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 Annex C to the Re port of the Panel to be found in document 
WT/DS320/R.  The other annexes can be found in the following addenda: 
 
 – Annex A: Add.1  – Annex B: Add.2  – Annex D: Add.4  – Annex E: Add.5 
 – Annex F: Add.6 
 – Annex G: Add.7  WT/DS320/R/Add.3 
 Page C-1 
 
 
  ANNEX C 
 
REPLIES OF THE PARTIES TO QU ESTIONS POSED BY THE PANEL 
AND OTHER PARTIES AFTER THE SECOND SUBSTANTIVE MEETING 
AND COMMENTS BY THE PARTIES ON THE OTHER PARTIES' REPLIES 
 
 
Contents Page 
Annex C-1 Replies of the European Communities to questions posed by the 
Panel after the second substantive meeting (18 October 2006) C-2 
Annex C-2 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 substantive meeting (31 October 2006) C-24 
Annex C-3 Replies of the United States to  questions posed by the Panel after 
the second substantive meeting (18 October 2006) C-40 
Annex C-4 Replies of the United States to questions posed by the European 
Communities after the second substantive meeting 
(18 October 2006) C-47 
Annex C-5 Comments by the United States on the replies of the European 
Communities to questions posed by the Panel after the second 
substantive meeting (31 October 2006) C-55 
 WT/DS320/R/Add.3 
Page C-2  
 
  ANNEX C–1 
 
REPLIES OF THE EUROPEAN COMMUNITIES TO QUESTIONS 
POSED BY THE PANEL AFTER THE SECOND SUBSTANTIVE MEETING 
 
(18 October 2006) 
  
Questions to all parties
 
 
Q1. With reference to the statemen t by the European Communities, inter alia  in para. 12 of 
the EC reply to Question 3 of the United States, do  the parties consider that a Panel is entitled to 
address "systemic claims" or issues related to "systemic obligations" and, if so, to what extent? 
 
1. By "systemic claims" and "systemic obligati ons" the European Communities is referring to 
obligations contained in the DSU that are relate d to the WTO dispute settlement mechanism as a 
system, are procedural in nature and independent of substantive obligations contained in other WTO 
agreements. A failure to bring a case under Article 21. 5 is a violation of a procedural obligation, 
irrespective of what the underlying disagreement on the question of compliance is about.  Equally, from the European Communities' point of view, the c ontinued application of sanctions in the face of 
presumed compliance and in the absence of a co mpliance review constitutes a violation of a 
procedural nature, irrespective of the subs tantive requirements of actual compliance. 
2. The Panel is not only entitled, but has an obliga tion to rule on claims of violation of such 
obligations under the DSU, which have been pr operly made by the European Communities in this 
dispute.  The European Communities further notes that  several Panels in the past have already ruled 
on Article 23 claims.
1 
Q2. With reference to the US rebuttal, para. 27,  do the parties consider that a measure that 
does not comply with the requirements of Articl e 5.7 SPS would automatically be in breach of 
Article 2.2 SPS, or Article 5.1 SPS, or both? 
 
3. In the European Communities' view this ques tion may be based on a misunderstanding of the 
point made in para. 27 of the US Rebuttal Submissi on. The United States is not arguing that a failure 
to meet the requirements of Article 5.7 automatically results in a violation of Articles 2.2 and/or 5.1. 
Rather the US is arguing that a measure has to sa tisfy the obligations under Articles 2.2 and 5.1 if the 
conditions of Article 5.7 do not apply. 
4. Indeed, assuming that a failure to meet the re quirements of Article 5.7 would automatically 
lead to a violation of Articles 2.2, 5.1 or both, woul d lead to absurd results. Picture a measure that is 
based on a risk assessment within the meaning of Article 5.1. That measure would not fulfil the 
conditions of Article 5.7, as it is  not provisional in nature, is not  based on "available pertinent 
information," has not been followed up through further research etc.   Nevertheless, the measure is of 
course perfectly in compliance both with Articles 2.2 and 5.1.  
5. At the same time, there is no doubt that if a measure that was thought to fulfil the 
requirements of Article 2.2. and 5.1-5.2 is found a Panel not to do so, it should be considered whether 
it fulfils the requirements of Article 5.7, in view of the lower amount of pertinent scientific evidence 
and the greater role which scientific uncertainties play  in the adoption of an Article 5.7 measure.  As 
the European Communities has argued in its reply to Question 66 of the Panel, Article 5.7 is a special 
                                                      
1 See only US – Certain EC Products , US – Section 301 ; EC – Vessels  ("Shipbuilding Subsidies").  WT/DS320/R/Add.3 
 Page C-3 
 
 
  regime in relation to Article 5.1. It applies to pr ovisional measures adopted in the face of insufficient 
scientific evidence and is in that sense also identified as lex specialis  to Article 2.2.     
Q3. When and how was each of the following documents made available to Canada and the 
United States?  Please answer independently for each of the documents mentioned below:  
 (i) 1999 Opinion; 
 (ii) 2000 Opinion;  (iii) 2002 Opinion; 
(iv) each of the "17 studies". 
 6. The European Communities has rep lied to this question in detail in its reply to Question 16 of 
the Panel (see paras. 79ff) and in par as. 111ff of its Second Written Submission. 
7. The 1999 Opinion
 was adopted on 30 April 1999 and put on the internet almost immediately 
thereafter, and was transmitted to the US and Canada . In bilateral contacts, both US and Canadian 
counterparts were made aware of this fact. As explai ned in para. 96 of its Oral Statement at the first 
substantive meeting as well as in para. 112 of its  Second Written Submission, a meeting between EC 
and US scientists was arranged in Washington in June 1999 to discuss the results of the 1999 Opinion. 
No such meeting took place, however, between Cana dian and EC scientists, as none was requested by 
Canada.  
8. The 2000 Opinion  was adopted on 3 May 2000 and put on the internet very shortly thereafter. 
In informal bilateral contacts, both US and Canadian counterparts were also made aware of this fact.  
9. On 3 November 2000 the EC draft legislation was notified to the SPS Committee 
(G/SPS/N/EEC/102). The notification (revised version submitted on 17 November 2000, see 
G/SPS/N/EEC/102/Rev.1), in point 12, refers both to the 1999 and the 2000 Opinion  and provides the 
internet link where the Opinions can be accessed. Ca nada submitted its comments on this notification 
in December 2000 (see EC-Exhibit 64) in which it stat ed that Canadian officials at Health Canada had 
reviewed the Opinions, so clearly Canada must have had access to them. 
10. The 2002 SCVPH's third assessment had been long  announced before it was actually carried 
out. The European Communities had made public the fa ct that it had launched 17 studies, the results 
of which would be reviewed in time.2 The 2002 Opinion , whose sole purpose was to review all the 
available evidence and in particular the results of the 17 studies, was adopted on 10 April 2002 and put on the internet shortly thereafter. In bilatera l contacts, both US and Canadian counterparts were 
made aware of this fact and actually have neve r complained that they had not received it.  
11. The preliminary findings from 17 scientific studies
 had already been taken into account in the 
1999 SCVPH opinion, as they were available at the ti me. The final results from the studies were taken 
into account and were cited and referenced in th e 2002 Opinion (page 28).  At the time of the 
adoption of the 2002 Opinion, only one study had not yet been published (that is Exhibit EC-29), 
whilst one study was from the start not meant for publication (Exhibit EC-7), as it contained the 
samples of meat collected from the US supermarke ts that was sent for analysis in the European 
laboratories.  Also one other study (Exhibit EC-30)  was partly published in Lange I.G., Daxenberger 
A., Meyer H.H., Rajpert-De Meyts E., Skakkebaek  N.E., Veeramachaneni D.N.: Related Articles, 
Links Abstract Quantitative assess ment of foetal exposure to trenbolone acetate, zeranol and 
melengestrol acetate, following maternal dosing in  rabbits. Xenobiotica. 2002 Aug; 32 (8):641-51. 
But in view of the breadth of its research it conti nued in collaboration with US  scientists after 2002. It 
appears that its final results have not been pub lished yet.  It should also be clarified that 
                                                      
2 Not least in Codex, see for example 11th session of the CCRVDF. WT/DS320/R/Add.3 
Page C-4  
 
  Exhibit EC-10 was published in AMPHIS 2001, vol. 109, p. 89-95, and it is contained also in 
Exhibit EC-65, at pages S426-432.  It should furt her be mentioned that some of the scientific 
experiments in view of their breadth have given rise to more than one publication (see list submitted 
by EC as Exhibit EC-7 through 42, see also reply to  Question 16). It follows that all of the studies, 
except two, where published and thus were publicly available at or before the 2002 SCVPH Opinion. 
Moreover, Exhibit EC-65, which is the result of an  international scientific conference of May 2001 to 
which many US scientists including from the US FD A had participated, published again a very large 
number of the 17 studies. They were thus acce ssible to the defending parties before 2002.  
12. As mentioned in para. 94 of the Second Writte n Submission, Canada, according to its own 
statements made on the internet, carried out an "intensive review" of the 17 studies
 (based on the 
reference list as annexed to 2002 Opinion), only the conclusion of which is reported on the internet 
(see footnote 77 at para. 94 for internet address).  
Q4. Has the European Communities assessed in a systematic manner the existence and level 
of risks from failure to observe good veterinary practices with respect to the administration of 
oestradiol 17 β as a growth promoting hormone to cattle, in particular in the United States' and 
Canada's markets?   If so, plea se indicate where this assessment is to be found in the evidence 
provided to the Panel. 
 
13. Yes, the European Communities has indeed assessed in a very systematic manner both the 
existence and the level of risks from failure to  observe GVP in the administration not only of 
oestradiol-17 β but also of the other five hormones when u sed for growth promotion, in particular in 
the US and Canada. Although it is not clear what  the Panel means by "systematic manner", the 
European Communities has performed this assessment as systematic as it can be and, in any case, in 
accordance to the indications contained in the 1998 Appellate Body report in the Hormones  case (at 
para. 207). There the Appellate Body has said that "systematic analysis" would entail to investigate 
and evaluate "the actual problems that have arisen  at the borders of the European Communities or 
within the United States, Canada and other c ountries exporting meat and meat products to the 
European Communities". The Eu ropean Communities has alread y explained the evidence and 
assessment it has made in some detail with its repl y of 3 October 2005 to wr itten questions no 17, 27 
and 31 from the Panel. 
14. More specifically a regards the existence of risk , the European Communities has already 
referred to the relevant evidence with its repl y of 3 October 2005 to question 17 (para. 89) and 
question 27 (at para. 154). The evidence is contained in Exhibits EC-11, 12, 16, 17, 18, 34, 47, 51B, 
52, almost all of which were also published in Exhibit EC-65 (in the form of a book). This evidence has clearly identified and characterised the hazard re sulting from the implants that are freely available 
in the US and the Canadian market. Moreover, pl ease note that most of the experts have confirmed 
(e.g. Dr. Boisseau) that if GVP is not observed th e ADIs and the MRLs proposed by Codex become 
useless. The experiments described in the Exhib its mentioned above were carried with hormonal 
implants that are actually licensed for use in the US and Canada and considered both their 
recommended use and situations of abuse and/or misuse.
3 
15. As regards the level of the risk , the European Communities has un dertaken specific studies to 
evaluate the exposure assessment from situations resulting from real as well as experimental  
situations of abuse and/or misuse in the market s of both defending members. Thus, it carried out 
specific veterinary inspections in the US (Exhib it EC-67) and Canada (Exhibit EC-68),  with the 
agreement of these countries, and has made a specific  calculation of the level of the risk for imports 
coming from both countries in Exhibit EC-73. This assessment of risk is not based on theoretical or 
                                                      
3 Since oestradiol-17 β is present in almost all of the licensed implants in the US and Canada, it is 
obvious that the evidence mentioned in the abov e EX Exhibits has also examined oestradiol-17 β.  WT/DS320/R/Add.3 
 Page C-5 
 
 
  hypothetical assumptions (as the US and Canada wrongly contend), but on examples from realistic 
conditions of use, taking into account specific, real and undisputed  instances of abuse and/or misuse 
that have occurred both in the US (see, e.g., Exhibits EC-53, 67, 69 and 96)4, and in Canada (see, e.g., 
Exhibits EC-53, 68 and 70).  In addition, the level of risk was further assessed in a specific study that 
imported in the EC hormone-free and hormone-treated meat sold in the supermarkets in the US (see 
Exhibit EC-53), and this was further compared with the situation in the EC (see, e.g., Exhibit EC-49). 
The European Communities submits that a more systematic assessment of realistic conditions of abuse and/or misuse cannot be carried out, and the evidence showed levels of exposure that exceeded 
the ADIs established by Codex, taking into account th e most recent detection methods and the levels 
of endogenous production by pre-pubertal children.  More importantly, the evidence shows beyond 
doubt that the situations of abuse/or misuse occu rring in the US and Canadian market are not 
exceptional nor occasional.  
16. It should finally be stressed that all these pieces of evidence were  assessed in the 1999 
Opinion (section 3.3, pages 30-32) and the 2002 Opinion (pages 10-12) of the SCVPH and have been taken into account by the risk manager for the adopt ion of Directive 2003/74/EC. It is noteworthy that 
the defending members have not really contested  this  evidence,  other than to  argue basically that the 
EC used "unrealistic misuse scenarios" (see, e.g., Canada's 2
nd oral statement of 2-3 October 2006, at 
para. 74;  and the US oral statement of 2 October 2006, at para. 60). It is amazing that the US for the first time tries to minimize the health risks from "extra-label use" and sale freely over the counter 
(ibid., at para. 61),  which are contradicted by the statements by the US FSIS.
5  Equally surprising is 
now the attempt by the US to downplay the importance of abuse and/or misuse ( ibid., at para. 62) 
arguing that there can be no 100% assurance. The US argues ( ibid., at para. 64) that "no food safety 
system is safe", implying that the other WTO memb ers are obliged  to accept the failures of the US 
system despite the risk to human health in the importing country which this kind of failures will 
inevitably have, as the experts have explained ( e.g. Dr. Boisseau and Dr. De Brabander). Moreover, 
the US does not explain why the statements by the US FSIS that " is concerned about the widespread, 
illegal use of drug implants in young calves that was discovered in 2004", and that "FSIS learned that 
the use of growth promoting implants was a widespre ad practice within the veal industry" (and the so 
many other examples cited in Exhibit EC-73) should not  be given the appropriate weight by the EC in 
its risk assessment.  
Q5. In its comments on comments of the United  States and Canada on experts replies to the 
Panel questions (in particular Question 13) , the European Communities indicates that 
oestradiol 17 β might be a "weak genotoxin" (para. 44).  At what doses is genotoxicity 
observable in vivo ?  How are these doses comparable to th ose found in meat from cattle treated 
with growth promoting hormones?  How would this  assertion affect the identification of adverse 
effects and the evaluation of potential occurren ce of these effects from consumption of meat 
from cattle treated with oestradiol 17 β for growth promotion purposes? 
 
                                                      
4 See Exhibit EC-102 which states, inter alia, that the US Food Safety and Inspection Services (FSIS) 
"is concerned about the widespread, illegal use of drug impl ants in young calves that was discovered in 2004". 
5 See above Exhibit EC-102 which states, inter alia, that the US Food Safety and Inspection Services 
(FSIS) "is concerned about the widespread, illegal use of drug implants in young calves that was discovered in 
2004". The same exhibit also states that "FSIS learned that the use of growth promoting implants was a 
widespread practice within the veal industry. However, the Food and Drug Administration has not approved 
growth promotion implants for use in food animals presented for slaughter as veal and considers their use to be a violation of the Federal Food, Drug, and Cosmetic Act". This example and so many other that have been 
identified demonstrate that, contrary to what the US has be en arguing before the Panel,  abuse and/or misuse is a 
"widespread practice in the US veal industry". Indeed, it cannot be otherw ise as long as these implants are 
available freely over the counter in both defending countries, and the manufacturers recommend multiple 
implanting with combinations of these hormones for faster growth of the animals. WT/DS320/R/Add.3 
Page C-6  
 
  17. The question concerns essentially whether oestradiol-17 β is mutagen in vivo , and, if so, at 
what dose. The 1999 SCVPH Opinion cites one study of mutagenicity in vivo (at p. 41). With its reply to Panel's Question no 13 to the experts, the Eur opean Communities has also provided further – more 
recent – references to in vivo  studies.  
18. The study by Cavalieri et al .
 (2006) (Exhibit 125) reported th at exposure of rats for 20 weeks 
(140 days) to oestradiol from Silastic capsules, which is a method to release low amounts of a 
compound over prolonged time periods, led to a statistically significant increase in mutagenesis in the 
inguinal mammary fat pads. A dose of 5 milligram of estradiol was used, which at first sight seems 
very high.  The precise amount released by the capsu les used in the Cavalieri et al. study was not 
determined.6 Assuming that the 5 milligrams were comp letely released within 140 days (which 
usually is not the case because the dose is designed high enough to secure that  the daily exposure is 
still the same on the last day), a rather conservativ e estimate based on the published findings would be 
about 1 microgram per day oestradiol release from th e capsules containing 5 mg oestradiol used by 
Cavalieri, and for a 330 g rat, this would be ab out a 3 microgram per kilogram per day dose of 
oestradiol (3000 ng / kg /day). This would mean that the MDD (Maximum Daily Dose) of estradiol in 
this rat study was at maximum about 35 micrograms7 or about 0.1 micromole or about 
200 micrograms per kilogram body weight.8  
19. If the daily production rates in pre-pubertal childre n, according to the original values from the 
Klein assay were taken into account (0.04 µg/day), the ADI established by JECFA (based on the very 
high rates of endogenous production of pre-pubertal ch ildren of 6.5 µg/day), may be exceeded at most 
around 1-2 fold, but not by orders of magnitude or "massively" higher, as the defending parties have 
argued. Moreover, they are still much less than the doses often used in toxicological studies of 
chemicals, where the lowest doses could be 2-3 orde rs of magnitude larger than the doses experienced 
by human consumers. 
20. Indeed, JECFA has determined that the maximum oestrogen derived from hormone-treated 
beef is 84 ng/ person / day that would be for a 60 kg adult 1.4 ng/kg/day. But for a 20 kg child, the 
amount would be 4.2 ng/kg/day. If so, this would mean  that oestradiol had a mutagenic effect at a 
                                                      
6 Normally such silastic tubes are made to ensure an even release over a  long time and to do that there 
must be a lot left at the end of the  experiment (other wise the dose would decrease du ring the experiment). On a 
daily basis this would be: "total amount of estradiol in implant" – "left over at end of experiment" / "days of 
exposure". Since there are values for how much is left in the hormonal-implants used in cattle at slaughter and 
given that it is the same principle as silastic tubes in rodents, the %-left-over could be comparable. If so the 
released amount in the rodents could be calculated. We understand that the underlying study which will provide these data is about to be published: P.C. Mailander, J. L. Meza, S. Higginbotham and D. Chakravarti, Induction 
of A.T to G.C mutations by erroneous repair of depurinated DNA following estrogen treatment of the mammary 
gland of ACI rats, J. Steroid Biochem. Mol. Biol., at the November issue, 2006. Moreover, as Dr. Guttenplan has been working with the same scientists in that study, so the Panel may wish to ask him to clarify this 
information. 
7 This estimate is likely to be on the high side at the end of the study at which point about 40% of the 
initial dose usually remains in the silastic capsule. 
8 However, from other experiments using similar silastic capsules the dose of oestradiol released from 
these capsules was reported. From an article published by Ewing et al. in 1979 who used the same Silastic 
capsules (OD 3.18 mm, ID 1.98 mm) used in the Cavalier i et al. 2006 study, the re ported release rate for 
oestradiol was 2.4 micrograms / cm /day, and according to another paper by Wang and Wong (1998), this would 
be if there was 25 mg of oestradiol packed into a 1-cm capsule. See Ewing, L.L., R.A. Gorski, R.J. Sbordone, J.V. Tyler, C. Desjardins and B. Robaire (1979): Test osterone-estradiol filled polydimethylsiloxane subdermal 
implants: effect on fertility and masculine sexual and aggressive behavior of male rats. Biol Reprod 21(4): 765-
72; and Wang, Y.Z. and Y.C. Wong (1998). Sex hormone-induced prostatic carcinogenesis in the noble rat: the role of insulin-like growth factor-I (IGF-I) and vascular  endothelial growth factor (VEGF) in the development of 
prostate cancer. Prostate 35(3): 165-77.  WT/DS320/R/Add.3 
 Page C-7 
 
 
  dose potentially within  the 1000-fold safety margin estab lished from a LOAEL, based on the 
assumption of a threshold for this effect !  
21. With respect to the other in vivo studies mentioned , the European Communities would like to 
clarify the following. The study in SENCAR mice showing mutagenicity of the 3,4-quinone of E2 (the putative mutagenic metabolite) used a dose of  200 nanomoled, which is about 60 microgram.  
Again, we do not know for sure how this relates to the daily amount of E2 in the mouse, but an 
educated guess is that the dose of 60 microgram is probably one or at th e most two orders of 
magnitudes above the endogenous production, and ca nnot be considered as huge dose either. As for  
the study on the mutagenicity in the mammary gland of ACI mice is so far available as an abstract only, so there is no much information available.  
22. Finally, the study showing the formation of the typical DNA adducts of E2-3,4-quinone in 
human breast tissue  (EC Exhibit 118) did not administer any exogenous E2. So the adducts are 
formed by the metabolites of the endogenously produced E2 alone.  
23. In conclusion , it is very important to understand that the issue of the dose administered is not 
very crucial for the in vivo  genotoxicity in the case of oestradiol-17 β, and that the defending parties 
have been trying to confuse the debate on the basi s of unscientific and simplistic allegations. Indeed, 
from the previous comments it appears that the doses used to elicite in vivo mutagenicity are not 
massively high. Quite the opposite, they seem to fa ll within the safety margin established by JECFA, 
which means that the residues in meat from hormone-t reated meat are also capable of producing this 
adverse effect. Moreover, there are many scientists  today who rightly believe that setting ADIs and 
MRLs would not be used for DNA-reactive subs tances which are both genotoxic and carcinogenic 
because "it is assumed that there is no exposure without  any potential risk, i.e. it is suggested that 
exposure to even a single molecule could produce DNA damage".9 
Questions to the European Communities : 
 Q6. Should the Panel agree with the European Communities' main claim that the United 
States and Canada have breached Article 23 of  DSU read together with Articles 21.5 and 22.8, 
what would be the consequences of such a conclu sion for the United States and Canada?  More 
particularly, would the United States and Canada:  
(a) be expected to withdraw the suspensions of concessions or other obligations or 
suspend their application? 
(b) be expected to initiate an Article 21.5 procedure against the EC? or 
(c) would they be expected to do both? 
(Please note that the Panel is fully aware of its obligations under Article 19 DSU) 
 
24. As explained in paras. 73 et seq. (WT/DS320) as well as in paras. 71 et seq. (WT/DS321) of 
its first written submission as well as in paras.  94 (WT/DS320) and para. 96 (WT/DS321) the 
European Communities' position is that Canada a nd the United States are at least under an obligation 
to do either  (a) or (b). However, the European Communities c onsiders that it would be appropriate if 
the United States and Canada did (c).  
                                                     
 
9 See S. Barlow et al ., Risk assessment of substances that are both genotoxic and carcinogenic – Report 
of an International Conference organised by EFSA and WHO with support of OLSI Europe, Food and Chemical 
Toxicology, 44  (2006) 1636-1650, at page 1637, available on line at www.sciencedirect.com. WT/DS320/R/Add.3 
Page C-8  
 
  25. In the absence of such a resolution to this di spute, however, there can be no doubt that the 
United States and Canada are under an obligation to  withdraw the suspension of concessions of other 
obligations or suspend their application, if they do not initiate a 21.5 proceeding. 
26. Equally, there can be no doubt that they are under an obligation to initiate a 21.5 proceeding if 
they continue to disagree on the compliance of the EC implementation measure (manifesting this 
disagreement through the continued appli cation of the suspension of concessions). 
27. In the case of a continued disagreement, as e xplained elsewhere, the European Communities 
is furthermore of the view that it would be a ppropriate for the United States and Canada to both 
suspend the application of the suspension of concessions and initiate 21.5 proceedings. This is what 
the European Communities has done in the FSC case.  
28. Of course and ideally, after the thorough debates at the expert meeting, the United States and 
Canada are free to abandon their disagreement a nd accept the European Communities implementation 
measure as compliant.  Thus, they would cease the a pplication of the suspension of concessions and 
there would be no need for a 21.5 proceeding.   
Q7. Is the Panel correct in understanding th at the European Communities pursues two 
different "matters" before the Panel: 
 
(a)  one regarding the United States' and Canada's unilateral determinations of 
violation by the European Communities fu rther to its notification of Directive 
2003/74/EC; and 
(b)  one regarding the maintenance of reta liations by the United States and Canada 
despite actual compliance; 
the latter being conditional upon the Panel rejecting the EC claims under the former? 
 
29. The European Communities is not sure to full y understand the meaning of this question. 
30. It seems appropriate to first recall the Appellate  Body's definition of the "matter" before the 
DSB:  
[t]he ' matter  referred to the DSB' ... consists  of two elements: the specific measures  at 
issue and the legal basis of the complaint  (or the claims ).
10  
31. On the basis of this definition, there is one single matter here and that is the matter as referred 
to in the European Communities' request for establishment of a Pane l. The request describes several 
measures and a number of different claims. These claims are further developed in the European 
Communities' First Written Submission and certain of  these claims have been made unconditionally 
while others are conditional.  For the sake of clarity, these unconditional and conditional claims are 
set out in two different parts, part one addressing claims based on Article 23 read together with 
Article 21.5 and with Article 22.8, part two addressi ng a direct violation of Article 22.8. The second 
part is conditional upon a negative finding on the first part.     
32. The above description of two supposedly different  "matters" does not reflect the fact of a 
single matter as just described, nor is it accurate in it self: the issue of a unilateral determination also 
relates to the maintenance of retaliation as evid enced through the claim based on Article 23 read 
together with Article 22.8.  
                                                      
10 AB Report Guatemala – Cement I , at para. 72.  WT/DS320/R/Add.3 
 Page C-9 
 
 
  33. Furthermore, the European Communities has not generally argued that the "notification" as 
such is the event that triggers the issue of a unila teral determination (see al so para. 44 of its Oral 
Statement at First Hearing). In the specific circumst ances of this case, it seems clear that both the 
United States and Canada have made such a un ilateral determination immediately following the 
notification. Furthermore, as explained in pa ra. 32 of its Rebuttal Submission the European 
Communities sees merit in the argument that the time factor may be relevant when for assessing when 
a "determination" has been made.     
Q8. The Panel understands that the European Communities initiated risk assessments with 
respect to all six hormones at issue (see, e. g., Directive 2003/74/EC, third  introductory 
paragraph). 
 
(a)  Could the European Communities co nfirm, with respect to oestradiol 17 β and in 
light of its statement in para. 192 of its rebuttal and its comments on Question 14 of the Panel to the experts, whether: 
(i) it proceeded through the four step s of risk assessment identified by 
Codex; or 
(ii) could have proceeded through the fo ur steps but decided not to do so in 
light of its findings on genotoxicity of oestradiol 17 β? 
(b)  Could the European Communities confirm, with respect to each of the other five 
hormones at issue, at what stage(s) of its risk assessment it considered that relevant scientific evidence was insufficient  and decided to provisionally ban the 
importation of meat treated with those hormones on the basis of available 
pertinent information.    
34. Ad (a).  The European Communities confirms its comments on the Question 14 of the Panel 
to the experts. As regards the statement in para. 192 of its Rebuttal Submission, the European 
Communities is grateful to the Panel for pointi ng out the error and oversight. The error is double 
because: first, the steps of a risk assessment as define d by Codex are four (not three) and, second, the 
terminology used in para. 192 to describe the first th ree of them is not correct either (see following 
para. 193 where the proper terminology is used for th e first three steps). The words used in para. 192 
is an isolated oversight and does not reflect the position which the European Communities has expressed in so many other places in its written subm issions and the oral hearing. Indeed, with its 
reply of 3 October 2005 to Written Question No 24 from the Panel, in  particular paragraphs 140-143, 
the European Communities has properl y described the four steps of a risk assessment and the reasons 
for which it thinks it has complied with them in this  case. See also paragraphs 145-152 of its reply of 
3 October to Written Question No 25 from the Pane l. Moreover, a careful examination of the 1999 
Opinion shows beyond doubt that the European Co mmunities has completed the four steps, albeit it 
made a qualitative exposure assessment for the reasons explained therein. 
35. Ad (a), (i) and (ii).  The European Communities has said and repeats that it has performed the 
four steps in its risk assessment for all these hormones. As regards the third step (exposure 
assessment), it performed both a quantitativ e estimation and a qualitative assessment.
11  T h e  
defending parties argue that the third step (expos ure assessment) is not properly performed, because 
they contest the data used for the quantitativ e assessment (they contest the Klein assay, the 
bioavailability rate, the rate of endogenous production by pre-pubertal children, etc.), and they also 
argue that the qualitative assessment lacks scientific rigour (US). The defending parties may disagree, 
                                                      
11 Inevitably, therefore, the fourth step was gl obally qualitative. See the 1999 SCVPH opinion, 
pages 69-73 and the replies to questions 1, 2 and 3, at pages 74-77. WT/DS320/R/Add.3 
Page C-10  
 
  but they cannot credibly argue that the European Communities has not completed the four steps of the 
risk assessment.  
36. For oestradiol-17 β
, section 4.1.5, pare 36- 39, of the 1999 Opinion is entitled "assessment of 
excess exposure to oestrogens from consumption of hormone-treated beef" and it explained why the 
JECFA ADI and the US acceptable levels are exceed ed. This is a quantitative estimation and is meant 
to address the assumption of JECFA and of the US that oestradiol-17 β acts only through receptor-
mediated mechanism. It concluded that: 
[T]he FDAs acceptable daily intake (102 ng/person/day, see above) could exceed the 
daily production rate of oestradiol by 1, 700 fold (of pre-pubertal children). While 
there is some experimental evidence in support of the currently used blood levels of 
oestradiol being 100 fold too high (Klein et  al., 1994), the other assumptions used in 
coming to this conclusion may be too conser vative. Thus, if absorption is reduced to 
10% and the MCR for children is only 1/2 that of adults, the FDA acceptable daily 
intake could still be 85 fold too high. 
37. In other words, the 1999 Opinion has made a quantitative estimate of the exposure assessment 
using the latest information and data available and also assumed 10% bioavailability, even if this low 
rate is scientifically questionable. Yet, even  under such estimation, it concluded that the US 
acceptable daily intake "could still be 85 fold too high" (and, consequently, also JECFA's ADI of 
0.50 ng/kg/bw/day would be exceeded).  Accordingly, the European Co mmunities fails to see why this 
is not the best possible quantitative estimate of th e exposure assessment, taking into account the latest 
scientific information.  
38. But the 1999 Opinion then goes on and contains sections 4.1.6 to 4.1.8, pages 39-43, which 
analysed the other mechanism by which oestradiol-17 β is believed to act, i.e. by direct genotoxicity. 
An exposure assessment is again performed, but this  time of a qualitative nature, where it states that: 
"[T]hese DNA-damaging effects indicate that no threshold exists for the risk from oestrogen metabolites" (at page 41).  It also states that: "N o data are currently available on the effects of 
exogenous low-dose oestrogens. However, genotoxic  effects independent from the presence of 
hormonal receptors have been recognised for metabo lites of certain oestrogens, as indicated above." 
(at page 42). It also states on the same page that: " These results indicate that
 induction of mammary 
tumors relies on the presence of E 2, but not that of the major oestrogen receptor, suggesting a 
genotoxic role of E 2 in the induction of these mammary tumors ." It also arrived at a qualitative 
conclusion as follows: 
In conclusion,  whereas it is clear that exogenous oestrogens, present in oral 
contraceptives or used in hormonal replacement therapy in women, are responsible for an increased risk of endometrial cancer a nd to lesser extent some increased risk of 
breast cancer, there is no direct evidence on the consequences of the contribution of 
exogenous 17 β-oestradiol originating from the consumption of treated meat. Yet we 
know from the data derived from human populations within the ranges of 
physiological values of hormones in blood, that high levels are associated with an 
increased risk of breast cancer. Also known are the carcinogenic effects of 17 β-
oestradiol in experimental animals as well as the deleterious effects in pre- and 
perinatal development (see sec tion 2). Finally, in considera tion of the recent data on 
the formation of genotoxic metabolites of o estradiol, suggesting that 17ß-oestradiol 
acts as complete carcinogen, by exerting tumour initiating and promoting effects, it has to be concluded, that no quantitative est imate of the risk related to residues in 
meat could be presented.  WT/DS320/R/Add.3 
 Page C-11 
 
 
  39. Ad (b).  The European Communities performed for the other five hormones  the same risk 
assessment as that for oestradiol-17 β. Indeed, a careful look at the 1999 SCVPH Opinion, confirms 
that all four steps were completed in the same way as for oestradiol-17 β. Whilst completing the four 
steps, the SCVPH Opinions of 1999, 2000 and 2002, have taken care (unlike JECFA's assessments) to 
point to the numerous new scientific evidence, to th e serious gaps in our know ledge and the scientific 
uncertainties surrounding many important aspects. It was the overall state of the file for each of these 
five hormones, and for each specific aspect required for the four steps of the risk assessment, which 
led the SCVPH to come to the overall conclusion that it was not possible to complete the risk assessment, in the sense of Article 5.1 SPS Agreement .  
40. In addition, as for oestradiol-17 β, the SCVPH performed an assessment of exposure 
assessment under realistic conditions of use of  these hormones, taking into account misuse and 
potential abuse. 
41. On the basis of these opinions the competent risk  manager decided to apply Article 5.7 of the 
SPS Agreement .  In particular, recital no 7 of the preambl e to the Directive 2003/74 explains that: " As 
regards the other five hormones (testosterone, progesterone, trenbolone acetate, zeranol and 
melengstrol  acetate), the SCVPH assessment is that , in spite of the individual toxicological and 
epidemiological data available, which where take n into account, the current state of knowledge does 
not make it possible to give a quantitative estimate of  the risk to consumers". In other words, the 
European Communities based its measure on all the available pertinent information for each of the 
four steps of the risk assessment which it had performed.  
Q9. Can the European Communities explain the meaning it gives to the term "mere doubt" 
in para. 181 of the EC second submission (US case)?  
42. The use of the terms "mere doubt" (in para. 181 of  the EC Rebuttal Submission) is made there 
in order to distinguish a situation where the availa ble relevant evidence is sufficient from the situation 
where the pertinent evidence is insufficient.  The term "mere doubt"  does not mean any kind of doubt 
but doubt that is scientifically established, in  other words in both cases the "sufficiency" or 
"insufficiency" of the relevant  evidence should be scientifically established. Indeed, mere doubt 
could be found to be sufficient to take a measure in  cases of substances or risks that are new or have 
not been evaluated before. For example, when in 1996 the European Communities took drastic 
measures against BSE the available relevant sci entific evidence was very-very meagre and the 
prohibition was based essentially on doubts and possible associations.  
43. Conversely, in situations where the substan ces have been evaluated before, the doubt should 
be serious, as the last sentence of para. 181 stat es.  Typically, reasonably serious doubts may exist 
when the pertinent availabl e evidence is contradictory, inconclusive  or incomplete. This is related not 
only to the quantity of the available evidence, but fr equently to the quality of the pertinent evidence. 
Serious doubts may appear or develop for the firs t time about the safety of a substance which is 
already authorised on the basis of developments in scientific research. The difficulty for the risk 
assessment and risk management is to decide when  the pertinent evidence moves from a situation of 
being previously thought to be "sufficient" into a si tuation that is now found to be "insufficient" for 
the purposes of assessing risk in a way that does not compromise the chosen level of protection. The 
formal requirement of having to conduct a risk assessment is not a problem, because a risk assessment 
(with all four steps in a quantitative or qualitative manner) is nearly always possible to perform. The 
problem is when the new evidence points to credible scientific uncertainties, incompleteness of the 
data or contradictory findings. That is why all le gal systems that aim to protect effectively human, 
animal or plant life and health provide that, in su ch situations, qualitative assessment is acceptable for 
some of the four steps in the risk  assessment. As Article 5.7 of the SPS Agreement  states, members 
may adopt measures "on the basis of available pertin ent information" and shou ld seek to obtain the 
additional information necessary "for a more objective assessment of the risk".  WT/DS320/R/Add.3 
Page C-12  
 
  44. The European Communities has given the example of Carbadox (at paras. 150-152), where 
JECFA waited for a period of about 10 years in or der to move from a situation of sufficient evidence 
to authorise Carbadox (in 1991) to a situation of sufficient evidence to prohibit Carbadox (2003). The 
question is who is to bear the responsibility for th e adverse effects on human health during the period 
of ten years that lapsed in between? An interpreta tion of Article 5.7 that does not allow taking into 
account credible scientific developments and scientif ic uncertainty that question previously held 
scientific views is not correct. This point is qu ite different from the point that science always 
develops. To guard against potential abuses, as e xplained above, the new evidence should not be 
arbitrary
12 but credible and should show that there is genuine scientific disagreement identified in a 
risk assessment. This kind of scientific uncertain ty should be acceptable under Article 5.7 of the SPS 
Agreement , if the right of members to choose their appropriate level of protection is to be preserved. 
Indeed, Article 2.2 of the SPS Agreement  requires a measure to be based on scientific principles and 
not maintained without sufficient scientific evid ence. But Article 2.2 does not lay down such 
requirements for provisional measures, because it st ates "except as provided for in paragraph 7 of 
Article 5".  
Q10. The European Communities specifies that "i t has issued a new call for scientific data 
and research from 2002 onwards, on substances with  hormonal activity which may be used for 
growth promotion purposes in bovine meat". Could the European Communities specify what information it has actually requested?  When does it expect to receive it? 
 
45. The European Communities has refe rred to this call for scientif ic data in Para. 264 of its 
Replies to the Panel's Questions after the first s ubstantive hearing and in Para. 169 of its Second 
Written Submission. A link to the OJ publication on the internet has been provided each time.  For 
ease of reference the European Co mmunities attaches the public call now as Exhibit EC-128.  As can 
be seen from the document, the information requested was  
any scientific evidence (from 2002 onwards) on substances with hormonal activity 
which may be used legally in Third Countries for growth promotion purposes in 
bovine meat having oestrogenic, androge nic or gestagenic action since the Last 
Review of the Assessment of Risks to Human Health from Hormone Residues in 
Bovine Meat and Meat Products  of the SCVPH in 2002 following the criteria 
outlined under item 3.  
46. Under item 3 cited above it is specified, inter alia , that: 
EFSA encourages the submission of peer-revi ewed data/publications (not just the 
reference) as the most rele vant and reliable documents. 
47. Five papers have been submitted following the call. EFSA is currently reviewing these five 
papers together with the final
 version of the UK Group report (see below Question 14) as it has been 
published in July 2006. An assessme nt is expected for April 2007. 
Q11. What is meant by no "additive risk"?   Please explain to which "risks" these are 
"additive". 
                                                      
12 It should be noted that the Appellate Body had found in its 1997 Hormones  report (at paras. 244-245) 
that the old EC Directive was not imposed for arbitrary or discriminatory protectionist reasons, contrary to the arguments of the defending parties at that time and the findings of the 1997 hormones panel. Moreover, none of 
the parties has argued in the present proceedings that  the new EC measure is is based on arbitrary or 
discriminatory evidence. All of the Panel's experts have confirmed that the different views held by the defending parties and JECFA, on the one hand, and the EC, on the other, are based on legitimate and genuine scientific 
disagreement.  WT/DS320/R/Add.3 
 Page C-13 
 
 
   
48. It is scientifically not disputed (in this cas e even by the defending parties) that life-time 
exposure of humans to the levels of endogenous production of oestrogen (and in particular to 
oestradiol-17 β and its metabolites) and, most likely, to the other two natural hormones (testosterone 
and progesterone) are sufficient to cause and/or promote cancer in some individuals. This is 
frequently called risk of cancer from background (e ndogenous) exposure. This kind of exposure (and 
the attentive risk of cancer) cannot be avoided .  
49. But humans are exposed daily to variable levels  of residues of these hormones, in particular 
estrogen (including oestradiol-17 β and its metabolites), from many exogenous sources where these 
hormones naturally occur, such as milk, eggs, brocco li, soya beans, etc. In scientific literature it is 
seriously disputed whether the estrogenic activity of residues in plants is the same, both as regards the 
mode of action and potency, when consumed by humans.13  It is nevertheless not disputed that human 
exposure to such residues adds some more burden to  the background levels. It is thus expected that 
this addition may increase the risk of cancer. It is im portant to note, however, that this kind of human 
exposure to levels of residues occurring in natural foods (e xogenous exposure) cannot be avoided , 
unless the consumption of such natural foods is redu ced or prohibited. But as the Appellate Body has 
explained in its 1998 Hormones  report (at para. 221), this kind of prohibition is not possible as it 
would require such a comprehensive and massive governmental intervention in nature and in the 
ordinary lives of people as to reduce the comparison itself "to an absurdity". Indeed, it would require 
changing human diet and habits that have been  practiced for centuries by human beings.   
50. The concept of "additive" risk refers to expos ure which is further added on humans from the 
levels of residues in meat from animals treated with  these hormones for growth promotion. The risk of 
cancer14 from this kind of exposure to residues from hor mone-treated meat is "added" to the cancer 
risk from the existing (endogenous) exposure through  the background levels of  hormones and through 
the exposure to (exogenous) sources as contained in non-treated natural food. It is not disputed (see, 
e.g., the 2002 US Report on Carcinogenesis) that "v eterinary use of steroidal estrogens to promote 
growth and treat illness can increase estrogens in  tissues of food-producing animals to above their 
normal levels", in general s ubstantially higher than the nor mal (endogenously produced) levels.15 
Therefore, it should be stressed that, unlike for the other two sources of exposure, exposure to 
residues from hormone-treated meat is avoidable  because these hormones are chemical substances 
that are deliberately added in meat.  See also the reply to Question 13 below for the regulatory 
implications from these different sources of exposure. 
51. The risk of cancer from the consumption of r esidues in hormone-treated meat are "additive" 
(to risk of cancer from the two other sources of exposure), irrespective of whether these hormones are genotoxic carcinogens or only promote cancer through receptor-mediated mechanisms. Indeed, if they 
cause cancer by direct genotoxic action, the addition of such exposure increases the likelihood of the 
adverse effect to occur. If they act only through receptor-mediated mechanism, the risk from such 
                                                     
 
13 See, e.g., Exhibit EC-35, which is a pioneering study in this area, of which neither the defending 
members nor JECFA were aware when they evaluated these hormones. 
14 For reasons of convenience, only the potential risk of cancer is mentioned here, although the 1999 
opinion of the SCVPH has identified a number of other possible adverse effects on humans from exposure to 
exogenous hormonal residues, in particular from hormone-treated meat.   
15 The 1999 SCVPH contains data on the higher re sidue level in treated an imals with these hormones 
(as compared to untreated animals) . See tables 2 (for oestradiol-17 β), 5 (for testosterone) and 7 (for 
progesterone). Since the other three synthetic hormones are not produced endogenously, their residues will always be additional. The 1999 SCVP H opinion is based on recent studies: s ee, e.g., Exhibit EC-11 (concerning 
melengestrol acetate showing that the US tolerance leve ls will be exceeded after administration of 1.5 mg/day, 
that is according to the recommended dosa ge of use in the US). See also Exhi bits EC-14, 16, 17 , 18, 47, 50, 53 
and 78, which prov ide the most recent measuremen ts of residues in meat fro m animals treated with these 
hormones for animal growth promotion according to GVP and in situations of abuse. WT/DS320/R/Add.3 
Page C-14  
 
  exposure will be again "additive", when they cause th e presumed threshold to be exceeded. The risk 
assessment of the European Communities has established that oestradiol-17 β is a proven genotoxic 
carcinogen and that the other two natural hormones (t estosterone and progesterone) are also suspected 
to be genotoxic. Moreover, the risk assessment of  the European Communities has also demonstrated 
that the ADIs recommended by JECFA for all these hormones will be exceeded under realistic 
conditions of use of these hormones in the US and Canada. They will also be exceeded in any case if 
the more recent data on the endogenous production of  the natural hormones by pre-pubertal children 
is taken into account.  
Q12. A 1999 Report of the Committee for Veteri nary Medicinal Products of the European 
Communities refers to  the low bioavailability of oestradiol 17 β.  How is this finding reconciled 
with references to bioavailability in the SCVPH Opinion?  (please refer to comments by the 
parties on the Panel's Question 43 to experts) 
 
52. The 1999 report of the Committee for Veterinary Medicinal Products (CVMP) (see Exhibit 
CDA-5) states, as regards oestradiol-17 β, the following: "the bioavailability of 17 β-oestradiol esters 
after oral administration is low (3% as unchanged 17 β-oestradiol), but might be higher if estron, an 
estrogenic active metabolite, is included" (at p. 2).  
53. First, it should be noted that the 1999 CVMP report does not cite any specific new literature 
in support of this statement. Indeed, of the scientif ic literature cited on pages 14 – 17 of that report, 
there appears to be no paper or study specifically relating to measuring bioavailability of oestradiol-
17β. Consequently, the CVMP opinion must be simply reproducing on this point the JECFA 
evaluations of 1988 and 1999 for oestradiol-17 β, and is not based on ne w scientific evidence.  
54. Secondly, it is important to note that the last sentence from the above quoted 1999 CVMP 
report states that: "… but might be higher if estr on, an estrogenic active metabolite, is included". 
Indeed, the JECFA reports and, by extension the 1999 CVMP opinion, have considered only some of 
the residues of oestradiol-17 β in meat; in particular, they have not considered the lipoidal (fatty acid) 
esters nor estrone residues.  This is important becau se lipoidal esters "represent about 40% of the total 
oestradiol-17 β esters in fat meat shown in the metabolic  study", and they are "about tenfold more 
active on uterotrophic assay than oestradiol-17 β when given orally" (see Exhibit EC-51A, page 18).  
The two scientific studies by the European Communities (Exhibit EC-51A, and Exhibit EC-51C, at page 32) concluded that the residues of lipoidal esters and of oestrone have not been considered so far 
by any risk assessment known at the time (either by the defending members or the 1988 and 1999 
JECFA assessments) and that it is imperative that they are taken into account in the calculation of 
bioavailability and the pharmacokinetics (see  also Exhibits EC-9 and EC-117, both confirming these 
findings). It follows that the 1999 CVMP report, which is based on the old JECFA evaluations on 
bioavailability, can no longer be considered relia ble. Conversely, the findings on bioavailability by 
the SCVPH in 1999 and 2002 are more accurate beca use they are based on more recent and pertinent 
scientific information. 
55. Moreover, the European Communities has comment ed in detail on the comments made by the 
defending members on the Panel's Question 43 to e xperts and maintains entirely the comments it 
submitted on 12 July 2006 (at paragraphs 150-1 54). With its comments the European Communities 
has tried to explain why the data on bioavailability used by the defending parties and JECFA are most 
likely to be wrong for two reasons: 1) as just bei ng explained above, because they do not take into 
account all the relevant residues in hormone-tre ated meat; and 2) because their estimate that 
bioavailability of oestradiol-17 β is <10%  is in itself not correct, for the reasons explained in the EC's 
comments of 12 July 2006 (at paras. 150-154).  
56. Canada's comments of 12 July 2006 (at para. 93) do not help develop the debate further 
because Canada seems to espouse the argument of Dr. Boobis about the ADI representing a  WT/DS320/R/Add.3 
 Page C-15 
 
 
  "bioavailability adjusted" does.  But even if  the arguments of Dr. Boobis were correct ( quod non ), 
determining with accuracy the level of bioavailability is very importa nt – instead of proceeding with 
mere assumptions as does JECFA – if we take into account the much lower endogenous production 
rates by pre-pubertal children in the calculation of the ADI and that multiple implanting of animals with these hormones is recommended by the manufact urers and currently practiced in the US and 
Canada. 
57. The comments of the US of 12 July 2006 (at paras. 124-128, as well as at paras. 119-120 
thereof) are confusing and misleading. Th e US comment (at para. 124) that "the Lampit  study very 
clearly indicates that, to overcome the low bioavailability of estradiol 17 β, very large amounts of the 
hormone must be administered orally to achieve a therapeutic effect" is wrong.  
58. The Lampit et al.  paper of 2002 (see Exhib it EC-99) states that: "The mini-dose of estrogen 
used here is based on an attempt to replace prepubert al estrogen levels. It is much lower than the low 
dose estrogen employed for growth acceleration in gi rls with Turner syndrome. Based on the relative 
estrogenic activity of conjugated estrogen and ethiny l E2 and a mean patient weight of 20 kg, it was 
calculated that the mini-dose is 12- to 28-fold w eaker than the usual low dose of 100 ng/kg ethinyl E2 
given for growth acceleration." (at page 689, footnotes omitted).
16 Contrary to what the US argues, 
therefore, the 2002 Lampit et al.  paper states that very low doses suffice to observe biological action 
in pre-pubertal children, which must mean  that bioavailability of oestradiol-17 β at those very low 
doses cannot be insignificant.  
59. More importantly, however, the US  comment s (in para. 124) that "very high doses are 
required to elicit the desired therapeutic effect " is misleading because such high doses are not 
administered (at least not only) in order to elicit th e desired therapeutic effect but in order to elicit it 
quickly , otherwise the treatment will not be therapeutic. Therefore, from the high doses used for 
therapeutic treatment, it does not follow (as the US argues) that such doses are necessary because of 
the low bioavailability of oestradiol-17 β. 
60. Finally, the other US comments of 12 July 2006 (at paragraphs 125-128) do not help us 
develop the debate further, as the US misint erprets the EC arguments and the opinion of 
Dr. Guttenplan. Moreover, the US comment in para . 128 is confusing, because all the scientists 
confirmed that the bioavailability of the three synthetic hormones (trenbolone acetate, zeranol and 
melengestrol acetate) is not known. Whether JECFA assumed 100% bioavailability for these synthetic hormones is another issue, as explained above, and this is not the point the EC was making when 
arguing that the bioavailability of the three natu ral hormones by the defending parties and in the 
JECFA evaluations has been underestimated.  
Q13. In its comments on replies of experts to  Panel Question 19 (para.75) Canada asserts that 
a recent Opinion of the European Food Safe ty Agency (EFSA) recognizes thresholds for 
genotoxic substances.  Please elaborate. 
 61. The European Communities fails to understand why Canada made the reference to the 
opinion of EFSA of 18 October 2005 (see also exhibit CDA-46), because that document does not support Canada's claim.   
62. It should first be noted that Canada does not quote in its entirety the paragraph in question 
from the EFSA's opinion (cited at para . 75 of Canada's submission). The paragraph in question reads 
as follows:  
                                                     
 
16 Incidentally, the 2002 Lampit et al. paper cite s with approval the calculations of endogenous 
production rates of pre-pubertal children estimated by th e Klein et al. assay, which the Lampit paper explicitly 
characterises "as the landmark report  by Klein et al." (at p. 689). WT/DS320/R/Add.3 
Page C-16  
 
  The Scientific Committee concludes that  based on the current understanding of 
cancer biology there are levels of expos ure to substances which are both genotoxic 
and carcinogenic below which cancer incidence is not increased (biological thresholds in dose-response), however, numerical values for such levels of 
exposure cannot be identified on scientific grounds at the present time.  (the 
highlighted phrase was left out by Canada). 
63. More importantly, however, the opinion of EFSA has clarified very clearly that the purpose 
for which it was provided is different from the one mentioned by Canada. The EFSA opinion states 
that the margin of exposure approach is for "c ases where substances that are both genotoxic and 
carcinogenic have been found in food, irrespective of  their origin, and where there is a need for 
guidance on the possible risks to those who are, or have been, exposed" (at page 21).  This means that 
this approach applies only for substances that occur or develop naturally  in food or the environment 
(e.g. the aflatoxins in dried food or the naturally occurring oestrogens in broccoli or in eggs, etc.).17  
This is explained at page 5 of EFSA's Opinion which states:  
Undesirable substances occur in food (for ex ample as an inherent natural constituent 
in the food plant or as contaminant thr ough their presence in the environment, 
through fungal contamination or through pr eparation processes). The general need to 
minimise exposure to such substances, wh en they are demonstrated to present a 
carcinogenic and genotoxic hazard, is expressed in the ALARA (as low as reasonably achievable) principle. The opinion of the Scientific Committee addresses approaches beyond the ALARA principle allowing a level of potency assessment of specific 
substances which are present in food and wh ich are both genotoxic and carcinogenic. 
Such an approach will not substitute for mi nimising exposure to all such substances. 
It will ensure that, where resources are limite d, the highest priority  is given first to 
those substances which present the greatest risk for humans.
18 
64. But acceptable margins of exposure do not apply for chemical substances (like the six growth 
hormones) which are intended to be deliberately  added (i.e. administered exogenously) to food. 
Authorisations for such chemical substances to be added deliberately to food, feed or the environment 
are not granted. Canada has apparently not read the other relevant parts of EFSA's Opinion which 
explain this as follows: 
The Scientific Committee is of the opinion th at in principle substances which are both 
genotoxic and carcinogenic should not be delib erately added to foods or used earlier 
in the food chain if they leave residues which are both genotoxic and carcinogenic in 
food. (at pages 5 and 21). 
65. The reason for which the EFSA opinion came to this conclusion is that:  
                                                      
17 See, e.g., Commission Regulation (EC) No 1525/98 (O.J. L 201, 17.7.98, p. 43) which has sought to 
eliminate or reduce exposure from aflatoxins in dried food or in milk on the following grounds: "Whereas 
aflatoxins, in particular aflatoxin B1, are genotoxic carcinogenic substances; whereas for substances of this type 
there is no threshold below which no harmful effect is observed; whereas no admissible daily intake can therefore be set; whereas current sc ientific and technical knowledge and improvements in production and 
storage techniques do not prevent the development of these moulds and consequently do not enable the presence 
of the aflatoxins in food to be eliminated entirely; wh ereas it is, therefore, advisabl e to set limits as low as 
possible" (see 5th recital of the preamble). 
18 Indeed, the EC has a consistent r ecord of taking the measures nece ssary to reduce or eliminate risks 
from the naturally occurring genotoxic and carcinogenic agents. See, e.g., Council Regulation (EEC) 315/93 laying down Community procedures for contaminants in food (O.J. L 37, 13.2.1993, p.1), which has been 
amended several times and most recently by Commission Re gulation (EC) 466/2001, O.J. L 77, 16.3.2001, p. 1.  WT/DS320/R/Add.3 
 Page C-17 
 
 
  For genotoxic substances which interact with DNA, directly or after metabolic 
transformation (direct-acting genotoxic chemicals), the absence of a threshold in their mechanism of action is generally assumed, i.e. there is no dose without a potential 
effect.  (at page 5) 
66. The European Communities takes this opportunity  to stress that it has a consistent and 
coherent record of prohibiting chemical subs tances that are both genotoxic and carcinogenic when 
applications for authorisation in order to be delib erately added to food, feed or the environment are 
made. It has prohibited a number of chemical substances once experiments on animals have shown that they are genotoxic carcinogens or they were su spected of having such properties, for instance:  
• the withdrawal of the authorisations  for Carbadox and Olaquindox in 1998,
19  well 
before JECFA and Canada did so; 
 
• the withdrawal of the authorisation for the coccidiostat Nifursol in 2002;20 
 
• the withdrawal of the authorisation for a number of flavouring substances, such as 
methyleugenol and estragol in 2002;21 propyl 4-hydroxybenzoate and pentane-2,4-
dione in 2005;22 and acetamide in 2006.23  
 
67. The European Communities would like to addr ess another related error in the reply of 
Dr. Boobis to written question No 11 of the Pane l, where he made reference to the pesticide 
daminozide (a suspected genotoxic carcinogen) and im plied that "there may be kinetic or dynamic 
factors indicating that although theoretically there was no exposure with zero risk, in practice the risk 
would be minimal and therefore acceptable". The statement by Dr. Boobis is misleading, however, 
because the administration of daminozide has not been approved for edible crops but only for non-
edible  plants (flowers), something he does not explain.24 
68. In conclusion, therefore, a distinction should be made between genotoxic carcinogens that are 
occurring or developing naturally in food (e.g. nitrat e, aflatoxins, broccoli, soyabeans, and eggs) and 
the chemical substances that are intended to be  added deliberately to food (e.g. carbadox, the six 
hormones for animal growth promotion, etc). For the former, there is not much that can be done other 
than take measures to reduce or eliminate the risk  to the extent possible. For the latter, however, 
refusal to authorise their use is an effective means of preventing their addition to food, so as to 
achieve the chosen level of protection. The Europ ean Communities hopes this will clarify that there is 
no basis in the confusing argument of the defending parties that, since human beings are exposed to estrogens from so many sources (endogenous animal  and human production and exogenous intake 
from natural foods), the small addition from the resi dues in hormone-treated meat would pose no risk. 
The European Communities contests the simplistic logic of this unscientific argument by the 
defending parties that, unfortunately, has found its  way also in the evaluations of JECFA.  
69. The European Communities can therefore confirm that it applies consistently a policy on risk 
analysis that prohibits the authorisation of chemi cal substances which are suspected or proven to be 
genotoxic carcinogens when they are intended to be a dded deliberately to food. This is in order to 
achieve its level of health protecti on of no (avoidable) risk, that is a level of protection that does not 
                                                     
 
19 See Commission Regulation (EC) No 2788/98,  OJ No L 347, 23.12.1998, p. 31-32. 
20 See Council Regulation (EC) No 1756/2002, OJ No L 265, 3.10.2002, p. 1. 
21 Commission Decision 2002/113/EC of 23.1.2002, OJ No L 49, 20.2.2002, p.1. 
22 Commission Decision 2005/389/EC of 18.5.2005, OJ No L 128, 21.5.2005, p. 73. 
23 Commission Decision 2006/252/EC of 27.5.2006, OJ No L 91, 29.3.2006, p. 48. 
24 See Commission Directive 2005/53/EC of 16.9.05, OJ No L 241, 17.9.2005, p. 51, at page 55, 
point 105. WT/DS320/R/Add.3 
Page C-18  
 
  allow any unnecessary addition from exposure to ge notoxic chemical substances that are intended to 
be added deliberately to food. The risk from residue s in hormone-treated meat is such an avoidable 
risk, and this is what the European Communities aimed to achieve when it adopted the Directive 
2003/74/EC. 
Q14. Has the draft assessment of the UK Gro up (referred to in para.187 of the European 
Communities' rebuttal submission) already b een assessed by EFSA or other relevant 
institutions?  If so, what are the conclusions? 
 
70. As mentioned in its reply to Question 12 above, the UK Group adopted the final
 version of its 
report in June 2006.25 EFSA is currently reviewing this report.  An assessment is expected for April 
2007. 
71. A mere reading of the report's conclusions  and recommendations, however, already shows 
that the UK Group has considerably changed its assess ment since the last assessment it  had carried 
out in 1999 (to which the SCVPH reacted with its 2000 Opinion). Indeed, while the 1999 UK assessment maked a number of bold "no evidence" conclusions, for example on mutagenic/genotoxic 
activity or threshold considerations, the 2006 UK repor t contains conclusions which are very nuanced 
and put heavy emphasis on the fact that the scientific  data are incomplete and that many uncertainties 
remain and need to be studied. The European Communities recalls that when Directive 2003/74/EC 
was adopted by the European Parliament and C ouncil, the United Kingdom did not vote against the 
Directive. 
72. Thus, on mutagenic/genotoxic activity, the repor t now refers to the "weight of available 
evidence [which] suggests that likely levels of human exposure to hormonally-active substances in 
meat from treated animals would not be sufficient to induce any measurable biological effect" and 
goes on to state that "specifically, it is very unlikely that the presence of 17 β-oestradiol and its 
metabolites in meat from treated animals would sign ificantly increase the risk of adverse effects in 
consumers."  That conclusion is based on a number  of important "qualifications and reservations" 
including the assumption that there is a "correct " or "recommended" use of the exogenous hormonal 
substances and the reservation that all scientific data  relate to single substances only and not to their 
combined use.  
73. Absence of information and scientific uncertainty is also the reason why not all of the 
conclusions were supported by all members of th e UK Group (note that the press release speaks of 
two dissenting opinions). Indeed, the following is stated under "qualifications and reservations": 
the Working Group had to decide what to do in the absence of information or where 
there was uncertainty of interpretation of  information. One Member expressed the 
view that for the substances under consideration, there was a large 
element of 
uncertainty, so the precautionary principle sh ould 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.
 
74. The report states clearly that "there are importa nt gaps  in the evidence base  that preclude 
producing definitive risk assessments for 17 β-oestradiol or the other five hormonally-active 
substances". (at point 6 of  the executive summary). It is significant to note that the report further 
states (at point 6) that:  
                                                      
25 Press release of 5 July 2006 and report available at http://www.vpc.gov.uk/.  WT/DS320/R/Add.3 
 Page C-19 
 
 
  Not all data gaps are equally important for the purposes of risk assessment and the 
Working Group highlighted a number that could improve future risk assessments. As an example, it would be helpful if the CVMP and JECFA could make available data 
on pharmacokinetics and metabolism of assess ed compounds that were supplied in 
manufacturers' dossiers. This openness and tr ansparency would allow greater public 
scrutiny of the facts and confidence in th e hazard and risk assessments produced.  
75. Indeed, this is what the Eur opean Communities has been arguing, namely that the CVMP and 
the JECFA evaluation would have to be opened to transparent procedures and provide the old 
evidence on which their assessments were based in order to enable an objective and transparent re-
evaluation of these substances. Moreover, the UK repor t's conclusions end with a list of things that 
"need to be established in order to improve future risk assessments."  It is worth quoting some of the 
important gaps that are  listed in  points 7 to 9  of the executive summary, as it takes up many of the 
points on which the European Communities has argued that there is scientific uncertainty: 
• the precise relationship between the pot ential use of growth-promoters and 
concentrations of residues in meat 
 
• levels of exposure in consumers 
 
• dose-response relationships for the effect of hormonally active substances (and their 
metabolites) in experimental animals and humans  
 
• the bioavailability, metabolism and possible bioaccumulation of lipoidal esters of 
oestrogen following ingestion of meat from implanted cattle  
 
• the possible synergistic effects of cocktails of hormonal substances  
 
• a validated technique to detect and assign lo w residual concentrations of oestradiol in 
the finished edible products to natural sources or implant residues. 
 Q15. What steps has the European Communities ta ken to request re-evaluation of the existing 
international standards for the five hormones,  according to the procedures of JECFA or 
Codex ?  Please provide documentation. 
 
76. First, it is worth recapitulating what the Europ ean Communities did (as described at para. 96 
et seq. (WT/DS320), paras. 79 et seq. (WT/DS321) of its Second Written Submission). The European 
Communities informed Codex and the JECFA Secret ariat in May 1998 that it was carrying out new 
risk assessments on the six hormonal substances in  question and that it had launched a series of 
specific studies.26  
77. Upon learning that JECFA, on its own initiative, has decided to re-evaluate the three natural 
hormones, the European Communities, by letter of 31 July 1998 to Codex and letter of 27 November 
1998 to JECFA requested that this re-evaluati on be postponed until the results of the studies 
commissioned have come in.27 An indicative list of the 17 studies wa s attached to the letter. However, 
both Codex and JECFA declined to heed to this request, without any valid reason.28 At the 11th 
                                                      
26 See reference to letter of 7 May 1998 in EC-Exhibit 63 – No 13: letter to Mr. Orriss, Chief of Joint 
FAO/WHO Food Standard Programme, dated 31 July 1998. 
27 See EC Exhibit 63 – No 13 and No 14 (letter of reply to letter sent on 27 November). 
28 See EC Exhibit 63 – No 14 (letter from Mr. He rman, JECFA Secretariat, dated 23 December 1998) WT/DS320/R/Add.3 
Page C-20  
 
  session of the CCRVDF in late June 1999, the Eur opean Communities re-iterated its request, to no 
avail.
29  
78. Second, according to JECFA's procedural rules there are five ways of placing veterinary 
drugs on the agenda for (re-)evaluation.30 These are the following31:  
1. Codex committees 
The Codex Committee on Residues of Veteri nary Drugs in Foods (CCRVDF) refers 
substances to JECFA based on priorities that  it establishes using criteria that it has 
developed that are in accord with accepte d procedures of the Codex Alimentarius 
Commission. 
2. FAO and WHO Member States 
FAO and WHO Member States may request the inclusion of veterinary drugs on the 
agenda of JECFA through a direct request to the FAO and WHO Secretariats. Such a 
request must be accompanied by a commitment to provide the necessary data 6-7 months before the meeting. 
3. Sponsors 
For veterinary drugs not previously evaluated by JECFA, an industry sponsor may 
forward a request for evaluation through the government of a Member State to CCRVDF, with a commitment to provide th e relevant data. Requests for the re-
evaluation of a veterinary drug that has been reviewed by JECFA previously may be forwarded directly to the JECFA Secretar iat. As with all other substances on the 
agenda, the Joint Secretariat includes the subs tance in the call for data for the meeting 
to ensure that all interested parti es have the opportunity to submit data. 
4. JECFA Secretariat 
The JECFA secretariat may place a veterinary drug on the agenda for re-evaluation 
even though no outside request has been received. 
5. JECFA itself 
The Committee often establishes a temporary ADI or recommends temporary MRLs, 
with a request for further data by a certain  time. These veterinary drugs, which have 
the highest priority for evaluation, are placed on the agenda of the appropriate meeting by the Joint Secretariat. 
79. The first listed here is the "priority list" proce dure described by Dr. Myagishima at the expert 
meeting.  The European Communities has, since the events described above, not made a formal 
                                                     
 
29 See para. 125 of the Report of the Eleventh Session of the Codex Committee on Residues of 
Veterinary Drugs in Foods (A LINORM 99/31), available at 
http://www.codexalimentarius.ne t/web/archives.jsp?year=99. 
30 Note that two sets of procedural guidelines govern JECFA's work, one issued by the WHO and one 
issued by the FAO. The former is available at 
http://www.who.int/ipcs/food/jecfa/procedural_g uidelines%20_drugs.pdf, the latter at   
ftp://ftp.fao.org/es/esn/jecfa/2002-09- 24_Vet_Drugs_Proc_Guidelinesb.pdf. 
31 In respect of the five ways of having a subs tance (re-)evaluated, the two abovementioned sets of 
guidelines are identical. The text reproduced above is the Annex 1 of the respective guidelines.  WT/DS320/R/Add.3 
 Page C-21 
 
 
  request to have any of the six hormonal substances in question put on the priority list.  As explained at 
the hearing, however, the European Communities may do so once the new risk analysis principles on 
residues in veterinary drugs have been adopted.32  
80. Note, however, that this first way, contrary perh aps to what may have transpired at the expert 
meeting, is not the only possibility for a Member to  request evaluation of a substance through JECFA.  
Indeed, as can be seen from the above point 2, there is also the possibility for a Member to directly 
request such evaluation from either FAO or WH O. What the European Communities has done as 
described above can be subsumed under this second way of requesting (re-)evaluation of substances. 
As seen above, the European Comm unities turned directly to FAO (the EC was only a member of 
FAO – not Codex Alimentarius – at that time) to  inform it of the new ongoing risk assessments on all 
six substances and to request th e postponement of the impending re-e valuation of the three natural 
hormones until after the results of the 17 studies would be available. Obviously, this implies a commitment to make the results of these risk assessm ents and 17 studies available to JECFA. Equally 
obviously, this avenue became obsolete with JECFA' s refusal to postpone for a period of 2-3 years the 
re-evaluation of the three natural hormones.   
81. Note, furthermore, that under the above rules (poi nt 4), the JECFA Secret ariat can also decide 
on the (re-) evaluation of a substance on its own initia tive.  This is what the JECFA Secretariat has 
indeed done with regard to the three natural hor mones. Note finally, that when performing an 
evaluation, the temporary advisor (i.e. a member of the JECFA secretariat put in charge of preparing working papers on the substance in question on the basis of available data) is asked to perform a 
literature search on the substance in question.
33 In light of these facts, it is clear that JECFA has had 
every opportunity, after the European Communities' repeated raising of the issue of the new risk 
assessments, to  postpone the 1999  risk assessment  and to place again these hormones for evaluation 
after 2002.  
82. Moreover, the Delegation of the European Community referring to its written comments 
contained in CX/RVDF 06/16/7, Add.1, stated th at the MGA was evaluated by JECFA as growth 
promoters and that such use of hormones with estrogenic, androgenic or gestagenic action was 
prohibited in the European Union. The prohib ition was permanent for Oestradiol 17beta and 
provisional for the other hormonal substances. The 2002 review of the Scientific Committee on Veterinary Measures (SCVHP) relating to Public H ealth considered the report on MGA prepared by 
the 54
th meeting of JECFA and observed that it provides a comprehensive review of the 
pharmacokinetic/toxicokinetic parame ters and toxicological properties of MGA in various species. 
The Delegation argued, however, that no original data  were presented in the review and the majority 
of references were reports that  had not been published in the p eer-reviewed scientific literature. 
Therefore, for MGA, concerns re mained that excess intake of horm one residues and their metabolites, 
endocrine, developmental, imm unological, neurobiological, immunotoxic, genotoxic and carcinogenic 
effects could be envisaged, in particular for su sceptible risk groups. For th ese reasons, the European 
Communities could not support the adoption of the MRLs proposed by the 66th  JECFA. This position 
was supported by two other delegations.  
                                                      
32 Proposed Draft Risk Analysis Principles applied by the Codex Committee on Residues of Veterinary 
Drugs in Food (for inclusion in the Codex Procedural Manual), Appendix VIII of ALINORM 06/29/31 (report of 16th CCRVDF) Available at http://www.codexalimentari us.net/web/archives.jsp?lang=en]. As explained at 
the hearing, the new Paragraphs 19 and following of th ese principles provide the CCRVDF as the risk manager 
with much more concrete possibilities to give specific instructions to JECFA on which aspects to cover in its risk assessment. Given that the EC risk assessments on the six substances in question raise many issues which 
have so far not been addressed by JECFA, it is obviou s that the European Communities would want JECFA to 
be instructed to specifically address these issues. 
33 Both the WHO and the FAO guidelines underline the importance of this literature search, see WHO 
guidelines, page 6 in bold, see FAO guidelines, point 5.2. WT/DS320/R/Add.3 
Page C-22  
 
  83. The following were the EC written comments on the matter delivered in time before the 
meeting and submitted to everybod y in CX/RVDF 06/16/7, Add.1: 
Melengestrol acetate: The substance was evaluated by JECFA for use as growth 
promoters. Such use of hormones with estr ogenic, androgenic or gestagenic action is 
prohibited in the European Union. This pr ovision is permanent for oestradiol 17B and 
provisional for the other hormonal substances. It is also in line with Article 5.7 of the 
SPS Agreement. It applies while the Comm unity seeks more complete scientific 
information. The European Commission (by means of the Scientific Committee on Veterinary Measures relating to Public H ealth – SCVPH, and now the European Food 
Safety Authority – EFSA) reviews regularly  any additional scientific data from all 
possible sources that is publicly available. This entails continuing to review, as done 
in 2000 and 2002, the availability of scien tific publications and evaluation reports.  
The 2002 review of the Scientific Comm ittee on Veterinary Measures relating to 
Public Health considered the report on melengestrol acetate prepared by the 54th meeting of JECFA and observed that it provides a comprehensive review of the 
pharmacokinetic/toxicokinetic pa rameters (adsorption, distribution, metabolism and 
excretion) and toxicological properties of MGA in various species. It criticised, however, that no original data are presented in this review and the majority of the 
references are to reports that have not been  published in the peer-reviewed scientific 
literature. The 54th JECFA report itself states that " Most of the studies were 
conducted before 1979 according to the standards in existence at that time and were 
not carried out in compliance with GLP " (page 65, 3
rd  
paragraph of 54th JECFA 
Report) and the 62nd  
JECFA presented only new information regarding the structure 
and activity of the metabolites of MGA (page 22 of 62nd JECFA Report).  
The EU scientific committee considered more recent investigations and summarised 
(see page 17 to of the SCVPH report of 2002 2). Preliminary data cited in this report:  
– indicated that the metabolism of MGA is more complex that previously 
assumed, but further experiments should verify the specific metabolite pattern in target animal species as well as man;  
– demonstrated that MGA has a very strong potential to bind to bovine 
progesterone receptors, although these data need further verification;  
– suggested that in utero or pre- and peripubertal exposure to hormones 
(including animal evidence on synthe tic products) may affect pubertal 
development and epidemiological studies with opposite sexed twins indicate that prenatal exposure to hormones may be linked to adult cancer risk;  
– showed that newer experiments clearly identify a risk for excessive exposure 
of consumers to residues from misplaced  or off-label used implants and 
incorrect dose regimes. In these cases, le vels of oestradiol and its metabolites 
in muscle, fat, liver and kidney from hor mone treated cattle may be 2-fold up 
to several hundred folds higher as compar ed to untreated meat. The level of 
increase depends on the treatment regime and the actual hormone levels in the implants used.  
Therefore for melengestrol acetate concerns remain that by excess intake of hormone 
residues and their metabolites, endoc rine, developmental, immunological, 
neurobiological, immunotoxic, genotoxic  and carcinogenic effects could be  WT/DS320/R/Add.3 
 Page C-23 
 
 
  envisaged, in particular for susceptible risk  groups persist. The European Community 
can therefore not support the adoption of th e proposal for maximum residue limits for 
this substance. The next revision of its scientific opinion by EFSA is to be presented 
later in 2006. There has been a respective call for data at: 
http://www.efsa.eu.int/index_de.html . The European Community suggests that this 
substance is sent back to JECFA for re-evalu ation in the light of the latest information 
provided in the 2002 and the expected 2006 risk assessments by the scientific committees of the European Community.  
Q16. Please explain the reason for the differences between the "list of the 17 studies" that was 
appended to the 2002 Opinion and the one that was provided to the Panel.  (please see 
paragraph 20 of the United States' Rebuttal Submission and its Table 1)  
84. As explained above under Question 3, when th e 2002 Opinion was issued all except two of 
the studies had already been published. Differences in  the two lists are mainly the result of further 
publications of partial aspects of the studies.  The European Communities is annexing as 
Exhibit EC-129 a commented version (track changes)  of the US Table 1 referred to in the above 
question. It sets out in detail where and when  the different studies have been published. WT/DS320/R/Add.3 
Page C-24  
 
  ANNEX C-2 
 
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 SUBSTANTIVE MEETING 
 
(31 October 2006) 
  Panel Questions to all parties
: 
 Q1. With reference to the statement by the European Communities, inter alia  in para. 12 of 
the EC reply to Question 3 of the United States, do  the parties consider that a Panel is entitled to 
address "systemic claims" or issues related to "systemic obligations" and, if so, to what extent? 
 1. There does not seem to be a disagreement among the parties as to the substance of this 
question: all agree that the Panel has the task of ruling on the claims that the European Communities 
has made under Article 23 of the DSU irrespective of  whether one wants to call them "systemic" or 
not.  
2. Obviously, the parties' views differ on the ques tion of how far the obligations contained in 
Article 23 go. Canada reiterates its vi ew that it is the EC and not Canada that is acting unilaterally by 
proclaiming compliance. In its response, Canada's al so overlooks one of the central EC claims in this 
dispute, namely the breach of Article 23 that lies in  the fact that the US a nd Canada failed to have 
recourse to the DSU to seek redress of a violation,  and instead unilaterally determined that the EC 
continued to be in breach of WTO obligations.  The US, while being polemic, does not bother to 
explain its view on the extent of these obligations . It merely dismisses the European Communities' 
reading as an attempt "to see the DSU redrafted, at least for purposes of this dispute."  
3. Fact is, however, that this Panel has the task of  applying Article 23 to the situation at hand: A 
Member, in good faith, presents its compliance measu re and nevertheless has to suffer continued 
application of sanctions, because the other si de denies that compliance has been achieved  and refuses 
to initiate the dispute settlement proceedings foreseen in Article 21.5. It is the first time that this 
situation arises in the dispute settlement system. Is it a situation that the DSU does not address? 
Neither side in this dispute says so. The parti es merely have differing vi ews on how to interpret 
Article 23 and Articles 21.5 and 22.8 wh en applied to this situation.  
4. For some of the parties involved in this dispute, these views, not surprisingly, are related to 
positions taken in the current DSU review, in Canada's  case since rather recently (see EC's response to 
Panel question No. 64)
1. Indeed, not surprisingly, the current DSU review, amongst other issues, 
addresses this one, in order to precisely solve – th rough negotiation – the existing divergence of views 
on how the DSU should be applied in this situati on.  This is a not uncommon phenomenon in the 
WTO system: The correct interpretation of obligatio ns is subject to disagreement among members and 
there is an initiative to settle that disagreement through political consensus.2 Such initiatives are not 
always crowned by success or – as the present case shows – do not reach a result in time to address a 
given situation when it arises.  The obligations – disputed as their content may be – do, however, 
exist.  Thus, in the absence of an explicit clarifi cation of the existing obligations by the collective 
                                                      
1 See paras. 205 et seq. of the EC Replies to Panel's Questions after First Substantive Hearing, 
erroneously called Question 60. 
2 Another example is the role of multilateral environmental agreements in the interpretation and 
application of the WTO agreements. "Zeroing" methodology may serve as a further example.    WT/DS320/R/Add.3 
 Page C-25 
 
 
  Membership itself, it is for the dispute settlement bod ies to discharge their duty to apply and interpret 
the rules that exist today.  Even if there were a pr ospect of a conclusion of the DSU negotiations in the 
very near future, there is in no event a non liquet  option of saying "we will wait for the outcome of the 
negotiations." 
Q2. With reference to the US rebuttal, para. 27,  do the parties consider that a measure that 
does not comply with the requirements of Articl e 5.7 SPS would automatically be in breach of 
Article 2.2 SPS, or Article 5.1 SPS, or both?  
5. There seems to be agreement among the parties on the point that there is no automatic breach 
of Articles 2.2 and 5.1, if a measure does not comply  with the requirements of Article 5.7. Indeed, the 
legality of a measure based on Article 5.7 can be determined independently of the requirements of 
Articles 2.2. and 5.1, since Article 5.7 is an exceptio n to both of them. This is because, in addition to 
the comments made at paras. 3-5 of the EC's rep lies of 18 October 2006, it is necessary to take into 
account the reasons for which, in a given situation,  all the requirements of Article 5.7 SPS are found 
not to have been complied with. It should be noted that the basic obligation under Article 2.2 SPS is to 
base the measure on sufficient scientific evidence. Th e performance of a risk assessment, in the sense 
of Article 5.1-5.2, is one way of providing such proof. However, as the experts have argued in the 
case of prohibiting tobacco smoking, it was not necessar y to perform a risk asse ssment in the sense of 
Article 5.1 before taking a measure in the light  of the overall scientific evidence available.  
6. The European Communities would, however, ag ree with the US and Canada that in the 
present cases the recommendations and rulings of the DSB had identified a breach of Article 5.1 
which the EC compliance measure needs to address. Bu t no such breach exists any longer, if either of 
the following two situations applies: the measure  is now based on a risk assessment and therefore 
consistent with Article 5.1; or the measure is based on Article 5.7 because the relevant scientific 
evidence is not sufficient to carry out a full risk assessment in the sense of Article 5.1 SPS.
3 However, 
the European Communities disagrees w ith the US comment (at para. 5 of   its reply of 18 October 
2006) that "the EC does not claim to  have performed a risk assessment consistent with Article 5.1".  
This is not true. The EC has performed such a risk assessment for oestradiol-17 β. Moreover, the EC 
has performed such a risk assessment  also for the other five hormon es. In the performance of such a 
risk assessment, however, the EC has come to the conclusion that for the five hormones it was not 
possible to complete the risk assessment because th e relevant scientific evidence was insufficient on a 
number of important issues and points that are clearly identified and explained in the risk assessment. 
That is why the EC had to base its measure for the five hormones on Article 5.7 SPS, until "the 
additional information necessary for a more objective  assessment of risk" becomes available.  
7. The basic error in the US's and Canada's reasoning stems from their narrow (black or white 
fashion) interpretation of the term "insufficient" : by employing default presumptions, safety factors, 
and the weight of evidence approach, they elimin ate any "insufficiency" that comes from incomplete 
or contradictory evidence or from divergent or mi nority scientific views. Their approach views as 
predominantly, if not exclusively, quantitative th e concept of "insufficient" evidence. This is, 
however, contrary to the findings by the Appellate Body which has stated that:  
"Article 5.1 does not require that the ri sk assessment must necessarily embody only 
the view of a majority of the relevant scie ntific community.  In some cases, the very 
existence of divergent views presented by qualified scientists who have investigated 
the particular issue at hand may indicate a state of scientific uncertainty.  Sometimes 
the divergence may indicate a roughly equal balance of scientific opinion, which may itself be a form of scientific uncertainty.  In most cases, responsible and 
                                                     
 
3 As is already known from previous submissions the parties disagree on the nature of Article 5.7. This 
does in principle not affect  the above statement.  WT/DS320/R/Add.3 
Page C-26  
 
  representative governments tend to base their legislative and administrative measures 
on "mainstream" scientific opinion.  In other cases, equally responsible and 
representative governments may act in good faith on the basis of what, at a given time, may be a divergent opinion coming from qualified and respected sources.  By itself, this does not necessarily signal th e absence of a reasonable relationship 
between the SPS measure and the risk assessmen t, especially where the risk involved 
is life-threatening in character and is pe rceived to constitute a clear and imminent 
threat to public health and safety.  Dete rmination of the presence or absence of that 
relationship can only be done on a case-to-cas e basis, after account  is taken of all 
considerations rationally bearing upon the issu e of potential adverse health effects." 
(at para. 194 of its report in Hormones),   
and that:  
 
"Thirdly, a panel charged with determin ing, for instance, whether "sufficient 
scientific evidence" exists to warrant the maintenance by a Member of a particular 
SPS measure may, of course, and should, bear in mind that responsible, 
representative governments commonly act  from perspectives of prudence and 
precaution where risks of irreversible, e.g. life-terminating, damage to human health 
are concerned." (at para. 124   of its report in Hormones)   
8. It follows from the above that a measure would be  in conformity with Article 5.1 if acted in 
good faith and on the basis of what may be a divergent opinion coming from qualified and respected 
sources. As the Appellate Body has said, such a measure would not necessarily signal the absence of a 
reasonable relationship with the risk assessment, in the sense of Article 5.1. SPS. A fortiori,  therefore, 
a good faith measure that is based not on the mainstream but on divergent scientific opinions would also be in conformity with Article 5.7 SPS.   
Q3. When and how was each of the following documents made available to Canada and the 
United States?  Please answer independently for each of the documents mentioned below: 
 (i) 1999 Opinion;  (ii) 2000 Opinion;  (iii) 2002 Opinion;  (iv) each of the "17 studies".  
 9. The European Communities considers that it has,  in its replies to Question 3 and 16 and on 
many instances previously, demonstrated in ample detail not only that all three Opinions and the 
17 studies (except two of them) were publicly ava ilable, but also that there was a continuous 
discussion about them with the defending parti es on the bilateral and on the multilateral level 
throughout these years. Any suggestion that a Member  was left in the dark about the progress and the 
results of the new risk assessment or that it w as not in the possession of the 17 studies is not only 
baseless but borders on bad faith.  
10. The US further argues (at paras. 7-10 of its reply of 18 October 2006) that the EC had to 
request from the US for the 2000 and 2002 risk ass essments "a discussion or a conference on the 
scientific underpinnings of the EC's ban", as it did for the 1999 risk assessment. But there is no 
provision in any of the WTO Agreements relevant to  this dispute that would place such a burden on 
the EC.
4  Quite the opposite, the important point is  whether the US could have had access to the 
relevant evidence underpinning the EC risk assessment, if it had so wished. Indeed, about this there is 
                                                      
4 The fact that the scientists from both sides met in July 1999 and discussed the first risk assessment 
was because of the good will of the EC, not because of  any particular obligation on the EC under the WTO 
Agreements applicable in this case.   WT/DS320/R/Add.3 
 Page C-27 
 
 
  no doubt since the 1999, 2000 and 2002 risk assessm ents and all the underlying evidence on which 
they are based were published in peer-reviewed jour nals and where thus accessible to the US. This 
contrasts sharply with the persistent refusal by the US and Canada (and also of JECFA) to make 
available the underlying scientific studies upon which th ey claim to have based their risk assessments. 
11. The burden, therefore, was on the US to subm it any observations and comments, if it had so 
wished.  The US failed to react ev en after the draft and the finally adopted EC measure was formally 
notified to the WTO in acco rdance with the SPS Agreement.5  The December 2004 request by the US 
is a belated attempt to camouflage its lack of due  diligence and bad faith for the resolution of this 
dispute. 
Q4. Has the European Communities assessed in a systematic manner the existence and level 
of risks from failure to observe good veterinary practices with respect to the administration of 
oestradiol 17 β as a growth promoting hormone to cattle, in particular in the United States' and 
Canada's markets?   If so, plea se indicate where this assessment is to be found in the evidence 
provided to the Panel. 
 12. The EC disagrees with the US comment that "t he EC has not even seriously argued in the 
course of these proceedings that it has done so" (at para. 11 of its repl y of 18 October 2006).  
13. The US resorts again to its favourite tactic in  arguing that the EC presented only "unrealistic 
misuse scenarios" and that the ev idence is "purely speculative and unsupported", without engaging in 
any serious discussion about the evidence that is presented to the Panel. Thus, the US does not 
mention nor discuss the following: 
14. In Exhibit EC-73 the following undisputed instances of misuse or abuse are clearly 
mentioned: 
• At para. 15: "In 1986, the USDA's Food Safety and Inspection Service (FSIS) 
reported a widespread misuse of hormone implants in the USA." 
 
• At para. 16: "European Commission inspection mission to Canada in 1998 reported 
that the official laboratory of the Cana dian Food Inspection Agency (CFIA) in 
Saskatoon had recently detected increased r esidue levels of beta-trenbolone in neck 
muscles of veal calves, exceeding the "administrative action level" of 2 ppb in muscle. The reported levels of up to 12 µg/kg in muscle cannot be achieved by 
implanting in the ear only in accordance with GVP." (footnotes omitted)
6 
 
• At para. 17: "It should also be noted that  neither the US nor the Canadian meat 
inspection regulations provide for regu lar checks of the carcasses for misplaced 
implants at slaughter. Neither the US nor Canadian authorities offer any other 
adequate information which would allow the European Communi ty authorities to 
verify the magnitude and frequency of misplacement of implants." (footnotes 
omitted) 
 
                                                      
5 The US argues (at para. 9 of its reply of 8 October 2006) that instead of evidence "the EC response 
contained internet links for the 2000 Review and the 2002 Opinion".  The important point to note, however, is 
that the US has apparently never tried to access the internet links provided by the EC, because had it done so it 
would have had access to all the references and mate rials on which the EC based its risk assessments.  
6 The EC Mission reports resulting from inspections carried out in Canada and the US are provided in 
Exhibits EC-67 and 68.  WT/DS320/R/Add.3 
Page C-28  
 
  • At para. 22: " Implanting strategies co mmonly applied in today's beef production 
include not only re-implanting as a rule, r esulting in the presence of several implants 
per animal, but also a shortening of interv als between the last application of an 
implant and the slaughter of the animal. Th ere is no legally prescribed withdrawal 
time for any of the approved implants in the USA and Canada. Table 3 gives an 
overview of implanting strategies currently applied in beef production, recommended 
"re-implant windows", i.e. optimum re-implant times, and calculated "optimum 
payout periods", i.e. the time during which an implant releases growth promoter 
above an effective growth stimulating le vel. For maximum benefit, farmers and 
animal producers are advised to keep the le vel of implant growth promotant above the 
effective growth stimulating level unt il slaughtering." (footnotes omitted)  
 
• At para. 31: "In the USA and Canada vete rinary prescription is not compulsory for 
approved hormonal growth prom oters. Supervision by a veterinarian is not required 
either. To the contrary, in both countri es hormonal growth promoters are freely 
available in the over-the-counter sale as we ll as in self-service at agricultural retail 
stores and even by mail." (footnotes omitted)  
 
• At para. 32: "Hormonal growth promoters ar e not approved for use in veal calves in 
Canada and the USA. There is nevertheless clear evidence that different hormones are being used in veal calves in both count ries. A European Commission inspection 
mission to Canada in 1998, intended to eval uate the Canadian residue control system, 
reported that the CFIA had recently perform ed two special surveys to evaluate the 
possible misuse of trenbolone in veal calves. The surveys were carried out in 
compressed time periods using random sa mples and produced the following results: 
The first survey covered the period betw een June and July 1997 and produced 91 
positive out of 281 liver samples taken (32.7%). The second survey covered the 
period from April 1997 through January 1998 and produced 85 positive out of 210 
liver samples taken (40%)." (footnotes omitted) 
 
• At para. 33: "The Canadian  Food and Drug Act and Regula tions do not define clearly 
extra-label or off-label use. The Canadian  authorities accept, however, that a farmer 
may use authorized hormone implants in veal calves on condition that residues in liver and muscle comply with the so-calle d "administrative action levels" established 
for bovine tissues.  In other words, the Ca nadian authorities tolerate the off-label use 
of hormone implants by farmers for gr owth promotion purposes and do not enforce 
the label instructions." (footnotes omitted)  
 
• At para. 34: "In the case of the USA, two European Commission inspection missions 
in 1989 and 1990 had already revealed that hormone implants are also used in veal calves. The European Commission inspector s themselves found implants in the ears 
of two out of ten veal calves they ex amined; however, no subsequent action was 
taken by the national authorities. Furthe rmore in a letter from the Center for 
Veterinary Medicine of the Food and Dr ug Administration (FDA) to the American 
Veal Association of 29 December 1989 the FDA expresses its concern about the misuse of hormone implants in formula-fed veal." (footnotes omitted)  
 
• At para. 35: "The most recent results of a study, which was commissioned by the 
European Commission as part of its complementary toxicological risk assessment of hormonal growth promoters and which w as intended to determine the amount of 
hormone residues in US meat and offal, confirms the off-label use of hormonal growth promoters in the USA. First, although no hormonal growth promoter is  WT/DS320/R/Add.3 
 Page C-29 
 
 
  approved for veal calves, residues of trenbolone acetate and zeranol were found both 
in calf liver from the US domestic market and in calf samples from US meat consignments sampled at the border inspec tion points of the EU. Second, although 
melengestrol acetate (MGA) is only approved fo r use in heifers, a substantial number 
of the meat samples that tested positiv e for MGA residues were subsequently 
identified by DNA gender identification to stem from male animals." (footnotes  
omitted)
7   
 
• At para. 39: "A further violation of GVP re lated to off-label use of hormonal growth 
promoters was reported from Canada. The re gistration requirements for the use of 
melengestrol acetate (MGA), a growth promoter  incorporated in the feed for heifers, 
stipulate that: " MGA must not be fed to heifers treated with other hormonal drugs. "  
Nevertheless, during the vis it of a European Commission inspection team in 1998 to a 
Canadian feedlot, the feedlot operator decl ared that until recently his heifers were 
treated simultaneously with Synovex®, an approved implant containing testosterone 
and estradiol, and with MGA." (footnotes omitted)  
 
• At para. 57: "Evidence on the existence of a black market for veterinary drugs and 
growth promoters in the USA and in Canada  can be inferred from publications of the 
FDA's Center for Veterinary Medicine. Th ese publications reveal that over the past 
years there has been a large-scale smuggling of  illegal animal drugs, e.g. clenbuterol, 
from Canada into the USA." (footnotes omitted)    
 
• At paras. 65 and 68: "In the USA a threshold level, utilisable for residue control 
programmes, has been established for onl y one of these six hormones, that is a 
tolerance level for melengestrol acetate. The other so-called " safe concentrations for 
total residues  in edible tissues " established for trenbolone acetate and zeranol and the 
so-called " increments " established for the three endogenous hormones are not suitable 
for a residue evaluation by routinely performe d examinations." and "It can, therefore, 
be concluded that in the USA only the to lerance limit for melengestrol acetate is 
appropriate to be used in a residue c ontrol programme."  (footnotes omitted)  
 
• At paras. 70, 71 and 73: "70. Despite clea r provisions in the Food and Drug Act and 
Regulations on the general zero tolerance w ith certain well-defined exemptions, the 
Canadian authorities have adopted so-called "administrative action levels" for certain 
substances, including trenbolone, zeranol an d melengestrol acetate, not listed in the 
Food and Drug Regulations. It has to be stressed that the application of the "administrative action levels" is not consistent with the Canadian Food and Drug Act. 
Although the "administrative action levels" ar e identical with the MRLs established 
by Codex it can be concluded that the Ca nadian authorities have not adopted legally 
enforceable threshold levels for the three approved synthetic horm ones.", and that:  
"71. It has to be noted that these "administr ative action levels" are applied also to veal 
calves, although the hormones in question are not authorised for this category of bovine animals.", and that: "73. It follo ws that the USA and Canada, with the 
exception for melengestrol acetat e in the USA, either lack enforceable residue limits 
or cannot or do not enforce the ones they have." (footnotes omitted)  
 
• At para. 81: "These findings have now been confirmed by the provisional results of 
the 1999 specific European Commission study on residue control of meat and liver 
imported from the USA under the Hormone Free Cattle Programme (HFC 
                                                     
 
7 The recent study in question is Exhibit EC-53. WT/DS320/R/Add.3 
Page C-30  
 
  Programme). The available preliminary results  of this study, based on US meat and 
liver samples collected at the border inspection posts of the EU, show that : " In total 
it is concluded from this study that the HFC Programme is not effectively controlled 
by the responsible US authorities. From th e residue findings the misuse of the US 
approved xenobiotic ‘hormones' tre nbolone, zeranol and MGA in this HFC 
Programme is shown in at le ast 12% of the samples. No definitive conclusions can be 
drawn from this study about the misuse in  the HFC Programme of the US approved 
hormones (17
β-)estradiol, testosterone or progesterone. However, for estradiol the 
misuse is indicated for at least one sample. No evidence has been found so far that in 
the HFC Programme other ‘hormones' are used than those approved in the USA. 
HFC violative products were exported to th e European Union by 3 out of 4 different 
USA meat sellers sampled in this study. " "(footnotes omitted)  
 
• At para. 90: "It must be underlined that there are no specific regulations in the USDA 
Code of Federal Regulations on disposal procedures for implantation sites, e.g. for 
implants in the ears." (footnotes omitted)  
 15. Further concrete evidence that misuses or a buses are not exceptional occurrences in the US 
and Canada is provided at the following Exhibits: 
• Exhibit EC-69, where in 2004 Guidance for Industry, the US FDA stated that "use of 
unapproved hormone implants in non-ruminating veal calves has occurred." Equally, 
Exhibit EC-70 for Canada. 
 
• Exhibits EC-96 and 103, which although c oncern the unauthorised hormone DES in 
1999-2000, do show that a black market also  exists in the US for these hormones as 
well as for other hormonal substances. Mo reover, Exhibit EC-69 contains several 
examples of misuse and black market activities in the US. 
 
• Exhibit EC-102, which states, inter alia, that the US Food Safety and Inspection 
Services (FSIS) "is concerned about the widespread, illegal use of drug implants in young calves that was discovered in 2004". The same exhibit also states that "FSIS learned that the use of growth promoting implants was a widespread practice within 
the veal industry. However, the Food and Drug Administration has not approved growth promotion implants for use in food animals presented for slaughter as veal 
and considers their use to be a violation of the Federal Food, Drug, and Cosmetic 
Act". This example demonstrates that, cont rary to what the US has been arguing 
before the Panel, abuse and/or misuse is  a "widespread practice in the US veal 
industry".  
 
16. It is, therefore, imperative that the US, instead  of avoiding the discussion by arguing that the 
EC has based its evidence on unrealistic or hypothe tical examples, to engage for once in a real 
discussion on the substance of the concrete evidence provided by the EC.  
17. The US comment (at para. 13 of its reply of 18 October 2006) and Exhibit US-28 confirm the 
EC findings. Exhibit US- 28 confirms that the aut hor of the NebGuidance (University of Nebraska) on 
re-implanting was himself confused  and perplexed by the possible interpretation of the NebGuidance, 
as so many less-educated farmers would undoubtedly have been for so many years that they have 
been following it. He nevertheless ag reed to propose to make revisions to it, but he still insisted that 
the corrections "should not be interpreted as a change in our recommendations."    WT/DS320/R/Add.3 
 Page C-31 
 
 
  18. Furthermore, it is important to note that the Ne bGuidance is not the only example of concrete 
evidence that recommends multiple re-implanting. Exhibit EC-17 explains on page 54 (with further 
citation of at least six scientific publications) that "the manufacturers' instructions provided with the 
preparations, for instance, do not contain any explic it warning against multiple application. Even in 
the scientific literature, repeated or  multiple treatment of different combined preparations is often 
recommended to achieve optimal results (4-9)".  The US has not replied nor has it ever contested the 
evidence contained in these scientific publications. 
19. The same applies to Canada's comments. Exhi bit EC-17 states on page 54 (with concrete 
reference to scientific literature) that: "Misuse of trenbolone acetate in calves was reported in Canada 
(10). According to that study, in 1996/97, 14% of 353 tested veal liver samples contained more than 
2 ng trenbolone-17a/g, and 5% even more than 10 ng/g".  
20. The US argues (at paras. 12 and 15 of its reply of 18 October 2006) that the EC has failed to 
provide any evidence that violative residue levels w ould result except in the most extreme overdosing. 
This is not correct. The 1999 SCVPH opinion contai ns Table 2 on page 35, which shows as regards 
oestradiol-17 β that the level of residues concentration in  lawfully treated animals according to GVP 
exceeds by several times the level of con centrations observed in untreated animals.8 Moreover, the 
study by R. Stephany 2001 (AMPIS 109, 357-346)  (see Exhibit EC-65, at page S357) found that meat 
from the regular US market contains on avera ge 7.5 times more estrogens than meat from 
untreated animals .  If the more recent data concerning the endogenous production by pre-pubertal 
children are taken into account, such treatment acc ording to GVP already leads to the ADI being 
exceeded. It goes without saying that multiple im planting, which necessarily leads to higher 
concentration of residues, would inevitably ex ceed even further the recommended ADIs by JECFA.9  
21. Contrary to the US statements (at para. 14-15 ), both Dr. Boisseau and Dr. De Brabander (to 
questions 45, 46, 48) have confirmed that if GVP  is not respected, the ADIs and MRLs become 
useless and risks to human health are likely to occur.10 Unlike the US argument (and the reply of Dr. 
Boobis to question 48), the EC has performed a qualitative assessment and a quantitative assessment 
(to the extent possible) of exposure to residues in  meat from animals treated not in accordance with 
GVP, even if a qualitative assessment alone would have  been sufficient (see section 3.3, pages 30-32 
of the 1999 SCVPH, and Exhibit EC-73).   
Q5. In its comments on comments of the United  States and Canada on experts replies to the 
Panel questions (in particular Question 13) , the European Communities indicates that 
oestradiol 17 β might be a "weak genotoxin" (para. 44).  At what doses is genotoxicity 
observable in vivo ?  How are these doses comparable to th ose found in meat from cattle treated 
with growth promoting hormones?  How would this  assertion affect the identification of adverse 
effects and the evaluation of potential occurren ce of these effects from consumption of meat 
from cattle treated with oestradiol 17 β for growth promotion purposes? 
 22. The EC contests the US argument (at para. 16) that the EC has presented "just one study" 
which addresses genotoxicity of estradiol-17 β in vivo . The 1999 SCVPH contains already reference to 
one such study (at page 41, section 4.1.7). Th e EC provided four more studies which discuss 
genotoxicity in vivo  on different animal tissues: see Exhib its EC-48, 118, 121 and 125. As regards 
Exhibit EC-125, the EC notes that the US has made  incorrect assumptions (at paras. 17-18) that are 
                                                     
 
8 The 1999 SCVPH opinion contains similar evidence for the other natural hormones.   
9 Another error of the US is to compare the level of residues resulting from treatment according to GVP 
with the level of circulating oestradiol-17 β in pregnant cows. This is wrong because in the EC pregnant cows 
are not slaughtered for human consumption. 
10 Moreover, despite the US argument to the contrary , Dr. Boisseau stated (reply to question 50) that 
farmers have "a temptation to use these hormones in a way different from the approved ones." WT/DS320/R/Add.3 
Page C-32  
 
  inconsistent with the data provided by the EC, ba sed on a substantial literatu re published over the last 
3 decades regarding the use of Silastic capsules to administer hormones to experimental animals and 
women. The implant in Silastic capsules for wome n was marketed as being effective for up to 5 years 
due to slow release of the steroid when it is pack ed into a capsule. As the EC pointed out, the daily 
release rate from a Silastic capsule used in the Cavalieri et al.  study containing a total of 5 mg 
oestradiol, that is intended for long-term studies a nd steady-state release over a long period of time, is 
about 1 microgram/kg/day. Clearly, the US assumption that the entire amount of oesttradiol-17 β in the 
capsule (5 mg) is released each day cannot be corr ect. Another issue is that the US response assigned 
a weight to rats of 250 mg, which is the weight of  a very young rat, and would not be the weight of a 
6-7 months old rat by the end of a study, in which the oestradiol-17 β was administered to adult rats 
for 140 days, as was done in the Cavalieri et al.  study. In this regard, the EC estimate of a weight of 
330 g is very conservative. Since the dose per day is expressed relative to body weight, by assuming 
an unrealistically low body weight, th e US is attempting to make it appear that the daily administered 
dose is higher than it really is. When this is ta ken together with the invalid US assumption that a 
Silastic capsule releases the entire amount loaded  into it each day (which would require it being 
refilled each day), it is clear that the US calculations of the oestradiol-17 β doses that result in 
mutagenesis are profoundly flawed. As the EC has e xplained with its reply of 18 October 2006, the 
mutagenic effect in Exhibit EC-125 was brought  about at a dose which is potentially within
 the 1000-
fold safety margin established from the lowest observed adverse effect level (LOAEL) on which JECFA's ADI is based.
11 Therefore, the dose at which in vivo  genotoxicity was observed was not 
"astronomically higher", nor "exponentially greater ", nor "massive", as the US (and Canada) has 
wrongly argued. Quite the opposite, it is not higher  than the dose normally used in experiments for 
the approval of chemical substances internationally. 
Panel Questions to the United States and Canada : 
 
Q18. Would you consider that, for the purpose of the DSU, Directive 2003/74/EC should be 
viewed as a new measure or as the continua tion of the previous measure found to be 
inconsistent with the WTO Agreemen t, since it still imposes a ban? 
 
23. There can be no doubt that following the DS B's rulings and recommendations a measure has 
been taken by the EC to comply with.  For the purposes of the DSU, therefore, there exists a new 
measure.  
24. First, Directive 2003/74/EC unquestionably is a new measure in that it came out of an entirely 
new legislative process, involving both the Europe an Parliament and the Council of the European 
Union as legislature. Second, the measure is by no m eans identical to the previous measure. It for the 
first time enacts a provisional ban with re gard to all substances but oestradiol-17 β, further restricts use 
for therapeutic and zootechnical purposes and abo lishes all other exemptions. Third, and most 
importantly, the new Directive is obviously based on a risk assessment taking into account the most 
recent scientific evidence available.  
25. Whether this new measure successfully implemen ts the rulings and recommendations of the 
DSB is a different question. Both Canada and the United States seem to argue that it is the only 
question that matters for the purposes of assessi ng whether they are entitled to continue the 
                                                      
11 The US attempts (at footnote 13 of its reply of 18 October 2006) to diminish the importance of the 
in vivo  studies performed with catechol metabolites and refers to an alleged statement of Dr. Metzler, which he 
has not made. The important point about catechol metabolites in treated meat is to note what Dr. Guttenplan has 
said (with his reply to question 17), namely that the sm all amount of catechol metabolite s detected in meat from 
treated animals is explained by the fact that "cattle do not efficiently metabolize estradiol to catechols", and that "the lack of catechols in meat does not imply that me at from estrogen-treated cattle is without risk for 
genotoxicity".   WT/DS320/R/Add.3 
 Page C-33 
 
 
  suspension of concessions. In the European Communities' view it is  not.  In the presence of an 
obviously new measure that has been adopted in a tr ansparent and good faith effort to implement the 
DSB rulings and recommendations, Article 23 DSU tri ggers an obligation on the original complaining 
parties to assess that new measure, to bring a 21.5 pr oceeding if they take the view that the measure 
does not achieve compliance (and) or (to suspend)  to cease the suspension of concessions. The latter 
obligation results from the fact that there is no multilateral determination that the new measure 
violates or continues to violate WTO obligations.  It follows that the burden is on the US and Canada in the first place to demonstrate that the EC has not  solved the nullification or impairment through the 
new measure once notified to the WTO. Indeed, ha ving followed an open and transparent procedure 
for the elaboration and adoption of the new meas ure, having notified it in accordance with the 
provisions of the WTO/SPS Agreements, and having  given the defending members the opportunity to 
submit their comments all along, it is reasonable to ar gue that the burden is on them to establish that 
the new EC measure does not solve the nullification or impairment. Any other interpretation would be 
unreasonable and would go against the object, purpose and structure of the WTO Agreements because it would enable recalcitrant WTO members to unlawfully affect international trade almost 
indefinitely. 
Panel Questions to the United States
: 
 
Q19. Does the United States argue a violation of Article 5.2 and of Article 5.6 SPS?  In other 
words, do you expect the Panel to issue fi ndings regarding the compliance of Directive 
2003/74/EC with those provisions? What is the purpose of the reference to Article 2.2 SPS in 
para. 27 of the US rebuttal submission? 
 
26. The European Communities takes note of the Un ited States' reply that the Panel would be 
required to look only at Articles 3.3, 5.1 (incl uding an examination of Article 5.2) and 5.7. 
27. Moreover, as the EC has explained above with its comments on the US reply to question 2, 
the US is wrong to argue that the EC has not b ased its measure on a risk assessment within the 
meaning of Article 5.1 and 5.2 SPS. The EC di d conduct such a risk assessment not only for 
oestradiol-17 β but also for the other five hormones. But fo r the reasons explained several times to the 
Panel, it could not complete the risk assessment for the five hormones because of  the insufficiency of 
the relevant information and the important gaps in our scientific knowledge. That is why it had to base 
its measure on Article 5.7 SPS. It should be noted that Article 5.1 SPS provides that the measure is 
based on an assessment "as appropriate to the circ umstances", and Article 5.7 states that a more 
"objective" assessment of risk would be performed on ce the missing pertinent information is obtained.  
Q20. Could the United States clarify whether its arguments regarding a violation of 
Article 3.3 SPS apply only in relation to the definitive ban on oestradiol 17 β or whether they 
apply also in relation to the provisional ban imposed on the other five hormones? 
 28. The European Communities would like to reca ll what it has understood to be the United 
States representative's statement at the second subs tantive hearing.  Mme Orozco had asked which 
Codex Alimentarius standards the United States was relying on for the purposes of its Article 3.3 
claim.  In reply to this question the United Stat es representative referred only to the standards adopted 
for testosterone, progesterone, zeranol and trenbolone acetate. No mention was made of the standard 
for oestradiol-17 β.  
29. Moreover, the US states (at paras. 27-28) a number of times that it has demonstrated that the 
EC has failed to provide a scientific justification. The EC does not agree that the US has managed to 
discharge its burden of proof.  WT/DS320/R/Add.3 
Page C-34  
 
  EC Questions to United States and Canada
: 
 Q1. Please explain, if possible in detail, what  kind of scientific evidence on exposure-
assessment from residues in meat treated with the six hormones for animal growth promotion 
was used by the United States and Canada when  these substances were authorised? Was this 
exposure assessment a quantitative one?  Plea se provide concrete reference to studies used in 
your exposure assessment and, if possible, to those of JECFA for the six hormones in question 
(in case you know the references).   
30. The US states (at para. 3 of its 18 October 2006 reply) that the US FDA "required the 
sponsors to conduct extensive residue studies". These  residues studies have never been published and 
the EC has never been given a copy fro review, whereas the US has had access to the more recent 
(same or similar) studies conducted by the EC. 
31. The US reply (at para. 5) confirms that the US FDA did not establish an ADI for the three 
natural hormones. Most importantly, it also conf irms that no extensive toxicological testing in 
experimental animals has been performed. In other words, it confirms that the US has not performed 
the full battery of toxicological testing in order to decide whether these hormones are carcinogenic and/or genotoxic. It also confirms that the "perm itted increased daily exposures" set by the US FDA  
are based on the assumption –  and no more than an assumption – that "the amounts of these hormones present in edible tissues of treated cattle were found to be very small relative to the 
endogenous production in humans". In other words, the US admits that it has not carried out the kind 
of quantitative exposure assessment of residues in  hormone-treated meat, which it now accuses the 
EC for not having performed. The reality, therefore, is that the US " permitted increased daily 
exposures " are based on simplistic and scientifically uns ound extrapolations an d assumptions, not on 
sound scientific experiments.  
32. The US refers (at para. 6 of its reply of  18 October 2006) to the "exposure assessment 
conducted by JECFA", thus again admitting implic itly that it has itself not conducted such an 
exposure assessment from residues in hormone-treat ed meat. However, as the EC has explained 
several times to the Panel, JECFA has not conduc ted such an exposure ass essment either. What 
JECFA has done so far was to review the old r esidues depletion studies from the 1970s provided to it 
confidentially by the US pharmaceutical industry (s ee e.g. Exhibits CAN-17 for the three natural 
hormones and the similar studies for the other three synthetic hormones) and established the ADI on 
the basis of assumptions, extrapolations and safety fa ctors. But the EC has also performed and made 
available to the public residues depletion studies fo r all these hormones similar to those used by 
JECFA. Moreover, the EC has in addition made  an exposure assessment, which Dr. Guttenplan 
explained in his reply to questi ons 52 and 55, as follows: "calcula tions are presented (EC rebuttal, 
para. 122) that suggest that even with low percenta ges of bioavailability of estrogen, the levels in 
meat could result in bioavailable estrogen exceeding the daily production rate of oestradiol in pre-
pubertal children". The US reply shows that it has not done so. 
33. Finally, the US and Canada's replies cannot  hide behind the argument that JECFA has 
performed a quantitative exposure assessment, because th e data claimed to be used by JECFA are the 
same data of the 1970s provided by the pharmaceutic al industry during the authorisation procedure in 
the US.  
Q2. Please  indicate, if possible in detail,  wh ether your risk assessments, and if you know 
those of JECFA, of the six hormones in questio n for animal growth promotion have attempted 
to calculate the risk to humans from the addi tional exposure resulting from the residues in 
hormone-treated meat when used according to GVP and when GVP is not respected. Was it a quantitative exposure assessment? If so, please provi de the precise reference to the data. (Please 
note that we are not referring here to residue -depletion studies contained in CAN Exhibit-17,  WT/DS320/R/Add.3 
 Page C-35 
 
 
  since the EC has also conducted such residues depletion studies for its 1999-2002 risk 
assessments). 
 
34. The US reply (at paras. 7-12) confirms  once again, as explained  above, that the US has not 
attempted to calculate itself the risk to humans  from the additional exposure to residues from 
hormone-treated meat. It refers to the JECF A monographs, which do not contain an exposure 
assessment, which is not different from that performed  by the EC, with the notable difference that the 
EC's assessment is based on more recent, publicly available and peer-reviewed scientific data.  
35. The same comment applies to the reply of Canada. Canada forgets that exposure to 
background (endogenous) levels alone  of the natural hormones has al ready found to cause cancer in 
humans and inappropriately assumes, like JECFA, th at the additional exposure from the residues in 
meat would not increase the risk. Canada, like the US, forgets that the EC has demonstrated (see, e.g., 
the study by R. Stephany 2001, AMPIS 109, 357-346, Exhibit EC-65) that meat from the regular US market contains on average 7.5 times more estrogens  than meat from untreated animals and that, even 
without misuse, the ADIs established by JECFA w ill be exceeded if the most recent values of 
endogenous production by pre-pubertal children is taken into account. 
Q3. The EC understands that some of the ex perts (Drs. Guttenplan, Sippel and Cogliano) 
have stated that it is not possible to determine with accuracy the dose-re sponse curve at the very 
low levels of exposure from these hormones in general and when used for animal growth 
promotion. Do you agree with these statements? If not, could you please provide the precise 
references to scientific studies where this has been done? What would be the implications of this 
impossibility for the need to perform a quantitat ive or qualitative exposu re assessment for these 
hormones when used for animal growth promotion? 
 
36. The EC notes first that the US does not correc tly represent (at para. 14 of its reply) the 
statement by Dr. Guttenplan at the meeting of the Panel with the experts. In that meeting, Dr. 
Guttenplan stated (as did three other scientists) that, in  his view, there will be a risk (which will be not 
zero but a small one) caused from the residues in me at from animals treated with these hormones for 
growth promotion. The same applies to the comme nt by Canada (at para. 9 of its reply).  
37. Furthermore, the US gives credit to the statemen t by Dr. Boobis that the "carcinogenic effects 
appear to be a consequence of its endocrine ac tivity", when the US admits that no long-term 
carcinogenicity studies have been performed when it approved these hormones for growth promotion.  
38. Furthermore, Canada argues (at para. 10 of its re ply) that the statements by Dr. Sippel and Dr. 
Cogliano "must yield to the expert advice of those who are qualified to eval uate actual carcinogenic 
potential at low doses". However, Canada forgets th at both Dr. Boisseau and Dr. Boobis are the same 
persons who have participated in the elaborati on of the JECFA report and, moreover, Dr. Boisseau 
admitted that he has never carried any toxicol ogical experiment with these hormones himself.  
Q4. If you were to agree that scientists cannot define the dose-response curve as explained in 
the previous question, would this state of sci entific knowledge be defined as "scientific 
uncertainty" in this area?  If not, please explain. 
 
39. The US reply (at paras. 15-16) is another distr action by referring to "theoretical risk", when 
the scientists agreed that the do se-response curve at low dose in th e case of these hormones cannot be 
defined. Moreover, given that in the calculations of the US and JECFA the existence of a threshold 
below which adverse effect is alleged not to occu r is a basic assumption, the EC question does not 
pertain to a theoretical risk but to a very real and undisputed one. The US and Canada (like JECFA) 
have not managed to explain how is it possible to establish a no hormonal effect level when the WT/DS320/R/Add.3 
Page C-36  
 
  scientists ignore the real dose-response curve of th ese substances when used for growth promotion 
purposes.  
40. In addition, Canada places (at para. 12) on the same side Drs. Boobis, Boisseau and 
Guttenplan, when the latter clearly st ated in the hearing that the risk  from residues in hormone-treated 
meat is small (but not zero) and Dr. Boissaeu ad mitted that he has no specific knowledge as he has 
never carried any experiment with these hormones. 
Q5. Could you please explain what is your positi on on the existence or non existence of an 
international standard for MGA for the purposes of Articles 2, 3 and 5 of the SPS Agreement in 
these disputes?  
 41. Canada argues that "other agencies and health  authorities have conducted similar assessments 
and have come to the same conclusion", but fails  to mention which are these other agencies and 
authorities nor does it provide copy of their assessments. If Canada im plies that these other authorities 
are the agencies of the US and Canada, the EC would be very happy to receive copy of their 
assessments and the underlying studies on which they  are based for review. Indeed, the EC urges 
Canada to submit such assessments, if they  really exist, to the Panel for review. 
EC Questions to the United States
: 
 
Q1. The 2002 US Report on Carcinogenesis (E xhibit EC-101) states inter alia that: 
"veterinary use of steroidal estrogens (to pr omote growth and treat illnesses) can increase 
estrogens in tissues of food producing animals to  above their normal levels" (p.8). How do you 
reconcile this with your proposition in para. 51 of your First Written Submission?  
42. The EC notes that the US is selectively quoting fi gures for different (male or female) animals 
and at different physiological state (pregnant or not) is order to sustain its claim that the residues are 
within the range of naturally observed levels. Ho wever, the US does not di scuss the other evidence 
presented by the EC showing that meat from the regular US market
 contains on average 7.5 times 
more estrogens than meat from untreated animals (see  Exhibit EC-65, at page 357, and the tables 2, 5 
and 7 of the 1999 SCVPH opinion). Furthermore, th e US keeps comparing the residues from treated 
animals with the levels of residues in pregnant ca ttle, when the EC has explained to the Panel that 
such pregnant cattle are practically not sl aughtered for human consumption in the EC.12  Pregnant 
cows, therefore, are not the appropriate comparator.  
Q2. What was the reason to conclude for the first time in the 2002 US Report on 
Carcinogenesis that estrogens (including oestradiol-17 β) are carcinogenic not only by receptor-
mediated effects but that in addition there are poss ibly by direct and indirect genotoxic mode of 
action? Was it because of new developments in scientific research that became available after 
1999? 
 43. The EC considers that the US reply (at para. 22 and footnote 14) confirms that oestradiol-17 β 
has moved from "reasonably anticipated to be human  carcinogen" in 1985 to be listed for the first 
time in 2002 as "known to be a human carcinogen".  Moreover, the 2002 US RoC links for the first 
                                                     
 
12 In any case, the US argument is also  factually not entirely correct because Table 2  of the 1999 
SCVPH opinion (at page 35) provides data showing that the concentration of E2 (oestradiol-17 β) residues in 
muscle of treated heifers (30 days) according to GVP are slightly higher (33.2 ng/kg) than the values for 
untreated pregnant heifers (32.7 ng/kg). The same applies to fat tissue, 86.7 ng/kg in treated heifers compared 
to76.5 ng/kg in untreated pregnant heifers, whilst the values for kidney are not substantially different. Moreover, the EC has shown that misuse or abuse of these hormon es leads inevitably to much higher concentration of 
residues in treated meat.  WT/DS320/R/Add.3 
 Page C-37 
 
 
  time the risk of cancer to residues in meat from animals treated with this hormone for growth 
promotion. The US claims (at paras. 23-24) that th e 2002 US RoC is not evidence of a risk from meat 
from cattle treated with estradiol for growth prom otion. However, the US cannot make this claim 
because it has not performed the necessary experiments after  the 2002 RoC has declared oestradiol-
17β a proven human carcinogen by direct genotoxic action. All the assessment which the US claims to 
have performed for these hormones for growth pr omotion date from the 1970s. Conversely, as the 
replies of Dr. Cogliano and Dr. Guttenplan to Panel question 26 have established, the data used by the 
EC to establish such an association are "at least consistent with a possible effect of hormones on 
breast and prostate cancer". Therefore, the US has fa iled to provide better evid ence to the one used by 
the EC. 
Q3. The 2002 US Report on Carcinogenesis stat es inter alia that: "The RoC does not present 
quantitative assessments of the risks of cancer asso ciated with these substances. Thus listing of 
substances in the RoC only indicates a potent ial hazard and does not establish the exposure 
conditions that would pose cancer risks to individuals in their daily lives. Such formal risk 
assessments are the responsibility of the appropriat e federal, state, and local health regulatory 
and research agencies." If so, have the compet ent US authorities made the quantitative 
assessment of the risks of cancer posed by the residues of six hormones in meat from animal 
treated for growth promotion?  If not, when are you going to do it? 
 
44. The EC notes that the US has carefully avoided (a t para. 25) to reply to this crucial question. 
Hopefully the Panel will be able  to draw, to the extent possi ble, the necessary inferences.  
45. The US statement (at para. 26) inappropriately  downplays the importance of evidence coming 
from epidemiological studies. In any case, the 2002 US RoC is not based only on epidemiological 
evidence, but also on the reported results from toxicological and carcinogenicity studies, as is the paper by Professors Liehr and Yager mentioned therein to demonstrate direct genotoxicity. 
46. The US for the first time admits (at para. 27) what the EC has always been arguing, namely 
that: 
"assessment of the risks to human health asso ciated with the use of sex steroids in 
food-producing animals presents unique challe nges due to the fact that exposure to 
the compound occurs against a background level of endogenous production in all 
segments of the population". 
47. As the EC mentioned above with its comments on the US reply to question 1 from the EC, the 
US has not conducted extensive toxicological tes ting, as should have done, and based its "permitted 
increased exposure" on pure assumptions and simplistic  extrapolations. Indeed, the US assumed that 
residues in hormone-treated meat would add very little to the endogenous production by humans. But 
the US assumption ignores the fact that exposure to  background (endogenous) levels of oestrogens 
already causes cancer in humans and any further a ddition to such exposure from exogenous sources is 
going inevitable to increase the likelihood of causi ng cancer. This is all the more so since the 
scientists do not know what is the dose-response curve from low exposure to these hormones in order 
to establish a safe threshold. 
Q4. The 2002 US Report on Carcinogenesis states inter alia that: "Estimating the extent to 
which listing a substance in the RoC protects public health is perhaps the most difficult task in 
preparing the RoC. The carcinogenic risk (i.e., the probability of developing cancer) depends on 
many things, including the intensity, route, a nd duration of exposure to a carcinogen. People 
may respond differently to similar exposures, depe nding on their age, sex, nutritional status, 
overall health, genetics, and many other factors. Only in a few instances can risk for cancer be 
estimated with complete confidence, and these estimations require studies of long-term human WT/DS320/R/Add.3 
Page C-38  
 
  exposures and cancer incidence in restricted envi ronments, which rarely are available." Despite 
this recognition of the difficulties, could you pl ease explain if you have nevertheless performed 
the long-term human exposures to the residues of  these hormones in treated-meat in order to 
quantify if they pose a risk to human health? Do you know if JECFA has performed such a specific quantitative dose-response assessment? 
 
48. The EC argues that the above-mentioned quot ation from the 2002 US RoC confirms its 
arguments that a quantitative exposure assessment is  not really possible and the US (and Canadian) 
criticism in this regard is unfounded. 
Q5. In relation to para. 8 of the US statement of 3 October please explain if you have now 
made a determination? If not, what does it mean "being in the process of reviewing? What are 
you doing exactly? Since the EC's risk assessment  dates of 1999 (and reviewed and confirmed in 
2000 and 2002), how long is your review process goi ng to take? Is there any information that the 
US is now missing? Is there any mechanism by wh ich the US will complete its review within a 
reasonable period of time now?  
 
49. The EC considers that the US reply confirms th at it has not yet completed its review and, 
apparently, is not likely to complete it any time soon. 
Q6. The US stated that the risk assessments performed by JECFA must be presumed to be 
in compliance with Article 5.1. of the SPS Agre ement. But the risk assessments performed by 
JECFA for these hormones for animal growth promoters do not contain the kind of quantitative 
or qualitative exposure assessment that Canada and the US criticise the EC for not having done. 
Nevertheless, the US and Canada appear to as sume that JECFA's assessments are consistent 
with Article 5.1. SPS.  Please explain why unde r these circumstances would the EC's risk 
assessment be inconsistent with Article 5.1. of the SPS Agreement. 
 
 
50. The EC notes that the US provides a general reply without any arguments nor specific 
reference to the documents showing that JECFA did the kind of exposure assessment which the US 
accuses now the EC for not having performed. As the EC has explained several times (see, e.g., EC Oral statement of 3 October 2006, at paras. 4-5), the kind of quantitative exposure assessment, 
claimed to have been done by the de fending members, cannot be performed. 
EC Questions to Canada
: 
 
Q1. In relation to your example for the oestroge n level in pregnant women (para. 53 of your 
Oral Statement) could you please comment on Exhibit EC-56 where there is evidence that in utero  exposure to oestradiol has given rise to a number of abnormalities and suspected of an 
increased rate of cancer? Assuming that this finding is related to the low-dose response 
uncertainty, do you have any evidence that the 2ng added to endogenous oestrogens production 
are not likely to have any such effect? 
 
51. The EC notes that Canada's reply is typical  of the unscientific assumptions and simplistic 
arguments it has been making all along in this dispute. The EC does not pretend to have found the ultimate truth. The study in Exhibit EC-56 builds on  existing scientific literature which postulates that 
"the risk of breast cancer is influenced by hormonal exposure in utero ". This proposition is not new 
(see the first five references to scientific literatu re provided in Exhibit EC-56).  The EC study 
provides further support to existing scientific evidence.  
52. The simplistic argument of Canada is to state that "as a result of the homeostatic control 
mechanism, endogenous production is  adjusted to take into account exogenous exposure. Thus, the 
low dose exogenous oestradiol to the mother does not translate into low dose to the foetus." The point  WT/DS320/R/Add.3 
 Page C-39 
 
 
  is that Canada has no scientific basis to make the simplistic assumption that the adjustment will take 
place or that it will take place in all cases. Equally, Canada has no scientific basis to argue that a 2ng 
added to endogenous oestrogens production are not lik ely to have any adverse effect. All the EC is 
saying on this point is that we do not know, and Ca nada knows no better. But what we do know is that 
the experiment in question provides further supp ort to existing evidence that hormonal exposure 
in utero  influences the risk of breast cancer.  Canada obviously does not believe that exposure to low 
level of residues in treated meat is likely to cause cancer. But this belief is  based on mere intuition, 
not scientific proof, because the experts of the Pa nel have confirmed that the dose-response curve 
from low exposure cannot be est ablished for these substances.  
Q2. As regards the reference to Carbadox (see para. 67 of Canada's oral statement of 
3 October): Could you please explain briefly what happened and what were the reasons for 
which you have changed your risk assessment for Carbadox? Was it simply on the ground that Carbadox was found to be genotoxic or was it because you have carried out before a 
quantitative or qualitative exposure assessment fo r the residues in pork meat treated with 
Carbadox? 
 
53. The reply of Canada avoids addressing the cruc ial point, namely why did it need almost ten 
years to admit what the EC has been arguing since 1996, namely that the metabolites of Carbadox are 
carcinogenic and genotoxic. What Canada calls now "n ew information" was available at the time of 
the first hormones panel in 1996, where Canada was still authorising Carbadox and was strongly 
arguing that the EC has been acting inconsistently. If  Canada is willing to keep making the same kind 
of mistake for these hormones as it did for Carbadox at the time for the sake of some small economic 
benefit, the EC is not prepared to sacrif ice its high level of health protection. 
 WT/DS320/R/Add.3 
Page C-40  
 
  ANNEX C–3 
 
REPLIES OF THE UNITED STATES TO  QUESTIONS POSED BY THE PANEL 
AFTER THE SECOND SUBSTANTIVE MEETING 
 
(18 October 2006) 
  
Questions to all parties
 
 
Q1. With reference to the statement by the Euro pean Communities, inter alia in para. 12 of 
the EC reply to Question 3 of the United States, do the parties consider that a Panel is entitled to address "systemic claims" or issues related to "systemic obligations" and, if so, to what extent? 
 
1. As noted in US Question 3 to the European Communities ("EC"), "systemic" and "direct" are 
terms used by the EC to describe its  claims against the United States.
1  Each of the EC's "in 
conjunction with" claims, through which it seeks to recast several provisions of the Understanding on 
Rules and Procedures Governing the Settlement of Disputes  ("DSU"), are couched as "systemic", 
while the EC claim of a US breach of DSU Article 22.8 (in and of itself) is described by the EC as a 
"direct claim."  Neither of these terms appears in th e DSU, nor are they part of customary rules of 
interpretation of public international law, as refl ected in Articles 31 and 32 of the Vienna Convention 
on the Law of Treaties. 
2. The question is not one of whether the EC has char acterized one of its claims as "systemic" or 
"direct".  Indeed, it is unclear what, exactly, the EC means when it uses these terms, other than to 
indicate in the case of a "systemic" claim that it  is unable to identify a particular obligation in a 
specific provision of the DSU which the United States ha d allegedly breached.  Rather, it is the role of 
the Panel to examine the actual obligations  set out in the DSU as it is currently drafted, and to analyze 
the arguments of the United States and the EC in li ght of those obligations.  Any EC claim must be 
grounded in the actual text of the DSU.  As the Un ited States has argued in several of its previous 
submissions, the EC claims which it terms "systemic"  merely reflect how the EC would like to see the 
DSU redrafted, at least for purposes of this dispute.  Through its "systemic" claims, the EC seeks license to depart from the agreed text of the DSU so as to insinuate new obligations into several 
provisions of the DSU.  The United States has demonstrated that there is no basis for finding a US 
breach of these so-called "systemic" obligations. 
Q2. With reference to the US rebuttal, para. 27 , do the parties consider that a measure that 
does not comply with the requirements of Articl e 5.7 SPS would automatically be in breach of 
Article 2.2 SPS, or Article 5.1 SPS, or both? 
 
3. Article 5.7 applies "[i]n cases where relevant sci entific evidence is insufficient" to perform a 
risk assessment.
2  Accordingly, an analysis under Article 5.7 presupposes that there is, or may be, a 
breach of Article 5.1 or Article 2. 2; otherwise, it would not be necessary for the Member maintaining 
a measure to assert that the requirements of Article 5.7 have been met.   
4. In original proceedings brought against a measure, the question of whether the requirements 
of Article 5.7 have been met might arise in respon se to a claim that a measure is inconsistent with 
Article 2.2 or Article 5.1.  In such a proceeding, the complaining party would have the burden of 
establishing a breach of Article 2.2 a nd/or Article 5.1.  It would not be sufficient for the complaining 
party to demonstrate that the requirements of Article 5.7 have not been met in order "automatically" to 
                                                      
1 US Questions to the EC, Question 3. 
2 Appellate Body Report, Japan – Apples , para. 179.  WT/DS320/R/Add.3 
 Page C-41 
 
 
  establish a breach of Articles 2.2 and 5.1.  For exampl e, where there is suffici ent scientific evidence to 
perform a risk assessment, a Member may not provisi onally adopt a measure pursu ant to Article 5.7.  
However, this is a separate question from whether a risk assessment within the meaning of Article 5.1 
has actually been performed.3 
5. In this dispute, the Dispute Settlement Body ("DSB") has already ruled that the EC import 
bans on meat from cattle treated with the five  hormones (for which the EC now asserts that the 
conditions of Article 5.7 have been met) breach  Article 5.1.  The EC does not claim to have 
performed a risk assessment consistent with Article 5. 1.  Against that background, the question in this 
dispute is whether the EC has established, in pursuing its claim under Article 22.8, that the EC has provided a solution to the nullification or impairme nt caused by the breach of Article 5.1 because the 
conditions of Article 5.7 have been met.  Since th e Article 5.7 conditions have not been met, the EC 
has not demonstrated that it has provided a soluti on to the nullification and impairment found by the 
DSB.  In that sense, the failure to meet the requi rements of Article 5.7 "automatically" leads to the 
conclusion that the Article 5.1 breach found by the DSB has not been removed. 
Q3. When and how was each of the following documents made available to Canada and the 
United States?  Please answer independently for each of the documents mentioned below: 
  (i) 1999 Opinion;  (ii) 2000 Opinion;  (iii) 2002 Opinion;  (iv) each of the "17 studies". 
 
6. As noted in the US response to Panel Question 49 after the first substantive meeting, the EC 
contacted the United States in 1999 to inform releva nt US regulatory agencies of its completion of the 
1999 Opinion
 on the six hormones at issue in the EC – Hormones  dispute.  At that time, the US Food 
and Drug Administration ("FDA") and Department of  Agriculture ("USDA") reviewed the documents 
put forward by the EC.  The response to those docum ents is contained in Exhibit US-21.  The United 
States and the EC then met during the summer of 1999 to discuss the results of the EC's 1999 Opinion. 
7. We have been unable to locate any records indicating that the EC provided its 2000 Review
 
or 2002 Opinion  to US authorities for a similar review or that it requested a scientific conference or 
discussions on the conclusions of those documents simila r to those held in 1999.  Similarly, we have 
no record of a requested discussion or conference on the scientific underpinnings of the EC's ban once 
it asserted in the fall of 2003 that it had develope d a risk assessment and brought its measure into 
conformity with DSB recommendations and rulings. 
8. The United States and the EC held a video c onference in the fall of 2003, during which the 
EC provided a brief PowerPoint presentation summariz ing its amended ban.  However, the EC did not 
provide any information on its 2000 Review  or 2002 Opinion , nor did it present any information on 
the scientific conclusions and analyses it viewed as  supporting its amended ban.  A copy of this 
presentation may be found in Exhibit US-22. 
                                                      
3 At the same time, the United States recognizes  that a responding Member would likely only have 
raised Article 5.7 in the context where the respondi ng Member does not claim to have performed a risk 
assessment meeting the requirements of Article 5.1 or that  there is sufficient scien tific evidence for purposes of 
Article 2.2.  In that situation, ther e would appear to be no dispute that th ere would be a breach of Article 5.1 or 
2.2 if the requirements of Article 5.7 are not met, and in that sense the breach of Article 5.1 or 2.2 would be 
"automatic." WT/DS320/R/Add.3 
Page C-42  
 
  9. The United States sent the EC an SPS Article 5.8 re quest in the fall of 2004, to which the EC 
responded on May 19, 2005.  A copy of the Article 5.8 request and the EC's response may be found at 
Exhibit US-23.  The EC's response contained internet links for the 2000 Review
 and 2002 Opinion . 
10. At no point in time prior to the initiation of this dispute was the United States in possession of 
all of the "17 Studies"  ostensibly underpinning the EC's "ris k assessment."  These materials were not 
provided by the EC in its response to the US Artic le 5.8 request and were produced in a piecemeal 
fashion throughout these proceedings.  We have disc ussed the EC's failure to produce these studies in 
detail in the US Rebuttal Submission (paras. 19-22) a nd have chronicled the (lack of) availability of 
these studies in Table 1 to that Submission. 
Q4. Has the European Communities assessed in a systematic manner the existence and level 
of risks from failure to observe good veterinary practices with respect to the administration of 
oestradiol 17ß as a growth promoting hormone to cattle, in particular in the United States' and Canada's markets?   If so, please indicate wher e this assessment is to be found in the evidence 
provided to the Panel. 
 11. The EC has not assessed the existence and leve l of risks from failure to observe good 
veterinary practices with respect to the admini stration of estradiol 17ß as a growth promoting 
hormone to cattle in the United States.  In fact, th e EC has not even seriously argued in the course of 
these proceedings that it has done so. 
12. As noted by the United States in several of its submissions, the EC presented a number of 
unrealistic misuse scenarios.  However, the actual occurrence of these scenario s in US feedlots is 
purely speculative and unsupported by evidence.
4  For example, in its 1999 Opinion , from 
pages 30-31 (§ 3.3), the EC presents several hypo thetical misuse scenarios but fails to assess the 
probability that any of these scenarios would occu r.  The EC postulates that ears from cattle 
containing growth promoting implants will enter th e human food supply.  When the United States 
asked whether the EC had provided any evidence that this has ever occurred or would ever occur, the 
experts (Drs. Boobis and De Brabander) noted that there was no such evidence.  The EC also 
concludes that there is a risk that a black mark et will exist in the United States for estradiol 17 β.  
(1999 Opinion, § 3.3.3).  However, the only evidence on the record regarding the existence of a black 
market demonstrates that such a market exists in the EC , where use of the hormone as a growth 
promoter has been banned.  Not only does the EC  fail to provide evidence of or assess the potential 
for misuse in its 1999 Opinion, even if  one were to assume misuse, the EC has failed to provide any 
evidence that violative residue levels would result except in the most extreme overdosing 
circumstances.5 
13. In its Exhibit EC-73 , the EC discusses several hypothetical misuse scenarios but similarly 
fails to assess, in any meaningful way, the likeli hood of the occurrence of any of these scenarios in 
US feedlots.  For example, the EC asserts that "stacking" of implants ( i.e., treatment with more than 
one dose of an implant at the same ti me) is commonplace in the United States.6  However, the 
evidence cited by the EC to support this argument  – a guidance document from the University of 
Nebraska – does not stand for this conclusion.  This  fact was confirmed by the author of the guidance 
cited by the EC.7  Further, the EC fails to examine the act ual workings of the US food safety system 
both in this document and in each of the three Opin ions comprising its "risk assessment."  The United 
                                                      
4 The United States discusses the EC's failure to assess the risk of misuse (or failure to satisfy good 
veterinary practices) at length in its Rebuttal Submission (pages 21-30) and its Oral  Statement at the Second 
Substantive Meeting (Expert Issues) (paras. 60-67). 
5 See US Rebuttal Submission (pages 21-30); Dr. Boobis' Response to Panel Question 62. 
6 Exhibit EC-73. 
7 See Letter from Dr. Dee Griffin, Exhibit US-28; US Rebuttal Submission, paras. 60-63.  WT/DS320/R/Add.3 
 Page C-43 
 
 
  States has discussed the actual workings of the US  food safety system at length and has demonstrated 
that the EC's speculation that a risk of failure exis ts is not based on any evaluation of any evidence.8 
14. It is essential to recall the views of the scientif ic experts on the issue of whether or not the EC 
has indeed assessed the risk of a fa ilure to meet GVPs.  Dr. Boisseau  noted that "as the [EC] did not 
conduct any quantitative risk assessmen t for growth promoters, it is not possible to say that the 
scientific evidence referred to by the [EC] assesses the risk to hu man health from residues resulting 
from these misuses/abuses."9  Dr. Boobis  agreed, stating:  "[t]here was no attempt to evaluate the risks 
from the resultant exposures on misuse or abuse, either  in the papers cited or by the SCVPH (2002) in 
their evaluation of these studies.  Indeed, the SCVPH (2002) simply noted that ‘[t]herefore, these data 
have to be considered in any quantitative exposure assessment exerci se', without undertaking such an 
exercise."10  While Dr. De Brabander  appears to disagree with Drs. Boobis and Boisseau , his 
responses fail to indicate whether or not he is of th e opinion that the EC actually assessed the risk of 
misuse, and in several instances his opinions are si mply based on anecdotal information and policy 
considerations, rather than scientific evidence or  citations to the EC's purported risk assessments.11  
15. Finally, it is necessary to recall that, even if one assumed that the EC actually assessed the 
risk of a failure to meet GVPs, the scientific evid ence put forward by the EC indicates that violative 
residues in meat would only occur as a result of that failure in the most extreme circumstances.  Dr. 
Boobis  provides a thorough review of the EC's materi als in his response to Panel Question 62 (at 
pages 50-52).  The United States has also reviewed these EC materials and commented on their failure 
to demonstrate violative residues excep t for in the most unrealistic scenarios.12 
Q5. In its comments on comments of the United  States and Canada on experts replies to the 
Panel questions (in particular Question 13) , the European Communities indicates that 
oestradiol 17ß might be a "weak genotoxin" (para. 44).  At what doses is genotoxicity observable in vivo?  How are these doses comparable  to those found in meat from cattle treated 
with growth promoting hormones?  How would this assertion affect the identification of adverse 
effects and the evaluation of potential occurren ce of these effects from consumption of meat 
from cattle treated with oestradiol  17ß for growth promotion purposes? 
 
16. To date, the EC has presented only one st udy (out of 127 Exhi bits) which addresses 
genotoxicity of estradiol 17ß in vivo .
13  In Exhibit EC-125, rats were treated with 5 milligrams of 
estradiol 17ß.  This dose of estradiol 17ß resulted in a two-fold increase in the number of mutations in 
mammary tissue.  However, as discussed in the meeti ng with the experts, the results of this study are 
highly questionable for a number of reasons, and th e doses involved in the study are not comparable 
                                                      
8 See US Rebuttal Submission, para. 55; US Comments on the Experts' Responses, paras. 105-106. 
9 Dr. Boisseau Responses (Question 48), p. 24. 
10 Dr. Boobis Responses (Question 48), p. 42.  See Dr. Boobis Responses (Question 62), p. 52 ("the 
data generated by the EU research in question do not provide any indication that it is not possible to conduct a 
risk assessment of the hormones used as growth promoters.") 
11 See, e.g., US Comments on the Responses of the Experts, para. 107. 
12 See US Comments on the Experts' Responses, Section C.6; US Rebuttal Submission, Section II.B.4. 
13 In paragraph 43 of its Comments on the US and Canada's Comments on the Experts' Replies, the EC 
claims to have "sufficient and constantly growing ev idence from studies in vivo  that show the direct 
genotoxicity of oestradiol 17ß and its catechol metabolites ...".  However, US review of the studies listed in 
paragraph 43 reveals that only one, EC-125, demonstrated genotoxicity of estradiol 17ß in vivo  (and only then at 
irrelevant doses) while the other studies were perform ed only with catechol metabolites.  This fact was 
confirmed by Dr. Metzler, member of the EC delegation, at the meeting with the experts on 28 September 2006.  
The distinction between estradiol 17ß and its catechol me tabolites is important because the EC has presented no 
evidence to show that the catechol metabolites are present in vivo  at levels comparable to those which produce 
genotoxic effects in vitro .  Moreover, the EC has presented no evidence to show that consumption of estradiol 
17ß residues in beef affects the productio n of catechol metabolites whatsoever.    WT/DS320/R/Add.3 
Page C-44  
 
  to residue levels found in meat from cattle treat ed with estradiol for growth promotion purposes.
14  
Indeed, the doses are exponentially greater than t hose necessary to elicit biological or endocrine 
effects (in other words, they are well above  the hormonal threshold).  
17. To compare the dose of estradiol 17ß used in  EC-125 to levels found in meat from cattle 
treated with growth promoting hormones, it is neces sary to examine the dose relative to body weight.  
A laboratory rat weighs approximately 250 grams.  Therefore, the dosage administered to the rats in 
EC-125 was 5 milligrams/250 grams, or 20 milligrams/k ilogram.   If a human (average weight of 70 
kg.) were treated with an equivalent dose of estradiol 17ß, the dose would be 1400 mg  (20 
milligrams/kilogram x 70 kg).  This dose is exponentia lly greater than residue levels found in meat 
from cattle treated with estradiol for growth  promotion purposes.  According to JECFA,15 a 
conservative estimate of the amount of estradiol 17ß in a 250 gram serving of meat from treated cattle 
is between 15 and 25 nanograms, or 0.00001 5-0.000025 milligrams .  In other words, in relative terms, 
the dose administered to the rats  in the EC's study (Exhibit EC-125) is more than 50 million times 
greater  than the amount of estradiol residues consum ed by humans in meat from treated cattle. 
18. Therefore, the dose of estradiol 17ß administered to rats in EC-125 was astronomically higher 
than that derived from eating a serving of beef from treated cattle.  The difference is even greater  
when one takes into account the different routes of administration of estradiol 17ß.  The rats in the 
study were treated estradiol 17ß via subcutaneous impl ants, which results in very high bioavailability.  
In contrast, only a small percentage ( ≤ 10%) of orally-ingested estradiol 17ß is bioavailable due to 
rapid metabolism in the liver and small intestine.  So, not only was the dose exponentially greater in 
the rat study but the dose was much more bioava ilable than would be the case from consuming 
residues in meat.  For these reasons, this study is not  relevant to the purported risk to human health 
associated with eating meat from cattle treated with growth-promoting hormones. 
Questions to the United States and Canada : 
 
Q17. What legal procedures were used in your respective domestic legal systems to adopt the suspensions of obligations at issue?  Would the same legal procedures apply to their abrogation? 
 
19. Under the US legal system, the applicable aut horities and procedures are set out in Sections 
301-309 of the Trade Act of 1974, as amended (codified at 19 U.S. C. 2411-2419) (commonly referred 
to as "Section 301").   
20. Suspension of obligations
:  On July 12, 1999, the arbitrator determined that the level of 
nullification and impairment suffered by the United States in this dispute was $116.8 million per year, 
and that the United States was entitled to suspend the application of tariff concessions up to that 
amount.  On July 26, the DSB authorized the Unit ed States to suspend the application of tariff 
concessions in this amount.  In accordance with the arbitrator's report and DSB authorization, the 
USTR determined that appropriate action under Secti on 301 in response to the EC's failure to comply 
with the DSB recommendations and rulings was to suspend the application of tariff concessions and 
increase tariffs on a specific list of EC products with an annual trade value of $116.8 million.  The 
USTR then published a Federal Register notice announcing the suspension of concessions in the form 
of increased duties on specific products of the EC.   
21. Termination of Suspension :  Section 301 provides that the USTR may terminate an action 
previously taken under Section 301 if, inter alia , the DSB adopts a report finding that the rights of the 
                                                      
14 See paragraphs 27-29 of US Oral Statement at th e Second Substantive Meeting (Expert Issues). 
15 See "Evaluation of certain veterinary drug residues in food", Fifty-Second Report of the Joint 
FAO/WHO Expert Committee on Food Additives, WHO T echnical Report Series: 893 (2000) ("52nd JECFA 
Report"), p. 83.  (Exhibit US-5).  WT/DS320/R/Add.3 
 Page C-45 
 
 
  United States under the trade agreement are not bein g denied.  Section 301 requires USTR to consult 
prior to terminating any action.  Upon making such  a determination, USTR would publish a notice in 
the Federal Register announcing the termination of the suspen sion of concessions and the restoration 
of regular MFN rates of duties on the affected products.    
Q18. Would you consider that, for the purpose of the DSU, Directive 2003/74/EC should be 
viewed as a new measure or as the continua tion of the previous measure found to be 
inconsistent with the WTO Agreemen t, since it still imposes a ban? 
 
22. Since the United States is not the complaining pa rty, there is no challenge to an EC measure 
in this dispute as such.  Rather, the question is wh ether the EC has demonstrated, within the meaning 
of Article 22.8 of the DSU, that the EC has remove d its WTO-inconsistent measures or has provided a 
solution to the nullification or impairment.16  If the EC has simply continued its WTO-inconsistent 
measure, then there would be no solution to the nullification or impairment.  If the EC has not 
demonstrated that it has solved the nullification or impairment through a new or revised measure, then 
the EC has not met its burden under Article 22.8.  Accordingly, the United States has not argued that 
the EC's amended bans are or are not new measures for purposes of the DSU.  Rather, we view the 
pertinent question to be whether or not the EC's ba ns in fact bring it into conformity with the DSB 
recommendations and rulings in the Hormones  dispute.  If there were a DSB finding that the EC has 
complied by basing its permanent ban on estradiol on a risk assessment within the meaning of SPS Article 5.1 and satisfying the four cumulative conditi ons of SPS Article 5.7 for its provisional bans on 
the other five hormones, then there would no longer be a basis to apply the suspension of concessions 
or other obligations.  This would be the case whether the EC's ban was a new measure or a 
continuation (albeit with modifica tion) of the previous measure. 
Questions to the United States
: 
 
Q19. Does the United States argue a violation of Article 5.2 and of Article 5.6 SPS?  In other 
words, do you expect the Panel to issue fi ndings regarding the compliance of Directive 
2003/74/EC with those provisions?  What is the purpose of the reference to Article 2.2 SPS in para. 27 of the US rebuttal submission? 
 
23. As the responding party, the United States has not made any claims of an EC breach of its 
WTO obligations.  The EC, as the complaining party, is responsible for bringing such claims and 
satisfying its burden of proof for each claim.  One of the EC claims in this dispute is that the United 
States has breached its obligations under DSU Article  22.8, which sets out the conditions under which 
a Member suspending concessions or other obligatio ns must cease to apply the suspension against 
another Member.  In order to satisfy its claim unde r DSU Article 22.8, the EC must demonstrate that 
it has either removed the WTO inconsistent measu re(s) or that it has provided a solution to the 
nullification and impairment of benefits.   
24. The EC clearly has not removed its import ba ns nor has it claimed to have done so.  
Therefore, in order to satisfy its burden in this  proceeding, the EC must demonstrate that it has 
brought its measure into conformity with the DSB recommendations and rulings in the  Hormones 
dispute.  Those recommendations and rulings incl ude findings of EC breaches of SPS Articles 5.1 and 
3.3.  The EC argues it has satisfied the DSB re commendations and rulings by basing its permanent 
ban for estradiol on a risk assessment and satisfyi ng the four conditions of SPS Article 5.7 for the 
other five hormones in lieu of a risk assessment.  These arguments call for findings as to whether or not the EC has in fact demonstrated that it ha s brought itself into conformity with the DSB's 
recommendations and rulings, as these findings are integral to the EC's Article 22.8 claim.   
                                                     
 
16 No party has argued that the third prong of the Article 22.8 test is involved here – reaching a 
mutually satisfactory solution. WT/DS320/R/Add.3 
Page C-46  
 
  25. The reference to SPS Article 2.2 in paragraph 27 of the US Rebuttal Submission was made in 
the context of describing how SPS Article 5.7 functio ns as a qualified, temporary exemption under the 
SPS Agreement.  The reference was not intended to elicit a finding of a breach of SPS Article 2.2.  
Rather, the appropriate finding would be that the EC, in failing to satisfy the co nditions of Article 5.7, 
has not solved the nullification and impairment of be nefits arising from its failure to base its measures 
relating to the five other hormones on a risk assess ment within the meaning of SPS Article 5.1.  The 
EC concedes that it has not b ased these measures on such an assessme nt; therefore, the EC has not 
brought its measures into conformity with the DSB recommendations and rulings. 
26. The United States believes that a finding of  compliance or non-compliance with the 
requirements of SPS Article 5.2 would be appropriate as part of the Panel's analysis of whether the EC 
has based its measure on a risk assess ment within the meaning of SPS Article 5.1.  Article 5.2 requires 
that risk assessments take into account certain elements, including available scientific evidence; 
relevant processes and production me thods; and relevant inspection, sampling and testing methods.  
Article 5.2 is not mutually exclusive of SPS Article 5.1; rather, it sets out the specific components of the risk assessment on which Members are require d to base their measures for purposes of SPS 
Article 5.1.  If the EC has not satisfied the requi rements of Article 5.2, it has not conducted a risk 
assessment, as appropriate to the circumstances.  Its measure (permanent ban on estradiol) therefore cannot be based on a risk assessment with in the meaning of SPS Article 5.1. 
Q20. Could the United States clarify whether its arguments regarding a violation of 
Article 3.3 SPS apply only in relation to the definitive ban on oestradiol 17 ß or whether they apply also in relation to the provisional ban imposed on the other five hormones? 
 
27. US arguments regarding a violation of SPS Artic le 3.3 apply in relation to each of the EC 
bans on meat from cattle treated with growth prom oting hormones for which international standards 
exist.  In other words, US arguments relate to each of the hormones at issue except for melengestrol 
acetate ("MGA"), for which JECFA has conducted a risk assessment, set an ADI and proposed an 
MRL, but for which Codex has not adopted an MR L.  SPS Article 3.3 requires that Members base 
their measures on international standards where they  exist and only permits Members to diverge from 
such standards if there is a scientific justificati on for doing so.  For purposes of this dispute, that 
scientific justification could have taken the form of a properly conducted risk assessment for estradiol 
or satisfying the four conditions of Article 5.7 fo r testosterone, progesterone , zeranol and trenbolone 
acetate.  The United States has demonstrated that th e EC has failed to provide such a justification. 
28. The United States has demonstrated that the EC has failed to satisfy the conditions of 
Article 5.7 for its provisional ban on MGA because, among other things, there is sufficient scientific 
evidence to conduct a risk assessme nt for MGA and the EC has not based its provisional ban on MGA 
on available pertinent information.  The United States has also demonstrated that the EC failed to satisfy the conditions of Article 5.7 for the othe r four provisionally banned hormones (testosterone, 
progesterone, zeranol, and trenbolone acetate).  WT/DS320/R/Add.3 
 Page C-47 
 
 
  ANNEX C–4 
 
REPLIES OF THE UNITED STATES TO QUESTIONS 
POSED BY THE EUROPEAN COMMUNITIES 
AFTER THE SECOND SUBSTANTIVE MEETING 
 
(18 October 2006) 
  
EC Questions to the United States and Canada
: 
 
Q1. Please explain, if possible in detail,  what kind of scientific evidence on 
exposure-assessment from residues in meat trea ted with the six hormones for animal growth 
promotion was used by the United States and Canada when these substances were authorised? 
Was this exposure assessment a quantitative one?   Please provide concrete reference to studies 
used in your exposure assessment and, if possibl e, to those of JECFA for the six hormones in 
question (in case you know the references).  
 
1. Of course, it is not US measures that are at issue here.  The European Communities ("EC") 
has chosen to ban the import of US meat and meat  products from cattle treated  with each of the six 
hormones for growth promotion purposes and it is ther efore an analysis of the EC's "risk assessment" 
and basis for its five "provisional bans" that is essential  to this dispute.  That being said, we are happy 
to provide more information for background, although we  note that this is the sort of question that the 
EC could have posed earlier to better inform its own risk assessment.   
2. The US Food and Drug Administration ("FDA" ) conducted quantitative exposure assessments 
for each of the hormones approved to promote growth  in cattle.  The procedures that FDA uses to 
evaluate the safety of edible products from anim als treated with veterinary drugs are publicly 
available and described in detail on the FDA web site.1  The exposure assessment component of the 
evaluation of the six growth-promoting hormones can be summarized as follows.   
3. For each of the six hormones, FDA required the sponsors to conduct extensive residue 
studies.  These studies provided information on total residue depletion and the metabolic fate of each 
hormone in edible tissues from cattle (muscle, liver, kidney and fat). 
4. For each of the three synthetic hormones, spons ors also performed extensive toxicological 
testing in experimental animals2 to determine the dose at which the hormone produced an adverse 
effect and the dose at which no effect was observed (no effect level or "NOEL").  The NOEL of the most sensitive toxicological effect ( e.g., reproductive, developmental, tumorigenic) in the most 
sensitive species examined ( e.g., rat, mouse, rabbit) was then divided by an appropriate safety factor 
to determine an acceptable daily intake ("ADI") .  The ADI was then used to calculate a safe 
concentration for each edible tissue from ca ttle as follows:  safe concentration = ADI × 60 kilograms 
(weight of average person) ÷ grams consumed per day.  The food consumption factors currently used 
by FDA are:  muscle, 300 grams; liver, 100 grams; fat and kidney, 50 grams each.
3  FDA determined 
that for each of the synthetic hormones, the total residues ( i.e., residues of toxicological concern) were 
less than those calculated from the respective ADI.  Therefore, FDA concluded that consumption of 
these residues in edible tissues from treated ca ttle does not pose a risk to human health. 
                                                      
1 http://www.fda.gov/cvm/Guidance/published.htm , Guidance 3 
2 This testing is also explained in FDA Guidance 3. 
3 At the time the hormones were approved, an even more conservative food basket was used and it was 
assumed that on any given day a person might consume up to 500 grams of muscle, 250 grams of liver, 167 
grams of kidney, or 125 grams of fat. WT/DS320/R/Add.3 
Page C-48  
 
  5. For the three natural hormones, FDA did not establish ADIs and concluded that human safety 
can be assured without the need for extensive toxicol ogical testing in experimental animals.  This is 
because the amounts of these hormones present in edible  tissues of treated cattle were found to be 
very small relative to the endoge nous production in humans.  F DA concluded that no additional 
physiological effect will occur from chronic ingesti on of animal tissues that contain a residue level of 
natural hormones equal to 1% or less of the amount  produced daily by the segment of the population 
with the lowest endogenous production.
4  Using food consumption factors, FDA set permitted 
increased daily exposures of 0.06 micrograms for es tradiol, 1.50 micrograms for progesterone, and 
0.32 micrograms for testosterone.  To obtain F DA approval for the natural hormones, the drug's 
sponsor was required to demonstrate that residu es of each hormone in edible tissues from treated 
cattle did not exceed the safe concentration.  This re quirement was satisfied for all three of the natural 
hormones. 
6. The exposure assessment conducted by JECFA for each of the six hormones was described in 
detail by the JECFA representative at the meeting w ith experts on 27-28 September 2006.  References 
describing JECFA's risk assessments for the horm ones can be found in the answer to Question 2 
below. 
Q2. Please  indicate, if possible in detail, whether your risk assessments, and if you know 
those of JECFA, of the six hormones in questio n for animal growth promotion have attempted 
to calculate the risk to humans from the addi tional exposure resulting from the residues in 
hormone-treated meat when used according to GVP and when GVP is not respected.  Was it a quantitative exposure assessment?  If so, please  provide the precise reference to the data. 
(Please note that we are not referring here to residue-depletion studies contained in CAN 
Exhibit-17, since the EC has also conducted such residues depletion studies for its 1999-2002 risk assessments). 
 
7. Again, this dispute settlement proceeding is not  concerned with the measures of the United 
States or any risk assessments of the United States.  And under Article 3.3 of the SPS Agreement the 
EC has an obligation to be familiar with the re levant international standards, guidelines or 
recommendations.  The United States wonders if the EC's question is an admission that the EC has 
failed to familiarize itself with the relevant JECFA material.   
8. That being said, we are happy to provide more  information for background, although we note 
that this is the sort of question that the EC c ould have posed earlier to better inform its own risk 
assessment.  As explained in the FDA Guidance
5 referenced in the response to Question 1, FDA 
requires that total residue depletion studies be c onducted using the dose that is the highest intended 
treatment level and that these studies should model the exposure received by the target animal.  In the case of the six hormones in question, the highest  intended treatment level was (and still is) one 
implant per animal, consistent w ith good veterinary practice.  
9. JECFA completed quantitative exposure assess ments for each of the six hormones. The 
process for conducting these assessments was described by the JE CFA representative at the meeting 
with the experts.  Food and Nutrition Paper ("FNP" ) 41/12 provides extensive compilations of residue 
data for each of the natural hormones and the analysis includes estimates of exposure from the 
consumption of the four edible tissues (muscle, liver, kidney and fat) from treated animals.   
                                                     
 
4 Sensitive subpopulations are prepubertal girls for te stosterone and prepuberta l boys for estradiol 17 
and progesterone. 
5 http://www.fda.gov/cvm/Guidance/published.htm   WT/DS320/R/Add.3 
 Page C-49 
 
 
  10. The exposure assessment for the th ree natural hormones, as well as the available residue data, 
metabolism data and analytical methods can be found at the JECFA website.6  The WHO Technical 
Report Series publication 893 summarizes all of th e relevant findings on additional estimated 
exposure from consumption of tissues from hormone-treat ed animals.  For total estrogens, the highest 
excess intake (from eating beef from treated cattle ) was 30-50 nanograms per person per day.  For 
progesterone, the estimated maximum daily exposur e was approximately 500 nanograms per day, and 
for testosterone, about 60 nanograms per day.  These figures represent less than 2% of the JECFA 
ADI for estradiol, 0.03% for progesterone and about  0.05% for testosterone.  That is, tissues from 
hormone-treated animals present hormone residues that are a minuscule percentage of daily allowances for ingestion of such hormones. 
11. The JECFA residue, metabolism and analytical method reports for the three synthetic 
hormones may be found at the website listed above.  Individual reports are contained in FAO FNP 41, 
41/2, 41/13, 41/16 and 41/17.  For each hormone, the approach used by JECFA was to establish an 
ADI and recommend MRLs that are consistent with the maximum theoretical residues determined by 
the ADI established on a μg/kg body weight basis.   
12. JECFA's evaluations of the six hormones are ba sed on data provided by sponsors which, in 
general, reflect good veterinary practices.  The Un ited States notes that, in continuing to raise the 
issue of good veterinary practices, the EC only undersco res its failure to meet its WTO obligations in 
this regard.  The experts have confirmed that the EC itself has failed to properly examine the 
likelihood of misuse or abuse of the hormones at issue as it was obligated to do pursuant to Articles 
5.1 and 5.2 of the SPS Agreement.
7  
Q3. The EC understands that some of the ex perts (Drs. Guttenplan, Sippel and Cogliano) 
have stated that it is not possible to determine with accuracy the dose-re sponse curve at the very 
low levels of exposure from these hormones in general and when used for animal growth 
promotion.  Do you agree with these statements ?  If not, could you please provide the precise 
references to scientific studies where this has been  done?  What would be the implications of 
this impossibility for the need to perform a qua ntitative or qualitative exposure assessment for 
these hormones when used for animal growth promotion? 
 
13. Drs. Cogliano, Sippell and Guttenplan  postulated that it is not possible to define with 
precision the low-dose response curve for estradiol.  However, it is necessary to examine this 
discussion in light of the available scientific evidence relating to estradiol and the experts' opinions on 
that evidence.  The scientific evidence indicates that there is a threshold for the genotoxic and 
carcinogenic effects of estradiol.  Genotoxic and carcinogenic effects are only observable at very high doses (both in vivo  and in vitro ) at or above this threshold.  This  threshold is orders of magnitude 
greater than the levels of estradiol found in resi dues in meat from cattle treated for growth promotion 
purposes.  There is no scientific evidence demonstr ating adverse effects at doses lower than the 
hormonal threshold.   
14. Dr. Guttenplan
 concluded that there is no risk fo r carcinogenicity below the acceptable daily 
intake level ("ADI") for estradiol at the meeti ng with the experts, thereby indicating that any 
                                                      
6 www.fao.org/ag/agn/jecfa/archive_en.stm  
7 See Dr. Boobis Responses (Question 62), p. 58 ("[t]he evidence obtained did not indicate any 
additional concern regarding the risk from exposure to residues of the hormones in meat from cattle treated for 
growth promotion"); Dr. Boobis Responses (Question 48), p. 42 (the EC has made "no attempt to evaluate the 
risks" from misuse, either in its Opinions or in underly ing studies); Dr. Boisseau Responses (Question 51), p. 25 
("the [EC] did not conduct a quantitative risk assessment from growth promoters, [and that] it is not possible to say the scientific evidence referred to by the [EC] assesse s the risk to human health from residues resulting from 
these misuses/abuses.")  See Appellate Body Report, paras. 205-207. WT/DS320/R/Add.3 
Page C-50  
 
  carcinogenic effects would be a result of doses above the threshold (levels exponentially greater than 
those found in residues in meat fro m treated cattle).  Dr. Boisseau
 noted that "the scientific evidence 
relied upon in the SCVPH Opinions does not support the conclusion that the carcinogenic effects of oestradiol-17 β are related to a mechanism other than hormonal activity."
8  As noted by Dr. Cogliano , 
"it has not been established by the EC that genot oxicity and cell proliferation would be induced by 
levels found in meat residues added to the pr e-existing levels occurring in exposed humans."9  Finally, 
Dr. Boobis  stated that "[t]he carcinogenic effects of o estradiol appear to be a consequence of its 
endocrine activity."10  In other words, carcinogenic effects were only observable at levels at or above 
the hormonal threshold.  In the absence of any scien tific evidence of adverse effects at doses below 
the threshold, arguing about the shape of the dose-response curve below the threshold is not 
informative.   In other words, there is no evid ence that estradiol will cause adverse effects below a 
definable threshold.  The EC has failed to present any such evidence in the course of these 
proceedings. 
Q4. If you were to agree that scientists cannot define the dose-response curve as explained in 
the previous question, would this state of sci entific knowledge be defined as "scientific 
uncertainty" in this area?  If not, please explain.  
15. As indicated in our previous response, the ques tion of the shape of the dose response curve at 
low doses is not reflective of any scientific uncertainty relevant to the risk at issue given the lack of 
scientific evidence of a risk  below the threshold for estradiol.  The United States summarized the state 
of scientific evidence relating to the genotoxicity an d carcinogenicity of estradiol in its response to 
Question 3 above.  The EC has attempted to cast this  lack of evidence of a risk at low doses as a 
relevant "scientific uncertainty."  But this lack of  evidence of a risk cannot be construed in turn as 
evidence of a risk or as a basis for the EC's ban.   
16. By arguing the presence of "scientific uncertainty " in a situation in which there is no evidence 
of a risk at relevant exposure levels, the EC app ears to be seeking nothing l ess than an assurance that 
there will never be evidence of a new risk from estradiol  at some point in the future.  As argued by the 
United States and discussed by the Appellate Body, th is is an uncertainty "that theoretically always 
remains since science can never provide absolute certa inty that a given substance will not ever have 
adverse health effects .  We agree with the Panel that this theore tical uncertainty is not the kind of risk 
which, under Article 5.1, is to be assessed ."11   This type of uncertainty is not evidence of a risk, nor 
may it serve as the basis for the EC's ban on meat a nd meat products treated with estradiol for growth 
promotion purposes. 
Q5. Could you please explain what is your positi on on the existence or non existence of an 
international standard for MGA for the purposes of Articles 2, 3 and 5 of the SPS Agreement in 
these disputes?  
 17. Please see the US response to Panel Question 20. 
EC Questions to the United States
: 
 
Q1. The 2002 US Report on Carcinogenesis (E xhibit EC-101) states inter alia that: 
"veterinary use of steroidal estrogens (to pr omote growth and treat illnesses) can increase 
estrogens in tissues of food producing animals to above their normal levels" (p. 8).  How do you 
reconcile this with your proposition in para. 51 of your First Written Submission? 
                                                      
8  Dr. Boisseau Responses (Question 16), p. 12. 
9  Dr. Cogliano Responses (Question 18), p. 1. 
10 Dr. Boobis Responses (Question 16), p. 19. 
11 Appellate Body Report, para. 167.  WT/DS320/R/Add.3 
 Page C-51 
 
 
   
18. The 11th Report on Carcinogens notes that "veterinar y use of steroidal estrogens (to promote 
growth and treat illnesses) can increase estrogens in tissues of food producing animals to above their 
normal levels."  Paragraph 51 of the US First Written Submission states that "[w]hile tissue 
concentrations of estradiol 17 β in treated cattle may be slightly higher than those in untreated cattle, 
this increase is much smaller than the large va riations observed in (reproductively) cycling and 
pregnant cattle and is thus well within th e range of naturally observed levels."   
19. The United States fails to see a discrepancy between  these statements but is pleased to be able 
to clarify the issue for the EC through reference to th e EC's own exhibits.  It appears that the source of 
the EC's confusion is use of the word "normal" in the Report on Carcinogens.  In this (biological) 
context, "normal" is a relative term which depe nds on the endogenous, baselin e levels of estradiol 17 β 
present in the animal treated with growth-promoting hormones.  For example, the "normal" levels of 
estradiol 17 β in steers (male cattle lacking testes) will be extremely low.  It stands to reason, 
therefore, that treatment of steers with estradiol 17 β to promote growth may increase concentrations 
of estradiol 17 β in edible tissues to levels that are above " normal" for this type of animal.  However, 
as illustrated in Table III of EC-3412, this increase may be small (1.1 to  2.3-fold) and, as illustrated in 
Figure 1 of EC-51A, is not detectable in every anim al.  Female cattle have higher "normal" levels of 
estradiol 17 β than steers and these levels may be more va riable due to changes in production of 
estradiol 17 β by the ovary throughout the (21-day) repr oductive cycle.  Treatment of female cattle 
(heifers) with estradiol 17 β to promote growth may also result in increased estradiol 17 β 
concentrations in edible tissues of heifers, and accord ing to Table III of EC-34, this increase is similar 
to that observed in steers (1.9-fold).   
20. The basis for the US statement that "this increa se is much smaller than  the large variations 
observed in (reproductively) cycling an d pregnant cattle and is thus we ll within the range of naturally 
observed levels" is clearly illustrated by comparing the levels of estradiol 17 β in edible tissues of 
treated steers and heifers shown in Table III of EC -34 with the naturally-occurring levels of estradiol 
17β in cattle shown in Table II of EC-34.  Concentrations of estradiol 17 β in muscle of treated steers 
and heifers ranged from 3-17 pg/g, while naturally-occ urring concentrations range from 1.3-14 pg/g in 
steers, 12-13 pg/g in heifers, and 16-860 pg/g in preg nant cattle.  Therefore, even though veterinary 
use of estrogens to promote growth can increase es trogens in cattle to above "normal" levels (11th 
Report on Carcinogens), this increase is well within the range of naturally ob served levels (US First 
Written Submission). 
Q2. What was the reason to conclude for the first time in the 2002 US Report on 
Carcinogenesis that estrogens (including o estradiol-17ß) are carcinogenic not only by 
receptor-mediated effects but that in addition there are possibly by direct and indirect genotoxic mode of action?  Was it because of new develo pments in scientific research that became 
available after 1999? 
 
21. As explained in the second paragr aph of the Introduction to the 11
th Report on Carcinogens 
(EC-101 and US-26), the Report on Carcinogens lists  all substances which are known (or reasonably 
anticipated to be) human carcinogens and to which a significant number of US residents are exposed.  
This report is routinely prepared every two to f our years by the National Toxicology Program and 
published by the Department of Health and Human Services.13  It follows, then, that each Report on 
Carcinogens will include update d information on each carcinogen as that information becomes 
available.   
                                                      
12 In Exhibit EC-34, Daxenberger et al. present findings derived from a comprehensive search of the 
scientific literature on estradiol 17 β residues in edible tissues of cattle. 
13 http://ntp.niehs.nih.gov/index.cfm?obj ectid=72016262-BDB7-CEBA-FA60E922B18C2540  WT/DS320/R/Add.3 
Page C-52  
 
  22. The 10
th and 11th Reports on Carcinogens were publishe d in 2002 and 2005, respectively.  
Steroidal estrogens were first listed as " known to be a human carcinogen" in the 10th Report.14  Both 
the 10th and 11th Reports include a section that discusses the evidence for genotoxic effects of 
steroidal estrogens.  This section is virtually identi cal between the Reports.  Cited in this section are 
two references:  one article published in 199615 and the 1999 IARC Monograph on Hormonal 
Contraception and Post-menopausal Therapy.  It is th erefore clear that the statements on genotoxicity 
in both the 10th and 11th Reports on Carcinogens – published in 2002 and 2005, respectively – were 
based primarily on the findings of the 1999 IARC Monograph and not prompted by new developments in scientific research th at became available after 1999.   
23. Again, it should be emphasized that the findings  of the Report on Carcinogens and the IARC 
Monograph speak to the general risk from estrogens at levels exponentially higher than those found in 
residues in meat from treated cattle.  The Appellate Body and the original Hormones  panel reviewed 
the earlier version of the 1999 IARC Monograph ofte n cited by the EC in these proceedings and 
confirmed that studies such as the Monograph: 
constitute[d] general studies which d[id] indeed  show the existence of a general risk 
of cancer; but they d[id] not focus on and d[ id] not address the particular kind of risk 
here at stake – the carcinogenic or genot oxic potential of the residues of those 
hormones found in meat derived from cattle to which the hormones had been administered for growth promotion purposes.
16 
24. The potential for adverse effects from hormones at these high levels is not in dispute.17  The 
materials and findings cited by the EC (1999 IARC Monograph; 11th Report on Carcinogens) are not, 
however, evidence of a risk from meat from cattle treated with estradiol for growth promotion 
purposes. 
Q3. The 2002 US Report on Carcinogenesis stat es inter alia that: "The RoC does not present 
quantitative assessments of the risks of cancer asso ciated with these substances.  Thus listing of 
substances in the RoC only indicates a potent ial hazard and does not establish the exposure 
conditions that would pose cancer risks to individuals in their daily lives.  Such formal risk 
assessments are the responsibility of the appropriat e federal, state, and local health regulatory 
and research agencies."  If so, have the competent US authorities made the quantitative assessment of the risks of cancer posed by the residues of six hormones in meat from animal 
treated for growth promotion?  If not, when are you going to do it? 
 25. The procedures used by FDA for assessing the human  safety of veterinary drugs used in food-
producing animals are publicly available and described in detail at http://www.fda.gov/cvm/Guidance/guideline3pt2. html.  For these compounds, FDA focuses its 
evaluations on the risks of intermittent, chronic e xposure of humans to relatively low concentrations 
of residues.  FDA tailors the type of toxicologi cal testing required to show the safety of each 
compound according to its proposed use, probable e xposure of humans to both the parent compound 
and its metabolites, and its possible effects as observed in biological systems.  For some compounds, 
                                                     
 
14 Prior to the 10th Report on Carcinogens, conjugated estrogens were listed in the 4th Report in 1985 as 
"known to be human carcinogens " and a number of individual steroidal estrogens (non-conjugated, including 
estradiol-17 β, estrone, ethinylestradiol, and mestranol) were listed as "reasonably anticipated to be human 
carcinogens." 
15 Yager JD and Liehr JG. Molecular mechanisms of  estrogen carcinogenesis.  Annu Rev Pharmacol 
Toxicol 1996; 36: 203-232. 
16 Appellate Body Report, EC – Hormones , para. 200. 
17 See, e.g., US First Written Submission, para. 141; US Rebuttal Submission, paras. 38-39.  WT/DS320/R/Add.3 
 Page C-53 
 
 
  only a minimum of testing is required while other compounds may require more extensive 
toxicological evaluation. 
26. In line with the 11th US Report on Carcinogens, FDA considers estradiol 17 β to be a human 
carcinogen.  (However, it should be emphasized that the carcinogenicity of estradiol 17 β in humans is 
based largely on epidemiological studies of women taking estradiol 17 β as post-menopausal therapy, 
the doses of which are exponentially higher do ses than those in residues of estradiol 17 β present in 
beef.18)  FDA concluded that estradiol 17 β is not a genotoxic agent, and that any carcinogenic effects 
of estradiol 17 β in experimental animals are a consequence of persistent overstimulation of the 
hormonal system.  If consumption of residues of estradiol 17 β in edible tissues of food-producing 
animals does not cause such persistent overstimulati on of the hormonal system in humans, then FDA 
concludes that individuals consuming those residues w ill not be subject to an increased risk of cancer. 
27. Assessment of the risks to human health associ ated with the use of sex steroids in food-
producing animals presents unique challenges due to the fact that exposure to the compound occurs 
against a background level of e ndogenous production in all segment s of the population.  FDA has 
concluded that for estradiol 17 β (and its simple ester derivatives), human safety can be assured 
without the need for extensive toxicological testin g in experimental animals.  This is because the 
amount of estradiol 17 β present in edible tissues of food-producing animals is very small relative to 
the endogenous production in humans.  FDA has concluded that no physiological effect (or 
pathological effect, such as cancer) will occur fro m chronic ingestion of animal tissues that contain a 
residue level of estradiol 17 β equal to 1% or less of the amount produced daily by the segment of the 
population with the lowest endogenous production (pre pubertal boys).  Based on this conclusion, 
FDA has set a safe concentration of 0.06 micrograms for estradiol 17 β.  To obtain FDA approval for 
drug intended for use in food anim als that contains estradiol 17 β, the drug's sponsor must demonstrate 
that residues of estradiol 17 β in edible tissues from animals treated with that drug will not exceed the 
permitted increased exposure.  This requirement has been satisfied for all of the veterinary drugs 
containing estradiol 17 β that are approved by FDA for use as growth-promoting agents in cattle. 
Q4. The 2002 US Report on Carcinogenesis states inter alia that: "Estimating the extent to 
which listing a substance in the RoC protects public health is perhaps the most difficult task in 
preparing the RoC.  The carcinogenic risk (i.e., the probability of developing cancer) depends on many things, including the intensity, route, and duration of exposure to a carcinogen.  People 
may respond differently to similar exposures, depe nding on their age, sex, nutritional status, 
overall health, genetics, and many other factors.  Only in a few instances can risk for cancer be 
estimated with complete confidence, and these estimations require studies of long-term human 
exposures and cancer incidence in  restricted environments, which rarely are available."  
Despite this recognition of the difficulties, could you please explain if you have nevertheless performed the long-term human exposures to th e residues of these hormones in treated-meat in 
order to quantify if they pose a risk to human  health?  Do you know if JECFA has performed 
such a specific quantitativ e dose-response assessment? 
 
28. For the US perspective on long-term human exposure to hormone residues in meat from 
treated cattle, please refer to our answer to Question 3 above. 
29. For JECFA's approach for assessing the effects of long-term dietary exposure to hormone 
residues, please see the 52
nd Report of the Joint FAO/WHO Expert Committee on Food Additives 
(WHO Technical Report Series 893, pp. 57-60, 2000) as well as the information provided by 
Dr. Tritscher , JECFA Secretariat, at the Meeting with the Experts held in Geneva on 
27-28 September 2006. 
                                                      
18 See US Rebuttal Submission, fn. 72. WT/DS320/R/Add.3 
Page C-54  
 
  Q5. In relation to para. 8 of the US statement of 3 October please explain if you have now 
made a determination?  If not, what does it me an "being in the process of reviewing"?  What 
are you doing exactly?  Since the EC's risk  assessment dates of 1999 (and reviewed and 
confirmed in 2000 and 2002), how long is your review process going to take?  Is there any information that the US is now missing?  Is th ere any mechanism by which the US will complete 
its review within a reasonable period of time now?   
30. At this stage of the proceedings, it is irre levant whether or not the United States has 
determined that the EC's bans are or not WTO-inc onsistent.  The determination of whether or not the 
EC has brought its measures into conformity with  DSB recommendations and rulings now rests with 
the Panel. 
31. As noted in paragraphs 19-22 a nd Table 1 of the US Rebuttal Submission as well as in the US 
Oral Statement (Legal Issues, paragraphs 9-10) at  the second substantive meeting with the Panel, the 
EC has produced materials related to its measures in a staggered, piecemeal fashion.  The question of 
whether the United States is still "missing" informat ion would perhaps be better suited for the EC, 
particularly in light of the fact that it attempte d to produce evidence in support of its measures as 
recently as the meeting with the scientific experts. 
Q6. The US stated that the risk assessments performed by JECFA must be presumed to be 
in compliance with Article 5.1. of the SPS Agreem ent.  But the risk assessments performed by 
JECFA for these hormones for animal growth promoters do not contain the kind of quantitative or qualitative exposure assessment that Canada and the US criticise the EC for not having done.  
Nevertheless, the US and Canada appear to as sume that JECFA's assessments are consistent 
with Article 5.1. SPS.  Please explain why unde r these circumstances would the EC's risk 
assessment be inconsistent with Article 5.1. of the SPS Agreement.  
 
32. As noted in the US response to EC Questi on 1 (to the United States and Canada) above, 
JECFA completed a quantitative exposure assessment for each of the hormone s at issue in these 
proceedings.  The EC's insistence on highlighting the shortcomings of its own "risk assessment" by 
comparing its efforts to those of JECFA is ther efore perplexing.  The United States would also 
reiterate that there are several additional reasons fo r finding that the EC has failed to conduct a risk 
assessment, as appropriate to the circumstances, for estradiol 17 β.  These include failing to satisfy 
other steps (of the four) for completing a risk  assessment and failing to support the scientific 
conclusions reached in its Opinions on scientific evidence.  The United States has discussed these 
shortcomings in detail in its prev ious submissions to the Panel. 
  WT/DS320/R/Add.3 
 Page C-55 
 
 
  ANNEX C-5 
 
COMMENTS BY THE UNITED STATES ON THE REPLIES  
OF THE EUROPEAN COMMUNITIES TO QUESTIONS 
POSED BY THE PANEL AFTER THE SECOND SUBSTANTIVE MEETING 
 
(31 October 2006) 
  1. The United States appreciates this opportunity to provide comments on the 18 October 2006, 
"Replies to Questions from the Panel after th e Second Substantive Meeting by European 
Communities" ("EC") to the 5 October 2006,  additional questions from the Panel. 
Questions to all the Parties
: 
 
Q1. With reference to the statement by the Euro pean Communities, inter alia in para. 12 of 
the EC reply to Question 3 of the United States, do the parties consider that a Panel is entitled to 
address "systemic claims" or issues related to "systemic obligations" and, if so, to what extent? 
 
2. The EC's response to Question 1  reemphasizes several points raised  in the US response to this 
question.  In our response, we explained how what  the EC refers to as EC's "systemic claims" are 
premised on the EC's view of how the Understanding on Rules and Procedures Governing the 
Settlement of Disputes ("DSU") should be rewritten rather than  grounded in the actual text of the 
DSU.  The EC's response highlights this fact.  For example, the EC argues that "from the EC's point 
of view , the continued application of sancti ons in the face of presumed compliance  and in the absence 
of a compliance review constitutes a violation of a procedural nature, irrespective of the substantive 
requirements of actual compliance ."  (Emphasis added).  This statement is remarkable for several 
reasons.   
3. First, rather than directing the Panel's attention to a specific obligation in the DSU which the 
United States has allegedly breached, the EC describ es a claim based on the "EC's point of view" of 
what the DSU should provide for.  As we have previously shown, the EC's point of view on the DSU does not equate with actual obligations of WTO Members under the DSU.  Second
, the EC relies on 
its theory of "presumed compliance", by which it  believes that through a simple declaration of 
compliance it in turn satisfied its burden of proof  as a complaining party in WTO dispute settlement.  
We have demonstrated in previous submissions th at a declaration of compliance does not amount to 
"presumed compliance" for purposes of dispute settlement.  Third , the EC argues that a US breach of 
these "procedural" or "systemic" obligations shoul d be found "irrespective of the requirements of 
actual compliance."  The EC's argument is untenab le.  A multilateral determination that the EC has 
complied with the Dispute Settlement Body's ("DSB's") recommendations and rulings in the 
Hormones  dispute is an essential prerequisite to any fi nding of a US breach of its obligations under 
the DSU.   
4. Finally, the EC again notes that "several Panels  in the past have already ruled on Article 23 
claims."  The United States has provided detailed arguments relating to these earlier proceedings and 
demonstrated how they are inapt to the situation at hand.1 
Q4. Has the European Communities assessed in a systematic manner the existence and level 
of risks from failure to observe good veterinary practices with respect to the administration of 
oestradiol 17ß as a growth promoting hormone to cattle, in particular in the United States' and 
                                                      
1 See, e.g., US Rebuttal Submission, paras. 6-8, 15-16. WT/DS320/R/Add.3 
Page C-56  
 
  Canada's markets?   If so, please indicate wher e this assessment is to be found in the evidence 
provided to the Panel. 
 
5. The EC's response to Question 4
 is flawed for several reasons.  Upon review of the materials 
put forward by the EC in support of its claim that  good veterinary practices ar e not adhered to in the 
United States, it is clear that the EC has neither de monstrated the existence of  such a risk, nor has it 
assessed the probability of the fa ilure of good veterinary practices in the United States. 
6. As noted by Canada in its response to Question 4 , the EC appears to rely on a draft document 
(Exhibit EC-73) that pur portedly assesses the "risk" arising from abusive use and difficulties of 
control of growth promoting hormones.  The EC h as not clarified the actual status of this draft 
document, and in its 1999 Opinion refers to it onl y briefly.  This draft document and the 1999 and 
2002 Opinions do not assess the risk of failure of cont rols or misuse in the United States for several 
reasons.  We have already highlighted the most significant shortcomings in these materials in our 
previous submissions to the Panel.2 
7. The EC claims to have demonstrated the "existence of a risk " of the failure to satisfy good 
veterinary practices in the United States.  In support of  this claim, the EC cites to several of its misuse 
studies, noting that the cited experiments "were carri ed [out] with hormonal implants that are actually 
licensed for use in the US and Canada and consid ered both their recommended use and situations of 
misuse and/or misuse."  The United States has provided detailed arguments demonstrating that these misuse studies are not representative of the actual use of the six hormones at issue for growth promotion purposes in the United States.  Rather, the studies portray unrealistic dosing scenarios, and 
only then demonstrate violative residue levels when animals are overdosed with numerous implants 
(stacking of implants).  Dr. Boobis
 described these studies and clarified that they are not  
representative of realistic conditio ns nor do they in any way meaningfully assess a risk from misuse.3 
8. Indeed, none of the experts (including Dr. De Brabander ) pointed to any evidence presented 
by the EC of an actual risk from the misuse of the six hormones as growth promoters in cattle in the 
United States.  Nor did any of the experts opine th at the EC had actually assessed in a proper manner 
the likelihood that such a  failure would occur.4 
9. The EC also claims to have undertaken studies or provided evidence demonstrating the "level 
of risk " from "situations of abuse and/or misuse."  However, none of the materials presented by the 
EC provide evidence of a risk of a failure of good veterinary practices, nor do they assess the risk that 
such a failure would occur.  The United States has discussed this gap in the EC's case (including the 
EC's failure to satisfy the requirements of SPS Article 5.2) in detail.5  In particular, we have noted the 
stark absence of any evaluation by the EC of the actual workings of the US food safety system, including oversight by federal inspectors and use of programs such as the National Residue Program 
to monitor the use of growth promoting hormones in  the cattle industry, as would be required by SPS 
Article 5.2.  We will not repeat those arguments here, but will instead highlight a few fundamental 
shortcomings in the EC's "assessment" of th e potential for the failure of controls.   
10. For instance, the EC's arguments relating to th e existence of a risk of multiple dosing, or 
stacking of implants  are misguided.  The EC argues that there are economic incentives to misuse 
growth promoting hormones ( i.e., not abide by on-label instructions).6  However, no such incentives 
                                                      
2 See, e.g., US Rebuttal Submission, Section II.B.4. 
3 See Response of Dr. Boobis to Panel Question 62. 
4 See US Response to Panel Question 4 after the Second Substantive Meeting. 
5 See, e.g., US Rebuttal Submission, Section II.B.4; US Comments on Responses of the Experts, 
paras. 101-112. 
6 See, e.g., Exhibit EC-73, para. 22.  WT/DS320/R/Add.3 
 Page C-57 
 
 
  exist, as individual implants are marketed to provide optimal doses.7  The EC's purported "evidence" 
of the risk for stacking of implants is the Univer sity of Nebraska Beef Cattle Update (Exhibit US-27), 
cited extensively in Exhibit EC-73.8  However, as noted by the Update's author, Dr. Dee Griffin, the 
Nebraska Beef Cattle Update does not  support the conclusion that stac king of implants is either a 
common or recommended practice in the United States.  To the contrary, Dr. Griffin notes: 
Using more than a single implant at the same time has been termed "double 
implanting" or "stacking".  Stacking implan ts, intentionally or unintentionally, has 
been known for decades to cause both gain and feed efficiency to be poorer than 
when FDA approved implants were used in accordance with the FDA approved label . 
... Stacking would cost our beef producers  $50 to $100 (USD) per animal in lower 
carcass value. 
11. In other words, according to Dr. Griffin, "[u] se of FDA approved growth promotants other 
than as labeled is a costly mistake ."  This is why "beef producti on specialists in the USA never 
recommend  simultaneous or double implant administration."9  The EC also notes (in its answer to 
Question 12) that "multiple implanting of anim als with these hormones is recommended by the 
manufacturers."  However, the EC provides no eviden ce to support this statement.  To the contrary, 
FDA approval of veterinary drugs includes the regu lation of manufacturers' la bels and none of the 
labels for the growth promoting hormones at issu e recommend treatment with more than one implant 
at a time.10 
12. The EC also cites to the results of its missions to the United States as "evidence" that there is 
a risk of failure of controls.  The cited materials conclude that hormone implants were being illegally 
used in the US veal industry .11  The EC contends that this illegal use of hormones in the veal industry 
is somehow evidence of a risk of failure of c ontrols in all sectors of beef cattle production.12  
However, growth promoting hormones are not approved in the United States for use in cattle intended 
for the veal industry.  Such use is illegal  and any carcasses or meat products from veal calves treated 
with growth promoting hormones would be deemed to be "adulterated" and prohibited from sale in 
the United States and for export.  Misuse in this sector  of animal agriculture cannot be extrapolated to 
a completely separate sector (feedlot cattle) in which the use of growth promoting hormones is 
approved and a system of controls exists for thei r legal use.  It is telling that the EC relies on 
anecdotal evidence from the veal industry in its atte mpt to cast aspersions on the efficacy of the US 
system of controls in feedlot cattle.  The absence of evidence of misuse in feedlot cattle is testament to 
the effectiveness of controls in that industry.  In any event, the United States took all necessary steps 
to deal with the problem of illegal use of implants in veal calves. 
13. For example, upon discovery of the illegal use of growth promoting hormones in the veal 
industry, the United States Department of Agricu lture's Food Safety and Inspection Service ("FSIS") 
published Notice 31-04: Verification of implant usage in non-ruminating calves (i.e., veal calves), 
                                                      
7 See Letter from Dr. Dee Griffin (Exhibit US-28). 
8 Exhibit EC-73, paras. 22 (fn. 35) and 47 (fn. 63), and fn. 37. 
9 Exhibit US-28 (emphasis added). 
10 For example, the manufacturer's label for Synovex Pl us implants (estradiol plus trenbolone acetate; 
http://www.wyeth.com/pr oducts?product=/wyeth_ht ml/home/products/anima l_health/SYNOVEX%c2%ae%20I
mplants/prescribinginfo.html ) states "DOSAGE: One implant (eight pellets), containing 200 mg of trenbolone 
acetate and 28 mg of estradiol benzoate, is administered to  each steer or heifer by su bcutaneous implantation in 
the middle one-third of the ear" and "DIRECTIONS: Implan t complete contents of one cartridge cell per steer or 
heifer." 
11 See, e.g., Exhibit EC-73, paras. 34-35; see EC Responses to Questions from the Panel After the 
Second Substantive Meeting, Question 4, paras. 15-16 and footnotes 4-5. 
12 See EC Responses to Questions from the Panel After the Second Substantive Meeting, Question 4, 
paras. 15-16 and footnotes 4-5. WT/DS320/R/Add.3 
Page C-58  
 
  providing instructions for inspection program pers onnel to use when they suspect the use of implants 
in non-ruminating calves .  This direction to field personnel ma de clear that any non-ruminating (veal) 
calf presented for slaughter with an implant or on which there is evidence of  implant use was to be 
condemned by USDA inspectors.  USDA inspectors vi sually inspect veal calves (and feedlot cattle) 
for any signs of implant use during ante-mortem (pre-slaughter) and post-m ortem (post-slaughter) 
inspection. 
14. Additionally, on 16 July 2004, the US Food and Drug Administration ("FDA") and FSIS 
jointly issued a letter to the American Veal Indus try, as well as to other trade associations, reiterating 
that the practice of implanting food animals that are to be marked as "veal" with growth promoting 
implants is illegal.  Finally, in order to ensure  that veal illegally treated with growth promoting 
hormones was not entering the US market or expo rted, FSIS included the testing of veal in its 
National Residue Program.  There have been no positive samples found in either 2004 or 2005
, a fact 
that is clear evidence of the effe ctiveness of FSIS/FDA's efforts to eradicate illegal use of hormones in 
this industry.   
15. In sum, upon learning of an illegal use of grow th promoting hormones in the veal industry, 
the FSIS and FDA took the necessary steps to stop this  illegal use.  These efforts are not evidence of a 
failure of controls in the feedlot cattle industry, for which the use of growth promoting hormones is 
approved.  If anything, the anecdotal evidence of th e illegal use of hormones in the US veal industry 
is evidence of the ability of the US food safety system  to isolate and deal with any potential problems 
in order to ensure that meat sold domestica lly, as well as for export, complies with federal 
requirements. 
16. Finally, the United States was surprised and disappointed to see that the EC has misquoted 
US arguments regarding the potential for the failu re of controls.  The EC ascribes the following 
statement to the United States:  "[t]he US  argues that ‘no food safety system is safe ,' implying that the 
other WTO members are obliged to accept the failures of  the US system."  To the contrary, what the 
United States actually said was that "[n]o food safety system is perfect ."  There is a vast difference 
between safety and perfection.  The US food safety system is "safe" and we have demonstrated how 
our system functions effectively and protects consumers.  In making the statement that no system is "perfect" at the second substantive meeting with th e Panel, the United States was simply highlighting 
the fact that the EC has apparently developed a stan dard for good veterinary practices that would not 
tolerate any failures whatsoever – a virtual 100% assu rance that controls would never fail.  The EC's 
position is ironic in light of the fact that the EC cannot control its own black market for the use of 
growth promoting hormones in cattle resulting from its  imposition of a ban on their use.  In other 
words, despite its ban, the EC fails to meet the ve ry standard it has set for good veterinary practices in 
these proceedings.  If this unrealistic and impractical  standard were to be adopted by all WTO or 
Codex members, countries would be able to ban the import of EC meat
 despite the EC's attempt to 
ban the use of growth promoting hormones. 
Q5. In its comments on comments of the United  States and Canada on experts replies to the 
Panel questions (in particular Question 13) , the European Communities indicates that 
oestradiol 17ß might be a "weak genotoxin" (para. 44).  At what doses is genotoxicity observable in vivo?  How are these doses comparable  to those found in meat from cattle treated 
with growth promoting hormones?  How would this assertion affect the identification of adverse 
effects and the evaluation of potential occurren ce of these effects from consumption of meat 
from cattle treated with oestradiol  17ß for growth promotion purposes? 
 
17. In an attempt to justify the dosage of estradiol administered to rats in the study by Cavalieri et 
al. (Exhibit EC-125) as "not massively high", the EC notes in its response to Question 5
 the imminent 
publication of an underlying study (Mailander et al.) which would supply additional information.  The 
cited study has since been published and, contrary to the EC's claims, it does not provide information  WT/DS320/R/Add.3 
 Page C-59 
 
 
  about actual exposure of rats to estradiol following im plantation.  In fact, it is a completely different 
study, in which rats were not treated with estradiol but with estradiol-3,4-quinone, one of the catechol metabolites of estradiol.  As the United States has pointed out in previous submissions, and as was 
confirmed by Dr. Boobis at the meeting with the experts, results obtained with the catechol 
metabolites of estradiol cannot be taken as eviden ce that estradiol will have the same effect in vivo  
(because it has not been established th at the catechol metabolites form in vivo  at concentrations high 
enough to cause deleterious effects).  Therefore, the report referred to by the EC in its response to 
Question 5
 (Mailander et al.) provides no additional information re levant to the study by Cavalieri et 
al. (Exhibit EC-125).  The United States reiterates its criticisms of the Cavalieri et al. study, in which 
the dose of estradiol was so high that it resulted in the death of nearly one half of the rats.  Such a 
dose is not relevant to the relatively minuscule am ounts of estradiol found in beef from cattle treated 
with estradiol 17 β for growth promotion purposes. 
Questions to the European Communities : 
 
Q6. Should the Panel agree with the European Communities' main claim that the United 
States and Canada have breached Article 23 of  DSU read together with Articles 21.5 and 22.8, 
what would be the consequences of such a conc lusion for the United States and Canada?  More 
particularly, would the United States and Canada:   (a) be expected to withdraw the suspensions of concessions or other obligations or 
suspend their application? 
 
 (b) be expected to initiate an Article 21.5 procedure against the EC? or   (c) would they be expected to do both?  
(Please note that the Panel is fully aware of its obligations under Article 19 DSU)  
 
18. As an initial matter, the United States is struck by  the fact that the EC purports to be able to 
respond to the Panel's question wit hout knowing what measure would be  found inconsistent or what 
the precise basis for the finding of inconsistency would be under the hypothetical.  The Panel in the 
question itself highlighted Article 19 of the DSU, which specifies the Panel's recommendation in the 
event of a finding of an inconsistency, and the EC  is aware that the Member concerned retains the 
discretion on how to implement any such recommendation.   
19. Consequently, the EC's response to Question 6
 is rather revealing.  First, the EC response is a 
telling snapshot of its overall failure to demonstrate that the United States has breached its obligations 
under the DSU by continuing to suspend concessions to  the EC despite the EC's unilateral declaration 
of compliance.  As a general matter, if the US suspension of concessions were a measure in breach of 
its WTO obligations, the United States would not be ab le to maintain them.  However, the EC's reply 
indicates that the United States would be free to c ontinue to apply the susp ension of concessions and 
related obligations pending the outco me of an Article 21.5 proceeding.13  The EC thus admits that 
even under its own theory, the US suspension of c oncessions is not inconsistent with the DSU.  
Furthermore, the EC thus admits that the susp ension of concessions is not related to any "new" 
determination by the United States, in breach of Article 23 of the DSU, that the EC measures taken to 
comply are inconsistent with the covered agreements. 
20. Second, the EC's reply confirms that the United States is not in breach of Article 21.5 of the 
DSU.  For example, the EC argues that "there ca n be no doubt that the United States and Canada are 
                                                      
13 See EC Responses to Questions from the Panel After the Second Substantive Meeting (Question 4), 
paras. 15-16. WT/DS320/R/Add.3 
Page C-60  
 
  under an obligation to withdraw the suspension of  concessions . . . if they do not initiate a 21.5 
proceeding."  However, to date, the EC has failed to identify any specific obligation in the text of 
Article 21.5 that has allegedly been breached by th e United States.  The United States has noted this 
failure on several occasions.
14  It is therefore remarkable that the EC avers that "there can be no doubt 
that [the United States] [is] under an obligation to initiate a 21.5 proceeding."  Rather than finding a 
basis for its claim in the text of Article 21.5, the EC's claim of a US breach is simply a product of its 
so-called "systemic" claims of a breach of the DSU which find no basis in the actual text of the DSU.
15 
21. As we have demonstrated, the United States would only be obligated to withdraw its 
application of the suspension of concessions upon a demonstration by the EC (as the complaining 
party) that it had satisfied one of the three cond itions of DSU Article 22.8.  The EC has failed to 
demonstrate that it has satisfied any of these conditions. 
Q8. The Panel understands that the European Communities initiated risk assessments with 
respect to all six hormones at issue (see, e. g., Directive 2003/74/EC, third  introductory 
paragraph). 
 
 (a) Could the European Communities confir m, with respect to oestradiol 17 ß and 
in light of its statement in para. 192 of its rebuttal and its comments on Question 
14 of the Panel to the experts, whether:  (i) it proceeded through the four step s of risk assessment identified by 
Codex; or 
 
(ii) could have proceeded through the fo ur steps but decided not to do so in 
light of its findings on genotoxicity of oestradiol 17 ß? 
 
 (b) Could the European Communities confirm,  with respect to each of the other five 
hormones at issue, at what stage(s) of its risk assessment it considered that relevant scientific evidence was insufficient  and decided to provisionally ban the 
importation of meat treated with those hormones on the basis of available pertinent information.   
 22. In its response to Question 8
, the EC again declares that "beyond doubt" it has "completed the 
four steps [of risk assessment]."16  The EC also comments that "[t]he defending parties may disagree, 
but they cannot credibly argue that the European Communities has not completed the four steps of the 
risk assessment."  Neither of these statements is grounded in the reality of this dispute, which includes 
consultation with scientific experts on the specific qu estion of whether the EC has satisfied these very 
same four steps in its risk assessment for estradiol 17 β.  Not only can the United States "credibly 
                                                      
14 See, e.g., US First Written Submission, Section IV.D.3 (a)(iii) (demonstrating, among other things, 
that Article 21.5 sets no deadline by which a party must  seek recourse to dispute settlement; Article 21.5 does 
not obligate the original complaining Member to initiate a compliance proceeding; and Compliance with Article 21.5 may be achieved through recourse to other provisions of the DSU). 
15 See US First Written Submission, Section IV.D.3(a)( iii); US Answers to Pane l Questions after the 
First Substantive Meeting, paras. 11, 16-17, 38-40; US Rebuttal Submission, paras. 5-12. 
16 Note that the EC apparently claims in paragraph 35 that it has conducted a risk assessment "for all 
these hormones."  To date, the United States was not aware that the EC claimed to have satisfied its obligations 
under SPS Article 5.1 for the five provisionally banned hormones.  WT/DS320/R/Add.3 
 Page C-61 
 
 
  argue" that the EC has failed to satisfy the four st eps, the Panel's scientific experts have confirmed 
that the EC has not satisfied each of the four steps.17   
23. In its attempt to demonstrate that it has completed a risk assessment for estradiol, the EC cites 
to section 4.1.5 of its 1999 Opinion in which it c oncludes that "the FDA's acceptable daily intake 
(102 ng/per person/day) could exceed the daily pr oduction rate of oestradiol by 1,700 fold (of 
pre-pubertal children)."  Taking the low bioavaila bility of estradiol into account and assuming the 
metabolic clearance rate of estradiol  in children is one half that of  adults, the EC then adjusts its 
"quantitative" estimate and concludes that "the FD A acceptable daily intake could still be 85 fold too 
high."  These statements are incorrect and unsup ported by scientific evidence or mathematical 
analysis.   
24. First, the FDA has never set an acceptable daily intake (ADI) for estradiol.  Instead, as 
explained in FDA Guidance for Industry No. 3,18 for endogenous sex steroids like estradiol, FDA sets 
a permitted increased exposure based on daily producti on of each steroid in the segment of the human 
population that synthesizes the least amount (prepubertal boys in the case of estradiol).   
25. Second, the EC's exposure calculations rely on results of the Klein assay (1994), which 
indicated that blood levels of estradiol in prep ubertal boys were 100-fold lower than previously 
reported.  The United States has demonstrated th e flaws of the Klein assay on several occasions19 and 
the validity of this assay was discussed in detail at the meeting with the experts.  While there seemed 
to be general agreement among the experts that blood levels of estradiol in prepubertal children may 
be lower than previously believed, the EC has not  established the magnitude of the difference, and 
there was certainly no agreement among the experts on the 100-fold difference cited by the EC.  The 
EC itself recognized the inaccuracy of the Klein ass ay results in its Comments on the Replies by the 
Panel Experts (Question 38).20  Equally as speculative in the EC's exposure calculation is the 
assumption that the metabolic clearance rate of estradio l in children is one-half that of adults.  No 
scientific data have been presented to support this assumption.   
26. Third, the EC's exposure calculations are flaw ed because they use U. S.-permitted incremental 
increases21 to estimate actual daily exposure to est radiol from eating beef.  These permitted 
incremental increases are levels of residues that are permitted in excess of increments above the 
concentrations of estradiol naturally present in  untreated animals; they do not represent actual 
amounts of estradiol found in edible tissues.  Theref ore, use of these numbers to derive an "acceptable 
daily intake" of 102 ng/person/day is factually incorrect.  As the United States has stated previously, a more accurate (and still very conservative) estimate of excess daily intake of total estrogens from 
eating beef from treated animals – 30-50 ng/person/day, i.e., one third to one half of the EC's 
                                                     
 
17 US Comments on the Responses of the Scientific Experts, paras. 18-32; see also  US Oral Statement 
(Expert Issues) at the Second Substantive Meeting, paras. 18-20. 
18 FDA Guidance for Industry No. 3: General principles for evaluating the safety of compounds used in 
food-producing animals.  http://w ww.fda.gov/cvm/Guidance/GFI003.pdf . 
19 See, e.g., US First Written Submission, paras. 84 (a nd footnote 92) and 159; US Rebuttal 
Submission, para. 44. 
20 Responding to Dr. Boobis' criticisms of the Klein a ssay, the EC stated "[t]he real values for serum 
17β -oestradiol in prepubertal children still remain to be properly documented." 
21 For veterinary drugs that occur naturally in animals, like estradiol, FDA does not set tolerances or 
maximum residue limits.  Instead, FDA establishes levels of  residues that are permitted in excess of increments 
above the concentrations of estradiol naturally present in untreated animals.  See 21 CFR § 556.240. WT/DS320/R/Add.3 
Page C-62  
 
  erroneous estimate of 102 ng/pe rson/day – can be found in the residue monograph from the 52nd 
JECFA meeting.
22 
27. In other words, the paragraph cited by the EC  is replete with inaccuracies and conclusions 
that are unsupported by scientific evidence, and do es not support the conclusion that the EC has, in 
fact, completed a risk assessment for estradiol.  In any event, there are numerous other reasons for 
concluding that the EC has failed to do so.  We have highlighted these in our previous submissions 
and several of these shortcomings have been discussed by the scientific experts. 
Q9. Can the European Communities explain the meaning it gives to the term "mere doubt" 
in para. 181 of the EC second submission (US case)? 
 
28. In its response to Question 9 , the EC defines "mere doubt" as "not any kind of doubt but 
doubt that is scientifically established."  The United St ates has not been able to locate, let alone find a 
definition of, the term "mere doubt" in any scientific  materials, the SPS Agreement, or WTO dispute 
panel or Appellate Body guidance.  The EC appears to have invented this term during the course of 
these proceedings, and now hopes to have its measures an alyzed against the backdrop of this fictitious 
(and self-defined) standard.  This is an untenable position and should be disregarded as such.  In any 
event, pursuant to the EC's own definition, a "mere doubt" must be a "scientifically justified" doubt.  The EC has failed to present any evidence that there is scientifically-justified doubt about the safety of 
any of the six hormones when used for growth pr omotion purposes in cattle.  Therefore, the EC has 
failed to satisfy its own standard. 
Q11. What is meant by no "additive risk"?   Please explain to which "risks" these are 
"additive".  
29. In its response to Question 11
, the EC states that "[i]t is scientifically not disputed (in this 
case even by the defending parties) that life-time  exposure of humans to the levels of endogenous 
production of oestrogen (and in particular to oestradiol-17 β and its metabolites) and, most likely, to 
the other two natural hormones (testosterone and pr ogesterone) are sufficient to cause and/or promote 
cancer in some individuals."  To the contrary, in  the course of these proceedings the United States has 
never argued that endogenous horm ones can cause or promote cancer.  Nor has the EC presented any 
convincing evidence that this is so.  It is overl y simplistic and unscientific to say that endogenous 
hormones are "sufficient" to cause cancer , and the EC's response to Question 11  appears to be nothing 
more than an attempt to attribute statements to the United States and Canada that they have never 
made.  Furthermore, the EC has failed to present ev idence that there is any "additive" risk from the 
consumption of meat from cattle treated with any of  the six hormones for growth promotion purposes. 
30. For example, the EC relies on the 10th and 11th Reports on Carcinogens  in support of its 
contention that consumption of estradiol residues in  meat from treated cattle will be "additive" to the 
risk of cancer from existing (endogenous) exposure and exposure from naturally-occurring sources of 
estradiol.  However, the EC is incorrect when it conc ludes that veterinary use of steroidal estrogens in 
food animals can increase estrogens in edible tissues to  levels "in general substantially higher than the 
normal (endogenously produced) levels ."  As demonstrated by th e United States in response to 
Question 1  from the EC following the Second Substantive Meeting, the EC's own exhibits (Exhibits 
EC-34 and 51A) clearly indicate that the increase in estradiol residues in muscle of treated cattle is 
usually small (1.1 to 2.3-fold) and that it was onl y detectable in some of the treated animals.  
Moreover, these increases result in residue levels that are within the range of naturally-occurring 
                                                      
22 See "Evaluation of certain veterinary drug residues  in food", Fifty-Second Report of the Joint 
FAO/WHO Expert Committee on Food Additives, WHO T echnical Report Series: 893 (2000) ("52nd JECFA 
Report").  FAO Food and Nutrition Paper 41/12.  (Exhi bit US-5).  www.fao.org/a g/agn/jecfa/archive_en.stm . 
  WT/DS320/R/Add.3 
 Page C-63 
 
 
  concentrations.  Therefore, the statement that leve ls of estradiol in meat from treated cattle are 
"substantially higher than the normal (endogeno usly produced) levels" is grossly inaccurate. 
31. Rather than citing to Exhibits EC-34 and 51A (som e of the EC's more recent data that show a 
small and in certain cases undetectable increase in residue  levels), the EC refers instead to Table 2 of 
its 1999 Opinion in its attempt to show that the resi due level increase is "substantial."  However, some 
of the data in Table 2 refer to veal calves and bu lls, neither of which are relevant to this dispute.23  
Further, neither the source nor the date of these data  is indicated in Table 2.  It is therefore not 
possible to evaluate the validity of these data or , more importantly, whether they accurately represent 
the average increase in estradiol  residues in treated cattle (ver sus the most extreme cases). 
Q12. A 1999 Report of the Committee for Veteri nary Medicinal Products of the European 
Communities refers to the low bioavailability of o estradiol 17ß.  How is this finding reconciled 
with references to bioavailability in the SCVPH Opinion?  (please refer to comments by the 
parties on the Panel's Question 43 to experts) 
 
32. The EC disagrees with the US statement that to overcome the low bioavailability of estradiol, 
very large amounts of the hormone must be administer ed orally.  However, rather than citing to any 
number of review articles available on this subject,24 the EC relies instead on a single pilot study in 
girls with central precocious puberty (Exhibit EC-99).  In this study, girls with central precocious 
puberty were administered estradiol orally to overcome the growth inhibition associated with GnRH agonist therapy.  The authors determined that a "mini-dose" of 8 micrograms (versus the adult dose of 625 micrograms) of conjugate d equine estrogen was sufficient to s timulate growth.  The United States 
does not disagree that 8 micrograms is a low dose compared to 625 micrograms, nor does it disagree 
that this dose was orally bioactive in these patients.  However, the relevant fact is that 8 micrograms 
of estrogen is exponentially greater
 than the amount of estradiol or its metabolites found in a serving 
of beef from treated cattle.25 
33. In addition, the EC states that JECFA, and by  extension the 1999 CVMP Opinion, considered 
"only some of the residues of oestradiol-17 β in meat; in particular, they have not considered the 
lipoidal (fatty acid) esters- nor estrone residues."  This statement is, at least in part, factually incorrect.  The residue monograph of the 52nd JECFA Meeting c ontains 23 tables describing concentrations of 
estrone in edible tissues from both untreated and treated cattle.  Theoretical daily intakes were 
calculated and clearly presented for estrone alone, est radiol alone, and estrone and estradiol together 
("total estrogens"). 
                                                     
 
23 The use of growth-promoting hormones in veal calves is not approved in the United States.  Relative 
to all beef cattle, the United States slaughters very few bulls for meat and there is no reason to implant these 
animals with hormones to promote growth.  Ironically, in contrast, the EC regularly slaughters bulls for human 
consumption, the meat from which may have endogenous testosterone levels much greater than that from steers (castrated male cattle) to which hormones have been ad ministered for growth promotion purposes according to 
good veterinary practice.  See US First Written Submission, para. 52, citing Eurostat data regarding meat 
production in the EU-15 (in which meat category v12 (bulls) comprises approximately 29.5%
 of total cattle 
slaughtered in the region).  (Exhibit US-8).  In contrast , less than 2% of cattle slaughtered in the US are bulls 
while approximately 50% are steer s (castrated male cattle).   
24 For example, Fotherby K.  Bioavailability of orally administered sex steroids used in oral 
contraception and hormone replacement therap y.  Contraception 1996; 54: 59-69. 
25 The difference between the dose of estrogen used in Exhibit EC-99 and the amount in beef is 
difficult to quantify precisely because co njugated equine estrogen, not estradio l, was used in the study.  Equine 
estrogens are mixtures of several estr ogen sulphates which, unlike estradio l, are water soluble.  Therefore, 
conjugated equine estrogens are believed to have a greater oral bioavailability than estradiol.  See footnote 19 
above (Fotherby). WT/DS320/R/Add.3 
Page C-64  
 
  34. Further, data in Exhibit EC-49 indicate th at treatment of cattle with a single implant 
containing estradiol may result in increased concentra tions of lipoidal estrogens in fat and liver, but 
not muscle or kidney; however, the data are difficu lt to interpret.   In Exhibit EC-51A, the authors 
concluded that "estradiol-17 β-17-esters assayed at significant concentrations in fat from 5 ppt in 
control to more than 100 ppt in 4-doses (sic) implan ted animals.  Curiously, mean concentrations of 
estradiol-17 β-17-esters in liver were not significantly modified by the implantation treatment."  These 
observations indicate that lipoidal estrogens are releva nt only for fat and not the other edible tissues.  
Most importantly, the EC has not provided any sci entific evidence indicating that consumption of 
lipoidal estrogens in meat from treated cattle resu lts in a health risk to the human consumer. 
Q16. Please explain the reason for the differences between the "list of the 17 studies" that was 
appended to the 2002 Opinion and the one that was provided to the Panel.  (please see 
paragraph 20 of the United States' Rebuttal Submission and its Table 1) 
 
35. The United States notes that the EC agrees that the two lists setting out its "17 Studies" are 
substantively different.  The EC describes this di fference as the result of "further publications of 
partial aspects of the studies."  Not only is this excu se unclear, it is patently insufficient.  Either the 
EC provided the United States with the necessary ma terials at the outset of these proceedings (when 
the United States filed its request under Article 5.8 of  the SPS Agreement), or it did not.  The EC's 
response to Question 16
 makes clear that the list of studies provided to the United States at that time 
(i.e., the list attached to the 2002 Opinion at the outset  of these proceedings) is different than the list 
put forward by the EC in the course of these proceedings. 
36. Also, the United States notes that the EC relies heavily on its Exhibit EC-65 (a book of 
studies) in support of its argument that the Unite d States was in possession of all of the necessary 
materials comprising the "17 Studies."  However, Exhibit EC-65, along with numerous other scientific 
documents, was only filed by the EC with its Rebuttal Submission (in other words, at the same time as 
the US Rebuttal Submission and Table 1 thereto).  In  addition, there are still gaps in the EC's attempt 
to reconcile its production of evidence with Table 1 to the US Rebuttal Submission.  For example, 
regarding Study Ten , the EC notes that "[t]his study was not yet published as research continued after 
2002.  It appears that it has not been published yet."  ( See Exhibit EC-129). 
 
__________