '3#".2',+$+%& '#d &*&-%1$%d "0 '# +#1.%'&%d .'$% "0 1'#1%.9 A&&*2+#( $/'$ $/+& 0+#d+#( +& .%,'$%d $" $/% ,"7Id"&% .%&-"#&% *#1%.$'+#$45 d" 4"* /'=% '#4 %=+d%#1% $/'$ $/% 2#( 'dd%d $" %#d"(%#"*& "%&$."(%#& -."d*1$+"# '.% #"$ ,+D%,4 $" /'=% '#4 &*1/ %00%1$9 01+ The E! notes that !anada;s re#l6 is t6#ical o$ the unscienti$ic assum#tions and sim#listic arguments it has &een ma=ing all along in this dis#ute+ The E! does not #retend to ha7e $ound the ultimate truth+ The stud6 in E hi&it E!-02 &uilds on e isting scienti$ic literature ,hich #ostulates that 9the ris= o$ &reast cancer is in$luenced &6 hormonal e #osure in utero9+ This #ro#osition is not ne, (see the $irst $i7e re$erences to scienti$ic literature #ro7ided in E hi&it E!-02)+ The E! stud6 #ro7ides $urther su##ort to e isting scienti$ic e7idence+ 02+ The sim#listic argument o$ !anada is to state that 9as a result o$ the homeostatic control mechanism: endogenous #roduction is adEusted to ta=e into account e ogenous e #osure+ Thus: the lo, dose e ogenous oestradiol to the mother does not translate into lo, dose to the $oetus+9 The #oint is that !anada has no scienti$ic &asis to ma=e the sim#listic assum#tion that the adEustment ,ill ta=e

'T()*320("(Add+3 %age !-39 #lace or that it ,ill ta=e #lace in all cases+ E5uall6: !anada has no scienti$ic &asis to argue that a 2ng added to endogenous oestrogens #roduction are not li=el6 to ha7e an6 ad7erse e$$ect+ All the E! is sa6ing on this #oint is that ,e do not =no,: and !anada =no,s no &etter+ .ut ,hat ,e do =no, is that the e #eriment in 5uestion #ro7ides $urther su##ort to e isting e7idence that hormonal e #osure in utero in$luences the ris= o$ &reast cancer+ !anada o&7iousl6 does not &elie7e that e #osure to lo, le7el o$ residues in treated meat is li=el6 to cause cancer+ .ut this &elie$ is &ased on mere intuition: not scienti$ic #roo$: &ecause the e #erts o$ the %anel ha7e con$irmed that the dose-res#onse cur7e $rom lo, e #osure cannot &e esta&lished $or these su&stances+ Q2. A& .%('.d& $/% .%0%.%#1% $" C'.3'd"8 ?&%% -'.'. F: "0 C'#'d'!& ".', &$'$%2%#$ "0 3 O1$"3%.@> C"*,d 4"* -,%'&% %8-,'+# 3.+%0,4 7/'$ /'--%#%d '#d 7/'$ 7%.% $/% .%'&"#& 0". 7/+1/ 4"* /'=% 1/'#(%d 4"*. .+&D '&&%&&2%#$ 0". C'.3'd"89 W'& +$ &+2-,4 "# $/% (."*#d $/'$ C'.3'd"8 7'& 0"*#d $" 3% (%#"$"8+1 ". 7'& +$ 3%1'*&% 4"* /'=% 1'..+%d "*$ 3%0".% ' ;*'#$+$'$+=% ". ;*',+$'$+=% %8-"&*.% '&&%&&2%#$ 0". $/% .%&+d*%& +# -".D 2%'$ $.%'$%d 7+$/ C'.3'd"89 03+ The re#l6 o$ !anada a7oids addressing the crucial #oint: namel6 ,h6 did it need almost ten 6ears to admit ,hat the E! has &een arguing since 1992: namel6 that the meta&olites o$ !ar&ado are carcinogenic and genoto ic+ 'hat !anada calls no, 9ne, in$ormation9 ,as a7aila&le at the time o$ the $irst hormones #anel in 1992: ,here !anada ,as still authorising !ar&ado and ,as strongl6 arguing that the E! has &een acting inconsistentl6+ <$ !anada is ,illing to =ee# ma=ing the same =ind o$ mista=e $or these hormones as it did $or !ar&ado at the time $or the sa=e o$ some small economic &ene$it: the E! is not #re#ared to sacri$ice its high le7el o$ health #rotection+

'T()*320("(Add+3 %age !-/0 ANNEX C3 REPLIES OF THE UNITED STATES TO QUESTIONS POSED BY THE PANEL AFTER THE SECOND SUBSTANTI E MEETING (18 Octo&er 2002) Q*%&$+"#& $" ',, -'.$+%& Q). W+$/ .%0%.%#1% $" $/% &$'$%2%#$ 34 $/% E*."-%'# C"22*#+$+%&5 +#$%. ',+' +# -'.'. )2 "0 $/% EC .%-,4 $" Q*%&$+"# 3 "0 $/% U#+$%d S$'$%&5 d" $/% -'.$+%& 1"#&+d%. $/'$ ' P'#%, +& %#$+$,%d $" 'dd.%&& 6&4&$%2+1 1,'+2&6 ". +&&*%& .%,'$%d $" 6&4&$%2+1 "3,+('$+"#&6 '#d5 +0 &"5 $" 7/'$ %8$%#$9 1+ As noted in 8* ?uestion 3 to the Euro#ean !ommunities (9E!9): 9s6stemic9 and 9direct9 are terms used &6 the E! to descri&e its claims against the 8nited *tates+ /2 Each o$ the E!;s 9in conEunction ,ith9 claims: through ,hich it see=s to recast se7eral #ro7isions o$ the Understanding on *ules and Procedures %overning t e Settlement o$ <isputes (9)*89): are couched as 9s6stemic9: ,hile the E! claim o$ a 8* &reach o$ )*8 Article 22+8 (in and o$ itsel$) is descri&ed &6 the E! as a 9direct claim+9 >either o$ these terms a##ears in the )*8: nor are the6 #art o$ customar6 rules o$ inter#retation o$ #u&lic international la,: as re$lected in Articles 31 and 32 o$ the Cienna !on7ention on the Da, o$ Treaties+ 2+ The 5uestion is not one o$ ,hether the E! has characteriFed one o$ its claims as 9s6stemic9 or 9direct9+ <ndeed: it is unclear ,hat: e actl6: the E! means ,hen it uses these terms: other than to indicate in the case o$ a 9s6stemic9 claim that it is una&le to identi$6 a #articular o&ligation in a s#eci$ic #ro7ision o$ the )*8 ,hich the 8nited *tates had allegedl6 &reached+ "ather: it is the role o$ the %anel to e amine the actual o&ligations set out in the )*8 as it is currentl6 dra$ted: and to anal6Fe the arguments o$ the 8nited *tates and the E! in light o$ those o&ligations+ An6 E! claim must &e grounded in the actual te t o$ the )*8+ As the 8nited *tates has argued in se7eral o$ its #re7ious su&missions: the E! claims ,hich it terms 9s6stemic9 merel6 re$lect ho, the E! ,ould li=e to see the )*8 redra$ted: at least $or #ur#oses o$ this dis#ute+ Through its 9s6stemic9 claims: the E! see=s license to de#art $rom the agreed te t o$ the )*8 so as to insinuate ne, o&ligations into se7eral #ro7isions o$ the )*8+ The 8nited *tates has demonstrated that there is no &asis $or $inding a 8* &reach o$ these so-called 9s6stemic9 o&ligations+ Q2. W+$/ .%0%.%#1% $" $/% US .%3*$$',5 -'.'. 2:5 d" $/% -'.$+%& 1"#&+d%. $/'$ ' 2%'&*.% $/'$ d"%& #"$ 1"2-,4 7+$/ $/% .%;*+.%2%#$& "0 A.$+1,% <.: SPS 7"*,d '*$"2'$+1',,4 3% +# 3.%'1/ "0 A.$+1,% 2.2 SPS5 ". A.$+1,% <.) SPS5 ". 3"$/9 3+ Article 0+4 a##lies 9OiPn cases ,here rele7ant scienti$ic e7idence is insu$$icient9 to #er$orm a ris= assessment+/4 Accordingl6: an anal6sis under Article 0+4 #resu##oses that there is: or ma6 &e: a &reach o$ Article 0+1 or Article 2+2@ other,ise: it ,ould not &e necessar6 $or the Mem&er maintaining a measure to assert that the re5uirements o$ Article 0+4 ha7e &een met+ /+ <n original #roceedings &rought against a measure: the 5uestion o$ ,hether the re5uirements o$ Article 0+4 ha7e &een met might arise in res#onse to a claim that a measure is inconsistent ,ith Article 2+2 or Article 0+1+ <n such a #roceeding: the com#laining #art6 ,ould ha7e the &urden o$ esta&lishing a &reach o$ Article 2+2 and(or Article 0+1+ <t ,ould not &e su$$icient $or the com#laining #art6 to demonstrate that the re5uirements o$ Article 0+4 ha7e not &een met in order 9automaticall69 to
/2 /4

8* ?uestions to the E!: ?uestion 3+ A##ellate .od6 "e#ort: =apan (pples: #ara+ 149+

'T()*320("(Add+3 %age !-/1 esta&lish a &reach o$ Articles 2+2 and 0+1+ 1or e am#le: ,here there is su$$icient scienti$ic e7idence to #er$orm a ris= assessment: a Mem&er ma6 not #ro7isionall6 ado#t a measure #ursuant to Article 0+4+ Bo,e7er: this is a se#arate 5uestion $rom ,hether a ris= assessment ,ithin the meaning o$ Article 0+1 has actuall6 &een #er$ormed+/8 0+ <n this dis#ute: the )is#ute *ettlement .od6 (9)*.9) has alread6 ruled that the E! im#ort &ans on meat $rom cattle treated ,ith the $i7e hormones ($or ,hich the E! no, asserts that the conditions o$ Article 0+4 ha7e &een met) &reach Article 0+1+ The E! does not claim to ha7e #er$ormed a ris= assessment consistent ,ith Article 0+1+ Against that &ac=ground: the 5uestion in this dis#ute is ,hether the E! has esta&lished: in #ursuing its claim under Article 22+8: that the E! has #ro7ided a solution to the nulli$ication or im#airment caused &6 the &reach o$ Article 0+1 &ecause the conditions o$ Article 0+4 ha7e &een met+ *ince the Article 0+4 conditions ha7e not &een met: the E! has not demonstrated that it has #ro7ided a solution to the nulli$ication and im#airment $ound &6 the )*.+ <n that sense: the $ailure to meet the re5uirements o$ Article 0+4 9automaticall69 leads to the conclusion that the Article 0+1 &reach $ound &6 the )*. has not &een remo7ed+ Q3. W/%# '#d /"7 7'& %'1/ "0 $/% 0",,"7+#( d"1*2%#$& 2'd% '='+,'3,% $" C'#'d' '#d $/% U#+$%d S$'$%&9 P,%'&% '#&7%. +#d%-%#d%#$,4 0". %'1/ "0 $/% d"1*2%#$& 2%#$+"#%d 3%,"7> ?+@ ?++@ ?+++@ ?+=@ )AAA O-+#+"#B 2000 O-+#+"#B 2002 O-+#+"#B %'1/ "0 $/% 6): &$*d+%&6.

2+ As noted in the 8* res#onse to %anel ?uestion /9 a$ter the $irst su&stanti7e meeting: the E! contacted the 8nited *tates in 1999 to in$orm rele7ant 8* regulator6 agencies o$ its com#letion o$ the 1999 O#inion on the si hormones at issue in the EC Hormones dis#ute+ At that time: the 8* 1ood and )rug Administration (91)A9) and )e#artment o$ Agriculture (98*)A9) re7ie,ed the documents #ut $or,ard &6 the E!+ The res#onse to those documents is contained in E hi&it 8* -21+ The 8nited *tates and the E! then met during the summer o$ 1999 to discuss the results o$ the E!;s 1999 O#inion+ 4+ 'e ha7e &een una&le to locate an6 records indicating that the E! #ro7ided its 2000 "e7ie, or 2002 O#inion to 8* authorities $or a similar re7ie, or that it re5uested a scienti$ic con$erence or discussions on the conclusions o$ those documents similar to those held in 1999+ *imilarl6: ,e ha7e no record o$ a re5uested discussion or con$erence on the scienti$ic under#innings o$ the E!;s &an once it asserted in the $all o$ 2003 that it had de7elo#ed a ris= assessment and &rought its measure into con$ormit6 ,ith )*. recommendations and rulings+ 8+ The 8nited *tates and the E! held a 7ideo con$erence in the $all o$ 2003: during ,hich the E! #ro7ided a &rie$ %o,er%oint #resentation summariFing its amended &an+ Bo,e7er: the E! did not #ro7ide an6 in$ormation on its 2000 "e7ie, or 2002 O#inion: nor did it #resent an6 in$ormation on the scienti$ic conclusions and anal6ses it 7ie,ed as su##orting its amended &an+ A co#6 o$ this #resentation ma6 &e $ound in E hi&it 8*-22+

At the same time: the 8nited *tates recogniFes that a res#onding Mem&er ,ould li=el6 onl6 ha7e raised Article 0+4 in the conte t ,here the res#onding Mem&er does not claim to ha7e #er$ormed a ris= assessment meeting the re5uirements o$ Article 0+1 or that there is su$$icient scienti$ic e7idence $or #ur#oses o$ Article 2+2+ <n that situation: there ,ould a##ear to &e no dis#ute that there ,ould &e a &reach o$ Article 0+1 or 2+2 i$ the re5uirements o$ Article 0+4 are not met: and in that sense the &reach o$ Article 0+1 or 2+2 ,ould &e 9automatic+9

/8

'T()*320("(Add+3 %age !-/2 9+ The 8nited *tates sent the E! an *%* Article 0+8 re5uest in the $all o$ 200/: to ,hich the E! res#onded on Ma6 19: 2000+ A co#6 o$ the Article 0+8 re5uest and the E!;s res#onse ma6 &e $ound at E hi&it 8*-23+ The E!;s res#onse contained internet lin=s $or the 2000 "e7ie, and 2002 O#inion+ 10+ At no #oint in time #rior to the initiation o$ this dis#ute ,as the 8nited *tates in #ossession o$ all o$ the 914 *tudies9 ostensi&l6 under#inning the E!;s 9ris= assessment+9 These materials ,ere not #ro7ided &6 the E! in its res#onse to the 8* Article 0+8 re5uest and ,ere #roduced in a #iecemeal $ashion throughout these #roceedings+ 'e ha7e discussed the E!;s $ailure to #roduce these studies in detail in the 8* "e&uttal *u&mission (#aras+ 19-22) and ha7e chronicled the (lac= o$) a7aila&ilit6 o$ these studies in Ta&le 1 to that *u&mission+ QC. H'& $/% E*."-%'# C"22*#+$+%& '&&%&&%d +# ' &4&$%2'$+1 2'##%. $/% %8+&$%#1% '#d ,%=%, "0 .+&D& 0."2 0'+,*.% $" "3&%.=% (""d =%$%.+#'.4 -.'1$+1%& 7+$/ .%&-%1$ $" $/% 'd2+#+&$.'$+"# "0 "%&$.'d+", ):M '& ' (."7$/ -."2"$+#( /".2"#% $" 1'$$,%5 +# -'.$+1*,'. +# $/% U#+$%d S$'$%&! '#d C'#'d'!& 2'.D%$&9 I0 &"5 -,%'&% +#d+1'$% 7/%.% $/+& '&&%&&2%#$ +& $" 3% 0"*#d +# $/% %=+d%#1% -."=+d%d $" $/% P'#%,. 11+ The E! has not assessed the e istence and le7el o$ ris=s $rom $ailure to o&ser7e good 7eterinar6 #ractices ,ith res#ect to the administration o$ estradiol 14Q as a gro,th #romoting hormone to cattle in the 8nited *tates+ <n $act: the E! has not e7en seriousl6 argued in the course o$ these #roceedings that it has done so+ 12+ As noted &6 the 8nited *tates in se7eral o$ its su&missions: the E! #resented a num&er o$ unrealistic misuse scenarios+ Bo,e7er: the actual occurrence o$ these scenarios in 8* $eedlots is #urel6 s#eculati7e and unsu##orted &6 e7idence+ /9 1or e am#le: in its 1999 O#inion: $rom #ages 30-31 (X 3+3): the E! #resents se7eral h6#othetical misuse scenarios &ut $ails to assess the #ro&a&ilit6 that an6 o$ these scenarios ,ould occur+ The E! #ostulates that ears $rom cattle containing gro,th #romoting im#lants ,ill enter the human $ood su##l6+ 'hen the 8nited *tates as=ed ,hether the E! had #ro7ided an6 e7idence that this has e7er occurred or ,ould e7er occur: the e #erts ()rs+ .oo&is and )e .ra&ander) noted that there ,as no such e7idence+ The E! also concludes that there is a ris= that a &lac= mar=et ,ill e ist in the 8nited *tates $or estradiol 14I+ (1999 O#inion: X 3+3+3)+ Bo,e7er: the onl6 e7idence on the record regarding the e istence o$ a &lac= mar=et demonstrates that such a mar=et e ists in the E!: ,here use o$ the hormone as a gro,th #romoter has &een &anned+ >ot onl6 does the E! $ail to #ro7ide e7idence o$ or assess the #otential $or misuse in its 1999 O#inion: e7en i$ one ,ere to assume misuse: the E! has $ailed to #ro7ide an6 e7idence that 7iolati7e residue le7els ,ould result e ce#t in the most e treme o7erdosing circumstances+00 13+ <n its E hi&it E!-43: the E! discusses se7eral h6#othetical misuse scenarios &ut similarl6 $ails to assess: in an6 meaning$ul ,a6: the li=elihood o$ the occurrence o$ an6 o$ these scenarios in 8* $eedlots+ 1or e am#le: the E! asserts that 9stac=ing9 o$ im#lants ( i.e.: treatment ,ith more than one dose o$ an im#lant at the same time) is common#lace in the 8nited *tates+ 01 Bo,e7er: the e7idence cited &6 the E! to su##ort this argument - a guidance document $rom the 8ni7ersit6 o$ >e&ras=a - does not stand $or this conclusion+ This $act ,as con$irmed &6 the author o$ the guidance cited &6 the E!+02 1urther: the E! $ails to e amine the actual ,or=ings o$ the 8* $ood sa$et6 s6stem &oth in this document and in each o$ the three O#inions com#rising its 9ris= assessment+9 The 8nited
The 8nited *tates discusses the E!;s $ailure to assess the ris= o$ misuse (or $ailure to satis$6 good 7eterinar6 #ractices) at length in its "e&uttal *u&mission (#ages 21-30) and its Oral *tatement at the *econd *u&stanti7e Meeting (E #ert <ssues) (#aras+ 20-24)+ 00 See 8* "e&uttal *u&mission (#ages 21-30)@ )r+ .oo&is; "es#onse to %anel ?uestion 22+ 01 E hi&it E!-43+ 02 See Detter $rom )r+ )ee 3ri$$in: E hi&it 8*-28@ 8* "e&uttal *u&mission: #aras+ 20-23+
/9

'T()*320("(Add+3 %age !-/3 *tates has discussed the actual ,or=ings o$ the 8* $ood sa$et6 s6stem at length and has demonstrated that the E!;s s#eculation that a ris= o$ $ailure e ists is not &ased on an6 e7aluation o$ an6 e7idence+ 03 1/+ <t is essential to recall the 7ie,s o$ the scienti$ic e #erts on the issue o$ ,hether or not the E! has indeed assessed the ris= o$ a $ailure to meet 3C%s+ )r+ .oisseau noted that 9as the OE!P did not conduct an6 5uantitati7e ris= assessment $or gro,th #romoters: it is not #ossi&le to sa6 that the scienti$ic e7idence re$erred to &6 the OE!P assesses the ris= to human health $rom residues resulting $rom these misuses(a&uses+90/ )r+ .oo&is agreed: stating: 9OtPhere ,as no attem#t to e7aluate the ris=s $rom the resultant e #osures on misuse or a&use: either in the #a#ers cited or &6 the *!C%B (2002) in their e7aluation o$ these studies+ <ndeed: the *!C%B (2002) sim#l6 noted that YOtPhere$ore: these data ha7e to &e considered in an6 5uantitati7e e #osure assessment e ercise;: ,ithout underta=ing such an e ercise+9 00 'hile )r+ )e .ra&ander a##ears to disagree ,ith )rs+ .oo&is and .oisseau: his res#onses $ail to indicate ,hether or not he is o$ the o#inion that the E! actuall6 assessed the ris= o$ misuse: and in se7eral instances his o#inions are sim#l6 &ased on anecdotal in$ormation and #olic6 considerations: rather than scienti$ic e7idence or citations to the E!;s #ur#orted ris= assessments+02 10+ 1inall6: it is necessar6 to recall that: e7en i$ one assumed that the E! actuall6 assessed the ris= o$ a $ailure to meet 3C%s: the scienti$ic e7idence #ut $or,ard &6 the E! indicates that 7iolati7e residues in meat ,ould onl6 occur as a result o$ that $ailure in the most e treme circumstances+ )r+ .oo&is #ro7ides a thorough re7ie, o$ the E!;s materials in his res#onse to %anel ?uestion 22 (at #ages 00-02)+ The 8nited *tates has also re7ie,ed these E! materials and commented on their $ailure to demonstrate 7iolati7e residues e ce#t $or in the most unrealistic scenarios+ 04 Q<. I# +$& 1"22%#$& "# 1"22%#$& "0 $/% U#+$%d S$'$%& '#d C'#'d' "# %8-%.$& .%-,+%& $" $/% P'#%, ;*%&$+"#& ?+# -'.$+1*,'. Q*%&$+"# )3@5 $/% E*."-%'# C"22*#+$+%& +#d+1'$%& $/'$ "%&$.'d+", ):M 2+(/$ 3% ' 67%'D (%#"$"8+#6 ?-'.'. CC@. A$ 7/'$ d"&%& +& (%#"$"8+1+$4 "3&%.='3,% +# =+="9 H"7 '.% $/%&% d"&%& 1"2-'.'3,% $" $/"&% 0"*#d +# 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ (."7$/ -."2"$+#( /".2"#%&9 H"7 7"*,d $/+& '&&%.$+"# '00%1$ $/% +d%#$+0+1'$+"# "0 'd=%.&% %00%1$& '#d $/% %=',*'$+"# "0 -"$%#$+', "11*..%#1% "0 $/%&% %00%1$& 0."2 1"#&*2-$+"# "0 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ "%&$.'d+", ):M 0". (."7$/ -."2"$+"# -*.-"&%&9 12+ To date: the E! has #resented onl6 one stud6 (out o$ 124 E hi&its) ,hich addresses genoto icit6 o$ estradiol 14Q in vivo+08 <n E hi&it E!-120: rats ,ere treated ,ith 0 milligrams o$ estradiol 14Q+ This dose o$ estradiol 14Q resulted in a t,o-$old increase in the num&er o$ mutations in mammar6 tissue+ Bo,e7er: as discussed in the meeting ,ith the e #erts: the results o$ this stud6 are highl6 5uestiona&le $or a num&er o$ reasons: and the doses in7ol7ed in the stud6 are not com#ara&le
See 8* "e&uttal *u&mission: #ara+ 00@ 8* !omments on the E #erts; "es#onses: #aras+ 100-102+ )r+ .oisseau "es#onses (?uestion /8): #+ 2/+ 00 )r+ .oo&is "es#onses (?uestion /8): #+ /2+ See )r+ .oo&is "es#onses (?uestion 22): #+ 02 (9the data generated &6 the E8 research in 5uestion do not #ro7ide an6 indication that it is not #ossi&le to conduct a ris= assessment o$ the hormones used as gro,th #romoters+9) 02 See: e.g.: 8* !omments on the "es#onses o$ the E #erts: #ara+ 104+ 04 See 8* !omments on the E #erts; "es#onses: *ection !+2@ 8* "e&uttal *u&mission: *ection <<+.+/+ 08 <n #aragra#h /3 o$ its !omments on the 8* and !anada;s !omments on the E #erts; "e#lies: the E! claims to ha7e 9su$$icient and constantl6 gro,ing e7idence $rom studies in 7i7o that sho, the direct genoto icit6 o$ oestradiol 14Q and its catechol meta&olites +++9+ Bo,e7er: 8* re7ie, o$ the studies listed in #aragra#h /3 re7eals that onl6 one: E!-120: demonstrated genoto icit6 o$ estradiol 14Q in vivo (and onl6 then at irrele7ant doses) ,hile the other studies ,ere #er$ormed onl6 ,ith catechol meta&olites+ This $act ,as con$irmed &6 )r+ MetFler: mem&er o$ the E! delegation: at the meeting ,ith the e #erts on 28 *e#tem&er 2002+ The distinction &et,een estradiol 14Q and its catechol meta&olites is im#ortant &ecause the E! has #resented no e7idence to sho, that the catechol meta&olites are #resent in vivo at le7els com#ara&le to those ,hich #roduce genoto ic e$$ects in vitro+ Moreo7er: the E! has #resented no e7idence to sho, that consum#tion o$ estradiol 14Q residues in &ee$ a$$ects the #roduction o$ catechol meta&olites ,hatsoe7er+
0/ 03

'T()*320("(Add+3 %age !-// to residue le7els $ound in meat $rom cattle treated ,ith estradiol $or gro,th #romotion #ur#oses+ 09 <ndeed: the doses are e #onentiall6 greater than those necessar6 to elicit &iological or endocrine e$$ects (in other ,ords: the6 are ,ell a&o7e the hormonal threshold)+ 14+ To com#are the dose o$ estradiol 14Q used in E!-120 to le7els $ound in meat $rom cattle treated ,ith gro,th #romoting hormones: it is necessar6 to e amine the dose relati7e to &od6 ,eight+ A la&orator6 rat ,eighs a##ro imatel6 200 grams+ There$ore: the dosage administered to the rats in E!-120 ,as 0 milligrams(200 grams: or 20 milligrams(=ilogram+ <$ a human (a7erage ,eight o$ 40 =g+) ,ere treated ,ith an e5ui7alent dose o$ estradiol 14Q: the dose ,ould &e 1/00 mg (20 milligrams(=ilogram 40 =g)+ This dose is e #onentiall6 greater than residue le7els $ound in meat $rom cattle treated ,ith estradiol $or gro,th #romotion #ur#oses+ According to AE!1A: 20 a conser7ati7e estimate o$ the amount o$ estradiol 14Q in a 200 gram ser7ing o$ meat $rom treated cattle is &et,een 10 and 20 nanograms: or 0+000010-0+000020 milligrams+ <n other ,ords: in relati7e terms: the dose administered to the rats in the E!;s stud6 (E hi&it E!-120) is more than 00 million times greater than the amount o$ estradiol residues consumed &6 humans in meat $rom treated cattle+ 18+ There$ore: the dose o$ estradiol 14Q administered to rats in E!-120 ,as astronomicall6 higher than that deri7ed $rom eating a ser7ing o$ &ee$ $rom treated cattle+ The di$$erence is e7en greater ,hen one ta=es into account the di$$erent routes o$ administration o$ estradiol 14Q+ The rats in the stud6 ,ere treated estradiol 14Q 7ia su&cutaneous im#lants: ,hich results in 7er6 high &ioa7aila&ilit6+ <n contrast: onl6 a small #ercentage ( 10J) o$ orall6-ingested estradiol 14Q is &ioa7aila&le due to ra#id meta&olism in the li7er and small intestine+ *o: not onl6 ,as the dose e #onentiall6 greater in the rat stud6 &ut the dose ,as much more &ioa7aila&le than ,ould &e the case $rom consuming residues in meat+ 1or these reasons: this stud6 is not rele7ant to the #ur#orted ris= to human health associated ,ith eating meat $rom cattle treated ,ith gro,th-#romoting hormones+ Q*%&$+"#& $" $/% U#+$%d S$'$%& '#d C'#'d'> Q):. W/'$ ,%(', -."1%d*.%& 7%.% *&%d +# 4"*. .%&-%1$+=% d"2%&$+1 ,%(', &4&$%2& $" 'd"-$ $/% &*&-%#&+"#& "0 "3,+('$+"#& '$ +&&*%9 W"*,d $/% &'2% ,%(', -."1%d*.%& '--,4 $" $/%+. '3."('$+"#9 19+ 8nder the 8* legal s6stem: the a##lica&le authorities and #rocedures are set out in *ections 301-309 o$ the Trade Act o$ 194/: as amended (codi$ied at 19 8+*+!+ 2/11-2/19) (commonl6 re$erred to as 9*ection 3019)+ 20+ *us#ension o$ o&ligations: On Aul6 12: 1999: the ar&itrator determined that the le7el o$ nulli$ication and im#airment su$$ered &6 the 8nited *tates in this dis#ute ,as Z112+8 million #er 6ear: and that the 8nited *tates ,as entitled to sus#end the a##lication o$ tari$$ concessions u# to that amount+ On Aul6 22: the )*. authoriFed the 8nited *tates to sus#end the a##lication o$ tari$$ concessions in this amount+ <n accordance ,ith the ar&itrator;s re#ort and )*. authoriFation: the 8*T" determined that a##ro#riate action under *ection 301 in res#onse to the E!;s $ailure to com#l6 ,ith the )*. recommendations and rulings ,as to sus#end the a##lication o$ tari$$ concessions and increase tari$$s on a s#eci$ic list o$ E! #roducts ,ith an annual trade 7alue o$ Z112+8 million+ The 8*T" then #u&lished a #ederal *egister notice announcing the sus#ension o$ concessions in the $orm o$ increased duties on s#eci$ic #roducts o$ the E!+ 21+ Termination o$ *us#ension: *ection 301 #ro7ides that the 8*T" ma6 terminate an action #re7iousl6 ta=en under *ection 301 i$: inter alia: the )*. ado#ts a re#ort $inding that the rights o$ the
See #aragra#hs 24-29 o$ 8* Oral *tatement at the *econd *u&stanti7e Meeting (E #ert <ssues)+ See 9E7aluation o$ certain 7eterinar6 drug residues in $ood9: 1i$t6-*econd "e#ort o$ the Aoint 1AO('BO E #ert !ommittee on 1ood Additi7es: 'BO Technical "e#ort *eries: 893 (2000) (902nd AE!1A "e#ort9): #+ 83+ (E hi&it 8*-0)+
20 09

'T()*320("(Add+3 %age !-/0 8nited *tates under the trade agreement are not &eing denied+ *ection 301 re5uires 8*T" to consult #rior to terminating an6 action+ 8#on ma=ing such a determination: 8*T" ,ould #u&lish a notice in the #ederal *egister announcing the termination o$ the sus#ension o$ concessions and the restoration o$ regular M1> rates o$ duties on the a$$ected #roducts+ Q)G. W"*,d 4"* 1"#&+d%. $/'$5 0". $/% -*.-"&% "0 $/% DSU5 D+.%1$+=% 2003/:C/EC &/"*,d 3% =+%7%d '& ' #%7 2%'&*.% ". '& $/% 1"#$+#*'$+"# "0 $/% -.%=+"*& 2%'&*.% 0"*#d $" 3% +#1"#&+&$%#$ 7+$/ $/% WTO A(.%%2%#$5 &+#1% +$ &$+,, +2-"&%& ' 3'#9 22+ *ince the 8nited *tates is not the com#laining #art6: there is no challenge to an E! measure in this dis#ute as such+ "ather: the 5uestion is ,hether the E! has demonstrated: ,ithin the meaning o$ Article 22+8 o$ the )*8: that the E! has remo7ed its 'TO-inconsistent measures or has #ro7ided a solution to the nulli$ication or im#airment+ 21 <$ the E! has sim#l6 continued its 'TO-inconsistent measure: then there ,ould &e no solution to the nulli$ication or im#airment+ <$ the E! has not demonstrated that it has sol7ed the nulli$ication or im#airment through a ne, or re7ised measure: then the E! has not met its &urden under Article 22+8+ Accordingl6: the 8nited *tates has not argued that the E!;s amended &ans are or are not ne, measures $or #ur#oses o$ the )*8+ "ather: ,e 7ie, the #ertinent 5uestion to &e ,hether or not the E!;s &ans in $act &ring it into con$ormit6 ,ith the )*. recommendations and rulings in the Hormones dis#ute+ <$ there ,ere a )*. $inding that the E! has com#lied &6 &asing its #ermanent &an on estradiol on a ris= assessment ,ithin the meaning o$ *%* Article 0+1 and satis$6ing the $our cumulati7e conditions o$ *%* Article 0+4 $or its #ro7isional &ans on the other $i7e hormones: then there ,ould no longer &e a &asis to a##l6 the sus#ension o$ concessions or other o&ligations+ This ,ould &e the case ,hether the E!;s &an ,as a ne, measure or a continuation (al&eit ,ith modi$ication) o$ the #re7ious measure+ Q*%&$+"#& $" $/% U#+$%d S$'$%&> Q)A. D"%& $/% U#+$%d S$'$%& '.(*% ' =+",'$+"# "0 A.$+1,% <.2 '#d "0 A.$+1,% <.F SPS9 I# "$/%. 7".d&5 d" 4"* %8-%1$ $/% P'#%, $" +&&*% 0+#d+#(& .%('.d+#( $/% 1"2-,+'#1% "0 D+.%1$+=% 2003/:C/EC 7+$/ $/"&% -."=+&+"#&9 W/'$ +& $/% -*.-"&% "0 $/% .%0%.%#1% $" A.$+1,% 2.2 SPS +# -'.'. 2: "0 $/% US .%3*$$', &*32+&&+"#9 23+ As the res#onding #art6: the 8nited *tates has not made an6 claims o$ an E! &reach o$ its 'TO o&ligations+ The E!: as the com#laining #art6: is res#onsi&le $or &ringing such claims and satis$6ing its &urden o$ #roo$ $or each claim+ One o$ the E! claims in this dis#ute is that the 8nited *tates has &reached its o&ligations under )*8 Article 22+8: ,hich sets out the conditions under ,hich a Mem&er sus#ending concessions or other o&ligations must cease to a##l6 the sus#ension against another Mem&er+ <n order to satis$6 its claim under )*8 Article 22+8: the E! must demonstrate that it has either remo7ed the 'TO inconsistent measure(s) or that it has #ro7ided a solution to the nulli$ication and im#airment o$ &ene$its+ 2/+ The E! clearl6 has not remo7ed its im#ort &ans nor has it claimed to ha7e done so+ There$ore: in order to satis$6 its &urden in this #roceeding: the E! must demonstrate that it has &rought its measure into con$ormit6 ,ith the )*. recommendations and rulings in the Hormones dis#ute+ Those recommendations and rulings include $indings o$ E! &reaches o$ *%* Articles 0+1 and 3+3+ The E! argues it has satis$ied the )*. recommendations and rulings &6 &asing its #ermanent &an $or estradiol on a ris= assessment and satis$6ing the $our conditions o$ *%* Article 0+4 $or the other $i7e hormones in lieu o$ a ris= assessment+ These arguments call $or $indings as to ,hether or not the E! has in $act demonstrated that it has &rought itsel$ into con$ormit6 ,ith the )*.;s recommendations and rulings: as these $indings are integral to the E!;s Article 22+8 claim+
>o #art6 has argued that the third #rong o$ the Article 22+8 test is in7ol7ed here - reaching a mutuall6 satis$actor6 solution+
21

'T()*320("(Add+3 %age !-/2 20+ The re$erence to *%* Article 2+2 in #aragra#h 24 o$ the 8* "e&uttal *u&mission ,as made in the conte t o$ descri&ing ho, *%* Article 0+4 $unctions as a 5uali$ied: tem#orar6 e em#tion under the *%* Agreement+ The re$erence ,as not intended to elicit a $inding o$ a &reach o$ *%* Article 2+2+ "ather: the a##ro#riate $inding ,ould &e that the E!: in $ailing to satis$6 the conditions o$ Article 0+4: has not sol7ed the nulli$ication and im#airment o$ &ene$its arising $rom its $ailure to &ase its measures relating to the $i7e other hormones on a ris= assessment ,ithin the meaning o$ *%* Article 0+1+ The E! concedes that it has not &ased these measures on such an assessment@ there$ore: the E! has not &rought its measures into con$ormit6 ,ith the )*. recommendations and rulings+ 22+ The 8nited *tates &elie7es that a $inding o$ com#liance or non-com#liance ,ith the re5uirements o$ *%* Article 0+2 ,ould &e a##ro#riate as #art o$ the %anel;s anal6sis o$ ,hether the E! has &ased its measure on a ris= assessment ,ithin the meaning o$ *%* Article 0+1+ Article 0+2 re5uires that ris= assessments ta=e into account certain elements: including a7aila&le scienti$ic e7idence@ rele7ant #rocesses and #roduction methods@ and rele7ant ins#ection: sam#ling and testing methods+ Article 0+2 is not mutuall6 e clusi7e o$ *%* Article 0+1@ rather: it sets out the s#eci$ic com#onents o$ the ris= assessment on ,hich Mem&ers are re5uired to &ase their measures $or #ur#oses o$ *%* Article 0+1+ <$ the E! has not satis$ied the re5uirements o$ Article 0+2: it has not conducted a ris= assessment: as a##ro#riate to the circumstances+ <ts measure (#ermanent &an on estradiol) there$ore cannot &e &ased on a ris= assessment ,ithin the meaning o$ *%* Article 0+1+ Q20. C"*,d $/% U#+$%d S$'$%& 1,'.+04 7/%$/%. +$& '.(*2%#$& .%('.d+#( ' =+",'$+"# "0 A.$+1,% 3.3 SPS '--,4 "#,4 +# .%,'$+"# $" $/% d%0+#+$+=% 3'# "# "%&$.'d+", ): M ". 7/%$/%. $/%4 '--,4 ',&" +# .%,'$+"# $" $/% -."=+&+"#', 3'# +2-"&%d "# $/% "$/%. 0+=% /".2"#%&9 24+ 8* arguments regarding a 7iolation o$ *%* Article 3+3 a##l6 in relation to each o$ the E! &ans on meat $rom cattle treated ,ith gro,th #romoting hormones $or ,hich international standards e ist+ <n other ,ords: 8* arguments relate to each o$ the hormones at issue e ce#t $or melengestrol acetate (9M3A9): $or ,hich AE!1A has conducted a ris= assessment: set an A)< and #ro#osed an M"D: &ut $or ,hich !ode has not ado#ted an M"D+ *%* Article 3+3 re5uires that Mem&ers &ase their measures on international standards ,here the6 e ist and onl6 #ermits Mem&ers to di7erge $rom such standards i$ there is a scienti$ic Eusti$ication $or doing so+ 1or #ur#oses o$ this dis#ute: that scienti$ic Eusti$ication could ha7e ta=en the $orm o$ a #ro#erl6 conducted ris= assessment $or estradiol or satis$6ing the $our conditions o$ Article 0+4 $or testosterone: #rogesterone: Feranol and tren&olone acetate+ The 8nited *tates has demonstrated that the E! has $ailed to #ro7ide such a Eusti$ication+ 28+ The 8nited *tates has demonstrated that the E! has $ailed to satis$6 the conditions o$ Article 0+4 $or its #ro7isional &an on M3A &ecause: among other things: there is su$$icient scienti$ic e7idence to conduct a ris= assessment $or M3A and the E! has not &ased its #ro7isional &an on M3A on a7aila&le #ertinent in$ormation+ The 8nited *tates has also demonstrated that the E! $ailed to satis$6 the conditions o$ Article 0+4 $or the other $our #ro7isionall6 &anned hormones (testosterone: #rogesterone: Feranol: and tren&olone acetate)+

'T()*320("(Add+3 %age !-/4 ANNEX CC REPLIES OF THE UNITED STATES TO QUESTIONS POSED BY THE EUROPEAN COMMUNITIES AFTER THE SECOND SUBSTANTI E MEETING (18 Octo&er 2002) EC Q*%&$+"#& $" $/% U#+$%d S$'$%& '#d C'#'d'> Q). P,%'&% %8-,'+#5 +0 -"&&+3,% +# d%$'+,5 7/'$ D+#d "0 &1+%#$+0+1 %=+d%#1% "# %8-"&*.%I'&&%&&2%#$ 0."2 .%&+d*%& +# 2%'$ $.%'$%d 7+$/ $/% &+8 /".2"#%& 0". '#+2', (."7$/ -."2"$+"# 7'& *&%d 34 $/% U#+$%d S$'$%& '#d C'#'d' 7/%# $/%&% &*3&$'#1%& 7%.% '*$/".+&%d9 W'& $/+& %8-"&*.% '&&%&&2%#$ ' ;*'#$+$'$+=% "#%9 P,%'&% -."=+d% 1"#1.%$% .%0%.%#1% $" &$*d+%& *&%d +# 4"*. %8-"&*.% '&&%&&2%#$ '#d5 +0 -"&&+3,%5 $" $/"&% "0 LECFA 0". $/% &+8 /".2"#%& +# ;*%&$+"# ?+# 1'&% 4"* D#"7 $/% .%0%.%#1%&@. 1+ O$ course: it is not 8* measures that are at issue here+ The Euro#ean !ommunities (9E!9) has chosen to &an the im#ort o$ 8* meat and meat #roducts $rom cattle treated ,ith each o$ the si hormones $or gro,th #romotion #ur#oses and it is there$ore an anal6sis o$ the E!;s 9ris= assessment9 and &asis $or its $i7e 9#ro7isional &ans9 that is essential to this dis#ute+ That &eing said: ,e are ha##6 to #ro7ide more in$ormation $or &ac=ground: although ,e note that this is the sort o$ 5uestion that the E! could ha7e #osed earlier to &etter in$orm its o,n ris= assessment+ 2+ The 8* 1ood and )rug Administration (91)A9) conducted 5uantitati7e e #osure assessments $or each o$ the hormones a##ro7ed to #romote gro,th in cattle+ The #rocedures that 1)A uses to e7aluate the sa$et6 o$ edi&le #roducts $rom animals treated ,ith 7eterinar6 drugs are #u&licl6 a7aila&le and descri&ed in detail on the 1)A ,e& site+ 22 The e #osure assessment com#onent o$ the e7aluation o$ the si gro,th-#romoting hormones can &e summariFed as $ollo,s+ 3+ 1or each o$ the si hormones: 1)A re5uired the s#onsors to conduct e tensi7e residue studies+ These studies #ro7ided in$ormation on total residue de#letion and the meta&olic $ate o$ each hormone in edi&le tissues $rom cattle (muscle: li7er: =idne6 and $at)+ /+ 1or each o$ the three s6nthetic hormones: s#onsors also #er$ormed e tensi7e to icological testing in e #erimental animals 23 to determine the dose at ,hich the hormone #roduced an ad7erse e$$ect and the dose at ,hich no e$$ect ,as o&ser7ed (no e$$ect le7el or 9>OED9)+ The >OED o$ the most sensiti7e to icological e$$ect (e.g.: re#roducti7e: de7elo#mental: tumorigenic) in the most sensiti7e s#ecies e amined (e.g.: rat: mouse: ra&&it) ,as then di7ided &6 an a##ro#riate sa$et6 $actor to determine an acce#ta&le dail6 inta=e (9A)<9)+ The A)< ,as then used to calculate a sa$e concentration $or each edi&le tissue $rom cattle as $ollo,s: sa$e concentration U A)< 20 =ilograms (,eight o$ a7erage #erson) grams consumed #er da6+ The $ood consum#tion $actors currentl6 used &6 1)A are: muscle: 300 grams@ li7er: 100 grams@ $at and =idne6: 00 grams each+ 2/ 1)A determined that $or each o$ the s6nthetic hormones: the total residues ( i.e.: residues o$ to icological concern) ,ere less than those calculated $rom the res#ecti7e A)<+ There$ore: 1)A concluded that consum#tion o$ these residues in edi&le tissues $rom treated cattle does not #ose a ris= to human health+
htt#:((,,,+$da+go7(c7m(3uidance(#u&lished+htm: 3uidance 3 This testing is also e #lained in 1)A 3uidance 3+ 2/ At the time the hormones ,ere a##ro7ed: an e7en more conser7ati7e $ood &as=et ,as used and it ,as assumed that on an6 gi7en da6 a #erson might consume u# to 000 grams o$ muscle: 200 grams o$ li7er: 124 grams o$ =idne6: or 120 grams o$ $at+
23 22

'T()*320("(Add+3 %age !-/8 0+ 1or the three natural hormones: 1)A did not esta&lish A)<s and concluded that human sa$et6 can &e assured ,ithout the need $or e tensi7e to icological testing in e #erimental animals+ This is &ecause the amounts o$ these hormones #resent in edi&le tissues o$ treated cattle ,ere $ound to &e 7er6 small relati7e to the endogenous #roduction in humans+ 1)A concluded that no additional #h6siological e$$ect ,ill occur $rom chronic ingestion o$ animal tissues that contain a residue le7el o$ natural hormones e5ual to 1J or less o$ the amount #roduced dail6 &6 the segment o$ the #o#ulation ,ith the lo,est endogenous #roduction+20 8sing $ood consum#tion $actors: 1)A set #ermitted increased dail6 e #osures o$ 0+02 micrograms $or estradiol: 1+00 micrograms $or #rogesterone: and 0+32 micrograms $or testosterone+ To o&tain 1)A a##ro7al $or the natural hormones: the drug;s s#onsor ,as re5uired to demonstrate that residues o$ each hormone in edi&le tissues $rom treated cattle did not e ceed the sa$e concentration+ This re5uirement ,as satis$ied $or all three o$ the natural hormones+ 2+ The e #osure assessment conducted &6 AE!1A $or each o$ the si hormones ,as descri&ed in detail &6 the AE!1A re#resentati7e at the meeting ,ith e #erts on 24-28 *e#tem&er 2002+ "e$erences descri&ing AE!1A;s ris= assessments $or the hormones can &e $ound in the ans,er to ?uestion 2 &elo,+ Q2. P,%'&% +#d+1'$%5 +0 -"&&+3,% +# d%$'+,5 7/%$/%. 4"*. .+&D '&&%&&2%#$&5 '#d +0 4"* D#"7 $/"&% "0 LECFA5 "0 $/% &+8 /".2"#%& +# ;*%&$+"# 0". '#+2', (."7$/ -."2"$+"# /'=% '$$%2-$%d $" 1',1*,'$% $/% .+&D $" /*2'#& 0."2 $/% 'dd+$+"#', %8-"&*.% .%&*,$+#( 0."2 $/% .%&+d*%& +# /".2"#%I$.%'$%d 2%'$ 7/%# *&%d '11".d+#( $" G P '#d 7/%# G P +& #"$ .%&-%1$%d. W'& +$ ' ;*'#$+$'$+=% %8-"&*.% '&&%&&2%#$9 I0 &"5 -,%'&% -."=+d% $/% -.%1+&% .%0%.%#1% $" $/% d'$'. ?P,%'&% #"$% $/'$ 7% '.% #"$ .%0%..+#( /%.% $" .%&+d*%Id%-,%$+"# &$*d+%& 1"#$'+#%d +# CAN E8/+3+$I):5 &+#1% $/% EC /'& ',&" 1"#d*1$%d &*1/ .%&+d*%& d%-,%$+"# &$*d+%& 0". +$& )AAAI2002 .+&D '&&%&&2%#$&@. 4+ Again: this dis#ute settlement #roceeding is not concerned ,ith the measures o$ the 8nited *tates or an6 ris= assessments o$ the 8nited *tates+ And under Article 3+3 o$ the *%* Agreement the E! has an o&ligation to &e $amiliar ,ith the rele7ant international standards: guidelines or recommendations+ The 8nited *tates ,onders i$ the E!;s 5uestion is an admission that the E! has $ailed to $amiliariFe itsel$ ,ith the rele7ant AE!1A material+ 8+ That &eing said: ,e are ha##6 to #ro7ide more in$ormation $or &ac=ground: although ,e note that this is the sort o$ 5uestion that the E! could ha7e #osed earlier to &etter in$orm its o,n ris= assessment+ As e #lained in the 1)A 3uidance 22 re$erenced in the res#onse to ?uestion 1: 1)A re5uires that total residue de#letion studies &e conducted using the dose that is the highest intended treatment le7el and that these studies should model the e #osure recei7ed &6 the target animal+ <n the case o$ the si hormones in 5uestion: the highest intended treatment le7el ,as (and still is) one im#lant #er animal: consistent ,ith good 7eterinar6 #ractice+ 9+ AE!1A com#leted 5uantitati7e e #osure assessments $or each o$ the si hormones+ The #rocess $or conducting these assessments ,as descri&ed &6 the AE!1A re#resentati7e at the meeting ,ith the e #erts+ 1ood and >utrition %a#er (91>%9) /1(12 #ro7ides e tensi7e com#ilations o$ residue data $or each o$ the natural hormones and the anal6sis includes estimates o$ e #osure $rom the consum#tion o$ the $our edi&le tissues (muscle: li7er: =idne6 and $at) $rom treated animals+ 10+ The e #osure assessment $or the three natural hormones: as ,ell as the a7aila&le residue data: meta&olism data and anal6tical methods can &e $ound at the AE!1A ,e&site+ 24 The 'BO Technical
*ensiti7e su&#o#ulations are #re#u&ertal girls $or testosterone and #re#u&ertal &o6s $or estradiol 14 and #rogesterone+ 22 htt#:((,,,+$da+go7(c7m(3uidance(#u&lished+htm 24 ,,,+$ao+org(ag(agn(Eec$a(archi7eVen+stm
20

'T()*320("(Add+3 %age !-/9 "e#ort *eries #u&lication 893 summariFes all o$ the rele7ant $indings on additional estimated e #osure $rom consum#tion o$ tissues $rom hormone-treated animals+ 1or total estrogens: the highest e cess inta=e ($rom eating &ee$ $rom treated cattle) ,as 30-00 nanograms #er #erson #er da6+ 1or #rogesterone: the estimated ma imum dail6 e #osure ,as a##ro imatel6 000 nanograms #er da6: and $or testosterone: a&out 20 nanograms #er da6+ These $igures re#resent less than 2J o$ the AE!1A A)< $or estradiol: 0+03J $or #rogesterone and a&out 0+00J $or testosterone+ That is: tissues $rom hormone-treated animals #resent hormone residues that are a minuscule #ercentage o$ dail6 allo,ances $or ingestion o$ such hormones+ 11+ The AE!1A residue: meta&olism and anal6tical method re#orts $or the three s6nthetic hormones ma6 &e $ound at the ,e&site listed a&o7e+ <ndi7idual re#orts are contained in 1AO 1>% /1: /1(2: /1(13: /1(12 and /1(14+ 1or each hormone: the a##roach used &6 AE!1A ,as to esta&lish an A)< and recommend M"Ds that are consistent ,ith the ma imum theoretical residues determined &6 the A)< esta&lished on a [g(=g &od6 ,eight &asis+ 12+ AE!1A;s e7aluations o$ the si hormones are &ased on data #ro7ided &6 s#onsors ,hich: in general: re$lect good 7eterinar6 #ractices+ The 8nited *tates notes that: in continuing to raise the issue o$ good 7eterinar6 #ractices: the E! onl6 underscores its $ailure to meet its 'TO o&ligations in this regard+ The e #erts ha7e con$irmed that the E! itsel$ has $ailed to #ro#erl6 e amine the li=elihood o$ misuse or a&use o$ the hormones at issue as it ,as o&ligated to do #ursuant to Articles 0+1 and 0+2 o$ the *%* Agreement+28 Q3. T/% EC *#d%.&$'#d& $/'$ &"2% "0 $/% %8-%.$& ?D.&. G*$$%#-,'#5 S+--%, '#d C"(,+'#"@ /'=% &$'$%d $/'$ +$ +& #"$ -"&&+3,% $" d%$%.2+#% 7+$/ '11*.'14 $/% d"&%I.%&-"#&% 1*.=% '$ $/% =%.4 ,"7 ,%=%,& "0 %8-"&*.% 0."2 $/%&% /".2"#%& +# (%#%.', '#d 7/%# *&%d 0". '#+2', (."7$/ -."2"$+"#. D" 4"* '(.%% 7+$/ $/%&% &$'$%2%#$&9 I0 #"$5 1"*,d 4"* -,%'&% -."=+d% $/% -.%1+&% .%0%.%#1%& $" &1+%#$+0+1 &$*d+%& 7/%.% $/+& /'& 3%%# d"#%9 W/'$ 7"*,d 3% $/% +2-,+1'$+"#& "0 $/+& +2-"&&+3+,+$4 0". $/% #%%d $" -%.0".2 ' ;*'#$+$'$+=% ". ;*',+$'$+=% %8-"&*.% '&&%&&2%#$ 0". $/%&% /".2"#%& 7/%# *&%d 0". '#+2', (."7$/ -."2"$+"#9 13+ )rs+ !ogliano: *i##ell and 3utten#lan #ostulated that it is not #ossi&le to de$ine ,ith #recision the lo,-dose res#onse cur7e $or estradiol+ Bo,e7er: it is necessar6 to e amine this discussion in light o$ the a7aila&le scienti$ic e7idence relating to estradiol and the e #erts; o#inions on that e7idence+ The scienti$ic e7idence indicates that there is a threshold $or the genoto ic and carcinogenic e$$ects o$ estradiol+ 3enoto ic and carcinogenic e$$ects are onl6 o&ser7a&le at 7er6 high doses (&oth in vivo and in vitro) at or a&o7e this threshold+ This threshold is orders o$ magnitude greater than the le7els o$ estradiol $ound in residues in meat $rom cattle treated $or gro,th #romotion #ur#oses+ There is no scienti$ic e7idence demonstrating ad7erse e$$ects at doses lo,er than the hormonal threshold+ 1/+ )r+ 3utten#lan concluded that there is no ris= $or carcinogenicit6 &elo, the acce#ta&le dail6 inta=e le7el (9A)<9) $or estradiol at the meeting ,ith the e #erts: there&6 indicating that an6 carcinogenic e$$ects ,ould &e a result o$ doses a&o7e the threshold (le7els e #onentiall6 greater than those $ound in residues in meat $rom treated cattle)+ )r+ .oisseau noted that 9the scienti$ic e7idence relied u#on in the *!C%B O#inions does not su##ort the conclusion that the carcinogenic e$$ects o$
See )r+ .oo&is "es#onses (?uestion 22): #+ 08 (9OtPhe e7idence o&tained did not indicate an6 additional concern regarding the ris= $rom e #osure to residues o$ the hormones in meat $rom cattle treated $or gro,th #romotion9)@ )r+ .oo&is "es#onses (?uestion /8): #+ /2 (the E! has made 9no attem#t to e7aluate the ris=s9 $rom misuse: either in its O#inions or in underl6ing studies)@ )r+ .oisseau "es#onses (?uestion 01): #+ 20 (9the OE!P did not conduct a 5uantitati7e ris= assessment $rom gro,th #romoters: Oand thatP it is not #ossi&le to sa6 the scienti$ic e7idence re$erred to &6 the OE!P assesses the ris= to human health $rom residues resulting $rom these misuses(a&uses+9) See A##ellate .od6 "e#ort: #aras+ 200-204+
28

'T()*320("(Add+3 %age !-00 oestradiol-14I are related to a mechanism other than hormonal acti7it6+9 29 As noted &6 )r+ !ogliano: 9it has not &een esta&lished &6 the E! that genoto icit6 and cell #roli$eration ,ould &e induced &6 le7els $ound in meat residues added to the #re-e isting le7els occurring in e #osed humans+9 40 1inall6: )r+ .oo&is stated that 9OtPhe carcinogenic e$$ects o$ oestradiol a##ear to &e a conse5uence o$ its endocrine acti7it6+941 <n other ,ords: carcinogenic e$$ects ,ere onl6 o&ser7a&le at le7els at or a&o7e the hormonal threshold+ <n the a&sence o$ an6 scienti$ic e7idence o$ ad7erse e$$ects at doses &elo, the threshold: arguing a&out the sha#e o$ the dose-res#onse cur7e &elo, the threshold is not in$ormati7e+ <n other ,ords: there is no e7idence that estradiol ,ill cause ad7erse e$$ects &elo, a de$ina&le threshold+ The E! has $ailed to #resent an6 such e7idence in the course o$ these #roceedings+ QC. I0 4"* 7%.% $" '(.%% $/'$ &1+%#$+&$& 1'##"$ d%0+#% $/% d"&%I.%&-"#&% 1*.=% '& %8-,'+#%d +# $/% -.%=+"*& ;*%&$+"#5 7"*,d $/+& &$'$% "0 &1+%#$+0+1 D#"7,%d(% 3% d%0+#%d '& 6&1+%#$+0+1 *#1%.$'+#$46 +# $/+& '.%'9 I0 #"$5 -,%'&% %8-,'+#. 10+ As indicated in our #re7ious res#onse: the 5uestion o$ the sha#e o$ the dose res#onse cur7e at lo, doses is not re$lecti7e o$ an6 scienti$ic uncertaint6 rele7ant to the ris= at issue gi7en the lac= o$ scienti$ic e7idence o$ a ris= &elo, the threshold $or estradiol+ The 8nited *tates summariFed the state o$ scienti$ic e7idence relating to the genoto icit6 and carcinogenicit6 o$ estradiol in its res#onse to ?uestion 3 a&o7e+ The E! has attem#ted to cast this lac= o$ e7idence o$ a ris= at lo, doses as a rele7ant 9scienti$ic uncertaint6+9 .ut this lac= o$ e7idence o$ a ris= cannot &e construed in turn as e7idence o$ a ris= or as a &asis $or the E!;s &an+ 12+ .6 arguing the #resence o$ 9scienti$ic uncertaint69 in a situation in ,hich there is no e7idence o$ a ris= at rele7ant e #osure le7els: the E! a##ears to &e see=ing nothing less than an assurance that there ,ill ne7er &e e7idence o$ a ne, ris= $rom estradiol at some #oint in the $uture+ As argued &6 the 8nited *tates and discussed &6 the A##ellate .od6: this is an uncertaint6 9that theoreticall6 al,a6s remains since science can ne7er #ro7ide a&solute certaint6 that a gi7en su&stance ,ill not e7er ha7e ad7erse health e$$ects+ 'e agree ,ith the %anel that this theoretical uncertaint6 is not the =ind o$ ris= ,hich: under Article 0+1: is to &e assessed+942 This t6#e o$ uncertaint6 is not e7idence o$ a ris=: nor ma6 it ser7e as the &asis $or the E!;s &an on meat and meat #roducts treated ,ith estradiol $or gro,th #romotion #ur#oses+ Q<. C"*,d 4"* -,%'&% %8-,'+# 7/'$ +& 4"*. -"&+$+"# "# $/% %8+&$%#1% ". #"# %8+&$%#1% "0 '# +#$%.#'$+"#', &$'#d'.d 0". MGA 0". $/% -*.-"&%& "0 A.$+1,%& 25 3 '#d < "0 $/% SPS A(.%%2%#$ +# $/%&% d+&-*$%&9 14+ %lease see the 8* res#onse to %anel ?uestion 20+

EC Q*%&$+"#& $" $/% U#+$%d S$'$%&> Q). T/% 2002 US R%-".$ "# C'.1+#"(%#%&+& ?E8/+3+$ ECI)0)@ &$'$%& +#$%. ',+' $/'$> 6=%$%.+#'.4 *&% "0 &$%."+d', %&$."(%#& ?$" -."2"$% (."7$/ '#d $.%'$ +,,#%&&%&@ 1'# +#1.%'&% %&$."(%#& +# $+&&*%& "0 0""d -."d*1+#( '#+2',& $" '3"=% $/%+. #".2', ,%=%,&6 ?-. G@. H"7 d" 4"* .%1"#1+,% $/+& 7+$/ 4"*. -."-"&+$+"# +# -'.'. <) "0 4"*. F+.&$ W.+$$%# S*32+&&+"#9 18+ The 11th "e#ort on !arcinogens notes that 97eterinar6 use o$ steroidal estrogens (to #romote gro,th and treat illnesses) can increase estrogens in tissues o$ $ood #roducing animals to a&o7e their normal le7els+9 %aragra#h 01 o$ the 8* 1irst 'ritten *u&mission states that 9O,Phile tissue
29 40

)r+ .oisseau "es#onses (?uestion 12): #+ 12+ )r+ !ogliano "es#onses (?uestion 18): #+ 1+ 41 )r+ .oo&is "es#onses (?uestion 12): #+ 19+ 42 A##ellate .od6 "e#ort: #ara+ 124+

'T()*320("(Add+3 %age !-01 concentrations o$ estradiol 14I in treated cattle ma6 &e slightl6 higher than those in untreated cattle: this increase is much smaller than the large 7ariations o&ser7ed in (re#roducti7el6) c6cling and #regnant cattle and is thus ,ell ,ithin the range o$ naturall6 o&ser7ed le7els+9 19+ The 8nited *tates $ails to see a discre#anc6 &et,een these statements &ut is #leased to &e a&le to clari$6 the issue $or the E! through re$erence to the E!;s o,n e hi&its+ <t a##ears that the source o$ the E!;s con$usion is use o$ the ,ord 9normal9 in the "e#ort on !arcinogens+ <n this (&iological) conte t: 9normal9 is a relati7e term ,hich de#ends on the endogenous: &aseline le7els o$ estradiol 14I #resent in the animal treated ,ith gro,th-#romoting hormones+ 1or e am#le: the 9normal9 le7els o$ estradiol 14I in steers (male cattle lac=ing testes) ,ill &e e tremel6 lo,+ <t stands to reason: there$ore: that treatment o$ steers ,ith estradiol 14I to promote growth may increase concentrations of estradiol 17 in edible tissues to levels that are above normal for this type of animal. !owever, as illustrated in Table """ of #$%&' 7&, this increase may be small (1.1 to ).&%fold* and, as illustrated in +igure 1 of #$% ,1-, is not detectable in every animal. +emale cattle have higher normal levels of estradiol 14I than steers and these levels may be more variable due to changes in production of estradiol 14I by the ovary throughout the ()1%day* reproductive cycle. Treatment of female cattle (heifers* with estradiol 14I to promote growth may also result in increased estradiol 14I concentrations in edible tissues of heifers, and according to Table """ of #$%&', this increase is similar to that observed in steers (1..%fold*. 20+ The &asis $or the 8* statement that 9this increase is much smaller than the large 7ariations o&ser7ed in (re#roducti7el6) c6cling and #regnant cattle and is thus ,ell ,ithin the range o$ naturall6 o&ser7ed le7els is clearly illustrated by comparing the levels of estradiol 14I in edible tissues of treated steers and heifers shown in Table """ of #$%&' with the naturally%occurring levels of estradiol 14I in cattle shown in Table "" of #$%&'. $oncentrations of estradiol 14I in muscle of treated steers and heifers ranged from &%17 pg/g, while naturally%occurring concentrations range from 1.&%1' pg/g in steers, 1)%1& pg/g in heifers, and 10%102 pg/g in pregnant cattle. Therefore, even though veterinary use of estrogens to promote growth can increase estrogens in cattle to above normal levels (11th 3eport on $arcinogens*, this increase is ,ell ,ithin the range o$ naturall6 o&ser7ed le7els (45 +irst Written 5ubmission*. Q2. W/'$ 7'& $/% .%'&"# $" 1"#1,*d% 0". $/% 0+.&$ $+2% +# $/% 2002 US R%-".$ "# C'.1+#"(%#%&+& $/'$ %&$."(%#& ?+#1,*d+#( "%&$.'d+",I):M@ '.% 1'.1+#"(%#+1 #"$ "#,4 34 .%1%-$".I2%d+'$%d %00%1$& 3*$ $/'$ +# 'dd+$+"# $/%.% '.% -"&&+3,4 34 d+.%1$ '#d +#d+.%1$ (%#"$"8+1 2"d% "0 '1$+"#9 W'& +$ 3%1'*&% "0 #%7 d%=%,"-2%#$& +# &1+%#$+0+1 .%&%'.1/ $/'$ 3%1'2% '='+,'3,% '0$%. )AAA9 21+ As e #lained in the second #aragra#h o$ the <ntroduction to the 11 th "e#ort on !arcinogens (E!-101 and 8*-22): the "e#ort on !arcinogens lists all su&stances ,hich are =no,n (or reasona&l6 antici#ated to &e) human carcinogens and to ,hich a signi$icant num&er o$ 8* residents are e #osed+ This re#ort is routinel6 #re#ared e7er6 t,o to $our 6ears &6 the >ational To icolog6 %rogram and #u&lished &6 the )e#artment o$ Bealth and Buman *er7ices+ 4/ <t $ollo,s: then: that each "e#ort on !arcinogens ,ill include u#dated in$ormation on each carcinogen as that in$ormation &ecomes a7aila&le+

43 <n E hi&it E!-3/: )a en&erger et al+ #resent $indings deri7ed $rom a com#rehensi7e search o$ the scienti$ic literature on estradiol 14I residues in edi&le tissues o$ cattle+ 4/ htt#:((nt#+niehs+nih+go7(inde +c$mRo&EectidU42012222-.).4-!E.A-1A20E922.18!20/0

'T()*320("(Add+3 %age !-02 22+ The 10th and 11th "e#orts on !arcinogens ,ere #u&lished in 2002 and 2000: res#ecti7el6+ *teroidal estrogens ,ere $irst listed as 9=no,n to &e a human carcinogen9 in the 10 th "e#ort+40 .oth the 10th and 11th "e#orts include a section that discusses the e7idence $or genoto ic e$$ects o$ steroidal estrogens+ This section is 7irtuall6 identical &et,een the "e#orts+ !ited in this section are t,o re$erences: one article #u&lished in 1992 42 and the 1999 <A"! Monogra#h on Bormonal !ontrace#tion and %ost-meno#ausal Thera#6+ <t is there$ore clear that the statements on genoto icit6 in &oth the 10th and 11th "e#orts on !arcinogens - #u&lished in 2002 and 2000: res#ecti7el6 - ,ere &ased #rimaril6 on the $indings o$ the 1999 <A"! Monogra#h and not #rom#ted &6 ne, de7elo#ments in scienti$ic research that &ecame a7aila&le a$ter 1999+ 23+ Again: it should &e em#hasiFed that the $indings o$ the "e#ort on !arcinogens and the <A"! Monogra#h s#ea= to the general ris= $rom estrogens at le7els e #onentiall6 higher than those $ound in residues in meat $rom treated cattle+ The A##ellate .od6 and the original Hormones #anel re7ie,ed the earlier 7ersion o$ the 1999 <A"! Monogra#h o$ten cited &6 the E! in these #roceedings and con$irmed that studies such as the Monogra#h: constituteOdP general studies ,hich dOidP indeed sho, the e istence o$ a general ris= o$ cancer@ &ut the6 dOidP not $ocus on and dOidP not address the #articular =ind o$ ris= here at sta=e - the carcinogenic or genoto ic #otential o$ the residues o$ those hormones $ound in meat deri7ed $rom cattle to ,hich the hormones had &een administered $or gro,th #romotion #ur#oses+44 2/+ The #otential $or ad7erse e$$ects $rom hormones at these high le7els is not in dis#ute+ 48 The materials and $indings cited &6 the E! (1999 <A"! Monogra#h@ 11 th "e#ort on !arcinogens) are not: ho,e7er: e7idence o$ a ris= $rom meat $rom cattle treated ,ith estradiol $or gro,th #romotion #ur#oses+ Q3. T/% 2002 US R%-".$ "# C'.1+#"(%#%&+& &$'$%& +#$%. ',+' $/'$> 6T/% R"C d"%& #"$ -.%&%#$ ;*'#$+$'$+=% '&&%&&2%#$& "0 $/% .+&D& "0 1'#1%. '&&"1+'$%d 7+$/ $/%&% &*3&$'#1%&. T/*& ,+&$+#( "0 &*3&$'#1%& +# $/% R"C "#,4 +#d+1'$%& ' -"$%#$+', /'J'.d '#d d"%& #"$ %&$'3,+&/ $/% %8-"&*.% 1"#d+$+"#& $/'$ 7"*,d -"&% 1'#1%. .+&D& $" +#d+=+d*',& +# $/%+. d'+,4 ,+=%&. S*1/ 0".2', .+&D '&&%&&2%#$& '.% $/% .%&-"#&+3+,+$4 "0 $/% '--."-.+'$% 0%d%.',5 &$'$%5 '#d ,"1', /%',$/ .%(*,'$".4 '#d .%&%'.1/ '(%#1+%&.6 I0 &"5 /'=% $/% 1"2-%$%#$ US '*$/".+$+%& 2'd% $/% ;*'#$+$'$+=% '&&%&&2%#$ "0 $/% .+&D& "0 1'#1%. -"&%d 34 $/% .%&+d*%& "0 &+8 /".2"#%& +# 2%'$ 0."2 '#+2', $.%'$%d 0". (."7$/ -."2"$+"#9 I0 #"$5 7/%# '.% 4"* ("+#( $" d" +$9 20+ The #rocedures used &6 1)A $or assessing the human sa$et6 o$ 7eterinar6 drugs used in $ood#roducing animals are #u&licl6 a7aila&le and descri&ed in detail at htt#:((,,,+$da+go7(c7m(3uidance(guideline3#t2+html+ 1or these com#ounds: 1)A $ocuses its e7aluations on the ris=s o$ intermittent: chronic e #osure o$ humans to relati7el6 lo, concentrations o$ residues+ 1)A tailors the t6#e o$ to icological testing re5uired to sho, the sa$et6 o$ each com#ound according to its #ro#osed use: #ro&a&le e #osure o$ humans to &oth the #arent com#ound and its meta&olites: and its #ossi&le e$$ects as o&ser7ed in &iological s6stems+ 1or some com#ounds: onl6 a minimum o$ testing is re5uired ,hile other com#ounds ma6 re5uire more e tensi7e to icological e7aluation+
6rior to the 12th 3eport on $arcinogens, con7ugated estrogens were listed in the ' 3eport in 1.1, as known to be human carcinogens " and a number of individual steroidal estrogens (non%con7ugated, including estradiol%17, estrone, ethinylestradiol, and mestranol* were listed as reasonably anticipated to be human carcinogens. 42 Hager A) and Diehr A3+ Molecular mechanisms o$ estrogen carcinogenesis+ Annu "e7 %harmacol To icol 1992@ 32: 203-232+ 44 -ppellate 8ody 3eport, EC Hormones, para. )22. 48 See: e.g.: 8* 1irst 'ritten *u&mission: #ara+ 1/1@ 8* "e&uttal *u&mission: #aras+ 38-39+
40 th

'T()*320("(Add+3 %age !-03 22+ <n line ,ith the 11th 8* "e#ort on !arcinogens: 1)A considers estradiol 14I to be a human carcinogen. (!owever, it should be emphasi9ed that the carcinogenicity of estradiol 14I in humans is based largely on epidemiological studies of women taking estradiol 14I as post%menopausal therapy, the doses of which are e:ponentially higher doses than those in residues of estradiol 14I present in beef.7.* +;- concluded that estradiol 14I is not a genoto:ic agent, and that any carcinogenic effects of estradiol 14I in e:perimental animals are a conse<uence of persistent overstimulation of the hormonal system. "f consumption of residues of estradiol 14I in edible tissues of food%producing animals does not cause such persistent overstimulation of the hormonal system in humans, then +;concludes that individuals consuming those residues will not be sub7ect to an increased risk of cancer. 24+ Assessment o$ the ris=s to human health associated ,ith the use o$ se steroids in $ood#roducing animals #resents uni5ue challenges due to the $act that e #osure to the com#ound occurs against a &ac=ground le7el o$ endogenous #roduction in all segments o$ the #o#ulation+ 1)A has concluded that $or estradiol 14I (and its simple ester derivatives*, human safety can be assured without the need for e:tensive to:icological testing in e:perimental animals. This is because the amount of estradiol 14I present in edible tissues of food%producing animals is very small relative to the endogenous production in humans. +;- has concluded that no physiological effect (or pathological effect, such as cancer* will occur from chronic ingestion of animal tissues that contain a residue level of estradiol 14I e<ual to 1= or less of the amount produced daily by the segment of the population with the lowest endogenous production (prepubertal boys*. 8ased on this conclusion, +;- has set a safe concentration of 2.20 micrograms for estradiol 14I. To obtain +;- approval for drug intended for use in food animals that contains estradiol 14I, the drug>s sponsor must demonstrate that residues of estradiol 14I in edible tissues from animals treated with that drug will not e:ceed the permitted increased e:posure. This re<uirement has been satisfied for all of the veterinary drugs containing estradiol 14I that are approved by +;- for use as growth%promoting agents in cattle. QC. T/% 2002 US R%-".$ "# C'.1+#"(%#%&+& &$'$%& +#$%. ',+' $/'$> 6E&$+2'$+#( $/% %8$%#$ $" 7/+1/ ,+&$+#( ' &*3&$'#1% +# $/% R"C -."$%1$& -*3,+1 /%',$/ +& -%./'-& $/% 2"&$ d+00+1*,$ $'&D +# -.%-'.+#( $/% R"C. T/% 1'.1+#"(%#+1 .+&D ?+.%.5 $/% -."3'3+,+$4 "0 d%=%,"-+#( 1'#1%.@ d%-%#d& "# 2'#4 $/+#(&5 +#1,*d+#( $/% +#$%#&+$45 ."*$%5 '#d d*.'$+"# "0 %8-"&*.% $" ' 1'.1+#"(%#. P%"-,% 2'4 .%&-"#d d+00%.%#$,4 $" &+2+,'. %8-"&*.%&5 d%-%#d+#( "# $/%+. '(%5 &%85 #*$.+$+"#', &$'$*&5 "=%.',, /%',$/5 (%#%$+1&5 '#d 2'#4 "$/%. 0'1$".&. O#,4 +# ' 0%7 +#&$'#1%& 1'# .+&D 0". 1'#1%. 3% %&$+2'$%d 7+$/ 1"2-,%$% 1"#0+d%#1%5 '#d $/%&% %&$+2'$+"#& .%;*+.% &$*d+%& "0 ,"#(I$%.2 /*2'# %8-"&*.%& '#d 1'#1%. +#1+d%#1% +# .%&$.+1$%d %#=+."#2%#$&5 7/+1/ .'.%,4 '.% '='+,'3,%.6 D%&-+$% $/+& .%1"(#+$+"# "0 $/% d+00+1*,$+%&5 1"*,d 4"* -,%'&% %8-,'+# +0 4"* /'=% #%=%.$/%,%&& -%.0".2%d $/% ,"#(I$%.2 /*2'# %8-"&*.%& $" $/% .%&+d*%& "0 $/%&% /".2"#%& +# $.%'$%dI2%'$ +# ".d%. $" ;*'#$+04 +0 $/%4 -"&% ' .+&D $" /*2'# /%',$/9 D" 4"* D#"7 +0 LECFA /'& -%.0".2%d &*1/ ' &-%1+0+1 ;*'#$+$'$+=% d"&%I.%&-"#&% '&&%&&2%#$9 28+ 1or the 8* #ers#ecti7e on long-term human e #osure to hormone residues in meat $rom treated cattle, please refer to our answer to ?uestion 3 a&o7e+ 29+ 1or AE!1A;s a##roach $or assessing the e$$ects o$ long-term dietar6 e #osure to hormone residues: #lease see the 02nd "e#ort o$ the Aoint 1AO('BO E #ert !ommittee on 1ood Additi7es ('BO Technical "e#ort *eries 893: ##+ 04-20: 2000) as ,ell as the in$ormation #ro7ided &6
49

See 8* "e&uttal *u&mission: $n+ 42+

'T()*320("(Add+3 %age !-0/ )r+ Tritscher: AE!1A *ecretariat: at the Meeting ,ith the E #erts held in 3ene7a on 24-28 *e#tem&er 2002+ Q<. I# .%,'$+"# $" -'.'. G "0 $/% US &$'$%2%#$ "0 3 O1$"3%. -,%'&% %8-,'+# +0 4"* /'=% #"7 2'd% ' d%$%.2+#'$+"#9 I0 #"$5 7/'$ d"%& +$ 2%'# 63%+#( +# $/% -."1%&& "0 .%=+%7+#(69 W/'$ '.% 4"* d"+#( %8'1$,49 S+#1% $/% EC!& .+&D '&&%&&2%#$ d'$%& "0 )AAA ?'#d .%=+%7%d '#d 1"#0+.2%d +# 2000 '#d 2002@5 /"7 ,"#( +& 4"*. .%=+%7 -."1%&& ("+#( $" $'D%9 I& $/%.% '#4 +#0".2'$+"# $/'$ $/% US +& #"7 2+&&+#(9 I& $/%.% '#4 2%1/'#+&2 34 7/+1/ $/% US 7+,, 1"2-,%$% +$& .%=+%7 7+$/+# ' .%'&"#'3,% -%.+"d "0 $+2% #"79 30+ At this stage o$ the #roceedings: it is irrele7ant ,hether or not the 8nited *tates has determined that the E!;s &ans are or not 'TO-inconsistent+ The determination o$ ,hether or not the E! has &rought its measures into con$ormit6 ,ith )*. recommendations and rulings no, rests ,ith the %anel+ 31+ As noted in #aragra#hs 19-22 and Ta&le 1 o$ the 8* "e&uttal *u&mission as ,ell as in the 8* Oral *tatement (Degal <ssues: #aragra#hs 9-10) at the second su&stanti7e meeting ,ith the %anel: the E! has #roduced materials related to its measures in a staggered: #iecemeal $ashion+ The 5uestion o$ ,hether the 8nited *tates is still 9missing9 in$ormation ,ould #erha#s &e &etter suited $or the E!: #articularl6 in light o$ the $act that it attem#ted to #roduce e7idence in su##ort o$ its measures as recentl6 as the meeting ,ith the scienti$ic e #erts+ QF. T/% US &$'$%d $/'$ $/% .+&D '&&%&&2%#$& -%.0".2%d 34 LECFA 2*&$ 3% -.%&*2%d $" 3% +# 1"2-,+'#1% 7+$/ A.$+1,% <.). "0 $/% SPS A(.%%2%#$. B*$ $/% .+&D '&&%&&2%#$& -%.0".2%d 34 LECFA 0". $/%&% /".2"#%& 0". '#+2', (."7$/ -."2"$%.& d" #"$ 1"#$'+# $/% D+#d "0 ;*'#$+$'$+=% ". ;*',+$'$+=% %8-"&*.% '&&%&&2%#$ $/'$ C'#'d' '#d $/% US 1.+$+1+&% $/% EC 0". #"$ /'=+#( d"#%. N%=%.$/%,%&&5 $/% US '#d C'#'d' '--%'. $" '&&*2% $/'$ LECFA!& '&&%&&2%#$& '.% 1"#&+&$%#$ 7+$/ A.$+1,% <.). SPS. P,%'&% %8-,'+# 7/4 *#d%. $/%&% 1+.1*2&$'#1%& 7"*,d $/% EC!& .+&D '&&%&&2%#$ 3% +#1"#&+&$%#$ 7+$/ A.$+1,% <.). "0 $/% SPS A(.%%2%#$. 32+ As noted in the 8* res#onse to E! ?uestion 1 (to the 8nited *tates and !anada) a&o7e: AE!1A com#leted a 5uantitati7e e #osure assessment $or each o$ the hormones at issue in these #roceedings+ The E!;s insistence on highlighting the shortcomings o$ its o,n 9ris= assessment9 &6 com#aring its e$$orts to those o$ AE!1A is there$ore #er#le ing+ The 8nited *tates ,ould also reiterate that there are se7eral additional reasons $or $inding that the E! has $ailed to conduct a ris= assessment: as a##ro#riate to the circumstances: $or estradiol 14I+ These include $ailing to satis$6 other ste#s (o$ the $our) $or com#leting a ris= assessment and $ailing to su##ort the scienti$ic conclusions reached in its O#inions on scienti$ic e7idence+ The 8nited *tates has discussed these shortcomings in detail in its #re7ious su&missions to the %anel+

'T()*320("(Add+3 %age !-00 ANNEX CI< COMMENTS BY THE UNITED STATES ON THE REPLIES OF THE EUROPEAN COMMUNITIES TO QUESTIONS POSED BY THE PANEL AFTER THE SECOND SUBSTANTI E MEETING (31 Octo&er 2002) 1+ The 8nited *tates a##reciates this o##ortunit6 to #ro7ide comments on the 18 Octo&er 2002: 9"e#lies to ?uestions $rom the %anel a$ter the *econd *u&stanti7e Meeting &6 Euro#ean !ommunities9 (9E!9) to the 0 Octo&er 2002: additional 5uestions $rom the %anel+ Q*%&$+"#& $" ',, $/% P'.$+%&> Q). W+$/ .%0%.%#1% $" $/% &$'$%2%#$ 34 $/% E*."-%'# C"22*#+$+%&5 +#$%. ',+' +# -'.'. )2 "0 $/% EC .%-,4 $" Q*%&$+"# 3 "0 $/% U#+$%d S$'$%&5 d" $/% -'.$+%& 1"#&+d%. $/'$ ' P'#%, +& %#$+$,%d $" 'dd.%&& 6&4&$%2+1 1,'+2&6 ". +&&*%& .%,'$%d $" 6&4&$%2+1 "3,+('$+"#&6 '#d5 +0 &"5 $" 7/'$ %8$%#$9 2+ The E!;s res#onse to ?uestion 1 reem#hasiFes se7eral #oints raised in the 8* res#onse to this 5uestion+ <n our res#onse: ,e e #lained ho, ,hat the E! re$ers to as E!;s 9s6stemic claims9 are #remised on the E!;s 7ie, o$ ho, the Understanding on *ules and Procedures %overning t e Settlement o$ <isputes (9)*89) should &e re,ritten rather than grounded in the actual te t o$ the )*8+ The E!;s res#onse highlights this $act+ 1or e am#le: the E! argues that 9$rom the E!;s #oint o$ 7ie,: the continued a##lication o$ sanctions in the $ace o$ #resumed com#liance and in the a&sence o$ a com#liance re7ie, constitutes a 7iolation o$ a #rocedural nature: irres#ecti7e o$ the su&stanti7e re5uirements o$ actual com#liance+9 (Em#hasis added)+ This statement is remar=a&le $or se7eral reasons+ 3+ 1irst: rather than directing the %anel;s attention to a s#eci$ic o&ligation in the )*8 ,hich the 8nited *tates has allegedl6 &reached: the E! descri&es a claim &ased on the 9E!;s #oint o$ 7ie,9 o$ ,hat the )*8 should #ro7ide $or+ As ,e ha7e #re7iousl6 sho,n: the E!;s #oint o$ 7ie, on the )*8 does not e5uate ,ith actual o&ligations o$ 'TO Mem&ers under the )*8+ *econd: the E! relies on its theor6 o$ 9#resumed com#liance9: &6 ,hich it &elie7es that through a sim#le declaration o$ com#liance it in turn satis$ied its &urden o$ #roo$ as a com#laining #art6 in 'TO dis#ute settlement+ 'e ha7e demonstrated in #re7ious su&missions that a declaration o$ com#liance does not amount to 9#resumed com#liance9 $or #ur#oses o$ dis#ute settlement+ Third: the E! argues that a 8* &reach o$ these 9#rocedural9 or 9s6stemic9 o&ligations should &e $ound 9irres#ecti7e o$ the re5uirements o$ actual com#liance+9 The E!;s argument is untena&le+ A multilateral determination that the E! has com#lied ,ith the )is#ute *ettlement .od6;s (9)*.;s9) recommendations and rulings in the Hormones dis#ute is an essential #rere5uisite to an6 $inding o$ a 8* &reach o$ its o&ligations under the )*8+ /+ 1inall6: the E! again notes that 9se7eral %anels in the #ast ha7e alread6 ruled on Article 23 claims+9 The 8nited *tates has #ro7ided detailed arguments relating to these earlier #roceedings and demonstrated ho, the6 are ina#t to the situation at hand+ 80 QC. H'& $/% E*."-%'# C"22*#+$+%& '&&%&&%d +# ' &4&$%2'$+1 2'##%. $/% %8+&$%#1% '#d ,%=%, "0 .+&D& 0."2 0'+,*.% $" "3&%.=% (""d =%$%.+#'.4 -.'1$+1%& 7+$/ .%&-%1$ $" $/% 'd2+#+&$.'$+"# "0 "%&$.'d+", ):M '& ' (."7$/ -."2"$+#( /".2"#% $" 1'$$,%5 +# -'.$+1*,'. +# $/% U#+$%d S$'$%&! '#d

80

See: e.g.: 8* "e&uttal *u&mission: #aras+ 2-8: 10-12+

'T()*320("(Add+3 %age !-02 C'#'d'!& 2'.D%$&9 I0 &"5 -,%'&% +#d+1'$% 7/%.% $/+& '&&%&&2%#$ +& $" 3% 0"*#d +# $/% %=+d%#1% -."=+d%d $" $/% P'#%,. 0+ The E!;s res#onse to ?uestion / is $la,ed $or se7eral reasons+ 8#on re7ie, o$ the materials #ut $or,ard &6 the E! in su##ort o$ its claim that good 7eterinar6 #ractices are not adhered to in the 8nited *tates: it is clear that the E! has neither demonstrated the e istence o$ such a ris=: nor has it assessed the #ro&a&ilit6 o$ the $ailure o$ good 7eterinar6 #ractices in the 8nited *tates+ 2+ As noted &6 !anada in its res#onse to ?uestion /: the E! a##ears to rel6 on a dra$t document (E hi&it E!-43) that #ur#ortedl6 assesses the 9ris=9 arising $rom a&usi7e use and di$$iculties o$ control o$ gro,th #romoting hormones+ The E! has not clari$ied the actual status o$ this dra$t document: and in its 1999 O#inion re$ers to it onl6 &rie$l6+ This dra$t document and the 1999 and 2002 O#inions do not assess the ris= o$ $ailure o$ controls or misuse in the 8nited *tates $or se7eral reasons+ 'e ha7e alread6 highlighted the most signi$icant shortcomings in these materials in our #re7ious su&missions to the %anel+81 4+ The E! claims to ha7e demonstrated the 9e istence o$ a ris=9 o$ the $ailure to satis$6 good 7eterinar6 #ractices in the 8nited *tates+ <n su##ort o$ this claim: the E! cites to se7eral o$ its misuse studies: noting that the cited e #eriments 9,ere carried OoutP ,ith hormonal im#lants that are actuall6 licensed $or use in the 8* and !anada and considered &oth their recommended use and situations o$ misuse and(or misuse+9 The 8nited *tates has #ro7ided detailed arguments demonstrating that these misuse studies are not re#resentati7e o$ the actual use o$ the si hormones at issue $or gro,th #romotion #ur#oses in the 8nited *tates+ "ather: the studies #ortra6 unrealistic dosing scenarios: and onl6 then demonstrate 7iolati7e residue le7els ,hen animals are o7erdosed ,ith numerous im#lants (stac=ing o$ im#lants)+ )r+ .oo&is descri&ed these studies and clari$ied that the6 are not re#resentati7e o$ realistic conditions nor do the6 in an6 ,a6 meaning$ull6 assess a ris= $rom misuse+ 82 8+ <ndeed: none o$ the e #erts (including )r+ )e .ra&ander) #ointed to an6 e7idence #resented &6 the E! o$ an actual ris= $rom the misuse o$ the si hormones as gro,th #romoters in cattle in the 8nited *tates+ >or did an6 o$ the e #erts o#ine that the E! had actuall6 assessed in a #ro#er manner the li=elihood that such a $ailure ,ould occur+83 9+ The E! also claims to ha7e underta=en studies or #ro7ided e7idence demonstrating the 9le7el o$ ris=9 $rom 9situations o$ a&use and(or misuse+9 Bo,e7er: none o$ the materials #resented &6 the E! #ro7ide e7idence o$ a ris= o$ a $ailure o$ good 7eterinar6 #ractices: nor do the6 assess the ris= that such a $ailure ,ould occur+ The 8nited *tates has discussed this ga# in the E!;s case (including the E!;s $ailure to satis$6 the re5uirements o$ *%* Article 0+2) in detail+8/ <n #articular: ,e ha7e noted the star= a&sence o$ an6 e7aluation &6 the E! o$ the actual ,or=ings o$ the 8* $ood sa$et6 s6stem: including o7ersight &6 $ederal ins#ectors and use o$ #rograms such as the >ational "esidue %rogram to monitor the use o$ gro,th #romoting hormones in the cattle industr6: as ,ould &e re5uired &6 *%* Article 0+2+ 'e ,ill not re#eat those arguments here: &ut ,ill instead highlight a $e, $undamental shortcomings in the E!;s 9assessment9 o$ the #otential $or the $ailure o$ controls+ 10+ 1or instance: the E!;s arguments relating to the e istence o$ a ris= o$ multi#le dosing: or stac=ing o$ im#lants are misguided+ The E! argues that there are economic incenti7es to misuse gro,th #romoting hormones (i.e.: not a&ide &6 on-la&el instructions)+ 80 Bo,e7er: no such incenti7es
See: e.g.: 8* "e&uttal *u&mission: *ection <<+.+/+ See "es#onse o$ )r+ .oo&is to %anel ?uestion 22+ 83 See 8* "es#onse to %anel ?uestion / a$ter the *econd *u&stanti7e Meeting+ 8/ See: e.g.: 8* "e&uttal *u&mission: *ection <<+.+/@ 8* !omments on "es#onses o$ the E #erts: #aras+ 101-112+ 80 See: e.g.: E hi&it E!-43: #ara+ 22+
82 81

'T()*320("(Add+3 %age !-04 e ist: as indi7idual im#lants are mar=eted to #ro7ide o#timal doses+ 82 The E!;s #ur#orted 9e7idence9 o$ the ris= $or stac=ing o$ im#lants is the 8ni7ersit6 o$ >e&ras=a .ee$ !attle 8#date (E hi&it 8*-24): cited e tensi7el6 in E hi&it E!-43+84 Bo,e7er: as noted &6 the 8#date;s author: )r+ )ee 3ri$$in: the >e&ras=a .ee$ !attle 8#date does not su##ort the conclusion that stac=ing o$ im#lants is either a common or recommended #ractice in the 8nited *tates+ To the contrar6: )r+ 3ri$$in notes: 8sing more than a single im#lant at the same time has &een termed 9dou&le im#lanting9 or 9stac=ing9+ *tac=ing im#lants: intentionall6 or unintentionall6: has &een =no,n $or decades to cause &oth gain and $eed e$$icienc6 to &e #oorer than ,hen 1)A a##ro7ed im#lants ,ere used in accordance ,ith the 1)A a##ro7ed la&el+ +++ *tac=ing ,ould cost our &ee$ #roducers Z00 to Z100 (8*)) #er animal in lo,er carcass 7alue+ 11+ <n other ,ords: according to )r+ 3ri$$in: 9OuPse o$ 1)A a##ro7ed gro,th #romotants other than as la&eled is a costl6 mista=e+9 This is ,h6 9&ee$ #roduction s#ecialists in the 8*A ne7er recommend simultaneous or dou&le im#lant administration+9 88 The E! also notes (in its ans,er to ?uestion 12) that 9multi#le im#lanting o$ animals ,ith these hormones is recommended &6 the manu$acturers+9 Bo,e7er: the E! #ro7ides no e7idence to su##ort this statement+ To the contrar6: 1)A a##ro7al o$ 7eterinar6 drugs includes the regulation o$ manu$acturers; la&els and none o$ the la&els $or the gro,th #romoting hormones at issue recommend treatment ,ith more than one im#lant at a time+89 12+ The E! also cites to the results o$ its missions to the 8nited *tates as 9e7idence9 that there is a ris= o$ $ailure o$ controls+ The cited materials conclude that hormone im#lants ,ere &eing illegall6 used in the 8* 7eal industr6+90 The E! contends that this illegal use o$ hormones in the 7eal industr6 is someho, e7idence o$ a ris= o$ $ailure o$ controls in all sectors o$ &ee$ cattle #roduction+ 91 Bo,e7er: gro,th #romoting hormones are not a##ro7ed in the 8nited *tates $or use in cattle intended $or the 7eal industr6+ *uch use is illegal and an6 carcasses or meat #roducts $rom 7eal cal7es treated ,ith gro,th #romoting hormones ,ould &e deemed to &e 9adulterated9 and #rohi&ited $rom sale in the 8nited *tates and $or e #ort+ Misuse in this sector o$ animal agriculture cannot &e e tra#olated to a com#letel6 se#arate sector ($eedlot cattle) in ,hich the use o$ gro,th #romoting hormones is a##ro7ed and a s6stem o$ controls e ists $or their legal use+ <t is telling that the E! relies on anecdotal e7idence $rom the 7eal industr6 in its attem#t to cast as#ersions on the e$$icac6 o$ the 8* s6stem o$ controls in $eedlot cattle+ The a&sence o$ e7idence o$ misuse in $eedlot cattle is testament to the e$$ecti7eness o$ controls in that industr6+ <n an6 e7ent: the 8nited *tates too= all necessar6 ste#s to deal ,ith the #ro&lem o$ illegal use o$ im#lants in 7eal cal7es+ 13+ 1or e am#le: u#on disco7er6 o$ the illegal use o$ gro,th #romoting hormones in the 7eal industr6: the 8nited *tates )e#artment o$ Agriculture;s 1ood *a$et6 and <ns#ection *er7ice (91*<*9) #u&lished >otice 31-0/: Veri$ication o$ implant usage in non9ruminating calves 8i.e.' veal calves:'
See Detter $rom )r+ )ee 3ri$$in (E hi&it 8*-28)+ E hi&it E!-43: #aras+ 22 ($n+ 30) and /4 ($n+ 23): and $n+ 34+ 88 E hi&it 8*-28 (em#hasis added)+ 89 1or e am#le: the manu$acturer;s la&el $or *6no7e %lus im#lants (estradiol #lus tren&olone acetate@ htt#:((,,,+,6eth+com(#roductsR#roductU(,6ethVhtml(home(#roducts(animalVhealth(*H>OCEGJc2Jae J20<m#lants(#rescri&ingin$o+html) states 9)O*A3E: One im#lant (eight #ellets): containing 200 mg o$ tren&olone acetate and 28 mg o$ estradiol &enFoate: is administered to each steer or hei$er &6 su&cutaneous im#lantation in the middle one-third o$ the ear9 and 9)<"E!T<O>*: <m#lant com#lete contents o$ one cartridge cell #er steer or hei$er+9 90 See: e.g.: E hi&it E!-43: #aras+ 3/-30@ see E! "es#onses to ?uestions $rom the %anel A$ter the *econd *u&stanti7e Meeting: ?uestion /: #aras+ 10-12 and $ootnotes /-0+ 91 See E! "es#onses to ?uestions $rom the %anel A$ter the *econd *u&stanti7e Meeting: ?uestion /: #aras+ 10-12 and $ootnotes /-0+
84 82

'T()*320("(Add+3 %age !-08 providing instructions $or inspection program personnel to use " en t e1 suspect t e use o$ implants in non9ruminating calves+ This direction to $ield #ersonnel made clear that an6 non-ruminating (7eal) cal$ #resented $or slaughter ,ith an im#lant or on ,hich there is e7idence o$ im#lant use ,as to &e condemned &6 8*)A ins#ectors+ 8*)A ins#ectors 7isuall6 ins#ect 7eal cal7es (and $eedlot cattle) $or an6 signs o$ im#lant use during ante-mortem (#re-slaughter) and #ost-mortem (#ost-slaughter) ins#ection+ 1/+ Additionall6: on 12 Aul6 200/: the 8* 1ood and )rug Administration (91)A9) and 1*<* Eointl6 issued a letter to the American Ceal <ndustr6: as ,ell as to other trade associations: reiterating that the #ractice o$ im#lanting $ood animals that are to &e mar=ed as 97eal9 ,ith gro,th #romoting im#lants is illegal+ 1inall6: in order to ensure that 7eal illegall6 treated ,ith gro,th #romoting hormones ,as not entering the 8* mar=et or e #orted: 1*<* included the testing o$ 7eal in its >ational "esidue %rogram+ There ha7e &een no #ositi7e sam#les $ound in either 200/ or 2000: a $act that is clear e7idence o$ the e$$ecti7eness o$ 1*<*(1)A;s e$$orts to eradicate illegal use o$ hormones in this industr6+ 10+ <n sum: u#on learning o$ an illegal use o$ gro,th #romoting hormones in the 7eal industr6: the 1*<* and 1)A too= the necessar6 ste#s to sto# this illegal use+ These e$$orts are not e7idence o$ a $ailure o$ controls in the $eedlot cattle industr6: $or ,hich the use o$ gro,th #romoting hormones is a##ro7ed+ <$ an6thing: the anecdotal e7idence o$ the illegal use o$ hormones in the 8* 7eal industr6 is e7idence o$ the a&ilit6 o$ the 8* $ood sa$et6 s6stem to isolate and deal ,ith an6 #otential #ro&lems in order to ensure that meat sold domesticall6: as ,ell as $or e #ort: com#lies ,ith $ederal re5uirements+ 12+ 1inall6: the 8nited *tates ,as sur#rised and disa##ointed to see that the E! has mis5uoted 8* arguments regarding the #otential $or the $ailure o$ controls+ The E! ascri&es the $ollo,ing statement to the 8nited *tates: 9OtPhe 8* argues that Yno $ood sa$et6 s6stem is sa$e:; im#l6ing that the other 'TO mem&ers are o&liged to acce#t the $ailures o$ the 8* s6stem+9 To the contrar6: ,hat the 8nited *tates actuall6 said ,as that 9OnPo $ood sa$et6 s6stem is #er$ect+9 There is a 7ast di$$erence &et,een sa$et6 and #er$ection+ The 8* $ood sa$et6 s6stem is 9sa$e9 and ,e ha7e demonstrated ho, our s6stem $unctions e$$ecti7el6 and #rotects consumers+ <n ma=ing the statement that no s6stem is 9#er$ect9 at the second su&stanti7e meeting ,ith the %anel: the 8nited *tates ,as sim#l6 highlighting the $act that the E! has a##arentl6 de7elo#ed a standard $or good 7eterinar6 #ractices that ,ould not tolerate an6 $ailures ,hatsoe7er - a 7irtual 100J assurance that controls ,ould ne7er $ail+ The E!;s #osition is ironic in light o$ the $act that the E! cannot control its o,n &lac= mar=et $or the use o$ gro,th #romoting hormones in cattle resulting $rom its im#osition o$ a &an on their use+ <n other ,ords: des#ite its &an: the E! $ails to meet the 7er6 standard it has set $or good 7eterinar6 #ractices in these #roceedings+ <$ this unrealistic and im#ractical standard ,ere to &e ado#ted &6 all 'TO or !ode mem&ers: countries ,ould &e a&le to &an the im#ort o$ E! meat des#ite the E!;s attem#t to &an the use o$ gro,th #romoting hormones+ Q<. I# +$& 1"22%#$& "# 1"22%#$& "0 $/% U#+$%d S$'$%& '#d C'#'d' "# %8-%.$& .%-,+%& $" $/% P'#%, ;*%&$+"#& ?+# -'.$+1*,'. Q*%&$+"# )3@5 $/% E*."-%'# C"22*#+$+%& +#d+1'$%& $/'$ "%&$.'d+", ):M 2+(/$ 3% ' 67%'D (%#"$"8+#6 ?-'.'. CC@. A$ 7/'$ d"&%& +& (%#"$"8+1+$4 "3&%.='3,% +# =+="9 H"7 '.% $/%&% d"&%& 1"2-'.'3,% $" $/"&% 0"*#d +# 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ (."7$/ -."2"$+#( /".2"#%&9 H"7 7"*,d $/+& '&&%.$+"# '00%1$ $/% +d%#$+0+1'$+"# "0 'd=%.&% %00%1$& '#d $/% %=',*'$+"# "0 -"$%#$+', "11*..%#1% "0 $/%&% %00%1$& 0."2 1"#&*2-$+"# "0 2%'$ 0."2 1'$$,% $.%'$%d 7+$/ "%&$.'d+", ):M 0". (."7$/ -."2"$+"# -*.-"&%&9 14+ <n an attem#t to Eusti$6 the dosage o$ estradiol administered to rats in the stud6 &6 !a7alieri et al+ (E hi&it E!-120) as 9not massi7el6 high9: the E! notes in its res#onse to ?uestion 0 the imminent #u&lication o$ an underl6ing stud6 (Mailander et al+) ,hich ,ould su##l6 additional in$ormation+ The cited stud6 has since &een #u&lished and: contrar6 to the E!;s claims: it does not #ro7ide in$ormation

'T()*320("(Add+3 %age !-09 a&out actual e #osure o$ rats to estradiol $ollo,ing im#lantation+ <n $act: it is a com#letel6 di$$erent stud6: in ,hich rats ,ere not treated ,ith estradiol &ut ,ith estradiol-3:/-5uinone: one o$ the catechol meta&olites o$ estradiol+ As the 8nited *tates has #ointed out in #re7ious su&missions: and as ,as con$irmed &6 )r+ .oo&is at the meeting ,ith the e #erts: results o&tained ,ith the catechol meta&olites o$ estradiol cannot &e ta=en as e7idence that estradiol ,ill ha7e the same e$$ect in vivo (&ecause it has not &een esta&lished that the catechol meta&olites $orm in vivo at concentrations high enough to cause deleterious e$$ects)+ There$ore: the re#ort re$erred to &6 the E! in its res#onse to ?uestion 0 (Mailander et al+) #ro7ides no additional in$ormation rele7ant to the stud6 &6 !a7alieri et al+ (E hi&it E!-120)+ The 8nited *tates reiterates its criticisms o$ the !a7alieri et al+ stud6: in ,hich the dose o$ estradiol ,as so high that it resulted in the death o$ nearl6 one hal$ o$ the rats+ *uch a dose is not rele7ant to the relati7el6 minuscule amounts o$ estradiol $ound in &ee$ $rom cattle treated ,ith estradiol 14I $or gro,th #romotion #ur#oses+ Q*%&$+"#& $" $/% E*."-%'# C"22*#+$+%&> QF. S/"*,d $/% P'#%, '(.%% 7+$/ $/% E*."-%'# C"22*#+$+%&! 2'+# 1,'+2 $/'$ $/% U#+$%d S$'$%& '#d C'#'d' /'=% 3.%'1/%d A.$+1,% 23 "0 DSU .%'d $"(%$/%. 7+$/ A.$+1,%& 2).< '#d 22.G5 7/'$ 7"*,d 3% $/% 1"#&%;*%#1%& "0 &*1/ ' 1"#1,*&+"# 0". $/% U#+$%d S$'$%& '#d C'#'d'9 M".% -'.$+1*,'.,45 7"*,d $/% U#+$%d S$'$%& '#d C'#'d'> ?'@ ?3@ ?1@ 3% %8-%1$%d $" 7+$/d.'7 $/% &*&-%#&+"#& "0 1"#1%&&+"#& ". "$/%. "3,+('$+"#& ". &*&-%#d $/%+. '--,+1'$+"#9 3% %8-%1$%d $" +#+$+'$% '# A.$+1,% 2).< -."1%d*.% '('+#&$ $/% EC9 ". 7"*,d $/%4 3% %8-%1$%d $" d" 3"$/9

?P,%'&% #"$% $/'$ $/% P'#%, +& 0*,,4 '7'.% "0 +$& "3,+('$+"#& *#d%. A.$+1,% )A DSU@ 18+ As an initial matter: the 8nited *tates is struc= &6 the $act that the E! #ur#orts to &e a&le to res#ond to the %anel;s 5uestion ,ithout =no,ing ,hat measure ,ould &e $ound inconsistent or ,hat the #recise &asis $or the $inding o$ inconsistenc6 ,ould &e under the h6#othetical+ The %anel in the 5uestion itsel$ highlighted Article 19 o$ the )*8: ,hich s#eci$ies the %anel;s recommendation in the e7ent o$ a $inding o$ an inconsistenc6: and the E! is a,are that the Mem&er concerned retains the discretion on ho, to im#lement an6 such recommendation+ 19+ !onse5uentl6: the E!;s res#onse to ?uestion 2 is rather re7ealing+ 1irst: the E! res#onse is a telling sna#shot o$ its o7erall $ailure to demonstrate that the 8nited *tates has &reached its o&ligations under the )*8 &6 continuing to sus#end concessions to the E! des#ite the E!;s unilateral declaration o$ com#liance+ As a general matter: i$ the 8* sus#ension o$ concessions ,ere a measure in &reach o$ its 'TO o&ligations: the 8nited *tates ,ould not &e a&le to maintain them+ Bo,e7er: the E!;s re#l6 indicates that the 8nited *tates ,ould &e $ree to continue to a##l6 the sus#ension o$ concessions and related o&ligations #ending the outcome o$ an Article 21+0 #roceeding+92 The E! thus admits that e7en under its o,n theor6: the 8* sus#ension o$ concessions is not inconsistent ,ith the )*8+ 1urthermore: the E! thus admits that the sus#ension o$ concessions is not related to an6 9ne,9 determination &6 the 8nited *tates: in &reach o$ Article 23 o$ the )*8: that the E! measures ta=en to com#l6 are inconsistent ,ith the co7ered agreements+ 20+ *econd: the E!;s re#l6 con$irms that the 8nited *tates is not in &reach o$ Article 21+0 o$ the )*8+ 1or e am#le: the E! argues that 9there can &e no dou&t that the 8nited *tates and !anada are
See E! "es#onses to ?uestions $rom the %anel A$ter the *econd *u&stanti7e Meeting (?uestion /): #aras+ 10-12+
92

'T()*320("(Add+3 %age !-20 under an o&ligation to ,ithdra, the sus#ension o$ concessions + + + i$ the6 do not initiate a 21+0 #roceeding+9 Bo,e7er: to date: the E! has $ailed to identi$6 an6 s#eci$ic o&ligation in the te t o$ Article 21+0 that has allegedl6 &een &reached &6 the 8nited *tates+ The 8nited *tates has noted this $ailure on se7eral occasions+93 <t is there$ore remar=a&le that the E! a7ers that 9there can &e no dou&t that Othe 8nited *tatesP OisP under an o&ligation to initiate a 21+0 #roceeding+9 "ather than $inding a &asis $or its claim in the te t o$ Article 21+0: the E!;s claim o$ a 8* &reach is sim#l6 a #roduct o$ its so-called 9s6stemic9 claims o$ a &reach o$ the )*8 ,hich $ind no &asis in the actual te t o$ the )*8+9/ 21+ As ,e ha7e demonstrated: the 8nited *tates ,ould onl6 &e o&ligated to ,ithdra, its a##lication o$ the sus#ension o$ concessions u#on a demonstration &6 the E! (as the com#laining #art6) that it had satis$ied one o$ the three conditions o$ )*8 Article 22+8+ The E! has $ailed to demonstrate that it has satis$ied an6 o$ these conditions+ QG. T/% P'#%, *#d%.&$'#d& $/'$ $/% E*."-%'# C"22*#+$+%& +#+$+'$%d .+&D '&&%&&2%#$& 7+$/ .%&-%1$ $" ',, &+8 /".2"#%& '$ +&&*% ?&%%5 %.(.5 D+.%1$+=% 2003/:C/EC5 $/+.d +#$."d*1$".4 -'.'(.'-/@. ?'@ C"*,d $/% E*."-%'# C"22*#+$+%& 1"#0+.25 7+$/ .%&-%1$ $" "%&$.'d+", ): M '#d +# ,+(/$ "0 +$& &$'$%2%#$ +# -'.'. )A2 "0 +$& .%3*$$', '#d +$& 1"22%#$& "# Q*%&$+"# )C "0 $/% P'#%, $" $/% %8-%.$&5 7/%$/%.> ?+@ ?++@ ?3@ +$ -."1%%d%d $/."*(/ $/% 0"*. &$%-& "0 .+&D '&&%&&2%#$ +d%#$+0+%d 34 C"d%8B ". 1"*,d /'=% -."1%%d%d $/."*(/ $/% 0"*. &$%-& 3*$ d%1+d%d #"$ $" d" &" +# ,+(/$ "0 +$& 0+#d+#(& "# (%#"$"8+1+$4 "0 "%&$.'d+", ): M9

C"*,d $/% E*."-%'# C"22*#+$+%& 1"#0+.25 7+$/ .%&-%1$ $" %'1/ "0 $/% "$/%. 0+=% /".2"#%& '$ +&&*%5 '$ 7/'$ &$'(%?&@ "0 +$& .+&D '&&%&&2%#$ +$ 1"#&+d%.%d $/'$ .%,%='#$ &1+%#$+0+1 %=+d%#1% 7'& +#&*00+1+%#$ '#d d%1+d%d $" -."=+&+"#',,4 3'# $/% +2-".$'$+"# "0 2%'$ $.%'$%d 7+$/ $/"&% /".2"#%& "# $/% 3'&+& "0 '='+,'3,% -%.$+#%#$ +#0".2'$+"#.

22+ <n its res#onse to ?uestion 8: the E! again declares that 9&e6ond dou&t9 it has 9com#leted the $our ste#s Oo$ ris= assessmentP+9 90 The E! also comments that 9OtPhe de$ending #arties ma6 disagree: &ut the6 cannot credi&l6 argue that the Euro#ean !ommunities has not com#leted the $our ste#s o$ the ris= assessment+9 >either o$ these statements is grounded in the realit6 o$ this dis#ute: ,hich includes consultation ,ith scienti$ic e #erts on the s#eci$ic 5uestion o$ ,hether the E! has satis$ied these 7er6 same $our ste#s in its ris= assessment $or estradiol 14I+ >ot onl6 can the 8nited *tates 9credi&l6 argue9 that the E! has $ailed to satis$6 the $our ste#s: the %anel;s scienti$ic e #erts ha7e con$irmed that the E! has not satis$ied each o$ the $our ste#s+ 92
See: e.g.: 8* 1irst 'ritten *u&mission: *ection <C+)+3(a)(iii) (demonstrating: among other things: that Article 21+0 sets no deadline &6 ,hich a #art6 must see= recourse to dis#ute settlement@ Article 21+0 does not o&ligate the original com#laining Mem&er to initiate a com#liance #roceeding@ and !om#liance ,ith Article 21+0 ma6 &e achie7ed through recourse to other #ro7isions o$ the )*8)+ 9/ See 8* 1irst 'ritten *u&mission: *ection <C+)+3(a)(iii)@ 8* Ans,ers to %anel ?uestions a$ter the 1irst *u&stanti7e Meeting: #aras+ 11: 12-14: 38-/0@ 8* "e&uttal *u&mission: #aras+ 0-12+ 90 >ote that the E! a##arentl6 claims in #aragra#h 30 that it has conducted a ris= assessment 9$or all these hormones+9 To date: the 8nited *tates ,as not a,are that the E! claimed to ha7e satis$ied its o&ligations under *%* Article 0+1 $or the $i7e #ro7isionall6 &anned hormones+ 92 8* !omments on the "es#onses o$ the *cienti$ic E #erts: #aras+ 18-32@ see also 8* Oral *tatement (E #ert <ssues) at the *econd *u&stanti7e Meeting: #aras+ 18-20+
93

'T()*320("(Add+3 %age !-21 23+ <n its attem#t to demonstrate that it has com#leted a ris= assessment $or estradiol: the E! cites to section /+1+0 o$ its 1999 O#inion in ,hich it concludes that 9the 1)A;s acce#ta&le dail6 inta=e (102 ng(#er #erson(da6) could e ceed the dail6 #roduction rate o$ oestradiol &6 1:400 $old (o$ #re-#u&ertal children)+9 Ta=ing the lo, &ioa7aila&ilit6 o$ estradiol into account and assuming the meta&olic clearance rate o$ estradiol in children is one hal$ that o$ adults: the E! then adEusts its 95uantitati7e9 estimate and concludes that 9the 1)A acce#ta&le dail6 inta=e could still &e 80 $old too high+9 These statements are incorrect and unsu##orted &6 scienti$ic e7idence or mathematical anal6sis+ 2/+ 1irst: the 1)A has ne7er set an acce#ta&le dail6 inta=e (A)<) $or estradiol+ <nstead: as e #lained in 1)A 3uidance $or <ndustr6 >o+ 3: 94 $or endogenous se steroids li=e estradiol: 1)A sets a #ermitted increased e #osure &ased on dail6 #roduction o$ each steroid in the segment o$ the human #o#ulation that s6nthesiFes the least amount (#re#u&ertal &o6s in the case o$ estradiol)+ 20+ *econd: the E!;s e #osure calculations rel6 on results o$ the Klein assa6 (199/): ,hich indicated that &lood le7els o$ estradiol in #re#u&ertal &o6s ,ere 100-$old lo,er than #re7iousl6 re#orted+ The 8nited *tates has demonstrated the $la,s o$ the Klein assa6 on se7eral occasions 98 and the 7alidit6 o$ this assa6 ,as discussed in detail at the meeting ,ith the e #erts+ 'hile there seemed to &e general agreement among the e #erts that &lood le7els o$ estradiol in #re#u&ertal children ma6 &e lo,er than #re7iousl6 &elie7ed: the E! has not esta&lished the magnitude o$ the di$$erence: and there ,as certainl6 no agreement among the e #erts on the 100-$old di$$erence cited &6 the E!+ The E! itsel$ recogniFed the inaccurac6 o$ the Klein assa6 results in its !omments on the "e#lies &6 the %anel E #erts (?uestion 38)+ 99 E5uall6 as s#eculati7e in the E!;s e #osure calculation is the assum#tion that the meta&olic clearance rate o$ estradiol in children is one-hal$ that o$ adults+ >o scienti$ic data ha7e &een #resented to su##ort this assum#tion+ 22+ Third: the E!;s e #osure calculations are $la,ed &ecause the6 use 8+*+-#ermitted incremental increases100 to estimate actual dail6 e #osure to estradiol $rom eating &ee$+ These #ermitted incremental increases are le7els o$ residues that are #ermitted in e cess o$ increments a&o7e the concentrations o$ estradiol naturall6 #resent in untreated animals@ the6 do not re#resent actual amounts o$ estradiol $ound in edi&le tissues+ There$ore: use o$ these num&ers to deri7e an 9acce#ta&le dail6 inta=e9 o$ 102 ng(#erson(da6 is $actuall6 incorrect+ As the 8nited *tates has stated #re7iousl6: a more accurate (and still 7er6 conser7ati7e) estimate o$ e cess dail6 inta=e o$ total estrogens $rom eating &ee$ $rom treated animals - 30-00 ng(#erson(da6: i.e.: one third to one hal$ o$ the E!;s erroneous estimate o$ 102 ng(#erson(da6 - can &e $ound in the residue monogra#h $rom the 02nd AE!1A meeting+101 24+ <n other ,ords: the #aragra#h cited &6 the E! is re#lete ,ith inaccuracies and conclusions that are unsu##orted &6 scienti$ic e7idence: and does not su##ort the conclusion that the E! has: in $act: com#leted a ris= assessment $or estradiol+ <n an6 e7ent: there are numerous other reasons $or
1)A 3uidance $or <ndustr6 >o+ 3: 3eneral #rinci#les $or e7aluating the sa$et6 o$ com#ounds used in $ood-#roducing animals+ htt#:((,,,+$da+go7(c7m(3uidance(31<003+#d$+ 98 See: e.g.: 8* 1irst 'ritten *u&mission: #aras+ 8/ (and $ootnote 92) and 109@ 8* "e&uttal *u&mission: #ara+ //+ 99 "es#onding to )r+ .oo&is; criticisms o$ the Klein assa6: the E! stated 9OtPhe real 7alues $or serum 14I -oestradiol in #re#u&ertal children still remain to &e #ro#erl6 documented+9 100 1or 7eterinar6 drugs that occur naturall6 in animals: li=e estradiol: 1)A does not set tolerances or ma imum residue limits+ <nstead: 1)A esta&lishes le7els o$ residues that are #ermitted in e cess o$ increments a&o7e the concentrations o$ estradiol naturall6 #resent in untreated animals+ See 21 !1" X 002+2/0+ 101 See 9E7aluation o$ certain 7eterinar6 drug residues in $ood9: 1i$t6-*econd "e#ort o$ the Aoint 1AO('BO E #ert !ommittee on 1ood Additi7es: 'BO Technical "e#ort *eries: 893 (2000) (902nd AE!1A "e#ort9)+ 1AO 1ood and >utrition %a#er /1(12+ (E hi&it 8*-0)+ ,,,+$ao+org(ag(agn(Eec$a(archi7eVen+stm+
94

'T()*320("(Add+3 %age !-22 concluding that the E! has $ailed to do so+ 'e ha7e highlighted these in our #re7ious su&missions and se7eral o$ these shortcomings ha7e &een discussed &6 the scienti$ic e #erts+ QA. C'# $/% E*."-%'# C"22*#+$+%& %8-,'+# $/% 2%'#+#( +$ (+=%& $" $/% $%.2 62%.% d"*3$6 +# -'.'. )G) "0 $/% EC &%1"#d &*32+&&+"# ?US 1'&%@9 28+ <n its res#onse to ?uestion 9: the E! de$ines 9mere dou&t9 as 9not an6 =ind o$ dou&t &ut dou&t that is scienti$icall6 esta&lished+9 The 8nited *tates has not &een a&le to locate: let alone $ind a de$inition o$: the term 9mere dou&t9 in an6 scienti$ic materials: the *%* Agreement: or 'TO dis#ute #anel or A##ellate .od6 guidance+ The E! a##ears to ha7e in7ented this term during the course o$ these #roceedings: and no, ho#es to ha7e its measures anal6Fed against the &ac=dro# o$ this $ictitious (and sel$-de$ined) standard+ This is an untena&le #osition and should &e disregarded as such+ <n an6 e7ent: #ursuant to the E!;s o,n de$inition: a 9mere dou&t9 must &e a 9scienti$icall6 Eusti$ied9 dou&t+ The E! has $ailed to #resent an6 e7idence that there is scienti$icall6-Eusti$ied dou&t a&out the sa$et6 o$ an6 o$ the si hormones ,hen used $or gro,th #romotion #ur#oses in cattle+ There$ore: the E! has $ailed to satis$6 its o,n standard+ Q)). W/'$ +& 2%'#$ 34 #" 6'dd+$+=% .+&D69 6'dd+$+=%6. P,%'&% %8-,'+# $" 7/+1/ 6.+&D&6 $/%&% '.%

29+ <n its res#onse to ?uestion 11: the E! states that 9OiPt is scienti$icall6 not dis#uted (in this case e7en &6 the de$ending #arties) that li$e-time e #osure o$ humans to the le7els o$ endogenous #roduction o$ oestrogen (and in #articular to oestradiol-14I and its meta&olites) and: most li=el6: to the other t,o natural hormones (testosterone and #rogesterone) are su$$icient to cause and(or #romote cancer in some indi7iduals+9 To the contrar6: in the course o$ these #roceedings the 8nited *tates has ne7er argued that endogenous hormones can cause or #romote cancer+ >or has the E! #resented an6 con7incing e7idence that this is so+ <t is o7erl6 sim#listic and unscienti$ic to sa6 that endogenous hormones are 9su$$icient9 to cause cancer: and the E!;s res#onse to ?uestion 11 a##ears to &e nothing more than an attem#t to attri&ute statements to the 8nited *tates and !anada that the6 ha7e ne7er made+ 1urthermore: the E! has $ailed to #resent e7idence that there is an6 9additi7e9 ris= $rom the consum#tion o$ meat $rom cattle treated ,ith an6 o$ the si hormones $or gro,th #romotion #ur#oses+ 30+ 1or e am#le: the E! relies on the 10 th and 11th "e#orts on !arcinogens in su##ort o$ its contention that consum#tion o$ estradiol residues in meat $rom treated cattle ,ill &e 9additi7e9 to the ris= o$ cancer $rom e isting (endogenous) e #osure and e #osure $rom naturall6-occurring sources o$ estradiol+ Bo,e7er: the E! is incorrect ,hen it concludes that 7eterinar6 use o$ steroidal estrogens in $ood animals can increase estrogens in edi&le tissues to le7els 9in general su&stantiall6 higher than the normal (endogenousl6 #roduced) le7els+9 As demonstrated &6 the 8nited *tates in res#onse to ?uestion 1 $rom the E! $ollo,ing the *econd *u&stanti7e Meeting: the E!;s o,n e hi&its (E hi&its E!-3/ and 01A) clearl6 indicate that the increase in estradiol residues in muscle o$ treated cattle is usuall6 small (1+1 to 2+3-$old) and that it ,as onl6 detecta&le in some o$ the treated animals+ Moreo7er: these increases result in residue le7els that are ,ithin the range o$ naturall6-occurring concentrations+ There$ore: the statement that le7els o$ estradiol in meat $rom treated cattle are 9su&stantiall6 higher than the normal (endogenousl6 #roduced) le7els9 is grossl6 inaccurate+ 31+ "ather than citing to E hi&its E!-3/ and 01A (some o$ the E!;s more recent data that sho, a small and in certain cases undetecta&le increase in residue le7els): the E! re$ers instead to Ta&le 2 o$ its 1999 O#inion in its attem#t to sho, that the residue le7el increase is 9su&stantial+9 Bo,e7er: some o$ the data in Ta&le 2 re$er to 7eal cal7es and &ulls: neither o$ ,hich are rele7ant to this dis#ute+ 102
The use o$ gro,th-#romoting hormones in 7eal cal7es is not a##ro7ed in the 8nited *tates+ "elati7e to all &ee$ cattle: the 8nited *tates slaughters 7er6 $e, &ulls $or meat and there is no reason to im#lant these animals ,ith hormones to #romote gro,th+ <ronicall6: in contrast: the E! regularl6 slaughters &ulls $or human consum#tion: the meat $rom ,hich ma6 ha7e endogenous testosterone le7els much greater than that $rom steers
102

'T()*320("(Add+3 %age !-23 1urther: neither the source nor the date o$ these data is indicated in Ta&le 2+ <t is there$ore not #ossi&le to e7aluate the 7alidit6 o$ these data or: more im#ortantl6: ,hether the6 accuratel6 re#resent the a7erage increase in estradiol residues in treated cattle (7ersus the most e treme cases)+ Q)2. A )AAA R%-".$ "0 $/% C"22+$$%% 0". %$%.+#'.4 M%d+1+#', P."d*1$& "0 $/% E*."-%'# C"22*#+$+%& .%0%.& $" $/% ,"7 3+"'='+,'3+,+$4 "0 "%&$.'d+", ):M. H"7 +& $/+& 0+#d+#( .%1"#1+,%d 7+$/ .%0%.%#1%& $" 3+"'='+,'3+,+$4 +# $/% SC PH O-+#+"#9 ?-,%'&% .%0%. $" 1"22%#$& 34 $/% -'.$+%& "# $/% P'#%,!& Q*%&$+"# C3 $" %8-%.$&@ 32+ The E! disagrees ,ith the 8* statement that to o7ercome the lo, &ioa7aila&ilit6 o$ estradiol: 7er6 large amounts o$ the hormone must &e administered orall6+ Bo,e7er: rather than citing to an6 num&er o$ re7ie, articles a7aila&le on this su&Eect: 103 the E! relies instead on a single #ilot stud6 in girls ,ith central #recocious #u&ert6 (E hi&it E!-99)+ <n this stud6: girls ,ith central #recocious #u&ert6 ,ere administered estradiol orall6 to o7ercome the gro,th inhi&ition associated ,ith 3n"B agonist thera#6+ The authors determined that a 9mini-dose9 o$ 8 micrograms (7ersus the adult dose o$ 220 micrograms) o$ conEugated e5uine estrogen ,as su$$icient to stimulate gro,th+ The 8nited *tates does not disagree that 8 micrograms is a lo, dose com#ared to 220 micrograms: nor does it disagree that this dose ,as orall6 &ioacti7e in these #atients+ Bo,e7er: the rele7ant $act is that 8 micrograms o$ estrogen is e #onentiall6 greater than the amount o$ estradiol or its meta&olites $ound in a ser7ing o$ &ee$ $rom treated cattle+10/ 33+ <n addition: the E! states that AE!1A: and &6 e tension the 1999 !CM% O#inion: considered 9onl6 some o$ the residues o$ oestradiol-14I in meat@ in #articular: the6 ha7e not considered the li#oidal ($att6 acid) esters- nor estrone residues+9 This statement is: at least in #art: $actuall6 incorrect+ The residue monogra#h o$ the 02nd AE!1A Meeting contains 23 ta&les descri&ing concentrations o$ estrone in edi&le tissues $rom &oth untreated and treated cattle+ Theoretical dail6 inta=es ,ere calculated and clearl6 #resented $or estrone alone: estradiol alone: and estrone and estradiol together (9total estrogens9)+ 3/+ 1urther: data in E hi&it E!-/9 indicate that treatment o$ cattle ,ith a single im#lant containing estradiol ma6 result in increased concentrations o$ li#oidal estrogens in $at and li7er: &ut not muscle or =idne6@ ho,e7er: the data are di$$icult to inter#ret+ <n E hi&it E!-01A: the authors concluded that 9estradiol-14I-14-esters assa6ed at signi$icant concentrations in $at $rom 0 ##t in control to more than 100 ##t in /-doses (sic) im#lanted animals+ !uriousl6: mean concentrations o$ estradiol-14I-14-esters in li7er ,ere not signi$icantl6 modi$ied &6 the im#lantation treatment+9 These o&ser7ations indicate that li#oidal estrogens are rele7ant onl6 $or $at and not the other edi&le tissues+ Most im#ortantl6: the E! has not #ro7ided an6 scienti$ic e7idence indicating that consum#tion o$ li#oidal estrogens in meat $rom treated cattle results in a health ris= to the human consumer+

(castrated male cattle) to ,hich hormones ha7e &een administered $or gro,th #romotion #ur#oses according to good 7eterinar6 #ractice+ See 8* 1irst 'ritten *u&mission: #ara+ 02: citing Eurostat data regarding meat #roduction in the E8-10 (in ,hich meat categor6 712 (&ulls) com#rises a##ro imatel6 29+0J o$ total cattle slaughtered in the region)+ (E hi&it 8*-8)+ <n contrast: less than 2J o$ cattle slaughtered in the 8* are &ulls ,hile a##ro imatel6 00J are steers (castrated male cattle)+ 103 1or e am#le: 1other&6 K+ .ioa7aila&ilit6 o$ orall6 administered se steroids used in oral contrace#tion and hormone re#lacement thera#6+ !ontrace#tion 1992@ 0/: 09-29+ 10/ The di$$erence &et,een the dose o$ estrogen used in E hi&it E!-99 and the amount in &ee$ is di$$icult to 5uanti$6 #recisel6 &ecause conEugated e5uine estrogen: not estradiol: ,as used in the stud6+ E5uine estrogens are mi tures o$ se7eral estrogen sul#hates ,hich: unli=e estradiol: are ,ater solu&le+ There$ore: conEugated e5uine estrogens are &elie7ed to ha7e a greater oral &ioa7aila&ilit6 than estradiol+ See $ootnote 19 a&o7e (1other&6)+

'T()*320("(Add+3 %age !-2/ Q)F. P,%'&% %8-,'+# $/% .%'&"# 0". $/% d+00%.%#1%& 3%$7%%# $/% 6,+&$ "0 $/% ): &$*d+%&6 $/'$ 7'& '--%#d%d $" $/% 2002 O-+#+"# '#d $/% "#% $/'$ 7'& -."=+d%d $" $/% P'#%,. ?-,%'&% &%% -'.'(.'-/ 20 "0 $/% U#+$%d S$'$%&! R%3*$$', S*32+&&+"# '#d +$& T'3,% )@ 30+ The 8nited *tates notes that the E! agrees that the t,o lists setting out its 914 *tudies9 are su&stanti7el6 di$$erent+ The E! descri&es this di$$erence as the result o$ 9$urther #u&lications o$ #artial as#ects o$ the studies+9 >ot onl6 is this e cuse unclear: it is #atentl6 insu$$icient+ Either the E! #ro7ided the 8nited *tates ,ith the necessar6 materials at the outset o$ these #roceedings (,hen the 8nited *tates $iled its re5uest under Article 0+8 o$ the *%* Agreement): or it did not+ The E!;s res#onse to ?uestion 12 ma=es clear that the list o$ studies #ro7ided to the 8nited *tates at that time (i.e.: the list attached to the 2002 O#inion at the outset o$ these #roceedings) is di$$erent than the list #ut $or,ard &6 the E! in the course o$ these #roceedings+ 32+ Also: the 8nited *tates notes that the E! relies hea7il6 on its E hi&it E!-20 (a &oo= o$ studies) in su##ort o$ its argument that the 8nited *tates ,as in #ossession o$ all o$ the necessar6 materials com#rising the 914 *tudies+9 Bo,e7er: E hi&it E!-20: along ,ith numerous other scienti$ic documents: ,as onl6 $iled &6 the E! ,ith its "e&uttal *u&mission (in other ,ords: at the same time as the 8* "e&uttal *u&mission and Ta&le 1 thereto)+ <n addition: there are still ga#s in the E!;s attem#t to reconcile its #roduction o$ e7idence ,ith Ta&le 1 to the 8* "e&uttal *u&mission+ 1or e am#le: regarding *tud6 Ten: the E! notes that 9OtPhis stud6 ,as not 6et #u&lished as research continued a$ter 2002+ <t a##ears that it has not &een #u&lished 6et+9 ( See E hi&it E!-129)+ NNNNNNNNNN