ATDEPARTMENT OF HEALTH AND HUMAN SERVICES

> FOOD AND DRUG ADMINISTRATION
>
> CENTER FOR FOOD SAFETY AND APPLIED NUTRITION
>
> **FOOD ADVISORY COMMITTEE**
>
> **METHYLMERCURY**
>
> Wednesday July 24, 2002
>
> 8:30 a.m.
>
> Sheraton College Park Hotel
>
> 4095 Powder Mill Road
>
> Beltsville, Maryland
>
> PARTICIPANTS
>
> Dr. Sanford Miller, Chairman
>
> Ms. Catherine DeRoever, Executive Secretary
>
> MEMBERS:
>
> Alex D.W. Acholonu, Ph.D.
>
> Francis Fredrick Busta, Ph.D.
>
> Annette Dickinson, Ph.D.
>
> Johanna Dwyer, Ph.D.
>
> Lawrence J. Fischer, Ph.D.
>
> Marion H. Fuller, D.V.M.
>
> Joseph H. Hotchkiss, Ph.D.
>
> Lawrence N. Kuzminski, Ph.D.
>
> Ken Lee, Ph.D.
>
> Thomas J. Montville, Ph.D.
>
> Robert M. Russell, M.D.
>
> Mr. Brandon Scholz
>
> Michael W. Shannon, M.D.
>
> TEMPORARY VOTING MEMBERS:
>
> H. Vas Aposhian, Ph.D.
>
> Sarah L. Friedman, M.D.
>
> Ms. Jean M. Halloran
>
> Margaret McBride, M.D.
>
> Richard E. Nordgren, M.D.
>
> Clifford Scherer, Ph.D.
>
> GUEST SPEAKERS:
>
> Dr. Elizabeth Southerland
>
> Dr. Henry Anderson
>
> Dr. John Middaugh
>
> Dr. Charles Lockwood
>
> Dr. Diane Zuckerman
>
> Mr. Richard Wiles
>
> Mr. Michael Bender
>
> Mr. Bob Collette
>
> [C O N T E N T S]{.underline}
>
> Call to Order, Dr. Sanford Miller 4
>
> Environmental Protection Agency,
>
> Dr. Elizabeth Southerland 4
>
> Questions of Clarification 21
>
> Alaska Advisory, Dr. John Middaugh 53
>
> Questions of Clarification 69
>
> American College of Obstetrics and Gynecology,
>
> Dr. Charles Lockwood 81
>
> Questions of Clarification 85
>
> National Center for Policy Research for Women and
>
> Families, Diana Zuckerman 103
>
> Questions of Clarification 116
>
> Environmental Working Group
>
> Mr. Richard Wiles 127
>
> Ms. Jane Houlihan 135
>
> Questions of Clarification 163
>
> Wisconsin Advisory, Dr. Henry Anderson 180
>
> Questions of Clarification 201
>
> The Mercury Policy Project, Mr. Michael Bender 211
>
> Questions of Clarification 226
>
> National Fisheries Institute, Mr. Bob Collette 236
>
> Questions of Clarification 252
>
> [P]{.underline} [R]{.underline} [O]{.underline} [C]{.underline}
> [E]{.underline} [E]{.underline} [D]{.underline} [I]{.underline}
> [N]{.underline} [G]{.underline} [S]{.underline}
>
> DR. MILLER: Let me welcome you to the second day. We have a lot of
> speakers and we need to make certain that everybody has enough time
> for their presentation. I will remind you when you have five minutes
> left for your presentation, and then when the time is up I will remind
> you of that and, if necessary, we will wrestle for the microphone.
>
> We are destroying more trees again this morning; the pile of papers
> that you have been given is increasing logorithmically. In view of the
> discussion we had yesterday about what was a tile fish and what was a
> mackerel, and so on, we have some pictures of both fish so we know
> what we are talking about. We don\'t have quite enough copies for
> everybody and you will have to share them, but I think that will
> answer the question, yes, Virginia, there is a tile fish.
>
> Our first speaker this morning is from the EPA, Dr. Elizabeth
> Southerland. Dr. Southerland?
>
> **Environmental Protection Agency**
>
> \[Slide\]
>
> DR. SOUTHERLAND: In the Office of Water at EPA we have a program that
> gives technical assistance to state and tribal health departments to
> help them put together fish consumption advisories, if they choose to
> do so.
>
> \[Slide\]
>
> Our program provides technical assistance, and we do a number of
> things. First of all, we have a national guidance that talks about
> what types of species you should sample; what analytical methods are
> available to give low detection limits in those species that are
> sampled. We have a risk assessment document that talks about once you
> get those concentrations in the fish, how would you calculate the
> number of meals that you want to recommend a person make of those
> species. Then, we have a risk management guidance and we also have a
> risk communication guidance, and I will talk about that a little bit
> later.
>
> We also have a national database. Since 1993 the states have
> voluntarily been giving us each year data of their fish consumption
> advisory. So, if you go on our web site you can see all the fish
> consumption advisories that consist of state health protection
> throughout the United States and that, again, has been occurring since
> 1993.
>
> We also have national conferences and workshops. Every year the states
> meet with us in a fish forum. Generally we do this with the American
> Fishery Society. This year it will be in October, in Burlington,
> Vermont when the states meet with us. We will be talking this year
> about emerging contaminants, some new pollutants that have started to
> show up in fish, and we will also be talking, of course, as always
> about the benefits of eating fish.
>
> We also have grants for sampling and analysis. In some cases a state
> will have a suspicion that there is some contamination in their fish.
> They just need a little bit of seed money from us to actually go out
> and measure to see if, in fact, there is a contamination problem.
> Whenever we can, we try to provide grants to states for them to do
> that.
>
> We also do special studies. We have been working on a random
> stratified sampling of all the lakes in the country. It is a big
> four-year study, multi-million dollar, in which we are randomly
> sampling lakes of all different sizes around the country and measuring
> them for over a hundred different contaminants. It is not just the old
> banned chemicals that we have already been concerned about, but it is
> a lot of new chemicals, new pesticides that are currently being used
> and we want to check and see if there are some emerging pollutants
> that currently we are not sampling for on a regular basis. So, that is
> one of the special studies we are doing.
>
> Finally, a number of times states, particularly in inter-state waters
> where there is a disagreement between states sharing a body of water
> over what kind of fish consumption advice they want to handle, they
> will often call us and we will provide technical assistance to the
> involved states.
>
> \[Slide\]
>
> I have done this just for lake acres. A similar pattern, however,
> would be shown for rivers. Across the X axis is the number of lake
> acres under advisory, and this is in millions of acres. Then, along
> the Y axis we have the five most frequently detected pollutants.
> Again, if you look at our web site you will see that state health
> departments have set fish consumption advisories for 39 different
> pollutants. These, however, are the five most frequent. Dioxin
> doesn\'t show on the graph. There are 75 fish consumption advisories
> in the country for dioxin. It is just that in terms of millions of
> lake acres it doesn\'t quite show on the scale.
>
> We have been measuring these advisories since 1993. The states have
> been giving us this data. So, you will see that the real trend in
> terms of increase in advisories is in mercury. Again, we don\'t think
> that that is an indication that there is some new contamination source
> of mercury, it is that the states have more and more over the years
> begun to monitor their fish for mercury concentrations. So, that is
> why you will see that that is now the most prevalent cause of fish
> consumption advisories put out by the state health departments, and it
> has been increasing, much more so than the other pollutants which have
> pretty much stayed about the same.
>
> \[Slide\]
>
> This is a really busy slide and I ask you to please look at the
> handouts. We have them at the front table, if you haven\'t already
> picked one up. This map shows several things and I will try to walk
> you through it and then we can talk more about it in the questions and
> answers, if you want.
>
> The states that are in white, they are ones that do not have any fish
> consumption advisories at all. It is mostly in the West and Alaska and
> Hawaii. The ones that are in pink, varying shades of pink, or striped
> pink, or red are states that do have fish consumption advisories. They
> may have statewide advisories that say all the freshwater fish in this
> country are under some kind of mercury advisory, or they may point out
> individual water bodies for fish consumption advisories. It is not
> necessarily all species of fish; it may be selected species of fish.
> It may not be all waters; it may be certain waters. So, it varies
> state by state but we are trying to show this to you on a national
> basis.
>
> The reason you have that blue line around the southeastern Atlantic
> coast and all of the Gulf of Mexico is that the states that border
> that coastline all have coastline advisories for mercury for a number
> of species of fish. So, that is why you will see the blue there.
>
> The other thing of interest here is that there is a little square in
> 11 of these states, and many of them are on the northeastern side so
> you can\'t even see it in the little tiny state itself but it will be
> written next to the state name. But it is a total of 11 states which
> have given their public advice on commercial species as well as on
> recreational species. The reason they did this is because they realize
> people do not only eat fish that they catch themselves, but they also
> go to the store and to the restaurant and they eat commercial fish
> too. So, these 11 states are giving advice to their public on eating
> commercial species of fish as well as recreational species. Nine of
> the 11 states that issue this commercial advice include tuna in their
> recommendations because so much of the diet that many people eat of
> fish are tuna fish sandwiches.
>
> We used these states as an example in trying to do our national
> recreational fish advisory. So, when I talk about that at the end of
> my presentation you will see that we included the FDA advice in with
> our recreational fish advisory to try to keep down confusion where we
> are seeing some difference for recreational fish than FDA is saying
> for commercial fish. So, we use the example of these 11 states as a
> model to follow, and I will discuss that at the end.
>
> \[Slide\]
>
> I know we went over this ad infinitum yesterday, but the reason I am
> repeating it now is as a reminder of what we use. EPA uses the RfD
> that the National Academy of Sciences recommended in July of 2000, and
> that is the 0.1 ug/kg body weight per day. ATSDR has a different
> number and FDA has yet again a different number. The reason I am going
> back through this is for the next slide.
>
> \[Slide\]
>
> If you look at the RfD that the states use for setting their mercury
> fish consumption advisories, it varies by the state. Again, if you
> look at the top graph, I think it adds up to 38 or 39 states that give
> advice that they call out just for adults. That means they are not
> differentiating women from men; they are just saying adults. Of those,
> 25 of the states that give advice for adults will use the 0.3, which
> is the ATSDR number. Seven of them use the National Academy of
> Sciences EPA number of 0.2 and then there are smaller numbers using
> RfDs on either side of the scale.
>
> If you drop down to the second graph, this is the number of states
> that are giving specific advice for women and children. These states
> generally, 23 of them, use the 0.1 or the EPA RfD. There are four of
> them that use the ATSDR number and then a few that use other numbers
> on here.
>
> So, when you drop down to women and children, it is generally the 0.1
> that is being used to give their fish consumption advice. It turns out
> that there is a total of 16 states who give both kinds of advice and
> use different RfDs depending on what public they are trying to look
> at. So, we call that a two-tiered advisory. What those 16 states do,
> they use the 0.3 RfD to give advice for women who do not wish to have
> children or are too old to and for men. That would be the adults.
> Then, for women of childbearing age and children they use the 0.1.
>
> So, that is generally what we would call two-tiered advice. All the
> other states that give advice use a consistent RfD for adults versus
> women and children. There is a lot of information there and, again, it
> is state by state so we can talk about that in questions and answers
> also.
>
> \[Slide\]
>
> When I talked about the national guidance that EPA puts out, again, we
> update this guidance about every two years just to keep current with
> the science. Again, the sampling information will talk about what
> species and what kind of analytical methods you should use to get as
> low as possible detection limits. Our risk assessment guidance is the
> type of equation that we would follow and that we use for our national
> recreational advisory. It is basically set up to calculate allowable
> meals or recommended meals based on the fish concentration that you
> have.
>
> Again, we have risk management and risk communication guidance. The
> risk communication guidance that we have has some really innovative
> things that several of the states have come up with on getting the
> word out very effectively, particularly to sensitive subpopulations
> who may not be English speaking, who may be low income people, who are
> not going to be able to use the same kinds of communication techniques
> that we do where you are looking in a big, giant booklet with 700
> pages of recommended fish consumption advice. So, we have some really
> neat things in volume four that the states have come up with on how to
> communicate effectively.
>
> \[Slide\]
>
> Of course, we use our own equation to come up with our national
> recreational fish consumption advisory. This is the one that we use.
> Of course, we use the NAS recommended RfD of 0.1 ug/kg body weight per
> day. We assume the body weight of 65 kg, looking at that as a woman\'s
> body weight. We looked at a meal size as 8 oz uncooked. Then, the
> concentrations of mercury that we looked at before we put together our
> advisory were all the ones that had been submitted to us by the states
> for our national listing of fish and wildlife advisories. That is what
> that NLFWA stands for. I am going to show you a chart that gives you
> all that concentration information in just a second.
>
> Basically, what we do is we take the maximum daily fish consumption
> rate, equal to the RfD times the body weight, divided by the
> concentration in the fish, and what I will show you next is a slide
> that shows the concentration of the fish and what that equates to in
> terms of a daily fish concentration rate.
>
> \[Slide\]
>
> When we look at this table, and that is using that calculation, if
> your fish concentration is 0.1 ug/kg, then you could eat nine meals
> per month. If it is 0.2, you could eat 4.5 meals per month, and it
> goes on down. This is generally how states will set up their fish
> consumption advisory. They generally do not say don\'t eat any fish at
> all; the consumption rate is zero. Instead, what they do is, based on
> the data they have about the concentration of their fish, they
> recommend a consumption rate because they want people to eat fish;
> they want to keep the fishery open as much as possible. So, they will
> always produce their advisory in the form of what they recommend for
> fish consumption of specified species that they have concentration
> data on.
>
> \[Slide\]
>
> If you look at this, the 4.5 meals per month comes right in at about
> 0.2 and you will see how we came up with our concentration rate to fit
> our national recreational advisory for the country. What we have here
> is a whole huge set of data that the states have given us of mercury
> concentrations they have monitored in their fish over the years.
>
> I am going to get to the statistics now. We had 66,000 samples from
> 8,000 stations, and that was provided by 44 states to make up this
> analysis that we did for the national recreational advisory. Alaska
> and five other western states did not provide any data at all. So,
> these 44 states that we have are missing information from Alaska or
> for those five western states.
>
> However, if you look at the N over here, the sample size number,
> generally we have at least a hundred or more for each species, and in
> some cases thousands of samples. We have the mean mercury
> concentrations if you go along the bottom axis, the X axis. If you
> come up at the one meal per week number, it would be 0.16 ppm. As you
> can see, that is protective for most of the species. It looks like it
> is over-protective for those species at the bottom of the graph where
> the line is to the right of those concentration numbers. However, if
> you look at those species, and we also did this analysis, they are
> generally ones that also have high PCB constituents.
>
> So here we go again, this is a mercury advisory, however, at the same
> time we don\'t want to focus only on mercury and then recommend that
> people eat lots of fish that may be high in PCBs. So, what we decided
> to do, and this was a judgment call, is to call it at one meal per
> week because that would be protective for most species for mercury and
> it would not be, we felt, too over-protective for the species that
> were kind of low in mercury because in the 44 states that gave us data
> on those fish, they were high in PCBs. So, again, a judgment call\--we
> came up with one meal per week.
>
> \[Slide\]
>
> Here is the test of what we said. First of all, we directed this not
> just at women of childbearing age but also nursing mothers and also
> young children. We recommended one meal per week for untested waters.
> This would be waters in which no one has any idea what the fish
> concentrations are. From our national database of mean mercury
> concentrations we wanted to give some kind of rule of thumb to the
> public when there was no testing information available; no advice
> available from their state health department or tribal health
> department. So, in that case, for that untested water we are
> recommending one meal per week.
>
> Because of the confusion over FDA also giving advice at the same time,
> and we did coordinate very closely on the release of our information
> with FDA\'s, we wanted to make sure and recognize this. So, what we
> said is for commercial fish we are recommending that you follow the
> FDA advice, and then we go on and say for the highlighted area here,
> in yellow, therefore, if in a given week you eat 12 oz of cooked fish
> from a store or restaurant\--the commercial fish covered by the FDA
> advice\--then do not eat fish caught by your family or friends that
> week.
>
> So, again, we tried to follow the model of those 11 states that
> currently give commercial and recreational advice. We recognize that
> people will eat a mix of fish generally in their diet. So, if you are
> eating the full amount that FDA recommends for commercial fish, we are
> recommending that that week you do not eat your own fresh caught fish.
>
> DR. MILLER: Dr. Southerland, five minutes.
>
> DR. SOUTHERLAND: Thank you, I am almost done.
>
> \[Slide\]
>
> We also went on to say EPA recommends that women who are or could
> become pregnant, nursing mothers and young children follow the FDA
> advice for coastal and ocean fish caught by family and friends. Again,
> our advisory was for lakes and rivers. Generally, the commercial fish
> cover the marine types of fish. So, we are also recommending that they
> follow FDA advice if they are catching their own ocean and coastal
> fish. Then we go on to talk about other sources of protein.
>
> \[Slide\]
>
> I just wanted to throw this in because we were excited to have the
> NHANES data also. We did a little different analysis than what was
> presented yesterday, and I am sure all of us will be doing different
> analyses over time. But when we took the NHANES data, of course, we
> wanted to look at the split out if you followed our advice, if you had
> just one fish meal per week.
>
> So, what we did is look at the total mercury blood levels, along the X
> axis, for those people who ate more than one per week or those people
> who ate less than one per week. What we saw for those people who eat
> one or more meal per week is the blood levels at or above 5.8 ug/L,
> which corresponds to the NAS EPA RfD of 0.1, and 15.3 percent of them
> were at or above the 5.8 ug/L. For those who ate less than one meal
> per week, it was 1.9 percent at or above 5.8.
>
> So, when we look at this data, and everybody has their own
> interpretation as we heard yesterday, we feel like we have come up
> with a good recommendation for people to keep those blood levels at a
> reasonable level of one meal per week for waters that are untested and
> you have no idea what the fish contamination is like in those waters.
>
> \[Slide\]
>
> We have done a lot of outreach on our advisory. Our advisory,
> remember, includes this connection to the FDA advice. We have worked
> with ATSDR to distribute this to pediatricians and obstetricians
> throughout the country. The 12 states that have statewide advisories,
> and that includes Alaska who says eat as much as you want, we have not
> sent this information to because we did not want to confuse the
> public. Those states that have their own statewide advice are free to
> give their own advice, but to those states that do not cover all their
> waters and have a lot of untested waters, we have sent this
> information out.
>
> We have advisory brochures now translated into seven different
> languages. Those are more generic advisories, not just for mercury, on
> how to trim and clean the fish to minimize your exposure to
> contaminants. Then, we have participated in many medical conferences.
> We even go to the midwives conferences, as well as pediatricians and
> obstetricians to make available our information. That is it.
>
> **Questions of Clarification**
>
> DR. MILLER: Thank you. Questions or comments? Dr. Russell?
>
> DR. RUSSELL: Thank you, that was very clear. There is some confusion
> about serving size and how 8 oz was picked. Could you clarify that for
> us? There was some data shown yesterday where the serving size that a
> woman actually eats is more like 2.6 oz.
>
> DR. SOUTHERLAND: Yes, the 8 oz came from what generally the state
> health departments had asked us to use as a recommended meal size.
> Jeff, do you have any more detail? We do all of our advice in
> conjunction with the states because ours is not a regulatory program;
> it is only a technical assistance program. The states have generally
> used 8 oz uncooked, which works out to 6 oz cooked for an adult.
>
> DR. RUSSELL: They may use it, but I am wondering does anybody know the
> origin of that.
>
> DR. HOTCHKISS: Joe Hotchkiss. I am just curious, to your knowledge, do
> all states or localities that have advisories say something to the
> effect that if you are pregnant or could become pregnant\--
>
> DR. SOUTHERLAND: Of childbearing age, yes, generally. Jeff, is there
> any exception to that?
>
> DR. BIGEL: \[Not at microphone; inaudible\]
>
> DR. SOUTHERLAND: His question was is there any exception to states? Do
> some states not say women of childbearing age? Do they say only
> pregnant women or something more restrictive?
>
> DR. BIGEL: \[Not at microphone; inaudible\]
>
> DR. SOUTHERLAND: But generally when they say women, they say women and
> children together.
>
> DR. HOTCHKISS: Thank you.
>
> DR. APOSHIAN: I have two questions, one very short one. Does the EPA
> have data going back, say, 25 years on fish from a given lake and
> whether the amount of mercury contamination is increasing?
>
> DR. SOUTHERLAND: Actually, the oldest data would be from the \'80\'s.
> Jeff, is there any analysis that shows that it is increasing or
> staying the same?
>
> DR. BIGEL: I am not familiar with that analysis. \[Not at microphone;
> inaudible\]
>
> PARTICIPANT: I am not aware of data directly in fish, but there are
> studies that are done \[not at microphone; inaudible\] and that shows
> low levels of industrial leaching \[inaudible\] and then sort of
> leveling off \[inaudible\] but there has been about 80 percent
> reduction in use of mercury in the economy. So, we expect to see some
> reduction \[inaudible\].
>
> DR. SOUTHERLAND: In our data set, which is just late \'80\'s and
> \'90\'s, we are not seeing a change but that is not really long enough
> to see much of a change.
>
> DR. APOSHIAN: The other question I have, perhaps you or someone might
> comment about it, I heard this morning that\--and I want to be certain
> that it is correct and that is why I am asking for comment\--that in
> those fish that have a high amount of mercury, as I understand it, and
> it is very important that it is clarified, those fish have a lower
> amount of essential fatty acids; that there is an inverse proportion.
> Now, we have Dr. Mahaffey here who is an icon as far as this sort of
> thing is concerned. She was very much involved in NHANES.
>
> DR. SOUTHERLAND: I am going to have to call on Kate for the fatty acid
> issue.
>
> MS. DEROEVER: Excuse me, could the speakers in the back please come to
> the microphone and introduce themselves so we have it on the record?
>
> DR. MAHAFFEY: I am Kate Mahaffey, from U.S. EPA. One of the things I
> have done recently is to sit down and look at some of the data on
> concentration of mercury in fish and the concentration of a couple of
> the essential fatty acids in the fish because the essential fatty
> acids are frequently cited as one of the major reasons for achieving
> benefits of fish consumption. There are data that show that certain
> fatty acid in fish are important for the neurological development of
> the central nervous system of the fetus. The abbreviation is DHA, and
> it is docosahexaenoic and it goes on from there.
>
> I looked at the species of fish that are the highest in mercury
> concentrations, the ones where the advisories are, which include tile
> fish, shark, king mackerel, swordfish. They are not particularly high
> in this DHA fatty acid that is essential for neurological development
> in the fetus. What the essential fatty acids seem most closely tied to
> is the percent fat in the fish which, of course, makes sense. So, you
> are not really having a tradeoff between how much of the essential
> fatty acid you get. In other words, it is not a one to one
> correlation. You can select fish that are relatively high in essential
> fatty acids, things such as salmon, things such as some of the
> mackerels, and are comparatively low in mercury.
>
> On the other hand, if you look at swordfish, tile fish, king mackerel
> and shark, they are relatively more lean fish and are comparatively
> low in essential fatty acids. So, it is not as though you give up the
> nutritional value. You simply have to exercise wise choices in the
> kinds of fish you select.
>
> I have not done this for another fatty acid that has an interesting
> acronym EPA, not us, because the nutritional content of fish is cited
> as a benefit in terms of coronary heart disease, yet, there are some
> interesting data out of Europe, specifically out of Finland and also a
> multicenter trial, longitudinal cohort studies, and for some reason
> they measured mercury. I honestly have no idea why they measured
> mercury in people\'s hair or people\'s nails, but what they found is
> that when the person\'s mercury exposure had been relatively higher,
> and in the Finnish cohort the demarcation was two or more parts per
> million in hair, the risk of coronary heart disease and the risk of
> deposition of fats in the carotid artery, and they imaged the
> carotids, was higher. So, again, what is going on at least in this
> Finnish study is that the higher exposures to mercury seem to
> attenuate some of the benefits of fatty acids and the nutritional
> benefits of fish.
>
> Again, it is one of these deals where, depending on the fish that is
> chosen, you get more or less benefit of the diet. People have said the
> Finnish study stands alone; we shouldn\'t ignore all the other studies
> that show benefits. The Finnish study appears not to stand alone
> because I am now told that there are reports coming out from a
> multicenter trial in Europe that are showing a parallel kind of
> finding.
>
> You can\'t ignore decades of advice on nutrition, but I think we can
> expand that advice in a way that gives people the benefits of fish
> without necessarily the higher exposures to mercury. So, for both the
> essential fatty acid that is important for CNS development in the
> fetus and also the risks of coronary heart disease it appears that you
> do not have to give up the nutritional benefits of fish in a tradeoff
> for mercury because it is not any sort of one to one correlation. It
> has as much to do with how fat the fish are in terms of the percent
> lipid in body composition as anything else.
>
> DR. MILLER: Dr. Lee?
>
> DR. LEE: Basically, I have the same question about mercury over time
> in fish. So, just to clarify that, one comment about the total
> mercury\--I take it total mercury is not methylmercury that we are
> talking about over time.
>
> DR. SOUTHERLAND: Oh, no, it is methylmercury that is measured in the
> fish.
>
> DR. LEE: But in environmental exposure that increased and has now
> plateau\'d.
>
> DR. SOUTHERLAND: I have to refer to Arnie on the sediment core data.
> Arnie?
>
> DR. KUZMACK: This is Arnold Kuzmack, EPA. That is total deposition of
> mercury of all sorts, mostly ionic mercury that is deposited. That is
> the source of the mercury that gets methylated in the aquatic
> environment and accumulates in the fish. Most of the methylation, of
> course, occurs in the top layer of the sediment at the bottom.
>
> DR. LEE: And you are saying that is in the lake beds? That kind of
> work has also been done on Antarctic cores?
>
> DR. KUZMACK: What kind of cores?
>
> DR. LEE: In the ice in Antarctica.
>
> DR. KUZMACK: Yes, there is some work on ice cores as well which I
> think shows a similar pattern. Lake core is done in various locations
> and typically shows peak levels, say, two to five times the
> preindustrial levels and what that is sort of depends on where you are
> located. If you are near industrial areas it is likely to be a higher
> ratio.
>
> DR. LEE: Thank you.
>
> DR. MILLER: Dr. Fischer?
>
> DR. FISCHER: I would like to ask whether the EPA recommends to the
> states the use of the EPA RfD for everyone\--women, children and other
> adults, or do they recommend a different set of restrictions for those
> two groups, adults versus women and children?
>
> DR. SOUTHERLAND: Right now we just have the 0.1 on the books for
> developmental effects. Because it is listed for developmental effects
> we are recommending it for women and children, but we have not taken a
> position on this two-tiered approach that some of the states have
> done. We do not have an IRIS value right now. It varies for the
> general population.
>
> DR. FISCHER: Why is that, that you don\'t do that?
>
> DR. SOUTHERLAND: Kate, I would have to ask you, the IRIS program is
> our official?
>
> DR. MAHAFFEY: Right. The way EPA\'s reference does this work is that
> they are set for the most sensitive subpopulation. It is not the most
> sensitive member of the subpopulation but the most sensitive
> subpopulation. Since most of what we deal with does not know
> boundaries in the sense that if you deal with an air contaminant or
> water contaminant you can\'t very well separate out the exposures for
> men, for women or for children, the underlying philosophy has been
> that you work to protect the most sensitive subpopulation. While this
> approach of a two-tiered advisory may be effective when you are
> dealing with a limited distribution or self- or family-caught fish, it
> is harder to enforce who eats the fish if it is winding up in
> commercial sales.
>
> DR. FISCHER: You know, it seems to me very hard for you to convince
> people that fish is good for them and that there is benefit of eating
> fish if you are regulating in that way. In other words, why are you
> restricting the consumption of fish to men of my age when, in fact, we
> aren\'t the most susceptible?
>
> DR. MAHAFFEY: Well, until we know more about the cardiovascular risk,
> I don\'t know that I am ready to go there.
>
> DR. FISCHER: I mean, I can\'t believe that you don\'t believe the
> immense literature out there on the benefits of fish consumption.
>
> DR. MAHAFFEY: If you look closely at the studies, they are not
> unequivocally supportive of the benefits. Some of those studies are
> mixed, and it is quite possible to choose kinds of fish that result in
> low mercury. As you can see with the NHANES data that we showed, while
> the percent of people who eat fish one or more times a week is a lot
> higher, in the 6 and above blood level, 85 percent of those people
> were able to select fish that are comparatively low in mercury and
> have blood values under the reference dose. So, it is more to do with
> the kind of fish selected than simply fish consumption. It is as much
> which fish rather than fish or not.
>
> DR. FISCHER: I understand that, but you can see the number of states
> who disagree with you here. Look at the number of states who have the
> two-tiered approach and are using it.
>
> DR. SOUTHERLAND: There are 16 states that have the two-tiered
> approach. It is a little confusing from the way I had to present the
> graph but 16 states do both. The other states, and there is a total of
> 43 that give advice on mercury, will use a consistent RfD. So, this is
> a new thing that states are starting to work on, the two-tiered
> approach.
>
> I am going to have to make a point of clarification here, though I
> don\'t want to interrupt the conversation between you and Kate, but we
> have no regulatory authority. EPA has no regulatory authority. All we
> do is talk to the states about advice, and the states have no
> regulatory authority. When they give advice on recommended meals, they
> are not seizing those fish out of people\'s hands and taking them to
> jail, or anything. They are just giving advice; we are just giving
> advice. There is no regulatory authority in EPA. FDA is the only
> agency that has that.
>
> DR. MILLER: Dr. Russell?
>
> DR. RUSSELL: There is a lot of interest now in DHA and EPA with regard
> to membrane stabilizing effects and sudden death, prevention of sudden
> death. Is there any data that high levels of mercury cancel out that
> effect? Because this is totally different from coronary-artery
> disease.
>
> DR. MAHAFFEY: I am assuming you are addressing that to me. As I recall
> the Finnish study, there was a greater incidence of mortality in the
> people that had the higher mercury levels. As you say, it gets into
> the underlying mechanism of oxidation and heavy metals such as mercury
> to promote oxidation.
>
> DR. RUSSELL: Well, these fatty acids specifically stabilize membranes.
> It is a physical-chemical thing.
>
> DR. MAHAFFEY: Right, but it is a highly unsaturated fatty acid.
>
> DR. RUSSELL: Yes, but it may not just be from oxidation.
>
> DR. MAHAFFEY: Exactly. Again, I am recalling this data from memory. I
> would be pleased to follow-up and provide the paper to you.
>
> DR. RUSSELL: Thank you.
>
> DR. MILLER: Dr. Aposhian?
>
> DR. APOSHIAN: I think it might also be a good idea, since we have Kate
> here because I have learned some things this morning that are very
> educational to me anyway, as you know there have been questions about
> the 60,000 children at risk that the National Academy of Sciences
> report pointed out. Yesterday some people questioned this as being too
> high. I believe Kate has some data that she might want to share with
> us, suggesting that the 60,000 National Academy of Science figure is
> too low.
>
> DR. MAHAFFEY: Again, this is from memory. I would be glad to go back
> and get the specific numbers, but as I am recalling this, there are
> about four million births in the U.S. per year. If you take the NHANES
> value, the 99 alone showed about 10 percent of women with blood
> mercury of 5.8 and greater, the combined 99 2000, the number turned
> out to be, I think, about 7.8. So, somewhere circa 8 percent. If you
> take 8 percent of one million, you are coming out with about, I would
> think, 320,000. If you take the 10 percent, it is 400,000 newborns a
> year. If you apply the NHANES data and the number of births, that
> would be the estimate of the number of infants born each year where
> you would expect to see their initial blood mercury higher than the
> value that EPA believes to be safe. So, we don\'t think the 60,000 is
> too high. If anything, the data suggest it is comparatively low. I am
> sorry, 10 percent of 4 million would be 400,000; 8 percent would be
> about 320,000.
>
> DR. DICKINSON: \[Not at microphone; inaudible\]
>
> MS. DEROEVER: Dr. Dickinson, would you please use the microphone?
>
> DR. MAHAFFEY: I see what you are doing, 60 million women of
> childbearing age approximately, the data show about 9 percent in that
> age group in a given year are pregnant. There is another number, I
> think it is 6.5 pregnancies per 1000 women. You know, we went through
> the math.
>
> DR. FISCHER: I would like to ask you to give us the calculation that
> you are speaking of\--
>
> DR. MAHAFFEY: Sure, that is fine.
>
> DR. FISCHER: \--so that we have it to look at.
>
> DR. MAHAFFEY: No problem.
>
> DR. MILLER: Dr. Scherer?
>
> DR. SCHERER: Yes, Cliff Scherer. I wanted to ask a question about the
> extent to which we have any information about the effectiveness of
> advisories. Do you know about to what extent states or how people are
> following advisories?
>
> DR. SOUTHERLAND: There have been some individual studies of that.
> Actually, we have been working with Cornell University and some others
> to do effectiveness measures. That risk commercial guidance document
> that we have actually has the best literature review of that type of
> effectiveness data. What they have generally concluded is if you are
> talking about educated, middle class people who are doing it for
> recreational purposes, those books that the states will give you when
> you buy your fishing license are fine. But when you are talking about
> people that have English as a second language or who are not buying
> fishing licenses, then that is obviously totally ineffectual. What
> they have found is that things like posters\--certain types of
> cultures react very well actually to comic book style posters. They
> also have posting in different languages that can be effective, and
> also big press events. Each year when a state updates their advisory,
> if they do a lot of press work. ORSANCO has been doing a lot of the
> effectiveness studies because they do the fish advisory publicity for
> all of the Ohio river basin. So, anyway, we have some good information
> on what works with what populations.
>
> DR. SCHERER: Do we know anything about the percentage of people that
> are paying attention to those kinds of messages?
>
> DR. SOUTHERLAND: I don\'t know if we have any percentage information.
> I know in the Great Lakes, for example, they have done a number of
> studies and in the Great Lakes, because it is such a high group that
> are eating fish, it is very well publicized. Also, in the Ohio River
> Basin I think they are getting fairly high effectiveness levels. In
> other parts of the country, not at all because, again, it is the level
> of publicity and the type of publicity.
>
> That is why when we have sent our posters out, we send them to the
> pediatrician and obstetrician offices for them to post right there.
> The women and children health clinics also like to get that kind of
> poster effect as opposed to a 700-page textbook.
>
> DR. MAHAFFEY: Michael Bolger told me that the calculation, I guess,
> shows around 350,000 to 400,000 is in your books.
>
> DR. BOLGER: If you look at your figure, you will see it gives you the
> number of women where it says 7 percent, but it is actually more like
> 8 percent based on data from Susan Schober. So, the number of women on
> annual basis who are pregnant is about 276,000 women. That is on an
> annual basis, the number of women who are pregnant who exceed the
> reference dose is about 276,000.
>
> DR. DICKINSON: This is Annette Dickinson. We had some discussion
> yesterday about the fact that that includes the ten-fold safety
> factor.
>
> DR. BOLGER: That is correct.
>
> DR. DICKINSON: So, given the fact that they exceed the RfD with a
> ten-fold safety factor and the effects on which the whole bench mark
> dose is based are effects in the most sensitive population, what is
> the implication of that, that they exceed the RfD? Does it just mean
> their safety factor is less, or does it mean they are actually at
> risk?
>
> DR. BOLGER: This is what I am going to talk about tomorrow. What
> implications you draw really are some of the things I am going to try
> to address tomorrow so I would hate to get ahead of myself today. But
> it is a very good question.
>
> DR. DICKINSON: But we are thinking about it today.
>
> DR. BOLGER: I understand. The margin of safety issue is what you are
> getting at.
>
> DR. MILLER: Ms. Halloran?
>
> MS. HALLORAN: To go back to the point raised just a minute ago about
> consumer awareness, the Northeast States for Coordinated Areas
> Management, which is an association of air pollution agencies in the
> east, reported in May, 1999 in a survey that they apparently did that
> of about 75 percent of their respondents who eat fish on a regular
> basis, about half said they knew about advisories issued by states or
> FDA and one-third said they knew what they meant.
>
> DR. MILLER: It is actually the question that I had, what data was
> there that looked at understandability? I mean, reading that advisory,
> the combined FDA-EPA advisory I found it totally confusing. Now, I may
> not be as clever about this as people who live near lakes, but I found
> that totally confusing. There are three messages, all in one document.
> I was just curious as to what kind of research was done.
>
> DR. SOUTHERLAND: We have not done any consumer research on our
> advisory because it is so new, but we do know that the 11 states that
> are currently giving both commercial and recreational fish advice have
> dealt with this issue before of how to do the tradeoffs between what
> you get from a store or restaurant and what you get caught by
> yourself.
>
> So, we just followed their model in putting out our advice because,
> otherwise, it looked like the two were totally unrelated. We were
> saying one meal per week; FDA was saying 12 oz. They are entirely
> different species involved.
>
> DR. MILLER: Mr. Scholz?
>
> MR. SCHOLZ: Brandon Scholz. I wanted to follow-up on a point that you
> made on EPA\'s outreach. You said it appears that most of your
> outreach is to healthcare professionals who deal with pregnant women.
>
> DR. SOUTHERLAND: And fishery groups, like the American Fishery
> Society.
>
> MR. SCHOLZ: Do you do any other outreach to retail or to restaurants?
> Any other distribution of your materials?
>
> DR. SOUTHERLAND: No, ours is strictly directed at recreational fishing
> groups, like Bass Masters and American Fishery Society, as well as
> health groups. The lead-off statement for us is fish caught by your
> family and friends. So, we do not cross over into the commercial fish
> advice at all. If anyone ever asks about commercial fishery we cite
> the FDA advice. Again, EPA has no regulatory authority for fish
> consumption advisories. We are strictly for technical assistance to
> the state health departments.
>
> DR. MILLER: Some of you may have wondered why I have allowed this to
> continue on, not exactly my usual style for these kinds of things. Not
> only is it an important issue, but our next speaker is not here.
>
> \[Laughter\]
>
> I just don\'t want you to get the wrong idea. Johanna?
>
> DR. DWYER: I wanted to agree with Dr. Miller that I found the advice a
> little confusing, and I kept coming back to the thought that for fish
> there are no recreational uses if you are fishing and you are the
> fish.
>
> \[Laughter\]
>
> I am also taken by some of the problems we hear on the dietary
> guidelines committee on the alcohol recommendations. You know, if you
> think about it, most of the problems with alcohol seem to come from
> the ethanol. Simplifying the advice to something where you can focus
> on that with a very, very simple message I think has gotten through to
> a lot of people, whereas 25 or 30 years ago it didn\'t.
>
> I guess what I am struggling with, and perhaps Dr. Miller is as well,
> for those of us who have to give a five-second sound byte in a clinic
> to a patient, I really need something that is a sentence or maybe two
> sentences.
>
> DR. SOUTHERLAND: I think the way we have tried to hone in on it, and I
> hate to say it because, again, the focus groups have struggled with
> this, but it is the species type. We deal with freshwater fish, fish
> that you would catch from a river or a lake. The marine species are
> generally the predominant commercial species. Now, what is the
> public\'s understanding when they see a species name as to whether it
> is freshwater or saltwater? That is where the confusion is coming in I
> believe.
>
> EPA\'s original recommendation for FDA was to try to do lists of
> species and, apparently, the focus groups just found that too
> confusing. Because if we had done a list of species, then we could
> have had unified advice from both EPA and FDA. I believe we could have
> worked that out but it was just too much detail.
>
> MS. HALLORAN: I hope I understand this correctly, the whole origin of
> the problem of EPA and FDA having to give different advice doesn\'t
> really come from a separate evaluation of the safety of freshwater
> fish and ocean fish. Ocean fish is not safer than freshwater fish, if
> I am correct. It is that FDA has made basically different judgments in
> the risk analysis. Is that correct?
>
> DR. SOUTHERLAND: And it is also the concentration of the species. I
> gave you the data that we have, and we have, again, 66,000 samples
> from 44 states and we are looking at our concentrations. I believe FDA
> is a little bit inhibited as they don\'t have as up to date data, and
> I don\'t know that they have as much data on their marine and coastal
> species as we do for our lake and river species. So, they were also
> looking at the concentrations that they had in their database.
>
> DR. MILLER: It seems to me, in response to that, listening to this
> discussion, it is not only that issue. That is one issue. The other
> issue is the fact that this increases the number of species that
> people have to worry about, and that is the problem with people saying
> they get confused when they see these lists even if they are
> identical. Indeed, if FDA lowers its action level, if you will, its
> advisory level, that species list would increase even more. The
> question from a procedural point of view is how do you give this
> advice to people in a way that they will use it and can use it? As far
> as I can hear, that problem has not been resolved.
>
> DR. HOTCHKISS: I want to make sure of your last statement. FDA is
> using an ADI of 0.4; you are using an RfD of 0.1. That is a four-fold
> difference. If you run through the calculations, that seems to me to
> be a major difference in the two agencies\' recommendations. Granted,
> you have different databases and so forth, but the major difference is
> simply that either acceptable daily intake or reference dose, or
> virtually safe dose or whatever you want to call it, is a four-fold
> difference between the agencies. Is that correct?
>
> DR. SOUTHERLAND: Yes, that is correct, but they also did look at their
> concentration ranges for saltwater fish compared to the concentration
> ranges for what we have in freshwater. At least in the lower 48 states
> our freshwater fish can be much more contaminated in some cases,
> particularly certain water bodies that have higher levels of mercury
> sometimes. Again, we were working with a richer database and also
> concentration information. But, yes, you are right, it is a
> combination of concentration and RfD difference.
>
> DR. MILLER: Johanna?
>
> DR. DWYER: I was very much surprised and pleased by the enormous
> number of chemical analyses that you have done on the mercury
> concentration of selected fish. I think it was in our handout. Does
> that go in any databases that are available on computer programs?
>
> DR. SOUTHERLAND: Yes, those are all the data that have been submitted
> to us by the states that do this monitoring and it is all on our web
> site. We have it all.
>
> DR. DWYER: No, I meant databases like the kinds of things people put
> on a laptop computer and dieticians use for example.
>
> DR. SOUTHERLAND: We haven\'t provided to those groups but they are
> readily available on our web site. Again, it is all voluntary. The
> states don\'t have to give us this information at all, but since 1993
> most of the states have been giving us tons of information, not only
> information on their advisory but on the fish concentrations that they
> have monitored.
>
> DR. DWYER: Is it collected in a random\--how is it done? How do you
> collect the data on these fish, and does it go into the standard
> reference database of the food composition for U.S.A.?
>
> DR. SOUTHERLAND: To my knowledge, it only comes to us on a voluntary
> basis. Each state has their own monitoring plan. Some have a rotating
> basin approach and for each year they try to go to another basin and
> they measure fish tissue. Others have a regular, you know, station
> that they monitor each year. It varies by the state and we take all
> the data they give us because it has all been through state QA/QC and
> their laboratories, and they are using it to make their fish
> consumption advisory decisions so it is good enough for us.
>
> DR. MILLER: Mr. Scholz?
>
> MR. SCHOLZ: I would like to ask one more question. You had mentioned
> that there is a Cornell study in place, or it has been done, gauging
> the effectiveness of the advisories?
>
> DR. SOUTHERLAND: Cornell has an investigator up there that we have
> worked with that has done these effectiveness studies. She has worked
> in the Great Lakes area and she has also worked in the Ohio River
> Basin.
>
> DR. MAHAFFEY: There is also additional work in the State of Maine on
> interpretation of the advisories and risk commercial evaluation
> process understanding. So, it is not as though this is a totally
> untapped area.
>
> MR. SCHOLZ: No, I understand that. I was just curious, is that a study
> that we can get? I mean, is that available to us? My question was is
> it ongoing or is it done?
>
> DR. SOUTHERLAND: She has some that are ongoing; she has some that are
> under way. So, I can get those to you, sure.
>
> MR. SCHOLZ: It would be interesting because generally coming from the
> Great Lakes and the Wisconsin area, you know, there is the annual
> story in the newspaper at the beginning of the year that says, in
> short, all fish have mercury; don\'t eat it. So, I would be curious
> what the study says because it doesn\'t seem that the way the press
> reports it is fair because it doesn\'t necessarily differentiate which
> fish, what level, for whom and, unfortunately, it is not a good way to
> come up with what we are trying to do.
>
> DR. SOUTHERLAND: I know that certainly in the Ohio River Basin where
> she did her study there is a big drop-off at the time of the press
> release. She did the analysis and she actually did a time series thing
> right around the press release she did questionnaires, telephone
> surveys and, of course, fish advisories. Then she did it several
> months later and then several months after that and, of course, it
> really drops off over time. That is why I think people are looking for
> things that are more permanent, like posters, signs or something
> either in the health clinics or actually at the point of fishing as
> something more substantive than just a big press release. Again, you
> know, our risk commercial document, and I can get you that also, has
> tons of references of the studies that have been done to look at
> effectiveness.
>
> DR. MILLER: Dr. Busta?
>
> DR. BUSTA: I would like to get back to this collection of data from
> the states. Do you have a distribution as to which states do the most
> analyses, and are they the states with the greatest pollution? Maybe
> the states with greater pollution, are they sampling more and are they
> sampling mainly the polluted areas? Have you any kind of information
> like that?
>
> DR. SOUTHERLAND: Well, actually it started like that in 1993 when we
> began our program and I could say definitely yes, everything that was
> in the database was from suspected problem areas. What has happened
> though, over time as people have become more and more concerned about
> mercury, and that is why they are starting to see these 12 statewide
> mercury advisories, as they went to more and more sites and checked to
> see if they had mercury concerns, they then said, you know, let\'s try
> pristine areas.
>
> This is what they did in Maine, for example, and that is when they
> found that even their pristine areas that did not have a discharge or
> a point source discharger, they found levels of concern for the
> mercury. That is why you see more and more states having these
> statewide mercury advisories because they just said what are we doing
> here? I mean, there is no sense waiting when we even have pristine
> areas because of the atmospheric deposition contributions of mercury.
> We are just going to go ahead and have some general recommendations
> statewide, and then we will continue to try to go water body by water
> body and confirm or deny that assumption. But right now that is what
> the statewides are based on, a general understanding that no matter
> where they looked they had some species that had concentrations of
> concern. It is an ubiquitous problem, it truly is.
>
> DR. FISCHER: I would like to see if we could get some information on
> the overlap between regulated commercial fish and sport fish\--
>
> DR. SOUTHERLAND: I am sorry, I lost you.
>
> DR. FISCHER: What I am trying to see is what is the overlap between
> sport caught fish, which EPA regulates, and\--
>
> DR. SOUTHERLAND: We don\'t regulate; we give advice through the
> states.
>
> DR. FISCHER: Excuse me, I made a big mistake there. I am sorry, I
> should have learned that by now. And, fish that the FDA takes care of,
> commercial versus sport caught. In the Great Lakes basin you can buy
> whitefish and walleyed and a lot of what we would call sport caught
> fish, lake trout. So, here are sport fish that are commercial fish. I
> just wonder how much of the total consumption is confused in this way.
>
> DR. SOUTHERLAND: There is definitely an overlap and the 11 states that
> have that little box in there that says they are giving commercial
> advice as well as recreational, they are the ones that definitely came
> up with this, and you will see there is a lot in the Great Lakes area
> because they said what difference does it make if they go down and
> catch this fish themselves or if they go to the nearby fish market
> where the fish that somebody else caught was put and they purchased
> it? There didn\'t seem to be any reason for there to be a separation.
> That is why the state health departments have decided to give advice
> across the board. Like I said, 9 of the 11 states that do this include
> tuna in their recommendations because they have found so many people
> were eating tuna fish sandwiches and then adding onto that their
> recreational or other commercial fish. So, they felt that they had to
> include the tuna fish in their advice too.
>
> DR. FISCHER: Michigan hasn\'t dealt with this problem at all, and they
> give no advice on purchased sport caught fish. I can\'t remember
> seeing other Great Lake states give it either. I know that creates
> confusion in the public\'s mind as to what they should do.
>
> DR. SOUTHERLAND: Several Great Lake states\--Henry Anderson was going
> to speak next and I know he gives that type of advice. Pam Schubat, in
> Minnesota, does. We have a number of states that give combined advice
> for the Great Lakes states.
>
> DR. MAHAFFEY: Just one comment, mercury, while it is a local problem
> in that there can be local discharge and local deposition, is also a
> national problem. Part of the mercury that goes into the environment
> enters a high atmospheric level pool of mercury that then can be
> deposited in precipitation. For example, it is the United Nations
> environmental program that this fall will do an assessment of mercury.
> The European Union has adopted U.S. EPA\'s reference dose for mercury
> and, again, is doing broad work on fish in Europe because of concern
> for mercury. There is not a clear separation between \"locally caught
> fish\" and fish that wind up in the commercial market. They come out
> of the same water.
>
> DR. MILLER: I think I am going to bring this discussion to a close. I
> think the point has been made. I think what is abundantly clear to me
> is that we are not really very close to a really effective
> communication system to get a relatively simple message that enables
> people to make appropriate decisions themselves. I doubt that we will
> come up with anything better in our time but we ought to be thinking
> about how to approach this particular problem.
>
> I also think that we have spent quite some time this morning
> emphasizing the importance of the issue. I am certain that this
> committee has a general recognition of the significance of the program
> and the importance of doing something about the problem. I think the
> debate that we are having over which number to use is important in
> implementation of any plan, but I don\'t think it reflects the fact
> that the members of the committee in any way take this thing as
> anything but quite seriously.
>
> So, at this point I am going to call this section closed. Thank you
> for this discussion, and we will move on to our next speaker. I assume
> Dr. Henry Anderson is not here. So, the next speaker is Dr. John
> Middaugh, from the Alaska Department of Health, talking about the
> Alaska advisory.
>
> **Alaska Advisory**
>
> DR. MIDDAUGH: Chairman Miller, and members of the Food Advisory
> Committee, I am John Middaugh, State Epidemiologist with the Alaska
> Division of Public Health. I am here today to provide information to
> the committee on behalf of the State of Alaska as a public health
> physician with responsibility for protecting the health of the
> citizens of Alaska. Thank you for providing the opportunity to bring
> to your attention Alaska\'s experience with fish advisories for
> methylmercury.
>
> I am pleased that the Food and Drug Administration is having this
> meeting. I believe that the committee has an important opportunity to
> clarify roles in attaining shared national goals to protect the
> environment and to protect the public health. To do so, it is
> essential to sort out federal agency authority and responsibility and
> to respect the balance between federal and state authority and
> responsibility.
>
> We also have before us new technology that can help us further
> scientific understanding. Finally, we can ensure that we behave
> ethically, adhering to fundamental principles of \"do no harm\" and
> weighing benefits and risks.
>
> Alaska\'s experience with national fish advisories has uncovered
> several major areas of concern and revealed potential unintended
> adverse consequences. Current national recommendations, a \"one
> size-fits-all\" approach, do not make sense in Alaska. National
> recommendations for fish consumption are not consistent with available
> evidence and are not consistent with Alaska recommendations.
>
> Considerable scientific controversy exists over the risks of low-dose
> methylmercury exposure. Data linking low-level methylmercury exposure
> to adverse health outcomes are weak. Adverse neurodevelopmental
> outcomes documented are subclinical, detectable only by sophisticated
> tests of unknown long-term significance. Results may be limited by
> potential confounding. Leading studies have not found similar results,
> and ongoing studies hold the promise of providing important
> information in the near future.
>
> Advisories based upon risk assessment without consideration of
> well-established public health benefits of fish consumption have great
> potential to harm public health if reductions in fish consumption
> occur. We have special concerns over the impact of fish advisories for
> Alaska natives and rural resident subsistence consumers who have few
> alternatives to fish. The public health harm caused by fish advisories
> has been well documented, especially in Canada. Fortunately, data from
> Alaska provide evidence that most, if not all, Alaskan exposures to
> methylmercury are below those of current concern, even applying
> conservative models.
>
> Finally, extensive international scientific investigation of Arctic
> contaminants under the Arctic Monitoring and Assessment Program of the
> International Arctic Science Council during the past eight years has
> led to the consensus Arctic recommendations that the health benefits
> of Arctic subsistence foods outweigh potential risks, and that local
> public health authorities need to take into account local information
> to craft dietary guidelines.
>
> We have a substantial body of scientific information on mercury in
> Alaska. I would like to provide a brief summary of some of the most
> germane studies that provide evidence that determined Alaska\'s
> current dietary recommendations.
>
> I have provided a detailed copy of handouts because there is a lot of
> data and I know that I can\'t present it in 20 minutes.
>
> \[Slide\]
>
> First, we analyzed ancient human hair from mummies from the Aleutian
> Islands in Alaska. The mummies were taken from islands out in the
> Aleutian chain during the 1920\'s when archeologists collected human
> remains and artifacts from burial sites.
>
> \[Slide\]
>
> This is an adult wrapped in reed tissue, and then underneath that
> wrapped in seal skins.
>
> \[Slide\]
>
> This was an infant in a basket.
>
> Our goal was to try to establish if methylmercury was present long
> prior to the industrial revolution and, therefore, represented
> naturally occurring exposure. After receiving permission from the
> Aleut Corporation and the Museum of Aleutians, we collected hair
> samples from four infants and four adults that radiocarbon dating
> established to be approximately 550 years old, dating to about 1450
> A.D.
>
> \[Slide\]
>
> The average level of methylmercury mercury in adults was 1.2 ppm in
> hair, and in infants was 1.44 ppm, with a range of 7 ppb to 4.61 ppm.
>
> \[Slide\]
>
> Segmental hair analysis showed patterns of higher and low
> methylmercury in centimeter segments, compatible with seasonal and
> event-specific changes in mercury exposure through a subsistence fish
> and marine mammal diet. These results are consistent with a few other
> similar studies of mercury in ancient human remains, supporting the
> hypothesis that humans have always been exposed to naturally occurring
> mercury through fish and marine mammals in the diet.
>
> Unlike many areas in the continental United States, there are no local
> industrial sources of mercury in Alaska. Extensive environmental
> sampling during the past ten years has documented that Alaska is one
> of the most pristine areas in the Arctic.
>
> I want to go over the next set of slides very quickly. They show some
> of the wealth of sampling data of fish species. These results are for
> 1993 from U.S. FDA. In red, you can see for salmon many of the results
> are undetectable.
>
> \[Slide\]
>
> This is from the ATSDR criteria document. Again, salmon is 0.035 ppm.
>
> \[Slide\]
>
> Again, our Department of Environmental Conservation lab, shows 1999
> results and again in red are highlighted the salmon results. They are
> almost all about 0.025 or non-detectable.
>
> \[Slide\]
>
> Researchers at our University of Alaska, measuring king salmon
> methylmercury levels are in this column, here, and all the results are
> very low.
>
> \[Slide\]
>
> Those are the same results in a graphic form. All of these are in your
> packet so you can study them later and figure out which of the species
> you want to eat, but these are the same results from the University of
> Alaska.
>
> \[Slide\]
>
> Arctic grayling, a form of trout, are all levels that are very, very
> low.
>
> \[Slide\]
>
> Northern pike are one of the freshwater species with the highest
> levels in Alaska, but most are also below one part per million.
>
> \[Slide\]
>
> Alaska freshwater fish, we have turbot, sheep fish, dolly varden
> trout, sucker fish, rainbow trout, whitefish.
>
> \[Slide\]
>
> Our Department of Environmental Conservation for southeast Alaska
> shows all the species are very low except for salmon shark.
>
> \[Slide\]
>
> Out in the Aleutians there is a small number of samples but, again,
> Dover sole, ocean perch and yellow fin sole all have very low levels.
>
> \[Slide\]
>
> Cook Inlet, which is near Anchorage\--all very low levels. I would
> like to skip through this and then I will go on, but in the packet you
> can see that there is an extensive amount of sampling and of most
> importance is that the levels of methylmercury in all species of
> salmon are among the lowest of all species of fish, ranging from
> non-detectable to about 0.05 to 0.08.
>
> Dietary surveys in Alaska document a wide-ranging exposure to multiple
> fish species in marine mammals. This overhead presents regional
> compositions of subsistence harvest by our rural residents in
> different parts of the State. There are considerable variations by
> region most notable in amounts of fish and marine mammals. Up in the
> north slope there is a lot of marine mammal that is whale, seal and
> walrus. In some of the other areas of the State there is mostly fish
> and of the fish, mostly salmon.
>
> \[Slide\]
>
> As you can see, fish comprises about 60 percent of Alaskan\'s rural
> subsistence harvest.
>
> \[Slide\]
>
> Mean salmon consumption in Alaska far exceeds the current EPA and FDA
> consumption advisory amounts, and you can see in these dotted lines
> are the FDA and EPA recommended consumption advisory levels, and these
> are mean harvest data for fish for different communities in Alaska.
>
> \[Slide\]
>
> The economic and nutritional values of subsistence foods in Alaska are
> huge. For the percent of population\'s required protein overall in
> Alaska subsistence harvest comprises about 65 percent or protein, 9
> percent of total calories. The estimated economic value in Alaska of
> subsistence harvest is 267 million dollars.
>
> \[Slide\]
>
> Currently, several major dietary surveys are under way in Alaska,
> including ones conducted by the Alaskan Native Tribal Health
> Consortium with EPA support, the Aleutian/Pribilof Island Association
> supported by the NIEHSS, the Alaska Native Health Board, supported by
> ATSDR, and the University of Alaska, supported NIH.
>
> In addition to these traditional sources of information, we also have
> new data on actual human exposure levels. Dr. James Berner, Alaska
> Native Tribal Health Consortium, is the principle investigator of an
> Alaska native maternal-infant cord blood contaminants study. This
> grassroots project was requested by local Alaska native communities.
> Funding of this effort is from EPA and the National Center for
> Environmental Health of CDC. In addition to actual measurement of
> heavy metals, persistent organic pollutants and radionuclides,
> long-term neurodevelopmental follow-up of the children is planned.
>
> Dr. Berner has given permission for me to share with you the initial
> results from this study. For 52 mothers who delivered babies from the
> Bethel area of Alaska, the median blood mercury level was 4.65 ppb
> with a maximum level of 21 ppb, and for 29 mothers from the Barrow
> area the median blood mercury level was 1.1 ppb with a maximum level
> of 4.5 ppb. Additional data include hair mercury results for 14
> mothers with a median level of 0.94 ppm in Bethel and 0.48 ppm in
> Barrow, and a maximum level of 1.9 ppm.
>
> Recognizing that these two populations have high subsistence intakes,
> levels show no cause for concern. The State recently established a
> statewide maternal hair biomonitoring program to provide, at no cost,
> measurement of mercury in the hair of all women who are pregnant. We
> just had the first results that were called in last night of the first
> 12 women participating. The hair mercury levels ranged from 0.03 ppm
> to 1.2 ppm, with a median of 0.26 ppm.
>
> \[Slide\]
>
> Balancing benefits and risks is essential in crafting public health
> recommendations. Some of the benefits of subsistence lifestyle are
> nutrition, taste, sociocultural values, fitness, cost, children\'s
> education and ecological knowledge. Some of the risks are accidents
> associated with hunting and fishing, and health risks include
> botulism, trichinosis and paralytic shellfish poisoning, for example.
> Then, there are the risks of not eating the traditional foods,
> obesity, diabetes and heart disease.
>
> \[Slide\]
>
> There are also many sociocultural benefits of traditional foods, what
> food is to a culture. The Alaskan native people have indicated that
> the issue of contaminants is the most important one facing them as a
> community. They have identified values of the subsistence reliance on
> traditional food and fish as physical fitness, recreation, the healthy
> foods, being in tune with nature, sharing, that it saves money and the
> value to their culture. Also, pride and confidence. For their
> children, their education, the natural environment, survival skills,
> food preparation techniques, practicing patience and respect.
>
> \[Slide\]
>
> There are well-known public health benefits from fish consumption.
> Fish provide high nutritional value, vitamins A, E and C, protein,
> energy, omega-3 fatty acids, monolipids, iron and zinc. Omega-3 fatty
> acids have proven benefits in preventing complications from diabetes,
> preventing coronary heart disease and atherosclerosis and preventing
> complications from arthritis, to name just a few. There are also major
> economic, cultural, spiritual and social benefits from subsistence
> practices.
>
> Experience in Alaska has documented adverse effects on public health
> and communities from fish advisories with subsequent abandonment of
> traditional diets. Alaska natives are experiencing a major increase in
> the prevalence of diabetes. Heart disease rates are increasing, and
> recent studies have documented vitamin A and D deficiencies.
>
> \[Slide\]
>
> For example, the prevalence of diabetes among Alaska natives has
> increased substantially in the past two decades. We are concerned that
> Alaska natives may be on the threshold of a major epidemic, similar to
> those of the Pimas. In addition, Arctic residents are faced with
> serious problems of alcohol use, lack of physical exercise and
> subsequent increases in obesity.
>
> The subsistence lifestyle and diet are of great importance to the
> self-definition, self-determination, cultural and socioeconomic and
> overall health and well being of indigenous peoples. Alaska natives
> have voiced their fears and concerns about the safety of traditional
> foods. However, native elders have also expressed concerns that the
> fear associated with the contaminants may cause greater harm than the
> actual presence of the contaminants themselves, and that health
> warnings regarding food consumption should only be made when there is
> strong evidence that the risks outweigh the benefits.
>
> There is a compelling need to incorporate benefits and risks in
> dietary recommendations. The precautionary rule seems most appropriate
> for taking actions to reduce industrial and other man-made pollutants.
> Alaskans have great concerns over the long-range atmospheric
> transportation of pollutants into the Arctic. The State of Alaska
> supports the POPs treaty and efforts to reduce anthropogenic
> pollutants, and use of the EPA RfD in reducing mercury emissions.
>
> But in creating public health recommendations for fish consumption, it
> is essential to weigh benefits and risks. Relying on the EPA RfD led
> to the question what is the public health risk of the uncertainty
> factor? The Belmont Report provides the foundation for U.S. policies
> for the protection of human subjects.
>
> The report outlines basic ethical principles, the principles of
> respect for persons, beneficence and justice. The Belmont Report
> formulated to general rules to complementary expressions of beneficent
> actions. One, do not harm and, two, maximize possible benefits and
> minimize possible harms. Justice has the sense of fairness in
> distribution or what is deserved. An injustice occurs when some
> benefit to which a person is entitled is denied without good reason,
> or when some burden is imposed unduly. The application of the general
> principles leads to considerations of risk/benefit assessment.
>
> In this context, the State supports the FDA\'s leadership in providing
> general public health-based dietary guidelines, including the
> flexibility to weigh benefits and risks and providing for substantial
> involvement of state and local public health agencies in applying
> local evidence in developing dietary guidelines.
>
> In response to the national fish advisories of January 2001, the
> Alaska Division of Public Health engaged in extensive consultations
> with Alaska stakeholders. After reviewing all of the available
> evidence, the Division of Public Health issued consensus
> recommendations for fish consumption in Alaska. The most important
> difference from national advisories is the following:
>
> The Alaska Division of Public Health continues to strongly recommend
> that all Alaskans, including pregnant women, women who are
> breast-feeding, women of childbearing age, and young children continue
> unrestricted consumption of fish from Alaskan waters.
>
> The State does not support national advisory recommendations to
> restrict fish consumption to 12 oz per week, nor the national advisory
> recommendations for pregnant women to restrict fish consumption to one
> meal per month.
>
> \[Slide\]
>
> The State, in consultation with the Food and Drug Administration,
> developed the following language that was included in the amended FDA
> advisory: Some kinds of fish that are known to have much lower than
> average levels of methylmercury can be safely eaten more frequently
> and in larger amounts. Contact your federal, state or local health or
> food safety authority for specific consumption recommendations about
> fish caught or sold in your local area.
>
> \[Slide\]
>
> The following agencies and organizations endorsed and contributed to
> the development of these recommendations: The Alaska Department of
> Environmental Conservation, the Alaska Department of Health and Social
> Services, the Alaska Native Health Board, the Alaska Native Science
> Commission, the Alaska Native Tribal Health Consortium, the
> Aleutian/Pribilof Islands Association, the Institute for Circumpolar
> Health Studies of the University of Alaska Anchorage, the North Slope
> Borough, the University of Alaska Fairbanks and the Yukon Kuskokwim
> Health Corporation.
>
> \[Slide\]
>
> As part of the State\'s development of its dietary recommendations,
> the State also made a commitment to supporting increased monitoring of
> mercury levels in fish, supporting the ongoing research being
> conducted by Dr. Jim Berner in his maternal-infant contaminants study,
> and developing and implementing a statewide maternal hair mercury
> biomonitoring program. These efforts are all underway.
>
> In conclusion, the State supports increased human exposure assessments
> such as the recent mercury studies of the NHANES by the National
> Center for Environmental Health of CDC; increasing human exposure
> assessments as proposed by the National Center for Environmental
> Health through expanding the national NHANES assessments to the state
> level; increased biomonitoring of fish species; increased
> consideration of benefits as well as risks; targeting fish advisories
> based on levels of mercury in key species and actual human exposure
> data; and increased and sustained efforts to reduce global
> anthropogenic emissions of mercury. Thank you.
>
> **Questions of Clarification**
>
> DR. MILLER: Thank you. Questions or comments? Dr. Hotchkiss?
>
> DR. HOTCHKISS: I think we would all agree that Alaskan fish are lower
> in methylmercury than fish available from most other parts of the
> country, which tells me if you don\'t throw mercury around in your
> environment you have fish with less mercury. But my question to you is
> if the fish consumed in Alaska had methylmercury levels that were more
> consistent with the rest of the U.S., or at least the higher portions
> of the U.S., would your position be the same on this issue?
>
> DR. MIDDAUGH: Well, I think that the methylmercury exposure is
> determined by fish, and I certainly think that there is an absolute
> need to have fish advisories especially for local contaminated areas.
> I believe that there is a great opportunity with new technology to
> make accurate measurement of human levels of mercury, at very little
> cost, to combine the risk assessment methodologies with actual
> exposure levels which are showing us, at least in Alaska, that the
> levels that we actually measure are far below those that we would have
> predicted to have found having only used data from fish species and
> these dietary projections of assumed amount of exposure.
>
> I also believe that the data are probably quite skewed, and our
> experience is that when we monitor fish we find very few that have
> higher levels and almost all the other fish have very low levels. I
> think that may be one explanation why we are seeing a disconnect
> between some of the predictions of exposure levels and some of the
> exposure levels when we actually go out and measure.
>
> The CDC and the Pugh Commission and the Trust for American\'s Health
> have all recommended increased biomonitoring to actually measure what
> the exposures are that are occurring among the U.S. population for
> these contaminants, and I think it is critical that we expand that
> knowledge database before we potentially warn people to avoid
> consuming a particular fish product that has huge documented public
> health benefits.
>
> DR. HOTCHKISS: I agree, but I am a little confused by your answer. Do
> we agree that in general fish caught in either marine or freshwater
> environments in Alaska are lower in methylmercury content than, let\'s
> say, fish caught in the region of the Gulf part of the U.S.?
>
> DR. MIDDAUGH: I can for sure say that the fish in Alaska have very low
> methylmercury levels. I believe that they are lower than in many other
> parts of the United States but I am not an expert on the levels in a
> lot of the rest of the country.
>
> DR. HOTCHKISS: Let\'s assume for the sake of discussion that they are.
> I think the data would bear out quite strongly that there is a
> difference from the Great Lakes, for example. I am just curious about
> your position. Is your position based on these low levels in Alaska,
> or is your position in general that we don\'t know enough about
> methylmercury nor the levels across the U.S. to make recommendations?
>
> DR. MIDDAUGH: Well, there are certainly two parts to my answer. The
> first one is that we were very pleased in Alaska, when we found all
> this data and did our measurements, to find that we have very low
> levels. That made it much easier for us to develop our Alaska
> recommendations. But they fly in the face of the national
> recommendations so we are confronted by having \"Brain Food\" on the
> computer that rural Alaska residents download which tell them not to
> eat their fish, and then what do they eat? We are part of the United
> States. So, that is a problem.
>
> Then, we also are concerned about the absence of benefit/risk
> evaluation in the national program. So, I think that the easy part for
> Alaska is that our levels are lower so it made it easier for us to
> come to consensus recommendations for people in our State. But we are
> also very hesitant about the reliance on the EPA RfD for crafting
> dietary recommendations for the American people.
>
> DR. HOTCHKISS: Thank you.
>
> DR. MILLER: Ms. Halloran?
>
> MS. HALLORAN: Could you say more about your hair monitoring program,
> how big it is and how much does it cost?
>
> DR. MIDDAUGH: We have just started this program, and the reason was to
> actually be able to try to provide ongoing surveillance evidence to
> document the validity of our dietary recommendations. There are around
> 12,000 live births in the State of Alaska. We just started the program
> in June. It is available to all women, free of charge to their
> provider to send their hair in to the state lab where it will be
> measured and the results will be reported back to the provider.
>
> We believe that by doing so, one, we will be able to follow trends
> over time. Two, if we find any evidence of unexpectedly elevated
> levels in any geographic area, any village, any sub-targeted component
> of the State, then we can go out and do more detailed evaluations and
> investigations to try to determine why the hair levels are higher and,
> if necessary, we can always develop targeted advisories.
>
> MS. HALLORAN: How much is this costing?
>
> DR. MIDDAUGH: We are using Frontier Geosciences. Dr. Nicholas Bloom\'s
> lab is a consultant to our State Health Department and has been for
> some time, but we are setting up to run mercury in our new state
> laboratory. So, we believe over the next six months we will be able to
> offer the mercury testing in our own state lab, not have to use a
> contractor. That will lower our cost, and we are estimating that as we
> gear up with the volume we anticipate we may get by with less than
> \$50 a test for all associated costs.
>
> DR. MILLER: Dr. Shannon?
>
> DR. SHANNON: I have a question and a comment. My question relates to
> your discussion of increasing rates of diabetes and obesity. In fact,
> you showed a slide of the increasing rate of diabetes. It wasn\'t
> clear to me if you were relating that to changes in fish consumption
> or mercury exposure and exactly what point you were trying to make
> there.
>
> DR. MIDDAUGH: Yes, very much so, there is a rich experience, well
> documented in Canada from 20 years ago when fish advisories were given
> in Quebec to the Ashkenazi, followed by complete abandonment of their
> subsistence intake of traditional foods. That led to tremendous
> community problems, and we are seeing tremendous problems in Alaska
> not just from mercury but also from other contaminants brought to
> Alaska from long-range atmospheric transportation, and then these
> tremendous warnings against the dangers of the contaminants, and
> people are abandoning the use of their traditional foods, including
> fish consumption. In the larger context of Alaska, the values of both
> nutrition and the potentials for severe public health problems have
> been played out and are a great concern.
>
> DR. SHANNON: I am still not sure I understood. You have clear evidence
> that the increased rate of diabetes and obesity is associated with
> decreased consumption of fish in Alaska?
>
> DR. MIDDAUGH: We have anecdotal evidence to support that association.
> It is clearly not the only factor going on. There is a tremendous
> increase in life expectancy so all the chronic diseases are
> increasing. But we also did extensive autopsy studies of Alaskan
> natives, looking at the association of omega-3 fatty acids and
> atherosclerosis, in collaboration with University of Louisiana and Dr.
> Jack Strong\'s group. Fifteen years ago we showed that the amount of
> atherosclerosis among Alaskan natives was about half of that of
> non-natives and there was a strong association between the amount of
> atherosclerosis and omega-3 fatty acids measured in the coronary
> arteries and also in perirenal fat. Now heart disease is increasing
> and we have evidence from dietary surveys that the amount of
> consumption of subsistence foods is declining.
>
> DR. SHANNON: You didn\'t present any of those data. Can you say a
> little bit more about that? How much is fish consumption declining in
> Alaska? How much has it declined over the last 10 to 15 years? I
> don\'t remember you saying anything.
>
> DR. MIDDAUGH: We don\'t have good quantitative data. What we have are
> subsistence harvest records. Harvest records are not dietary
> consumption records, but we have numerous anecdotal reports from the
> physicians around Alaska, from our nurses in the villages and, of
> course, the whole issue of contaminants has been one of headlines in
> the papers routinely for the last eight to ten years.
>
> DR. SHANNON: I have to push you on this. I think any good scientist
> would want more than anecdotal data that you think there have been
> important declines in consumption. Do those data not exist, or why
> hasn\'t that been investigated?
>
> DR. MIDDAUGH: I mentioned that there are four major dietary survey
> projects that have been developed in the last several years, funded by
> ATSDR, EPA, NIH and CDC, and we are hoping that that information will
> provide some of the quantitative evidence that we can use to compare
> dietary consumption practices today versus the data that was
> accumulated 15 or 20 years ago by nutritionists with the Indian Health
> Service.
>
> DR. SHANNON: Maybe I misinterpreted your introductory comment, but if
> I understood you to say that you thought that low level of mercury
> exposure may not have an effect, and if it does, it is subclinical
> and, therefore, probably unimportant and it isn\'t clearly
> irreversible, my comment would be that I don\'t think that the weight
> of scientific evidence that we have now would support those
> statements. Maybe that is not what you said.
>
> DR. MIDDAUGH: Well, I would say that in Alaska, for example, we have
> the highest rate of fetal alcohol syndrome in the world and we have
> tremendous problems with infant mortality and nutrition and recent
> studies have documented borderline vitamin A and vitamin D deficiency
> among newborns and infants. We have very serious, well-documented,
> very significant public health problems and we believe that
> abandonment especially of fish consumption but also other traditional
> food consumption would cause a great public health tragedy among
> Alaskans.
>
> DR. SHANNON: Right, but we are here to talk about mercury and the
> issue is whether mercury exposure is important or not and it just
> seemed like you minimized it. Again, my only comment is that I don\'t
> think that the weight of scientific evidence would support that.
>
> DR. MIDDAUGH: I would only respond to that by saying that we are very
> concerned about mercury exposure in Alaska. That is why we have
> developed some of these studies. That is why we launched the statewide
> monitoring program because our available evidence is suggesting that,
> at least in Alaska, our exposures are very low, far lower than we
> would have predicted based on consumption and fish species mercury
> level monitory data, and it is something that we intend to pursue with
> great vigor in the future.
>
> DR. MILLER: Dr. Dwyer?
>
> DR. DWYER: Thank you for a very interesting presentation, and I wanted
> to congratulate you for this monitoring program that you are putting
> in place.
>
> The question I have is how will that work? It really isn\'t
> necessarily the people in Fairbanks and Anchorage that you are
> interested in. It is the people in the little, tiny towns that are
> very isolated and hard to get to. I know a former colleague and
> friend, Betsy Nobman, has done some of the studies that Dr. Shannon
> was asking about and I know how difficult it is to get food
> consumption data in some of those places. I wondered how you are going
> to get the samples of the hair and so forth in these remote villages
> that are very inaccessible in many cases.
>
> DR. MIDDAUGH: Yes, actually Betsy Nobman is continuing to work on
> these dietary surveys that I have mentioned. Dr. Berner\'s infant cord
> blood study is based on the rural hospital hubs to which pregnant
> women come in to deliver, and the Alaska Tribal Health Consortium in
> Anchorage has about 100 births per month, again, in many cases high
> risk pregnancies that are flown in from the villages. But the hair
> program is a component of Dr. Berner\'s study so it is located in
> those rural hospital areas. Then, should we find any evidence of
> elevated mercury, we can go out to the village and offer mercury
> testing not just to pregnant women but to women of childbearing age.
>
> So, initially we focused on pregnant women, one, because they are of
> greatest concern for their own actual exposures and the fetal
> exposure, but also in terms of just the amount of money we have
> available to support the program. But the full intention is that
> should we find any elevated levels or higher levels than expected,
> then we can go back out to that area, the geographic area or to those
> villages, and do much more extensive testing and then liken that to
> detailed dietary exposure to determine if there is some unusual
> exposure or some unexpected elevated levels of mercury which we were
> unaware of, or for which a local advisory might be appropriate.
>
> DR. MILLER: Other comments?
>
> \[No response\]
>
> Thank you. I have just been informed that Dr. Anderson will be
> arriving here at about one o\'clock. The thunderstorms last night have
> prevented him from landing at Reagan. In order to accommodate this, I
> would like to change the agenda just slightly. I wonder, Dr. Lockwood,
> if you would mind making your presentation now, before the break? I
> understand you will just need about five or ten minutes.
>
> **American College of Obstetrics and Gynecology**
>
> DR. LOCKWOOD: Thank you. I am Charles Lockwood. I am an obstetrician
> and I was the former chair of the American College of Obstetricians
> and Gynecologists, Committee on Obstetrical Practice that acts sort of
> like a clearinghouse for information that is then disseminated to the
> 40,000 or so fellows in the College. Virtually all obstetricians and
> gynecologists in the United States are fellows in the college so it is
> relatively unique as a combination trade and educating society in
> medicine.
>
> The mission, of course, of the American College of Obstetricians and
> Gynecologists is to improve the health care of women and their
> fetuses, and we are somewhat confused and very, very anxious to be
> able to communicate with our fellows and, through our fellows, our
> patients precisely what message should be given to them regarding the
> safety of their food supply, and specifically the amount of fish that
> they can take in that is safe.
>
> The College is concerned particularly because we have been urging
> patients to eat fish for the past ten years because there is evidence
> that it may improve health outcomes, reduce the risk of preeclampsia,
> perhaps affect premature labor and so forth. Although none of the
> literature is particularly robust, certainly the bulk of it suggests
> that fish intake may be beneficial.
>
> We are also very concerned that there may be, as has been implied
> already today and I suspect discussed yesterday, significant
> variability in the content of mercury in fish among different regions.
> It is very nice that Alaska has such a low supply of mercury, and that
> is very good for the pregnant women in Alaska but we are very
> concerned about the other regions of the country that might have
> substantially higher contents of mercury and applying a uniform
> standard. This is sort of the federalist response to the Alaska
> statement, we are concerned that applying a single standard may, in
> fact, underestimate the risk to the newborn.
>
> Although I certainly am very sensitive to the notion that different
> regions need to educate their people, our problem is that we can only
> communicate with our 40,000 obstetricians and that message has to be
> short, sweet, clear and concise. It needs to be able to then be
> translated and given to their patients. If we rely on the states to do
> that, since there is substantial variability in their monitoring and
> also in their communication of the levels that might be elevated for
> mercury in different water sources, that is going to lead to complete
> chaos amongst obstetricians and gynecologists.
>
> So, we do applaud the EPA and the FDA for giving us some guidelines
> and a fairly simple message to convey. However, having said that, we
> are concerned that, in fact, we don\'t know enough about the
> neurodevelopmental effects of mercury. The literature has been, at
> best, unconvincing. We would like to urge the NIH and other federal
> agencies to support research to establish in a much more precise and
> rigorous way what mercury does to the developing infant\'s brain. We
> would like fairly exhaustive studies done in primates and [in
> vitro]{.underline} studies to assess the effects of mercury on nerve
> development, and so forth. In addition, we would like far more
> detailed epidemiological studies, coupled with child development
> studies, to be able to get some sense of whether there is at least a
> crude correlation between fetal [in utero]{.underline} exposure to
> mercury and subsequent neurodevelopment and its effects. So, research
> I guess is the message there.
>
> We would also like studies to establish whether or not mercury is
> teratogenic. It is pretty clear that in high concentrations it can
> induce fetopathy but it is not so clear that it causes birth defects
> and we would like to know that.
>
> Finally, I guess we would urge that if you are planning to change the
> RfD that is used by the FDA that you do err on the side of being
> conservative, err on the side of, for example, accepting the Institute
> of Medicine\'s recommendations because we don\'t want to discover 15
> years from now that, in fact, the level was too high and we have had
> an effect on the development of the next generation of our citizens.
> Thank you.
>
> **Questions of Clarification**
>
> DR. MILLER: Thank you. Any comments or questions? Yes, Dr. Nordgren?
>
> DR. NORDGREN: Dr. Lockwood, your organization is in the front lines on
> this issue, and I think it sounds like your organization has very
> carefully studied the issue that we are all facing here. My question
> to you, and the reason I am asking this question is, dealing with
> fetal alcohol syndrome in the past, I think many obstetricians were
> way behind the eight ball as far as recommendations in their practice
> as to good scientific knowledge. My question is do you think within
> your organization this information is filtering down? That is a hard
> question to answer.
>
> DR. LOCKWOOD: It is a hard question to answer. The life of an
> obstetrician is difficult. We have really added substantially to the
> burden of information that we have to convey to our patients. Some of
> that is actually regulated by states and some of it has, in a sense,
> been de facto regulation by the College endorsing certain programs and
> policies, for example, cystic fibrosis screening and universal HIV
> screening, and so forth so that a substantial amount of time is spent
> by the average obstetrician counseling patients.
>
> So, if you are attempting to pay your \$115,000 a year malpractice
> premium, as you would in Long Island for example, and you are
> attempting to support your staff and so forth, and increasingly large
> staff since more and more counseling is done by nurses, etc., and you
> are facing a 50 percent reduction in the average reimbursement of your
> services by managed care organizations, which we have over the past
> ten years, and, therefore, you are forced to see many more patients in
> a shorter period of time, it becomes increasingly more difficult to
> add to the burden of information in the time that is available.
>
> This is not to say that we don\'t have an obligation to do the very
> best we can with every patient, but from a practical perspective,
> there is only so much we can do; there is only so much information we
> can convey and at some point this all becomes crippling. You know, I
> live in a lovely Ivy League world with plenty of time to spend with
> every patient and, yet, even for me it is becoming incredibly
> difficult to give all the information that we have. We have to talk
> about exercise. We have to talk about vaccinations. We have to talk
> about infectious disease exposure. We have to talk about screening for
> aneuploidy or Down\'s syndrome. Now we have to talk about cystic
> fibrosis screening; a variety of other ethnic specific genetic
> disorders, and on, and on, and on.
>
> So, to be able to convey the complexity of these issues to the average
> pregnant woman is impossible. It can\'t be done. We can provide
> educational resources. We can provide information on web sites. We can
> have patient handouts, and we are more than happy to do all that, but
> we do need a very simple, clear message to our patients and I think
> that the College was happy to pass on the information that the EPA and
> the FDA produced but we understand that, in fact, that may be a
> fairly\--depending on your political perspective\--conservative or
> liberal recommendation. So, we will follow whatever the
> recommendations are, but our bias would be that those recommendations
> be as conservative as possible from the perspective of the developing
> fetus. I hope that answers your question.
>
> DR. MILLER: Dr. Lee?
>
> DR. LEE: I was just following up on a casual mention you just made. Is
> there a single source or clearinghouse of information for pregnant
> women to go to for recommendations on prenatal care and diet? Do you
> point them to a particular site, or do you have just a whole array of
> brochures?
>
> DR. LOCKWOOD: The bible for provision of prenatal care, if you will,
> is contained in \"Guidelines for Prenatal Care,\" the fifth edition of
> which is about to come out. Having helped write that, I am embarrassed
> to say that I don\'t believe we incorporated any recommendations about
> mercury. There may be time, and I will work on that right away to be
> able to do that. It would be nice, of course, if you changed your
> recommendations you would do that in the next 25 minutes so I would be
> able to do that\--
>
> \[Laughter\]
>
> The second line of information, and the one that is much more time
> sensitive is the Committee opinion which is rendered by the Committee
> on Obstetrical Practice and that is distributed via publication in the
> [Journal of Obstetrics and Gynecology]{.underline} to virtually all of
> the fellows of the College. Rarely will we actually do direct mailing.
> For example, if tomorrow the [New England Journal of
> Medicine]{.underline} pointed out that exposures of mercury are
> substantially higher than the current recommendations would allow
> caused neurodevelopmental abnormalities, we would send a Committee
> opinion and literally mail it to every single member of the College
> with new recommendations. So, we can effect rapid change and those
> opinions are looked at very carefully because they are construed by
> our trial lawyer colleagues\--I hope none of them are in the room\--as
> the standard of care in the United States.
>
> DR. LEE: That is a very good mechanism for communicating directly with
> your members, but is there any attempt to communicate directly with
> your patients?
>
> DR. LOCKWOOD: We do assume that physicians speak to their patients,
> particularly if the topic is critically important. But, in addition,
> there are handouts that are available that are published by the
> College that most obstetricians and gynecologies have in their office.
> So, if there is a new recommendation that is going to be made, we
> could certainly incorporate that into the general educational efforts
> the College makes directly to patients.
>
> DR. MILLER: Dr. Dwyer?
>
> DR. DWYER: I just wondered, given the current state of information we
> have available, what do you intend to put in the ACOG handbook? What
> is the one-liner that you want your ACOG members to have?
>
> DR. LOCKWOOD: We would put in the \"Guidelines for Prenatal Care\"
> what we already put into our general publication. There is yet a third
> layer of communication and that is a newsletter that goes out to all
> of our fellows, and we have already put in that newsletter the
> recommendations of the EPA and the FDA regarding the amount of fish to
> eat and the various other aspects of whether, you know, it was
> commercially obtained.
>
> DR. DWYER: But do you really expect an obstetrician to have enough
> time to go through all of that? I mean, what would be the one-liner?
>
> DR. LOCKWOOD: Yes, these are one-liners. Most obstetricians do read
> that. Whether they incorporate it into their practice is up to them.
> We don\'t have any way of monitoring at this point what obstetricians
> actually tell their patients in their offices.
>
> DR. MILLER: Dr. Acholonu?
>
> DR. ACHOLONU: Thank you. I have a very similar question to Dr.
> Dwyer\'s. You made a statement, and please correct me if I have put it
> down wrongly, that we don\'t know enough about the neurodevelopmental
> effects of mercury. I have been sitting here, listening to summaries
> and reading about the Faroe Islands Study and the Seychelles study.
> What is the ACOG opinion of those studies?
>
> DR. LOCKWOOD: We certainly understand, based on the exposures that
> occurred in the Minamata Bay, what substantial exposure would do to
> the developing fetus, and that the manifestations of cerebral palsy
> and major retardation and the other various neurodevelopmental
> abnormalities that occurred in response to that exposure are pretty
> straightforward. I don\'t think there is much debate about that. The
> thresholds that have been calculated on the basis of those exposures I
> think are robust and no one is going to dispute them.
>
> Reviewing the data from the Faroe Islands and the Seychelles Islands,
> as well as the New Zealand study leaves us a little bit more lost. It
> is unclear whether or not you can set a specific exposure level that
> would be safe and, conversely, one that would represent the lower
> limit of absolute risk. It is unclear, sort of like the fetal alcohol
> story, whether there is an absolute discrete threshold below which
> there is no risk to neural development, or whether this is a
> continuous exposure.
>
> I think we would like to see literally a dose response study and, if
> you will, a time course study to inform the recommendations that you
> all are going to be making. But I don\'t see at this point, based on
> the information that I have been given, that you can say that a
> certain level is safe or that a certain level is absolutely unsafe. In
> general, what we have ended up doing with fetal alcohol is to say that
> we are not sure that any level of alcohol intake by a pregnant woman
> is safe. Most obstetricians will say it is okay to have a glass of
> wine once a week or so and it probably is okay but, in fact, since we
> never could establish an absolute limit to alcohol exposure that could
> be deemed safe we general proscribe the use of alcohol in pregnancy.
>
> I suppose at this point, if we are left with increasingly concerning
> information about the lack of a lower limit of mercury exposure,
> pregnant women will stop eating fish, but there are a lot of health
> benefits to eating fish and it is a relatively cheap source of
> protein. There may be some additional benefits of reducing oxidative
> stress that might induce preeclampsia or per-term delivery; may affect
> fetal growth restriction by impairing placentation. So, there are a
> lot of reasons to think that fish might be useful for pregnant women
> to take in but apparently, if we want to be absolutely safe, we have
> to tell them that they have to go to Alaska and eat fish with very low
> levels of mercury.
>
> DR. ACHOLONU: I think you have answered most of my questions, but did
> I understand you to advocate that NIH and other groups should give
> research grants to your organization or to other people do to research
> on the effect of mercury on the developing fetus? Is it to your
> organization?
>
> DR. LOCKWOOD: Not through our organization, we don\'t conduct original
> research. It would be up to the appropriate academic medical center to
> do that. But, yes, I think we need to have more research on the topic.
>
> DR. ACHOLONU: Do you have any more areas where you want the research
> to be concentrated because a lot of work has been done on the effect
> of mercury on children and prenatal effects? What area of research do
> you want this thing to be concentrated on?
>
> DR. LOCKWOOD: We would like a body of research that informs our
> counseling about fetal alcohol syndrome, which is a substantial amount
> of research, done in animal models and in humans, with long-term
> follow-ups, and an enormous effort made to understand precisely what
> the effects of fetal alcohol exposure were. I don\'t think there is
> anywhere near the quantity or quality of research that was done in
> that area in this area.
>
> Now, in a world of limited resources that may not be a reasonable
> expectation, particularly if the stock market goes down again today.
> But, in fact, I and the rest of our Committee and the rest of the
> College\'s leadership is not convinced that the information that is
> available is adequate.
>
> DR. MILLER: Ms. Halloran?
>
> MS. HALLORAN: Some women in the United States don\'t get prenatal care
> from a physician. Do you have any advice on how to get this message to
> those women?
>
> DR. LOCKWOOD: Well, there are several reasons women don\'t get
> prenatal care. One rare reason might be physical access. That might be
> a bigger issue in Alaska. But, generally speaking, people who don\'t
> seek prenatal care are less likely to be responsive to messages about
> the health of their fetus or behaviors that should be avoided that
> might impair the health of their fetus. So, I would wonder right off
> the bat whether whatever I recommend or am about to recommend would be
> cost effective in that particular group of patients. That is a real
> dilemma with fetal alcohol syndrome, drug abuse and a whole variety of
> other exposures.
>
> But it is a little hard for me to imagine that that population can be
> easily accessed and that that information could be easily conveyed or
> be readily accepted. There are issues with language barriers, and
> there are issues with poverty and crime, and many other things.
>
> The March of Dimes has been very, very effective I think in spreading
> the message that folic acid supplementation is something that should
> be begun by women of all childbearing ages. There is evidence that the
> amount of folic acid used in women who are anticipating being pregnant
> has increased substantially, and I think if a solid recommendation
> comes out of this body and it is based on good scientific evidence and
> everybody can get their hands around it, and feels comfortable with
> it, the March of Dimes would be an excellent organization to help
> disseminate that information, provided, of course, that they also were
> comfortable with the content. But they seem to do a much better job at
> reaching everybody than we do as physicians.
>
> DR. MILLER: Dr. Nordgren?
>
> DR. NORDGREN: I would just like to follow-up on Dr. Lee\'s question. I
> don\'t think you really answered his question. You didn\'t say your
> organization has a consumer web site like, for instance, the Academy
> of Neurology that has a web site so that people who want information
> about neurologic disorders can go to. Your organization doesn\'t have
> such a thing?
>
> DR. LOCKWOOD: We do. We do have a web site that consumers can access
> and there is patient information there.
>
> DR. MILLER: Dr. Friedman?
>
> DR. FRIEDMAN: I just want to make a little comment about the research
> that you are advocating. I am from the National Institute of Child
> Health and Human Development, and I will take the message back, but
> most of the research that NIH supports is investigator initiated
> research. So, I think the word needs to go out to researchers in your
> community to ask those questions and through submitting publications.
>
> DR. LOCKWOOD: An RFA would help.
>
> DR. FRIEDMAN: Okay, I will pass on the word.
>
> DR. MILLER: Dr. Fischer?
>
> DR. FISCHER: Dr. Lockwood, I would like to ask whether you think that
> the fellows in the College would support and participate in a national
> monitoring program for mercury exposure. To do that would require a
> lot of effort from a lot of people, I suppose, including those in your
> organization. Do you think that that would be possible?
>
> DR. LOCKWOOD: I think not only would it be possible, but there would
> be great enthusiasm for it. I was very intrigued by what Alaska is
> doing. I think that sort of cuts to the chase and gives us a lot of
> valuable information. Speaking for my organization, I don\'t know what
> my bosses are going to say but I would say that that would be
> something we would enthusiastically embrace. You know, if we had
> envelopes and we could snip some hair and it was relatively a
> straightforward process, I think we would be happy to contribute to
> that.
>
> DR. KUZMINSKI: I have one more question.
>
> DR. MILLER: Go ahead.
>
> DR. KUZMINSKI: I would just like to return, Dr. Lockwood, to the
> question asked earlier. Perhaps you could give us an example from
> another area of a message that works for your fellows in the College.
> You mentioned that you put in the EPA and the FDA recommendations on
> fish consumption. We have had discussion here that one person reading
> all of those messages together might get confused. So, as a guidance
> to this committee, can you give us the one-liner that has been
> referred to from another area of advice that gynecologists or
> obstetricians give to their patients?
>
> DR. LOCKWOOD: As an example, I think folic acid is a good one. We
> recommend that all pregnant women take a milligram of folic acid. We
> recommend that, in fact, you begin the consumption of folic acid
> really during your childbearing years and certainly if you anticipate
> being pregnant in the near future since folic acid reduces the risk of
> neural tube defects only if the exposure occurred prior to the
> development of neurulation in the embryo. That is a message that seems
> to be working. The prevalence of neural tube defects is dropping.
> Enrichment of the food supply may have helped as well, but it is clear
> that most pregnant women currently begin folic acid supplementation
> prior to conception. So, there is an intervention that works. It is
> cost effective. It has reduced a really terrible birth defect, and it
> is done in a way that doesn\'t invoke abortion or other things that
> society doesn\'t like to discuss.
>
> DR. MILLER: Thank you very much, Dr. Lockwood. We are going to have a
> break now. Would you please return in 20 minutes? That makes it 11:05.
> Thank you.
>
> \[Brief recess\]
>
> DR. MILLER: Before we go to the next speaker, an issue has come up.
> Over the last two days we have been receiving enormous amounts of
> information with sets of numbers derived from different sources, and
> so on, and Dr. Kuzminski has a recommendation which I think we would
> follow in order to clarify some of this.
>
> DR. KUZMINSKI: Thanks for bringing it up, Dr. Miller. I am just
> reflecting a little session three or four of us had after Dr. Miller
> adjourned us yesterday afternoon, but I know I certainly, personally,
> would find it helpful as part of the total information flow if I had
> in front of me\--and perhaps the rest of the committee would find it
> helpful too\--something that we could get from the FDA on one piece of
> paper, the various levels\--we hear 0.1, 0.3, 0.4 from the various
> sources and agencies, sources for those numbers\--how that translates
> into blood level mercury; how that translates to hair level mercury;
> how that translates to consumption of perhaps high level fish, low
> level fish, medium level fish. Again, just as a piece of information,
> one part of the jigsaw puzzle as I mentioned yesterday, of the total
> information flow to help us have deliberations.
>
> As I keep going back to the five questions that the agency has posed
> to us, the charge and the questions, I think that one-page summary
> would be helpful. I have been making notes. I am not sure that they
> are correct and I just want to avoid any chance of error.
>
> DR. MILLER: What I am going to do is to ask the secretariat to get
> together with our FDA colleagues and provide us with as much of that
> information as they can, and get this distributed to the committee
> before tomorrow. Yes, Robert?
>
> DR. RUSSELL: Included in that, there was a translation being made
> between parts per million of fish and the 0.1, 0.3, 0.4. I would like
> to see that as part of the column as well. By the way, it was never
> explained exactly how that is transformed, parts per million into 0.1
> ug/kg/day.
>
> DR. MILLER: I think it was based on consumption.
>
> DR. RUSSELL: Assuming 8 oz, a half a pound of fish per serving?
>
> DR. MILLER: Well, that ought to be specified.
>
> DR. RUSSELL: Yes, that is what I would like to see, if we could.
>
> DR. BOLGER: Since I am the one who is going to have to do this, I want
> to make sure I understand what you want. I mean, I understand how this
> gets terribly confusing because you have these different terms that
> are used and it is unclear what they really mean, but they are really
> different terms for the same thing. So, I am trying to get a handle on
> what it is you want. I mean, trying to translate an ADI, MRL, RfD,
> TDI, whatever you want to call it, those are all different terms for
> the same thing. They are safe levels of exposure.
>
> The FDA\'s ADI is really not relevant for this consideration because
> the ADI was based on the adult endpoint; it was not based on the fetal
> endpoint and was never part of the consideration of this advisory
> because the advisory is focused on fetal sensitivity. So, that is
> really not germane. The TDI WHO is also based on the adult endpoint;
> it is not based on fetal. So, that too is not germane to the advisory.
>
> Translating a dose level, a safe dose level to a concentration in fish
> is all predicated on what residue level you use in the fish and what
> level of consumption you use to derive an estimated exposure.
>
> DR. MILLER: I think that this will take a real long time and should be
> helpful, not confusing. Can I suggest that you and Larry Kuzminski get
> together for a couple of minutes and see if you can clarify what it
> is.
>
> DR. BOLGER: Right, so I have a clear idea of what it is they want.
>
> DR. KUZMINSKI: I would be glad to do that, but I would invite anyone
> else on the committee to join us.
>
> DR. MILLER: I don\'t want you to run out now.
>
> DR. BOLGER: Well, can I leave?
>
> \[Laughter\]
>
> DR. MILLER: You not only can leave; you have to leave. Our next
> speaker is Dr. Diana Zuckerman, of the NCPR, to talk about their
> recommendations.
>
> **National Center for Policy Research for Women and Families**
>
> DR. ZUCKERMAN: Thank you very much. I am Dr. Diana Zuckerman. I am
> president of the National Center for Policy Research for Women and
> Families. I am really delighted to be here and I thank you for
> inviting me to speak.
>
> CPR for Women and Families is a nonpartisan, nonprofit organization
> that reviews scientific and medical research, and explains the
> implications of that research for public policy and for the health and
> well being of women, children and families. Our mission is to ensure
> that research information is made available and understandable for
> policy makers and the public, to support policies that benefit public
> health, and to help ensure that consumers can make educated choices.
>
> Just as an aside, my own training is in epidemiology and psychology,
> and my policy perspective comes from working in the House of
> Representatives, the Senate, briefly the White House and, most
> recently, working for and with many nonprofit organizations that are
> very focused on consumer issues. This is a combination that doesn\'t
> come in too handy very often, but I think might actually be the right
> combination for what I am going to talk about today.
>
> Our Center is very concerned about methylmercury exposure, especially
> for children and pregnant women. We believe that the Food and Drug
> Administration\'s current efforts at protecting the American public
> from the health risks of methylmercury are not adequate to protect the
> public or to educate them so that they can protect themselves.
>
> We are concerned because the FDA does not adequately monitor
> methylmercury levels in commercial fish supplies. These levels may
> change over time but the FDA does not collect data to determine if
> that is true so we think surveillance is really essential and needs to
> be improved.
>
> We are concerned because the current FDA advisory is incomplete. The
> advisory should be revised to include information about tuna. Although
> the levels of methylmercury in tuna, and especially canned tuna, are
> lower than in other fish that are included in the current advisory,
> the amount of tuna consumed is typically so much higher that a public
> health perspective requires that the FDA widely disseminate risk
> information about fresh tuna and canned tuna.
>
> Our third main point is that we are concerned because FDA\'s
> dissemination of information about methylmercury exposure has not
> reached most consumers. Even health-conscious consumers are unaware of
> the overall risks of methylmercury in fish and they don\'t know which
> fish pose the greatest problems.
>
> More than a year and a half ago I attended a small meeting with Joe
> Levitt and other consumer groups to talk about FDA\'s plans regarding
> methylmercury advisory. It was really an excellent meeting and the
> major focus of the discussion, as I recall it, was whether the FDA
> should include information about canned tuna in their advisory. It
> seemed to be already assumed that fresh tuna would be included.
>
> Most of the consumer groups strongly urged that canned tuna be
> included in the advisory and we spent a lot of time talking about how
> to make that information available to consumers; what do you need to
> do to make sure that consumers know not just about tuna but about all
> the fish involved in the advisory. We talked about the need to have
> labels on food that is sold in supermarkets and fish markets, and also
> about the need for information on restaurant menus.
>
> So, I was certainly very disappointed and actually extremely surprised
> when the advisory came out and it didn\'t mention tuna at all, and
> very disappointed at the lack of dissemination of information once the
> advisory came out.
>
> It seemed to us that FDA was making little or no effort to inform
> consumers of these risks at the time when it would do the most good,
> which is when they are buying fish when they are in the market, in the
> supermarket or ordering it in a restaurant.
>
> Based on the National Academy of Sciences report, we are convinced
> that the FDA should be doing more to protect vulnerable populations,
> as you know, pregnant women, women who might become pregnant, nursing
> mothers and young children. In our experience, the National Academy of
> Sciences is actually pretty cautious. So, when they suggest that
> 60,000 newborns each year might be at risk for neurological problems
> due to methylmercury we take that estimate very seriously even though
> we understand very clearly that it is just an estimate.
>
> Given my training in epidemiology, I am really very interested in data
> and I strongly believe that we need better data, and it would
> certainly be preferable to be making these kinds of decisions based on
> better data. The American public relies on the FDA to require or to
> collect data so that we will better understand the risks of exposure,
> in this case exposure to methylmercury in the fish that we eat or the
> fish that we want to eat.
>
> It seems to me that the epidemiological research suggests that
> methylmercury in fish can potentially pose very serious problems
> especially, of course, in the developing fetus. But there are two ways
> to be exposed to this. One would be to consume fish that are high in
> methylmercury. That is what is in the advisory right now. But what is
> less understood is what happens when women consume large amounts of
> fish that have moderate amounts of methylmercury, fish like tuna.
>
> My feeling is this is not rocket science. We can get just as
> overweight from eating lots of light ice cream as we can from eating a
> smaller amount of Haagen-Dazs. So, it is an issue of not just which
> fish but how much fish people are consuming and, obviously, tuna is a
> popular fish.
>
> We believe tuna should be included in the advisory because Americans
> eat a lot of tuna and American women eat a lot of tuna, both canned
> tuna and fresh tuna. We looked at the government data that you all
> have in your book. We looked at even the U.S. Tuna Foundation\'s
> estimates that the one percent of women that eat the most tuna eat
> almost 7 oz a week. Then, there were other estimates that were for 8
> oz or more. Then we were wondering what about the top half of one
> percent, how much tuna are they consuming? That is still a lot of
> women in this country that are being exposed to potentially harmful
> levels.
>
> Canned tuna is a convenience food because you can buy it now and eat
> it almost any time, and because almost anybody in the United States
> can afford it. Just last week, the CVS stores offered cans of
> brand-name tuna for 44 cents a can. There just aren\'t that many main
> courses in America that you can buy for that amount of money. Most of
> them, including other favorites for children like hot dogs and
> bologna, are perceived to be rather unhealthy. So, this makes canned
> tuna especially appealing to low income women, including pregnant
> women and the mothers of young children.
>
> If you believe, as we do, that an FDA advisory should reflect the
> science, then I think you will agree that a very popular fish such as
> tuna needs to be included in the advisory. If scientists at the FDA
> believe that the level of methylmercury in canned tuna is not
> sufficient to warrant being included in the advisory, it seems to us
> they need to prove that. They need to prove it by providing current
> data. It is not enough to say that the evidence is unclear; they need
> to collect the evidence that will either support or refute those
> concerns.
>
> The current FDA advisory is entitled, quote, an important message for
> pregnant women and women of childbearing age who may become pregnant
> about the risks of mercury in fish. At the bottom of the page it
> mentions, almost casually, that, quote, it is prudent for nursing
> mothers and young children not to eat these fish as well. I think it
> is obvious that those warnings deserve more attention than they have
> in the current advisory.
>
> We all know that most foods have risks and benefits. We know that
> cheese provides calcium, but it can also be high in fat. Juices can
> provide vitamins, but pediatricians warn parents of young children to
> limit their juice consumption. So, it makes sense to us to include
> both sides of the issues, the benefits and the risks, for fish as well
> in an advisory and in any kind of information that is being
> disseminated. But we also share your concerns that it is difficult to
> do this succinctly and in ways that consumers can understand.
>
> So, we think that it is important what is in the advisory, but also
> how that information is disseminated to the general public. Obviously,
> the advisory needs to reach more people. For example, how many people
> know that the FDA believes that pregnant women and women who might
> become pregnant should limit their consumption of cooked, store-bought
> fish to an average of 12 oz a week? I would have to say I have asked
> several health-conscious, fish-eating types of people and none of them
> were aware of it. In fact, I asked a pediatrician who teaches at a
> major university and is active in the American Academy of Pediatrics,
> a man who does not eat red meat and considers himself very
> health-conscious, and happens to be married to me, and\--
>
> \[Laughter\]
>
> \--he barely knew what methylmercury is, and he certainly knew nothing
> about the 12 oz limit for pregnant women.
>
> What efforts has the FDA or the fish industry made to get information
> from the FDA advisory into women\'s magazines, parenting magazines, or
> other publications that are read by women of reproductive age? Why not
> have PSAs on TV talking about this issue? Because if they are on TV,
> they are going to reach a lot more women than anything else that the
> FDA could possibly do.
>
> Since the FDA advisory states that fish consumption should be limited
> to an average of 12 oz per week for pregnant women and women who might
> become pregnant, why not place that information directly on menus and
> all fish products that are sold, including canned tuna? Well, I think
> we know why not. This is a very controversial issue. But we can\'t let
> public policy be dictated by concerns about controversy.
>
> In the absence of complete information about methylmercury
> contamination of fish, we believe that the FDA should warn vulnerable
> populations not to eat swordfish, shark, king mackerel, tile fish and
> fresh tuna since they have previously been shown to contain unsafe
> levels of methylmercury.
>
> We believe that the risks outweigh the potential benefits since at
> risk consumers can simply switch from eating one kind of fish to
> another kind of fish. Fish are healthy but there are many different
> kinds of choices of fish. We also believe that consumers should be
> advised to limit their consumption of canned tuna.
>
> We realize that companies are concerned that people will stop eating
> tuna, particularly canned tuna, if there was such an advisory. I
> looked at the data from the focus groups that was on the CD disc that
> you all received, and obviously those focus groups were quite
> persuasive in saying we want simple information\--is the fish good or
> bad? We want to know which fish are good. We want to know which are
> bad and we want to not eat the ones that are bad.
>
> But as somebody who has worked on research for a long time, and those
> of you who have know focus groups are not necessarily the best source
> of information about what people actually do in their real lives,
> particularly when a focus group is first given information that might
> be shocking or disturbing, they are likely to respond in a more
> radical way than they would as time goes on.
>
> Let\'s face it, millions of Americans still eat hot dogs despite
> warnings about nitrites, and remember when there was a time when it
> seemed like nobody was ever going to eat a hot dog again. We eat
> processed foods despite warnings about salt content. We still eat
> fresh fruits and vegetables, not as many as we should, despite
> warnings about pesticides.
>
> I think there would be an initial shock if there were labels on food
> and it would probably result in lowered consumption for a short period
> of time, but over time people learn\--they will learn with fish, just
> as they have learned with other food products, that moderation is the
> key; that there are certain foods that might not be for pregnant women
> but that doesn\'t mean that other people can\'t eat them, and that
> there are certain foods where the levels are such that eating in
> moderation is important and they shouldn\'t overdo it. We certainly
> managed to get that message out on a lot of other foods, whether it is
> ice cream or alcoholic beverages or cakes or cookies, otherwise our
> kids would be eating nothing but cakes and cookies I think. So, there
> is no reason to think that in the same way that we teach people about
> moderation in all kinds of foods we can\'t teach them that about
> canned tuna.
>
> DR. MILLER: Five minutes.
>
> DR. ZUCKERMAN: Five minutes? Fine. When consumers purchase swordfish,
> shark, king mackerel, tile fish and fresh tuna that is either
> prepackaged or packaged at a fish counter, we believe the package
> should bear a label that tells pregnant women, women who might become
> pregnant, nursing mothers and young children not to eat it. At
> restaurants, a similar warning should be on menus if those items are
> served.
>
> Labels are also needed for canned tuna, and we urge that the FDA
> advise vulnerable populations to consume canned tuna infrequently
> until a more comprehensive analysis of the methylmercury content of
> canned tuna can be performed that is more reassuring than the
> information we have now. Obviously, we think that analysis should be
> done as soon as possible.
>
> Our recommendations are consistent with the precedents that have been
> set to provide clear warnings for pregnant women and children, even in
> the absence of data establishing a specific risk. I think the most
> obvious example would be the warnings on alcoholic beverages. There
> are warnings on every alcoholic beverage that pregnant women should
> not consume them, even though there really are not data that support
> the idea that no pregnant women should ever drink any alcoholic
> beverage.
>
> My final brief remark has to do with regulatory standards. We urge the
> FDA to set a regulatory limit that is consistent with the EPA standard
> since that has been scientifically justifiable for the protection of
> public health according to the National Academy of Sciences. We
> strongly believe the FDA should monitor the levels of methylmercury in
> shark, swordfish, king mackerel, tile fish and fresh and canned tuna,
> and if problems arise and with this monitoring they find that the
> levels are higher than expected, we believe that those fish should be
> removed from the market.
>
> Thanks very much for the opportunity to speak with you today, and I am
> happy to answer any questions.
>
> **Questions of Clarification**
>
> DR. MILLER: Thank you. Comments or questions? Dr. Dwyer?
>
> DR. DWYER: I wonder if you know of any advisories in Scandinavia or
> other countries that have taken actions on this, and the effectiveness
> of those advisories.
>
> DR. ZUCKERMAN: I am not familiar with that. You know, I don\'t have
> that information. We do know that there are all kinds of advisories
> but people get a lot of their information from the media, and I think
> it is very unfortunate that the FDA across the board does not make
> better use of the media in getting the word out on a wide variety of
> issues but, in this particular case, I think, you know, people do care
> about what they eat and I think that magazines and newspapers and TV
> would care about this.
>
> It is a little scary working with the media on issues like this
> because you are so afraid you are going to get these extreme headlines
> and these very extreme statements so you just have to keep at it until
> the message comes out that is accurate. I am not saying that is easy,
> but I am saying it is possible, and I also have no doubt that the
> folks who sell these products will do their very best to promote them
> and that will counterbalance the warnings. So, I think that we can get
> to a point where consumers are reasonably educated. They are not going
> to perhaps understand all the nuances, but they will be reasonably
> educated and will be able to make reasonable choices and we will have
> provided information to enable them to do that.
>
> DR. APOSHIAN: Ten years ago our laboratory did a study at the
> University of Arizona where we studied students as far as the urinary
> mercury was concerned for, I think, it was a 24-hour period. When we
> got the results in we had three outliers, about ten percent at least,
> maybe a little more. An outlier is always a problem. You want to know
> why.
>
> So, when I talked with each of these outliers, and they happened to be
> women, young college women, I asked them what they had had for dinner
> or lunch, what they had eaten because part of receiving their
> honorarium was signing something that said they had not eaten seafood
> for a week. That was spelled out, seafood. Each of them said they had
> had a can of tuna fish for lunch. And, I said, \"how could you do
> that? You accepted our honorarium; you signed an agreement.\" And,
> they said, \"we just didn\'t think of tuna as seafood.\"
>
> Now, in much of the literature that we have, they talk about swordfish
> and they talk about fish, and when I did my little survey on how much
> mercury was in tuna fish cans, I went to each can of tuna fish sold at
> the supermarkets in Tucson and nowhere does the word \"fish\" appear
> on a can of tuna. My wife, when I talked this over with her, and I
> should even mention this, my wife, who is a 40-year collaborator of
> mine, said \"everyone knows that tuna is fish.\" But I wonder with the
> educational level in our country\--
>
> \[Laughter\]
>
> \--how many people really know that tuna is fish, and I would really
> like to suggest that it is very easy for a company to put the word
> \"fish\" on a can of tuna. I think that there is a real need for
> education, as I am sure you all realize, for this whole problem of
> mercury in all kinds of fish.
>
> DR. MILLER: I hope that that experience doesn\'t reflect the quality
> of your students\--
>
> \[Laughter\]
>
> DR. APOSHIAN: I must say that one of these young women was a graduate
> student, a year away from her Ph.D. and she is now a department head
> of the leading biotech company in the world, a very educated woman.
>
> DR. ZUCKERMAN: I know you didn\'t exactly have this question but I do
> want to follow-up on the issue of outliers because I think it is
> really important. I will admit to something that I probably never said
> to anyone in my life, and that is that when I started graduate school
> I only knew how to make four things pretty much, hamburgers, hot dogs,
> tuna noodle casserole and tuna salad. So, there are people who eat a
> lot of certain foods, particularly students who are certainly of
> reproductive age. So, there are outliers out there and we have to care
> about the outliers and if we don\'t have warnings that warn those
> outliers, there are people who can be harmed.
>
> DR. MILLER: It just occurs to me, as we were talking before, I think
> the real problem is to translate knowledge into action, and that is
> where the hard thing comes because very often from a number of studies
> that have been done over the years, people, particularly students, can
> be extremely knowledgeable about the subject but their behaviors are
> unchanged. I don\'t know the solution to that problem; I am not sure
> anybody does.
>
> DR. ZUCKERMAN: Yes, I agree but I guess I don\'t think it is the role
> of the FDA or even the responsibility of the FDA to do that. I think
> it is the role of the FDA and the responsibility of the FDA to make
> products safer by regulating and to get information so consumers can
> make the right choices. I think the FDA should do everything it can to
> make that information available in a way that people can use, but
> ultimately it is our decision. We make a lot of foolish choices in how
> we eat and how we live our lives, but it shouldn\'t be based on lack
> of information.
>
> DR. MILLER: Other comments or questions? Yes?
>
> DR. HOTCHKISS: FDA has in its arsenal of public health tools a number
> of avenues that it can pursue, along with what at least are naturally
> occurring or adventitious toxicants\--one could take aflatoxin, for
> example, that FDA has chosen to take regulatory action for above a
> certain limit\--rather than the way it has chosen methylmercury which
> is more to try to advise consumers about the safety or lack of safety.
> What would your organization\'s opinion be about what choice FDA has
> made in the case of methylmercury? Would you rather see something more
> along other adventitious toxicants, lead for example, or do you think
> they have chosen the right path in terms of warnings to consumers?
>
> DR. ZUCKERMAN: I am not sure I understand the question. I will answer
> the best I can, and please follow-up if I miss the point here.
> Obviously, we think that first of all you deal with advising
> consumers. We also think that the regulation has been inadequate. We
> think that there is more information needed and more action needed if
> the information provides clear concerns about toxicity levels.
>
> I guess the bottom line is it is not enough to have a two-page piece
> of paper that says this is what the FDA believes, and the FDA did have
> something in their magazine that has nice illustrations but, still, I
> think it is clearly at the college level, college reading level and,
> anyway, who reads that? So, I think that the FDA has really not gotten
> the word out. I mean, people do know a lot more about lead, for
> example, and it is much more rigorously regulated in a variety of ways
> but I think some of those are state and local decisions, I believe,
> not just FDA decisions. I don\'t know if I am responding adequately.
>
> DR. HOTCHKISS: I think you are but let me be more specific. In the
> case of lead, for many years FDA had a very rigorous research program
> and in the days when there was lead used in manufacture of cans,
> rather than going out and telling select groups of consumers at large
> to limit their consumption of certain canned foods that they knew
> would be high in lead, they chose to regulate product and not try to
> have the consumer self-regulate. They could do that, I presume, in the
> case of methylmercury and I was just wondering about your opinion
> about whether they should take that approach or the current approach.
>
> DR. ZUCKERMAN: Sure, I agree. I mean, the preference would be to
> regulate the product and make it safer. I guess there are situations
> where a product can be safe for most people but not be safe for
> pregnant women or nursing women for example. Certainly, FDA has gone
> in the direction of putting a lot of responsibility on the consumers.
> Our organization feels they have gone too far in that direction, and I
> guess this is just one example of it where, yes, it is nice for
> consumers to have choices, but in this country people believe that the
> FDA makes sure that products are safe. So, no matter what you tell
> them, there is this underlying belief I think that if this product is
> being sold in my supermarket it is safe, and if these pills are being
> sold in my drug store, they are safe but, unfortunately, that is not
> always the case because they can be safe for some people and not
> others.
>
> So, I agree that the FDA should be doing more to regulate the product,
> but if there are reasons why certain products can be healthy and good
> for many people but not for pregnant women, then I think it is okay to
> have warning labels but they have to be really clear ones so that
> pregnant women, nursing mothers and mothers of young children know
> that.
>
> DR. MILLER: Dr. Friedman?
>
> DR. FRIEDMAN: I want to ask you to help me resolve a cognitive
> dissonance. Okay? You were emphasizing the importance of more research
> surveillance data and for more information about the connection
> between exposure and fetal development and infant development. So, you
> are saying there isn\'t enough knowledge out there about the ill
> effects. On the other hand, you are speaking with great enthusiasm
> about enforcing regulations maybe or advisories that are much more
> stringent than the ones that are out there, and making it more known
> to greater segments of the population. So, how does this fit together?
>
> DR. ZUCKERMAN: That is a fair question. Let me clarify, my concern
> about surveillance is actually not so much about lack of epidemiologic
> research. I mean, there is epidemiologic research; it is progressing.
> There is some, I think, very clear data that methylmercury exposure is
> dangerous to children, to fetal development under certain conditions.
> What we don\'t know is exactly what conditions. But I think it is very
> clear that it is dangerous.
>
> So, when I was talking about surveillance I was really talking about
> the levels in fish, current levels in fish. I think that a lot of the
> data are based on older information and we need current information.
> So, when I was talking about surveillance, that is actually what I
> meant.
>
> DR. FRIEDMAN: So, you think there is enough in the mixed literature
> that exists now to warrant the recommendations that you made?
>
> DR. ZUCKERMAN: Yes. I mean, I would personally like better data. I
> don\'t want to say that I think the data we have is adequate. You
> know, I am a researcher by training and I always want more data. But I
> think that there is enough. I think the previous speaker said
> something about erring on the side of caution and I think there is
> every reason to err on the side of caution in a situation where there
> are other alternatives that pregnant women can eat. You know, if this
> was the only fish available and fish was so great nutritionally for
> other reasons, that would be different. But there are other fish
> available.
>
> DR. MILLER: Any other comments or questions?
>
> \[No response\]
>
> Thank you.
>
> DR. ZUCKERMAN: Thanks very much. I have copies of my statement which I
> can leave.
>
> DR. MILLER: We are now supposed to break for lunch. We are scheduled
> to come back at 1:30. I would ask you, if you would, to come back
> about one o\'clock because we would like to get Dr. Anderson in this
> afternoon and we need to make up some time in that respect. Thank you,
> all, very much.
>
> \[Whereupon, at 11:45 a.m., the proceedings were adjourned for lunch,
> to reconvene at 1:00 p.m.\]
>
> [A F T E R N O O N P R O C E E D I N G S]{.underline}
>
> DR. MILLER: We are ready to start the afternoon session. I want to
> remind the speakers that it is important that they keep exactly to
> their time so everybody has a fair shake at making their
> presentations. I will provide a five-minute warning before the end of
> their time. The first speaker this afternoon is Mr. Richard Wiles and
> Ms. Jane Houlihan. Ms. Houlihan instructed me to point out she
> doesn\'t have a doctorate and she didn\'t want me to continue calling
> her doctor. I want you to understand it was her idea, not mine.
>
> **Environmental Working Group**
>
> MR. WILES: Thank you. I am just going to read a little statement and
> then Jane will make the bulk of the technical presentation. My goal is
> just to give you the goals of our presentation and our ongoing work on
> mercury.
>
> I am Richard Wiles. I am senior vice president of the Environmental
> Working Group. EWG is a nonprofit environmental research advocacy
> group, with offices in Washington, D.C. and Oakland, California. We
> are entirely foundation funded. We have no members and accept no money
> from industry or government.
>
> EWG has a long track record in working with the pesticide program at
> the U.S. EPA on issues directly relevant to the issue before the
> committee today. We have developed and presented two probabilistic
> exposure models to the EPA scientific advisory panel, one for acute
> exposure to organic phosphate insecticides and another for chronic
> exposure to arsenic by arsenic-treated lumber. Both of these models
> were embraced by the EPA and have formed the basis for significant
> changes in the way that EPA assesses exposure and risk to these types
> of substances.
>
> The acute exposure model for OP insecticides is particularly relevant
> to today\'s discussion. This model has moved EPA away from regulating
> pesticides on the basis of average exposures or even fixed point
> statistical estimates such as the 98th percentile to risk assessment
> methods and regulatory policies for non-cancer health risks, such as
> those we are dealing with today, that are designed to identify and
> predict, in EPA\'s case, at least 99.9 percent of the most vulnerable
> population.
>
> We are deeply troubled by the FDA\'s antiquated exposure and risk
> assessment model for methylmercury, and the fact that these models and
> methods have produced a mercury health advisory for pregnant women
> that allows thousands of unborn children to be exposed to unsafe
> mercury levels each year.
>
> But let me be clear. We are not asking the FDA to adopt our model per
> se any more than they should adopt the models of the seafood industry
> per se. What we are saying is that the FDA needs to conduct its own
> probabilistic risk assessment through a public and transparent process
> and issue a comprehensive list of fish that women should avoid during
> pregnancy and, equally important, and I want to emphasize this and I
> am going to emphasize it over and over again, a list of fish that are
> low in mercury and high in omega fatty acids that women should eat
> more of during pregnancy.
>
> The charge to the committee was to determine whether the agency\'s
> consumer public health advisory on methylmercury is adequate to
> protect the health of those who follow that advice. That is a quote
> from the charge. Our 2001 report, \"Brain Food,\" addressed this
> question exactly and found, without question, that the current advice
> is not safe for those who follow it. Indeed, we found that if FDA\'s
> advice were followed nationwide one out of every four pregnancies
> would be exposed to a maternal blood mercury level above the NRC
> recommended level for at least one month. That is a quarter of all
> pregnancies.
>
> Let me make clear our goals. We want the FDA to, one, adopt the NRC,
> NAS blood level for methylmercury. We know that is beyond the charge
> of this committee today but we mention it because it is critical.
>
> We want FDA to conduct a one-time sample of the top 40 or 50 most
> consumed fish, particularly those where they have very limited data,
> so that the agency is operating from a position of knowledge when
> advising pregnant women on fish consumption. This testing should
> include important seasonal sport fish that can be a significant source
> of mercury for thousands of pregnant women.
>
> They should conduct and make public a state-of-the-art Monte Carlo
> style exposure and risk assessment of fetal mercury exposure. They
> should issue a mercury health advisory that protects 99 percent of the
> pregnant women at least for methylmercury while, at the same time,
> recommending fish and other foods that are low in mercury and high in
> omega-3\'s. This second step is critical because it is the list of
> safe fish that makes possible a truly comprehensive list of fish that
> pregnant women should avoid.
>
> We are not asking for tolerance of methylmercury nor a lowering of the
> mercury action level. The action level is not enforceable; it is not
> enforced; and it would do as close to nothing to protect pregnant
> women and their children from mercury as any action the government
> could take.
>
> Above all, we are asking the FDA to change the way that it looks at
> fetal risks for methylmercury exposure. All the pregnancies at risk
> for methylmercury occur above the 98th percentile of exposure, as Jane
> will explain. But this is a huge number of pregnancies, as many as
> 400,000 per year. FDA has been overlooking these exposures and the
> seafood industry has been more than eager to support this policy.
>
> This attitude and approach is no longer acceptable but, more
> importantly, it is no longer necessary. There are sufficient data on
> mercury levels in canned tuna, tuna steaks and several other fish to
> support their addition to the FDA methylmercury health advisory. For
> scores of other important fish, the FDA only needs better data on fish
> contamination with mercury to issue a sound advisory. The agency
> stopped monitoring seafood for mercury in 1999, as I presume you have
> heard, and we presume that everyone would agree that this program
> needs to be restarted and that the FDA needs to monitor the seafood
> supply for mercury.
>
> With better data on mercury contamination of fish, the FDA could
> monitor mercury exposure for nearly all important fish with reasonable
> confidence at the 99th percentile of exposure and above, enough
> confidence to support a strong protective mercury advisory for
> pregnant women and to produce a list of fish that are low in mercury
> and safe for consumption during pregnancy.
>
> A protective mercury health advisory for pregnant women is not about
> banning tuna consumption, although we feel quite strongly that
> pregnant women should avoid canned tuna. And, it is not about denying
> women the benefits of omega-3 fatty acids. It is about developing a
> health-based standard for mercury exposure that protects all the
> nation\'s unborn children from unsafe levels of mercury, while
> providing nutritional, low mercury alternatives for these same women.
>
> The seafood industry and their consultants would love this, an
> argument about the future of the fish industry and about how
> ill-informed consumer advocates want to deny women and children the
> proven health benefits of fish consumption. Nothing could be further
> from the truth. Women should eat more fish. There is no doubt about
> that. At the same time, women should be protected from mercury. There
> is no doubt about that. What the seafood industry would have you
> believe is that you can\'t have it both ways. You either have no fish
> or suck it up and eat the mercury. It is very effective PR and it is
> simply not true.
>
> In the midst of this onslaught, the FDA rightly sees itself with two
> obligations, to protect the fetus from methylmercury exposure and to
> provide those developing babies with the best nutrition possible. The
> problem is that the agency has adopted essentially the industry view
> that these two goals are mutually exclusive. Until today or this
> meeting, the agency had essentially given up trying to protect women
> from mercury in seafood. They stopped monitoring seafood for mercury
> in 1998. They have not adopted the NRC recommendations for mercury
> levels in blood, and they have not provided a sound rationale for not
> doing so, and they have not been able to provide the Congress, or
> anyone, with a physical, actual copy of a risk assessment underlying
> their health advisory.
>
> In the end, the agency limited its methylmercury health advisory to a
> short list of fish based on antiquated science and a misplaced fear
> that a longer list would deprive women of the nutritional benefits of
> fish. Yet, at the same time, the agency has done nothing to help women
> identify the fish and other foods that are low in mercury and high in
> omega-3 fatty acids. This is particularly ironic because it is
> precisely the creation of a good fish list that would provide the
> nutritional rationale for a comprehensive list of fish to avoid during
> pregnancy.
>
> When Jane and I met with Joe Levitt and his staff, he asked us what we
> wanted and I will tell you today what I told him then. Don\'t
> laugh\--we want a refrigerator magnet or a card a woman can put in her
> wallet with two lists of fish on it, one, a list of
> mercury-contaminated fish that women should avoid when pregnant and,
> two, a list of fish that are low in mercury and high in omega-3\'s
> that pregnant women should eat more of. Very simple. This is not a
> complicated problem.
>
> We then want the FDA to work with healthcare providers, not the
> seafood industry, to ensure that every pregnant woman in America gets
> these simple lists, just like lead. No regulations. No tolerances. No
> bans on any fish. Just the best information based on the best science
> available on how pregnant women can protect their babies from mercury
> and provide them with good nutrition at the same time. Thank you.
>
> MS. HOULIHAN: I have some copies of the presentation I am about to
> give. Good afternoon. As Richard mentioned, I want to share with you,
> maybe not so briefly, some of the analyses that we have done regarding
> methylmercury exposures in women of childbearing age. I understand you
> had some presentations made yesterday that also looked at this issue
> so some of this should sound a little bit familiar.
>
> \[Slide\]
>
> First of all, I want to talk briefly about what led us to do this
> work.
>
> \[Slide\]
>
> As you have all heard by now, on January 12, 2001 FDA issued its first
> consumer advisory to pregnant women regarding methylmercury in
> seafood. That advisory contained two main points. First of all,
> pregnant women should completely avoid eating four fish, shark,
> swordfish, king mackerel and tile fish. The second part of that
> recommendation is that pregnant women can safely eat up to 12 oz of
> any other kind of fish throughout pregnancy.
>
> We have done work on methylmercury in the past and we are familiar
> enough with the mercury data to know that there are some fairly high
> mercury fish that did not appear in FDA\'s advisory.
>
> \[Slide\]
>
> So, we asked ourselves the question at that time what would happen if
> a pregnant woman followed FDA\'s advice and actually did eat 12 oz, or
> about two servings of fish a week, except for shark, swordfish, king
> mackerel and tile fish. The pertinent question is would her mercury
> exposures exceed the safe levels that have been derived from available
> epidemiology studies, levels recommended by the National Academy of
> Sciences and applied by the Environmental Protection Agency for
> example.
>
> \[Slide\]
>
> I am going to jump straight to the answer to that question before I
> give more details of the model. The answer is, and I will explain the
> graph in a second, that the model shows that if pregnant women
> followed FDA\'s advice and ate 12 oz of supposedly safe fish a week,
> and ate that in normal national consumption patterns so they are far
> more likely to eat canned tuna, for instance, than any other kind of
> fish, more than a quarter of all pregnancies would be exposed to
> mercury at levels above the reference dose for at least a full month
> of pregnancy.
>
> The graph is a little complicated but, of course, the X axis is total
> time during pregnancy. That is any three-month, any four-month,
> five-month chunk of time during pregnancy. On the Y axis we have the
> percent of babies exposed [in utero]{.underline} to methylmercury
> levels above the reference dose for that given time span or longer.
>
> For instance, if you look at one month on the X axis and go up through
> the graph, you are seeing about 28 percent of all pregnancies that
> would be exposed to methylmercury above the reference dose for at
> least one month of pregnancy. You also see maybe midway through
> pregnancy, say, four and a half months, that you are almost at one in
> ten pregnancies being exposed above the reference dose for half their
> pregnancy if women actually ate 12 oz of fish and followed FDA\'s
> recommendation.
>
> I will get into the details of that model and how we produced that
> answer, and also in this presentation I will focus in on some other
> examples.
>
> \[Slide\]
>
> This is really the outline of my talk. First I will talk about our
> modeling method and go into more detail on the results and how those
> were produced. Second, I will describe some of the underlying
> biological parameters in the model. That would be things like how a
> woman absorbs and excretes mercury. Third, I will talk about fish
> consumption and now much fish do women really eat. Of course, there
> aren\'t a lot of women eating 12 oz of fish a week but I will look at
> proportions of women who do eat a lot of fish, based on national
> databases. Fourth, I will talk about methylmercury exposure, in
> particular focusing on canned tuna because it is the top seafood eaten
> in the U.S. and a lot of high seafood consumers focus pretty heavily
> on canned tuna. Fifth, I will highlight some other examples from
> real-world data user examples that are found in government and market
> company databases of real women reporting large amounts of fish that
> were actually eaten during different periods in their life. Last, I
> will just sum up what we would like to see come out of FDA on the
> subject.
>
> \[Slide\]
>
> Modeling approach, the underlying structural technique in this model
> is called a Monte Carlo method. It is a probability method. What it is
> really good at is allowing for an accounting of biologic variability.
> Differing individual consumption patterns and ranges of mercury
> concentrations in seafood are all incorporated into the model. So,
> compared to, say, looking at an average woman paired up with a high
> end consumption, this model lets you look at the full range of
> exposures across the population accounting for the fact that people
> are different; they eat in different ways; and they are eating seafood
> that varies widely in its concentrations of mercury.
>
> Second, the underlying mathematical representation in this model, is a
> non-steady state or transient one-compartment pharmacokinetic model,
> developed and verified\--one place it is presented is Dr. Gary
> Ginsberg\'s work from the Connecticut Department of Public Health in
> peer reviewed literature. It is a model that looks in particular at
> mercury concentrations in blood and how they vary with time as a woman
> eats seafood.
>
> How do we vary the way that women eat seafood? We account for biologic
> variability in a couple of different ways. We rely on data from CDC\'s
> National Health and Nutrition Examination Survey, or NHANES, and we
> also rely on studies of absorption and excretion of methylmercury that
> appear in the peer reviewed literature, which were summarized in a
> paper written by Alan Stern, of the New Jersey Department of
> Environmental Protection, that appeared in peer reviewed literature in
> 1997.
>
> \[Slide\]
>
> The model also accounts for the different ways that people eat
> seafood, different consumption rates. The scenario I showed you first,
> which is everybody is eating 12 oz of fish a week, is a hypothetical
> scenario. But today I will present data that is based on real
> consumption data from national databases that include low fish eaters
> and high fish eaters as well. We used two different databases to do
> this. One is CDC\'s newly released 30-day recall seafood consumption
> study that includes over 1000 women of childbearing age and what they
> ate in the past 30 days. We use that in combination with the National
> Eating Trends database from a major market survey organization, called
> the NPD Group. This database we use in particular because it is really
> powerful. It contains data on almost 8000 women so it is many, many
> more women than CDC\'s recall file.
>
> \[Slide\]
>
> Lastly, mercury concentrations in seafood, the model accounts for the
> widely occurring concentrations of mercury in different fish species.
> To account for that, we compiled mercury data from seven different
> government databases of mercury and fish tissue. These came from FDA,
> NOAA and EPA, seven databases and 50,000 records altogether of
> numerous different fish species.
>
> \[Slide\]
>
> I will just talk briefly about how a Monte Carlo model works, for
> those of you who haven\'t used this technique before. It is
> conceptually pretty simple. You know, you start off any model with the
> exercise of what questions you want answered. So, we are first of all
> answering the question what would happen to mercury exposures if
> pregnant women followed FDA\'s advice and ate 12 oz of fish a week
> throughout pregnancy, barring the four black-listed fish. Would her
> mercury exposure exceed safe levels derived from available
> epidemiology studies?
>
> The first step in the model is that the model begins simulation. It
> basically creates a woman and the model randomly assigns that woman a
> unique combination of body weight, blood volume, the fraction of
> mercury that will be absorbed through the gut and the fraction of that
> mercury that will be distributed to blood as opposed to what is stored
> in other tissues, like the brain, and an elimination rate constant
> which is a measure of how quickly a woman can excrete that mercury
> from her body. So, that is basically the model, a person in all her
> associated biologic parameters that all come from measured data in the
> peer reviewed literature.
>
> \[Slide\]
>
> The second thing the model does, it assigns this woman an initial
> blood concentration. In other words, women are eating seafood
> throughout their life and at some point, you know, a woman who decides
> to have a child gets pregnant and she has a starting concentration of
> methylmercury in her blood. That is called her initial methylmercury
> concentration and that is where the model starts her off as she begins
> to eat seafood through pregnancy.
>
> The third thing the model does is it allows the woman to eat the
> prescribed number of fish servings through pregnancy, so in this case,
> if I am doing two servings, two 6 oz servings of fish a week, it will
> loop her through two meals per week in the model.
>
> \[Slide\]
>
> As it does that, it does the fourth thing, which is track the woman\'s
> blood mercury concentrations as she eats fish through pregnancy. The
> program maintains statistics on her blood mercury distribution through
> time. So, in other words, a woman eats the fish. A fraction of the
> mercury in that fish is absorbed through the gut and is distributed to
> the blood. Through the bloodstream, it is then distributed to the
> various tissues in the body and then is excreted through time,
> depending on that individual woman\'s excretion capacity.
>
> This is where the Monte Carlo part comes in. It repeats that, in this
> case, 299,999 times for example. So, in essence, it simulates 300,000
> unique women and at the end of the model we can compute composite
> blood mercury statistics on that whole population of modeled women.
>
> So, you can see how this modeling technique is really powerful because
> you are essentially creating women in this model based on real
> biologic variability and some of them will be particularly sensitive
> to mercury, will absorb a higher quantity, excrete a lower capacity,
> and those women, in combination with high consumption rates, is where
> some of the biggest problems lie and the model takes all that into
> account.
>
> \[Slide\]
>
> When we did this exercise of two servings of fish a week, as I have
> already discussed, this is one of the basic answers that came out of
> the model, that women really cannot safely eat two servings of fish a
> week through pregnancy and FDA\'s advice. If women actually followed
> it, you know, more than a quarter of all pregnant women would be in a
> zone that exceeds a safe level for at least a month of pregnancy.
>
> \[Slide\]
>
> Another thing that this model lets us do is segregate fish according
> to their relative safety. For instance, I can construct fish scenarios
> where I say let\'s let a woman eat sea bass and nothing but sea bass
> and see what that does to the answers in the model, how women fare. It
> turns out that sea bass, tuna steaks, halibut and white croaker are
> high enough in mercury, according to the measured data, that if women
> routinely ate those fish, or ate almost any of them, they would put
> themselves into a zone where their mercury levels might exceed safe
> levels.
>
> This chart is a little hard to read but it does segregate out by
> species which is one valuable thing we can see. On the X axis is how
> many meals per month of that particular fish a woman would be eating,
> so a meal per month up to two meals per month basically on the bottom
> of the chart. Then, the Y axis is the percent increase in the number
> of women whose blood mercury level exceeds the reference dose for more
> than a month of pregnancy. So, this is fixed at one month.
>
> But you can see that sea bass, tuna steaks, halibut and white croaker
> have really high mercury concentrations relative to the fish that fall
> out at the bottom of the chart. At the bottom of the chart we have
> things like salmon, wild Pacific salmon, farmed catfish, farmed trout,
> summer flounder. They are all much lower in methylmercury
> concentrations and, therefore, are associated with much lower risk
> levels as women eat them through pregnancy. So, the take-home message
> is that individual species vary pretty widely in their mercury
> concentrations.
>
> \[Slide\]
>
> I want to briefly go over some of the underlying biologic parameters
> in this model. The biologic parameters that govern absorption and
> excretion of mercury, as I mentioned, were taken from the NHANES
> program and from combinations of studies that appear in the peer
> reviewed literature, largely summarized by Stern in a paper from 1997.
>
> Body weight of women is assigned at the beginning of the model. We
> used data for 4935 women of childbearing age from CDC\'s NHANES
> survey.
>
> Blood volume is calculated from body weight. Blood volume correlates
> really strongly with body weight and increases, of course, as body
> weight goes up.
>
> Elimination rate constant is a measure of how quickly a woman can
> excrete mercury from the body. It follows a first order exponential
> decay pattern according to a number of studies in people, with a mean
> and standard deviation that I give here.
>
> Fraction of ingested dose that is absorbed\--every woman has her own
> unique capacity to absorb mercury through the gut after she eats the
> fish. The fraction of that absorbed dose is then distributed to the
> blood. So, the mercury enters the blood and is distributed throughout
> the body, goes to various tissues where it is stored, brain and other
> tissues, but some of it remains in the blood and that is the
> concentration that we keep in the model.
>
> \[Slide\]
>
> This is just what the initial concentration distribution looks like.
> This is data from NHANES arbitrarily separated out by age of women so
> you can actually see all the dots. But there are 1645 women whose
> blood mercury was measured in CDC\'s latest NHANES data release. One
> reason I post this is because it has become pretty apparent from work,
> in particular by Ben Raines, in Alabama, that when you focus studies
> on women who are frequent fish consumers, these women aren\'t
> necessarily represented in this data set. Ben Raines tested mercury in
> 65 women and he found that 51 of those women exceeded the reference
> dose in his measurements. So, some of them are a substantial amount
> higher than what is shown in this population of 1645 women.
>
> What we do know is that in that data set, although it is a large data
> set from CDC, we are not necessarily representing women who eat a lot
> of fish. There are a lot of women missing from that.
>
> \[Slide\]
>
> Fish consumption\--I just want to talk a little bit about the fish
> that women eat. As I mentioned, we rely on two primary databases to
> look at consumption. One is the 30-day seafood consumption recall file
> from CDC\'s NHANES program released a couple of weeks ago. The other
> is the National Eating trends database that gives us data on
> approximately 8000 women. I focus on that database here because it
> gives us so much more resolution at the tail where women are really
> eating a lot of fish.
>
> When we break that data down we find a lot of women in that tail and
> this is, in particular, focused on canned tuna. So, this graph
> basically highlights how many women are eating a lot of canned tuna.
> Let\'s just look at that center bar which is five or more servings of
> tuna per week. This is women who eat five or more canned tuna servings
> per week. When we extrapolate the data out to the population of women
> of childbearing age that corresponds to 52,000 women. There are also
> women who even eat seven servings or more of tuna a week. Three or
> more servings of tuna, 210,000 women of childbearing age, when you
> extrapolate this data, they are eating at least three servings of tuna
> a week. If we focus on the 52,000 women that are eating five or more
> servings of tuna a week, I can safely say that all those women will be
> above the reference dose for methylmercury.
>
> \[Slide\]
>
> So, I did a simulation looking at real consumption patterns pared down
> to only canned tuna so this is nothing except canned tuna. This is
> measured data from 8000 women. They are true consumption patterns,
> extrapolated to represent all women of childbearing age.
>
> I want to talk for a minute about concentrations of mercury in canned
> tuna because that, of course, is an integral part of this model and
> the scenarios that I do focus on are canned tuna. In our database we
> have 479 test results for canned tuna. Most of these come from FDA.
> FDA tested 219 samples in a special canned tuna survey in 1993. We
> have 115 samples from FDA\'s seafood surveillance database before they
> stopped testing domestic seafood; 27 samples from the total diet study
> and we have supplemented that with relatively new data from the State
> of Florida with 118 samples that they submitted to FDA about the time
> that the advisory was issued.
>
> So, we have a lot of canned tuna data. You can see that it varies
> widely in concentration, averaging about 0.2 but there are many
> individual cans of tuna that have concentrations far above that. I
> understand Dr. Aposhian tested cans of tuna and had a result even
> exceeding what is on this chart. So, there are a lot of cans of tuna
> that have very high levels.
>
> \[Slide\]
>
> I ran the model using real consumption patterns for women of
> childbearing age. As it turns out, the consumption comes from 7319
> women of childbearing age who eat canned tuna. We find that even
> forgetting all other fish, canned tuna consumption alone drives high
> blood mercury because it is such a high proportion of seafood that is
> eaten in the United States. There are about 40,000 pregnant women
> every year, and this is based on real consumption data so this is a
> picture of what is actually happening, an estimation of what is
> happening. There are 40,000 women in the U.S. every year, pregnant
> women who exceed the reference dose for at least three months of
> pregnancy based on canned tuna consumption alone. That is the bar that
> is associated with three months. So, they are over the safe dose for
> at least three months of pregnancy. That is 40,000 pregnancies. That
> is one percent of all pregnancies in the U.S. just from canned tuna.
>
> If we think about women exceeding the safe dose for at least a month
> of pregnancy, we are up to about 90,000 pregnancies going over a safe
> dose just from canned tuna consumption. So, you can see that the
> canned tuna consumption really drives a good percent of the risk in
> the U.S. in terms of women who are facing high methylmercury
> exposures.
>
> \[Slide\]
>
> I next focus in on a particular woman in a model, just a little window
> of what is happening in the model to the mercury in her blood. Between
> days 12 and 22 of the model she had a number of eating occasions in
> which she ate canned tuna that had quite a bit of mercury in it. You
> can see that her intake is exceeding her excretion capacity. That is
> what happens in this model, blood levels can build up and then
> decline. If you exceed excretion capacity, your mercury levels go
> higher and higher, and then maybe you eat some more mercury fish and
> levels decline but the model is accounting for all of that. So, you
> can see her mercury level is building up through this ten-day period
> just because of the tuna fish that she is eating. She is a frequent
> tuna consumer. She is eating it almost every day but the same thing
> happens for women who are eating it less frequently.
>
> \[Slide\]
>
> The next thing I did was a basic reality check on the model to see if
> it was consistent with what CDC had measured. The top blue line is the
> real world. That is the distribution of blood mercury levels that CDC
> measured in women of childbearing age, and it
> represents\--what?\--11600 women. That is the real world. Blood
> methylmercury concentration is on the X axis. The Y axis represents
> the percent of women who are at or below that methylmercury level. For
> instance, about 20 percent of all women are at or below 2 ppb of
> methylmercury in blood. That is how you would read that.
>
> Now, if I plot on top of that one of the answers from our model, the
> red line, that red line is the model results. It is a snapshot of
> blood mercury levels at model day 100. I could pick any day of the
> model. This happens to be model day 100. That is the distribution in
> all 300,00 women in the model at model day 100, what their blood
> mercury distributions looked like.
>
> As you would expect, you can see, number one, canned tuna consumption
> doesn\'t account for all the methylmercury in the population but it
> accounts for a substantial fraction. It is consistent with consumption
> patterns in the U.S.
>
> The second thing you can see, and this is important, if you subtract
> one line from another, so if you take background exposures that are
> represented by CDC\'s data in that top line and you subtract out the
> canned tuna line and you are basically saying let\'s look at what
> happens if people don\'t eat canned tuna, you suddenly find the
> exposures are substantially lower and you are getting a much higher
> percentage of women who are in a safe zone throughout pregnancy. So,
> the bottom line is canned tuna is a big driver of women exceeding a
> safe dose during pregnancy just because consumption is so very high,
> especially at the tail end of the data.
>
> \[Slide\]
>
> That is canned tuna. That is real good consumption data. I want to
> point out a couple of other examples of particular women where we know
> their consumption pattern in detail. First of all, FDA conducted some
> focus groups in the fall of 2001 which are real interesting reading if
> you are so inclined, but there are a number of women in these focus
> groups who talked about how much fish they were eating or did eat
> during pregnancy.
>
> One woman said in these focus groups, \"when I had my first son I had
> gestational diabetes and I was put on a very strict diet, and one of
> the things I could eat was a can of tuna and two tablespoonfuls of
> mayonnaise for lunch every day, five days a week.\" She said, \"so
> every day, five days a week for lunch, for seven weeks of my
> pregnancy, so for seven weeks I am eating more than they recommend.\"
> So, she ate tuna every day for seven weeks, and that is perfectly
> consistent with some of the data that is in the measured databases.
>
> A second woman said, \"I was doing it, eating canned tuna, because I
> was planning to get pregnant and as part of the Atkins diet you can
> have stuff like that, fish or chicken. So, I ate a bag of salad, a can
> of tuna. That was my lunch.\" So, she was on a special high protein
> diet and she was eating a lot of canned tuna.
>
> Let\'s look at what the databases tell us about how consistent those
> anecdotes are with real-world data. Well, in CDC\'s NHANES 30-day
> recall seafood consumption database, there is a 29-year old woman who
> reported eating 30 servings of tuna over 30 days. She eats canned tuna
> every single day. In the National Eating Trends database two women,
> ages 22 and 24, reported eating 15 servings of canned tuna over 14
> days, about a can a day. A 23-year old woman reported eating 14
> servings of canned tuna over 14 days. So, there are people for whom
> canned tuna is a staple. They are eating it every day for lunch or
> dinner.
>
> \[Slide\]
>
> I took one of these examples and ran it through the model. I looked at
> the focus group woman from Calverton, Maryland who said she ate a can
> of tuna every day for seven weeks of pregnancy. She delivered early so
> that was the end of her pregnancy, but during that seven-week time, if
> you think of the Y axis as the percent chance that she would go over a
> safe dose for this given time span during her pregnancy, let\'s look
> at four weeks. For that seven weeks of pregnancy there is about a 65,
> 70 percent chance that she will go over the safe dose for well over
> half of the rest of the duration of her pregnancy. So, she has
> substantial chances that she is over the safe dose through almost all
> of the remaining period of her pregnancy. That is just seven weeks.
> So, for women who really are eating a lot of tuna throughout their
> entire pregnancy, they are getting into very high probability that
> they are exceeding the reference dose through almost all of their
> pregnancy.
>
> \[Slide\]
>
> The next thing I would point out is that this is women who happened to
> eat fish that Ben Raines tested from the Gulf of Mexico. He tested a
> handful of fish. One was an amber jack that was caught in the Gulf of
> Mexico and had a mercury concentration of 1 ppm. The other was a
> yellow fin tuna that had a concentration of 0.83 ppm of methylmercury.
> These are averages based on number of samples. If a woman ate that
> fish for four servings of that fish at the beginning of her pregnancy
> so she is only eating four servings of fish only over four days\--the
> time span during pregnancy is shown on the X axis and the percent
> chance that she would be exposed to methylmercury reference dose for
> that time span or longer is on the Y axis. So, if we just look at,
> say, one month she is going over the reference dose for at least a
> month of pregnancy.
>
> We see for the yellow fin tuna there is a 60 percent chance she would
> be over the reference dose for at least a month. For the amber jack,
> she would be up to an 80 percent chance that she would be over the
> reference dose for a full month of pregnancy.
>
> So, you can see these fish with high concentrations which are in the
> database\--these fish are out there, they are being sold in the
> marketplace, and a very few servings of those fish will really drive a
> substantial percent chance that a woman would go over a safe limit for
> a long period of her pregnancy.
>
> \[Slide\]
>
> Last, our recommendations to FDA\--because FDA has really such a
> limited consumer advisory to pregnant women, a lot of states are
> taking up the slack and trying to give women supplemental advice.
> There are at least nine states that advise women to limit their tuna
> consumption, and I think Michael Bender will talk about this in more
> detail later. Connecticut, for instance, you know, fresh tuna once per
> month, canned tuna one to two meals a week; Wisconsin, one meal per
> week of canned tuna, one meal per month of fresh tuna; Michigan, one
> meal per week of canned tuna.
>
> You know, FDA is advising women that they can safely eat up to 12 oz
> of fish a week that includes canned tuna and tuna steaks, and these
> states have said, wait a minute, that might not be safe. So, they have
> tried to issue some supplemental advice to women to get the message
> out about mercury in fish that FDA does not have in their advisory.
>
> \[Slide\]
>
> This is a plot of omega-3 fatty acid content, a rough estimate of
> omega-3\'s in various kinds of fish versus the mercury concentrations
> in those fish. The wide bars are the omega-3 fatty acid content. The
> first point is that fish vary pretty widely in their omega-3 content.
> This is an average level based on USDA\'s nutrient database for that
> group of fish that I show on the X axis. Herring, sable fish, salmon,
> very high in omega-3\'s. Scallop and clams are on the other end of the
> graph, generally a lot lower in omega-3\'s, and everything else is in
> between.
>
> On top of that you see the dark bars. That is average methylmercury
> concentration in those fish. It is interesting to note that there
> doesn\'t seem to be much correlation at all between omega-3 content
> and methylmercury concentration. The good news in that is that they
> are not mutually exclusive and it is possible to come up with a list
> of high omega-3 fish that are low in methylmercury. One really great
> example of that is wild Pacific salmon, which is the third fish over
> on the bottom. It is very high, on average, in omega-3 fatty acids and
> very, very low in methylmercury. So, that would be a great fish
> according to the data that we have in-house for pregnant women to eat
> during pregnancy. They could safely eat it and still get the nutrients
> that they need.
>
> Let\'s also juxtapose a couple of examples of how many of these fish
> FDA has tested. For herring, which has fabulously high omega-3\'s on
> average, FDA has eight samples. Whitefish, high in omega-3\'s and you
> would want to be able to recommend that to pregnant women and FDA has
> tested two whitefish. They have tested two bluefish; about ten of some
> of the species of sea bass, ten snapper, ten perch. So, methylmercury
> sampling has not been sufficient, to say the least.
>
> \[Slide\]
>
> FDA\'s summary, their own summary that is on their web site\--they
> released a summary of methylmercury concentrations in seafood after
> they released their consumer advisory, and it shows that their
> monitoring program has major testing gaps. They focused their testing
> really heavily on seafood that women are advised not to eat. For
> swordfish, for example, they have 598 samples listed; for shark, 394
> samples. I pointed out some of the other fish that have promising
> sources of omega-3\'s for women, and there are only two tests for
> whitefish, two for bluefish, eight for herring, ten for ocean perch,
> nine for orange ruffy. In so many cases the mercury concentrations
> have not been adequately characterized that you could actually be
> certain that women are getting good advice if you recommended those
> fish for them to eat during pregnancy.
>
> \[Slide\]
>
> The bottom line, I just want to reiterate some of the things that
> Richard said. This is what we would like to see FDA do. We would like
> for FDA to adopt the NAS recommendations for a safe level of exposure.
>
> We would like FDA to conduct a one-time sampling program for the most
> consumed fish species. For so many of these fish there is not enough
> data to fully characterize mercury concentrations. We want FDA to do a
> major one-time sampling program of, say, the top 50 fish eaten in the
> U.S. to really get a grip on what is going on with the mercury.
>
> Third, we would like FDA to conduct and make public a risk assessment,
> to do a risk assessment. We are recommending a probabilistic exposure
> risk assessment that would allow FDA to get really good resolution at
> the tail end of the data where women are consuming a lot of fish.
>
> Number four, we would also like FDA to issue a public health advisory
> that protects a very high percentage of women from mercury exposure
> that exceeds the NAS recommendations and that ensures women eat low
> mercury fish, high omega-3\'s. As we saw in the canned tuna data,
> about one percent of women are going over a safe dose under model
> predictions for at least three months of pregnancy just from canned
> tuna consumption, and that really is what is happening based on all
> the data that we have put together. Those exposures could be mitigated
> if FDA would give the public, particularly women, comprehensive advice
> on what fish to avoid during pregnancy and what fish they should eat
> during pregnancy that are high in omega-3\'s and low in mercury.
>
> That is all I have to say. So, is it question time?
>
> **Questions of Clarification**
>
> DR. MILLER: Thank you. Comments? Dr. Nordgren?
>
> DR. NORDGREN: I have two questions. The first is how accurate do
> people estimate these 30-day recall things are for actual fish
> consumption? The second question is, is there any evidence out
> there\--if fish are like humans, there must be tremendous levels in
> variation in species so if you measure a shark in Cape Cod versus
> somewhere else, why aren\'t their levels fluctuating, and why only one
> sampling?
>
> MS. HOULIHAN: Why not more sampling? So, the first question was how
> accurate is the 30-day recall file. That is a question I don\'t have
> an exact answer to, but I can tell you that it is the most
> comprehensive long-term survey done by the government on safe food
> consumption. That is not the underlying data in the scenarios I
> presented today. I used the National Eating Trends database, which
> records what you eat as you eat it for 8000 women. It is a food diary
> that is kept for a two-week period. It gave me so much better
> resolution at the tail end of the data that I used this for the canned
> tuna scenarios. I think the 30-day recall file is generally consistent
> with the NPD data though there is a substantial fraction of women in
> that who are eating a lot of seafood, reporting eating a lot of
> seafood.
>
> The second question was why not test more. We are sort of calling on
> FDA to do a big one-time sampling program because we think that would
> be a fabulous start. And, that is the kind of underlying data that you
> would want FDA to have as they go through doing their own risk
> assessment and exposure analysis. There are many species of fish that
> I was not able to include in my model because there is just not enough
> data. So, for FDA really to take a good initial comprehensive look at
> this, they need to do a comprehensive sampling program. I would
> advocate for continuing to test for mercury, but I think a big
> one-time testing program of a lot of samples for the top fish is a
> really good place to start.
>
> DR. MILLER: Johanna?
>
> DR. DWYER: Do you mean actually do the mercury analyses in these
> various types of fish, or do you mean collect data that already exist
> in the literature and put them into some uniform database? Which is
> it? Are you calling for the analytical work, or informatics work, or
> both?
>
> MS. HOULIHAN: Both would be fabulous because there are a number of
> states who have tested some marine species that maybe FDA doesn\'t
> have data for. But, you know, FDA should conduct their own
> comprehensive sampling program at the same time. It makes a lot of
> sense for FDA to try to get together a comprehensive database of what
> has been done to date as well for methylmercury testing in seafood.
>
> DR. MILLER: Dr. Russell?
>
> DR. RUSSELL: Thanks for the very clear analysis that you have given.
> Your analysis, of course, is based on the acceptance of the NAS
> guidelines, which was based primarily on the Faroe Islands study. The
> other serious scientific attempt, it seems to me, to arrive at a safe
> level was the ATSDR study or analysis using as the lead study the
> Seychelles study, which came out with a level that was 0.3 instead of
> 0.1 as being a safe level. Can you explain how you analyzed or what
> you thought of that ATSDR analysis and why you rejected it, or why it
> is being rejected in favor of the NAS study? Is it because it is more
> conservative and you want to err on the safe side, or are there some
> other reasons, scientific reasons?
>
> MS. HOULIHAN: You know, in the world of risk assessment or toxicity
> risk assessment in particular, it is pretty traditional when you are
> trying to protect public health to look at the study that showed
> measurable effects at the lowest levels and to use that as a basis for
> public health protection. I think that makes a lot of sense. Instead
> of choosing a study that showed a higher level, you want to do
> something that actually ensures a higher level of protection.
>
> No one is disputing, I think, that they are credible studies, the
> Seychelles, Faroe and all the other studies that have been conducted,
> but the idea behind risk assessment is to take the data as a whole,
> look at the most sensitive endpoint and apply that as the starting
> point for your reference dose.
>
> DR. RUSSELL: Just to carry that one step further, I agree in general.
> Another question that I would have for you is do you think that the
> Faroe Island study is more comparable to what happens in the U.S., or
> do you think the Seychelles study, with regard to dietary patterns, is
> more comparable?
>
> MS. HOULIHAN: I think there are a lot of women in the U.S. who eat a
> lot of seafood. I will say that. I know that there were questions
> brought up during the National Academy study of possible confounding
> with PCBs, and those questions were addressed. It is not PCBs, it is
> methylmercury that seems to be associated with the neurodevelopmental
> decrements. There are other studies as well that show consumption
> patterns that closely resemble ours where we don\'t have those sort of
> episodic spikes where effects are seen in those consumption patterns
> as well.
>
> I would also say that when we are modeling methylmercury in blood we
> are not really reproducing the spikes. In the model results that I
> showed, when you see a spike in the model, that is not the true spike.
> I did neglect to point that out, that that is already the
> post-distributed mercury concentration.
>
> DR. MILLER: Dr. Lee?
>
> DR. LEE: Somewhat as a follow-up, I admire your conservative approach,
> erring on the safety of the women and the children, but both the Faroe
> and the Seychelles studies were done in a double-blind fashion so you
> remove any investigator bias. But it seems to me that in this modeling
> study that you did you selected data based on a conservative outcome
> that you knew. So, some of the model variables that you have picked,
> like the body weight and the blood volume and elimination, could have
> been influenced by the need to demonstrate the outcome.
>
> MS. HOULIHAN: You are saying that I chose biologic parameters that
> would drive up mercury exposures?
>
> DR. LEE: No, I am saying that you didn\'t choose your parameters in a
> double-blind or even in a single-blind fashion. You were looking at
> data that would help demonstrate the need for action.
>
> MS. HOULIHAN: I chose the underlying biologic parameters that are in
> the model based on what is in the peer reviewed literature and I
> didn\'t cut anything out. Say, for instance, elimination rate
> constants and the volume that is absorbed through the gut, those were
> taken from a survey that Dr. Stern, from New Jersey, did where he
> considered all the available data from the peer reviewed literature
> and I don\'t think he purposely cut any data out of his analysis.
>
> DR. LEE: Okay, that was a review that Dr. Stern did?
>
> MS. HOULIHAN: Right, a paper he published in 1997.
>
> DR. LEE: So, is that all the available information on that absorption?
>
> MS. HOULIHAN: Well, that is an issue that FDA should take up as they
> build their own model because there have been data published
> subsequent to Dr. Stern\'s review that should also be included in
> those kinds of distributions. That is an important question.
>
> DR. LEE: Okay, thanks.
>
> DR. MILLER: Dr. Fischer?
>
> DR. FISCHER: I would I guess have a comment that your whole
> presentation seemed to indicate, at least to me, that you knew what
> level of mercury exposure was safe and what level was unsafe and that,
> of course, was the EPA RfD. Except, I think we all, from our
> discussions up to this point, have heard other people say that they
> weren\'t certain exactly what level is safe and what level is unsafe.
>
> The fact is that we really don\'t know where the safe level is at this
> point. What we have to work with is a number that comes from a risk
> assessment procedure which can be used for regulation. So, the
> terminology that is used, safe versus unsafe, when used in the way you
> are using it tells the public that they are being subjected to a lot
> of risk that they believe is actual. But we know there is a lot of
> uncertainty.
>
> I just wish, for example, when you presented your data from your model
> that you would have shown us, instead of percent of women above a
> certain regulatory level, the model blood levels of methylmercury of
> these women, or hair levels so we could compare with actual blood and
> hair levels that have been seen, like the NHANES levels and others. It
> would allow at least me, who looks at blood levels and hair levels, a
> better picture of actually how well your model is doing.
>
> MS. HOULIHAN: Well, you will see in your slides that I did present a
> picture of the blood levels, the composite model results from all
> 300,000 women and compared them directly with CDC\'s background
> distribution. So, you can look through your presentation slides and
> see exactly the distribution that the model predicted from real
> consumption patterns.
>
> I agree there will always be uncertainty in these kinds of problems
> for what level is toxic to a particular person, what is safe, what is
> not safe, is there a safe level of exposure but in the end, when you
> are doing a risk assessment and trying to protect public health you
> have to make decisions. For instance, what percentage of the
> population are you trying to protect from what level of exposure, and
> you have to make those decisions in order to do the risk assessment
> and protect public health. Whether that is a bright line, a fuzzy
> line, a grey line, you know, I don\'t know but right now there is not
> really a line; it is just don\'t eat sharks or king mackerel or tile
> fish, and that is not really doing it for keeping blood levels down to
> levels that the National Academy and the Environmental Protection
> Agency say are protective of public health.
>
> DR. FISCHER: I understand perfectly the decision-making process. It is
> communication that I am talking about. Whether it is scientific or not
> scientific, it seems to me we should be honest and truthful about how
> we are presenting the information to each other and to the public. It
> is a matter of semantics I guess.
>
> MR. WILES: We would be glad to provide the committee with blood level
> distributions for any particular slide that was up here, if that is
> going to help clarify matters in any way.
>
> DR. FISCHER: Yes, I would like to see the blood levels. Wonderful.
>
> MS. HOULIHAN: Yes, if you have a particular thing you want to see
> besides what I showed here, which is blood levels for a particular
> period of time, I could show you other periods of time or other
> scenarios if that is interesting or useful.
>
> DR. MILLER: Dr. McBride?
>
> DR. MCBRIDE: I may be confused a little bit by your model, but I
> understood you to say that you took into account the initial
> methylmercury levels in these women based on, I presume, a population
> study.
>
> MS. HOULIHAN: Right.
>
> DR. MCBRIDE: And then you added to that what would happen if they ate
> the top limit of fish.
>
> MS. HOULIHAN: Right.
>
> DR. MCBRIDE: Well, that doesn\'t take into account that a good number
> of them are already eating that or more.
>
> MS. HOULIHAN: Well, on any day in the U.S. there is a particular
> distribution of blood mercury levels that is going on in the United
> States. So, the point when a woman starts pregnancy falls somewhere in
> that distribution. She starts her pregnancy with one of those
> concentrations, and that is what the model does. It assigns her one of
> those concentrations. Then, through pregnancy she continues to eat
> fish. So, she is doing her thing, eating fish as she normally would,
> and days subsequent in her pregnancy she still falls some place in the
> U.S. distribution.
>
> So, there is no inconsistency between using a measured set of
> population values as she begins pregnancy with then continuing to let
> her eat fish through pregnancy because that is what people do. What is
> important is that as the model runs and reproduces population-wide
> statistics, those statistics remain consistent with what we know about
> population-wide blood mercury levels, and that does happen when we
> check the model out. It is consistent with what CDC measures in the
> general population.
>
> DR. MCBRIDE: Then, do I misunderstand to think that during your
> modeling the levels would all have to be higher?
>
> MS. HOULIHAN: No, they do not. Some women drop off because they are
> eating low mercury fish or few fish.
>
> DR. MCBRIDE: Women\'s blood volume goes up considerably in pregnancy,
> actually by a greater percent than their weight. Is that included in
> your model?
>
> MS. HOULIHAN: That is not included and I haven\'t seen it in any
> assessments that have been done to date. The EPA doesn\'t consider it.
> I would have liked to add that to my model but I had trouble finding
> studies that would let me quantify that.
>
> DR. MILLER: Other comments or questions? Yes?
>
> DR. ACHOLONU: During your presentation you talked about the frequency
> in the consumption of tuna fish for instance. You say that eating it
> very frequently, you used the word, \"drives up\" the concentration of
> blood mercury. You also talked about the absorption and excretion of
> mercury. There are some studies that say that the half-life of mercury
> in the human blood is 70 days.
>
> MS. HOULIHAN: Yes.
>
> DR. ACHOLONU: And that you get a steady state or equilibrium between
> absorption and excretion in about a year if you are exposed to it
> every day. How does this ameliorate your fear about the frequency of
> eating tuna fish?
>
> MS. HOULIHAN: Well, it doesn\'t ameliorate my fear at all for women
> who eat tuna really frequently. If they do eat fish frequently enough
> to reach what you would call in the modeling world a steady state, it
> is still a level that is much higher than the NAS and EPA
> recommendations.
>
> DR. MILLER: Dr. McBride?
>
> DR. MCBRIDE: How many ounces of tuna fish are in a typical small can
> of tuna?
>
> MS. HOULIHAN: That is a 6 oz can or 3 oz small can.
>
> DR. MCBRIDE: Three? So, the women eating two cans a week were eating 6
> oz of tuna.
>
> MS. HOULIHAN: Right, and in this model run that I showed that focused
> on canned tuna, it tends to damp out the tails. It doesn\'t show as
> many women in the high ends of risk because I fixed the model on a
> typical tuna serving. The next step if I continued this work would be
> to use actual measured distribution that includes women eating lots
> and lots of tuna as well as small amounts of tuna.
>
> DR. MILLER: Dr. Shannon?
>
> DR. SHANNON: If you could help me understand one issue that has come
> up repeatedly over yesterday and today,
>
> and that is establishing what mercury level in a woman would lead to
> unsafe concentrations in the fetus. I think we have been looking
> primarily at a blood level of 5.8 ug/L in a woman, assuming that that
> would correspond to a cord blood mercury of 5.8 ug/L. If the
> concentration of mercury in a fetus is 50 percent higher than the
> blood mercury in a woman, and I have heard many others say it is
> credible that the cord blood level would be higher, then I guess I
> already know the answer but that would mean that you really should be
> looking at a lower blood mercury in a woman that is potentially
> hazardous. So, my question to you is have you looked at your model at
> that lower level of blood mercury in order to kind of explore what
> that means in terms of impact?
>
> MS. HOULIHAN: No, but that is a great idea. I mean, it would
> obviously\--well, I don\'t want to say it would drive the numbers up.
> Yes, it would make the risks higher.
>
> DR. MILLER: Dr. Nordgren?
>
> DR. NORDGREN: Would it be appropriate to ask Dr. Lockwood a question
> at this point?
>
> DR. MILLER: It would.
>
> DR. NORDGREN: Dr. Lockwood, a very simple question, are there good
> studies studying levels of methylmercury that you are aware of in
> pregnant women that changes? Are there any good studies that document
> what happens to methylmercury levels during pregnancy?
>
> DR. MILLER: Dr. Lockwood, could you use one of the microphones,
> please?
>
> DR. LOCKWOOD: It is a great question. In fact, I was thinking two
> things from a basic toxicology perspective. The first is from the
> fetus\' perspective, does a given level of mercury have the same
> effect at given gestational ages? You would assume that a first
> trimester exposure would potentially have a more toxic effect than an
> exposure later in gestation. We don\'t have the data to model that. I
> don\'t think they exist anywhere but if anyone has it, I would be
> interested in knowing that.
>
> The second is that, as with many drugs and many substances, the volume
> of distribution of the drug in a woman\'s body changes across
> gestation. Metabolism in the liver, not that that is necessarily
> relevant to this particular exposure, changes and the entire
> metabolism of a woman changes, and it may alter either favorably or
> unfavorably the build-up of mercury.
>
> So, it is a great question and it is another reason for the NICHD to
> have an RFA to address all these issues. But the answer from a
> theoretical perspective is, yes, it probably does. I don\'t know. I
> don\'t know the answer but it probably does.
>
> DR. NORDGREN: But you are not aware of a study that has documented
> that?
>
> DR. LOCKWOOD: No.
>
> DR. MILLER: Any other comments? Go ahead.
>
> MR. WILES: I just want to say one thing. These are all great questions
> and I just want to remind the committee that we are not expecting
> anyone to just adopt this model. What we want is for FDA to go and do
> this on their own and, through an open and transparent process,
> address these questions. But let\'s do it. Let\'s use our model, the
> seafood industry model or whatever. We need to move forward with a
> real exposure assessment that gets at these questions because it is
> clear that something is going on at the high end of the curve here,
> and whether it is 40,000, 100,000 or 60,000, whatever the number is,
> we think it is clearly greater than zero and it needs to be addressed,
> and we think this is the general way that it needs to be done.
>
> What we are basically saying is that the FDA needs to go ahead and do
> it, not necessarily per se our results, our model or the seafood
> industry model or whatever. So, I just wanted to clarify that.
>
> DR. MILLER: Just as a matter of scientific interest, and you can\'t
> stop scientists from being scientists, when you looked at your model
> there is a difference in the increase in risk depending on how far
> above the RfD the blood concentrations are or exposure.
>
> MS. HOULIHAN: In these simulations I didn\'t pull out results for
> particularly high values so it didn\'t distinguish.
>
> DR. MILLER: But can your particular model give you a distribution?
>
> MS. HOULIHAN: Absolutely, yes, to get statistics on even higher levels
> of exposure.
>
> DR. MILLER: Or even lower levels.
>
> MS. HOULIHAN: Or lower levels.
>
> DR. MILLER: How many of those over the RfD are within ten percent of
> the RfD?
>
> MS. HOULIHAN: Right, that can all be done if you guys would find that
> useful.
>
> DR. MILLER: Thank you. If there are no other questions, thank you very
> much. Our next speaker is the long awaited Dr. Henry Anderson.
>
> **Wisconsin Advisory**
>
> DR. ANDERSON: I am a fairly late edition to the agenda here and I
> didn\'t really have the charge questions that you had or a clear idea
> of what you wanted to hear so I am going to give you a smattering of a
> little bit of everything as it relates specifically to Wisconsin.
>
> \[Slide\]
>
> I will begin with a little bit of our history as it relates to
> mercury; how our advisories for sport fish have gone over time; and
> then give you some of the information from what we consider to be a
> comprehensive type of program, not just development or issuing of
> advice.
>
> \[Slide\]
>
> Just to give you a sense of Wisconsin, while we are not the size of
> Alaska, we do have 40,000 miles of rivers and 15,000 lakes, all of
> which are teeming with fish, filled with tourists who want to harvest
> those fish.
>
> \[Slide\]
>
> We, of course, have a history of point source pollution. We are also
> part of the industrial Midwest. This happens to be the Fox River with
> one of the largest PCB sources at the time, in 1973. We also have
> mercury point sources as well. I am going to talk not about point
> source issues, but you have to keep in mind that when we deal with
> localized fish, if they are not pelagic species that move around a lot
> you have to pay attention to where the fish came from, the question of
> the sharks, or whatever. If you have a ground fish which lives in a
> given area and that happens to be where toxic waste has been dumped
> for a long period of time, those fish will be different than other
> fish.
>
> \[Slide\]
>
> From a public health perspective, over the years we have always
> advised that fish is good to eat. You may recall people saying fish is
> \"brain food.\" It is also good for the heart and, kind of the
> Hobson\'s choice, it comes with toxic chemicals, as was mentioned
> earlier. Hobson\'s choice, if you remember your literature, was a
> buggy renter in England who said when you want a horse for your buggy,
> you can either have the horse nearest the door or no horse at all. So,
> basically it is not a choice. You take the horse. It was always kind
> of thought, well, the choice is you eat fish and you take the mercury
> or you don\'t eat fish. In reality, the message we have been trying to
> give is that that is not true.
>
> \[Slide\]
>
> This is back in 1970 is when the mercury was first begun to be
> identified in the Midwest. This is from the Wisconsin Conservation
> Bulletin.
>
> \[Slide\]
>
> Here, in 1971, is one of the early publications pointing out where
> sampling of fish was going on and warning areas. This was the
> scientists issuing advice or fish consumption warning concerns.
>
> \[Slide\]
>
> It wasn\'t until 1975 that Wisconsin issued their first advisory. What
> was done in the early years was to use the FDA market fish as a
> reference.
>
> \[Slide\]
>
> Basically, our target audience from 1975-86 was to provide the angler
> a qualitative comparison to market fish. People wanted to know how
> does this compare to the fish I can buy in the store. So, we were able
> to say, well, this fish is better than the guidelines by FDA and in
> Wisconsin we were not giving advice on how much is safe, or how much
> fish can I eat. We were not risk based; it was strictly
> comparative\--if you eat this fish you get four times as much as this
> basically, not commenting on the extent of the hazard.
>
> Key messages, again, were to eat fish, avoid the most highly
> contaminated fish, target where you fished and the species, and then
> kind of common sense, easily remembered, small fish, younger fish,
> lower on the food chain are likely to have the least contaminants. Oh,
> people would always point out, \"but where that battery manufacturer
> discharged, those fish we can wring the mercury out of.\" So, there
> are always localized sites and there will always be a need for
> specialized advice in local areas but, in general, common sense, good
> advice that people can remember is this type of advice and most states
> have been issuing this for many years.
>
> \[Slide\]
>
> Back in about 1986\--I didn\'t go through all my old files because I
> couldn\'t get them back from the historical society in time, but early
> on what changed many of the states was FDA acknowledging that
> tolerance levels may not be appropriate for consumers who regularly
> eat locally caught fish; also the issue of cost benefit coming into
> it, and so states were left with, well, we need to do something on our
> own and. At that time, being the last in the Great Lake States,
> Wisconsin decided what people really want and what we are being asked
> for is not which are the worst fish but how much can I eat. So, we got
> into the risk assessment business of trying to issue advice on how
> much fish people could eat. Again, the issue of safety is always a hot
> item. We tried to avoid the issue of safety.
>
> \[Slide\]
>
> So, what we came up with at the time was working with our border
> states. One of the common things you will find in issuing advisories
> is if you have a cacophony of voices, as we do at the national level
> which is partly why you are here, the public tends to say, \"well,
> they can\'t agree, why should I pay any attention to this advice at
> all?\" So, one of the things that we have done\--there are portions of
> the Great Lakes where, if you are on one side of the boat you are in
> Michigan, if you are on the other side of the boat you are in
> Illinois, and the other Wisconsin, and if we all have different
> advice, it is the same fish and you just fish on the side that has the
> advice you want to follow. Obviously, that is not at all an
> appropriate thing but it was pointed out to us why don\'t you have the
> same advice on mercury? We share considerable water with Minnesota so
> a lot of these advisories were done to have some uniformity at least
> on border waters.
>
> This is just early on when we went to the assessment, we separated the
> advice for pregnant women and children, but predominantly pregnant
> women, from the rest of the population. This just goes through the
> advisory as it was done earlier. By the year 2000, we had 1200 water
> segments that we had tested, and for 340 of those we had some type of
> mercury advisory on.
>
> \[Slide\]
>
> Then, along came the EPA reference dose and we began looking at how
> would that fit with our current process and this just gives you what
> we came up with. We also felt, again talking with many of the other
> states, that it did make some sense. There was the strongest evidence
> for a sensitive population. You notice we aren\'t saying women and
> children because there may be more sensitive populations than just
> them. Those are the ones the scientists have focused on.
>
> The general population is another group, again recognizing that the
> reference dose is supposed to accommodate all individuals, and much of
> the uncertainty was related to adult effects from the different
> studies. Two of them showed cardiovascular effects at levels actually
> lower than for the growth and development issues for the fetus, and
> 0.05 fit with our previous advice of where we would put an unlimited
> consumption level, from there up to 0.22 is about the one meal per
> week level. Then up to 1. We really didn\'t want to be issuing advice
> or recommending eating fish that were over the FDA tolerance so we
> have sort of drawn the line at 1, as you can see, in the general
> population. You can do with one meal a month up to 2.81 ppm in the
> fish tissue. We felt that we would rather keep it at a lower level and
> be consistent at least on the end with the common sense of, \"well, if
> it is safe to buy it in the store it ought to be safe for me to eat.\"
> Conversely, \"if I can\'t buy it in the store there must be something
> wrong with it.\" Therefore, it was fairly well accepted to keep the 2
> on the top end but issue advice separately below that point.
>
> \[Slide\]
>
> When you look at that slide and you look at our fish tissue samples,
> basically we have very few fish that are below 0.05. So, going to
> multiple advice levels we really felt we needed to take a look at a
> more general guideline. We were also hearing from the public and some
> of our survey work that, in fact, we had gotten a very small segment
> of the population. When they catch a fish, do they note the time of
> the moon, the size of the fish, where they caught it, time of day,
> look what was in its stomach? They have a log going back over all the
> years. Those people who are very data oriented, they wanted to know
> exactly how many inches, the size of the fish, the location of the
> fish for an advisory, and when you have 1200 bodies of water that gets
> you a pretty good sized book and most people just couldn\'t remember
> the advisory. It was scientifically consistent with risk numbers but
> made for
>
> very confusing type of advice.
>
> So, what we decided to do is step back, go back to a somewhat more
> qualitative approach and look at where do the various fish species
> fall, and try to come up with some general guidelines for most inland
> waters. There were some specific hot spot areas, which now comes down
> to 92, where the data shows that we needed more stringent advice. But,
> again, when you are looking at 15,000 different lakes, to have a list
> of 92 it fits on the back of a single page.
>
> \[Slide\]
>
> So, what we ended up with is not exactly using the FDA. Keeping in
> mind that we had an advisory, yes, it has to have a science base but
> it doesn\'t have to be a strict regulatory application of a number.
> So, for women of childbearing age and children we went with one meal a
> week for pan fish, including bluegill and sunfish, and these are what
> the vast majority of the population catch. It happened to be trout
> unlimited, so you see the fly fishing rod here. That is something that
> a lot of people use when we are trying to encourage that as a sport,
> especially for women.
>
> \[Slide\]
>
> Childbearing age women could eat, in addition to the one meal a week,
> one meal per month of game species, which is walleye, northern pike
> and the bass species, catfish. Some might argue that a sucker isn\'t a
> game species but the size of the suckers in Wisconsin\--
>
> \[Laughter\]
>
> \--I am just kidding. Actually, there is a fairly substantial netting
> season for white suckers. For the others, unlimited amounts of pan
> fish. If you look at our creel census, this is the class of fish that
> are low on the chain, they are in every lake and it is something that
> just about everybody can catch; you don\'t even have to have a boat.
> So, this is our number one consumable sport fish.
>
> \[Slide\]
>
> For those not covered by the women of childbearing and kids, they went
> to one meal a week for game fish.
>
> \[Slide\]
>
> And, what we found when we started to look at mercury, and I will give
> you a little of our survey data on that and that is what you have been
> hearing and is perhaps one of the reasons the group is here is, as we
> began to look at mercury and fish consumption, unlike our other
> advisories for PCBs and dioxin, PCBs are not a serious or significant
> contaminant in most commercial species where mercury is quite
> comparable to much of our sport fish. So, what people wanted to know
> is, well, how does this compare to fish I buy in the store? If I
> don\'t eat walleye and I go and buy Canadian walleye, or I go and buy
> cod, or tile fish from the store, is that better or am I getting more?
>
> So, we really felt we needed to move into having a combined advisory.
> Up to this point we had always segregated the commercial fish which
> are under a regulatory approach from the sport fish which was a strict
> advisory. I guess because salmon is amongst the most commonly eaten we
> included that, but you can see it is basically a very low level fish
> compared to some of the others. You can read here basically what we
> are saying. So, this is a little segment that is in our advisory,
> telling people a little bit about it.
>
> \[Slide\]
>
> One of the things that we are moving towards in Wisconsin and other
> states as well\--the last slide showed you the commercial fish and
> then you have the sport fish advisory and people want to know, well,
> how do I combine these? How does this fit with that one? So, this is
> from our women and children\'s guide to eating fish from Wisconsin
> including sport and commercial. Here we kind of lay it out since white
> tuna is one of the most common fish eaten and most commonly people
> will ask, \"well, what if I eat tuna too?\" So, we have one meal a
> week of tuna, a 6 oz can being one meal. Then, in addition to that,
> you could have another meal of a sports species or other commercial
> fish that you would buy or eat in a restaurant. Then, in addition to
> that, one meal a month of the sports species and then we list the
> FDA\'s \"do not eat fish.\"
>
> Where we are intending to go is to, hopefully, get some additional
> data, and we may want to add some of the commercial fish into the one
> meal per month category so that people will understand how it compares
> to their sport-caught fish.
>
> DR. MILLER: You have five more minutes.
>
> DR. ANDERSON: Okay.
>
> \[Slide\]
>
> I am going to go quickly here. This is also in the women\'s guide,
> some pictures and then you will see the little red, yellow and green
> spots there by the level of contamination of the fish.
>
> \[Slide\]
>
> I just want to say that really the advisory program at the state level
> is a joint activity between the environmental agencies and the state
> agencies. Typically, the monitoring is done by those individuals in
> the environment; the health side deals with human monitoring. I am
> going to show you a little data from some of our other grant-funded
> activities.
>
> \[Slide\]
>
> Just to give you a sense of what we do in Wisconsin, our average
> sample is about 800 fish per year. You can compare that to what the
> commercial fish monitoring program is. You can see we have a lot of
> data for a lot of different species and a lot of sites in the state,
> roughly 2600 samples in our database.
>
> \[Slide\]
>
> One of the things we found is that if you are a sport fish consumer,
> on average you will eat about a third or more total fish than the rest
> of the population. So, there is a reason why you like to fish, you
> like to eat the fish and, if you are successful, you may have more
> sport fish in your diet; if you are less successful you may still be
> eating a lot, supplementing with fish from the store.
>
> \[Slide\]
>
> For our one survey on mercury, we did a 12-state survey. It is a joint
> project between Maine and Wisconsin.
>
> \[Slide\]
>
> Very quickly, what we did was we asked how much fish they ate and here
> you can see what most surveys find, about 87 percent of people eat
> fish every year; 13 percent don\'t eat any fish. So, fish is pretty
> big. You can see 3000 women we surveyed had reported eating sport
> fish, but the vast majority of the fish eaten was fish fillets and
> tuna.
>
> \[Slide\]
>
> This jut shows the meal per year. Again, fish and tuna is the
> predominant number. The average of sport fish, of course, is four. if
> you say, well, 25 percent of the people are eating that, you multiply
> that by 4. If you are a sport fish eater, you are eating like 16 meals
> a year.
>
> \[Slide\]
>
> This just shows you there are differences by state. The red dots are
> pretty even between the states but you can see sport fishing
> consumption varies from a low of 10 percent to a little over 40
> percent in the group.
>
> \[Slide\]
>
> We asked them what do they know about mercury. They did real well on
> recognizing the hazards, that it harms a developing child. So, we
> thought, gee, they have pretty good information.
>
> \[Slide\]
>
> Where we fell down is that we have been too successful with our PCB
> long-term lipophilic chemical advisories saying remove the fat, get
> rid of the skin and you will reduce your exposure by 50 percent. So,
> the women said where do you find mercury? In the fat? Wrong. Where do
> you find it? You find it in the muscle. So, if they thought they were
> protecting themselves from mercury by removing the fat and skin, it is
> a misperception.
>
> \[Slide\]
>
> This is no news to most of you but, again, where do people get their
> information? You can see that government is right down at about eight
> percent. In fact, we haven\'t gotten much information out to
> physicians as they are a little lower than government. So, we have a
> long way to go. If you think what you are doing here is going to reach
> people, you are going to have to have a pretty aggressive program.
>
> \[Slide\]
>
> This just shows advisory awareness. We chose states that all had
> advisories, different types of advisories, but here you can see we
> really are not doing too well getting the women to even know their
> state had an advisory. Every state had an advisory. Fortunately,
> Wisconsin and Maine were leading the charge and had the money to put
> more information out. Arkansas also had a new initiative, and
> Minnesota. We were on the top end of the list but you can see states
> on the lower end have a pretty random chance that the women\--they may
> have been trying to please us by saying, \"oh, yes, I know we have an
> advisory.\"
>
> \[Slide\]
>
> We asked for women to volunteer to send in hair for analysis. Over 80
> percent said yes. When they got the packet of what they needed to send
> in, participation fell off but actually it was fairly representative.
> This just gives you the distribution of the hair mercury levels. The
> highest we had was 4.6.
>
> \[Slide\]
>
> When we looked at what they ate and what their hair mercury levels
> were, this is just how much they ate not looking at interactions here,
> the best predictor of their hair mercury level was total fish
> consumption. Interestingly, shellfish came up second. That should be
> tuna and other fish fillets; sport fish and then the state advisory
> sport fish that specifically were covered by the state as either \"do
> not eat\" or a severe limitation and there wasn\'t much of that fish
> being eaten but, again, you can see it was significantly correlated
> but not as strong as total fish consumption. So, you can see why we
> need to include all fish if we are giving advice and not just focus on
> the last two columns.
>
> \[Slide\]
>
> I am reluctant to do this because the strength of the NHANES is far
> superior to our methodology, but everybody wants to know how does our
> distribution compare to the national average. You can see our sample
> falls pretty much within their confidence limits within the various
> percentages.
>
> \[Slide\]
>
> Our recommendations are we really need to have more information on
> commercial fish monitoring, and it needs to be not designed from a
> regulatory standpoint but from an advisory standpoint. Can we place
> fish into various groups? We need to increase human biomonitoring. The
> RfD is in micrograms per kilogram per day, and how do we then convert
> that back to humans? Well, it started from a bench mark of 12 ppm in
> hair. So, we converted to human data into a micrograms per kilogram
> per day data and then we convert it back if people want to know levels
> in hair and blood. It is relatively inexpensive. It is a test that can
> be done and we need more actual, real-world measurement data for
> targeted populations.
>
> We need to do more health research. The adult population has been left
> out of this. We have focused all these large studies on kids. We do
> know that mercury is likely to have adult effects. We have adult data.
> Those of us who have split advisories, we use the adult data from the
> Iraqi study, if you remember back in the \'70\'s. That is about the
> only human data where you can do methylmercury dose response
> information on health effects, and that is pretty poor. So, we need to
> have better data to address the predominant population which is
> noon-pregnant, non-kids.
>
> \[Slide\]
>
> Lastly, what we need is state-specific integrated sport and commercial
> advice. While it is helpful to have FDA give advice and do
> measurement, I would say right now those states that are issuing
> mercury advisories are recognizing that we have to have integrated
> advice. The best place to issue that integrated advice is at the state
> level. So, we need to have greater integration and coordination
> between federal and state agencies. Again, the key thing is to get,
> whether it is negotiated or otherwise, uniform consumption advice. It
> has to be able to include site specific information that states have;
> fish that don\'t move around; fish that are different. But for fish
> that are in the commercial market, we need to have those so that we
> can add those into our comparative database.
>
> Another issue that needs to be looked at special circumstances. They
> may support a need for reduced margin of safety. In other words, the
> RfD has built into it an uncertainty factor of ten to accommodate
> adults as well as other potential health effects but, again, in
> special circumstances it may be an appropriate public health activity
> to accommodate a slightly lower, say a factor of five, in that process
> because of the local circumstances.
>
> Again, the goal is to eat the same amount of fish you always ate but
> select fish that are low in mercury. That is the advice and
> information in Wisconsin we started with in the \'70\'s. We are now
> back to focusing more on that and less on the risk assessment.
>
> \[Slide\]
>
> This is what we have distributed to all our physicians. We decided
> that rather than to going with a detailed advisory, our public
> relations people said go with a two-stage message. Give them something
> that they like. It is a poster. This is also on cups. We have sippy
> cups for moms. We have growth charts. We have refrigerator magnets.
> They are all saying here is where you call. Get them interested and
> they call and they can get the additional information. So, most states
> that had low budgets could only go with putting a little advice out to
> the angler in the fish advisory or in the fish regulations, and we
> found that mostly the guys who were fishing, they brought the fish
> home and said \"cook it,\" and the information never got transferred
> over. So, we are now targeting specific information to specific
> populations.
>
> \[Slide\]
>
> Again, \"come to Wisconsin and fish.\" These are not fish you are
> going to eat but these are fish you are going to get\--
>
> \[Laughter\]
>
> These you put on the wall.
>
> DR. MILLER: Are you about finished?
>
> DR. ANDERSON: I am done; that is it.
>
> **Questions of Clarification**
>
> DR. MILLER: Thank you. I was wondering if there were any more
> advertisements that you had!
>
> \[Laughter\]
>
> DR. NORDGREN: I would be interested in the variation you did have
> within species and different sites. We don\'t need a long expose but,
> obviously, there are variations at various sites within the same
> species in Wisconsin.
>
> DR. ANDERSON: In general, the range is about an order of magnitude,
> maybe 20. We no longer have many fish over 2. Now, the fish that are
> over 2 I would say are trophy fish and nobody is catching enough of
> those to eat enough of them. There are some, like the big muskies,
> that can get old and will have higher levels but most of the fish fall
> into the 0.2, 0.161 to 0.5 range. The 92 lakes that are over that
> average over 0.5, lakes and river stretches, and those are the ones
> that we have more restrictive advice on. So, the fish are pretty
> tightly bunched. I would say much more bunched than they are on the
> commercial side.
>
> DR. MILLER: Dr. Dwyer?
>
> DR. DWYER: Just two things. I really like the integration of the
> message on the sports fishing and the commercial together for the
> consumer. I thought that is really great. But just carrying it a
> little further, remembering my own time in Wisconsin and seeing people
> fishing, have you ever thought of incorporating alcohol use advice?
> Sorry!
>
> \[Laughter\]
>
> DR. ANDERSON: There is lots of public health advice. I am here,
> talking fish today. We have a big alcohol program. One of the most
> effective tools for alcohol regulation on the lake is wardens, and you
> may no longer drink and drive. Driving includes boats. So, if you
> happen to be stopped throwing a beer can over, that is a \$250 fine
> for the can. If you happen to be over the drunk driving limit, you
> lose your boat as well. So, that doesn\'t necessarily stop anything
> but it is a fairly powerful incentive to pay attention.
>
> DR. MILLER: Dr. Aposhian?
>
> DR. APOSHIAN: I was interested in your asking people, or women I
> guess, where did you learn about methylmercury in fish. Also, I could
> read your advisories very well. I want to compliment you on that. Why
> doesn\'t the State do anything about distributing the advisory to
> pregnant women, like making copies and putting them in obstetricians
> offices?
>
> DR. ANDERSON: Well, we have done that. Thank you for reminding me.
>
> DR. APOSHIAN: Because one of our problems is, and I think the
> committee agrees, trying to get this information to pregnant women and
> women of childbearing age.
>
> DR. ANDERSON: This is our little women\'s guide to eating fish in
> Wisconsin. I will hand it around. That has gone out. The second to the
> last little poster there was specifically distributed to all
> physicians\' offices. We try to encourage them to have a kind of a
> public health display where they have vaccination information and
> STDs, along with now a poster and the fish advisory.
>
> Our major emphasis right now is with the WIC program. Forty percent of
> the pregnancies in Wisconsin go through the USDA WIC program. That is
> a dietary program, and they have all of the materials as well, as I
> say, the refrigerator magnets, T-shirts, sippy cups and things like
> that. So, we are now in the process of another survey in the field to
> find out if we have raised the awareness, as is Maine with a little
> different program, just to see whether we can do that. We are trying
> to get more information out and get it distributed to the individuals
> that need to know.
>
> DR. APOSHIAN: May I ask one more question? I know Wisconsin has always
> been a very progressive State and certainly many of us admire both the
> health and educational benefits of living in Wisconsin. I am impressed
> that you have done so much with sport fish. Does your State do
> anything about analyzing commercial seafood? Does it analyze cans of
> tuna fish for example? Or, do you feel that is not within your
> jurisdiction?
>
> DR. ANDERSON: At this point in time we have not done it. All of the
> targeted commercial fish is for regulatory purposes. I think we have a
> few commercial fishermen still in the State. So, our department of
> agriculture will monitor the whitefish, the smoked chubs, but largely
> they are targeted, as you saw the FDA program, on fish that they may
> need to take out of the marketplace. So, at this point we are not
> doing commercial. If we have to, we will move into doing that but
> right now the dollars for the screening programs come from the
> licenses that anglers pay. They don\'t really want us to use that for
> other food safety issues.
>
> DR. APOSHIAN: If I understand it correctly then, you take the advice
> the FDA gives you on commercial fish brought into the State of
> Wisconsin.
>
> DR. ANDERSON: Yes, they are the regulators of commercial interstate
> transport.
>
> DR. APOSHIAN: So, it is the FDA and not the Department of Agriculture?
> It is the FDA that you depend on?
>
> DR. ANDERSON: I believe the State may implement, but the regulatory
> underpinning is our FDA.
>
> DR. APOSHIAN: Thank you.
>
> MS. HALLORAN: In preparing this very good brochure, did you look into
> PCB levels in fish and consider them?
>
> DR. ANDERSON: We also have PCB information but this was specifically
> focused on the mercury issue. You know, we have been beating on PCBs a
> lot longer. Most of the mercury fish are not high PCB fish. Mercury is
> an inland lake problem; PCBs are a Great Lake problem right now,
> except for a few areas with paper mills on the river. But we are
> trying to integrate the general advice. Some of the fish get in
> different places because of PCBs, some are there because of mercury.
> We take whichever is the most conservative advice even though we are
> not sure that the two have the same mode of action for the advice. So,
> we are trying to combine it.
>
> MS. HALLORAN: So, in terms of the fish you are recommending, those are
> all okay in terms of PCBs?
>
> DR. ANDERSON: These would all be consistent. If you used PCBs for the
> advisory, they would be consistent with it. Mercury happens to drive
> these. All the pan fish are very, very low in pesticides.
>
> DR. MILLER: Dr. Fischer?
>
> DR. FISCHER: Henry, could you tell us a little bit about the human
> monitoring effort that Wisconsin is doing or planning? I think you
> mentioned that, didn\'t you?
>
> DR. ANDERSON: Yes, we have several projects under way. The one I
> talked about is the 12-state survey. We also have an indicator project
> that is being implemented in WIC clinics along the Great Lakes to give
> dietary histories of fish consumption, hair samples and to a lesser
> degree also look at some PCBs so we can look at an age-specific group
> over time because if the levels are down we don\'t know if they are
> down because of following the advisory or because the levels are lower
> in the fish. So, we are trying to tease that out in this population.
>
> DR. FISCHER: These are done in the research mode as opposed to
> surveillance?
>
> DR. ANDERSON: These are done under a public health surveillance mode
> because it is part of our advisory information. It is being
> implemented under our statutory authority to monitor the general
> population, just as we do lead poisoning.
>
> DR. MILLER: Dr. Scherer?
>
> DR. SCHERER: I was just wondering. In your little brochure here you
> have swordfish and shark marked as \"do not eat.\" Then, over on the
> other side you have northern pike and walleye that are also high but
> no indication of concern. In looking at it, that seems inconsistent
> from a consumer point of view.
>
> DR. ANDERSON: Well, if you look at the first thing, the tear-off, all
> of those fish are in the one meal a month. Those are the game fish.
>
> DR. SCHERER: Okay, but the inconsistency is that they are also
> indicated as high, and are red in the chart, as are the two that say
> \"do not eat.\"
>
> DR. ANDERSON: The \"do not eat\" have Xs through them. You don\'t know
> how long it took and, you know, we worked with Maine and they use a
> thermometer, and our thermometer people were upset that we are using a
> thermometer to give how high it is.
>
> \[Laughter\]
>
> Then it had to be quantitatively similar. This one, even though it
> doesn\'t say it, must be 0.1 and that must be 0.6. There are so many
> ways you can do it. Again, what we did with this is take it out to
> women at the WIC clinic and ask if this makes sense to them. How would
> you interpret it? If they were comfortable with it, even if our
> science folks were a little miffed, we went with the people whom we
> wanted to reach.
>
> DR. MILLER: Other questions? Dr. Fuller?
>
> DR. FULLER: I just want to clarify and follow-up on a question because
> I don\'t recall from your talk, were the concentrations in the pike
> and walleye comparable to the concentrations that are X\'d out, the
> swordfish and the shark?
>
> DR. ANDERSON: No, they are lower.
>
> DR. FULLER: Thank you.
>
> DR. ANDERSON: On average. What we tried to do is look at what are
> people actually catching, and if there is a fish there that you
> shouldn\'t eat but nobody has caught one, you know, why issue advice
> to not eat it? That is sort of the way we went. So, the two that I
> showed at the end, they are \"do not eat\" not because of the mercury
> but because of the PCBs, but they are nice fish.
>
> DR. MILLER: Dr. Lee?
>
> DR. LEE: There seems to be somewhat of a tradition in Wisconsin to eat
> fish on Friday. I was just wondering have there been any attempts to
> getting this kind of information to point of consumption, particularly
> in restaurants, and do we have any wild guess as to how much exposure
> might come from restaurant fish in Wisconsin?
>
> DR. ANDERSON: No. Restaurant, we call that commercial fish. When we
> ask people, \"so what kind of fish did you eat?\" Most people don\'t
> know. They would be able to say it was a shellfish or shrimp or it was
> a fish, and it was a white fish or it might have been a darker color.
> They typically know salmon because salmon is pink. They know trout
> because they come with a head on them.
>
> \[Laughter\]
>
> But other than that, you have a standard fish in the restaurant, and
> you don\'t know what it is or where it came from so we just count
> those as fish meals. We tried that and nobody knew.
>
> DR. MILLER: Other questions? Dr. Dwyer?
>
> DR. DWYER: I was just wondering, I know we have a lutifisk expert over
> there but where does that fall?
>
> DR. ANDERSON: Where does what fall? Lutifisk? Lutifisk is low, high in
> sodium\--
>
> DR. MILLER: Low in taste.
>
> DR. ANDERSON: High pH.
>
> DR. MILLER: I was tempted to indicate that at least your people seem
> to know what a fish is!
>
> \[Laughter\]
>
> DR. ANDERSON: We don\'t have to deal with a dolphin fish versus a
> dolphin and those kinds of things.
>
> DR. MILLER: And tuna fish! All right, thank you. We are going to take
> a break and be back at 3:15.
>
> \[Brief recess\]
>
> DR. MILLER: A couple of things before we begin the afternoon session.
> I would appreciate it if anybody who has an active cell phone, if they
> would put it on silent, vibration or whatever. When it rings it tends
> to interrupt the discussion. The second thing is for Dr. Aposhian.
>
> DR. APOSHIAN: This morning Kate talked to you about the work of the
> NHANES. She brought today a group of papers that she thought the
> committee would like that, hopefully, have been distributed to you by
> the FDA staff, dealing with possible relationship of mercury levels
> and coronary heart disease and other cardiovascular problems that have
> appeared in peer reviewed journals and she thought might be of
> interest to you.
>
> DR. MILLER: And we can consider that as part of the EPA presentation.
> Our first speaker this afternoon is Mr. Michael Bender, from the
> Mercury Policy Project. He will talk about mercury contaminated
> seafood state advisories and other protective steps.
>
> **The Mercury Policy Project**
>
> MR. BENDER: Thank you, Mr. Chair. Good afternoon. Before beginning, I
> would like to, first of all, express my appreciation to Mr. Joseph
> Levitt for inviting me here today. I didn\'t realize that I was going
> to be presenting at this meeting until just very recently, and so I
> apologize for maybe not being so well versed in my homework
> assignment.
>
> DR. MILLER: Excuse me, could you adjust the microphone so you can talk
> right into it?
>
> MR. BENDER: Of course. Again, I apologize for not maybe being as
> prepared as I could. I did the best that I could under the
> circumstances.
>
> I am pleased to announce that we recently got a bill out of the U.S.
> Senate Environment and Public Works Committee that will ban the sale
> of mercury fever thermometers. There are ten states nationally that
> have done this and everyone else went on vacation. It is sort of like
> you are in a line and everybody else steps back and you realize you
> have been volunteered. So, I spent a number of days having to deal
> with that situation, but it was well worth it and we will keep our
> fingers crossed.
>
> In any event, also in addition to expressing my appreciation to Mr.
> Levitt, I have a packet of information for all the committee members.
> Included in that packet is joint FDA-state conference call minutes
> that I put together prior to the issuance of the consumer advisory in
> January of 2001. Also in that packet is a briefing statement that
> perhaps you might have seen from the National Fishery Service. It is
> very specific to this issue. Also, my presentation.
>
> The reason why I mentioned in particular the state-FDA minutes is
> because even though I commend the organizers on the depth of this
> meeting, and I was very pleased to see Dr. Henry Anderson here, and I
> recognize that some of the panelists are from the states, I would just
> submit that the states that are involved in this issue should also be
> heard and a number of them have emailed me, and I will do my best to
> convey some of that information from the states, but the minutes speak
> for themselves. They are also on our web site.
>
> \[Slide\]
>
> To start, the Mercury Policy Project is a nonprofit project. We are
> dedicated to reducing human exposure to mercury. We are also dedicated
> to reducing man-made mercury uses and emissions. For more information
> about our work, I encourage you to visit our web site at
> www.mercurypolicy.org.
>
> \[Slide\]
>
> I apologize for the resolution of this slide. It is on our web site.
> It is part of a report that we released in 2000, and it was based in
> large part on an FDA data set from 1992 to 1998. One of the first
> things that jumped out at us was that we were startled to discover
> that FDA hadn\'t tested canned tuna since 1995. The data set also
> revealed\--although you obviously can\'t see it here but it will be in
> your packets and you can see it later\--that in addition to the shark
> and swordfish some tuna, the large tuna exceeded FDA\'s 1 ppm action
> level.
>
> \[Slide\]
>
> While we were working on this issue we were noticing that the southern
> states were very active regarding the issue of king mackerel. Leading
> up to 2000, when they issued their joint advisories, they had issued
> individual state advisories. One thing I really would like to point
> out is that these advisories really pay attention in the testing and
> sampling to the size of the fish. It is a very important point. I was
> recently at a meeting in Mobile where the southern states and also
> EPA, and I believe, National Marine Fishery co-sponsored that meeting.
> When we do our fish data, it is very important to also be tracking
> size of fish so that we can make a correlation between the size of the
> fish and the amount of mercury to provide more accurate warnings.
>
> \[Slide\]
>
> So, in addition to the king mackerel, as I said in the beginning, a
> considerable number of states have issued commercial seafood
> advisories. To a large extent, these advisories are more stringent
> than FDA. I am sorry this graph isn\'t all that clear, but for
> children under six, eight or whatever it might be, for the large tuna
> Connecticut, Massachusetts, Minnesota, Washington State and Wisconsin
> all advise children to limit or not consume fresh tuna.
>
> A number of states, including New Jersey and Florida, have conducted
> their own mercury seafood testing. Minnesota is actively testing and
> enforcing FDA\'s 1 ppm standard and, in effect, is not allowing fish
> exceeding the FDA\'s action level to be sold in the state. Here you
> have a state that is literally interpreting the FDA guidance and
> whenever shark or swordfish are brought in the state, the state has a
> very aggressive program. They go out, they test the fish and pretty
> much those fish aren\'t being sold in the state because they
> predominantly exceed the 1 ppm.
>
> In addition, the Mobile register in Alabama recently tested and found
> that many seafood, including black grouper, red fish, cobia, amber
> jack and triple tail may have average mercury levels greater than 1
> ppm, although it is a very small data set.
>
> Due to the issues raised in the Gulf, and recently President Bush
> initiated an international mercury task force related to oil rigs and
> mercury contamination, the National Marine Fishery Service and EPA
> plan to carry out a sampling survey over the next year to analyze 2500
> popular marine and recreational seafood fin-fish for mercury.
>
> \[Slide\]
>
> One of the focuses in the southern states is fish specific to that
> region, but why are we so concerned about canned tuna and the general
> population? One of the reasons is because if you look, and although
> this is 1997 and the source is the annual report of the seafood
> industry, one of the largest consumptions, average consumption, is the
> home canned tuna sandwiches. In addition, in the June 2001 issue of
> consumer reports, there was a statement in there that canned tuna may
> be the only seafood that many children eat.
>
> \[Slide\]
>
> While there is a general lack of current data on mercury levels in
> canned tuna, we combined the data sets, the earlier one which you
> can\'t see, from the FDA and it took us two years to get that
> information by FOIA, and the Florida data from 1990 and 1991 and
> another data set in Florida in 2000, which is actually on the FDA\'s
> web site now.
>
> What these samples indicate is that there are quite a number of
> samples over 0.3 ppm and in some years upwards of 10 percent are over
> the FDA\'s action level of 0.5 ppm. Those are the references where
> some of this data came from. I understand that there was a \'92 year
> study which was a far greater sample size and indicated I think an
> average consumption of 0.17.
>
> What concerns us from a public advocacy standpoint is that people
> don\'t eat averages. I am not quite sure how the average rationale
> comes around, but I find that very problematic when it comes to
> sensitive populations.
>
> \[Slide\]
>
> When we look at what is going on now with the states, starting in 1997
> and some of these dates might not be exactly right but we did the best
> we could in less than one week in gathering information from the
> states. We had our own file plus some of this information that is now
> available on the EPA\'s web site under commercial advisories that the
> states are issuing. But if you look right down the line, what we are
> talking about compared with the FDA which is 12 oz of canned tuna per
> week, the states are coming in at a much more cautious level. It
> really varies, but, as you can tell, there is a real trend now where I
> guess because we don\'t have data\--I think that is one the biggest
> problems that we have, the biggest challenge that we have right now
> that there is so much uncertainty out there that the states are
> saying, based on what the NAS said, we need to take a more prudent
> approach.
>
> \[Slide\]
>
> I apologize for this slide. Actually, the one I wanted to highlight is
> the marlin. This is the recent data set from the British Food
> Standards agency which issued a consumer advisory for pregnant women,
> women who intend to become pregnant, infants and young children under
> 16 years of age. In addition to a recommendation that they avoid
> eating shark and swordfish, they also recommend that they avoid marlin
> as well.
>
> According to the British agency, and this is right off their web site
> and I am quoting, these seafood can harm the nervous system of an
> unborn child if the fish is eaten regularly by its mother. Infants and
> children may also be at greater risk for mercury poisoning because
> they eat more food relative to their body size in comparison with
> adults, according to the agency.
>
> \[Slide\]
>
> So, just to wrap up here, in terms of recommendations and these really
> build off our earlier recommendations in our \"One that Got Away\"
> report in the year 2000. First of all, FDA should develop effective
> surveillance, monitoring, testing, enforcement and consumer programs
> for methylmercury in commercial seafood in conjunction with consumer
> groups and the fishing industry and appropriate federal, state and
> local government agencies.
>
> Part or the rationale, as I mentioned in the beginning\--I only spend
> a certain amount of my time in trying to raise awareness about the
> need to reduce human and wildlife exposure to mercury. Much of my time
> is spent on efforts at the state and national level to reduce and
> eliminate man-made mercury emissions. Actually, I am pleased to say
> that the United Nations is doing their first ever global assessment of
> mercury. I will be representing the NGOs from the northern countries
> in Geneva in September, and will be working on recommendations to the
> governing counsel at their meeting, in Nairobi, in February.
>
> So, we are seeing our state and local governments and our federal and
> state governments spending millions of dollars each year tracking
> every other aspect of the mercury problem. Yet, how can the U.S.
> measure meaningful progress in reducing mercury pollution over time if
> we are leaving out testing one of the most critical indicators,
> methylmercury levels in seafood? I think as most of you are aware,
> that is the predominant fish source for most Americans.
>
> Secondly, some of the existing federal and state data for mercury is
> decades old and needs to be reevaluated for accuracy and applicability
> in the light of modern state-of-the-art testing methodologies,
> approaches and equipment.
>
> Also, critical fish size data, as I mentioned earlier, was not
> incorporated into those data sets, and it must be included as part of
> any comprehensive seafood testing and monitoring program for
> methylmercury.
>
> Finally, and this is just my first recommendation, while the National
> Marine Fishery and EPA are on the verge of testing popular marine and
> recreational fin-fish for methylmercury in the Gulf, their primary
> intent does not appear to be testing methylmercury levels in commonly
> available, commercially harvested seafood species. That is according
> to the March 27, 2002 National Marine Fishery\'s briefing statement
> which you will see in your packet.
>
> \[Slide\]
>
> In light of the most recent science, FDA should establish a regulatory
> level for methylmercury that is fully protective of the U.S.
> population and, in particular, women of childbearing age, pregnant
> women and nursing mothers and children.
>
> Also, FDA should expand its list of \"do not consume seafood known to
> have high mercury levels.\" The rationale? In the past FDA has all but
> ignored the findings of the 1991 studies by the National Academy of
> Sciences and the U.S. General Accounting Office, and one wonders aloud
> if this will happen again, history repeating itself.
>
> For over ten years FDA has been evaluating the hazards of mercury in
> seafood but has never issued the results. In 2002 GAO released the
> report on the inadequacy of FDA\'s hazard analysis critical point
> regulations. According to GAO, FDA does not provide adequate guidance
> to the fishing industry to identify and prevent seafood contaminated
> with methylmercury from exposing consumers. GAO recommended that FDA
> complete its hazard assessment for mercury in seafood soon.
>
> The third point, the July, 2000 NAS report endorsed EPA\'s reference
> dose, as has the European Union. As I have mentioned earlier, this
> issue is getting more global in scale every day and it is a welcome
> sign because the United States has to play a leadership role
> internationally if we are really going to address the problem. Because
> the fish that we are catching are from the open seas we need a global
> solution to this problem.
>
> As also discussed, 20 percent of the state health departments in the
> nation appear to be applying some variation of the NAS approach to
> advise sensitive populations about methylmercury in canned tuna.
>
> I don\'t mean to harp on canned tuna. There are a number of other fish
> that have levels very comparable to this in terms of the risk factor
> for sensitive populations. In addition, there are many commonly
> consumed seafood, including but not limited to marlin and tuna, and
> indicators from the Mobile register testing clearly exceed the FDA\'s
> current action level at least part of the time. Again, people don\'t
> eat ranges; people eat individual servings of fish.
>
> \[Slide\]
>
> Finally, our recommendation number three, FDA must recognize, as does
> the National Marine Fishery Service now, based upon a briefing
> statement I mentioned earlier, that, quote, subsistence commercial and
> marine recreational fishermen and their families represent a new
> subpopulation of the seafood consuming public that will likely require
> additional safeguards in order to protect them against excessive
> methylmercury ingestion via seafood.
>
> Again, according to the briefing statement of the National Marine
> Fisheries, there is a portion of the public that consumes seafood in
> excess of 15 lbs per year, and they also consume large quantities of
> seafood that are harvested for personal consumption. In particular,
> subsistence commercial and marine recreational fishermen and their
> families are at risk of exceeding the methylmercury consumption
> guidelines as they may be consuming seafood well in excess of 15 lbs
> per year, and they may be consuming non-commercially harvested seafood
> that is not subject to the FDA\'s 1 ppm methylmercury monitoring
> restrictions.
>
> I guess, in closing, we have been around the barn on this issue for
> several years. There are major inconsistencies between what the states
> are doing, what FDA is doing, what EPA is doing, what ATSDRs MRL are.
> Members of Congress have written letters. We have had meetings
> sponsored by the White House to address this issue.
>
> I think when it comes down to it, I guess the main point I would like
> to leave you with is that there are uncertainties and there will
> remain uncertainties. The reason the mercury study report to Congress
> got held up for three years, from 1994 to 1997, was over this issue.
> And, part of what it is about, it is about a number of different
> business groups weighing in. It is about government agencies weighing
> in and all the rest.
>
> But I guess I would go back to what I said in the beginning. Without
> adequate data, I think we need to do something similar to what they
> just did in Britain. They issued some kind of interim advisory. I
> asked FDA to do this a few years ago. I said let\'s set something in
> place. Well, we don\'t want to do that because, you know, all of these
> reasons. Let\'s set something in place, and part of the reason is
> because we need to protect those populations and we don\'t know
> whether we are or not.
>
> The other part of the reason is if we set something in place, I can
> assure you it would be a very strong impetus for all the parties
> involved to want to support having FDA and the other federal and state
> agencies going out and doing those tests and coming back with the data
> and monitoring the political pressure that it is going to take to
> convince Congress to allocate the funding for FDA to do an adequate
> job in this area. Let\'s come back in a couple of years. Let\'s issue
> some interim advisories that are more consistent with where the states
> are as a prudent public policy approach, and then let\'s get FDA the
> money to do its job, mandated by Congress.
>
> Everyone wants the answer. I just got a call from a reporter, and I
> don\'t know if the gentleman is here, from a Pittsburgh paper. They
> want to duplicate the Mobile register findings and it is beyond my
> comprehension that we have to have newspapers in this country
> performing the role that government should be performing. Thank you.
>
> **Questions of Clarification**
>
> DR. MILLER: Thank you. Comments? Questions?
>
> DR. NORDGREN: I couldn\'t read the ranges in the English study. Could
> you go back to that slide?
>
> MS. DEROEVER: Dr. Nordgren, could you please use the microphone?
>
> DR. NORDGREN: I couldn\'t read the ranges in that English study.
>
> MR. BENDER: I could pass those out if that would be helpful to the
> committee, Mr. Chair.
>
> DR. MILLER: Yes.
>
> MR. BENDER: Can I pass out the information that my slide wasn\'t able
> to convey?
>
> DR. MILLER: Of course.
>
> MR. BENDER: The pages aren\'t numbered, I apologize. It is after the
> mercury and tuna methylmercury advisories. It is titled, mercury
> levels in fish, shellfish, a recent survey. The mean is 1.091; the
> range is 0.409 to 2.204. Again, the sample size is very small, only
> four samples.
>
> DR. NORDGREN: One other question, milligrams per kilogram, how does
> that come out in parts per million?
>
> MR. BENDER: I would have to defer on that to someone else.
>
> DR. MILLER: Other comments? Annette?
>
> DR. DICKINSON: You indicated that you thought FDA should set an action
> level for fish that is consistent with the EPA RfD. What would that
> number be, in your opinion?
>
> MR. BENDER: Actually, first of all, I would just like to say that I
> don\'t think that FDA should go with an action level anymore. They
> need a regulatory limit or we are going to be in waffle-land for the
> next twenty years. With all due respect, I think that is a problem.
>
> When I had asked FDA a few years ago when we had the meeting with the
> states and Mr. Levitt on the phone, what I said was can we have two
> approaches, one for the general population and one for sensitive
> populations? That is what most of the states are doing right now
> because we don\'t want to discourage the consumption of fish. There
> are many species out there that are very low in mercury. Salmon is one
> of my favorites.
>
> What we want to do is get the message to the populations most at risk
> until we have enough of an adequate data set to be able to have a more
> accurate read of what is going on here. If we are seeing a data set
> like the one out of Florida where they were up at something like 0.24
> ppm on average rather than 0.17, I think that really requires some
> rethinking of FDA\'s approach.
>
> But, yes, I don\'t have a science background so all I can say is based
> on what the experts I speak with say, and most of the experts I speak
> with are state health department officials, and that is what I work
> with. Unofficially, that is my team on this issue. I used to run a
> state and local government association and I feel very comfortable
> working with the states. I feel very comfortable working with the
> experts in this area. As I said in the beginning, I am just
> disappointed that there aren\'t more state health department officials
> here.
>
> DR. DICKINSON: Mr. Chairman, the EPA speakers are still here, I think,
> in the audience. Could we ask them what they believe a translation
> would be of their RfD number into a general action level or regulatory
> level for FDA?
>
> DR. MILLER: Yes.
>
> DR. DICKINSON: We have had some people talking as though the 0.1 ug is
> how it would work out in fish, and I wonder if we could hear from EPA
> whether that is how they would interpret that.
>
> DR. SOUTHERLAND: I will refer you back to the table I had in my
> presentation. It depends on the number of fish meals that you are
> concerned about in terms of what that equates to in terms of
> concentration. I think that is what you are asking, what fish tissue
> concentration of methylmercury would we recommend for an action level
> or tolerance level. Joe?
>
> MR. LEVITT: We are going to be addressing that tomorrow morning.
>
> DR. SOUTHERLAND: But I would refer you back to that table. It depends
> on what you are looking at in terms of fish meals that you want to
> recommend because the RfD multiplied by the number of meals that you
> have gets to the concentration that you are concerned about. That is
> why on our table we showed you varying concentrations that go from 0.1
> to 0.9, depending on what number of meals you think are appropriate.
>
> DR. DICKINSON: Right, and that may be relevant to a consumer making
> their own judgment about what they are eating and how often they are
> eating it, but from the point of view of just wanting a number to
> apply as a regulatory matter\--I realize we are going to her from FDA
> on this tomorrow but I don\'t know if you are going to be here
> tomorrow. I just wondered what FDA\'s interpretation would be when
> someone says you should use the RfD as the basis for a number. What
> does EPA think that would mean?
>
> DR. MAHAFFEY: Kate Mahaffey, EPA. One of the complications in this is
> that there are a number of nutritional messages, including American
> Heart Association which says we recommend you eat two fish meals a
> week. So, if you take those kinds of recommendations and translate
> this to some estimate of the quantity of fish it should represent and
> take a look at the reference dose, you can sort of back your way into
> a level that we would believe would be safe.
>
> Now, part of the dichotomy here is that things like the American Heart
> Association recommendations are primarily aimed at another age group.
> So, how you translate this between avoiding cardiovascular risk and,
> yet, being protective of the developing fetus is one of these judgment
> issues that needs to be data driven, but it is one where we have a lot
> of factors to consider.
>
> DR. MILLER: We will discuss that at greater length tomorrow.
>
> DR. KUZMACK: Arnold Kuzmack, EPA. One brief additional comment is when
> you are talking about an action level you are talking about a level at
> which you would seize the fish, which is different from the level that
> you think is allowable in fish.
>
> DR. MILLER: All of these have been recommended by one person or
> another for action, so it is important to get these numbers to make
> sure we all understand exactly what these numbers represent. So, we
> will discuss this at greater length tomorrow.
>
> DR. KUZMACK: In order to come up with anything meaningful, you can
> make some additional policy judgments.
>
> DR. MILLER: A very straightforward policy, as many people have said
> is, well, let\'s eat salmon because it is low in mercury. But what
> happens if it turns out that salmon is high in some other contaminant,
> fat soluble contaminant?
>
> DR. KUZMACK: That is a good point and I do think that even though I
> work on mercury policy issues, I have been around long enough to
> recognize that you need to have an integrated message. How many
> messages can you send out and have the public receive at one time? I
> am not a professional risk communicator here, but it is obviously
> something that those folks need to be looking at.
>
> DR. MILLER: That is clearly going to be the challenge.
>
> DR. MCBRIDE: How is the Mercury Project funded?
>
> MR. BENDER: By foundations.
>
> DR. MCBRIDE: What type of foundations?
>
> MR. BENDER: I don\'t understand the question. What do you mean?
>
> DR. MILLER: I am not sure that that is relevant for discussion. I
> don\'t think it is important to this issue. Dr. Dwyer?
>
> DR. DWYER: Thank you for an interesting presentation. I was a little
> surprised\--I have been surprised all day about many things, but
> particularly about the number of samples that are around where people
> have looked at fish, and there are databases I just didn\'t know
> about, state databases, some of the EPA and other databases. Then, I
> also hear in several presentations people saying there aren\'t enough
> values; we need to get more; do more. Is the problem that it is not a
> random or representative sample? You mentioned in your presentation, I
> believe, that they were doing work down in the Gulf where they are
> picking samples but they were picking them for another purpose. Is
> there a way to have a subset of those fish that are being analyzed?
> Can we somehow get a sampling frame that would give us data that would
> be more meaningful for human consumption?
>
> PARTICIPANT: \[Not at microphone; inaudible\].
>
> MR. BENDER: Right, but that is recreationally caught, not commercially
> caught. Whenever we present ideas like this to federal government
> agencies part of the challenge we run into is whether or not those
> federal agencies are willing to accept that data. When we provide them
> with information, the question back is, is this peer reviewed
> information? So, I think just by its very nature of where we want to
> end up with the federal agencies, it really has to have their blessing
> in terms of how we go about doing it, and they have experts that
> understand sampling size, methodologies and testing. I mean, they have
> a whole section in their agency that is involved with looking at that.
>
> So, yes, I guess the simple answer to your question is, yes, we could
> compile that information. The question to FDA is would you use that
> information? Would you be willing to use that information? I am sure
> the response back is, well, it depends.
>
> DR. DWYER: Well, I think it does depend. At least, we need to know
> where the samples came from; we need to know the analytical method and
> so forth. You know, just throwing numbers at problems doesn\'t get
> very far. But the question is are those data collected in a good way.
> If they are available and a complete description can be made of how
> they were collected, it may be not necessary to do a whole bunch of
> new data.
>
> MR. BENDER: If I could, I will just reiterate what I said earlier. It
> took us two years to get that 1992 data, which is the second slide in
> your packet. The little story on that is we FOI\'d FDA. We got a very
> concise range of numbers. Then a reporter FOI\'d FDA and they got that
> huge data set of hundreds and hundreds of data entry points.
>
> So, I think one of the challenges in terms of something like that is
> that the FDA, in my experience, has not been forthcoming in the past
> in terms of wanting to share that information. We always have to, you
> know, go through the Freedom of Information Act to get it.
> Unfortunately, I don\'t really understand what the relationship is
> between the states and the FDA. I understand that some of the states
> do the testing for FDA, but I don\'t have anything that I can site for
> you.
>
> DR. MILLER: Other comments or questions?
>
> DR. DWYER: I have one other question. Is it true that king mackerel is
> king fish?
>
> PARTICIPANT: Yes.
>
> DR. DWYER: I am making a little vocabulary here!
>
> DR. MILLER: Thank you very much.
>
> MR. BENDER: Thank you very much.
>
> MS. DEROEVER: Mr. Chairman, I have a brief statement to make. We do
> have Dr. Connor on the phone. I think there was a lot of noise and
> people may not have heard that. Mr. Collette is going to making the
> initial presentation\--
>
> DR. CONNOR: Hi.
>
> MS. DEROEVER \--and Dr. Connor is going to be helping out with some
> questions.
>
> DR. MILLER: I think we better tell Dr. Connor he is coming through
> loud and clear!
>
> \[Laughter\]
>
> MS. DEROEVER: It has been reported to FDA that both Mr Collette and
> Dr. Connor do have financial associations with the seafood industry,
> for the record.
>
> **National Fisheries Institute**
>
> MR. COLLETTE: Good afternoon, Mr. Chairman and committee. I am Bob
> Collette, vice president of science and technology for the National
> Fisheries Institute. As has been said, Dr. Connor, who is
> collaborating on the presentation, is joining us via a telephone
> conference call.
>
> \[Slide\]
>
> For the committee\'s information, the presentation is a collaborative
> effort between NFI and Dr. Connor, who is a medical doctor and
> researcher currently affiliated with Oregon Health Sciences
> University. Dr. Connor has been teaching and conducting research in
> the area of clinical nutrition and lipid metabolism for over 40 years,
> and is particularly well qualified to review the current scientific
> body of information on the positive health benefits associated with
> fish consumption.
>
> For your further information, the National Fisheries Institute is a
> nonprofit trade association representing the commercial fish and
> seafood industry. NFI is located in Arlington, Virginia and has been
> in existence for over 50 years.
>
> \[Slide\]
>
> The purpose of this presentation is to discuss the strong positive
> role fish and seafood has on the nutrition and health status of U.S.
> consumers, and to ask the committee and ultimately FDA to carefully
> consider the possible negative public health impacts should these
> benefits be diminished as a result of reduced fish consumption.
>
> \[Slide\]
>
> NFI believes FDA acted responsibly in developing its fish consumption
> advisory. It was a deliberative process including scientific
> information from the scientific community, consumer groups, health
> organizations and the seafood industry.
>
> NFI recognizes that FDA\'s national fish consumption advisory is an
> important tool for ensuring the protection of sensitive consumers. In
> recognition of the importance of the advisory, NFI has created a
> direct link to it in the consumer section of our NFI web site. The
> consumer section is called aboutseafood.com.
>
> NFI also believes that fish is an important part of a healthy diet for
> many consumers, therefore, government agencies must have sound
> scientific justification before they tell people to further limit the
> consumption of fish. Decisions about protecting consumers, therefore,
> must be based on a thorough assessment of scientific data and the
> public health impacts, both positive and negative.
>
> In order to make the comparison, we thought it useful to review what
> specific benefits could be lost or diminished and what nutritional
> consequences might occur if an expanded advisory were issued and
> resulted in a decrease of fish.
>
> \[Slide\]
>
> Fish provides comparable amounts of protein but for most species
> contributes less fat, calories and particularly saturated fat when
> compared to other animal protein foods. Fish are a good source of most
> B vitamins and vitamin B12, which is not obtainable in vegetable
> products, and only animal proteins, found in fish in large quantities.
> Fish products, particularly tuna products, are also excellent sources
> of selenium, an important dietary antioxidant.
>
> \[Slide\]
>
> Because fin-fish products contain substantial amounts of protein and
> relatively low concentrations of fat, saturated fat and cholesterol,
> health professionals, as part of a heart healthy diet, have promoted
> consumption of these foods. Indeed, both the American Dietetic
> Association and American Heart Association recommend consuming at
> least two fish meals per week, as we have heard already a couple of
> times.
>
> When AHA released its dietary guidelines in the fall of 2000, they
> said because of the beneficial effects of omega-3 fatty acids on the
> risk of coronary-artery disease, as well as other diseases such as
> inflammatory and autoimmune diseases, the current intake which is
> generally low should be increased. At least two servings of fish per
> week are recommended to confer cardioprotective effects.
>
> The AHA statement provides a good segue to Dr. Connor\'s review of the
> scientific literature. I want to quickly point out that fish and
> shellfish are far better sources of omega-3 fatty acids, particularly
> EPA and DHA, than other animal sources.
>
> \[Slide\]
>
> The following portion of the presentation really is what constitutes
> Dr. Connor\'s scientific review and, had he physically been here, this
> is what he would be covering.
>
> \[Slide\]
>
> Interest in the n-3 fatty acids began some thirty years ago in
> Greenland Eskimos when it was discovered that coronary disease,
> diabetes and cancer had a remarkable low incidence in this population.
> Eskimos at that time lives on seafood, especially fish and seal, which
> contain large quantities of n-3 fatty acids, namely eicosapentanoic
> acid, EPA, and docosahexaenoic acid, DHA. EPA and DHA are found in
> fish, shellfish and sea mammals, and are very low in quantity or
> absent in land animals and plants.
>
> Since then, there has been remarkable concurrence and congruence about
> the importance of n-3 fatty acids, as indicted by several thousands of
> papers that have appeared in the literature.
>
> \[Slide\]
>
> There is little doubt that n-3 fatty acids have a decisive importance
> in human nutrition. These fatty acids, particularly EPA and DHA, are
> present in human diets largely as fish. N-3 fatty acids are essential
> fatty acids necessary from conception through pregnancy, infancy and
> undoubtedly throughout life. A major reason for considering the need
> to maintain adequate intake of fish in the diet is the important role
> of the n-3 fatty acid family in the prevention and modulation of
> certain diseases.
>
> \[Slide\]
>
> A partial listing can be seen in the table on the this slide. I
> apologize, it came out a little crooked.
>
> The rest of the review provided by Dr. Connor we focus on the first
> two disorders because they are two of the most studied areas and form
> the most compelling body of evidence that fish consumption, with its
> requisite n-3 intake, benefits consumers from birth throughout
> adulthood.
>
> \[Slide\]
>
> There are two critical periods in life for the acquisition of
> essential n-3 fatty acids, during fetal development and after birth
> until the biochemical development of the brain and retina is
> completed. DHA is an important constituent of membrane phospholipids
> of these neural structures.
>
> A typical example is phosphatidyl ethanolamine which is especially
> rich in the brain and retina. The specific findings of n-3 fatty acid
> deficiency are manifested in both the blood and the tissue chemistry.
> One note is a strikingly low concentration of DHA which may fall to as
> much as one-fifth or the normal amount in blood and tissues. In
> addition, the body attempts to replace the deficiency with another
> high polyunsaturated fatty acid of the n-6 series that does not
> function as well Alzheimer\'s disease DHA. That would be in a diet
> deficient in DHA that we are referring to.
>
> In the rhesus monkey an n-3 deficient diet, administered to a pregnant
> animal and then continued after birth, induces profound functional
> changes such as reduced vision, abnormalities of the
> electroretinogram, impaired visual evoked potential, more stereotypic
> behavior and perhaps disturbances of cognition.
>
> Some of these findings have also occurred in human infants fed diets
> deficient in n-3 fatty acids, particularly those based on corn oil and
> coconut oil.
>
> Although the experimental protocols in human studies have been less
> rigorous because of ethical considerations, in most studies of
> premature infants there have been visual impairment and abnormal
> electroretinograms unless the formulas contain DHA. A recent study of
> full-term infants comparing a standard infant formula with human milk
> and formulas enriched with DHA provided unequivocal evidence of
> considerable differences in visual evoked potential.
>
> In all of the human infant studies the biochemical evidence in plasma,
> red blood cells and occasionally in tissues from autopsied infants
> have substantiated the n-3 fatty acid deficiency state.
>
> \[Slide\]
>
> Infants fed formula without DHA have lower concentrations of DHA in
> the brain than infants that were fed human milk which contained DHA.
> They also have lower intelligence.
>
> \[Slide\]
>
> During pregnancy the maternal stores of n-3 fatty acids and the
> dietary intakes of n-3 fatty acids by the pregnant women are of
> importance both in ensuring that the fetus has adequate amounts of n-3
> fatty acids at the time of birth. All polyunsaturated fatty acids,
> including DHA, are transferred from the mother across the placenta
> into the fetal blood. Several studies in monkeys have indicated that
> when the maternal diet is deficient in n-3 fatty acids, the infant at
> birth is, likewise, deficient in n-3 fatty acids.
>
> In humans, a recent study demonstrated that the administration of fish
> oil or sardines to pregnant women led to high levels of DHA in both
> maternal plasma and red blood cells, and in the fetal cord blood
> plasma and red blood cells at time of birth.
>
> Several associational studies have indicated the importance of n-3
> fatty acids from fish to the pregnant state itself and the delivery of
> a healthy infant. Premature infants clearly have a higher mortality
> than full-term infants.
>
> \[Slide\]
>
> In the Scandinavian countries, women who eat a higher consumption of
> EPA and DHA from fish and seafood have a lower incidence of preterm
> labor, and deliver larger babies with an increased survival capacity.
>
> In another study from Scandinavia, seafood consumption during
> pregnancy was associated with a reduction in postpartum depressive
> symptoms in women.
>
> There are also several studies showing that n-3 fatty acids from fish
> may ameliorate the symptoms of attention deficit disorder, though
> long-term clinical trials have yet to be conducted.
>
> \[Slide\]
>
> Turning to cardiovascular effects, the strongest scientific evidence
> relates to the inverse relationship between the amount of n-3 fatty
> acids in the diet and in the blood and tissues and the occurrence of
> coronary heart disease and its many complications. The effects of n-3
> fatty acids on coronary heart disease are based upon hundreds of
> experiments in animals, humans, tissue culture studies and even
> clinical trials.
>
> While saturated fat and cholesterol in a diet are pathogenic for
> coronary heart disease, the n-3 fatty acids from fish are actually
> protective and, by a variety of mechanisms, prevent coronary deaths
> and, in particular, cardiac arrest or sudden death.
>
> \[Slide\]
>
> In this table you can see a number of actions by which n-3 acts to
> prevent coronary disease.
>
> \[Slide\]
>
> Some 100,000 Americans each year die suddenly from cardiac
> arrhythmias. Many are previously well individuals. This is a
> tremendous public health problem. There is strong evidence that n-3
> fatty acids from fish can prevent sudden death. EPA and DHA have a
> strong anti-arrhythmic action on the heart. In experimental animals
> and tissue culture systems EPA and DHA prevent the development of
> ventricular tachycardia and ventricular fibrillation.
>
> Even total mortality has been improved in several studies in which n-3
> fatty acids from fish intake was high. Those men in the Seattle study
> who consumed salmon at least once a week had a 70 percent less
> likelihood of sudden death. They had high levels of EPA and DHA in
> their blood.
>
> In another study by Burr and Wales, overall mortality was decreased by
> 29 percent in men with overt cardiovascular disease who were given n-3
> fatty acids from either fish or fish oil. This is probably by the
> reduction in cardiac arrest.
>
> \[Slide\]
>
> A most recent study about fish consumption and the risk of sudden
> cardiac death was from the Physicians Health Study in the U.S., in
> which 20,551 male physicians participated. The consumption of at least
> one fish meal per week was associated with a 51 percent lower risk of
> sudden death compared with minimal fish consumption. The total
> mortality in this example was also reduced by those who ate fish.
>
> \[Slide\]
>
> The Nurses Health Study examined the association between fish and n-3
> fatty acid intake and the risk of coronary heart disease in a sampling
> of 84,688 women. Both fish intake and n-3 fatty acid intake were
> associated with a lower risk of coronary heart disease.
>
> It is of interest that both men and women in these two massive studies
> derived great benefit from fish consumption. Besides benefits for
> coronary patients, the Nurses Health Study also showed that fish
> consumption was positively associated with fewer thrombotic strokes.
> Women who ate fish two or more times per week had greater than 50
> percent reduction in strokes.
>
> These studies provide support for dietary advice such as that of the
> American Heart Association which recommends that Americans consume two
> fish meals a week to maintain a healthy lifestyle. The pronounce
> effect of fish oil on hyperlipidemia is especially well documented and
> is supported by precise dietary studies in a diet rich in salmon oil.
> Fish oil especially lowers plasma cholesterol and triglyceride
> concentrations.
>
> DR. MILLER: Mr. Collette, five more minutes.
>
> MR. COLLETTE: Thank you. Pronounced postprandial lipemia occurs after
> the absorption of fatty meals with a high fat content. Pretreatment
> with fish oil greatly lessens the postprandial lipemia and this effect
> should be considered both anti-atherogenic and antithrombotic.
>
> \[Slide\]
>
> This would be the summarization of Dr. Connor\'s review. In summary,
> the evidence is now very strong that the n-3 fatty acids are essential
> for human development in the fetus and infant, and are likely to have
> a role throughout life. The antiarrhythmic effect of n-3 fatty acids
> is a discovery that has great relevance to the prevention of sudden
> death from ventricular fibrillation.
>
> Fish consumption in this country and in the world has a profound
> effect for improving health and preventing disease, as indicated by
> public health agencies such as the American Heart Association.
>
> \[Slide\]
>
> That basically is the presentation of Dr. Connor. I would like to
> conclude with some NFI comments. First, fish and seafood provide a
> multitude of nutritional health benefits, especially as a unique
> source of essential n-3 fatty acids.
>
> Public health organizations, such as AHA and ADA, have concluded that
> n-3 intake is low in general and fish consumption should be two meals
> a week or more to derive the benefits associated with n-3\'s.
>
> \[Slide\]
>
> Health benefits from fish could be lost or diminished with an
> expansion of the national fish consumption advisory. If the
> restrictions are too extensive and/or if the consumer message becomes
> too alarming or too confusing to fish consumers, although we cannot be
> sure how all consumers would respond to yet another FDA advisory,
> there are signs that even the experts are confused. A doctor on the
> \"Today\" program in July of 2000 regarding the health effects of
> mercury on pregnant women concluded, \"I say eat quiche.\" But,
> seriously, the prudent step right now is probably to limit fish
> consumption until we can be assured by both the EPA and FDA that this
> wonderful and tasty source of protein and other nutrients is safe.
>
> What was the take-away message? \"Eat quiche instead of fish?\" Limit
> fish? What fish? All fish? An EPA fact sheet on mercury and fish
> advisories notes that the RfD is not a bright line between safety and
> toxicity. NHANES data suggests that 92 percent of sensitive women are
> below the RfD.
>
> According to Clewell\'s presentation yesterday and his analysis, there
> are less than one-half of one percent of those in the NHANES who are
> above ATSDR\'s MRL and none are at the PMDA level.
>
> Consideration must be given to the negative impacts of pursuing zero
> risk in terms of RfD through increasingly complicated and extensive
> advisories. At what point do fish just become too scary to eat?
> Expanded warnings could come at the cost of reduced fish consumption
> for many consumers, including some pregnant women who will lose the
> beneficial effects of n-3 fatty acids.
>
> If you put a warning label on canned tuna, how many women will
> purchase it? Not everyone can afford more expensive fish and some do
> not like to prepare it. What will be their substitute for their n-3
> sources? Will it be canned salmon or canned sardines? Not for many
> folks because most U.S. consumers like bland fish.
>
> There are also some suggestions of species that I have seen throughout
> the presentation. I would just like to also mention that we need to be
> cautious when we recommend substitutions. Many of the fish listed,
> like bluefish and herring, also fall into the category of fish\--it is
> like salmon, you have people who eat those fish and then you have
> other people who would never eat those fish because they are not
> bland. Then, some of the species also that were mentioned are under
> strict fisheries management controls.
>
> DR. MILLER: Can you come to a summary please?
>
> MR. COLLETTE: Okay. Essentially then, the reality is that in reviewing
> the advisory the committee, and ultimately FDA, must carefully weigh
> all of the information available and consider all the impacts on the
> consumer health, both positive and negative. Thank you.
>
> **Questions of Clarification**
>
> DR. MILLER: Questions or comments? Dr. Hotchkiss?
>
> DR. HOTCHKISS: Maybe you can help me understand this. I don\'t think
> there is a lot of debate about the positive health benefits of
> seafood, but it seems to me most of those benefits accrue to a
> different population than the one that is of greatest concern for
> methylmercury, in other words, more adult populations. Maybe you
> answered this, but would your organization then support a two-tiered
> approach in which those populations that would likely benefit from
> fish consumption are encouraged to eat more fish, but that population
> which may be at greater risk, during pregnancy particularly and young
> children, would be discouraged from eating fish? Do you see those as
> mutually exclusive?
>
> MR. COLLETTE: I am not sure and maybe Dr. Connor may want to actually
> comment on the protective effects of n-3 and how that relates to your
> question. There is a growing body of science though that does relate
> to the importance of n-3 in fetal development. It is an area that
> started after a lot of the cardiovascular research but it is an
> emerging area of scientific exploration, and it does seem that there
> are some pretty compelling studies that are coming out showing that
> there is a benefit to the pregnant mom and her developing fetus.
>
> With respect to a level for children, it seems to me that the NHANES
> data, if I recall, showed that they were essentially I think all under
> the RfD. I guess the bottom line answer really is that I think the
> consumer message has to be pretty straightforward, and I think having
> two messages out there would be rather confusing. I think it would
> need some real serious study in terms of what kind of impact it would
> have.
>
> DR. HOTCHKISS: As I recall, there are something like 16 states that
> have a two-tiered message out there. It seems to me there is some
> experience with this kind of message. I noticed that you didn\'t talk
> much in your review of positive health benefits about that to the
> fetus and so forth. So, I am a little confused about your answer. You
> are saying that we don\'t know enough about the positive health
> benefits; that we should recommend low consumption for this population
> and high consumption for another population.
>
> MR. COLLETTE: No, I guess the point of my answer was that it seems to
> me that both populations can benefit from the n-3. I don\'t think we
> would want to discount the utility to the other population you are
> speaking of.
>
> I guess the other point too is that I think that the FDA advisory is
> really designed for that sensitive population you are referring to.
> So, the one advice that does exist is designed to address that
> particular group the greatest.
>
> DR. MILLER: Dr. Aposhian?
>
> DR. APOSHIAN: This is a difficult talk to respond to because the first
> part has some very good science and the second is obviously
> commercially related. Dr. Connor, can you hear us?
>
> DR. CONNOR: I can hear you if you speak loudly.
>
> DR. APOSHIAN: All right, I will try to speak loudly. Let me first of
> all say I admire your work; I am very much aware of it and I
> congratulate you on your accomplishments.
>
> I was just wondering though about the Framingham Study, the nurse
> study, the men\'s study. Fish intake says nothing about the mercury
> content of the fish that people were eating in that study. I am very
> curious, and we appreciate your comments about the study in Finland
> which more or less suggests, and members of our committee have these
> papers which were handed out just a little while ago, that mercury
> even in subtoxic amounts is a risk factor for coronary and fatal
> cardiovascular disease, and that is based on the Finnish studies. Do
> you have any comments about the Finnish studies?
>
> DR. CONNOR: I don\'t know the Finnish study. I have before me a study
> by Kales and Goldman which came from Harvard School of Public Health
> and the Children\'s Hospital in Boston. Obviously, the problem of
> mercury and contamination of the oceans is a real one. I think we have
> to weigh the benefits versus the benefits of excluding fish from the
> diet or advising people not to eat fish against the very positive
> health benefits which I think pertain throughout life.
>
> There is one consideration for infants I think. The infant formulas
> now have DHA and arachidonic acid added to them. These are available
> in the U.S. and probably will be used by more and more mothers. So,
> this takes away the need for infants to eat fish that might be
> contaminated by mercury. I think the danger of mercury to the central
> nervous system is obviously more during the time of development than
> later in life.
>
> I don\'t, myself, see hazards from mercury in the limits that we are
> ingesting them for adults that are susceptible for coronary heart
> disease.
>
> The other question pertains to the habits of life. Certainly, if
> people have never eaten fish because they thought it was toxic for
> them and then they are encouraged by their doctors to eat fish at age
> 50, they might have difficulty. So, the habitual diet is of some
> importance too. I don\'t know if that answers your question.
>
> DR. APOSHIAN: Yes and no. I will be certain copies from my office are
> sent to you. You might be interested in these papers from Finland
> because during the NRC meetings the papers were debated and finally
> some comments were made about that as far as the importance of the
> amount of mercury in the fish and the incidence of cardiovascular
> disease in the Finnish men population, not the younger people. I
> appreciate your comments very much.
>
> If I can now address a couple of comments to Mr. Collette please, I
> think one of the major problems is the ignorance of the American
> people. And, I think that if an educational program was put forth by
> the FDA or by the fish industry or a combination of people that one
> could call impartial, I think it would be a great help to educate
> people, especially pregnant women and women of childbearing age, as to
> the benefits of fish and the problems with certain kind of fish. I
> don\'t think anyone on this committee would want to see pregnant women
> not eat fish. I would be surprised if anyone wanted that.
>
> But I think the problem is, and perhaps the fishing industry does not
> realize this, the problem is that pregnant women and women of
> childbearing age have to be informed and educated. So far, neither the
> FDA is doing that nor is the fish industry doing that. No one wants to
> put the fish industry out of business. Everyone would like to see
> everyone improve their economic status, but I don\'t think it is
> unreasonable, if the fishing industry does not want to pay for it, to
> ask Congress for a pork pie allocation to set up an educational
> program for the American woman that is going to be pregnant.
>
> I spend a month a year near a fishing population, the oldest fishing
> village in the United States, and no one questions the desire or the
> wish of the working fishermen. They have no desire to hurt people.
> There should be some kind of an educational program. In the many years
> that I have been around, I have never seen anyone in the fishing
> industry try to support such a program, impartial program. There is no
> question about Dr. Connor\'s work. It is first-class work. It is about
> the fatty acids. But it does not take into consideration for us right
> now the amount of mercury in fish. No one says you should not eat
> fish; the question is which fish should we eat or how much of certain
> fish we should eat. I wish the industry would try to address that
> program in the future.
>
> MR. COLLETTE: Thank you for that comment. It is interesting, we have
> trouble raising money in our industry just to market our product. So,
> the resources to do that are certainly an issue.
>
> I would like to point out again though that we do have an educational
> area on our web site. We do have information about mercury. There is a
> direct link to the FDA advisory. So, with our web site we have tried
> to provide some information.
>
> I would also like to point out that in the packet that you received
> yesterday there is a group called International Food Information
> Council, and they have done a balanced piece on fish that is in that
> packet. In it they do talk about the benefits of fish and seafood, but
> they actually have the exact wording of the advisory, or very close to
> it, and I do believe they put this out as a peer reviewed piece of
> information before they published.
>
> So, that is something that is out there. Our organization also has
> tried to help get this out to people. So, there are some materials out
> there and there are some efforts on education. But resources certainly
> are an issue.
>
> DR. MILLER: Dr. Shannon?
>
> DR. SHANNON: My questions were answered.
>
> DR. MONTVILLE: I was just wondering if you have done any back of the
> envelope calculations on what percentage of the bad fish is actually
> eaten by women of childbearing age, and if a strong message went out
> on good fish/bad fish, that might not be more than offset by the
> encouragement to eat the good fish.
>
> I also think this idea that people might stop eating fish because of
> this, if you look at the example of the alcohol advisories for
> pregnant women, it is certainly not true. Once they are done being
> pregnant they drink again. And, the alcohol industry is doing fine
> despite that warning.
>
> MR. COLLETTE: The basic answer to your question is, no, we have done
> that kind of a calculation. I think it does get down to the part of
> the FDA message that maybe needs to be brought out more strongly, and
> that is that consumers should be eating a variety of fish. If you look
> at the top 20 most commonly consumed commercial fish species in the
> United States, and if you take sort of a weighted average of all those
> and then basically you take the data in the FDA data set and make a
> calculation, the weighted average of methylmercury there is actually
> quite low.
>
> I guess what I am trying to say is that for most of the top commercial
> species that are sold in the United States, the ones that most people
> eat, upwards of 85 percent fall into that low category. So, that is
> where we need to get people to go, in my opinion, to point out the
> major commercial species and to say eat a variety of fish. It appears
> further down in the advisory. Maybe it needs to be brought up and be
> pronounced more but I think that may be one thing to consider.
>
> DR. MILLER: Dr. Nordgren?
>
> DR. NORDGREN: I am addressing this to both of you, and I am
> concerned\--
>
> DR. MILLER: Could you speak directly into the mike?
>
> DR. NORDGREN: Yes. The essential fatty acids, and the question I have
> is are these essential fatty acids necessary as a dose, or is it like
> a vitamin? You need some and that is enough, and you don\'t need tons
> of it? Have these studies addressed this issue?
>
> MR. COLLETTE: I hope Dr. Connor heard the question.
>
> DR. CONNOR: I didn\'t quite hear the question. Bob, perhaps you could
> repeat it for me.
>
> MR. COLLETTE: Well, I think the question essentially was, in the
> various studies that were reviewed in your paper, did the studies
> examine sort of a dose response? Is that how you put it?
>
> DR. NORDGREN: Yes, are these essential fatty acids necessary as a
> minimal amount or is more better? Is there any evidence one way of
> another along those lines? Any good scientific evidence that the more
> you get into your system the smarter you are going to be?
>
> MR. COLLETTE: Did you hear that?
>
> DR. CONNOR: Yes, I heard the question. Those studies have been done in
> human infants by various investigators and I think the amounts that
> infant formula manufacturers are now putting into the formulas, Mead
> Johnson and Abbott Ross Laboratories, are probably in the middle range
> to have both safety and enough of these fatty acids. For example,
> two-tenths to three-tenths to four-tenths of a percent of total fatty
> acid as DHA is being added by the infant formula manufacturers. We do
> not know if more than that would be better. We do know that throughout
> the world human breast milk differs greatly in the DHA content. In the
> developing world and in China DHA may be as high as one percent. In
> the U.S. it is about two-tenths of a percent or lower, probably
> because of the influence of the diet of the lactating woman. So, I
> hope that that answers your question. I think we have tried to stay in
> the middle ground in the recommendations. The World Health Association
> has made similar recommendations about the content that needs to be
> present in infant formulas to simulate as much possible human milk.
>
> DR. DWYER: Isn\'t it true that the soon to be released micronutrient
> report of the National Academy of Sciences will cover fat and fatty
> acids? I believe you, Dr. Miller and also Dr. Russell, maybe others,
> were on those panels.
>
> DR. CONNOR: I could answer that to some extent. I think a number of
> people have communicated with the Food and Nutrition Board, National
> Academy Sciences report. As far as I know the one on essential fatty
> acids is still being compiled. So, that isn\'t out yet but I would
> agree with you that that would be of great help in establishing
> certain standards of adequacy. But I sort of summarized for you the
> literature as I have been able to understand it.
>
> DR. MILLER: Other comments or questions? If not, thank you very much.
>
> MR. COLLETTE: I would like to thank the committee, especially so late
> in the day, for your attention.
>
> DR. MILLER: Knowing how anxious we all are to get away from the table,
> I am going to beg your indulgence for a couple more minutes for some
> discussion about what is going to happen tomorrow.
>
> In the first place, we have a limitation on time because a number of
> you have to make planes out of Reagan and out of BWI and get there
> early enough to get through security, and so on. The secretariat has
> arranged for shuttles to take you to the airport. In order for this to
> really work, we have to try to be done by about 3:30 or it is going to
> make things very tight.
>
> What we are going to do tomorrow in order to facilitate this is after
> the remarks made by members of CFSAN, we will go into a session to try
> to look at three major areas that should be able to support our\--what
> is being distributed, by the way, are FDA statements for tomorrow.
>
> Anyway, there are three areas, toxicology, consumption and risk
> communication and I have asked three of our colleagues to lead those
> discussions, Dr. Fischer for toxicology; Dr. Dwyer for the consumption
> data; and Dr. Scherer for the risk communication. Hopefully, we will
> have 20 or 25 minutes for that. Following that, I will then operate in
> the following way: We have five questions that we have to respond to
> and, rather than trying to gain a consensus directly of the committee,
> I will poll each member of the committee separately and ask for your
> remarks on the question that is being asked of us, and do that for all
> five. Hopefully, we can get all of your remarks on this and try to
> develop some kind of a sense of what the committee\'s feelings are and
> provide a record of what each individual committee member\'s responses
> to the questions. These will be transcribed and can be made available
> to the committee. The entire transcript of the entire three days will
> be on the FDA web site and can be obtained there. But our discussions
> will be made available to each member of the committee.
>
> The agency then will take this advice from the members of this
> committee and will generate a course of action based on our
> recommendations. So, hopefully, by doing it that way we can get done
> in time for people not to miss their airplanes. So, think about it
> tonight and we will begin tomorrow morning at 8:30 as usual, on the
> dot, assuming we can get through the traffic.
>
> \[Whereupon, at 4:30 p.m. the proceedings were adjourned, to resume on
> Thursday, July 25, 2002 at 8:30 a.m.\]

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