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EC Measures Concerning Meat and Meat Products (Hormones) Complaint by the United States Report of the Panel (Continued)
Chairman
545. But it is a standard procedure
which is applied to healthy animals?
Dr. André
546. It is familiar procedure.
It is applied in sheep mainly. More in sheep I think than in
cows.
Mr. Thompson (Canada)
547. Can I understand you to
say, Professor André, that farmers did it to their whole
herds at a single time in order to assist conception occurring
at the same time?
Dr. André
548. If your question is to know
if they can buy this product freely, the answer is no. This product
is always under veterinary control.
Mr. Thompson (Canada)
549. I had not asked that question.
May I proceed with my next question Mr. Chairman?
550. Again I have a somewhat
compound question. In answer to question 30 of the Panel concerning
the potential adverse effects on human health from residues of
carbadox, monesin, olaquindox, avoparcin, benzylpenicillin and
carazolol, ivermectin and organophosphorus compounds, some of
the experts noted that when used correctly, the residues from
approved veterinary drugs should not produce adverse effects in
the human population.
551. In question 17 of the Panel
the experts were asked to consider the implications for human
health of residues from the misplaced implants or improper administration
of the six hormones in dispute. And I wonder if the experts could
extend their analysis and comment in respect to the residues of
the veterinary drugs I read out and listed in question 30, as
to what are some of the implications for human health when they
are misused in a similar way described in question 17? For example,
could the experts explain what adverse health effects may result
if a hypersensitive person ingests meat or milk from an animal
that was treated with benzylpenicillin, when the required withdrawal
period has not been observed and the residues from benzylpenicillin
in such meat or milk exceeds prescribed MRLs, as an example.
Dr. Arnold 552. Maybe I can partly cover this question. I am a little bit reluctant to compare the hormones with carbadox because both substances have been regulated, or proposals have been made by JECFA concerning these substances, that in both cases if good practises are observed there is no appreciable risk. So I could say they are equally safe if good veterinary practices are observed. Because although carbadox itself is a genotoxic carcinogen, it is so quickly metabolized that if good practices are observed
neither carbadox nor its main
carcinogenic metabolite is present as a residue. Only an innocent
metabolite quinoxaline carboxylic acid, which has been extensively
tested including carcinogenicity, and this is the compound on
which the MRL has been proposed.
553. If somebody does not respect
the withdrawal time there might be an increase in this innocent
metabolite, but the closer you come to the administration there
is an increasing risk that the carcinogenic compound itself or
its metabolite is present. For example, at zero time of withdrawal
it is obvious that it would be present and that now you have a
different quality of risk and how do you compare this? If I am
a little bit reluctant and I must insist that it is the aim of
our procedures, to check whether conditions of use can be proposed
which if followed guarantee that there is no appreciable risk.
And if the possible risk is qualitative in nature how do you
prepare this? This is the first part of my lengthy answer. 554. Concerning benzylpenicillin, I had looked carefully at benzylpenicillin, I was consultant to WHO at the time benzylpenicillin had been evaluated. What is interesting to see is that about 15 per cent of the world population, some figures are higher, other figures are lower, are sensitized against benzylpenicillin. But we have carefully looked at all the reported cases. Only a very small number of cases one can discuss between five and ten but in no way more than ten, have been observed over the many years of use. Billions of doses administered of benzylpenicillin to human individuals causing sensitization but few cases where residues were the cause of an allergic reaction. The levels proposed by JECFA of benzyl penicillin are so low that in the whole literature you find only three cases where a lower level has caused an effect in a human being. The dairy industry needs these low levels too because the most sensitive population in this case are the starter cultures used for yogurt production, for example. They are much more sensitive than human beings. So the human consumer benefits from this that the mix cannot be used for food processing purposes if it contains high levels of penicillin.
Chairman
555. Thank you Dr. Lucier.
Dr. Lucier
556. I have a couple of questions,
before I attempt to answer the question. So carbadox does produce
tumours in the long term bioassays in rodents, is that correct?
And are there multisites more than one site of cancer in
the animals?
Mr. Thompson (Canada)
557. I don't know if I'm qualified
to answer that question. I understand that it's 11 out of 12
sites; perhaps Man Sen Yong can answer the question for us?
Dr. Man Sen Yong (Canada)
558. Well, actually I think the
JECFA has done the concrete evaluation of the toxicology of carbadox,
including the genotoxicity and carcinogenicity. So maybe I would
have the JECFA persons to answer for that.
Dr. Lucier
559. Let me ask one other question
while you are looking that up. How are, in relation to Dr. Arnold's
answer, carbadox residues ever found in products consumed by people?
And if so are the MRLs exceeded from time to time?
Dr. McLean
560. An MRL was not set for carbadox
and nor was ADI specified. And it's permitted for use providing
with a sensitive regulatory method you cannot detect residues.
It's a metabolite desoxycarbadox that's carcinogenic. It's a
short-term intermediate metabolite between carbadox and quinoxaline
compound. And also quinoxaline-2-carboxylic acid, the end-metabolite,
there were carcinogenicity studies on that as well as the intermediate
desoxycarbadox. So you have the parent compound desoxycarbadox
and the final metabolite. It's a compound that's used widely
in some countries including the EU and the recommendation of JECFA
was that they could not on the evidence presented state an ADI
or an MRL for genotoxic carcinogenic.
Dr. Lucier
561. So residues are never detected
I guess of carbadox?
Dr. Arnold
562. If the withdrawal time is
observed we will not even find it quinoxalinic acid with routine
methods. However, with more sophisticated methods you can show
that up to 70 days after treatment this metabolite persists.
Chairman
563. Can I briefly just for my
clarification now ask the Panel whether they consider it possible
to compare the use of the hormones we are talking about and the
substances we were just discussing, you were reluctant to do so.
Could I have the views of the others whether this is coming into
a category where we could really start comparing the use.
Dr. McLean
564. I will try and shed some
light on it Mr. Chairman. When an ADI set for a compound, providing
that ADI is not exceeded, then the risk associated with consumption
of produce containing the compound in question up to the ADI is
essentially zero. Now I use the word essentially to putting emphasis
on the fact that zero risk is not an obtainable figure. However,
if you exceed the ADI, then the nature of the risk varies from
compound to compound. For example, if you seriously exceeded
the intake of certain compounds, then depending on this toxicological
profile, you may cause some quite serious effects. However, many
of the ADIs are set on a relatively minor change such as a body
weight change and change in an organ weight, some minor variations
in some constituents of blood. So therefore to exceed the ADI
in that case would not be as serious. And so what we do is we
determine a level where there is no observed effect in the test
animal systems, then we apply a safety factor and by doing that
you essentially reduce the risk of consuming an amount equal to
the ADI on a daily basis for lifetime to zero. However, once
you begin to exceed that ADI you introduce risk. The rate at
which that risk comes in, if I can put it that way, and the intensity
of that risk varies from compound to compound, depending on that
toxicological end point which made the no effect level upon which
you derived the ADI. You've got a further question I guess?
Chairman
565. Dr. Lucier, on this comparison
question.
Dr. Lucier
566. That's where I was trying
to get some information so that I could determine whether or not
such a comparison could be made, in terms of at least carcinogenic
risk. I think that what Dr. McLean was talking about was not
essentially a carcinogenic risk that was a hormonal activity risk.
So they are two different things, two different methods to establish
risk, but I was just trying to determine with the information
available if it would be possible to compare the carcinogenic
risk at residues that might be normally encountered versus the
residues that might be normally encountered from the six hormones
in question.
Dr. Ritter
567. But the issue Mr. Chairman,
I think as a number of people have already attempted to explain,
is that at permitted residue levels, none of these compounds constitute
a risk. That's the nature of the process of establishing an ADI
and subsequently a MRL. It presumes that there can be lifetime
dietary exposure, every day of your life, and that continuous
dietary consumption will pose, for lack of a better term I'll
say essentially no risk at all. The question that you are asking
in fact is what if that residue level is exceeded? It goes beyond
what's been specified in the regulation, or internationally, and
I think the attempt that's being made by way of explanation is
that it would be potentially misleading to suggest to you that
these risks can be compared, because the ADIs that we've referred
to repeatedly are based on entirely different end points. They
can range from something relatively innocuous, in which case if
an ADI is exceeded the consequence would be relatively trivial.
And they can on the other hand extend to such issues as carcinogenicity,
in which case it would be potentially a very serious consequence.
So to compare the two, simply because they both have an ADI,
presumes that that ADI has been established on a similar end point.
Which is almost never the case.
Chairman
568. Would you think that the
fact that the use above the ADI levels varies greatly also induces
the possibility to have them regulated differently?
Dr. Ritter
569. I think the nature, having
been involved in the process of setting ADIs both nationally in
my own jurisdiction and participating in the process on an international
scale, one is left with the impression that the nature of the
process is such that there is a significant margin built into
the process, that in fact will have the effect of compensating
for that in any case. I briefly alluded to some of those yesterday.
For example the assumption is, one of the assumptions we discussed
yesterday, is the consumption of 500 grams of meat per day. I
mean I think we can all probably agree that in first principles
that's an overestimate. And so the risk has probably been exaggerated
in the calculation. That you will consume that risk every day
of your life and so on and so forth. So I think collectively
as toxicologists involved in that kind of a process, we have the
impression that MRLs that are temporarily exceeded, occasionally
exceeded, infrequently exceeded, are not likely to result in a
significant health consequence, because the calculation has already
built in so much overcompensation, that these occasional transgressions
are not likely to produce an adverse effect. That's the inherent
nature of the calculation itself.
Chairman
570. Is this a view shared by
the Panel?
Dr. Lucier
571. I'm still searching for
an answer to help me. I recognize that the carcinogenic risk
of these agents is very low. Within that range of zero to very
low, if I could get information I could say whether or not the
risks were comparable for cancer. Now this is the genotoxic carcinogen,
one accepts an ADI is established not on the basis of carcinogenicity
for genotoxic carcinogens its on the basis of something else.
Dr. Ritter
572. In the case of carbadox
I think Dr. Lucier, what has been explained is that there is no
ADI and there is no MRL, because it was the consensus of the Panel
that reviewed the material that as a genotoxic carcinogen we were
unable to establish what would popularly be referred to as an
acceptable intake. The acceptable intake is nothing.
Dr. McLean
573. We would not normally set
even an end point based on carcinogenicity, because generally
carcinogenicity occurs at much higher doses than we would set
a no-effect level. If the no-effect level was based on carcinogenicity,
we would look at the compound and alter safety factors and other
things, or again we might not permit it. And so in this process,
in managing the risks through the ADI, the aim is really to make
sure that you don't end up with carcinogens, as a result at least
of animal toxicity studies, in the food chain.
Chairman
574. Perhaps, Dr. Lucier, you
mentioned two different methods of determining risks. One would
be for hormonal action and the other for carcinogenic effect.
It seems to me that we have an established method for the first
one and the second one is somewhat new to the field here. Could
you elaborate a little bit on the second method and how you see
the implications in that particular field here, in particular
when we talk about whether these substances can be compared or
be treated alike and so on.
Dr. Lucier
575. If I saw the tumour data
for carbadox, I could establish a level at which a certain proportion
of the animals got tumours, and as best I could, I could extrapolate
down into the very low level risks what people might be exposed
to. There would have to be some residues left of carbadox, just
maybe not detectable, there have to be some residues left. And
I could compare that carcinogenic risk to that from oestradiol
or any of these other hormones in question. Now, that's a comparative
risk of carcinogenicity the comparative potency in what people
ingest from 500 grams of meat a day. So that would be a direct
comparison. I would have to assume what carbadox levels exist
and that was why I was wondering how often they are detected in
fact in meat samples, if ever, and what the limits of detection
would be. Then I could take, you know, something below the limits
of detection of what people are exposed to and do the calculation
on a rough estimate with considerable uncertainty but at least
to see if the carcinogenic potency is in the same ball park or
not. That's all that I'm after.
Chairman
576. Is such data available or
not? May I ask the experts?
Dr. Arnold
577. I have never seen positive
results and I see residue monitoring data since many years. But
it has not been intensively monitored on the other side, that
is the other difficulty. But I could perhaps say that at least
in the Community it is only used in piglets up to a maximum age
of 4 months, so it's quite realistic that the withdrawal times
are observed and then there is no carcinogenic residue in the
tissues, just maybe a trace of this innocent metabolite.
Dr. Lucier
578. I won't belabour this any
more after this one point. If apparently there is tumour data
that is summarized, if I could look at that sometime during the
afternoon I'll do my little calculations. My intuition tells
me that the risks are going to be similar, carcinogenic risks.
Mr. Thompson (Canada)
579. I'm advised that there may
be residue data for desoxycarbadox, but perhaps if I could restate
the question. I think we are not coming directly with what I
was getting at, we have heard statements and, I think Dr. Ritter
was drawing attention to the fact that when JECFA and Codex review
and approve things and set standards it is assumed that there
is no risk associated with any of these substances, any of the
six hormones at issue, or carbadox, or carazolol or the benzylpenicillin.
The experts had been asked to speculate if the standard administration
procedures are abused in respect to hormones and proper procedures
are not followed, is there a possibility of a carcinogenic effect.
And we have heard that in respect of some of the hormones the
answer was, while close to zero risk, yes. And I've been asking
in respect to something like carbadox, which has also been described
as genotoxic carcinogenic, where an MRL and an ADI cannot be set
because of it, if we take the hypothetical situation where it
has been abused, administration has not been properly followed,
can we draw the same conclusions? Or to put the matter another
way, is there a rational reason to distinguish between permitting
substances which are genotoxic carcinogenic is like carbadox and
permit their use, while imposing a total ban on hormones which
are said to have no risk, verging on zero as well?
Chairman
580. Who would like the floor?
Dr. Arnold
581. Since you are asking for
data, maybe for the record I could tell you what we have seen
at JECFA when pigs were treated with carbadox. The residue level
of this, I call it innocent metabolite, quinoxaline carboxylic
acid was 18.9 micrograms per kilogram at 30 days withdrawal;
was 5.5 micrograms per kilogram at 45 days, 1.3 microgram per
kilogram at 70 days withdrawal.
Chairman
582. This goes to the previous
question. Would you come back on the figures here?
Dr. Lucier
583. I actually do have the tumour
data. Carbadox is a pretty potent carcinogen in terms of multisites.
So the answer to your question is yes if improperly used and
there were residues it would pose a carcinogenic risk.
Mr. Thompson (Canada)
584. And just before we leave
that perhaps I could ask Dr. McLean to expand on his answer to
question 11 where he discusses organophosphorus compounds and
the health effects there. Perhaps I could ask him to comment
on carazolol which I understand is used for transporting pigs
immediately prior to slaughter and the comparative withdrawal
periods, and whether there are any risks associated with the use
of that drug.
Dr. McLean
585. In relation to the organophosphorus
compounds, they are quite powerful neurotoxins in humans and in
animals, and are used generally to kill insects although there
are other uses for them such as removing foliage from certain
crops. There are two problems with them, one is delayed nerve
damage and that is generally a result of direct exposure of operators
and the like. However, under some circumstances residues in crops
in excess of the no-effect level have caused problems, acute problems
of organophosphorus poisoning. And some of them are carcinogenic
and so therefore safety factors to remove the carcinogenic hazard
in the appraisal, that's been taken into account although, generally,
the safety limits are based on acute effects that the poisoning
effects that you see. But they have been associated with poisoning
associated with exceeding the MRL. In relation to carazolol,
carazolol does have an effect of lowering blood pressure and heart
rate, it's related to the drugs commonly used in human to control
blood pressure and heart rate. It is also used to prevent a specific
form of stress in pigs during slaughter. And of course pigs are
sent from the farm directly to slaughter generally and if you
are going to have an effective treatment for the stress associated
with transport, then you have to treat them just before transport
so that the drug is effective during the transport process. And
there has been concern that if people were to ingest carazolol
at the site of injection then they may get a dose which could
have effects on heart rate and blood pressure. The sensitive
human population that was taken into account in this assessment
are those people already under treatment with this group of agents
for the control of blood pressure and associated cardiovascular
disorders, and if one was to superimpose a dose of carazolol on
top of the existing medication then there could be a problem.
So these two compounds in various ways, if the ADI is exceeded
can cause difficulties.
Mr. Thompson (Canada)
586. Just a quick follow up.
Are the organic phosphates ever used in animal production?
Dr. McLean
587. They are commonly used in
animal production to keep under control insects on animals, relatively
widely used.
Mr. Thompson (Canada)
588. Yesterday the European Communities
quoted fingers, sorry figures, on the number of tests they do
for residues of hormonal substances. We understand that Professor
André's expertise is in the residue testing. He noted
that the EC has developed multiresidue tests. And I wonder,
Professor André, could you describe what substances
the European Communities test for and comment on how many of these
tests come back positive and for what substances?
Dr. André
589. I can give you some comments
in the field of my competence, that means on hormones, on thyrostatic
compounds and on beta agonist compounds. Concerning the first
part of your question I cannot give you a complete list, so today
of all the xenobiotic compounds which are looked for in a real
multi-residue analysis, but you can imagine that they include
progesterone, nandrolone, oestradiol and many others, usually
30 different compounds are looked systematically for. Concerning
the thyrostat they are just about 6 compounds usually, small compounds,
and they are all of the same groups and derivatives of uroside
compounds, true - uroside compounds. And concerning beta agonists
the classical research includes now something as ten different
compounds from clenbuterol and its group, I mean manbuterol and
others and salbuterol as well as ractopamine and many others.
All these compounds have been banned in EC and we are looking
for potential misuse of these compounds. The level of detection
of this research is very important to consider and its always
below 2 ppb. and sometimes reach more sensitive levels as some
10 or 20 ppb's. for looking at residues in meat specifically.
Concerning the second part of your question, in terms of percentage
of positive results I cannot answer this question as a scientific
people and the numbers I can give to you would be wrong numbers
for different reasons. The reason is personally I am in charge
of an official national laboratory and I have more positive than
usual because I confirm results of other laboratories. This question
has to be asked to official bodies or maybe to our representative
of official Community reference laboratories but not to me.
Mr. Thompson (Canada)
590. I understand Dr. Arnold
might be aware of results of testing of residues of hormonal substances
in the EC and in particular a study or testing done in Belgium.
Could you help us with that Dr. Arnold?
Dr. Arnold
591. I think François
André made a good suggestion since the results of the residue
testing in the EU are given to all reference laboratories. It's
a good suggestion that maybe someone from these laboratories answer
the question. On the other hand I also see these results on a
regular basis and I, what I can say is something that I have already
said yesterday, we have to discriminate between random sampling
which gives you a more relevant picture and sampling of suspect
animals. And I said yesterday already and I would like to confirm
this, if we take the results of random sampling it's not so bad
the picture. In the majority of the member States you find nothing.
There are some member States, I would not name the member States,
but there are some member States where in veal calf there seem
to exist problems, mainly with the natural hormones. If we go
to suspect sampling then the picture is totally different, then
we have member States where we find trenbolone, zeranol, where
we find protestosterone, sometimes just a few samples, sometimes
a higher amount. But this higher figure is not representative
for the situation because this then sometimes are follow up analysis,
so I hope I made clear what my point is. Based on random sampling
the situation seems to be relatively okay, with the exception
of veal calves in some countries. Based on suspect sampling,
we find all 30 things sometimes in some samples.
Dr. André
592. May I add just a short complement
to these two communications. First of all, its clear that all
the compounds I speak about are not looked for in any other countries
as in EC. And when we discover some misuse of such compounds,
usually and quite systematically I think, the meat is not delivered
to human consumption.
Mr. Thompson (Canada)
593. Yesterday we heard quite
a bit of discussion concerning hormone levels and I would like
to clarify with the experts what is a physiological range and
how that range is determined and what controls that range. In
particular I believe Dr. Liehr cautioned us that permitting the
use of growth-promoting hormones in meat might upset the balance
of hormones in a human ingesting the meat. Can the experts describe
what the balance of hormones in the body is; is it fixed or does
it change on a daily or weekly basis? And if hormones are added
directly to a human, what effect does this have on that hormonal
balance? Perhaps some comparisons between the ubiquitous 500
grams of meat and a couple of eggs or a glass of milk which are
also ingested on a regular basis would be a useful comparison.
Dr. André
594. Concerning the balance of
hormones we need to maybe a week for discussion to explain what
is now known about the inter-relations between hormones and the
complex feed-backs phenomena and so on. Just to have an idea
of the effect of injection of hormones to human beings, it's well
known I think that body-builders or sportsmen who are using hormones
as anabolizing agents, with higher doses as usually used in growth
promotion it's clear, but these people have always later very
many problems in terms of reproduction and sterility its clear.
That is one idea to illustrate what can a hormone do in human
beings.
Dr. Lucier
595. I agree with what Dr. André
said. The hormonal situation in your body is changing as we speak.
It's changing in my body, you get nervous your glucocorticoids
go up, that does other things to you, so they are constantly changing,
in constant state of flux. How each of the hormones regulate
each other is not an entirely known fact, in fact its not really
known at all, except that that type of balance does occur. There's
tremendous inter-actions, cross talk as we call it, between different
hormonal systems. When this is disrupted there can be a whole
cascade of events which could result in changes in biology and
potentially adverse effects. After having said that, the amount
that one would take in from say if we come back to the example
of 17 beta oestradiol in eating 500 grams of meat a day, you basically
take in one molecule of oestrogen if you were a women to every
280,000 in your body. So the chances that that would cause an
endocrine disruption is probably very very slight, remarkably
close to zero. If you are a man your levels would be one-fifth
that so it would be one molecule to every 50,000 molecules or
something like this, so the chance that that would cause in itself
an endocrine disrupting event is of course highly unlikely. There's
no doubt that it's causing endocrine disruption in the animals
that are receiving it, that's why they grow because their hormone
system is disrupted and modified and the balance is changed.
It's a question of amount.
Dr. McLean 596. Just by way of illustration of the variation, if people want to turn to the attachment of my submission, you will see the enormous ranges in pregnant cattle, or in cattle of progesterone, oestradiol and testosterone; the ranges and the variations e.g. in pregnant cattle in muscle for example, the levels are 10,000 nanograms per kilogram plus or minus 6,600. Enormous variations. And I think that just reflects the individual animals and so it's terribly difficult to tie this down absolutely and precisely.
Chairman
597. I mean a very popular comparison
alluded to, the egg, the amount of hormones you eat with an egg
and then it's compared to what you eat when you have an intake
of hormone treated meat. Is that a comparison which can be done
and could you elaborate on this?
Dr. Ritter
598. Well I'm thinking we could
and in fact a number of responses contain that direct comparison.
The steroid levels would be contained in a glass of milk, for
example. The steroid levels that would be contained in a feeding
of breast milk to a new-born infant would be thousands of times
higher than what one might expect in a steak or a hamburger.
But if you would like a more precise number I'm just going to.
Chairman
599. It is just whether one can
make these comparisons, whether they are sound.
Dr. Ritter
600. I think what I'm intimating
Mr. Chairman, is that one really can't because they are in different
worlds...
Chairman
601. ... You can't ...
Dr. Ritter
602. Let me put it another way.
One can physically make those comparisons, the numbers are available.
But there is no basis for comparison. The steroid levels associated
with a glass of milk or human breast milk or any number of foods
would be many many many times greater...
Chairman
603. ... Yes, but these are the
same steroids?
Dr. Ritter
604. Exactly the same. We are
talking orders of magnitude difference in terms of the dimension
vis-a-vis the levels of exposure from a hamburger resulting from
an animal that has been treated, when compared to a glass of milk
that you might have from an animal that's never been treated at
all.
Dr. Arnold
605. My colleagues have limited
their statements to the identical molecules. If we would add
to those identical molecules other naturally-occurring hormones
in food which have a different potency maybe less potent, but
have oestrogenic action for example, then we would discover that
in many kinds of natural food including plant origin we find such
activity. The steroids and their derivatives, as I said yesterday,
were very successful in evolution. So, even if you go down to
molluscs to sea urchins, you find these substances, you can't
escape eating these substances, or similar substances with related
biological potential every day. So, there is no way even if you
decide to castrate yourself, in addition to starve to death, to
escape these hormones.
Dr. Ritter
606. My colleague Professor McLean
points out that in the second submission of the United States
(28 October 1996) that sort of comparative table, I have
personally not verified each one of these numbers, but that sort
of comparative table is in fact is presented on page 4. The intake
of oestrogen or oestrogenic equivalents ranges from tens of thousands
in the case of soya beans; the case of in an egg, you referred
to an egg as 17,015 nanograms, and when we are looking at an oestradiol
implanted steer, levels that have been estimated are somewhere
in the order of 11 nanograms. A glass of milk might represent
75 nanograms in this table, cabbage 24,000 nanograms. I emphasize
that these are oestrogen equivalents because in some cases it
is oestrogen directly, in other cases these will be what is sometimes
referred to as phyto-oestrogen which are compounds which are not
quite oestradiol but are known to have an activity that is what
we sometimes refer to as an oestrogen mimic, it's an oestrogen
want-to-be. Zeranol is in fact produced for exactly that purpose.
It is not oestradiol directly, but it is clearly, it is produced
as a result of a fungus, but it has an action which is so similar
to oestradiol although the potency is somewhat different, that
we call it an oestrogen.
Mr. Thompson (Canada)
607. Just to follow up on that
a little bit, as is obvious to every one I'm not a scientist and
simple examples help me. Someone has suggested an example for
dealing with physiology is to compare it to a thermostat in a
house where there is a range of temperature that is contained
and within that range are normal things that occur, and the temperature
may vary up and down but that's a normal occurrence. And when
one drinks milk or eats eggs or consumes cabbage there will be
an increase within that normal physiological range. One of the
things I wanted to follow up on, and perhaps Dr. Lucier can help,
as he drew the comparison with the 500 grams of treated beef of
one molecule from 28,000, by comparison are you able to help us
with how many molecules per 28,000 we might find with a glass
of milk in a pre-pubertal boy, the glass of milk for breakfast?
Dr. Lucier
608. Just say young boy! to
save further embarrassment!
609. Now the numbers for milk
I have are a little bit different. I have them for 17 beta oestradiol
and they are a little bit higher than what you see in muscle tissue,
I have no way to know, since I haven't done the measurement myself,
which numbers are accurate. These things as has been stated before,
are present in milk and virtually everything we eat, oestrogen.
So, you get an oestrogen load in addition to your endogenous
oestrogen from a number of different sources. Not only the natural
17 beta oestradiol from what you eat but also from the phytooestrogens
and the fungal oestrogens that were already talked about. There's
a considerable amount of phyto-oestrogens in soya products especially
soya oil. So we are exposed to a lot of different kinds of oestrogens
just from day-to-day living that are exogenous, not produced by
our own body. It would be very difficult for me to total them
all up and that's one of my actual research interests to try and
do that to see what the body burden oestrogen that we encounter
from day-to-day living from exogenous sources, to get some idea
what the risk of various kinds of disease might be because of
those exogenous sources. So I cannot give you a very good answer
except to say this would only be, the amount one received from
eating 500 grams of meat, would be relatively small compared to
the other sources of exogenous oestrogen one receives.
Dr. André
610. Mr. Chairman may I give
you another example of hormone interactions, in relation to the
quantity of hormones in order just to illustrate what has been
said previously. We have known hormone the name is cortisone
which has various properties and anti-inflammation properties.
And we have always a secretion inside of these compounds. When
you have, for example, an acute inflammatory process the physician
will give you a high dosage of exogenous or similar compounds
as cortisone, for example. And then your own secretion will decrease
dramatically in place of the exogenous compound but after this
maybe a week later you will no more need the ....... [tape ends]
611. For a chronic skin disease
you will take very, very small doses of the same compound, cortisol
or cortisone or another one, and your own secretions will decrease
very, very slowly. But if you take these very small compounds
as drugs during months, and then when you will stop, you will
never recover your own secretions. It will have stopped definitely.
612. That's the difference between
an occasional use and a permanent use.
Chairman
613. What will be the conclusion?
Dr. André
614. We cannot compare the food
intake of drugs or hormones in meat occasionally, or the consumption
of a pregnant cow, beef for example, which can give you a lot
of hormones and the small amount of hormone food intake for all
the population during months and years. It is two very different
things.
Dr. McLean
615. If I could give you another
example, as a male contraceptive agent, male humans are given
testosterone, which by feedback mechanism, inhibits the production
of sperm. This form of contraception in human males is being
trialed at the moment. In other words, you are giving extra testosterone
and the pituitary gland sends a message down that there is too
much testosterone and shuts off the natural production, but at
the same time, it shuts off some of the hormones associated with
sperm production, and renders the individual temporarily sterile.
And of course once you remove the testosterone being administered
to the male, then it all comes back to normal. That is therapy
that is undergoing trial, at the moment, in a number of countries
of the world.
Chairman
616. Could I just come in with
one question which puzzles me? When we see these naturally-occurring
high exposures in milk or eggs, how does that relate to the cancer
research we heard yesterday? Is the risk that is being assessed
today where we have seen some thesis on it, is that equally valid
for this naturally-occurring intakes every day or is there something
special when we talk about growth promoters? Could Dr. Lucier
perhaps elaborate?
Dr. Lucier
617. Let me do the best I can
on that. If you start out with a premenopausal woman and
her oestrogen level which of course is very high, this results
by a tumour-promoting mechanism, and I don't think I need to go
into that at this point, in about one woman getting cancer in
every ten. So, out of every ten women in their lifetimes, one
of them will get cancer. And that's primarily the consequence
of her naturally-occurring oestrogens. And that's the point,
and I've made a lot of comparisons throughout this meeting.
618. If you look at the beef,
eating 500 grams of beef, you would get one molecule for every
28,000, the premenopausal woman normally has, and one could
estimate a cancer risk based on that.
619. If one says then from other
sources, besides beef, there is a hundred molecules, and I'm just
pulling that number out of the air, but say it's a hundred, and
that's probably a conservative estimate. Then, that would contribute
a hundred molecules and so the cancer risk from all other sources
of exogenous oestrogens would be a hundred times that what it
is in beef, from a growth promoted animal.
620. So the risk would be very,
very small. Eating meat from a growth promoted animal would only
represent a small fraction of the total cancer burden caused by
exogenous oestrogens, not normally produced by the body. Again,
it's impossible to give a precise number for the reasons I said,
because there is a vast number of environmental oestrogens out
in the environment and we only know about a few of them. We certainly
don't know about all of them.
621. I think my conclusion would
be based on the assumption that all the oestrogens are acting
alike, that they all interact with the oestrogen receptor and
stimulate the same battery of genes as a naturallyoccurring
17 beta oestradiol. That's certainly true for the more potent
oestrogens, some of the fungal oestrogens, some of the phytooestrogens,
these kinds of things. They activate the same kind of genes so
there is a reasonable scientific foundation, for my conclusion,
although there is some uncertainty in it.
Chairman
622. Mr. Thompson.
Mr. Thompson (Canada)
623. Professor André,
there are a couple of questions I have concerning some of your
answers to the Panel and I am hoping you can clarify them for
me, in particular, your answer to Question 2. You state in part:
624. When we go to the source
of Lowman, the statement does not seem to be supported. I could
read from page 48 of the Lowman Report. It says:
as opposed to a significant alteration,
as mentioned in your quote. It goes on:
625. In respect of the Gerkin
Article, where you have indicated the Gerkin article identifies
a significant loss of tenderness, at page 3323 of the Gerkin
Article, the author states:
626. Can you help me with how
these articles support your statement?
Dr. André
627. It's clear that I have not
invented this assertion and that they are also inside. When you
see only Lowman abstract, in the last sentence. It says:
That means that there is a small
reduction of eating quality but there is one.
628. If you discuss about the
difference between significant and marginally, marginally can
be significant, statistically! Sorry, but statistically, it can
be small, but significant!
Mr. Thompson (Canada)
629. I also had a question about
Question 6A.
630. This is dealing with whether
there is any more recent scientific evidence available with respect
to the effects on human or animal health of the use of the six
hormones in dispute, especially when used for growth promotion
purposes, other than the evidence already taken into account by
Codex. And you state as follows:
and you cite Nimrod and Benson:
631. When I look at the source,
namely Nimrod and Benson, it appears that the conclusion that
sperm counts have declined, is in fact controversial. And the
only reported decrease in human sperm count refers to counts of
men in Paris, over the past 20 years, which is within the European
Community and unlikely to be directly related to eating hormone-treated
beef.
632. Can you help me with the
correlation between the decrease in sperm and the sex hormones
at issue for growth promotion here? This question is addressed
to Dr. André.
Dr. Lucier
633. The sperm count issue is
controversial. Some people feel that sperm counts in the industrialized
world are going down, other people feel that they are not. And
there is a lot of methodological issues, without going into the
details, that are creating the controversy.
634. The decreased sperm count
has been reported in more than one publication, however, but that
has not removed the controversy in this legitimate scientific
debate. It is not only men in Paris. For example, men in California
only have half the sperm as men in New York. I'm not sure why!
The men in New York are very proud.
635. It is a very a controversial
issue. There are data from experimental animals that show that
neonatal exposure to oestrogenically active agents does cause
a decrease in sperm count, later in life, in the male offspring,
and there are plausible biological mechanisms for that. 636. But again, the question of whether or not, the amount received, I think it is highly questionable that the amount received in eating beef from hormone treated animals would be necessary to produce that. TO CONTINUE WITH EC MEASURES ON MEAT - COMPLAINT BY THE U.S. |
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