CANADA – CONTINUED SUSPENSION OF OBLIGATIONS IN THE EC – HORMONES DISPUTE
Document: Report of the Panel Addendum
Date: 31 March 2008
Document codes: WT/DS321/R/Add.3; WT/DS321/R.
Complainant: EU
Respondent: Canada
Third parties: Australia, Brazil, China, Taiwan, India, Mexico, New Zealand, Norway, U.S.
Dispute stage: Appellate Body
Agreements cited: Art. I, II  GATT 1994Art. 3.7, 22, 23.1, 23.2, 21.5  Dispute Settlement Understanding (DSU)

CANADA – 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
 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

ANNEX C

REPLIES OF THE PARTIES TO QUESTIONS 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 Canada to questi ons posed by the Panel after the second
substantive meeting (18 October 2006)
C-40
Annex C-4 Replies of Canada to questions posed by the European
Communities after the second substantive meeting
(18 October 2006)
C-47
Annex C-5 Comments by Canada on the replies of the European Communities
to questions posed by the Panel after the second substantive
meeting (31 October 2006)
C-53

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 substantive 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").

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 replied to this question in detail in its reply to Question 16 of
the Panel (see paras. 79ff) and in paras. 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 stated 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 never 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 time. 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.

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 accessible 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 17β 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-17β 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 the 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 undertaken 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 above EX Exhibits has also examined oestradiol-17β.

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 17β 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 implants 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.

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 conservative 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 micrograms 7 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 children 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 th e doses often used in toxicological studies of
chemicals, where the lowest doses could be 2-3 orders 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 m ean 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 during 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.

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.

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 application 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 fully 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.

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 17β?
(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.

but they cannot credibly argue that the European Communities has not completed the four steps of the
risk assessment.
36. For oestradiol-17β
, 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 Communities 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 17β-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.

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 preamble 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 available 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".

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 relevant 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 assessment 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.

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-17β 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 SCVPH opinion is based on recent studies: see, 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.

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-17β, and is not based on new 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-17β 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 commented 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-17β 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

"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 weak er 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-17β.
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).

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 that 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 Regulation (EC) 466/2001, O.J. L 77, 16.3.2001, p. 1.

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 suspected 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.

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/.

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 the 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 11 th

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. Herman, JECFA Secretariat, dated 23 December 1998)

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 substance in the call for data for the meeting
to ensure that all interested parties 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.net/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_guidelines%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.

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 (point 4), the JECFA Secretariat 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 remained that excess intake of hormone residues and their metabolites,
endocrine, developmental, immunological, 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 66 th 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.

83. The following were the EC written comments on the matter delivered in time before the
meeting and submitted to everybody 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 provision 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 Health – 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 scientific 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 62 nd

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 20022). 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

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-evaluation 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.

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 when 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 – through 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 obligations 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.

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 prospect 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 assessment 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.

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.

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 they 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 17β 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 reply 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 materials 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.

• 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 level of implant growth promotant above the
effective growth stimulating level until 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

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 visit 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 control 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 "administrative 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.

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 least 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 author 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."

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 would 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-17β 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 exceed 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 h ealth are likely to occur. 10 Unlike the US argument (and the reply of
Dr. Boobis to question 48), the EC has perfo rmed 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 assessmen t 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 17β 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-17β 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."

inconsistent with the data provided by the EC, ba sed on a substantial literature 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-17β 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 Agreement, 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 regard to all substances but oestradiol-17β, 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 metabolites 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".

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 triggers 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 (including 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-17β 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 once 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-17β.
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.

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 and 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,

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-response 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 exposure 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 th e 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 meat from animals treated with these hormones
for growth promotion. The same applies to the comment by Canada (at para. 9 of its reply).
37. Furthermore, the US gives credit to the statem ent 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 reply) that the statements by Dr. Sippel and
Dr. Cogliano "must yield to the expert advice of those who are qualified to evaluate actual
carcinogenic potential at low doses". However, Canada forgets that both Dr. Boisseau and Dr. Boobis
are the same persons who have participated in th e elaboration of the JECFA report and, moreover,
Dr. Boisseau admitted that he has never carried any toxicological 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

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 stated 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 implies 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.

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 evidence 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 possible, 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

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 going 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 defending 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

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 Canada 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 established 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 sacrifice its high level of health protection.

ANNEX C-3

REPLIES OF CANADA 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 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. The Panel has been asked to determine whethe r Canada and the United States acted contrary
to Articles 23.1 and 22.8 of the DSU by continuing to suspend concessions after the EC claimed
compliance. Part of such a determination is a dete rmination of whether the EC's measure originally
found to be non-compliant has been "removed". The EC's distinction between its "systemic claims"
and its "direct claims" reflects the distinction between its claim that its measure should be presumed to
have been "removed" (i.e., brought into compliance) and its subsequent arguments that it has actually
brought its measure into compliance. By addressing whether the EC's unilateral claim of compliance
is sufficient to satisfy Article 22.8, the Panel will be addressing the EC's so-called "systemic claims".
Canada has already argued in its various submis sions that the EC's unilateral declaration of
compliance is insufficient to satisfy the requirements of Article 22.8, and therefore there is no merit to
the EC's "systemic claims". It is only by having the Panel confirm that it has, in fact, complied (i.e., its
"direct claims") that the EC can prevail on its claims against Canada and the United States.
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?

2. Canada agrees with the statement by the Un ited States in paragraph 27 of its Rebuttal
Submission that, because the EC's ban fails to meet the requirements of Article 5.7, the EC is not
exempt from satisfying its obligations under Article 2.2 and Article 5.1.
3. However, Canada does not read this statemen t as implying that a failure to comply with
Article 5.7 "automatically" leads to a breach of Artic les 2.2 and 5.1, in a legal causative sense. As the
Appellate Body in Japan – Agricultural Products II stated, Article 5.7 operates as a qualified
exemption from the obligation under Article 2.2 not to maintain SPS measures without sufficient
scientific evidence.
1 A failure to satisfy the requirements of Article 5.7 technically means that the
qualified exemption from the obligations in Article 2.2 does not apply.
4. That being said, if a Member claims that its SPS measure is consistent with Article 5.7 on the
basis that relevant scientific ev idence is insufficient to conduct a risk assessment, the Member is
implicitly acknowledging that its SPS measure is ma intained without suffici ent scientific evidence.
Were it otherwise and sufficient scientific evidence ex ists to maintain an SPS measure, then it follows
that the relevant scientific evidence is sufficient to perform a risk assessment and Article 5.7 would
not apply. If, having claimed consistency with Artic le 5.7, a Member fails to satisfy the first and
second requirements of Article 5.7, it is difficult to envision how the Member can also comply with its

1 Japan – Measures Affecting Agricultural Products , Report of the Appellate Body, WT/DS76/AB/R,
adopted March 19, 1999, at para. 82.

obligations of Article 2.2. In such circumstances, the failure to comply with the requirements of
Article 5.7 would imply a breach of Article 2.2.
5. Similarly, if a Member claims that relevant scientific evidence is insu fficient to enable the
performance of a risk assessment, the Member is, in e ffect, conceding that it is unable to comply with
Article 5.1. If the Member fails to satisfy the requi rements of Article 5.7, then the Member will have,
in effect, breached Article 5.1 with no valid justification.
6. In this case, it is not necessary for the Pane l to determine the precise legal relationship
between Articles 2.2, 5.1 and 5.7. Here, the Panel's ta sk is straightforward. The EC claims that it now
complies with the recommendations and rulings of th e DSB. In terms of the five provisionally banned
hormones, the EC seeks to demonstrate compliance with the recommendations and rulings by
showing that its ban is consistent w ith Article 5.7, not Article 5.1. By resorting to Article 5.7, the EC
acknowledges that its provisional measures are no t based on a risk assessment as required by
Article 5.1, but claims that its measure nonetheless complies with the DSB recommendations and
rulings because it is consistent with Article 5.7. Thus, consistency with Article 5.7 acts as an
exemption from the obligation in Article 5.1. Howeve r, as the experts advised, the relevant scientific
evidence is sufficient to enable th e performance of a risk assessment. As a result, the EC is unable to
satisfy the first requirement of Article 5.7 and therefore is not exempt from complying with
Article 5.1. As the EC has conceded that its measu re is not based on a risk assessment by claiming
consistency with Article 5.7, the EC is unable to demonstrate compliance with the recommendations
and rulings of the DSB.
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".

7. The 1999 Opinion was made available to Canada and transmitted by letter of May 1, 1999
from the European Commission.
8. Canada is unable to indicate when exactly the 2000 Opinion became available to it.
9. It is clear from e-mail correspondence betwee n the Canadian Mission to the EC and the
European Commission in April 2002 that the 2002 Opin ion was available to Canada shortly after its
adoption.
10. Following the release of the 2002 Opinion, Canada , through its own efforts, obtained copies
of most of the published papers that were based on the 17 Studies and that were publicly available in
2002 or became publicly available relatively soon thereafter.
11. As part of the EC's response to Panel Ques tion 16 (following the First Substantive Meeting),
on October 3, 2005, the EC filed as Exhibits a larg e number of documents that were part of the 17
Studies. These EC Exhibits were subsequently renu mbered and are now known as Exhibits EC-7A to
EC-60 (inclusive). Of these Exhibits, the following were not published and therefore not available to
Canada before October 3, 2005: EC-7A, 7B, 10, 29, 30A, 30B, 30C, 50, 51A, 51B, 51C, 52A, 52B,
53, 54, 55A, 55B, 56, 57, 58, 59 and 60. Exhibits EC-39, 40 and 41 were published in 2004 but only
came into Canada's possession when filed as Exhi bits by the EC in October 2005. Canada has

nonetheless reason to believe that the material avai lable to it to date still does not constitute the
complete record of the 17 Studies.
2
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 17β 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.

12. The EC has not assessed, let alone in a systema tic manner, the existence and level of risks
from failure to observe good veterina ry practices with respect to the administration of oestradiol 17 β
as a growth-promoting hormone to cattle in Canada. In its Rebuttal Submission, at paragraphs 107 to
109, the EC appears to claim that the SCVPH asses sed the risks associated w ith misuse and abuse of
growth-promoting hormones and refers in its footno tes to various documents that purportedly support
this claim. However, as Canada explained in its Comments on the EC Comments on the Answers by
the Experts
3 and in Canada's Oral Statement at the Second Substantive Meeting (Legal Arguments) 4,
none of these documents evaluates the potential adve rse effects from misuse and abuse in Canada,
taking into consideration the factors set out in Article 5.2 of the SPS Agreement. Accordingly, the EC
has failed to perform a risk assessment appropriate to the circumstances in relation to alleged misuse
and abuse in Canada.
13. In paragraph 108 of its Second Written Submission, the EC refers in a footnote to a "draft"
"working document" that purports to be an assessment of risks arising from abusive use and
difficulties of control of hormonal growth promoters.5 The EC has failed to clarify the actual status of
this "draft" "working document". The 1999 SCVPH Opinion only briefly refers to this document in its
cursory analysis of exposure considerations in situations of misuse.6 Notably, the EC failed to disclose
this document in its response to Panel Question 16 (following the First Substantive Meeting), which
requested that the EC identify all documents that comprise its risk assessment of the hormones in
question. Indeed, to Canada's knowledge, the first time this "draft" "working document" was made
public was in the EC's Second Written Submission, well after the EC claimed that Canada was in
breach of its WTO obligations for refusing to accep t the EC's unsubstantiated assertion that it had
complied with the recommendations and rulings of the DSU – hardly consistent with the EC's claim
that it has been fully transparent in relation to its data and scientific analysis.

2 For example, Canada notes that under the rubric of Study 6 ("Analysis of 500 Samples for the
Presence of Growth Promoters") the EC filed only Exhibit EC-19, which is a very short article by Dr. Rainer W.
Stephany, entitled "Hormones found in Meat Samples from Regular Controls within the European Union and
from US Imports". By comparison, another article by Dr. Stephany, entitled "Hormones in meat: different
approaches in the EU and in the USA", which was filed by Canada as Exhibit CDA-12, refers in references 25
and 26 to interim reports by Dr. Stephany and Dr. F. André that are apparently part of Study 6. Reference 25
reads as follows: "Stephany RW, André F. (rapporteurs) Results of "hormone" residue analyses of bovine meat
and liver imported into the EU and originating from th e USA "Hormone Free Cattle Program" [,] First Interim
Report, CRL document 389002 091, May 1999, Bilthoven, The Netherlands, 34 pp." Reference 26 reads as
follows: "Stephany RW, André F. (rapporteurs) Results of "hormone" residue analyses of bovine meat and liver
originating from the USA domestic market, Second Interim Report, CRL document 389002 093, June 2000,
Bilthoven, The Netherlands, 38 pp." This suggests that Exhibit EC-19 does not present the complete results of
Study 6.
3 Canada's Comments on EC Comments, July 12, 2006, at paras. 94-108.
4 Canada Oral Statement, October 2 and 3, 2006, at paras. 71-78.
5 EC Second Written Submission, fn. 81, Exhibit EC-73 (formerly EC-17).
6 1999 SCVPH Opinion, at pp. 30-32 (Exhibit CDA-2). The "draft" "working document" is not
attached as an Annex to the SCVPH Opinion.

14. In any event, Canada has already explained th e flaws and deficiencies in the EC's purported
assessment of risks of misuse. It is sufficient here to reiterate the most glaring deficiencies in its
purported risk assessment.
15. The EC claims that the SCVPH Opinion's findings are "based on realistic conditions of use". 7
This leads the EC to conclude that "abuses or misuses of these hormones … are not uncommon" in
Canada and the United States. 8 This claim is simply absurd. Not only does the EC fail to present any
evidence of misuse and abuse in the feedlot beef industry, for which the hormones have been
approved, the EC actually ignores evidence that confli cts with its desired conclusion. The findings are
in fact based on erroneous assumptions and imagined worst-case scenarios that bear no relationship to
realistic conditions of use. Here are a few examples:
16. First, the EC assumes that there are economic incentives to misuse approved products. As
Canada has explained, this is simply not the case. Implants have been calibrated to provide an optimal
dose.9 Overdosing has a negative impact on growth pe rformance, marbling of fat and carcass grade
quality and likely increases negative behaviours in animals. Contrary to the EC's self-serving
assumptions, cattle farmers in North America, where growth promoters are legal, stand to lose money
from misusing these hormones.
17. Second, the EC relies exclusively on the repor ted misuse of trenbolone acetate in the veal
industry in Canada in the late 1990s to support its cl aim that there is more ge neral misuse and abuse.
However, growth-promoting hormone s have never been approved fo r the veal industry, a small
specialty industry in Canada. Consequently, any mi suse that has occurred in the veal industry cannot
be extrapolated to those sectors of the industr y for which growth-promoting hormones have been
approved (i.e., feedlot beef cattle). As is the case in Europe, where a product is not approved for use,
there may be economic incentives for operators to engage in illegal use, because any use is prohibited.
But this does not imply that misuse and abuse o ccurs where hormones have been approved for use
under specific conditions. Tellingly, the EC fails to present any evidence that approved implants are
being improperly administered in the beef industry in Canada. Moreover, in its analysis of reported
misuse of trenbolone acetate in the veal industry, the EC conveniently ignores relevant residue testing
data. These data show that, even in the limited nu mber of cases where a residue was detected, the
amount of residue for the most part never exceed ed the MRL. Consequently, even where misuse
occurred, residues were within the safe thresholds established by Codex.
18. Third, the SCVPH speculates about the possibility of misplaced implants. However, the
labelled instructions for the administration of horm ones are clear: the implants containing the slow-
release pellets are to be injected subcutaneously in the animal's ear and the ear is to be removed from
the food chain at slaughter. Out of the literally millions of cattle slaughtered every year in Canada, the
only evidence presented to support th e speculative claims of misplacing implants is a single finding
reported by Canadian authorities back in 1998 of trenbolone residues in veal calves which were
attributed to either "misplaced implants or fro m illegal treatment via intramuscular injection."
10 As is
the case in Europe, where a product is not approved for use, operators engaging in illegal use have
incentives to use clandestine methods of administrati on, such as intramuscular injections, in order to

7 EC Second Written Submission, at para. 108.
8 Ibid.
9 See letter from Dr. Dee Griffin, University of Nebraska, to Dr. Adele Turzillo, FDA Center for
Veterinary Medicine, October 20, 2005 (Exhibit US-28).
10 European Commission, Assessment of Risks of horm onal growth promoters in cattle with respect to
risks arising from abusive use and difficulties of control, Draft Report by special working group of external
private experts and European Commission officials, Brussels, 29 April 1999, at p. 10 (Exhibit EC-73, formerly
EC-17).

avoid detection. There is no reason to use such cl andestine methods if the product is approved for use
and used properly.
19. Fourth, the EC selectively ignores evidence that contradicts its fundamental premise. The EC
fails to take into account what is arguably the mo st pertinent and direct evidence concerning misuse
and abuse of hormones in Canada, namely, the results of on-going random and suspect testing
conducted under Canada's official National Chemical Residue Monitoring Program. The results of this
monitoring program are provided annually to authorities in EC Member States. That the EC has
ignored this evidence is not surprising give n that, far from supporting the EC's speculative
assumptions, it manifestly contradicts them.
20. Fifth, the EC fails to take into account in spection and control procedures at federally
inspected slaughterhouses. The EC twists examples of successful detection of non-compliance into a
systemic failure of controls. On this logic, as EC authorities have detected numerous examples of
misuse and abuse in Europe, the EC's complete ban on the use of growth-promoting hormones, and
the control measures adopted to enforce that prohi bition, have been an abject failure. Without
analyzing the frequency of non-compliance, argumen ts of this nature say nothing about the
effectiveness of the control mech anisms in place to prevent misuse and abuse. The EC also ignores
the significant regulatory and economic disincen tives for abusing and misusing hormone growth
promoters. At the slaughterhouse, detention of car casses, or a group of car casses, causes disruption,
ties up on-site storage pending residue testing results and is therefore avoided whenever possible by
major processors. Product recall in Canada, or rej ection of export shipments, incurs a significant
financial loss. These real costs are in addition to the ever-present prospect of prosecution for
applicable regulatory offences.
21. Sixth, the EC erroneously assumes that the pr oblem with "black market" growth-promoting
hormones in Europe is extended to Canada. Canada recognizes the concern of EC authorities on this
issue, given the documented widespread use of such products in EC Member States and the reported
involvement of organized crime.
11 Fortunately, Canada has not experienced the problems associated
with the use of black-market drugs of the nature an d extent experienced in Eu rope. The illegal use of
any veterinary drug is a concern of authorities wo rld wide, including in Canada. But use of illegal
anabolic substances, whether for bodybuilding purpo ses or animal growth promotion, does not imply
misuse of legal growth-promoting hormones. Reason s uggests that if a safe legal product is available,
calibrated for optimal performance at the specified dose, there is little incentive to engage in black-
market drugs.
22. Seventh, by suggesting that the growth-promoti ng hormones in use in Canada are "sold freely
‘over the counter'",12 the EC implies that there is no veterina ry supervision of these substances. This
distorts the reality of the modern beef industry in North America. In Canada, only federally regulated
meat-processing facilities are authorized to expo rt meat products from Canada. These meat-
processing facilities typically deal with large commer cial feedlots. These feedlots in turn typically
have in place animal health plans developed and implemented under the superv ision of veterinarians
and animal nutritionists. Thus, while a veterina rian generally does not directly supervise the

11 Agence France Presse , June 3, 2002, "BELGIAN COURT FINDS FOUR MEN GUILTY IN
"HORMONE MAFIA" MURDER TRIAL". The article reads in part: "A Belgian court has, according to this
story, found four men guilty of the 1995 murder of a veterinary inspector who was probing a scam involving
illegal animal hormones, according to a verdict made public late Monday. The story adds that the men are to be
sentenced on Tuesday, almost two months after their trial began. The case of what became known as the
"hormone mafia" caused an outcry in Belgium, after Karel Van Noppen was found shot dead in his white
Mercedes in a lonely country lane in the northwestern city of Wechelderza nde. Arms dealer Carl De Schutter,
livestock dealer Germain Daenen, breeder Alex Vercautere n, and Albert Barrez, described as a travelling fair
worker, were found guilty of the 1995 murder."
12 EC Second Written Submission, at para. 108.

administration of the implants, animal health professionals are involved indirectly in the
administration of growth-promoting hormones by way of developing animal health protocols. If the
availability of "over the counter" drugs is of such a concern, the EC could restrict imports of meat
products only from facilities that have in place animal-health management plans overseen by
veterinarians.
23. In sum, the EC's purported assessment of the risks of misuse and abuse relies, not on available
direct evidence from on-going random residue mon itoring programs and realis tic conditions of use,
but on erroneous assumptions, invalid extrapola tions and selective evidence. In conducting its
purported assessment, the EC has failed to take into account process and production methods and
relevant inspection and control measur es, as required by Article 5.2 of the SPS Agreement. As such,
the EC's purported risk assessment fails to properly evaluate the potential for adverse effects arising
from misuse and abuse in Canada and as a consequen ce fails to satisfy the requirements of a risk
assessment under Article 5.1 of the SPS Agreement.
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 17β for growth promotion purposes?

24. The identification by the EC of oestradiol 17 β as a "weak genotoxin" is a further indication of
the questionable nature of the evidence on whic h the SCVPH based its conclusions. Based on the
observation that the "magnitude of DNA adduct le vels and mutagenic activities reported in these
studies is not very high and seems to be much lo wer than encountered with most known genotoxins",
the EC concludes that oestradiol 17 β may be a "weak genotoxin". However, a more plausible
conclusion, in light of the artificial test circumstances that produced these "weak" results,
13 is that
oestradiol 17β is not genotoxic in vivo at any dose that is relevant to exposure to oestradiol 17 β from
meat from treated cattle.
25. In fact, none of Drs. Boobis, Boisseau and Guttenplan, the only three of the experts who are
qualified to comment on issues related to genotoxic carcinogens, considered that there is evidence that
oestradiol 17 β is genotoxic in vivo . Even Dr. Guttenplan, who had some methodological
disagreements with Dr. Boobis, ultimately conclude d that "if you are talking about cancer, I don't
think there is a risk from consumption below the ADI".14
26. Therefore, the studies relied upon by the EC to conclude that oestradiol 17 β is a "weak
genotoxin" do not support the conclusion that oestradiol 17 β is genotoxic in vivo. These studies are
therefore not relevant to the evaluation of the poten tial occurrence of adverse effects from exposure to
oestradiol 17β from meat from treated animals.

13 The reaction, for example, of Dr. Boobis to the test conditions underlying the EC's "evidence" is
notable. In particular, he rejected the results reported in Exhibit EC-125, in which the doses needed to achieve a
genotoxic effect were far, far in excess of any normal dos es, and in fact ended in the death of a large number of
the study animals.
14 Due to the possibility of transcription inaccuracy , Dr. Guttenplan's exact wording may have differed
slightly, but his meaning was clear.

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?

27. The suspension of the obligations at issue was effected by Canada through the adoption of the
European Union Surtax Order , the text of which was reproduced in Exhibit EC-4 (the Order). The
Order was adopted on July 28, 1999 by the Governor General in Council ( i.e., the Governor General
acting on the advice of Cabinet) and ente red into force on August 1, 1999. The Order was based on
statutory authority contained in subsection 53(2) and section 79 of the Customs Tariff and was
adopted pursuant to authorization granted to Canada by the DSB on July 26, 1999. The termination of
the suspension of obligations would be effected by an Order in Council revoking the earlier Order,
i.e., through an executive act.
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 Agreement, since it still imposes a ban?

28. Directive 2003/74/EC is a measure which purports to bring into compliance a previous
measure (i.e., Directive 96/22/EC) found to be inconsistent with the WTO Agreement. In doing so, it
simply amends several provisions of the original non -compliant measure, all the while reaffirming the
original ban and setting out new reasons ( i.e., the conclusions of the SCVPH opinions) that purport to
justify that original ban. Therefore, since the ma in issue is whether the amendments brought by the
new Directive rectified the inconsistencies of th e old Directive, for the purposes of determining
whether the EC has "removed" the inconsistenci es, there is essentially only one measure that is
continuing.

ANNEX C-4

REPLIES OF CANADA TO QUESTIONS POSED BY THE
EUROPEAN COMMUNITIES AFTER THE SECOND SUBSTANTIVE MEETING

(18 October 2006)

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 th ose of JECFA for the six hormones in question
(in case you know the references).

1. The EC's repeated attempts to redirect the fo cus from its risk assessment to those of Canada
and the United States are irrelevant and unhelpful in assisting the Panel in resolving this dispute. The
pertinent issue in this case is whether the EC ha s complied with the recommendations and rulings of
the DSB, including, inter alia, whether the EC's continued ban on imported meat from cattle that have
been treated with growth-promoting hormones is based on a risk assessment, as required by
Article 5.1 of the SPS Agreement . Thus, whether or not Canada has conducted an exposure
assessment, quantitative or otherwise, is not legally relevant to the i ssues in this case. In any event,
Canada's measures in regard to the hormones at issu e are consistent with the international standards
set by Codex.
2. In terms of the JECFA risk assessment, JE CFA conducted detailed exposure assessments for
each of the hormones at issue based on realistic conditions of use. The exposure assessments are
contained in the Residue Monographs for each horm one published by JECFA. It is frankly quite
surprising at this late stage in this dispute th at the EC seems to be unaware of these detailed
documents and of the detailed analysis in this regard undertaken by JECFA.
3. For the Panel's ease of reference, Canada provides the following table identifying the
exposure assessments conducted by JECFA:
Substance JECFA Document Exhibit #
Oestradiol 17β FNP 41/12 CDA-17
Progesterone FNP 41/12 CDA-17
Testosterone FNP 41/12 CDA-17
Zeranol FNP 41/1 CDA-39
TBA FNP 41/2 CDA-38
MGA FNP 41/13
FNP 41/14
FNP 41/16
CDA-37
CDA-35
CDA-33

4. In terms of the exposure assessment for each natural hormone, the objective of JECFA's
intake calculations was to "obtain conservative estim ates of the theoretically possible excess dietary
intakes of preferential eaters of meat that could be attributed to the approved uses of the products

reviewed".
1 If data for several time points after implantation were available, JECFA used the time
points with the highest values to reflect the fact that no withdrawal period had been established for
these products. Using JECFA's conservative food b asket (300g muscle, 100g liver, 50g fat, and 50g
kidney), the residue data were converted into human intake estimates, referred to as "Theoretical
Maximum Daily Intakes" (TMDI). From the TMDI, JECFA subtracted estimated intakes of hormones
from the untreated control population, in order to arrive at an "excess intake" value. This excess intake
value was then compared with the ADI. In the case of each natural hormone, this conservatively
inflated "excess intake" was only a fraction of the ADI: for oestradiol 17 β, progesterone and
testosterone, the figures are 2%-4%, 0.003% and 0.2%, respectively. 2 JECFA noted that "hormone
concentrations found in individual populations of treated animals … were well within the
physiological range of these substanc es in bovine animals. In add ition, the calculated excess intakes
contributed only a small additio nal hormonal burden to the background dietary intakes resulting from
the consumption of other normal foods of both animal and plant origin".3 On this basis and because of
the wide margins of safety built into the analysis, JECFA concluded that "there would be no need to
specify numerical MRLs for the three hormones".4
5. In terms of the exposure assessment for sy nthetic hormones, the procedure was more
straightforward. JECFA calculated MRLs for each of the substances that ensured that consumption of
meat products according to JECFA's conservative food basket would not lead to exposure in excess of
the ADI. The residue depletion studies confirmed that residue levels in each of the target tissues
would not exceed the recommended MRLs. In each case, however, JECFA used residue depletion
studies based on realistic conditions of use, which is to say, according to the labelled instructions and
good veterinary practice.
Q2. Please indicate, if possible in detail, wh ether your risk assessments, and if you know
those of JECFA, of the six hormones in question 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 pr ovide 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).

6. The answer to Question 1 also applies to this question. As is apparent from the answers
above, in terms of the natural hormones, JECFA looke d specifically at "excess intake", equivalent to
what the EC refers to as "additional" exposur e, of natural hormones from their use as growth
promoters. The residue depletion studies set out in the Residue Monograph in Exhibit CDA-17
calculate levels of natural hormones in both treated and untreated control populations specifically to
determine this "additional" exposure. Importantly, because the additional expo sure is such a small
fraction of the ADI, JECFA concluded that it was not necessary to set MRLs.
7. The EC appears to be claiming that the additi onal exposure to natural hormones when used as
growth promoters creates risks. However, as the experts have explained, the EC simply fails to
conduct exposure assessments to support this clai m. Without an exposure assessment, it is not
possible to conduct a risk characterization to de termine whether the additional exposure at issue
would be sufficient to push total exposure to natural hormones from all dietary sources over the ADI.

1 JECFA, Residues of some veterinary drugs in animals and foods , FAO Food and Nutrition Paper
No. 41/12, at p. 83 (Exhibit CDA-17).
2 Ibid.
3 Ibid., at pp. 83-84.
4 Ibid., at p. 84.

8. With reference to the EC's claim that it has conducted residue depletion studies, the only such
studies that the EC has conducted for its 1999-2002 opinions appear to involve contrived misuse
scenarios for the synthetic hormones that do not reflect realistic conditions of use ( e.g., Exhibits
EC-11 and EC-17). In any event, as Dr. Boobis has explained in detail in his response to Panel
Question 62, several studies show that ev en with unrealistic misuse scenarios ( e.g., 10-fold increases
in dose) exposure would only barely exceed recomm ended MRLs. It is hardly surprising that MRLs
may be exceeded if one pumps an animal full of veterinary drugs in doses that well exceed the
recommended level. That they may be exceeded , however, says nothing about the occurrence or
frequency of overdosing under realistic conditions of use.
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-response 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 exposure assessment for these
hormones when used for animal growth promotion?

9. In indicating that it is not possible to determine with accuracy the dose-response curve at very
low doses, these three experts were referring to the difficulties inherent generally in linear modelling
of dose-response curves far below th e lowest experimental doses. Tho se experts, such as Drs. Boobis
and Boisseau, who reviewed the specific toxicologica l evidence related to actual adverse effects from
oestradiol 17β, as opposed to modelled effects, concluded that oestradiol 17 β is not genotoxic in vivo.
They were categorical about this in both their written answers and their a dvice to the Panel. Even
Dr. Guttenplan, who appeared to have some meth odological disagreements with his colleagues,
ultimately responded that "if you are talking ab out cancer, I don't think there is a risk from
consumption below the ADI".
5 Therefore, since these experts confirm that there is a dose below which
adverse effects do not occur (as a result of the iden tification of NOAELs), there is no need to use the
uncertain modelling techniques referred to by the three experts mentioned in the question.
10. In any event, Drs. Sippell and Cogliano ar e not qualified to comment on the evidence of
thresholds for potential carcinogenic potential of oestradiol 17 β at low doses. This is not their field of
expertise. While they may have professional opi nions on the weaknesses of linear dose-response
modelling techniques in determining the shape of the dose-response curve at low doses, these
opinions must yield to the expert advice of tho se who are qualified to evaluate actual carcinogenic
potential at low doses. In other words, the specific advice of Drs. Boobis, Boisseau and Guttenplan is
the relevant advice for assessing the risk s from low-dose exposures to oestradiol 17 β from meat from
treated animals.
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.

11. The issue is not whether the advice of the e xperts revealed the existence of "scientific
uncertainty" or "vivid debate" on certain issues. Ra ther, the issue is whether there is "scientific
uncertainty" about the specific issues that are relevant to this dispute. As described in the answer to
the question above, uncertainty or debate between the experts about the limitations in techniques for
modelling the shape of the dose-response curve is not relevant in light of the unanimity expressed by
the most qualified experts that there are doses of exposure to oestradiol 17 β below which cancer does
not result. In other words, since the qualified expert s have identified that there are thresholds below

5 Due to the possibility of transcription inaccuracy , Dr. Guttenplan's exact wording may have differed
slightly, but his meaning was clear.

which adverse effects will not occur (as a result of th e identification of NOAELs), there is no need to
engage in uncertain linear modelling of the dose-re sponse curve. As such, any uncertainty that may
persist when such modelling is employed is not rele vant to the evaluation of carcinogenic potential of
oestradiol 17β at low doses from meat from treated animals.
12. It is therefore not sufficient to point to gene ral disagreement between the experts on any issue
and claim that there is scientific uncertainty such that a minority scientific opinion exists. It is
necessary to look at the nature and relevance of th e issue of purported uncertainty, the relevance of
the respective qualifications of the participants in the debate, and the nature of the evidence relied
upon by each participant to support their respective in terpretation. In this case, the opinions of the
generalists (Drs. Sippell and Cog liano) as to uncertainty inherent when modelling techniques are
employed are not relevant in light of the expert advice of the cancer specialists (Drs. Boobis, Boisseau
and Guttenplan) that the carcinogenic potential of oestradiol 17 β exhibits a threshold below which it
will not occur.
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?

13. As a result of opposition by the EC in Codex, that organization has not yet adopted as an
international standard the revised recommendations by JECFA for MRLs for MGA. There is therefore
currently no international standard fo r the purposes of Article 3 of the SPS Agreement . However,
JECFA has conducted a risk assessment of MGA and has allocated an ADI. This means that it has
concluded that there are "no appreciable risks" to human health from exposure to residues of this
hormone from meat from treated animals. Other agencies and health authorities have conducted
similar assessments and have come to the same c onclusion. Therefore, the EC's divergent conclusion
that there is insufficient evidence to conduct a risk assessment of MGA is not justified, such that its
provisional ban on MGA is not jus tified by Article 5.7 of the SPS Agreement. As a result, the EC has
also failed to base its ban on MGA on a risk assessment appropriate to the circumstances, contrary to
Article 5.1 of the SPS Agreement.
EC Questions to Canada

Q1. In relation to your example for the oestrogen 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 2n g added to endogenous oestrogens production
are not likely to have any such effect?

14. The EC misstates the conclusion of the study in Exhibit EC-56, which was Study 13 (Kaijser
et al., 2001). That study does not provide "evidence that in utero exposure to oestradiol has given rise
to a number of abnormalities and suspected of an increased of cancer", as claimed by the EC.
15. The study set out to explore the hypothesis that the risk of br east cancer is influenced by
hormonal exposure in utero by comparing breast cancer rates in twins. However, the study does not

conclude that exposure to oestradiol gives rise to a number of abnormalities and an increased risk of
cancer. In fact, the study concludes that for female co-twins with male co-twins , a high birth weight
constitutes a strong independent risk factor for breast cancer. The same relationship between high
birth weight, which is often seen as a proxy for oest rogen exposure, and risk of breast cancer was not
seen in female twins with female co-twins . The authors speculated that the presence of androgens
produced by the male co-twin, not oestrogens, may he lp explain the increased risk. It is a stretch of

Herculean proportion to conclude, as the EC does, that this study is evidence that in utero exposure to
oestrogen causes an increase in cancer.
16. In any event, as Dr. Boobis states in his answer to Panel Question 62, "given that exposure to
oestradiol from meat of treated animals would be extremely low, particularly relative to endogenous
hormone levels, which increase during pregnancy, (e.g. see Weiss, 2000) the findings of the Kaijser et
al study provide no evidence for risk from exposur e to oestradiol residues in meat from treated
animals".
17. The second part of the EC's question is prem ised on a nonsensical theory of low-dose
exposure. Pregnant women produce daily in the range of 37,000,000 ng of oestradiol, much of this
produced in the placenta adjacent to the developi ng fetus. As Dr. Boobis noted, exogenous natural
hormones are indistinguishable from their endogenous counterparts once absorbed into the human
system. Thus, the 2 ng of bioavailable oestradiol from meat is quickly integrated into the circulating
levels of endogenously produced oestradiol. As a result of the homeostatic control mechanism,
endogenous production is adjusted to take into account exogenous exposure. Thus, the low dose of
exogenous oestradiol to the mother does not translate into a low dose to the fe tus. Moreover, even if
the background circulating levels were increased by 2 ng, it is absurd to claim that the fetus is exposed
to a "low dose", given its pre-existing exposure to substantially greater amounts of oestradiol
endogenously produced by the mother.
18. One is comforted in concluding that the EC's speculative propositions in this regard have no
scientific justification as, to Canada's knowledge, no European health authority is advising pregnant
women to avoid consumption of foods containing oestrogens out of concern for potential adverse
effects on the fetus. If the EC truly believed that the negligible amount of oestrogens from dietary
sources was a risk factor for reproductive cancers in the fetus, then one would expect responsible EC
health authorities to act to protect, or at the very least advise, the unsuspecting public. Tellingly, they
have not done so.
Q2. As regards the reference to Carbadox (see para. 67 of CDA'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 for the residues in pork meat treated with
Carbadox?

19. The reference to carbadox in paragraph 67 of Canada's Or al Statement on 3 October 2006 is
simply to illustrate a point raised by the JE CFA representative during the session with the Panel's
expert advisors. Codex provides a mechanism whereb y its Members can bring new information to the
attention of the responsible bodies and request a re-evaluation of existing standards, recommendations
or guidelines. Indeed, this mechan ism is routinely used by Codex members. As many countries base
their domestic SPS measures on Codex standards, recommendations and guidelines, as required by
Article 3.1 of the SPS Agreement, one would expect that, if a Memb er of Codex had new, pertinent
information that it claims casts doubt on the validity of an existing Codex standard, it would, as a
responsible member of Codex, avail itself of the re-evaluation procedure in order to protect not just its
own citizens but those of other countries that rely on such standards. Tellingly, in this case, the EC
has failed to do so.
20. As to the history of the re-evaluation of carbadox, at the Thirteenth Session of the Codex
Committee on Residues of Veterinary Drugs in Food (CCRVDF) ad hoc working group on priorities,
Canada requested a re-evaluation of carbadox on the basis of new information, including analytical
information showing the presence of the metabolite desoxycarbadox in the tissues of pigs. Japan and
Thailand also made similar requests in relation to other veterinary drugs ( e.g., flumequine). The

Working Group recommended that these veterinary drugs be re-evaluated and forwarded these
recommendations to the CCRVDF.
6

6 CCRVDF, Report of the Ad Hoc Working Group on Priorities, 4-7 December 2001, Thirteenth
Session, Agenda Item 13, CRD 2, at para. 4.

ANNEX C-5

COMMENTS BY CANADA ON THE REPLIES
OF THE EUROPEAN COMMUNITIES TO QUESTIONS
POSED BY THE PANEL AFTER THE SECOND SUBSTANTIVE MEETING

(31 October 2006)

INTRODUCTION

1. In this document Canada provides comments on the EC 's answers to questions 1, 2, 3, 4, 5, 6,
8, 9, 11, 12, 13, 14 and 15 from the Panel afte r the Second Substantive Meeting, as filed on
18 October 2006.
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?

2. In its response to this question, the EC characterizes its "systemic claims" as being
"procedural in nature" and "inde pendent of substantive obligations". This reasoning reflects the
fundamental flaw that has driven the EC's actions in this dispute from the beginning, and it is simply
not supported by the text of the DSU. The DSB authorization of Canada's suspension of concessions
is based on findings of breaches by the EC of its "s ubstantive obligations". That authorization, and
any measures taken pursuant to it, cannot therefor e be rendered without effect simply through
"procedural" manoeuvring that is independent of an assessment of the underlying "substantive
obligations". The EC challenges Canada with claims that are "procedural in nature" precisely to avoid
having to demonstrate its compliance with its subs tantive obligations. However, the only way for the
DSB authorization no longer to have effect is fo r the EC to confirm compliance with its substantive
WTO obligations (i.e., by succeeding on its "direct claims").
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. Canada has no comment on the EC's response to Question 2, other than to note that Canada
has addressed in paragraphs 113 to 119 in Canada 's Second Written Submission the EC's argument
that Article 5.7 creates a "special regime".
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".

4. In discussing those of the 17 studies that the EC failed to disclose to the defending parties, the
EC refers to one study that "was from the star t not meant for publication (Exhibit EC-7), as it
contained the samples of meat collected from the US supermarkets that was sent for analysis in the

European laboratories".
1 However, Exhibit EC-7 appears to relate to Commission Study 1 and
involved a comparison of assay methods for detecting hormone residues in meat, not analyses of meat
samples collected from US supermarkets. The study of meat samples from US supermarkets appears
to be one of the studies conducted by Professor Ra iner Stephany for the Community Reference
Laboratory in Bilthoven, The Netherlands, under the rubric of Commission Study 6. The EC has not
disclosed the results of this study, but submitted instead an article by Dr. Stephany for an NGO
newsletter (Exhibit EC-19).
2 Dr. Stephany appears to have issued three interim reports analyzing
various samples of meat and meat products from the United States:
• The first interim report is entitled "Results of 'hormone' residue analyses of bovine
meat and liver imported into the EU a nd originating from the USA 'Hormone Free
Cattle Program' ", First Interim Report;3

• The second interim report is entitled "Results of 'hormone' residue analyses of bovine
meat and liver originating from the USA domestic market", Second Interim Report; 4
and

• The third interim report is entitled "Results of 'hormone' residue analyses of bovine
liver originating from the USA and imported into the EU as petfood ", Third Interim
Report.5

5. What is remarkable is that of the three interi m reports authored by Dr. Stephany specifically
analyzing samples of meat and meat products from the United States, only th e results of the third
report have been submitted to the Panel. This study, Exhibit EC-53, relied upon by the EC in response
to Panel Question 4, relates to petfood
.6 Those studies that specifically measured the level of hormone
residues in meat samples for human consumption appear to have been withheld by the EC on the basis
that "they were not meant for publication". Furthermore, in what is clearly an error, the EC refers to
Exhibit EC-53 (petfood!) to buttress its argument that it has assessed the level of risk from meat sold
in US supermarkets.
6. The disclosure of petfood results while withholdi ng actual human food results is particularly
troubling given the EC's assurances that it conduc ted an "exposure" assessment. But what better
evidence to assess exposure than r esults from samples of actual human food. Ignoring this evidence,
the EC instead relies on hypothetical scenarios of mi suse in an attempt to demonstrate likelihood of
risk. Moreover, not only did the EC fail to take da ta from actual human exposure into consideration in
assessing exposure, it withheld these data from the Panel and the defending parties. It cannot be
excluded that the data assembled by Dr. Stepha ny did not support the EC's absurd conclusions
concerning the extent of misuse and abuse in Cana da and the United States. Indeed, it is entirely
plausible that these data confirm the results of Ca nada's Codex-consistent national residue monitoring
program, results which the EC has also ignored. Thus, the failure to take into consideration actual data

1 EC's Responses to Questions to the Parties from the Panel in Connection with the Second Substantive
Meeting (EC's Responses after the Second Meeting), at para. 11.
2 Also see Rainer W. Stephany, "Hormones in meat: different approaches in the EU and in the USA"
(Exhibit EC-49, also Exhibit CDA-12).
3 See Canada's Responses to Questions to the Parties from the Panel in Connection with the Second
Substantive Meeting, Canada's response to Panel Question 3, fn 2. Also see Exhibit EC-49 (also Exhibit
CDA-12), ref. no. 25. The existence of the first report is confirmed by referen ces to it in the 1999 SCVPH
Opinion, at pp. 31 and 117 (Exhibit CDA-2), and the Draft Assessment of Risks of Abusive Use, fn. 24
(Exhibit EC-73).
4 See Exhibit EC-49 (also Exhibit CDA-12), ref. no. 26.
5 R.W. Stephany and F. André, "Results of "hormone" residue analyses of bovine liver originating from
the USA and imported into the EU as petfood, Final Report" (Exhibit EC-53).
6 EC's Responses after the Second Meeting, at para. 15.

from meat samples taken in US supermarkets implies that the EC has been selective and self-serving
in the data that it considered. Given the EC's underl ying theme that it lacks modern residue data, it is
all the more surprising that the EC buries these data under the proviso that they were "from the start
not meant for publication".
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 17β as a growth promoting hormone to cattle, in particular in the United States' and
Canada's markets? If so, please indicate where this assessment is to be found in the evidence
provided to the Panel.

7. Canada has several specific points to make in relation to the EC's response to Panel
Question 4. As a general comment, however, the EC pers ists in its practice of referring to exhibits to
support its claims in the apparent hope that nobo dy will read the exhibits. A close review of these
exhibits indicates that, in many cases, they simply do not support the EC's position. Accordingly, the
Panel would be well-advised to scrutinize closely the EC's putative supporting evidence.
8. First, in paragraph 14, the EC refers to a numbe r of exhibits that iden tify a potential hazard.
Not surprisingly, if one administers a veterinary drug in amounts well in excess of approved doses
(e.g., 10-fold) it is plausible, although not necessarily so,
7 that residues of that drug could exceed
recommended MRLs. Thus, many of the articles cite d by the EC are hardly groundbreaking science.
Although the EC identifies a potential hazard, the EC 's exhibits say nothing about the frequency with
which their concocted, experimental scenarios woul d occur under realistic conditions of use. Without
an assessment of frequency, the EC's analysis canno t be said to evaluate th e likelihood of adverse
effects occurring, as required for a risk assessment consistent with Article 5.1 of the SPS Agreement.
The defectiveness of the EC's approach is perhaps best illustrated by an analogy. It is possible that in
European abattoirs contaminants, such as animal feces, could enter the human food system. Animal
feces potentially carry numerous bacteria, which are potentially hazardous to human health. Thus,
having identified a human health hazard, would it be acceptable for a WTO Member to ban European
meat on the basis that feces could potentially enter the human food chain, without doing any analysis
of the frequency with which animal feces actually en ter the system? Canada thinks not. By extension,
it is not acceptable merely to identify potential health hazards from the abusive use of hormones
without any analysis of the frequency of such misuse under realistic conditions of use.
9. Second, contrary to the EC's claim in paragra ph 14, none of the Experts confirmed that "if
GVP is not observed the ADIs and the MRLs proposed by Codex become useless." The EC would be
well-advised to familiarize itself with the role of MRLs in its own residue-monitoring program.8 Quite
simply, ADIs and MRLs are not "useless" if GVP is not observed. MRLs provide a means for
detecting whether, as a result of the failure to follow GVP or some other reason, residues exceed
acceptable limits such that ADIs are likely to be exceeded.
9 As with any veterinary drug (or pesticide,
for that matter), MRLs provide a mechanism for dete cting potential abuse (over-use, failure to follow
withdrawal periods, etc.). For all the EC's talk of misuse and abuse in Canada and the United States, it
puts forth no data that attempt to quantify the frequency with which residues in Canada actually

7 See Dr. Boobis' review of Exhibit EC-17 (study 5) (Iris G. Lange, A. Daxenberger & H.H.D. Meyer,
"Hormone contents in peripheral tissue after correct a nd off-label use of growth promoting hormones in cattle:
Effect of the implant preparations Finaplix-H®, Ralgro®, Synovex-H® and Synovex Plus®") where he quotes
the authors of the study as concluding "[t]reatment with zeranol and testosterone propionate, even after multiple
application does not cause any problems , as far as infringement of threshold levels is concerned", Panel
Questions to the Experts, Dr. Boobis' response to Question 62, at p. 50.
8 Questions and Answers on Residues and Contaminants in Foodstuffs, Brussels, February 19, 2003,
online at: http://ec.europa.eu/food/food/chemicalsafety/residues/fcr_qanda_en.pdf.
9 See Panel Questions to the Experts, Dr. Boobis' response to Question 46, at pp. 41-42.

exceed recommended MRLs. And because it has no evid ence, it attempts to discredit the universally
accepted concepts of ADI and MRL.
10. Third, in terms of the EC's evaluation of the level of risk from imports coming from Canada
and the United States, the EC cites its obviously self-serving "draft" "working document", filed as
Exhibit EC-73.
10 The EC claims that this document takes into account "specific, real and undisputed
instances of abuse and/or misuse". 11 This is simply a further attempt by the EC to use distortions,
inappropriate extrapolations a nd unfounded assumptions to undermin e Canadian control practices.
Canada has addressed in its answer to Panel Quest ion 4 the major flaws in the EC's putative risk
assessment.
11. Fourth, as Canada indicated in its comments on Question 3, the EC cites Exhibit EC-53, a
review of petfood samples, as support for its assertion that meat sold in US supermarkets was
assessed. Curiously, rather than data from human f ood samples (which the SCVPH failed to consider
and the EC has withheld from this Panel), the EC cites petfood data. Although the relevance of
residues from hormonal treatment of cattle found in li ver destined for use in petfood to food destined
for human consumption is debatable, the petfood da ta do not support the EC's conclusions regarding
misuse and abuse of growth-promoting hormones in Canada or the United States:
• first, it is not surprising that residues would be found in some livers, as tissues
destined for manufacture of pet food may be from animals considered unfit for human
consumption;

• second, despite this, none of the residue results reported (Annex 5 of the report)
exceeded the Codex MRLs for trenbolone in cattle liver or the MRLs recommended
by JECFA for MGA in cattle liver. In add ition, no confirmed residues of zeranol or
its metabolites were found in any samples (thus, even in animals unfit for human
consumption, there is no evidence of zeranol use, let alone misuse);
12

• third, the two analytical laboratories also reported analytical results for oestradiol,
progesterone and testosterone but stated that there was no basis for classifying the
results in terms of "normal" or "abnormal" . Since the EC cannot distinguish between
"normal" and "abnormal" levels of these compounds, one must wonder on what basis
their so-called "additional risk" can be associ ated with the consumption of meat from
treated animals produced in North America; and

• fourth, no evidence of use of "black market" or unauthorized hormones was found in
these samples.

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 17β 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 aff ect the identification of adverse effects and
the evaluation of potential occurrence of these effects from consumption of meat from cattle
treated with oestradiol 17β for growth promotion purposes?

10 European Commission, Assessment of Risks of hormonal growth promoters in cattle with respect to
risks arising from abusive use and difficulties of contro l, Draft Report by special working group of external
private experts and European Commission officials, Brussels, April 29, 1999.
11 EC's Responses after the Second Meeting, at para. 15 (emphasis omitted).
12 R.W. Stephany & F. André, "Results of "hormone" residue analyses of bovine liver originating from
the USA and imported into the EU as petfood, Final Report", at pp. 28-31 (Exhibit EC-53).

12. The first thing to note about the EC's response to this question is that the EC has very
conveniently stopped referring to oestradiol 17 β as "genotoxic" and has begun referring to it as
"mutagenic". This is perhaps not surprising in light of the advice of experts such as Dr. Boobis that
"not all genotoxicity is necessarily mutagenic".13 The EC has realized that even establishing oestradiol
17β as genotoxic is insufficient to demonstrate adverse effects; it must also establish it is mutagenic,
so it has switched the terms it uses in its responses. The reality is, however, that the Experts advised
that there is no evidence of in vivo genotoxicity of oestradiol 17β, let alone evidence of mutagenicity,
which would be required for oestradiol 17 β to be considered carcinogenic through a mode of action
other than its hormonal activity.
13. The lengths to which the EC goes to defend its reliance on Exhibit EC-125 are also quite
remarkable. Responding to criticism that the dose used in the study was too high to be relevant to
conclusions about genotoxicity u nder realistic conditions, the EC ass erts that negative conclusions
should not be drawn from the "very high" dose because the precise dose is not known as the study did
not determine it. Undaunted by the absence of this information, the EC simply makes it up. Based on
"assumptions" and "estimates", the EC derives a figure for the rats' daily expo sure to oestradiol 17 β,
and then suggests that the dose u sed in the study was not unreasonable after all. However, applying
the calculations made by the United States in its answ ers to this question, even the EC's "estimated"
daily exposure of 200 micrograms/kg/bw is still 8, 000 greater than that from meat from treated
animals.
14. Moreover, in its efforts to portray the test cond itions in that study in the most favourable light
possible, the EC overlooks one critical piece of info rmation: a large number of the animals in the
study died
 from the dose administered. In other words, no amount of recalculation based on
assumptions and estimates can alter the fact that th e dose actually administered in the study was so
great as to overwhelm the normal bodily functions such that the animals died before any genetic
effects could be observed. Whatever notional number the EC places on the daily dose in that study, it
is not comparable to the dose received from meat from treated animals, such that the results of that
study would be relevant to exposure to meat from treated animals.
15. The EC then quite confusingly, in paragraphs 19 and 20, relates the results of the rat studies to
estimates of daily production rates in pre-pubertal children. By arguing that the rat study demonstrates
that oestradiol 17 β has "mutagenic effect" at a dose "within the 1000 safety margin", the EC appears
to be making a significant change to its interpre tation of the evidence. The SCVPH concluded that
oestradiol 17β was "genotoxic" and that there is no threshold below which this genotoxic effect would
not occur. The EC now seems to be saying that ther e is a threshold for "mutagenic effects", but that
this threshold is within the safety margins implic it in the JECFA ADI. Since this new conclusion is
based on a combination of two very different sets of data ( i.e., the EC's own estimates of the daily
dose in the rat study and the Klein estimates of daily production), neither of which has been proven to
be valid, the EC's arguments have strayed so far from actual scientific evidence to barely warrant
comment.
16. In any event, the SCVPH declined to conduc t a dose-response assessment as a result of its
conclusion that oestradiol 17 β is genotoxic and does not exhibit a threshold. Therefore, even if the
EC's interpretation of Exhibit EC-125 were correct – and it is not – it would amount to nothing short
of a concession by the EC that a dose-response assessment should have been conducted by the
SCVPH in order to determine the threshold of mutagenicity.

13 See Panel Questions to the Experts, Dr. Boobis' response to Question 2, at p. 9, as well as Dr. Boobis'
advice during the meeting with the Experts.

17. Finally, the EC claims that the "dose administered is not very critical for in vivo
genotoxicity", but this precise claim has been directly countered by Dr. Boobis, the most qualified of
the Experts to advise on this point.
14 He advised that understanding the mode of action of the potential
genotoxicity of a substance is critical in unders tanding whether there will be a threshold. The
observation of genotoxicity at very high doses is not conclusive of whether oestradiol 17 β can be
considered genotoxic in vivo. In fact, the failure to observe th e same genotoxic effect at low doses
confirms that the mode of action is such that a threshold is present.
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. There is no merit to the EC's claims that provisions of the DSU acquire a different meaning
when "read together" with other provisions than they would have when read on their own. Article 23
read in conjunction with either of Article 22.8 or 21.5 cannot create obligations for Canada that it does
not have under Article 23 on its own. The issue, therefore, is not what additional obligations under the
DSU these three provisions together create for Canada to act, but what Canada's obligations are under
the DSU. On that point, if the Panel were to accept the EC's claims on DSU grounds alone, the EC's
response that the Panel should find that Canada must both
 cease its suspension of concessions and
initiate compliance proceedings under Article 21.5 is al so totally without merit. If the Panel were to
accept a claim under the DSU, only one of the two options, and not both, can be a consequence.
19. On the one hand, if the Panel should find, simply on the basis of the EC's DSU claims, that
Canada has an obligation to withdraw its suspen sion of concessions, there cannot be findings of an
obligation to initiate, at the same time, Article 21.5 proceedings. To require both would be tantamount
to turning Article 21.5 into a pos itive obligation always to initiate compliance proceedings in the
event of a disagreement. This is not the intent of that provision. On the other hand, a finding by the
Panel that Canada had an obligatio n to initiate Article 21.5 proceedings only makes sense if the Panel
finds simultaneously that the suspension of concess ions may remain in force until the dispute is
resolved.
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:

14 Ibid., Dr. Boobis' responses to Question 16, at p. 19, and Question 19, at p. 22, as well as Dr. Boobis'
advice during the meeting with the Experts.

(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 17β?

 (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.

20. In its response to Question 8, the EC again claims that the SCVPH has conducted all four
steps of a risk assessment and then claims, in paragraph 35, that Canada's main objection is that the
SCVPH has not conducted an exposure assessment (the third step). Both of these claims are wrong.
21. With respect to the four steps of the risk asse ssment, Canada's main claim is that the SCVPH
did not properly complete the second step
 of the risk assessment, the hazard characterization, as a
result of its scientifically unjustified interpretation of the evidence related to genotoxicity and the
potential for endocrine disruption. Based in particular on its unsupported conclusions about
genotoxicity, the SCVPH declined to conduct a dose-r esponse assessment (which is part of the hazard
characterization) of oestradiol 17 β. It also failed to assess the dose at which there are risks of
endocrine disruption, particularly among pre-pubertal children. The Experts confirmed these failures.
22. With respect to the EC's purported exposure ass essment, the EC seems also to have confused
what in fact constitutes an exposure assessment. The EC's claims to the contrary, the SCVPH's
assessment in section 4.1.5 of its 1999 Opinion does not amount to a complete "exposure assessment".
At best, that section draws conclusions (incorrect, as Canada has explained el sewhere) about relative
exposure ( i.e., the ratio of exogenous exposure to endogenous production). It provides little
information on the overall exposure to hormon es from exogenous sources, and it provides no
assessment whatsoever on the implications of a change in the understanding of this ratio (even were it
to be confirmed, which it has not) for the identifica tion of adverse effects on pre-pubertal children. It
certainly does not, as suggested by the EC, call into question the ADI set by JECFA, as that ADI is
not based on a calculation of endogenous produc tion in population sub-groups. Rather, the SCVPH
simply asserts, without evidence or justification, th at new data regarding exposure levels relative to
endogenous levels reveal new risks.
23. Moreover, even if this section were to be c onsidered an exposure assessment, the calculations
contain several problems. First, the SCVPH assumes an "acceptable daily intake" of
102 ng/person/day. This value was derived from US Food and Drug Administration tolerances for
permitted incremental increases of oestradiol over a nd above the concentrations naturally present in
untreated animals. However, this value does not represent the actual amounts of estradiol found in
edible tissues and so does not represent an estimat ed amount to which consumers will be exposed. A
more accurate (yet still very conservative) estimate of excess daily intake of total estrogens from
eating beef from treated animals is 30-50 ng/person/day ( i.e., one-third to one-half of the EC's
erroneous estimate). This figure is based on actual residue depletion data assessed by JECFA.
15
24. Second, the SCVPH based its calculation on th e results of the Klein assay, which indicated
that blood levels of estradiol in prepubertal bo ys were 100-fold lower than previously reported.
Canada has demonstrated the flaws of the Klein assay on several occasions and the validity of this

15 JECFA, Residues of some veterinary drugs in animals and foods, FAO Food and Nutrition Paper No.
41/12, at p. 83 (Exhibit CDA-17).

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 estr adiol in prepubertal children may be lower than
previously believed, there was no consensus reached on the magnitude of the difference, and none of
the Experts provided convincing scientific evidence in support of the 100-fold difference cited by the
EC. The EC has itself recognized the inaccuracy of the Klein assay results.
16
25. Third, the EC speculates that the metabolic clear ance rate of estradiol in children is one-half
that of adults. No scientific data have been pr esented to support this speculation. As a result of
numerous methodological and calculation errors, the portion of the SCVPH opinion that the EC
claims constitutes the "exposure assessment" simply do es not satisfy what is required of an exposure
assessment.
26. The SCVPH's failure to complete a hazard char acterization or proper exposure assessment in
the end prevented it from completing a proper risk characterization. The EC defends the SCVPH's risk
characterization as "qualitative", but this simply am ounts to an acknowledgement that the SCVPH did
not have the information it needed to characterize th e risk, because it did not attempt to produce that
information.
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)?

27. In paragraph 181 of its rebuttal submission (U.S. case), the EC stated that "[u]nder Article 5.7
a mere doubt must be sufficient", suggesting that mere doubt about the sufficiency of scientific
evidence would satisfy the first requirement of Article 5.7. In its answers to Panel Question 9, the EC
backtracks from this untenable position and suggests that the doubts must be "reasonably serious", as
would be the case where the pertinent available evidence is "contradictory, inconclusive or
incomplete." The EC appears to suggest that wh ere the pertinent information is "contradictory,
inconclusive or incomplete", the relevant scientif ic evidence will be insuffi cient to perform a risk
assessment.
28. Several points should be emphasized. First, new evidence must be assessed in the light of all
relevant evidence, including the pre-existing evid ence. As Dr. Boobis indicated during the meeting
with the Experts, all evidence is not of equal pr obative value and a weight -of-evidence approach is
necessary to determine the comparative weight to be gi ven to particular data in the light of the total
available evidence. Second, the new evidence must lead to the conclusion that the totality of relevant
scientific evidence is insufficient to perform a risk assessment. This is a question of fact. Third,
contrary to the EC's suggestion, the determinati on of whether a WTO Member has acted consistently
with the requirements of Article 5.7, including the determination of whether the evidence is
insufficient to perform a risk assessment, is a questi on to be determined objectively by the Panel, not
subjectively by a Member, "depending on the Member's chosen level of protection", as the EC puts it.

17 Fourth, in the specific circumst ances of this case, no Expert advised that the so-called "new"
evidence adduced by the EC demonstrates that important gaps, insufficiencies or contradictions in the
relevant scientific evidence exist such that a risk assessment could not be performed. Indeed, in terms
of the five provisionally banned growth promoters, several Experts specifically advised that the new

16 See EC Comments on the Replies by the Panel Experts, Question 38.
17 See Canada Oral Statement, October 2 and 3, 2006, at para. 66. Canada refers the Panel to the
unadopted panel report in European Communities – Measures Affecting the Approval and Marketing of Biotech
Products, at paras. 7.3233-7.3246. That panel dismissed similar arguments advanced by the EC that the
appropriate level of protection influences the determination of "insufficiency" of evidence.

data do not demonstrate any important gaps, insufficien cies or contradictions in the relevant scientific
evidence.18
29. In relation to carbadox, cited by the EC in paragraph 44, the EC makes the rather obvious
point that sometimes the re-evaluation of substanc es on the basis of new information may lead to
different conclusions. The fact that JECFA revised its conclusions concerning carbadox after a request
to re-evaluate this substance by a Codex Member (Canada) illustrates how the system should function
and says nothing about whether, in respect of the substances at issue before the panel , new
information casts doubt on the previous conclusions. As discussed above, clearly it does not.
Q11. What is meant by no "additive risk"? Please explain to which "risks" these are
"additive".

30. In its response to this question, the EC re peats the erroneous and unsupported assumptions
and claims that have from the beginning plagued its approach to the regulation of these hormones. It
claims that there is a risk of cancer from normal background levels of hormones, that exposure to
exogenous sources automatically increases these bac kground levels, and that this increase in the
background levels automatically alters the ex isting risk. These claims constitute a serious
misrepresentation of the scientific evidence.
31. First, the EC has submitted no ev idence that "life-time exposure
 of humans to the levels of
endogenous production of oestrogen … are sufficient to cause and/or promote cancer in some
individuals", despite its claim that this is "scientifically not disputed". 19 To the extent that the EC is
suggesting that exposure to hormones has a cumula tive effect, that background levels alone have
adverse effects and that hormones initiate cancer, these assertions are all simply wrong. The only
conclusion that is not scientifically disputed is that hormones can promote cancer growth, but they do
so through receptor-mediated modes of action that exhibit a threshold below which it does not occur.
The evidence of this effect comes from studies involving hormone replacement therapy and oral
contraceptives, both involving high-dose exogenous exposures, and not from "life-time" cumulative
endogenous production. To the extent, therefore, that there is scientific evidence of a background or
baseline risk, it exists only in circumstances involving sustained high-dose exogenous exposure.
32. Second, flowing from its erroneous conclusion th at there is always a "background risk", the
EC simply assumes that any additional exposure "may increase the risk of can cer". This claim suffers
from at least two flaws: not all exogenous exposure alters endogenous levels (also referred to as
background or circulating levels), which would at a minimum be required for risk to be altered; and
even if background levels are altered, it is not automatic that "background risk" (were any to exist)
would also be altered. With respect to the first point, Dr. Boobis explained how the body's system of
homeostatic control compensates for variability in endogenous production and exogenous exposure.
This system operates to ensure that endogenous hormone levels remain at the optimal level for a given
physiological state. Additional exogenous expos ure may result in compensation in the endogenous
production such that the level remains unchanged. With respect to the second point, in light of natural
variability in background levels, even if a given e xogenous exposure leads to levels that are higher
than would be present without that specific exposure, this will not necessarily be outside the range of
normal variation, such that there will be any increase in any risk that may be present.
33. Third, the EC claims that these risks are "a dditive" regardless of the mode of action ( i.e.,
genotoxic or receptor-mediated). This is incorr ect. Understanding the mode of action determines
whether there is a threshold for adverse effects. In the case of these hormones, the mode of action of

18 See Panel Questions to the Experts, Dr. Boisseau's reponse to Question 62, and Dr. Boobis' response
to Question 62, at p. 58.
19 EC's Responses after the Second Meeting, at para. 48 (emphasis added).

carcinogenicity (i.e., receptor-mediated) is well established to have a threshold. And since there is a
threshold, there is also an exposure below which there is no risk
, and no amount of additional
exposure changes that risk as long as that exposure remains below the threshold. To conclude, as does
the EC, that all exogenous exposure alters b ackground levels and that all changes in background
levels alter background risks is simply a fundamental misrepresentation of the scientific evidence.
34. In fact, the EC appears to conflate the evaluation of risk with the evaluation of mere exposure.
In paragraph 49, it reiterates that exposure to hormones from natural sources "cannot be avoided",
then cites the Appellate Body finding in EC – Hormones that it is not arbitrary for governments to
regulate natural sources differently from non-natura l sources. However, the EC misinterprets the
meaning of these findings by failing to acknowledge the difference between "exposure" and "risk".
The Appellate Body findings only mean that once a substance has been identified as creating a risk ,
governments may be justified in reacting to that risk differently from natural sources than from non-
natural sources. In this case, however, the EC has not demonstrated that there are risks from any
source, natural or non-natural (other than sources that come in very high doses, e.g., hormone
replacement therapy), so it makes no sense to talk about avoiding one source and not the other. In
other words, the EC is using the Appellate Body fi ndings in an unjustified attempt to exempt itself
from establishing the threshold question of whet her there are risks from any source of these
hormones. It attempts to reduce this question to whether the exposure is unavoidable (natural) or
avoidable (non-natural), rather than whether th ere are risks from the substance from any source.
Ultimately, the EC's whole argument about the "add itive" nature of the risks is a secondary question
to whether there are risks at all from normal exposures. On this point, the Experts have indicated that
there are not.
35. A final point to be made about the EC's respon se is that the EC's references do not support its
simplistic assertions. In paragraph 49, the EC cite s Exhibit EC-35 to support the conclusion that the
estrogenic activity of residues of phytoestrogens is seriously disputed. That may be the case.
However, the article does not provide "indisputable " evidence that exposure to phytoestrogens "adds
some more burden to background levels", nor do es it support the conclusion that this addition "may
increase the risk of cancer". For in stance, the authors point out that the circulation concentration of
isoflavones, a class of phytoestrogens, in infa nts fed soy-based formula are "13000-22000 times
higher than plasma estradiol concentrations [in the same infants]".20 The authors conclude:
However, despite the concern derived from cell studies on endocrine effects of soy-
based infant formulas, the clinicians continue to consider them a safe and
nutritionally complete feeding option for most infants. There is no reported evidence
of endocrine effects in humans from consumption of these soy-based formulas.
Although these is indeed no indication of adverse effects of soy infant formulas to the
newborn, the tremendous plasma concentr ations of isoflavones after consumption
have not yet been thoroughly evaluated with respect to biological relevance and
should not be overlooked.
 21
36. The authors suspect that the high levels of isoflavones resulting from the consumption of soy-
based infant formula should have a biologic effect, but cannot explain the absence of reported adverse
affects. However, the absence of reported adverse effects contradicts the EC's speculative conclusion
that "this addition may increase the risk of cancer." Indeed, to the contrary, there is no evidence that
this particular addition has any impact whatsoever on the risk of cancer.

20 Dolores Ibarreta, Andreas Daxenberger & Heinri ch H.D. Meyer, "Possible health impact of
phytoestrogens and xenoestrogens in food", at p. S409 (Exhibit EC-35).
21 Ibid., at p. S410.

37. Finally, in footnote 13, the EC criticizes th e defending parties and JECFA for not being
"aware [of Exhibit EC-35] when they evalua ted these hormones", even though the study was
published only in 2001, a full two years after JECFA considered the three natural hormones. This is
all the more surprising given the fact that SCVP H itself practically ignores the article in its 2002
Opinion, thereby suggesting that the SCVPH did not c onsider the article to be sufficiently pertinent to
the issues at hand.
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 SCVP H Opinion? (please refer to comments by the
parties on the Panel's Question 43 to experts)

38. In response to this question, the EC attempts to undermine the scientific credibility of one of
its own scientific bodies. One wonders how the CVMP would respond to this attack, particularly to
the assertion that "the CVMP opinion must be
 simply reproducing on this point the JECFA
evaluations of 1988 and 1999 for oestradiol-17 β",22 which suggests that the CVMP failed to exercise
independent scientific judgment in assessing the bioavailability of oestradiol 17β.
39. In any event, the EC confuses the question of bioavailability with the question of whether all
relevant residues of oestradiol 17β, in free and conjugated forms, including lipoidal (fatty acid) esters,
and its metabolites have been ade quately taken into account in dete rmining residue levels. These are
two separate questions. The low bioavailability of oestradiol 17 β is not influenced by the fact that
some saturated fatty acid forms of oestradiol 17 β may not have been taken into account. Increasing
the level of exposure to a substance does not in crease its bioavailability. The EC is simply
conceptually confused.
40. That being said, the question of whether all pertinent residues of oestradiol 17 β, including
lipoidal esters, have been taken into account was addressed in Exhibit EC-47, a study by D. Maume
referenced in the 2002 SCVPH Opinion.23 In characteristic fashion, the SCVPH fails to note that even
if oestradiol 17β residues in the form of lipoidal esters are taken into consideration, the total oestradiol
17β exposure in meat from untreated and appropriately treated cattle meat is, respectively, 0.2% and
1.3% of the ADI! This is in the same range as JECFA's estimate of additional oestradiol 17 β exposure
from meat from treated animals (2% of ADI). 24 Thus, the calculations presented in the study relied
upon by the SCVPH simply do not support its conclu sion that "these data indicate that lipoidal esters
… may contribute considerably to an additional oestrogen exposure via meats". 25
41. In paragraph 56, the EC fails to understand the explanation provided by Dr. Boobis that the
ADI is "bioavailability adjusted". 26 As the ADI is based on a No-observed-effect-level (NOEL)
derived from a human study with an oral route of exposure, a change in our understanding of the
bioavailability of a substance does not alter the ADI . The risk to prepubertal boys from eating eggs
and drinking milk does not change because our calcu lations of the bioavailability of oestradiol 17 β
have changed from 5% to, for the sake of argument, 10% or 20%. It is unfortunate that at this late
stage of the process the EC has not appeared to grasp this basic point.

22 EC's Responses after the Second Meeting, at para. 53 (emphasis added).
23 2002 SCVPH Opinion, at p. 10 (Exhibit CDA-7).
24 JECFA, Residues of some veterinary drugs in animals and foods, FAO Food and Nutrition Paper No.
41/12, at p. 83 (Exhibit CDA-17).
25 2002 SCVPH Opinion, at p. 10 (Exhibit CDA-7).
26 See Panel Questions to the Experts, Dr. Boobis' response to Question 43, at p. 40.

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.

42. The EC in its response to this question attempts to explain away the very clear fact that even
the EC's own regulatory agency accepts that there are genotoxic substances for which thresholds exist.
The EC claims that the "other relevant parts" of EFSA's opinion somehow justify keeping the six
hormones at issue here out of the food chain. Th e implications of the EFSA opinion on the EC's
claims are not that even if oestradiol 17 β is proven to be genotoxic in vivo it should still be added to
the food chain, which seems to be how the EC has interpreted Canada's reference to the EFSA
opinion. Oestradiol 17 β has not been demonstrated to be genotoxic in vivo, so that is not the issue.
Rather, EFSA's conclusion that genotoxic substances can exhibit a threshold contradicts the SCVPH's
decision not to complete a dose-response assessmen t because of its conclusion that oestradiol 17 β is
genotoxic and hence does not exhibit a threshold. Ther efore, even though it concluded (incorrectly, as
Canada has explained elsewhere) that oestradiol 17 β was genotoxic, its conclusion that there is no
threshold, such that it need not conduct a dose-response assessment, was not justified.
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?

43. In response to this question, the EC again rais es the issue of incomplete data and scientific
uncertainty, this time in the context of selectivel y excerpted portions of the Final Report of the UK
Veterinary Products Committ ee (June 2006) (VPC Report).
27 The EC fails, however, to quote the
relevant conclusions of that report. For example, the report concludes that,
Following a critical evaluation of the scientific reasoning and methods of argument
adopted in the key papers and studies c ited in the SCVPH 2002 Report, the Working
Group were unable to support the conclusion reached by the SCVPH that risks
associated with the consumption of meat from hormone-treated cattle may be greater
than previously thought.
28
44. The VPC Report further confirmed the non-contr oversial scientific finding that exposure to
these hormones could have biological effects "if exposure is at a sufficiently high level "29 and
therefore concluded that "key issues" were the conduct of a dose-response assessment and an
evaluation of the additional exposure from meat from tr eated animals. Therefore, contrary to the EC's
claim that this report validates its ban, the report does the exact opposite. That is, it confirms that the
EC's ban is not based on a risk assessment appropriate to the circumstances because the purported risk
assessment on which the ban is based ( i.e., the SCVPH opinions) does not include a dose-response
assessment.
45. Nowhere does the VPC Report corroborate the SC VPH's claim that any of the six hormones
is mutagenic, which would be the minimum require d for a risk assessor to decline to conduct a dose-
response assessment. In fact, commenting on the SC VPH's own conclusions related to genotoxicity,
the VPC Report concluded that "the studies on which the SCVPH based their Opinion were all non-
standard studies …, or were unconvincing due to the absence of a dose-response".
30 Further on, the
report indicated that most of these studies produced "information of questionable relevance to effects

27 The Draft Report, which Canada understands is materi ally identical to the Fina l report released this
summer, is Exhibit CDA-26.
28 Ibid., at p. 3.
29 Ibid., at p. 4 (emphasis added).
30 Ibid., at p. 24.

that may occur in the intact animal" and were of "poor quality". 31 The key study was found to suffer
"methodological and interpretation flaws". 32 Echoing the advice of Dr. Boobis, the VPC Report finds
that,
Although there is evidence that oestroge n metabolites may be directly genotoxic in
vitro, in vivo their formation is affected by opposing activation and inactivation
metabolic pathways, the presence of anti- oxidants and DNA repair capacity and thus
it is likely this genotoxicity will have a th reshold response. … To date, there are no
standard tests conducted in vivo, even on 17β-oestradiol metabolites, which indicate a
mutagenic potential for 17β-oestradiol in vivo.33
46. While the EC selectively reproduces from the VPC Report quotations that identify other areas
of research that could be pursued, or that indicate that the "definitive" risk assessment has not yet been
completed, none of these "qualifications and reser vations" justifies the conclusions drawn by the
SCVPH. The VPC Report explicitly concluded this. In fact, the findings of the VPC Report are that a
dose-response assessment is a required component of a risk assessment of these six hormones,
something the SCVPH failed to do.
47. More evidence and information can be genera ted, of course, and the "definitive" risk
assessment has not yet been comp leted. But as Dr. Boobis advised during the meeting with the
Experts, it will always be possible to generate more evidence and information. However, risk
assessors cannot let uncertainty about information they do not think they have keep them from making
decisions based on the information they do have. And with respect to these six hormones, anyone who
has evaluated the available information, and who is not associated in some fashion with the EC's
hormones ban, has concluded that there are no risks from exposure to these hormones from meat from
treated animals.
48. With respect to the EC's clai m that the VPC Report further demonstrates the existence of
scientific uncertainty, as Canada explained in its answer to Question 4 to the United States and
Canada from the EC, there is no uncertainty about any i ssue that is relevant to the issue of whether or
not the SCVPH's conclusions regarding these hormon es are justified. While the VPC Report points to
several issues about which more information woul d be useful, none of those issues justifies the
SCVPH's failure to conduct a dose-response assessment with respect to oestradiol 17 β, and certainly
none of them justifies its failure to conduct a risk assessment at all with re spect to the other five
hormones.
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.

49. In short, the EC's answer to this question conf irms that it has not taken any steps to request
the re-evaluation of the existing international st andards for the five hormones, according to the
procedures of JECFA or Codex. The EC's response is a creative attempt to recast in as favourable
light as possible its failure to take these basic and straightforward steps.
50. Furthermore, the EC's criticism of JECFA's d ecision to re-evaluate the natural hormones in
February 1999 is without merit. The EC faults JECF A for its "refusal to postpone for a period of 2-3
years" its February 1999 re-evaluation in order to await the outcome of the EC's 17 new studies. 34

31 Ibid., at p. 27.
32 Ibid.
33 Ibid.
34 EC's Responses after the Second Meeting, at para. 80.

This criticism is ill-founded for several reasons. Firs t, given the position of the EC before the first
panel and the Appellate Body in EC – Hormones that "new" evidence demonstrated that oestradiol
17β is a direct-acting genotoxic carcinogen, it is hardly surprising that JECFA would act immediately
to review this "new" evidence.
35 Second, the EC is being hypocritical: after criticizing JECFA for
"waiting" 10 years to re-evaluate carbadox, the EC now criticizes JECFA for not "waiting" to re-
evaluate other substances, despite the alarmist position it adopted in the previous panel and appellate
proceedings concerning "new" evidence. Lastly, reca ll that the SCVPH issued its first Opinion in
April 1999, less than three months after JECFA's Fe bruary 1999 re-evaluation, indicating that JECFA
was not alone in its "refusal" to wait the two to three years for this "newer" evidence. We can only
speculate as to the importance the SCVPH attached to the 17 studies, given its refusal to wait for their
results.
51. One final point in relation to MGA. The EC, in objecting to the adoption of MRLs for MGA
at the recent 66th JECFA meeting, reiterates the same old, tir ed objections concerning old data and the
putative need for additional research. 36 In addition, the EC reiterat es its mantra concerning the
potential misuse of oestradiol implants, implying that misuse of MGA may pose safety risks.
However, the EC's own evidence shows that (a ) consumption of 10 times the maximum approved
dose only slightly exceeds JECFA's ADI 37 and (b) a 3-fold and 10-fold increase in the approved dose
of MGA reduces the levels of oestradiol 17 β and estrone to below the levels found in control
animals.38 This is not compelling evidence of human hea lth risks in the unlikel y event that producers
overdose their animals.