> UNITED STATES DEPARTMENT OF AGRICULTURE
>
> **FOOD ADVISORY COMMITTEE**
>
> **CONTAMINANTS AND NATURAL TOXICANTS SUBCOMMITTEE**
>
> Thursday, December 5, 2002
>
> 8:34 a.m.
>
> The Inn and Conference Center
>
> Founders Ballroom
>
> University of Maryland University College
>
> 3501 University Boulevard East
>
> Adelphi, Maryland 20783
>
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> [E]{.underline} [E]{.underline} [D]{.underline} [I]{.underline}
> [N]{.underline} [G]{.underline} [S]{.underline}
>
> DR. BUSTA: Good morning, everyone. Happy holidays.
>
> DR. FULLER: We may be here awhile.
>
> DR. BUSTA: It\'s beginning to look like a holiday. This was very
> fortuitous, that we had the meeting in the same place that we were
> staying. We appreciate Dr. Downer getting here from her home. She got
> a little excitement this morning, so her blood is rushing. Some of the
> rest of us are just waking up.
>
> This morning, you see on our agenda, the first presentation will be by
> Dr. Terry Troxell, who is going to summarize the Plan and Charge, tell
> us what we\'re supposed to do from here on.
>
> DR. TROXELL: Thank you. Well, the northerners on the committee, we
> have come through for you with snow. The university is closed, so
> maybe we should just shut down and go build a snowman and have snow
> fights. They closed everything last night even before the snow
> happened, but that\'s Washington for you.
>
> Okay, get down to serious business: the Action Plan. So I have 15
> minutes to summarize everything everybody did yesterday. But just
> briefly, let\'s just reup a few things.
>
> We talked about the analytical method yesterday, that we need to
> further validate the definitive methods.
>
> We have the need for proficiency samples so that we can assure that
> everyone around the world is\--in this country and so on are getting
> the same kinds of results.
>
> It would really be desirable to have alternative methods. We\'re
> looking at LCUV as a quicker, cheaper method that can be done with
> instrumentation that is, we believe, very prevalent. This would be
> prevalent not only in companies so they can do QC or, you know, can
> follow the research on new products and so on, but also for developing
> countries where they don\'t have LC/MS/MS equipment and so on.
>
> It would have been desirable, of course, to have something simpler,
> like an amino assay. But as we looked at the size of the molecule,
> people that advise me\--leave that, it really wouldn\'t\--we wouldn\'t
> likely get very definitive antibodies. But if that\'s something the
> committee thinks we should explore, I suppose that would be another
> approach to getting something cheaper for doing some screening.
>
> Then the next component really gets down to incidence and levels, all
> the way through the exposure assessment. We\'ve done an exploratory
> survey; we need to\--obviously, as we talked\--expand that more
> comprehensively to assure that we get similar results around the
> country. We need to get enough information to make it so that we can
> have a degree of robustness in exposure assessment.
>
> We are starting to analyze this as part of our Total Diet Survey,
> which is a survey of foods as consumed. Therefore, the foods are baked
> and so on, so there\'s a certain degree of consumer preparation in
> that study. The consumers that are preparing that, which happens to be
> a church group, prepare the foods according to recipe. So there is a
> certain amount of the consumer-preparation angle in there.
>
> But the other\--you know, in addition to serving to help provide data
> for the exposure assessment, this is going to be kind of weather-vane,
> as it is for the other chemicals we analyze\--it\'s a weather vane on
> trends, so we\'ll be able to measure progress in reduction of
> acrylamide by using\--this is one of our tools. No one tool general is
> the end-all, so we look at\--one always looks for a series of
> measures.
>
> Then the next component, of course, is the formation. We have very
> good information at this time on a major mechanism. Obviously, some
> more work needs to be done to check out other potential mechanisms in
> various foods.
>
> And when one thinks about reduction, there\'s probably three general
> strategies. One, of course, is to remove the reactants. So remove
> those precursors, asparagine and reducing sugars. So are there ways to
> minimize the presence of those. And then the second would be to stop
> the reaction from going, or slow the reaction\--so the ways to prevent
> the reaction from occurring, whether one puts inhibitors in there or
> temperature changes or whatever. And then finally, of course, is once
> it forms, is there some way that it can be destroyed after it is
> formed. So that kind of maybe divides that territory.
>
> Then the next thing, of course, was the toxicology. Obviously, we need
> to understand the toxicokinetics, particularly the comparative
> metabolism between animals and man. Biomarkers are going to be very
> useful. Some people look at biomarkers on the exposure side, but
> biomarkers are, of course, critical on the tox side, too, so we can
> relate the dose to the hemoglobin adducts, to the DNA adducts in the
> tissues, and then do comparisons between those adducts in animals and
> man and so on, so we can do a good risk assessment.
>
> And then, of course, there\'s the three major end points under
> consideration. There\'s the cancer end point, there\'s the neurotox
> end point, and the germ cell mutagen end point. The two latter, the
> neurotoxin and the germ cell, of course, are at much higher levels in
> exposures. Of course, the animal carcinogen end point is also
> occurring at a much higher level than food exposures, but there
> is\--part of the neurotox is to try to define if there\'s
> additional\--well, to define that point more precisely and to look at
> effects, whether there might be some neuro-developmental end points or
> whether there\'s an effect from long-term exposure compared to the
> exposures under which the current studies were done. And these things,
> then, will be fed into risk assessments, which will then feed into
> risk management and looking at different risk management options.
>
> The next component of our Action Plan is to foster those partnerships.
> You know, this is a large amount of work to do when you look at the
> different components. But then, on the other hand, there is also an
> intense interest out there, and one of our considerations is how to
> harness that interest so that there\'s a concerted, coordinated
> program, and we\'re fostering that through the JIFSAN work and through
> JIFSAN\'s running the Infonet. And in addition, we\'re independently
> working inter-agency to coordinate our efforts, and we\'ll do
> everything we can to support or facilitate coordination not only to
> help the JIFSAN effort but also independently in the international and
> so on.
>
> One illustration of the need for that coordination is that the
> mechanism was announced independently by about five different\--at
> least five labs, I mean, five we know of. I think there were other
> people out there who discovered the mechanism at the same time. And
> while it would have been nice for, say, two laboratories to do that,
> the other three labs could have been making progress on something
> else.
>
> There are many difficulties in the coordination in this, including the
> basic nature of scientists. Their lives and their creativity depend on
> kind of holding things tight, not being scooped, writing papers that
> they can publish and not announcing them ahead of time because they
> won\'t allow them to publish. But all that, of course, will minimize
> the progress and increase the level of duplication. So we\'ll do
> everything we can to encourage people to provide the information at
> the earliest point. Certainly FDA scientists, as government officials,
> will be releasing information as soon as it\'s ready.
>
> Then the last component was to inform and educate consumers and
> processors about the potential risk, provide options on how to reduce
> the risk as long as there\'s gain. We have provided an initial
> consumer message. We\'ve also publicized our scientific agenda and
> what we understand about the risk in order to assure the public that
> we are taking the necessary steps and appropriate action to protect
> them.
>
> So that\'s, in a nutshell, the Action Plan. Then turn to the Charge
> again. We\'re asking the committee to evaluate whether the research
> steps outlined in the Action Plan are scientifically adequate to
> describe and address the public health significance of acrylamide in
> foods. And based on what you heard, we would like you to provide
> questions, we would like to have your views and expert advice on
> whether the research steps are appropriate to describe and address
> that public health significance. And then, are there gaps in areas
> that there should be increased emphasis. And then, finally, the
> question of the priority of research needs\--what is more important to
> get done early. And also, I would suggest you think about what can
> practically be done early. I mean, obviously, you can\'t get a
> bioassay done in six months.
>
> Anyway, so some of the presenters are here, not all of them, but I
> think we\'ll be able to answer any questions you may have during the
> session. And I turn it back to you, Chair. Thank you.
>
> DR. BUSTA: Don\'t run away. I\'ve got a couple of questions. Number
> one, is there\--you mentioned risk assessment, risk management, and
> then the third step is all this risk communications. I see the
> educational component as risk communications, right?
>
> DR. TROXELL: And risk management. Risk communication has many
> components\--it communicates to consumers, industry; it also
> communicates back to the researchers and risk assessors. So I mean
> it\'s\--basically, risk communication covers everybody\'s involvement
> throughout the process.
>
> DR. BUSTA: And I see a lot of risk assessment. I\'m trying to
> understand the risk management component of this.
>
> DR. TROXELL: We have not laid out potential risk management options at
> this time, but one of them\--I mean, actually, our first risk
> management we have done is to put out a consumer message. We\'d like
> people to eat that balanced diet according to the pyramid and so on,
> and we think if they moved in that direction\--and most of us
> don\'t\--you know, there would be some reduction in acrylamide by that
> move. So that is a risk management approach right there.
>
> And then, you know, there\'s\--one can envision a series of risk
> management options, but we\'re not\--I mean, that\'s not what
> we\'re\--
>
> Would you like more?
>
> DR. BUSTA: I just wanted to make sure it didn\'t go by me.
>
> Second question I have is, is there an indication of the amount of
> effort that is going to be put in on each one of these five steps, and
> is there an indication of budget amounts? Or is that what you\'re
> looking for from us? How much effort will be put in on the assay
> versus the other concurrent activities?
>
> DR. TROXELL: I think you should address it scientifically and tell us
> what you think are the important things to do, whether they\'re
> critical things to do, and if you want to say, you know, this is the A
> list versus the B list and the C list, then we\'ll try to figure out
> how to get that money and the funding. There is, as I said, tremendous
> interest out there. I mean, Europeans are spending a lot of money on
> this; industry is already spending a lot of money. There are a lot of
> ways to ultimately fund this work over and above federal funding. And
> then, we just have to kind of check to see, you know, here\'s the
> list, are people doing it, is it credible work, and where should we
> fill in the gaps. But I would not right now think\--put a lot of
> weight on, you know, the particular cost. You might want to comment
> that that\'s very expensive, possibly, for what we might get back,
> but\--
>
> DR. BUSTA: Okay.
>
> DR. TROXELL: Other questions?
>
> DR. BUSTA: As I see us proceeding\--you can help if you see me going
> down the wrong track\--but as I see us proceeding this morning, is to
> go through the five areas that we have on our agenda and discuss those
> with your questions, if we need clarification, what we see as evidence
> or need of evidence, discuss them as thoroughly as we feel we need to.
> And if it appears to any of you that those are not\--that we should
> not separate and try and stay in that order, we could rearrange it. I
> don\'t have any problem with starting with the bottom one of the list
> or whatever. And after we\'ve exhausted ourselves, we will then go on
> to the three main questions.
>
> And we do not have to take the entire morning for discussion. If we
> feel we\'ve gotten the information that we need, we can move forward
> into discussing each of the three questions that have been posed to us
> and we will go around and each make comments on the questions,
> individual responses on each of the three questions. We have plenty of
> time to discuss the various aspects.
>
> DR. HOTCHKISS: I just wanted to ask Dr. Troxell kind of an umbrella
> kind of question, in part because he mentioned it as part of the
> committee\'s Charge. Throughout the presentations and in your
> summation, the agency has gone through the same order of steps in the
> Action Plan. But you haven\'t added the would \"priority\" to this or
> a sequence. Have you decided or thought about a priority, or are you
> asking us to advise you on that?
>
> DR. TROXELL: Well, I think in the Charge we do outline the various
> components done concurrently. Certainly, if you see some sequence,
> we\'d like to hear about it. I think, you know, we have always thought
> that, for example, it doesn\'t do much good to analyze a lot of
> samples without a solid method, so we built that method first to our
> satisfaction. And now we have probably the round-off thing of, you
> know, doing the inter-lab peer verification and so on. But
> we\'re\--you know, so we have that done. Yet clearly, I think, one
> wants to construct a plan with the right sequence of events, and I
> think that\'s where the priority also comes in. So I think you can
> help us to identify what needs to be done first and second. I think
> there are also independent things, like one really needs to not wait
> to work on formation and find out if there\'s a way to reduce the
> amount of acrylamide in the food supply for the final word coming in
> from the risk assessment. So that\'s why we have these things going on
> concurrently.
>
> DR. HOTCHKISS: Thank you.
>
> DR. BUSTA: Before you go, in your question, I\'m interpreting in that
> Question 1, the sequence of\--you have the first sequence, and then it
> says \"concurrent with formation studies and toxicity studies\"\--and
> the \"and\" meaning a third concurrent activity, right? If I interpret
> that way that\'s blocked, there are three concurrent activities going
> on? I just want to make sure I\--
>
> DR. TROXELL: Right, the\--yeah, there\'s three. Yes.
>
> DR. BUSTA: Three concurrent, okay. That\'s what that \"and\" means.
> Okay. I just don\'t want to get off here.
>
> The alternative approach to discussing, whether we go\--whether in
> toxicology and analytical methods, formation, et cetera, would be to
> go through the Action Plan that started with Testing of Foods. Which
> is more comfortable? Do we want to start off with questions and
> discussion about toxicology, or\--Dr. Hotchkiss?
>
> DR. HOTCHKISS: Because FDA has set a sequence, for my own thinking, I
> would think we would want to go through the sequence they have set up
> before discussing\--it also seems like a logical sequence to me.
>
> DR. BUSTA: \"Sequence\" being the Action Plan?
>
> DR. HOTCHKISS: The Action Plan.
>
> DR. BUSTA: Okay. Is that all right with everyone who are poised to
> talk about toxicology right away?
>
> DR. HOTCHKISS: I assume we\'ll get to toxicology. I have a number of
> questions about that as well.
>
> DR. BUSTA: And why doesn\'t that surprise me? No.
>
> All right, well, let\'s look at testing. We had a presentation on
> testing. Questions, discussion on the testing of foods, which includes
> the methods development and approach to occurrence?
>
> DR. FISCHER: You\'re not looking at the draft Action Plan, right,
> you\'re looking at the slides?
>
> DR. BUSTA: Yes.
>
> DR. FISCHER: Is that the way you\'re going to go through the Action
> Plan?
>
> DR. BUSTA: Well, we can go with the draft Action Plan. Tab 5. Would
> you prefer that one?
>
> DR. FISCHER: It would seem like that\'s the best thing to do.
>
> DR. BUSTA: All right. So that when we get to number 2\--or do you want
> to look at the major goals or just start into the discussion? Any
> comments, questions on the background? Any clarification needed on the
> Major Goals?
>
> DR. TROXELL: I would like to make a suggestion. While the draft Action
> Plan is, you know, in more of a summary format, the presentations were
> intended to provide more depth, so I would use them in conjunction, at
> least.
>
> DR. BUSTA: One comment when I look at the Major Goals is that \"risk\"
> shows up in at least three places and is inferred in others, and I
> think that it\'s obvious that the risk-assessment component is going
> to be the focus and I think that\'s been identified as we\'ve gone
> through, that eventually we have to get to risk assessment. So as
> we\'re looking at that, we can think of all the concerns that there
> are to try and get risk assessment.
>
> Number 2 on the Action Plan is Testing of Food.
>
> DR. FULLER: Before we move off that, just a comment. And perhaps I\'ve
> just missed it in all the discussion, but I think the\--at least as
> I\'m trying to get to the basics of things here\--the issue of looking
> at occurrence of acrylamide in foods, and variability, et cetera, et
> cetera, et cetera, I think what I haven\'t seen yet is on\--and
> perhaps someone from\--maybe Dr. Troxell could help on this\--is at
> what point\--has there been any consideration at what point that
> part\'s going to start and risk assessment to begin, based on
> information that is currently available on the tox data? Am I making
> any sense? Are you following my question? When do you have enough of
> the exposure information? And I just want\--because we could do that
> forever.
>
> DR. CANADY: We\'re already in risk assessment, in the sense that
> we\'re doing a\--we\'ve done a safety risk assessment, we\'ve done
> evaluations like that. We recognized early on that we needed a lot of
> information regarding exposure, regarding occurrence in order to do a
> full risk assessment. I think you\'re right. We\'re at the stage where
> we can start framing the models, start putting the models together,
> figuring out what questions we need to ask of the risk assessment. And
> so we are doing that. Of course, it\'s an iterative process, so we
> have to have enough information about where it occurs, obviously,
> before we can start understanding exposure enough. I think we\'re to
> that point almost. There are still a few more, you know, basic shapes
> to fill out, but, yeah, I think we\'re to that point.
>
> And again, we need to understand variability to some degree, but then
> risk assessment is going to help us understand, through sensitivity
> analysis, for example, which are the important exposure elements,
> which are the important toxicity elements, and so on. Again, though,
> we need to think what are the questions we\'re asking a risk
> assessment to help us with.
>
> DR. FISCHER: Well, I\'m confused about the exposure, after you said
> that you\'ve started with risk already. Because I thought you were
> doing the exposure analysis in two steps. One is that you were going
> to do this\--not monitoring, but this broad-picture thing, not taking
> time to get enough measurements or data to do a risk assessment. Now
> at first, you were looking at where it is, as opposed to how much it
> really is in a given food group.
>
> DR. CANADY: Right.
>
> DR. FISCHER: And you\'re in this first stage now. You\'re just looking
> things up and seeing whether it\'s there. And you have some numbers,
> but those aren\'t enough data to do the exposure part of a final risk
> assessment with. Am I correct?
>
> DR. CANADY: I think you\'re both correct. I mean, the point is we\'re
> trying to understand when a full risk assessment, when is a complete
> risk assessment going to be done. And my answer is, you know, it\'s an
> iterative process, again. I hate to keep saying that, but we\'re at a
> stage where we can use the current data to start framing the risk
> models that can then help us understand what further data we need. I
> don\'t think we\'re to a stage where we can do a full-blown risk
> assessment that answers all the questions we need to answer.
>
> DR. TROXELL: Let me also add that, as Dr. DiNovi said yesterday, that
> they\'re already in the process of doing an initial exposure
> assessment. As you all know, exposure assessments are going to have
> more certainty or less, depending on the amount of data you have in
> there. If we have 1 point per food, we\'re going to have a tremendous
> amount of uncertainty. So, you know, that\'s part of getting the kind
> of critical mass of information to have a reasonable level of exposure
> assessment. Also, on the tox side, you have a tremendous number of
> uncertainties, so if we get some of the\--you know, what would be the
> critical quick data that would help us zero that in so we can do that
> next iterative step and, you know, do a risk assessment that has less
> uncertainty so we\'d be more comfortable it would be predictive,
> rather than the risk assessment just saying, well, you know, these are
> the other research steps we should do.
>
> I mean, risk assessments can be used for\--you know, to assist risk
> management, but they also can be used for determining where the gaps
> are so we can reduce uncertainties.
>
> DR. BUSTA: Questions?
>
> DR. FISCHER: Well, it seems to me the other way to do it would be to,
> at this point in time or at some time soon, decide where it\'s likely
> that the largest risk is going to come from\--what food group, for
> example, or what group of foods represent the largest exposure; and
> then get the necessary data on those groups and do a risk assessment.
> So what you\'re doing is looking at a worst-case situation first to
> get a good idea about what the risk might be, as opposed to doing an
> awful lot of work directed at the whole sphere of foods. I\'m
> suggesting to focus that on what you can determine might be the most
> serious problem. There may be two or three food or food groups that
> you would look at. If you want to do it quickly, it seems to me that
> would be a better way of doing it, more convincing, than this
> iterative thing\--just keep going, getting more and more data, and
> trying to decide, okay, when should we stop and do something about
> risk.
>
> DR. HOTCHKISS: Those groups have probably already been identified.
>
> DR. FISCHER: Yeah, that\'s what I have in mind.
>
> DR. BUSTA: Dr. Gray now, and then we\'ll get Dr. Canady.
>
> DR. GRAY: Well, I was going to say I agree with Larry. That would
> be\--that\'s sort of the way to take an approach. In some ways that
> has been done. We have some estimate of exposure, and you can do a \--
> calculation that tells you this is potentially a bigger risk than
> almost anything we\'ve got out there in the food supply. That\'s why
> we have to know a whole lot better on the exposure and on the tox side
> how much confidence we can have in those, sort of, worst-case things
> that have already been done. But those have been done, and those are
> the kinds of things that make people sit up and say all around the
> world we\'ve got to spend some time on this.
>
> So I would agree with you, though, that this exposure\--there are ways
> to think about doing out exposure, to work with, sort of, the
> risk-assessment approach that says where are the big sources of
> exposure, how can we nail those down\--what are the sources of
> variability in exposure, how can we nail those down to understand this
> better. Because part of what you\'re also hoping to do is to get to a
> place where you can learn, if it has to be managed, how to manage that
> risk.
>
> But the worst-case things have been done, and they\'ve scared the hell
> out of people.
>
> DR. BUSTA: Are you saying that you think there\'s enough data on these
> what you\'ve identified are the worst-case to start doing a risk
> analysis with that information?
>
> DR. GRAY: Yeah, I think they suggest that much more detailed work has
> to be done at this point. Because using the worst-case approaches,
> which have been done\--the WHO looked at that with exposure, we\'ve
> got 20 years of regulatory experience with acrylamide in other
> settings\--using t kind of information, it\'s sufficient there to say
> this needs more attention. The big question is where do you put more
> attention to really try to do a good job of understanding those risks.
>
> DR. BUSTA: Dr. Canady?
>
> DR. CANADY: I think maybe part of the issue we\'re discussing here is
> sort of a formalized definition of risk assessment as the be-all and
> end-all and \"the\" document; and the process of assessment, which, as
> Dr. Gray has just said, is already going on, the process of risk
> assessment. And what I was trying to say is that using this assessment
> modeling would help us understand where to look first and where to
> look the hardest and where we need to focus on reducing uncertainty
> the most, for example.
>
> I don\'t think we\'re disagreeing. I think we\'re having a little
> problem with the definition of risk assessment and, you know, is there
> a formalized meaning. That\'s all.
>
> DR. BUSTA: I\'m assuming that you have good statisticians that can
> determine when you\'re at a point, an asymptote of having enough data
> in a given sampling system to say we don\'t have to iterate it any
> longer or we change the sampling, not just keep taking more and more
> samples.
>
> DR. CANADY: Well, the direct answer is yes, of course we do. The
> indirect answer is that\'s something that is influenced by the framing
> questions and what are the countervailing risks, what decisions do you
> need to make. So you know you have enough if you can make a decision
> that doesn\'t have a high cost in terms of health or in terms of other
> things.
>
> DR. BUSTA: A very judicious answer.
>
> Other comments on this specific topic? How much more sampling do you
> think is needed? I mean, this has been\--we\'ve got this 700 samples.
> George?
>
> DR. GRAY: My thought here is, I hope that there is good communication
> between the folks doing the exposure assessment and the folks doing
> the sampling. Because I really think that by doing this preliminary
> exposure assessment, where you\'re working with the data that are
> available on the kinds of foods that people consume and whatever level
> of aggregation you have there, you can understand from trying to do
> that estimation what kind of data you need that helps you understand
> what level of detail and aggregation you need at the sampling level.
> And it may be for some foods you\'ve already got enough sampling to
> adequately describe the variability in those and we don\'t need to go
> to finer levels of detail\--by brand, by potato, by season or
> something like that; or it may be that those things are big enough
> that we need to do those better for certain of the categories of
> foods.
>
> So it\'s just sort of\--it\'s very much in fitting with what Rick
> said, that you want to use the way that you\'re going to approach the
> problem, the model way you\'re going to try to estimate exposure from
> how much is in which foods that people eat how much of, to understand
> where you need to get more information. So there, sort of, aren\'t
> numerical cut-offs for sampling; it\'s much more\--I think should be
> related to the way in which you\'re going to use that information. And
> I just hope that communication is going out. I\'m pretty confident it
> probably is.
>
> DR. BUSTA: For example, my gut reaction is that the information on
> infant formula so far has been essentially negative. So to continue to
> sample infant formula might be a waste of effort. Is that\--
>
> DR. GRAY: That would probably be\--sure. And that\'s part of the
> statistical analysis that you talked about, of how many zeroes to I
> have to get to believe that everyone\'s going to be close enough to
> zero that I\'m not going to do any more? That has to do with what you
> expect for variability, though, which we\'ve seen is kind of high.
> This isn\'t an easy sample question.
>
> DR. BUSTA: Dr. Hotchkiss?
>
> DR. HOTCHKISS: That really gets to the heart of the question that I
> asked yesterday about comparing analytical data or inserting
> analytical data in the databases which calculate consumption figures,
> and when you do that, you begin to\--you get what percentile you\'re
> covering for a given food product and so forth, and then once you have
> that information you can decide whether you have made a sufficient
> number of samples or not a sufficient number of samples relatively
> easily. And that\'s the reason I raise that. Dr. DiNovi assured us
> that\--and Dr. DiNovi is an expert in this, spent his career in this,
> and knows what he\'s talking about in this, he knows the
> databases\--assured us that that would happen, and I\'m confident it
> will. The agency has great expertise in that area.
>
> I would, though, really, to ensure\--or to be more comfortable with an
> answer to this question, suggest in the draft document of Action Plan
> in 2 that the first major goal is to assess dietary exposure, and I
> think that is the first priority. Under that it has a number of
> consequences, analysis in analytical chemistry, for example, but there
> are two major parts in order to assess dietary exposure, one of which
> is measuring levels in foods, and that\'s listed as how to do that,
> but that is in itself not sufficient.
>
> The other part is using the best available food consumption databases,
> and I would recommend that that phrase or something akin to that be
> added to that major goal. When you do that, when you plug in your
> analytical data into a good consumption database, all of a sudden you
> begin to answer the question of how much confidence you have or don\'t
> have that you have covered the waterfront for that particular food.
>
> DR. BUSTA: You\'re suggesting that goes in on goal number 1?
>
> DR. HOTCHKISS: Yes, under Major Goal 1, the first bullet point under
> that is assess dietary exposure, and I think that\'s absolutely
> correct. But there are two parts to that, the first of which is
> mentioned under that\--along with that bullet, that is, measurement.
> But the second part is to use that measurement in what I would call
> the best available consumption database. This changes all the time,
> but FDA has access to these databases, as Dr. DiNovi discussed
> yesterday.
>
> DR. BUSTA: Other comments on this specific topic? Ken?
>
> DR. LEE: I\'m very interested in ways that we can solve this problem
> in that\--you know, best-case scenario would be to reduce the level of
> acrylamide in foods to zero. And I think those Industries that are
> most affected by this, by having the highest levels, are going to do
> work that will likely lead to a reduction in that level, if not
> ultimately reach that goal of zero.
>
> However, I\'m also concerned by how that occurs in cooperation with
> the Food and Drug Administration. We saw, for example, the posting of
> brand names and acrylamide contents on the World Wide Web, with, of
> course, the footnote that these are incomplete data sets and you
> shouldn\'t put any credence in these data. But if I was a very
> litigious person, I would just be drooling at that list. And that
> doesn\'t really serve the scientific interests or the best interests
> of consumers. Because if this situation gets tied up in the courts,
> and if industries are afraid to come forward with forthright data or
> data on how their process variables affect acrylamide content of food,
> we\'re going to be set back quite significantly.
>
> So I would encourage any system that allows free and unencumbered
> exchange of acrylamide information in a way that it\'s blinded to
> brand identify.
>
> DR. BUSTA: Dr. Kuzminski.
>
> DR. KUZMINSKI: Thank you, Ken, for making that point. I believe\--gut
> feel, without any personal knowledge\--I said it yesterday, and at the
> risk of nauseating the rest of the subcommittee, I\'ll say it one more
> time, that there\'s probably data out there in industry that is good,
> reliable, solid data in terms of occurrence in finished product, and
> probably data out there in terms of occurrence throughout a process to
> make that product. And I think the agency, should they be able to
> create an environment and situation and procedures where that data is
> accessible, might save themselves a lot of time, a lot of effort, and
> probably a lot of money in terms of getting that information. How they
> use that in terms of in combination with consumption data to come up
> with the true exposure and risk information, then can follow.
>
> But again, just going from experience, the way this issue suddenly
> bloomed last spring, there\'s been several months passed since that
> time, and the reputable companies have been all over this, just all
> over this issue. It does a responsible company no good in the long
> run\--and this is a long-run issue\--to generate data that is not
> good, analytically not good from a sampling methodology, because their
> own credibility goes down the tube.
>
> So I would just echo your comments, Ken, that I would strongly
> encourage the agency to do this.
>
> DR. BUSTA: Dr. Hotchkiss.
>
> DR. HOTCHKISS: In a switch from several hats, and as a former FDAer
> and having been intimately involved in a problem or an issue very
> similar to this before, one has to recall that FDA is an agency based
> on statutory law and must ultimately answer to that statutory law. As
> well, the agency has an obligation to maintain its appearance of
> credibility\--not just its credibility, its appearance of credibility.
> While the agency should take into account industry-generated data and
> so forth, it also must realize that it does not have control over that
> data, the way that data is collected, the quality of that data. And
> therefore, when push comes to shove in a legal sense, the agency
> probably does not want to rely on that.
>
> In the past, particularly with the nitrosamines in beer issue, this
> was settled quite nicely, actually, by going to a\--the industry went
> to a third party, a quite credible third party. That third party did
> analyses for the industry, essentially sanitized that data by company
> name, gave that data to the agency. The agency felt that that was a
> good measure of what was going on out there. That data eventually was
> all published in the peer-reviewed literature and saw the light of
> that venue and so forth. But in the end, when the agency set action
> levels, which they did\--that is, they took legal regulatory steps
> around the issue\--the data generated by industry was not used for
> that because it was illegal; but on the other hand, the agency took
> that data by going through a third party which sanitized the data.
>
> So there is room for compromise here, but in the end the agency has to
> remember that it has the force of law.
>
> DR. BUSTA: Terry.
>
> DR. TROXELL: Thank you. I just wanted to point out that this data will
> probably be available through JIFSAN. I mean, they\'re setting up this
> Infonet. As Dave Lineback said yesterday, industry will be able to
> submit in a blinded way before it comes to JIFSAN. We have heard at
> the JIFSAN workshop that there\'s probably 2,500 samples been analyzed
> out there around the U.S., and then we\'ve heard since then that
> there\'s some 4,000 analyses in Europe that are being compiled by the
> U.K. in a database. This is going to shed a lot of light on just how
> many zeroes do we need in some things to say, well, we don\'t have to
> worry about that.
>
> The other thing, of course, it\'s going to\--I think, while there\'s
> some data on particular products, a lot of effort has gone in with
> many of these analyses to try to figure out what in the chain of
> production is contributing. So that kind of linkage is very important.
> And that doesn\'t necessarily fit into the database, but that also
> would be very valuable, again, to link into this information network
> in a blinded way so everybody can benefit from it.
>
> DR. BUSTA: Other comments on this area? We\'ll be getting back to
> exposure more later, right? I have a question on exposure, but I\'ll
> wait for that one. Some people trust NHANES more than I do.
>
> The next item in the Plan is the toxicology. We had presentations as
> well as the development of new data on toxicology. Comments and
> discussion in this area? We had Dr. Canady up there on and on and on,
> and he\'s here smiling and ready to go again. Dr. Hotchkiss.
>
> DR. HOTCHKISS: In my view, clearly, most of the items outlined in the
> draft Action Plan are certainly needed and should be undertaken,
> particularly those that correlate some of the biomarkers with
> exposure\--although my own view is that a fair amount of that work has
> been done, particularly by Tannenbaum and Farmer, through cigarette
> smoking. There\'s actually a very good database that correlates number
> of cigarettes consumed per day and hemoglobin adducts and so forth,
> which is obviously not foods, but by a different route of exposure.
> But you would assume, I think probably correctly assume, that
> inhalation would be the worst-case scenario compared to ingestion, and
> so that database seems to me to be very strong and worthy of careful
> attention, and may in fact be sufficient to make some conclusions. But
> still, I think, biomarkers are important\--biomarkers on target
> tumors, very important correlation between exposure and genetic
> adducts and genetic materials, clearly important.
>
> The one area of the Plan that\'s a little hazy to me\--and maybe it
> could be further clarified for me\--is the chronic tumorigenicity
> study. Apparently FDA four years ago or so found the data of
> sufficient quality to actually\--and formally concluded, through the
> Cancer Risk Assessment Committee, that the data was robust enough to
> actually set what amounts to an ADI kind of number and so forth. I
> just wonder, by spending all that time and money in a chronic rodent
> assay what would be expected to be learned that\'s not already known?
> And what would the\--I mean, I think I\'d bet the mortgage
> that\--it\'s not much of a mortgage, but I\'d bet the mortgage anyway
> that you\'re going to find out in fact it is a carcinogen in the rat,
> and you may get a little bit different answer than the previous
> studies, but it\'s probably going to be well within an order of
> magnitude of the answer you already have.
>
> The rest of the toxicology I think is great, the one about spending
> millions of dollars to do that kind of study.
>
> DR. BUSTA: Dr. Canady.
>
> DR. CANADY: Thank you for that comment. I think your two comments, or
> the two areas you commented on, are actually related, though, in the
> sense that one of the reasons we\'re very interested in doing an NTP
> bioassay is that we can fold in biomarker data, DNA adduct data and
> those sorts of things with the end points that would be considered
> under a chronic assay. So that\'s one point. The second point is that
> early information from the bioassay will also be very useful to us,
> dose-ranging studies, corollary studies, and so on.
>
> So, while I understand that going into a multi-year process to get to
> an answer that may not be substantially different from what we already
> have in hand is something you might question. I would make the point
> that the information we could get by bringing more advanced
> technologies\--or rather, bringing a fuller suite of technologies to
> bear on the problem may give us a better understanding of the
> extrapolation from the rat to the human than we currently have. Having
> it all in one package with the same animals is going to help us make
> that low-dose extrapolation a lot more confidently.
>
> And that\'s that argument I would make for having the bioassay. The
> other thing is that we talked about zero as a goal. We\'re not going
> to get to zero for quite a long time. This is not going to be an issue
> that\'s going to go away.
>
> DR. HOTCHKISS: If I could just follow that up. I\'m sorry, I don\'t
> want to sound too lawyerly\--I\'d rather sound human than lawyerly. As
> I read what actually was available to the agency and considered in
> depth by the agency in \'97, and I believe before that, was\--I don\'t
> want to give you the quote, but it\'s something like the agency
> considers the data robust or sufficient to make this kind of\--in
> other words, none of the issues that you raised were raised apparently
> three or four years ago when acrylamide toxicity, as it relates to
> potential migration from food contact materials, was an issue at the
> agency. But now you feel that at that time the agency felt that it was
> sufficient, but now it doesn\'t. Is that the deal?
>
> DR. CANADY: Decision context is always something that I think you need
> to consider in these situations. And at that time the decision was
> that food contact exposure\--which was, if I remember correctly, three
> orders of magnitude below what we\'re considering now, perhaps
> more\--in that context the dose-response information was clearly
> adequate. It was clearly sufficient for us to make a decision that
> that use was one that did not present an unacceptable risk.
>
> When you consider in contrast the broad exposure that we\'re currently
> considering, you have to ask the question, I feel, do we have
> sufficient information, again, for this new decision context. And
> that\'s the question that we\'d like to have the committee address,
> really.
>
> DR. BUSTA: Could I just ask the question\--yesterday, someone said it
> was a flat extrapolation.
>
> DR. HOTCHKISS: It comes from FDA\'s document.
>
> DR. BUSTA: Yeah. Flat\--could you explain \"flat,\" to make sure that
> I\'m not misinterpreting? Does this mean that at low concentrations
> it\'s potentially more hazardous or less hazardous?
>
> DR. GRAY: Can I just\--I mean, from my read of this document, when FDA
> reviewed this, it simply says that the dose-response information in
> the range at which it was tested, which is still very, very high, was
> relatively flat, meaning that between controls and dose groups the
> tumor rate didn\'t go up like this; it went up\--it was a very flat
> dose response curve.
>
> DR. HOTCHKISS: Yeah.
>
> DR. GRAY: That\'s all I was saying. And that\'s in the range of doses
> that are thousands of\--well, hundreds of times higher than what
> we\'re talking about today.
>
> DR. CANADY: Actually thousands is right.
>
> DR. GRAY: Yeah.
>
> DR. FISCHER: I still don\'t understand that. Meaning\--
>
> DR. HOTCHKISS: What it says is the response is not tightly correlated
> to dose. In other words, if I go up in dose, I would expect a number
> of tumors, number of animals and so forth to in some way
> proportionally go up. But those curves were relatively flat. That
> doesn\'t mean that the chemical is not a carcinogen; it just raises a
> flag, I think, for many toxicologists that there is more to the story
> that\'s not understood, that it\--in most cases, \"more\" produces
> more response; in this case, for some reason, maybe it\'s saturating
> some kind of system that\--a system that converts it into the
> penultimate or the actual carcinogen. Maybe it\'s saturating that
> system, so when you double the dose you don\'t get double the
> response. Something like that. There\'s more to the thing. It raises a
> flag that we don\'t know everything there is to know about it.
>
> DR. BUSTA: But in reverse, does this mean that when it\'s flat it
> means you could get\--you know where I\'m going. If it\'s flat enough,
> then you could go very down, very low doses and still get a response.
>
> DR. HOTCHKISS: Your operative would of \"could\" is right\--a lot of
> things could happen.
>
> DR. GRAY: But if you look at these data, what most of them say is that
> things\--the low-dose groups have very little going on. They\'re flat
> with the controls, too. So I mean it\'s\--this all depends on
> ultimately what sort of choices of models and such are used to extend
> those data. So that\'s\--you know, that dose-response data is
> moderately interesting in that high-dose range.
>
> In fact, if I could make a comment, I mean, I think one of the
> problems we have here is that this particular issue is a challenge to
> the traditional ways that these risks have been assessed. Either the
> reliance on high-dose rodent cancer bioassays\--do we believe that a
> rodent carcinogen is always a human carcinogen? Or the models that are
> used, the linear no-threshold model that\'s used to extend the dose
> response from animal data to human\--is that correct or is it not
> correct? And also, what levels we think are important levels to manage
> risk. Are hazard quotients of 1 something we get worried about when we
> compare it to the ADI?
>
> So this is a tough one. And one of the things that I\'d actually like
> to perhaps see a little bit more of in the Action Plan is, I agree
> that these research data-gathering goals that are set out here are
> very good and very appropriate. But what I\'d like to see is\--think a
> little bit more about is how those data are going to be used. And I
> think one of the most important things that we could recommend very
> early on is to use things like the toxicokinetic data and things like
> that that are going to come. Put them into some kind of
> physiologically based pharmacokinetic models, things that are going to
> let us look at the assumptions that are based\--that are in the
> traditional approach.
>
> And with those kinds of things, we can look at the difference between
> routes or food matrices and we could say pretty quickly\--and I think
> Dr. Hotchkiss is probably right, by the time we get to the right doses
> and another rodent bioassay, we\'re going to get about the same
> response. We can look at the different routes of exposure, the
> inhalation data from Epi, which is probably equivalent to a
> considerably higher oral dose. If we had good pharmacokinetic data, we
> could relate that\--and we might be getting closer to doses that
> people are getting\--and have maybe more confidence in what the Epi is
> telling us compared to the animal bioassays.
>
> So I guess I\'d like to see a little more discussion about how these
> data are then going to feed back into the process and be used. And
> some of them will be much more useful in the shorter term than the
> time that it will take to get a new rodent bioassay done, which, under
> any circumstances, won\'t be sooner than three years from today and
> will probably be longer than that.
>
> I\'d also, sort of along the same lines\--and this is echoing remarks
> we\'ve had from others\--is urge the FDA to use some of those data
> that are coming from industry, especially some of that really
> impressive stuff we saw that\'s being done by the chemical industry
> around acrylamide. Those human studies will be extremely helpful in
> trying to do a good job with PB PK. I was at the Chicago meeting, and
> the head of the company was there offering to allow all of the medical
> monitoring data and all of their plants to be used for Epi studies.
> That seems like something that should at least be investigated and
> potentially used. It\'s another opportunity, again, if we\'re going to
> question this use of the high-dose rodent bioassay as the basis,
> let\'s get in there and get some more and some better Epi data to help
> us have some comfort with what we\'re going to do.
>
> So I guess the thing I\'d like to see is, in addition to the science
> that\'s laid out\--and I think it is the right science that answers a
> lot of the questions that need to be answered\--is think about how
> that\'s going to be used, both in the short term, when it can help us
> answer questions today, and in the longer term, when it comes to
> ultimately making decisions.
>
> DR. BUSTA: Dr. Fischer.
>
> DR. FISHER: I would like to know whether\--I can\'t recall whether
> there was going to be a mouse component. Are mice going to be used as
> well as\--okay. Because they\'re supposed to be somewhat more
> sensitive. So I suggest that the mouse\--it\'s a good idea.
>
> I think it\'s worth\--I never am sure whether it\'s worth to do the
> rodent bioassay the way it\'s usually done, with high doses, to do
> risk assessment with. Clearly, I think what we know already from the
> bioassay is that it\'s a carcinogen. I mean, there\'s a lot of
> evidence to back that up. But what we don\'t know is whether it causes
> an increased risk of cancer at very low doses. And the only way we\'re
> going to know that is, I guess, repeating the assay with lower doses,
> trying to see a better dose-response relationship than we\'ve got now.
> We know at high doses we can see this, but how about at lower doses in
> between the NOAEL and the doses that produce tumors?
>
> But in repeating the bioassay, I certainly think it ought to be a
> mechanistically oriented exercise. And I think Dr. Gray has already
> talked about that, I think. We need to\--certainly in its plan to
> measure biomarkers and so on, that\'s definitely something that should
> be done. But I think they ought to think carefully about other
> information that they might be able to get, toxicokinetic information,
> from these animals that are used in the assay. This is being done for
> other compounds by the EPA to do a very mechanistically based
> bioassay. And I think here we have a good chance to get a lot of
> information from these animals, who are going to be dosed for a long
> period of time, in terms of toxicokinetics and mechanisms if we make
> the right measurements.
>
> So having said that, I think it wouldn\'t be a bad idea to get the
> National Cancer Institute and NIEHS interested in acrylamide research
> based upon the mechanistic aspects of the outcomes that are expected,
> or not expected. Couldn\'t NCI put some money into mechanistic
> research, maybe even tying it in to the cancer bioassay; and couldn\'t
> NIEHS look for mechanisms, or examine mechanisms which may be active
> in these animals that are getting dosed for two years, and so on?
>
> So\--and perhaps they could do this by putting out RFAs for research
> on acrylamide-induced toxicity, cancer and other things\--reproduction
> and so on. Neurotoxicity. I think it\'s worth a try to get these
> funding agencies interested in helping with the mechanistic data that
> we need to understand a toxicity, cancer and others. I don\'t know
> what the FDA thinks about that, whether that\'s possible. But I
> certainly suggest that that be done.
>
> DR. HOTCHKISS: Let me point out that the IARC Monograph, Vol. 60 of
> the IARC Monograph, which details a great deal of toxicology\--as
> you\'re all aware IARC monographs do\--points out that acrylamide has
> been tested in both mouse and rat. Its probable route of metabolism to
> the ultimate carcinogen has been studied in some detail, but \-- never
> proved these things. But given the history of epoxides, beginning with
> aflatoxin metabolism and going through cyclopropenes and a whole
> variety of epoxides, I think that most cancer toxicologists would
> feel\--would, again, bet mortgages larger than mine that that is the
> proper route. In other words, much of what we\'re discussing is, I
> think, reported in the IARC Monograph, which is in fact a very
> detailed and\--I haven\'t counted the references, but probably a
> hundred or more references on the toxicology of this compound. This
> compound has been known to be a carcinogen for more than two decades,
> its metabolism widely studied, its epidemiology studied in
> occupational environments and so forth. This is a little bit of an
> unusual thing from the standpoint of food contaminants in that we have
> all this history to it, and I don\'t think the agency should spend a
> lot of time reinventing the wheel, but rather trying to decide what to
> do about the wheel.
>
> DR. BUSTA: Dr. Lee.
>
> DR. LEE: Yeah, there\'s a lot of talk about animal studies. I\'m not a
> toxicologist, so I\'m really speaking out of a quest for more
> information. It appears to me that the relevance to the human is the
> most important thing when it comes to food exposure, particularly from
> the Food and Drug Administration\'s point of view. So I would just
> underscore what Dr. Gray alluded to.
>
> We heard briefly yesterday from, I think, Dr. Friedman about a Covane
> study in Madison, Wisconsin, where 24 sterile males were being fed
> three-dose levels of acrylamide, and\--I mean, I think this was a
> casual mention, but to what extent is this going on with human
> studies? And I don\'t have that information in front of me. So I need
> to know, is there a lot of feeding going on of human beings with
> acrylamide, and what useful information could come out of these
> studies?
>
> DR. BUSTA: Sterile males?
>
> DR. LEE: Yeah.
>
> DR. BUSTA: Dr. Whitaker. I presume it was voluntary.
>
> DR. WHITAKER: I would just like to amplify on what Dr. Lee said. My
> thought my process is as I sat here and listened\--I\'m not a
> toxicologist, so I feel like I\'m on the outside looking in. But I\'ve
> had many years of exposure to aflatoxin, through the Codex system, of
> trying to set limits and understand what the consequences of aflatoxin
> was in humans. And nobody could every agree on the rat studies. And
> the definitive studies that seemed to break the ice dam was the
> Chinese study. And so it\--I don\'t know whether the analogy still
> holds here with acrylamide, but maybe the emphasis should be headed
> more towards the human effects if indeed that data is out there. I\'ve
> heard you mention\--Dr. Lee mention, Dr. Gray mention\--so maybe those
> studies are the ones that should be emphasized, because we may head
> down the same road that we did for 25 years with aflatoxin and its
> effects on humans.
>
> DR. BUSTA: And we don\'t want to do that.
>
> DR. LEE: I can add that they used sterile males because the concern
> was \-- reproductive effects.
>
> DR. BUSTA: Dr. Fuller.
>
> DR. FULLER: Thank you. I\'m pretty comfortable as well with FDA\'s
> action plan on all of this, and I\'d like to reiterate, I guess, a
> couple of the points that Dr. Gray. And also, just to\--back to FDA,
> to ensure that they are looking at and in consultation with the
> chemical industry on the studies and aren\'t repeating any of the
> studies that\--and I didn\'t have a good sense of how familiar FDA was
> with the work that Dr. Friedman was telling us about at the end of the
> day yesterday.
>
> DR. CANADY: I think the best way to share that information is through
> the Acrylamide Infonet, to make people aware of studies, what their
> protocols are, when the results are expected. And then the point was
> made earlier that we\'re constrained by what we can use in regulatory
> purposes, so it needs to be peer-reviewed and published, obviously, as
> well, before we can ultimately use it to make regulatory action. That
> would be my understanding.
>
> DR. FULLER: Is there no mechanism under which you can review at this
> stage, if it\'s made available to you, the conduct of the studies, et
> cetera, to provide some reassurance? And I\'m just thinking of let\'s
> don\'t duplicate if it\'s not necessary. And I appreciate that the
> constraints being a regulatory body and needing to maintain integrity,
> et cetera, et cetera, et cetera. At the same time, I hate to see a lot
> of resources spent if there are some\--if there are good data that are
> being generated that would either prevent the necessity of doing a
> particular study or, more importantly, change the emphasis or what
> you\'re looking at in a particular study.
>
> DR. CANADY: Yeah, I think this underscores the fifth component of the
> Action Plan, and that is collaborations are an essential part of
> collecting information, making sure there isn\'t replication and those
> sorts of things\--or actually, making sure the replication is
> knowingly done, to the degree that you can.
>
> So, yeah, I think, again, this is part of the Plan that we\'ve laid
> out, that we would look to all sources and collect information where
> it\'s available and avoid unnecessary duplication where we can.
>
> DR. FULLER: Has\--and I\'m sorry, I just\--maybe you are answering the
> question, I\'m just not hearing it. Is that happening now, in the
> planning stages, based on\--and have you had that collaboration, or is
> there something about to happen with that? I just didn\'t hear that in
> the presentation.
>
> DR. CANADY: Yeah, I think the first time that I heard about the
> studies that were mentioned yesterday was at the June consultation at
> Geneva. And at that time, we asked for the protocols. We\'ve again
> asked for the protocols, I think it was at the Chicago meeting. And we
> heard the same offer; it was made by SNF. So we\'re willing to look at
> them, receive them and so on.
>
> DR. FULLER: Thank you.
>
> DR. TROXELL: So again, we\'re fully aware what they\'re doing; and
> secondly, you know, as with food additives, we review any studies that
> are submitted, and we\'ll use them to the fullest extent. We obviously
> want to minimize duplication. We\'re very interested in seeing what
> the results are of their human exposures so we can learn what we can
> about the adducts.
>
> DR. FULLER: Thank you.
>
> DR. ACHOLONU: The material given us here says there are uncertainties
> about the impact of acrylamide on public health. There are
> uncertainties. Yes, tests have been done on rats, on mice. We have
> tested food to find out the content of acrylamide in food. Until we
> find a way to connect it to human beings, it will be causing
> unnecessary alarm to the public. If we no get out information saying
> that acrylamide is carcinogenic, yes, it is carcinogenic to rats. The
> genetic makeup of rats and human beings are quite different. Of
> course, we have got mammals. But we have to be aware of that and be
> apprised of it. But to connect this with human nature, we cannot say
> that we have gone far in making people aware of the dangers of
> acrylamide.
>
> And this is the point I want to make. Whatever we do, whatever study
> we conduct, should lead us to connecting it to human beings. That is
> the comment I wanted to make.
>
> DR. BUSTA: I don\'t want to change the topic here, but there\'s a fair
> amount of mention about glycidamide, and yet we just talk about
> acrylamide. If that is the mode of action, or apparent mode of action,
> why aren\'t we doing more testing on glycidamide?
>
> DR. CANADY: I\'m not sure I heard your question right. Did you mean in
> the last case to say \"acrylamide\"? Could you restate the question?
> I\'m sorry. I didn\'t quite understand it.
>
> DR. BUSTA: Well, you know, it\'s my understanding that glycidamide is
> the step of the toxicity. Is that right?
>
> DR. CANADY: It\'s one of the proposed mechanisms. There\'s some debate
> for neurotoxicity and for the reproductive effects, for that matter,
> as to what the active moiety is. And that\'s one reason to do the
> mechanistic work that has been underscored several times and that we
> have a lot of interest in doing. And that is to understand what
> happens between the higher doses we have information for animals and
> humans in and the lower doses that we see in foods\--understand that
> relationship. One of the steps in there is figuring out which chemical
> actually causes the damage in the body, which converted chemical or
> which parent chemical causes the damage, so that we can make that
> extrapolation and understand how rats or mice differ from humans and
> what we would expect to happen in humans compared to what we see in
> rats and mice.
>
> DR. BUSTA: And the glycidamide, is that the adduct?
>
> DR. CANADY: It is one of the two adducts that forms with hemoglobin.
> Acrylamide and glycidamide both form adducts. The argument has been
> made that direct interaction with DNA only occurs for glycidamide. The
> argument has been made both ways with regard to neurotoxicity whether
> acrylamide or glycidamide is the active agent. I\'m trying to state
> this neutrally. I mean, this is the way the arguments have been laid
> out.
>
> DR. BUSTA: But I hear very little\--it\'s mentioned, but I hear very
> little about research on glycidamide.
>
> DR. CANADY: I\'m sorry. The nomination to the NTP was for both
> glycidamide and acrylamide. And that was, again, recognizing the need
> to understand the mechanism for low-dose toxicity. And again, one of
> the main reasons for doing the NTP studies is to understand this
> transition from high-dose animal to low-dose human. I mean, that\'s a
> very important part of why we nominated acrylamide and glycidamide, so
> that we could do the mechanistic work, essentially.
>
> DR. BUSTA: Other questions around this point?
>
> As I look at\--we\'re working through here, toxicology moves on to
> methodologies.
>
> DR. GRAY: Could I just ask, what tab are you on? I\'d like to be
> following along.
>
> DR. BUSTA: Well, tab 5 is the general one, and then I keep flipping
> back to the presentations. Formation would be the next item in the
> draft plan, and we have presentations on formation by Lauren Jackson,
> who\'s here. She got here\--that\'s impressive.
>
> Questions and comments on formation?
>
> DR. FISCHER: Well, I would like to see\--there\'s two ways to look at
> this. I think I mentioned this the other day. We need information for
> the person who\'s doing the cooking at home on ways to prevent the
> formation of acrylamide. And of course industry needs to know the same
> kind of information so that can put out products that have less
> acrylamide, if it\'s needed.
>
> So who should do the research? Should the government do the research
> for the homeowner who is producing acrylamide at home, and industry do
> research to reduce acrylamide in their products, and not have the two
> talk to one another? That seems\--I imagine that could actually
> happen, but it seems crazy to have it happen.
>
> So I think the two groups, those doing research with federal money and
> those doing research with their own money on their own products, ought
> to be talking to one another and sharing information. And I know the
> FDA says that they have good collaborations with industry, but I would
> question whether they really have the way to get the information that
> they need from industry. For example, we just heard that they have not
> yet gotten the protocols from the studies being done by the chemical
> industry on acrylamide, after having asked for them. So I wonder
> whether there really is this good collaboration going on.
>
> So who should\--I think there should be not only a communication, but
> there should be some way that the information that industry knows
> about the formation of acrylamide be passed along to others so that it
> can be widely distributed. And I\'m not confident at this time, after
> just listening this short amount of time, that this is going to happen
> as smoothly as one would hope.
>
> DR. BUSTA: Well, I\'ve heard on several occasions now that JIFSAN will
> be the potential route of that. Dave\'s not here. Do we have any idea
> how much information is moving in that route now? Has that been well
> adopted? Does anybody\--
>
> DR. CANADY: It\'s just started.
>
> DR. BUSTA: It\'s just started. So it\'s hard to know what\--not
> everyone has raced to put their data in there immediately.
>
> DR. CANADY: It\'s hard to really respond to that. It\'s just a few
> weeks old.
>
> DR. LEE: As I understood from Dave Lineback, the Infonet is a
> worldwide linkage\--it\'s a World Wide Web site that will link to data
> that you have either posted on your own website, your company\'s
> website, your scientific website or wherever. So in that way, it is
> already in the public domain. But I did ask Dave yesterday what is
> going to motivate me if I have a company and I have a product that has
> acrylamide that\'s a thousandfold higher than everyone else\'s; am I
> going to put that on the Web? Okay? I don\'t think I will. And I think
> Dave agreed that a company is not motivated to do that.
>
> DR. BUSTA: But we heard NFPA, I think, offered to sanitize data? Is
> that an appropriate interpretation? It\'s blind data\--nice word.
> Blind data. Is NFPA involved in JIFSAN? Were they\-- Okay. So that\--
> okay, Henry just said that I\'ve got to get this on the record. Can I
> interpret the shaking of a head?
>
> DR. JARMAN: Yes. That\'s a yes.
>
> DR. BUSTA: Rick Jarman, NFPA, indicated that NFPA would blind
> information through them and put it onto JIFSAN if there was a concern
> about that. So that\'s at least one mechanism. Will JIFSAN accept
> blinded data? Terry?
>
> DR. TROXELL: Yes. They\'re willing. As Dave Lineback said yesterday
> with respect to the sampling data, that they expect companies to blind
> the data either through associations or lawyers and so on to put it
> in. And I think the same kind of mechanism would work for research on
> formation. I think more of the hindrances are that scientists or even
> companies may not want to give up initially what they have learned
> until they can, you know, see further that it\'s going to work or that
> they can publish a paper. I think that\'s where the FDA is going to
> keep working to encourage and jaw-bone everybody to, you know, do the
> right thing so we can get to the answers as quickly and efficiently as
> possible.
>
> Let me mention also that in addition to the JIFSAN mechanism, I mean,
> we do have our consortium, the National Center for Food Safety and
> Technology, that is a very mature organization. And that\'s
> where\--really, that\'s where our food processing research is
> conducted. We have a full division out there. And they have a very
> strong relationship with the industry and IIT, and they have a very
> strong program of food processing work. And this is clearly one of the
> priorities now for the NCFST, and I think that, you know, through
> Lauren and the staff out there, Dr. Sadler and IIT, there\'s going to
> be a\--there\'ll be a strength of focus to really get to that
> formation research. And we\'ll keep checking in with various\--whether
> it be industry and Europe and so on\--various people that are doing
> research. We\'ll\--I mean, you\'re right. We have to keep pushing to
> make sure we\'re gathering the information that people are developing.
>
> DR. ACHOLONU: I have a question. Yesterday, when we were discussing
> this formation of acrylamide, I made some statements with respect to
> each connection, the chemical process. And I read some materials where
> they talk about migration of acrylamide into food from plastic. And
> then, when you talk about formation of a chemical material, you have
> to come up with a simple equation that says from this\--if you add
> this to this, you get this. I think we should pay more attention to
> finding out how acrylamide is formed chemically, and go from there.
> Maybe the chemists or the biochemists should go into this. We have
> given it a name.
>
> I have read the material given. There are lots of\--some equations
> here, and they talk about acrylamide from Maillard reaction products.
> Still, that doesn\'t give what we are looking for when we talk about
> the chemistry of the material, the substance. Could we go more into
> this aspect? Because it said formation chemical mechanisms governing
> the production of acrylamide is unclear. I think FDA should spend some
> time trying to make this clear.
>
> This is the comment I want to make. When you say you\'re forming
> something, the public, the scientific world has to know how this
> material is formed chemically. Thank you.
>
> DR. BUSTA: Dr. Downer?
>
> DR. DOWNER: I wanted to just respond to Dr. Fischer\'s comment about
> the groups who should disseminate this information. And I think it
> should go beyond just the FDA and the industry, but look at some of
> the professional organizations like the American Dietetic Association,
> like the American College of Nutrition, and other home economics
> groups that would be a good conduit for this information to get to
> John Public, who\'s actually cooking at home.
>
> DR. BUSTA: Dr. Gray.
>
> DR. GRAY: Well, the first thing I want to say is that I do\--I think
> the formation research is very important. And I think even there,
> there are these opportunities perhaps to do some kind of mechanistic
> or empirical work, and would suggest, as I think others have, that,
> for example, trying to correlate levels of free asparagine in foods to
> levels of acrylamide is the kind of thing that can help build a link
> to understanding both formation and perhaps control.
>
> But I\'m using this as an opportunity because it\'s mentioned in this
> particular bullet point. It\'s the first place communication comes up.
> I want to follow on Dr. Downer\'s points. And I think this is a place
> where we really do need to be making some effort.
>
> I think one of the themes\--I participated in the Chicago meeting on
> acrylamide and risk communication. One of the themes there was an
> important fact that even follows from this Action Plan is we\'re going
> to be having information coming out continually over the next probably
> five years, and much of it is going to be led by exposure information.
> We\'re going to learn what foods it\'s in. It\'s already now on the
> World Wide Web. You can look and see if it\'s in your favorite
> breakfast cereal. And we\'re just going to have more and more of that.
> We\'re going to have the NHANES data finding the material in blood, of
> you, me, our kids. These are going to be communication challenges
> that, if we think about them now, we\'ll do a better job of dealing
> with them.
>
> And for that, I want to suggest that FDA take advantage of its own
> strength in consumer research, that it work with these
> industries\--these food industries do an awful lot of consumer
> research as well; there\'s a lot of knowledge there. How can we the
> message that is appropriate? And I would suggest that FDA\'s message
> so far has been very, very good, including\--I want to recognize their
> recognition of the potential for tradeoffs here, that there are no
> simple solutions to this. How can we get that message to people,
> whether it\'s leveraging the professional organizations, physicians,
> people who interact with people and have some moral\--not moral,
> authoritative\--an authoritative voice with them. Don\'t attribute too
> much. Or if these are things that have to be done directly. If we\'re
> working with the news media, how do we make sure that these messages
> are well done?
>
> And I think one of the things we have to think about is there\'s a big
> world out there that studies risk communication. When we\'ve got a
> strong consumer component, including the fact that you and I are
> making acrylamide at home when we make toast and we make bread, we
> have to think very carefully about how we\'re going to communicate
> those things.
>
> And then finally, I guess, but along those same lines, one thing that
> I\'ve found, I didn\'t\--well, it didn\'t sit quite right with me in
> the Action Plan\--is a fundamental assertion right off the bat that
> what we want to do is reduce acrylamide levels. I think there is
> still\--we\'re recognizing that there is scientific uncertainty;
> we\'re not sure the levels at which this is a problem. And I think
> even if the Action Plan recognizes it, there\'s some uncertainty.
> We\'ve got to learn something before we even think it\'s good to do
> that\--that helps with communication. If we have an Action Plan that
> says get as much of it out as we can today, and then say don\'t worry,
> eat your regular balanced diet, those mixed messages make it a lot
> harder to communicate.
>
> DR. BUSTA: Dr. Lee.
>
> DR. LEE: I\'m glad that Dr. Gray and Dr. Downer introduced the idea of
> communication. And I think it might be appropriate, certainly not
> today, but perhaps FDA or some other body would like to make a
> determination whether or not acrylamide is a natural substance or it
> is a manmade substance, or perhaps it\'s both. Because that, of
> course, has a lot of implications when it comes to communication and
> it also has a lot of implications when it comes to litigation.
>
> DR. DOWNER: That was going to be my point.
>
> DR. ACHOLONU: What is this idea of its migration? Why are some
> documents, some publications making reference to acrylamide migrating
> into food? Could somebody please explain that to me? Because in the
> biological sense, things that migrate are under their own locomotion.
> Is the migration by active transport or by passive transport? How is
> it occurring? How does it migrate from plastic into the food? Would
> somebody please explain that to me?
>
> DR. BUSTA: Dr. Canady, do you want to\--
>
> DR. CANADY: I think the reference is being made to prior FDA decisions
> about food contact materials\--the wrappings, the packagings for
> foods. The situation we\'re talking about today refers to incurred
> acrylamide through cooking. In other words, you cook the food\--it
> doesn\'t migrate to the food during the cooking process, rather it\'s
> created during the normal cooking process. So the issue of migration
> affects our current situation in the sense that it talks about how
> acrylamide might move out of the food that\'s been caused to have the
> acrylamide in it through the normal cooking process.
>
> DR. ACHOLONU: But you know it\'s in the literature, right? Apart from
> what you gave us, check in on acrylamide. I see it used constantly,
> \"migrating into food.\"
>
> DR. BUSTA: I have a question on formation. Some of that data are
> really straight\--I mean they\'re just so obvious, they really hit you
> in the face with the presence of glucose and asparagine, I mean,
> produce all kinds of acrylamide. When I look at that, I sort of say
> all we have to do is apply that. Is there still\--am I simplifying
> that too much? I look at some of the materials that Dr. Jackson
> presented, and it\'s sort of, well, if you\'ve got a free reducing
> sugar and asparagine and you heat it up, you\'re going to get
> acrylamide. I mean, it seems just right there, and I don\'t\--what are
> the big questions on formation?
>
> DR. FULLER: You\'re asking him how much more work is needed.
>
> DR. BUSTA: Yeah, it seems I\--or is it\--are we going to look into
> food systems or whatever, but, I mean, it seems like it\'s answered;
> it\'s there.
>
> DR. DOWNER: But is it just glucose and asparagine in the absence of
> the temperature and the exposure?
>
> DR. BUSTA: My understanding is it\'s a reducing sugar and asparagine,
> maybe cystine, and heat. And we get acrylamide. Is that\--
>
> DR. FISCHER: I don\'t think that\'s true, is it? I don\'t think this
> is true, because they say\--they\'ve told us that if you microwave the
> products, you don\'t get it. So that\'s heat and temperature\--
>
> DR. BUSTA: It\'s not hot.
>
> DR. FISCHER: Sure it\'s hot.
>
> DR. BUSTA: Not hot enough.
>
> DR. FISHER: It\'s hot. Put your finger in a piece of bread\--
>
> DR. DOWNER: It\'s exposure time.
>
> DR. BUSTA: It\'s only 100 C.
>
> DR. HOTCHKISS: Never above 100 C.
>
> DR. FISCHER: Never above 100 C?
>
> DR. HOTCHKISS: Only at the surface. You can\'t raise the temperature
> until you get rid of the water.
>
> DR. LEE: Well, you can pop popcorn at a lot higher temperature.
>
> DR. FISCHER: It seems to me there was something with the browning
> reaction.
>
> DR. LEE: Those data are incomplete. I don\'t know if microwave popcorn
> has acrylamide or not.
>
> DR. FISCHER: It think it\'s in the list.
>
> DR. LEE: All right, let me look at the list.
>
> DR. BUSTA: Dr. Troxell?
>
> DR. TROXELL: Thank you. Well, if it\--maybe you should, if it\'s
> obvious, and professor emeritus, I would go back and figure out how we
> can do it. We\'re all stumped.
>
> You know, this is you got components of living food materials,
> potatoes and so on, how do you\--you know, you could eliminate this if
> you could eliminate the sugar and the free asparagine. Well, I\'m not
> sure we have food by eliminating those things, or I\'m not sure we
> have tasty food by eliminating sugar. So the question is, is how to
> maybe reduce the levels in key things so we\'re\--and then\--or how to
> target inhibition of a reaction. Because there\'s an extremely complex
> series of reactions.
>
> So it\'s one thing to say we understand the mechanism, and it\'s
> another thing to\--a totally different world to try to capitalize on
> that which everybody is feverishly working on now. They\'re feverishly
> working on capitalizing this, to prevent the formation or reduce the
> formation in foods. And as far as the temperature, it doesn\'t form
> below about 120 C, so you need to get at least the surface temperature
> of the food above 120 and probably substantially above that to really
> start pushing the reaction along.
>
> DR. BUSTA: In regard to microwaves, that\'s one of the problems
> that\'s one of the problems. It doesn\'t brown. And so you\--
>
> But what I\'m trying to get to is we\'re fairly knowledgeable about
> the formation mechanisms, and it\'s the control of the formation and
> modification of formation that is the research interest. Is that\--I
> mean, Stadler published this one graph that seems so dramatic that it
> seems like we have a pretty good idea about mechanisms.
>
> DR. FISCHER: I saw there\'s some question marks in the scheme. I
> don\'t understand, and apparently no one else does either, why
> there\'s such variability in the formation of acrylamide, that we\'ve
> seen the data that nobody understands. That tells me, anyway, that
> there is some factor, or factors, involved that we don\'t know about
> that\'s causing this variability. Sometimes in the same batch of
> products you\'ve got pieces that are much higher than others. So
> there\'s something unknown.
>
> DR. BUSTA: Dr. Jackson, then Dr. Lee.
>
> DR. JACKSON: I think when you look at the data, you\'re seeing the
> variability. There are two sources of variation there, one with the
> processing, the other with the raw material. If you look at a batch of
> potatoes\--and I haven\'t tested this myself, but from when I\'ve
> talked to the people in the potato industry, you grab one potato out
> of a bag, they\'re going to be very different even though they\'re
> stored the same. They\'re a living plant. And you\'re going to have
> variation in the free asparagine and the sugar levels.
>
> And I don\'t know how you\'re going to eliminate this problem\--I
> mean, Ken Lee talked about this\--I don\'t think you\'re going to be
> able to eliminate the acrylamide levels to zero, because you can\'t
> eliminate asparagine from foods. I mean, that\'s an amino acid
> required for the structure and the plant.
>
> So I think what\'s going on, at least from when I\'ve talked to the
> people that are doing the potato\--you know, the fries\--what they\'re
> trying to do is look into storage of potatoes and trying to reduce
> levels by storing the potatoes and testing, you know, different
> conditions where they can store and lower the levels of free
> asparagine and sugars that way. Another way that they\'re looking into
> this also is looking into different variety of potatoes that might
> have lower free asparagine as well or free reducing sugars.
>
> But processing, I think, is the only controllable way, I think, that
> we can look at this problem as an agency. I don\'t know how we can do
> it any other way.
>
> DR. BUSTA: And that\'s\--we have a fairly good idea of the formation;
> it\'s the control and the variability and the other things influencing
> that formation that are the real questions.
>
> DR. JACKSON: I think one of the areas that we\'re going to research is
> to separate and determine where the variability is, if it\'s in the
> process and in the raw material, because\--I didn\'t include the data
> in the presentation yesterday, but when we did fry three different
> batches of potatoes, same temperature\--they were all stored the
> same\--the three batches, no matter how well I tried to control the
> temperature in that oil, we got very different levels. Especially when
> you got to the higher temperatures, where you got probably more
> browning and things going on, it was very difficult to control the
> acrylamide. You\'d get tight\--you know, the replicates were very
> different.
>
> So there\'s something going on. And that\'s why I\--it points to using
> model systems, because you can control the raw material going in and
> then you can see if there\'s variability in the process. And that\'s
> what we intend to do as well.
>
> DR. BUSTA: Dr. Lee.
>
> DR. LEE: Thanks, Lauren, for the comment. You know I have very high
> confidence in you as a scientist as well as your colleagues in
> Argo-Summit.
>
> And formation and control, I think, are the same argument, because if
> you know how it forms, you know how to control it. But I would venture
> a guess, just speculate, that the industry is going to be the first
> people on the block to understand how to control this. Because they
> have far greater vested interest in controlling it, and they also have
> a much more controllable process. The consistency of manufacture is
> such that you\'re in control of almost everything you can possibly
> measure.
>
> So again, I would just put in a plug here that we make it easy and in
> industry\'s best interest to share both their data on occurrence and
> process variables that control. Now, when you\'re sharing process
> variables, you\'re sharing brand identify, so this has to be done in a
> double-blind fashion, if at all possible.
>
> And then a quick segue\--two people have mentioned microwave. You
> know, if we have data on our website now, 157-181 micrograms per
> milligram to microwave popcorn. So, you know, it\'s not supported that
> microwaving is going to give you an acrylamide-free product.
>
> DR. BUSTA: Dr. Kuzminski.
>
> DR. KUZMINSKI: Just an observation just to follow up on some of the
> discussion.
>
> I think that this problem creates a number of opportunities and
> challenges, challenges for the trade associations, if you will. When a
> company\--just from experience, when a company is asked to share
> processing information, my experience is\--in terms of process
> variables, my experience is that that\'s proprietary information.
> It\'s part of the formulation to produce that finished product.
>
> So the challenge, as I see it, to\--and yet we have a situation here
> where we know that it exists in finished products, we know that
> there\'s variability in the raw materials going into that finished
> product, yet we know that that process to produce that finished
> product creates conditions that produces acrylamide. So the challenge,
> I think, to industry is to\--and to the trade associations that
> represent them, is to figure out a way whereby valid information can
> come forward that would help with the levels in finished product. And
> I suspect it will be a very gut-wrenching exercise for that body of
> society to come up with a way to come forward with process variables.
>
> The conundrum for a company, as I look at it, is that they have a
> product that\'s out there with an established market share, whatever
> that share is. And that product is achieving that share through a
> number of means and also because it has a certain product image to the
> consumer. And that image to the consumer is responsible for some of
> its success. Changing the process to change that image is the big
> challenge to a company, to the industry.
>
> So it\'s not an easy problem for them to solve. I\'d like the
> committee to fully realize that, in terms of coming to grips with
> sharing that kind of process information. Not an easy problem at all.
> But it\'s a challenge to the trade associations and to industry to
> come to grips with it.
>
> DR. BUSTA: Dr. Whitaker.
>
> DR. WHITAKER: Lauren, I would just like to comment that there is
> another source of uncertainty, and that\'s in the acrylamide test
> procedure. And this is what I was trying to get to yesterday with
> Steve Musser.
>
> I suspect the greatest variability would be from potato to potato, but
> your sample preparation and your analytical components of your test
> procedure also contribute to the uncertainty. But my guess is those
> lower two components, the sample preparation and the analytical, are
> small compared to potato-to-potato. But I think it has to be
> acknowledged or understood that that\'s also there and characterized.
>
> DR. BUSTA: Are there any other points?
>
> DR. JACKSON: Actually, I wanted to add something. We talked about
> potatoes and grain products where the asparagine-sugar mechanism\'s
> probably the main mechanism. Coffee we didn\'t talk about very much.
> Coffee\--there might be some other mechanisms going on, mainly because
> you go to very high temperatures, you know, over 500 Fahrenheit, 250
> degrees C. So there might be some other mechanisms going on there, and
> that needs to be fleshed out as well.
>
> DR. BUSTA: Dr. Lee.
>
> DR. LEE: Lauren, it was you that showed data that at very high
> temperatures acrylamide contents were lower.
>
> DR. JACKSON: That\'s right.
>
> DR. LEE: So you\'re speculating that there\'s another mechanism there?
> Or do you have any clues as to what\'s going on?
>
> DR. JACKSON: We don\'t really know. I know from what the Nestle
> people\--we had this meeting out in Chicago. Stadler from Nestle was
> talking about coffee. And what they do, is they measure the different
> roasts of coffee from the light roasts all the way to the dark roasts.
> So they measured the acrylamide levels from light roasts to dark
> roasts, and they didn\'t find any differences. Which suggests, maybe,
> there\'s some type of degradation going on as well as formation. You
> know, you\--we don\'t really know.
>
> So that needs to be understood, too. The formation as well as
> degradation. I showed there was a dip in the graph there. That really
> needs to be understood as well.
>
> DR. ACHOLONU: This glucose and asparagine reaction, are you using it
> as an example of a way acrylamide can be formed, or is it the general
> way it is formed every time, every time?
>
> DR. JACKSON: According to the research we\'ve seen so far, that is the
> main mechanism. I mean, if you look at the yields of acrylamide\--if
> you look at the yield of acrylamide in a model system, Moltram and his
> colleagues, when he did his reactions, .3 percent of the asparagine
> actually became converted to acrylamide. If you look in a food that\'s
> fried, you get roughly the same percent conversion. So they kind of
> match up there. But if you look at other amino acids\--methionine, the
> other ones, cystine\--the amounts, the yields you get from those amino
> acids just don\'t compare. They just don\'t\--couldn\'t account for
> all the acrylamide that you do form in food.
>
> DR. ACHOLONU: So if you fry french fries, you are assuming that you
> have asparagine there and you have glucose\--of course we know that
> french fries has glucose\--and that any kind of combination that comes
> up, and we say acrylamide is in this food after it was fried or baked,
> that this is the very process that took place chemically? Is this what
> you\'re saying.
>
> DR. JACKSON: I understood your question. If the french fry, the raw
> material, has asparagine and glucose, you can pretty much bet, if you
> get the temperature to the right temperature, you\'re going to have
> acrylamide in that food. You saw that one piece in one of the slides,
> the Procter & Gamble people depleted all of the asparagine, or most of
> the asparagine in the potato, fried it, and then didn\'t form
> acrylamide. So that\--I think that\'s pretty good evidence there that
> asparagine is the key amino acid in acrylamide formation, at least in
> the potato, and in grain probably as well.
>
> DR. ACHOLONU: Would you assume that there are other ways that we
> don\'t know at this present time?
>
> DR. JACKSON: There could\--yeah, there very well could be. There very
> well could be.
>
> DR. BUSTA: If you notice, there\'s an asterisk that says the Chairman
> has the \"perogative\" of calling a break.
>
> DR. LEE: PRE-rogative.
>
> DR. BUSTA: Whatever. I would just like to make one comment\--again,
> taking my opportunity\--and reiterate what Dr. Gray said earlier.
> We\'ve just been discussing about getting rid of the acrylamide,
> controlling acrylamide, it being there, et cetera, and we\'re really
> not sure that it\'s a problem yet. I mean, we really don\'t know if
> it\'s a problem in food. And I think\--I have to keep reminding myself
> of that. We\'re so enthusiastic to reduce it, measure it, check it,
> get rid of it, and even talk zero levels and we have no idea if it\'s
> a problem.
>
> Now, if none of you wish to attack me on that statement, we will take
> a 15-minute break.
>
> DR. FISCHER: I do want to ask you whether you\'re saying that we
> shouldn\'t do any research on formation until we know there\'s a
> problem.
>
> DR. BUSTA: No, no. I just\--I think we should not declare it a
> problem\--
>
> DR. LEE: Not a human health hazard, right.
>
> DR. BUSTA: \--a human health hazard until we\'ve got a little better
> information.
>
> DR. LEE: It is a problem, it\'s just not\--
>
> DR. FISCHER: It is a hazard, I think. The definition of a hazard is
> it\'s something that causes a\--that has a potential for harm.
>
> DR. LEE: Right.
>
> DR. FISCHER: And this is a hazard. It may not be a\--
>
> DR. BUSTA: May not be a risk?
>
> DR. FISCHER: Yeah, may not be a risk, but it\'s a potential.
>
> DR. LEE: Okay.
>
> DR. BUSTA: With that, we need a break.
>
> \[Recess.\]
>
> DR. BUSTA: If there\'s no more comment about formation\--
>
> DR. FULLER: One.
>
> DR. BUSTA: Okay, we\'ve got a comment on formation here.
>
> DR. FULLER: Thank you. I just want to sort of go back to a point we
> were talking as we ended just a minute ago, about message and the
> point that Dr. Gray brought up about issues concerning\--perhaps the
> group looking at the message that we want to say or comment back to
> FDA on, and that was getting to the point on reducing the amount of
> acrylamide prior to clear knowledge of a risk or a significant hazard,
> significant risk.
>
> And I think, personally, I did not\--I don\'t think you were, Dr.
> Gray\--and correct me\--I don\'t think you were saying to ignore this
> as a potential risk, but just to, in that message, clarify; or at
> least I would suggest that the committee just clarify that the
> significance of a risk is unknown at this point, not\--and there is
> some concern about stressing too greatly reducing a risk with an
> assumption that\--or reducing, excuse me, reducing exposure based on
> an assumption that there is significant risk when, indeed, we A)
> don\'t know that there is a significant risk. There is certainly
> calculable or theoretical\--there\'s potential for it. I\'m not saying
> this very well.
>
> But I think we want to\--does the committee want to address that issue
> and more clearly\--or clarify that issue?
>
> I\'m getting a bunch of blanks.
>
> DR. FISCHER: Well, I think you\'re talking about the last bullet here,
> Information\--develop/foster public-private partnership, gather
> scientific information for assessing a human\-- No, you\'re not.
> Excuse me. Educate Consumers.
>
> DR. BUSTA: The second-to-last one.
>
> DR. FISCHER: Yeah, second-to-last one.
>
> DR. FULLER: Yeah, it came up at the end of our discussion just a
> moment ago. And I don\'t think\--I think we need to be careful, and
> maybe we should just hold this off till that bullet, but I just think
> we need to be careful about the message that we send to the consumer.
> And we can address it at that point, if that would be more
> appropriate. I\'ll leave it to our Chair to\--
>
> DR. BUSTA: Well, we\'ll be there shortly.
>
> DR. FULLER: Okay. We\'ll do it then.
>
> DR. BUSTA: It\'s my thought that some of you may get antsy before 3
> o\'clock. So if we can sort of look at moving reasonably fast and
> maybe even having a relatively short lunch and come back, if that\'s
> all right with you. If it\'s all right with you, we\'ll get back to
> the education component, as I see it, on the next page. If there\'s no
> other urgency on formation, or discussion\--and we\'re all going to be
> talking about this one more time, when we make our statements.
>
> Methodologies is basically the next item. Is there any comment about
> methods, current methods, evaluating the screening? Any discussion or
> need for clarification?
>
> DR. FISCHER: Well, I can say we discussed a little bit, maybe it was
> at dinner, about how difficult it might be\--and I think it was
> mentioned here this morning\--how difficult it might be to develop an
> immunoassay-based screening effort.
>
> DR. BUSTA: Yeah, that was mentioned this morning.
>
> DR. FISCHER: It would be great to be able to do that because it would
> be so fast and so on. But I\'m wondering whether we really know we
> have the information to eliminate that possibility altogether. For
> example, you can use an assay based on antibodies or you can use an
> assay based on a receptor for acrylamide in cells. I don\'t know
> whether we know whether there is a receptor that\'s involved for
> causing neurotoxicity or whatever else, but if you had the receptor,
> then you could base an assay on that receptor.
>
> We don\'t know whether acrylamide is actively transported across
> membranes, or at least I haven\'t read of that. I may have missed it.
> But if it\'s actively transported, there\'s another receptor and
> possibility for a specific binding for an assay.
>
> So I guess what I\'m saying is that I wouldn\'t throw away the
> possibility of going the routes of that type of an assay. It\'s worth
> investigating to see whether it\'s possible.
>
> DR. BUSTA: It\'s my understanding that FDA will be evaluating
> screening methodologies, not necessarily developing them. Is that
> correct? Are you developing rapid, quick, and fast, easy methods?
>
> DR. TROXELL: One of our groups is at this point looking into an LCUV
> method. And if the committee thinks that we should looking into other
> quick assays such as\--see if there\'s a possibility for immunoassay
> or something, then we would carry that advice back and see, you know,
> if we should look into that further.
>
> DR. BUSTA: Dr. Hotchkiss?
>
> DR. HOTCHKISS: In the past history of these kinds of contaminants, the
> agency and others have, I think, very logically developed two levels,
> if you will, of analysis. One is a screening or presumptive analysis;
> the other is a confirmatory analysis typically used more in a
> regulatory sense. The agency, I think, has to date developed a
> first-rate confirmatory analysis for which I think there will be no
> argument with other than the cost.
>
> My reading of the literature, however, is that there already is a what
> appears to be a relatively quick and nice screening method based on
> bromination and electron capture or gas chromatography. And I suppose
> I\'ve, given what I read, urged the agency to round-robin, maybe
> through AOAC, that procedure because EC detection, because of the
> pesticide issues in food, is very widely available, routinely done by
> hundreds and hundreds of labs around the world and thousands of
> samples per day. It seems to me that this method would give a very
> quick screening method that could be in place in probably a matter of
> weeks if people really wanted to do it.
>
> DR. BUSTA: Any other comments on methods? Let\'s move forward, then,
> to Meetings and Collaborative Projects in the draft Action Plan. There
> are a number of bullets on here. Are there any comments on that area?
> That\'s on page 4 and 5 of the draft Action Plan, under tab 5.
>
> DR. DOWNER: I\'d just like to see we include the nutrition
> professional and academic groups included in this, and home economics
> groups, particularly for the consumer\'s interest.
>
> DR. BUSTA: Okay. I would think when you include academics, you\'d
> include, for example, the extension service that, hopefully, still has
> a connection with the consumer.
>
> Any other comments on the meetings, public meetings, subcommittee
> meetings of this committee?
>
> DR. HOTCHKISS: Just to congratulate FDA, who, as these issues have
> unfolded in the past, has not always been so cognizant of the
> importance of bringing a variety of stake-holders into the picture.
> This seems to be a very good trend, very good move.
>
> DR. BUSTA: Well, let\'s move on to Consumer Messages. And we had a
> presentation by Dr. Acheson. And we have these consumer messages that
> we\'re\--Dr. Downer and then Dr. Fuller.
>
> DR. DOWNER: My major concern with the consumer message as it\'s
> outlined, and particularly in our presentation yesterday, was it gave
> the impression that eating a balanced diet may have a protective
> factor against acrylamide. And we don\'t know this. Because he kept
> saying eat a balanced diet, one with fruits and vegetables. And so
> what I quickly got from it was if I\'m eating a balanced\--whatever
> \"balanced\" is\--I\'d really put it as the term \"healthful,\"
> healthful diet. We need to make that clear, because it\'s quite
> confounding.
>
> As I said before, it appears to me that if we\'re eating a balanced or
> healthful diet that it gives a person\--that\'s a protective factor
> against acrylamide or what may come with it. If we\'re going to put
> this and couch this in a message for the consumer, I hope that it will
> be clear, with something\--for example, saying \"In addition to eating
> a healthful diet and handling food safely,\" make sure that you do
> so-and-so. I don\'t want to see one message replacing the other or
> causing additional confusion.
>
> DR. BUSTA: Dr. Fuller.
>
> DR. FULLER: Let me come back to that. I want to compose my thoughts a
> little bit more coherently, particularly in light of that comment. So
> let me come back to that in just a minute. I think Dr. Gray is
> interested in a comment.
>
> DR. GRAY: Well, actually my comment is slightly different, but it\'s
> sort of a communication idea that goes to Dr. Downer\'s comment as
> well. I wonder if we could, or whether FDA could, using its
> exposure-assessment models and such, compare sort of a total-diet
> survey, what-do-people-really-eat diet to a food-pyramid healthful
> diet, in terms of acrylamide content, just as another way to show
> people that if you follow this advice that says eat a balanced,
> healthful diet with a variety of foods, in addition to all the other
> good things it does, your acrylamide exposure will be lower as well.
>
> DR. DOWNER: May I respond? The problem with that is we recommend that
> you eat six to 11 servings from the breads and cereal group. That\'s
> the big group. And that\'s the group where acrylamide is most
> contained in meal preparation. So again, you see how the message
> has\--
>
> DR. GRAY: Well, it may well be that I\'m wrong that doing that would
> make a difference. But it also\--part of it is which choices are made
> even within those groups. And I\'m sure that the American Dietetic
> Association or someone like that has particular recommendations within
> those groups that may be different than what people are actually
> doing.
>
> DR. DOWNER: Well, the government actually\--the FDA and USDA, they\'re
> the ones who put out the food guide pyramid. And I think my\--it\'s
> not the food so much alone, but how it\'s prepared, is what we\'re
> hearing now. And so that\--the message will be meal preparation rather
> than the food guide pyramid. I think if we put the food guide pyramid
> and put it in place with the acrylamide message, we may end up having
> a hornet\'s nest. So that\'s\--we have to be careful as well.
>
> DR. BUSTA: Dr. Lee?
>
> DR. LEE: This is kind of a segue from the prior discussion of
> meetings. You know, every time you call a meeting or have some kind of
> action, the media watches. So each one of these meetings represents
> some opportunity to communicate to the consumer. The release of the
> information on the website triggered something on the CBS News this
> morning about acrylamide, which\--unfortunately \"eat a balanced
> diet\" is not news. We know that. If it bleeds, it leads, okay.
> Usually news is negative, it\'s bad. So the news, of course, is, \"Oh,
> my God, did you know this stuff was in baby food\" or whatever. So I
> don\'t know if there\'s a conscious effort on anybody\'s part to work
> with media or to control the net impression that people get from all
> this news on acrylamide.
>
> But I\'m kind of uncomfortable going forward to the consumer with a
> message when we sit here and say, look, we really don\'t even know if
> this stuff is a human risk, we don\'t know how to control it, there\'s
> a lot of unknowns. So, yes, one should always be cognizant of the
> consumer message, but I just don\'t know what that message needs to be
> at this point.
>
> DR. BUSTA: Dr. Fuller.
>
> DR. FULLER: Well, that does help. And I guess I\--my personal feeling
> is that the message does need to be couched carefully. We have
> information this is a rodent carcinogen, we don\'t know perhaps the
> significance of the rodent data to human exposure and human risk. But
> we also can\'t say that there is not\--that we can go la-di-da along
> our merry way and forget it.
>
> I do have more confidence, perhaps, than some in a carefully crafted
> message to the public that says very clearly here\'s what we do know,
> here\'s what we don\'t know, here are the areas of uncertainty. And
> yes, I realize that this is a complicated message, but I disagree that
> your message always has to be a sound bite. And I think you can
> carefully craft that message and give information to the consumer, or
> at least information that will point the consumer to where they can
> get good, reliable information in a form they can understand, and
> point to, okay, yeah, there\'s something here; no, I don\'t need to
> give up potatoes from my diet, but perhaps I should consider not
> having as\--maybe I should not go with the french fries every day for
> lunch, but perhaps I should go with something different\--potato salad
> rather than french fries.
>
> So I think we can carefully craft that message, and I actually think
> FDA is doing a pretty good job in that thus far. I don\'t think they
> have given the message that says stop, halt, you\'ve got something in
> the diet that is of immense risk. They are saying that we are looking
> at ways to reduce this exposure. The only part that I haven\'t heard
> is\--perhaps that I might emphasize a little bit stronger\--is the
> uncertainty of the information to date. But I don\'t find tremendous
> fault with the message thus far.
>
> DR. BUSTA: Dr. Hotchkiss.
>
> DR. HOTCHKISS: Yes, I have a question for Dr. Acheson or whoever may
> know about this. Has the agency put together any communications, for
> example with the consumer safety officers in the regional offices, or
> is there anything to be done in the FDA Consumer or other
> agency-controlled public vehicles for providing information on this
> topic?
>
> DR. ACHESON: What we\'re currently doing is developing a talk paper to
> try to address some of those issues to get that message out.
>
> DR. HOTCHKISS: Let me tell you the reason I ask that question. I
> presume all of you have seen this morning\'s USDA\--Freudian
> slip\--USA Today. You haven\'t seen it? There\'s a relatively
> significant article that names brands and products and so forth based
> on yesterday\'s discussion in this meeting\--quotes agency officials
> by name and so forth in this morning\'s paper. What that does, as you
> all well know, is leaves the agency in a position of responding, of
> reacting to the media and others. And if you read that article, as we
> did this morning, I think you\'ll find it not to be a very good
> representation of what went on in this room yesterday\--at least in my
> view it wasn\'t.
>
> We in New York State have a very efficient system of getting consumer
> responses back through our county agents. And I know what\'s going to
> happen when I get back\--assuming I do sometime in the future. When I
> do get back, we are going to have\--we have a system for every
> consumer inquiry to a county cooperative extension agent gets back to
> the university, and very specific. I know, based on what\'s in that
> article, we will have a series of them, questions, for which we\'ll
> quickly put something together and put it back. The problem with that
> is that this puts us, and more importantly the agency, on the defense,
> rather than being proactive to say this is what we know, this is what
> we don\'t know, the kinds of things you\'re going to do in putting it
> out.
>
> I think the major consumer concern as we get these back through the
> county agencies is not specifically Frito Lay potato chips versus
> other things\--it is when they read it in the paper\--but what they
> really want to know is, is anybody at home on the issue, what are they
> doing about it, what is the game plan, are they looking at this, what
> do we know, what do we don\'t know? They\'re interested just in
> knowing that somebody\'s there taking care of us and trying to
> straighten it out. And that means that then the press response to FDA
> or other authorities rather than FDA responding reactively.
>
> DR. BUSTA: Dr. Troxell.
>
> DR. TROXELL: Thank you, Terry. The talk points have gone to a public
> affairs officers, so when they see the questions they\'ll be able to
> address them. And secondly, there is an article in draft for the FDA
> Consumer, so there\'ll be something in that venue also.
>
> DR. BUSTA: You said what kind of paper is being prepared?
>
> DR. TROXELL: There\'s a talk paper to give the public affairs
> specialists a basis to field questions on this issue and the survey.
> That has gone out. And there\'s also an article that is, you know,
> close to final that is going to be published our FDA Consumer in the
> next month or two on acrylamide and the actions we\'re taking, that
> we\'re addressing the research needs, and also will have the consumer
> message in.
>
> DR. HOTCHKISS: Will that talk paper go out to the regional consumer
> affairs officers?
>
> DR. TROXELL: Yes\--our public affairs officers is what they\'re called
> now.
>
> DR. BUSTA: Dr. Acholonu.
>
> DR. ACHOLONU: I just want to amplify what Dr. Fuller said. I remember
> the last person I spoke to yesterday, Mr. Stier. He took time to
> emphasize the fact that we must be careful about what we put out to
> the public, that there has been no correlation so far between
> acrylamide and human beings. I do know that an ounce of prevention is
> better than a pound of cure. The FDA is doing the right thing to make
> the public know about its concern about acrylamide. So every effort
> should be made to publicize this as widely as possible, possibly by
> radio and TV and any other means.
>
> But the message must contain the fact very clearly that so far there
> is no connection known between the effect of acrylamide on mice and
> rats and the effect of acrylamide on human beings, that study is still
> going on, and maybe in the due course of time we will find out if it
> is carcinogenic to man.
>
> So that\'s the point I wanted to make. As you put out the information,
> the message to people, make it clear that it is still in the realm of
> probability, of possibility, that it is not a foregone conclusion that
> acrylamide is carcinogenic to man.
>
> DR. BUSTA: Dr. Lee.
>
> DR. LEE: I\'d like to agree very much with Dr. Hotchkiss in that the
> message that somebody\'s at home, somebody\'s watching the issue,
> we\'re taking care of it, we\'re on top of it can very well be the
> message here with acrylamide. Because I think the agency\'s doing a
> great job of being very proactive in looking at this from every
> possible angle.
>
> And therein also lies an opportunity. Joe mentioned the county and the
> extension apparatus. Every state in the nation has extension
> capability, and I would think that there\'s an opportunity here as a
> generic template to extend the FDA\'s reach by interfacing effectively
> with land grant university campuses that have extension.
>
> DR. BUSTA: Even if those are USDA. Dr. Kuzminski.
>
> DR. LEE: Agency rivalries aside.
>
> DR. KUZMINSKI: The tab 5 that we\'re looking at, it\'s a draft Action
> Plan. And I think personally that the agency has done a very good job
> of trying to manage the scientific information from around the world
> and trying to funnel it through vehicles that exist to make that
> information available. And because it\'s a draft action plan, it\'s a
> plan in process, I guess. I think number 7, as it reads\--Consumer
> Messages as it now reads in our binders, to me sounds a little weak, a
> little wishy-washy. And it could be embellished by some of the
> comments that have been made today in terms of more specifics of
> we\'re doing this talk paper, whatever they want to call it, articles
> will be published in the FDA Consumer and other documents.
>
> Because sometimes in reading this kind of material and listening to
> the amount of work that\'s going on, maybe this was your point,
> Marion\--I know we talked about it yesterday\--how much knowledge is
> enough knowledge before you come out with some sort of proclamation or
> a position or a preliminary risk assessment? I know this is a
> difficult area for the agency to deal with, a preliminary kind of
> basis, but in order to continue the fine managerial leadership they
> shown on the scientific and technical basis, I think that same kind of
> leadership should be exercised on the consumer-communication basis.
>
> DR. FULLER: I\'ll add just one more comment, and that is perhaps part
> of the message needs to be that the message\--acknowledge up front
> that the message is going to change as more information comes in. And
> I think we sometimes fail to say that up front. It\'s always an
> underlying assumption, but having been through some shorter-term,
> high-profile incidents in which the message was having to change on a
> fairly short-term basis, my personal experience has just been if you
> are very up-front with what you know, what you don\'t know, you can
> say \"this is what we think at this point in time, there are problems
> with what we think, here are the problem areas, and this will change
> as these studies come in.\" And it may go \"our concern may increase
> or in fact may decrease, depending on the data that are generated.\"
> And you said it very well. Thank you.
>
> DR. BUSTA: All right. The only other item on the draft document that
> we haven\'t discussed is Regulatory Options. Does somebody have some
> burning feeling on that? To me, that\'s policy and\--
>
> Oh, Kenny pointed out, thank you, we went running quickly past
> Exposure. And we discussed that and it\'s not highly identified as a
> heading. Are there any points or discussion on exposure that you wish
> to talk about before we go into the questions? We\'ve been alluding to
> exposure a lot, as I see many of these comments on education, et
> cetera. And earlier, I think, Dr. Gray\--well, a number of the
> individuals have commented on real-diet intakes and things of that
> type on exposure. Are there any other discussions on exposure, or
> questions about exposure?
>
> DR. LEE: Where is Exposure in this outline?
>
> DR. BUSTA: It\'s in\--some in Toxicology and in Testing, Total Diet
> Study, and\--
>
> DR. FISCHER: There\'s a section called Testing of Food.
>
> DR. BUSTA: In Testing. Under Testing of Food, under Actions, there\'s
> Total Diet Study in that.
>
> DR. HOTCHKISS: Dr. Busta?
>
> DR. BUSTA: Yes.
>
> DR. HOTCHKISS: Yesterday, during the\--before I got here, then
> yesterday during the presentations, I thought, well, gee, maybe
> Exposure should be taken out as a major goal, as a section unto
> itself. But I think that\'s really in some ways redundant, they\'re
> not going to do all these other things unless they do exposure; really
> is a matter of choice of how you want to emphasize it. Obviously\--at
> least, I think, to virtually everybody in this room\--it\'s obvious
> that exposure is a key element here. If you want to make it obvious to
> those who it might not otherwise be obvious, then you could put it
> out. But it is under Major Goals. It is the first bullet under Major
> Goals, and so\--and when the analytical discussion occurred yesterday,
> I think right at the front it was said that the reason for doing this
> analytical work is so that we can accurately assess exposure. So
> certainly this has not escaped the notice of the agency that this is
> primary. On the other hand, if this is a public document and someone
> were going to make it more obvious, you could put a bullet or a number
> in here to bring out exposure.
>
> The technical issues, in my view, around exposure are not analytical.
> As I said yesterday, FDA is a first-rate organization in that. The
> technical issue is connecting the analytical data with best available
> consumption data, which FDA is also first-rate on doing, and I\'m sure
> they were doing\--it\'s just not very obvious in the document. And
> that\'s why this morning I recommended using\--some mention of using
> the best available database should be put into the document.
>
> DR. BUSTA: Dr. Lee?
>
> DR. LEE: I don\'t know where to put this, so I mention it under
> Exposure. I still don\'t know for sure whether or not you have de novo
> synthesis of acrylamide or have some in vivo formation of it. There\'s
> really no human population that I know that does not eat cooked foods,
> so the only populations I can think of that don\'t eat cooked foods
> are wild animals and\--it was just mentioned casually that
> acrylamide\'s been detected in those creatures. So there are some
> things that I have yet to understand about exposure.
>
> DR. BUSTA: Other comments? Is the subcommittee ready to start
> addressing questions?
>
> DR. HOTCHKISS: I am.
>
> DR. BUSTA: All right, I\'ll start off with Question No. 1. You have
> that in your Charge and Questions.
>
> Given what we know about acrylamide\'s toxicology, occurrence,
> formation, exposure, and risk, are the following research steps
> appropriate to describe and address the public health significance of
> acrylamide in food? There are three items below that. Number one, the
> following sequence of a current study \-- variability, exposure
> evaluation, concurrent with formation studies and concurrent with
> toxicity studies. Are those appropriate to describe and address the
> public health significance of acrylamide in food?
>
> I thought we would rotate around the room, unless someone has a
> burning desire to be first. Is Dr. Downer ready to respond?
>
> DR. DOWNER: Are the research steps appropriate? I think that they are.
> I think the preliminary steps are fine, but that more research is
> needed on information regarding absorption, metabolism, distribution,
> and excretion of acrylamide in humans so that we can estimate the
> risk, relay the risk to humans that can be made.
>
> DR. BUSTA: Okay. Dr. Hotchkiss.
>
> DR. HOTCHKISS: In general, the research steps and plan put forth by
> FDA, in my view, are quite appropriate, logical, and will serve the
> public interest of public health. My only caveat or disagreement is
> that I don\'t see the benefit of the long-term cancer bioassay surveys
> per southeast. I do see a considerable need for much of the pharmaco-
> and toxicokinetic work, much of the biomarker work, the germ cell
> genotoxicity, all of those kinds of things, but I don\'t believe that
> the long-term carcinogenicity assay is required to gather information
> from those.
>
> Other than that one part of that, I think that FDA has, as I said
> before, put forth a comprehensive and logical plan. I think that, and
> I think it will be addressed in our Question 3, I think priority of
> work is important in this, and I want to reserve comment for that.
>
> DR. ACHOLONU: It is my opinion that FDA has done well so far. But
> we\'re expecting more in the future. Thank you.
>
> DR. GRAY: Well, I\'d like to echo the others who say that this is a
> very well thought out action plan and I think that it covers, at this
> point, all the bases for developing\--most of the bases for developing
> information to describe the risks. The one thing I don\'t see here,
> and it may be implicit, is discussion of the tools and the approaches
> and potential research that needs to be done for methods of using this
> information to describe the risk. And here I\'m thinking particularly
> about evaluating particular risk assessment approaches that can be
> used in this setting.
>
> And the one other thing I would suggest that isn\'t here that may be
> appropriate, and this has to do with both resource and timing
> considerations that I\'m not very good at estimating, is a question of
> whether further epidemiologic work would be helpful. It\'s not
> currently in the plan, and given that a large part of our concern is
> the potential relevance of the animal data to humans, more data on
> humans may help to resolve that.
>
> DR. BUSTA: Dr. Kuzminski is not a voting member, but you can make a
> comment if you wish.
>
> DR. KUZMINSKI: Oh, thank you. I think the elements that are contained
> in bullet one are\--it\'s a good plan. We\'ve heard discussion. I
> think there are a couple of things that could be in different order in
> the written material here, like validation of method ahead of survey,
> but we\'ve heard discussion that that indeed was the priority.
> Somewhere in there, the need for work on and use of risk assessment as
> knowledge is generated needs to be included.
>
> I guess my other comments will be addressed by bullets two and three.
>
> DR. BUSTA: Dr. Whitaker.
>
> DR. WHITAKER: I do think that the steps as outlined here are
> appropriate. I think it shows FDA spent a lot of time thinking through
> the process, and the steps seem to be logical.
>
> I think that there\'s not much said in Question 1 about priority, but
> I assume that, from what we\'ve said here yesterday and today, that
> those priorities are probably understood, such as analytical
> validation should be done before anything else.
>
> And this is a lot of research. And I don\'t know that FDA necessarily
> will do it all itself, and it should try to make use of industry and
> academics to attack these goals in terms of a research process.
>
> DR. BUSTA: Dr. Fischer.
>
> DR. FISCHER: I agree with everyone regarding the completeness and
> applicability of the plan to what needs to be done to understand
> acrylamide\'s potential role in causing harm from the food supply. I
> think it\'s a well thought out, good plan.
>
> I agree with Dr. Gray that what it lacks is specific statements of
> intended research, or research needs in humans. I think in the end we
> always like to see the human data. We\'ve already, I think, talked
> about the inadequacy of the present data in that these were worker
> studies, in the main. And I would say, from what I can see in my
> experience, that worker studies are never looked upon as being
> sufficient when you\'re looking at a low-dose situation like we\'re
> looking at now, particularly with food being the matrix in which
> exposure occurs.
>
> So there\'s a\--any chance to increase the information in humans, I
> think, ought to be taken. That includes toxicokinetic studies as well
> as some way to get some epidemiological information. It seems to me
> we\'ve kind of ruled out the possibility of doing any epidemiology,
> either on exposure or exposure and outcomes. And maybe there is a way
> to do it. Maybe somebody\'s got a creative way of getting a population
> that we could look at who is more highly exposed than other
> populations.
>
> So I would agree that we need to consider more information in humans.
>
> DR. BUSTA: Dr. Fuller.
>
> DR. FULLER: Like everyone else, I applaud the efforts and the plan, I
> think, is also very carefully thought out. I have some ambivalent
> feelings, like Dr. Hotchkiss, on long-term studies. I do think,
> though, that they\'re\--I don\'t know that it would be\--that I would
> agree or suggest that they should not be done. I think there is
> potential there for those to be further enlightening, although how
> much more so and how much bang for that buck, I\'m not as certain
> there. But I don\'t know that my uncertainty is such that I\'d say
> don\'t do it.
>
> Otherwise, I think\--the points that have been made I won\'t
> reiterate, and I just think it\'s a pretty thorough plan.
>
> DR. BUSTA: Dr. Lee.
>
> DR. LEE: Being near the end risks redundancy, but I\'ll leave the
> ultimate redundancy to our chairman, Frank Busta.
>
> Yes, the steps are appropriate and are in the interests of the public
> good, and I agree with prior comments. The occurrence survey requires
> good cooperation now underway both with international organizations
> and the food industry. But more importantly, to understand the
> mechanism and means to minimize the chemical, the cooperation of the
> total research community is needed.
>
> In particular, understanding process variables will require active
> participation by industry in a way that does not disclose proprietary
> information or single out a particular brand or product as a target.
> The JIFSAN Infonet appears to be a good start, but there needs to be
> some active management of that.
>
> DR. BUSTA: Ken always has described me very well\--the ultimate
> redundancy.
>
> DR. LEE: Put that on record, will you?
>
> DR. BUSTA: Put that on record.
>
> I am impressed by the unanimity of the entire committee, in that there
> is extensive support, strong support for the research steps. I think
> the concurrent activities, of three activities going on at the same
> time, are very appropriate and a very logical approach to the research
> needs.
>
> I believe that the role of food in not only the formation of
> acrylamide but its occurrence and the toxicity are all valid and
> important research activities. So that I know we talk about model
> systems, and I know we look at mechanistic approaches and we measure
> the occurrence of acrylamide, but I think there\'s a need to factor in
> the specific food matrix systems and the processing in those
> considerations and try and link them across all three of the areas.
> Because there may be a dramatic variation between what we\'ve seen so
> far in other products and maybe the food matrices will give us an
> answer to that.
>
> I concur with all the individuals who\'ve commented about the
> cooperative research activities, and would like to emphasize that the
> academic opportunities are here as well. Unfortunately, frequently
> academic research is terribly slow, especially with graduate students.
> It takes time. And the information is not terribly readily available
> until they\'ve concluded their effort. But I think there are
> opportunities, at least in the long run, for academic participation in
> some of the fundamental work here, as well as industry and the
> government agency.
>
> I also concur with the need for the human consideration all the way
> through, including exposure and the kind of eating patterns. I think
> that a 13-year-old young man eating a variety of different foods is a
> consideration that may not fit in a lot of the other databases and
> needs to be thought through. I think that it relates to the home
> cooking activity and it relates to the toxicity problems, at least in
> concentration.
>
> And when I look at the toxicity studies, I see the order of priority
> just the way they\'re listed on the Charge. I think mechanistic
> studies to support low-dose concentration is probably the most
> pertinent because of that low-dose extrapolation, and then going down
> through the rest; because the long-term cancer studies may not serve
> us as well, at least for our immediate research needs.
>
> Finally\--and two people have mentioned it, and I would like to say it
> again, as long as I\'m being totally redundant\--the epidemiology
> seems to have more promise than I\'ve heard put forth here. It just
> seems to me that we could find a population somewhere in this world
> that doesn\'t like or eat browned foods\--maybe a North Alaskan Inuit
> population or some population somewhere that does not consume highly
> browned foods; and in some way try and get a matched population to do
> the epidemiology to see if that\--and that may be based on a lot of
> markers that are still not proven as well. But it seems to me that
> that would address some of the questions that Ken has mentioned about
> endogenous generation of acrylamide, et cetera.
>
> A long and windy answer, but I had to, you know\-- It\'s nearly 12
> o\'clock, so we can take a break and come back for Questions 2 and 3.
> And we\'ll try and have a reasonably quick lunch and be back between
> 12:30 and quarter to 1:00.
>
> DR. FISCHER: You don\'t want to finish up? I mean, we\'re so close to
> finishing.
>
> DR. BUSTA: Okay. Is that what I\'m hearing, let\'s keep it on a roll?
>
> DR. HOTCHKISS: I would like to finish because\--I agree we are quite
> close and I think we could finish this up and lunch will be about the
> same temperature.
>
> DR. BUSTA: It really is\--from my experience, it takes somewhere
> between two and four hours before you\'re really up at the hazard
> realm. Unless it\'s been there since 10 o\'clock.
>
> DR. LEE: So it\'s not just temperature, it\'s time too.
>
> DR. BUSTA: All right. If that\'s the\--
>
> DR. HOTCHKISS: Go for it.
>
> DR. BUSTA: Now I will do a reverse and start with Dr. Lee on the
> second question.
>
> Are there gaps in the research plan or areas where emphasis should be
> increased?
>
> DR. LEE: You fooled me by doing that.
>
> Are there gaps in the research plan? I think toxicity studies should
> take full advantage of any information developed by the acrylamide and
> related manufacturing industries, because industry cooperation, again,
> is needed to solve this problem if the problem truly is significant.
>
> The best interests of consumers is preempted, perhaps, by legal
> actions, and the means to minimize this hazard will dissipate if data
> is sequestered by the courts and made unavailable by industries who
> seek self-protection.
>
> There is questionable value in posting incomplete data sets and brand
> names on the World Wide Web, as was recently done.
>
> And to the extent positions, a system for free and unencumbered
> exchange of data must exist. Industry data on acrylamide contents of
> foods and process variables that favor or inhibit its formation are
> critical parts to this puzzle. A blind system that protects brand or
> process identify is essential, and this represents a potential gap in
> the plan.
>
> DR. BUSTA: Dr. Fuller.
>
> DR. FULLER: I didn\'t see any overt gaps. And I would just stress the
> issues that we talked about a little earlier on the use of data in
> risk assessment and communication. I won\'t go into long, lengthy
> comment on that, but\--because I think we\'ve addressed it previously.
>
> DR. BUSTA: Dr. Fischer.
>
> DR. FISCHER: As far as gaps goes, I think we addressed\--in my last
> comment, we addressed a gap, and that is a human angle. And I think
> that\'s there.
>
> The other thing I think I don\'t see is\--another way to get a better
> idea of whether the human might be susceptible to a particular
> toxicity if you don\'t have any human data is to have good information
> on species differences. And I don\'t think I see that stressed much in
> the plan. So if we could have\--if we could find a reasonable species
> that is much less sensitive, for example, or much more sensitive, it
> would give us a good idea of whether we can extrapolate to the human.
> If all the species we study look about the same, then we have a good
> idea that the human might be susceptible. So a little more attention
> to species differences might be helpful in the end.
>
> DR. BUSTA: Dr. Whitaker.
>
> DR. WHITAKER: I know we all have our own ideas as to what is important
> and what is not so important, but I only listed two things that I
> thought were\--that I felt strongly about, and one is the human
> studies, which has already been mentioned.
>
> The other has to do with variability. And I\'m talking about
> variability now at the bottom of the pyramid. We\'ve heard about
> variability from food to food and variability from brand to brand. But
> I know that eventually somebody in FDA is going to want to know how
> accurately and how precisely are we measuring acrylamide in a lot. So
> I would like FDA to also take it one step lower in their thought
> processes, and that is to understand the variability that\'s
> associated with sampling, sample preparation, and analysis.
>
> DR. BUSTA: Dr. Gray.
>
> DR. GRAY: The only comment I would make here is that I do think that
> area that could benefit from some increased emphasis here is simply
> the notion of communication, that we think very hard about how to
> communicate with people over the entire period of execution of this
> plan and into the future after that.
>
> DR. BUSTA: Dr. Acholonu.
>
> DR. ACHOLONU: I\'m impressed with what has been done so far. But I
> want to reiterate what I said about connecting whatever they do with
> human beings. I want to say that rats, mice are rodents. They don\'t
> come close to human beings. I\'d like to recommend to FDA to consider
> carrying out some experiments with monkeys or apes, then eventually to
> man. So that\'s my recommendation.
>
> DR. BUSTA: Dr. Hotchkiss.
>
> DR. HOTCHKISS: Yes, the question are there gaps in the research plan?
> At least explicitly, perhaps. Let me give you, or in my view, some
> specifics. The first recommendation I would have relates to the issue
> of human epidemiology. This acrylamide is an unusual substance in
> that, as I\'ve said before, there is substantial occupational
> exposure, and a number of epidemiological studies have been conducted
> on that. The question is whether or not those epidemiological studies
> are applicable to a different route of exposure, a different level of
> exposure, which is probably considerably lower but also over a very
> longer period of time. It seems to me those are important questions. I
> would recommend to the agency that they, either in-house or
> externally, contract a group to address those specific issues around
> epidemiology and to advise them whether or not they feel that the
> current epidemiology is applicable or not applicable and to what
> degree.
>
> The second area is, I guess, implicit in the plan but not specifically
> mentioned or addressed in terms of methodology, and that is really
> risk assessment. I think that that is the absolute key thing here.
> We\'re dancing around this issue because there is no credible risk
> assessment conducted, at least for this exposure. There is a\--risk
> assessment has been conducted by the agency itself on acrylamide as a
> migrant, but not in the context of a food contaminant. And I think if
> we had that risk assessment\--of course, I understand there are lots
> of things implied in that in terms of analytical methodology and the
> quality of sampling and so forth. But still, it seems to me that\'s a
> key piece of information, is what\'s the risk and how do we compare
> that risk to other risks.
>
> In the toxicology studies, perhaps again implicit, but I think there
> are two issues that seem to me to be fairly straightforward to address
> in the right toxicology study, and that\'s germ cell toxicity and
> neurotoxicity.
>
> Neurotoxicity is typically most sensitive during fetal development,
> and there are a number of protocols for assessing neurotoxicity in
> animal models during fetal development. If you don\'t see toxicity in
> that, it\'s unlikely you, at those doses, will see toxicity elsewhere.
> Those are the most sensitive systems. Those are relatively well
> established and straightforward.
>
> The other is germ cell threshold, and it\'s again a similar kind of
> thing. Probably, or it\'s possible that there is a threshold for germ
> cell toxicity, and again those protocols for those kinds of assays are
> fairly well developed, again, in young animals during maturation.
> There are certain stages of the maturation process that the germ cells
> are very susceptible to toxicants.
>
> Those kinds of studies probably would put this issue to rest, again
> assuming it has not already been put to rest because of the
> occupational exposures. But in general, it is those kind of specific
> things that I think perhaps could be included in the draft plan.
>
> DR. BUSTA: Dr. Downer.
>
> DR. DOWNER: Thank you. I concur with my colleagues that we need some
> information on human subjects. However, I also think that biomarkers
> to include both short-term and long-term exposure should be
> investigated further. Bioavailability of acrylamide, or its metabolite
> glyceride \[ph\], from food needs to be looked at also. And I\'d also
> like us to look at the food consumption data and compartmentalize it
> into not just what general Americans eat, but look at the different
> ethnic groups, look at the different age group categories, and also
> look at some of the socioeconomic data to get a better picture of
> what\'s going on. Because we know that these different groups have
> different health issues that go along with it, and I suspect we may
> find some correlation there.
>
> DR. BUSTA: Dr. Kuzminski.
>
> DR. KUZMINSKI: Thank you, Frank. I think there are two gaps that are
> areas where emphasis should be increased. One is the use of risk
> assessment at an appropriate point in time\--and there\'s big quotes
> around that would \"appropriate.\" And I don\'t know the answer that,
> and I don\'t think a lot of people in this room know the answer to
> that, but some decision needs to be made in terms of managing this
> entire process both from a technical information-gathering viewpoint
> and from a communication to consumer viewpoint. So that\'s one.
>
> The other gap and area where emphasis should be increased is on the
> role of data that could be obtained not just from government agencies
> but external data, industrial data, if you will. I must be frank; I
> didn\'t hear much passion on either side of the coin, by either
> industry or by the agency, in terms of talking about that\'s a source
> of data that we\'re working on through JIFSAN. I think it\'s a huge
> area that could be exploited, exploited to benefit in terms of helping
> to solve the problem and helping to define further the problem and
> then solve it, if there indeed is one.
>
> DR. BUSTA: Joe?
>
> DR. HOTCHKISS: I just wanted to make a comment about the epidemiology
> that perhaps not everyone is aware of. But the epidemiology around
> fried foods would be extraordinarily difficult if not impossible to do
> for a variety of reasons, one of which is that the general conditions,
> at least as we know it now, in which acrylamide is formed in foods
> happens to be exactly the same conditions that a whole variety of
> other, I think on an equal basis, more toxic compounds\--the
> heterocyclic amines and a whole variety of those kinds of
> compounds\--are formed. So if you compare a population that is a
> fried-potato eater against a non-fried-potato eater, you\'re going to
> face the question of acrylamide versus heterocyclic amine versus a
> variety of other issues as well. So recommending to the agency to do
> something like a fried-food epidemiology is rather a difficult if not
> impossible task.
>
> DR. BUSTA: I think that was aimed at me.
>
> DR. FULLER: Perhaps.
>
> DR. BUSTA: Just confirming the difficulty.
>
> I won\'t be as redundant this time as I was last time, or at least go
> on as long. I concur. I haven\'t heard any of these comments that I
> disagree with. The gaps that were identified, I think, are significant
> and important\--by the other members of the committee. I feel that the
> emphasis that was stated earlier in just running what I said, where I
> thought mechanistic studies could be emphasized initially and that
> exposure information and the role of food, I think, are indications of
> my opinion of where emphasis can be increase, or at least placed.
>
> Any other gaps stirring anyone else? All right.
>
> Number 3. Now, I started this way\--I\'m trying to spread this around.
> Number 3, I\'ll start: Priority research needs that should be
> addressed first.
>
> I\'ll just be redundant on what I just said, and that is that I think
> we need to look at the\--on Consumption, I think we need to look at
> exposure levels with the emphasis, in addition to analyzing some of
> the foods. And I have heard of the design of these food studies, and
> the combination of information from around the world, as being
> significant in achieving the first of the concurrent research
> activities that are stated here.
>
> I think that the role of food, again, is very important both in
> toxicity studies and in formation and control studies. And that\'s why
> I think the emphasis should be placed first.
>
> Let\'s start with Dr. Kuzminski. We\'ll come up this way.
>
> DR. KUZMINSKI: Thank you, Frank. I must defer to the toxicologists in
> terms of the time that it takes, just in the time that it takes to
> come up with the research answers to some of these topics that are
> proposed. My sense is that it takes a longer time than it takes to do
> some of the others, just based on some very limited experience in some
> toxicity tests that I have been involved in.
>
> So I think the methodology, the occurrence, and the formation and the
> exposure mechanisms, that mix of investigative pathways as outlined in
> their sequence here is taking priority, has taken priority over the
> last several months and should be maintained. But the others should be
> clicking in pretty promptly.
>
> DR. BUSTA: Dr. Whitaker.
>
> DR. WHITAKER: I wasn\'t sure how to address this question, because in
> my way of thinking FDA has already started the process as they should
> have; and to be commended for that, not to wait on us.
>
> If I laid out the priorities, and I look at what FDA has done or has
> started to do already, I would agree with it. I think the first thing
> you have to do is make sure the analytical method is giving you
> correct answers, and they\'ve done that and they should continue. And
> I would have gone into occurrence, exposure, and risk. And I think
> that\--at least what I\'ve gotten out of this\--is the way they have
> gone, along with some other areas also.
>
> So I think, based upon the way they have started and what way I would
> look at it, that they\'re on a turn.
>
> DR. BUSTA: Dr. Fischer.
>
> DR. FISCHER: Well, I find this a difficult one as well. Certainly,
> exposure is an important factor and should be among the first things
> done. It\'s already under way, so I don\'t have any worry that we\'re
> not going to have exposure data probably first.
>
> The toxicity studies and mechanistic studies do take a longer time,
> and for that reason I guess one way to look at it is why put them off?
> If in fact they\'re going to take a long time, maybe you ought to get
> them started. And I think that that\'s being done as well. So I agree
> to that.
>
> I would say, if I had\--what I would start almost right away is
> thinking about risk communication\--not a research need, but maybe you
> could call it research. I\'d start thinking about scenarios where
> you\'re going to have to respond to the public\'s concern and crafting
> the kind of response that you may need to make. And maybe already some
> is needed. So I wouldn\'t put off communicating with the public about
> this issue.
>
> DR. BUSTA: Dr. Fuller.
>
> DR. FULLER: I\'ll be honest; I don\'t think I have anything meaningful
> to say, so I won\'t.
>
> DR. BUSTA: Dr. Lee?
>
> DR. LEE: I wish I had faculty like you.
>
> DR. BUSTA: You wish you had faculty.
>
> DR. LEE: Yeah, right.
>
> Are there priority research needs? I believe there is no shortcut to
> determining if acrylamide is a significant health hazard or a food
> compound that has negligible toxicological effects. Nonetheless, the
> FDA will be doing its job by first placing its finite and often meager
> resources where consumer interests are best served. This could include
> rapid, inexpensive tests for the compound, means to reduce the total
> dietary exposure, and an informed public that has science-based
> information on which to make dietary choices.
>
> It may be useful to determine if acrylamide is a natural product, a
> man-made product, or both. It would be helpful if research could
> provide a basis for the answer to this question.
>
> And in the context of total food risk\--that includes issues such as
> security, food counterfeiting, diversion, food-borne pathogens or
> prions in chronic wasting disease\--acrylamide appears to be a lesser
> immediate threat to the human condition and thus a lesser priority.
>
> DR. BUSTA: Dr. Gray.
>
> DR. GRAY: Thanks. Recognizing the timing difficulties involved with
> much of the toxicological research, the main suggestion I would make
> in the way of priorities is, to the greatest extent possible, moving
> along the toxicologic data and the tox analysis and risk analysis in
> order to provide context for the exposure information that we know is
> going to be coming soon, both in the forms of specific foods with
> acrylamide contents and things like adduct levels in the population.
>
> So this is just, as soon as we can, even as uncertain as it might be,
> to be able to provide some context to these exposure levels that are
> going to be coming first.
>
> DR. BUSTA: Dr. Acholonu.
>
> DR. ACHOLONU: I think that FDA could spend more time working on the
> kinds of food prepared. To what extent is the level of acrylamide
> found in fried food, in broiled food, in baked food, and in roasted
> food? It may be good to do some work, and grade them. Find out where
> the level is found to be highest.
>
> The next thing I feel we should go into is work on safe limits of
> acrylamide in food. To what extent can you take in acrylamide, to make
> sure that it is safe for health, that it will not be carcinogenic?
>
> Next, I don\'t know if we addressed the issue of cumulative action.
> Can acrylamide, when it gets into you, be metabolized and taken out or
> excreted; or does it accumulate? As you get exposed to it and as you
> eat, does it keep on increasing to the level then causing cancer in a
> human being? So we need to go into that aspect.
>
> And as I\'ve said before, priority. We are making this study assuming
> that it can do something to man. So emphasis, anything we can do, any
> research we carry out should bring us closer to confirming that it is
> carcinogenic to man\--not just say it is probable, it is assumed.
> Everything we have said so far, what has been written so far has been
> speculative as far as human beings are concerned. So any research, any
> work we do should point towards confirming that acrylamide is
> carcinogenic to man. Thank you.
>
> DR. BUSTA: Dr. Hotchkiss.
>
> DR. HOTCHKISS: The question as framed is are there priority research
> needs that should be addressed first? In my view, the answer to that
> is emphatically yes. Is FDA doing that? It seems by de facto, yes. As
> we see the FDA ongoing and planned work in this area, it seems to be a
> logical sequence. Have FDA prioritized their work? It seems certainly
> not. I\'ve seen nothing in here to really prioritize it. They\'ve done
> it in kind of a de facto way. My recommendation is that FDA say, yes,
> this is our priority, this is the sequence of events we\'re going to
> unfold. There is a timing frame back in here that actually puts timing
> \-- that implies priority but does not state so.
>
> My own priority would be a post haste risk assessment, and not
> necessarily waiting for all data. You never get all data for risk
> assessment. You\'ll refine your risk assessment. And as a matter fact,
> as I\'ve painfully pointed out to the FDA, they\'ve already conducted
> a risk assessment for acrylamide and have published that risk
> assessment. With the available current data, they should either
> conduct a subsequent risk assessment or say why that cannot be done,
> because it really is the key element here, is risk.
>
> If we knew the risk assessment\--and, of course, implied in \"risk
> assessment\" is a lot of things. Exposure, you can\'t do a risk
> assessment without exposure, and you can\'t do exposure without all
> the analytical kinds of things and those things that FDA is doing. But
> if we had our best current guess on risk now, then that would
> certainly guide us better in the future. So that would be my first
> priority.
>
> Along with that, clearly the major risk is going to be
> carcinogenicity. It virtually always is. But along with that, the
> short-term, oral-dose neurotoxicity and germ cell experiments, I
> think, should also be a priority because that will either take those
> issues off of the table or bring them to the forefront on the table,
> depending on how those specific outcomes are seen. My guess is what\'s
> going to happen is the tumorigenicity risk
> assessment\--tumorigenicities at low dose is going to be the primary
> thing\--but until that works, then you don\'t know that\--and then a
> risk assessment.
>
> Other than that, I think, in a practical sense, FDA is prioritizing
> these things in a de facto sense very well.
>
> DR. BUSTA: Dr. Downer.
>
> DR. DOWNER: I think the FDA has already started on the priorities, and
> my recommendation that I\'m going to make is simply adjunctive rather
> than a priority. I think one of the things to look for would be
> whether or not acrylamide, at the levels found in food, is of any
> toxicological significance. I would also want to look to see, if we
> make changes or recommendations with regard to food preparation, what
> are some of the tradeoffs to ensure microbial safety and definitely to
> maintain organoleptic properties.
>
> DR. BUSTA: There\'s time for a last statement if any of you feel that
> you have anything further to add to the record. Dr. Downer.
>
> DR. DOWNER: I just want to thank you all for the opportunity to be on
> this committee and for the white papers and the presentations that
> were made. I certainly came here, after reading the documents, with
> one perception, and was able to be swayed and educated further to make
> some of the decisions I made today. So thank you.
>
> DR. BUSTA: Dr. Lee.
>
> DR. LEE: Well, I don\'t want to roll credits, but I want to thank Dr.
> Henry Kim for being very comprehensive in preparing everyone for this
> meeting, and his e-mails were very helpful.
>
> DR. BUSTA: Dr. Kuzminski.
>
> DR. KUZMINSKI: I would just like to thank our Chair for the job he\'s
> done.
>
> DR. DOWNER: Ditto.
>
> DR. KUZMINSKI: You\'ve done a good job.
>
> DR. LEE: I appreciate the Chair for his redundancy.
>
> DR. BUSTA: I think this has been a very excellent experience. The
> committee is so compatible, they took over my last statement. I\'d
> like to, of course, thank FDA for all their efforts and Henry for
> sitting here watching me closely to make sure that I really don\'t get
> myself into trouble. And this entire subcommittee, I think we\'ve had
> a good day and a half. And I think we\'ll have another opportunity to
> experience some of this again when we have the full committee.
>
> Thank you, and for those of you that can make it home tonight, good
> luck.
>
> DR. DOWNER: You\'ll have to come to my house.
>
> DR. BUSTA: Those of you that can\'t, good luck. Terry?
>
> DR. TROXELL: I\'d like to have the last word.
>
> DR. BUSTA: You\'re on.
>
> DR. TROXELL: I want to thank the committee, for the FDA, for CFSAN,
> for myself, for the tremendous amount of work you have done and the
> advice you have given us; for braving the weather, braving the trip
> home. We wish you a safe and speedy trip home, and hope the folks
> heading to Florida can get to the sunshine.
>
> Thank you again, everyone.
>
> \[Whereupon, at 12:23 p.m., the meeting was concluded.\]

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