 Well good morning to everybody and welcome back to the second day. I'd like to have everybody here. There are three things in particular that I'd like to accomplish with the champ today to throw me adjourned. One of them is to continue to discuss risk assessment but the piece of this that you want to focus on this morning is how will we use the data that we have from the hazard index, the exposure data, how will we use that information to determine recommendations to CPSC. So we want to discuss how we make a decision that something might be banned or inter-banned or no action today. So that's one of the three things. The other one is we need to review what are the holes in our outline that had the premise on it. Are there particular things that we need to have somebody assume responsibility for that becomes part of the report that we didn't anticipate when we put that outline together earlier. Then the third thing is to make sure that we have a discussion about dates for the next meeting before we leave today. One other piece of information Dr. Chris Borgert has presented a paper at the Society of Toxicology meeting recently that is relevant to our topic and as chat members we receive copies of three poster sessions posters that were given that they were difficult to read. Well this brought copies of his poster in large enough print that you can read easily. So they're on the table so if you want the copy of his talk that was given at the SOT meeting it's there and it's relevant to anti-androgens and their activity. Any other comments before we start through the discussion on risk decisions this morning? If anything the weather is getting bad rather than good but I anticipate that we will be done in time today that hopefully we would not compromise your ability to get home. I can't speak to those of you going later on this evening but this afternoon I'm hoping that we can get up for whether we'll sell. Okay then you should have had a handout at your desk this morning that was something that I just put together last night after thinking about this some more and where we stopped yesterday was a suggestion of the possibility that we would begin this discussion about making risk decisions by looking at criteria and criteria for a ban would be a place to start. So there's an error in here later on. There's a greater than one that should be a less than one under criteria for no action. Otherwise this is a very it's a draft of rough thinking and it's presented only to stimulate discussion and I would welcome your suggestions for what are better criteria and how to modify these criteria some of them require discussion. So just to get us started the criteria for a ban and one of the things that I understood from yesterday is that if there is a hazard index equal to a greater than one that was a signal that something needed to be done. Some kind of a regulatory decision or non-regulatory but the next decision to limit exposure in some way regulatory or not. Another criterion could be that the responses in key toxicity studies are considered relevant for humans. I mean that's one of the things we want to know before we would impose any kind of an action and if we know that the titans in toxicity studies are relevant for humans and I'm distinguishing assumed relevant here from those that we know to be relevant then it's plausible that we should be concerned about human safety. Another one is that the effects expected or seen in humans are a serious health effect. So we're not talking about dermatitis. We're talking about a health effect that is a considerable concern. It might be mutagenic damage. It might be growth defects. It might be developmental effects that are not malformations. It might be cancer. It might be any one of a number of things that we really wouldn't want to have people experience from chemical exposure. I think it would be critical that Ketox College studies are replicated with similar results from multiple laboratories. So we would not recommend taking an action on one study for one laboratory even if it was a well-designed study. I think it's important that findings can be replicated in another laboratory before. The yellow flag might be raised at the first finding but it would sure be nice to see it replicated in another lab. It's important that the identity of the toxic agent in animal studies and in the human environment is confirmed with analytical methods of sufficient sensitivity, specificity, and limited detection. Again, multiple laboratories. So we don't have a situation where there's only one lab in the world that can detect this stuff and they have found it and they coincidentally have done the talk study as well. That's not a situation that we would want to find ourselves in to make a serious regulatory decision. And then also the levels of human exposure are sufficiently high to cause adverse effects in humans. We would know that either from extension of the animal data or from known human experience. I suspect by the time a decision of this kind would be prompted, we would probably have enough human exposure to see if they are showing some signs either through blood levels or urine levels or some toxic response. So those are my first thoughts in putting down the criteria that might be used to determine a recommendation that something might be better. Discussion? Chris? So one thing I might, a couple things. One is the first part about the hazard index being greater than or equal to one. We pointed out yesterday that sometimes the hazard index is used as a screening tool when a lot of very diverse chemicals are put together. And in that case, it might be that we would go back and look for similar chemicals in constructing the hazard index. I think in what we're working on here is in the case of having similar chemicals. It's not as Andre said yesterday, apples and pears, I think he kept saying. I think we do have apples and apples here. When you start talking about things being replicated, part of what we're using the toxicology studies for to get estimates for points of departure and you know there's variation in those estimates from a single study. So replicated maybe in quotes in the sense of not really exact numbers or whatever, but in the ballpark, you know, what's close enough to being replicated and that's the gray part of that. And I think what we're seeing yesterday is that in terms of how we're using these results from multiple studies is a little bit of variation in a point of departure estimate may not matter that much. So I guess I would just point out how strict you mean by the work. Thank you because I should have expanded on that a little bit more by replicated. I mean that if you if one laboratory has done a study, let's say they found a significant increase in tool response in a specific target order, let's say by replication. I mean that somebody else does another study and it's a reasonable strain of animal that has we have laboratory experience in. The study is a sufficient duration to detect a tumor response if there's going to be one. The dose levels are sufficiently high. They don't have to be the same, but they cover the same range that might be determined on the basis of a maximum tolerated dose in case there is a strain difference in sensitivity to the limiting factors. As you all know, the NOAAIL is largely a function of experimental design and dose selection. So you may have a fair amount of variability in NOAAILs just based on how the studies are designed. So in that sense it would be a lot better to have two of them and it would be just to have one where perhaps the NOAAIL is really a strange number because the dose levels were spread so widely compared to a tighter one which you'd have a NOAAIL and a NOAAIL fairly close together. So that's what I meant by replication. It doesn't have to be in, it shouldn't be in the same lab, it shouldn't necessarily be in the same strain. It might even be in a different species. You might have rat and mouse data. But the ability to replicate, it doesn't have to be a liver tumor. I mean for was, it's a little more confidence, but if the response in the mouse is different than the one in the rat, that's not uncommon. But the fact that you have two responses in two different studies is pretty significant. So does that help clarify what I meant by replication? I'd like to come back to what Andreas said yesterday. Do we want to use the hazard index which is actually a risk index as the sole trigger to talk about the ban or not a ban? Or shouldn't we really talk also about the hazard, but also not only the risk? So we have seen that the hazard index in itself has a certain variability. We can use case one which is, use the hazard index of 1.3 and in case two we have a hazard index of 0.8. So do we want to make a mean of it? So it's 1.1, now it triggers action, no? So I would be reluctant to accept this hard formulation here if the hazard index is above 1, it triggers something. I would certainly agree with that. I mean we went over that yesterday with the question of what do you do with a 0.9. So I didn't mean that any one of these is sufficient to automatically demand that a ban would be recommended. It's still a judgment. I mean even if we had some of these we might still make a judgment that we would recommend a ban based on three or four of these criteria, but they don't all have to be met. And I agree about looking at the hazard and that's why I mentioned in here that these expected or seen effects of humans would have a serious health effect. So that I was getting at the hazard consideration by saying that. Andres? Can I just expand on this a little? I totally agree with what Holger said, simply because a hazard index exceeds 1, it doesn't mean you should ban anything or do anything as such. So I think it's also a dangerous criterion to, it's a dangerous criterion for any ban or such like things because as I said yesterday, imagine any form of risk assessment indicates that exposure to DHP currently exceeds and making up numbers here, what is considered to be tolerable. So this could be arrived at by something equivalent to a hazard index consideration or we can simplify this just by doing it for a single chemical, the standard way. So then if you want to go down that route, in other words risk assessment gives the criteria for deciding on a ban or not, you would then decide okay DHP should be banned or the existing ban should be continued. In the same way you might for example find that because current exposure to DVP are rather low and therefore the quotient of daily intake and reference dose for the DVP is below 1, very far below 1. So that risk assessment consideration would indicate no case to answer. Would you then therefore say all of a sudden we don't ban DVP? That would be nonsense because if you ban for example in this in this thought experiment, if you ban DHP on the basis of a risk consideration, you open the door for a substitution process whereby for example a phallite like DVP could become more useful or some such anything. The consequence of that would be that exposure to DVP rises and say in a couple of years time risk assessors will find a whore. Now it is about what is considered tolerable and then the game begins again. So from this I deduce that any consideration looking at risk or assessing risks are pretty useless for justifying or otherwise any action like a ban. So that means in my opinion that that has to rest solely on consideration of toxicological profile whether or not the phallite in question induces elements of the phallite syndrome all or some etc. So solely considerations of that nature. The hazard index considerations which we discussed yesterday they are important though. They are important vis-a-vis some of the some of the remit some of the charges we have to answer in section 108. But I would really strongly argue against hanging any decisions on banning something or otherwise on considerations of hazard index or any risk assessment. This will lead into a terrible dilemma. It has to be based in my opinion solely on hazard on toxicological profiles. And it's inconsistent with what you said yesterday because there's no exposure and there is no reason to ban. You benefit as a hazard. I know that. That was nonsense. I sometimes say nonsense. I mean let me put it this way. I would object seriously with that. There's no there's only a hazard. It's not an exposure. It's a meaningless thing to ban. Because no one is being exposed and why the hell are we bothering with it? So therefore I do not think it was nonsense. I think the truth because there are situations and uses of materials where there'll be no exposure. So just basing it on hazard I think is wrong. A little bit further. For example let's talk about dipethyl delate. It is known to be one of the most critical delates. It's that critical that it's produced. So there's no exposure so the hazard index is zero. So we could allow it because there's some exposure. If we just waste a one criteria. I don't think this. Yeah so the criteria is just one itself. Well hazard and exposure. But you said if there was no exposure all right you have to find out if it's being used. If it's not being used then the hazard index is meaningless because there's no numerator because there's nothing to multiply numeric. So therefore the use of the hazard index is bogus. Okay since there is no use of the material. If there is some material then you can have a hazard index because it means there's some or some person out there who actually is being exposed. And we have to determine whether the exposure is meaningful. So if there's no exposure the hazard index is a bogus of calculation. Yeah. Yeah we agree on that. Yeah. Can I just point out that if we had done the work that we've done up to now and we found that the hazard indices the distributions that we've been looking at were you know down in the neighborhood of you know 0.001. You know given the exposure given the toxicology data combined together we probably walk home and say it's fine not to ban anything because it's so removed. I think I think what we're getting at is sort of a combination of thinking about all this together and that is we are in a situation now where there are some exposures that are in the region of concern. Very likely if some things are banned others are going to move around and the profile is going to change and I think in that situation what I'm saying makes a lot of sense because it's you know in the sense that we're in the region of concern we don't want to get back into that region of concern based on incomplete action without thinking about you know alternatives. It would seem unlikely that we would recommend banning something based on only one single one of these. It's a composite and it's a judgment and the recommendation will be a textual description not just ban it. We're not going to produce a list of chemicals that we recommend be banned. So I think it would look strange for all of the effort that we're putting into the hazard index evaluation for it not to be considered in this list. So I would leave it there as one of the things that we would consider and it has value beyond that individual chemical. So one of the things that would be a preliminary comment here is that there isn't any one criterion that by itself would determine whether a chemical would be banned, interim banned, or recommended for no action. All of that composite information has to be taken into account. I would argue that some of the criteria have a stronger weight than others. Oh I would agree yes and depending on the profile of information that's available that may highlight that one is most important for this chemical another one is most important for another chemical. So I would agree that these are not of equal weight. In fact that also let's remind ourselves we are not pontificating about a blanket ban here where this is about use in children's toys. Yeah and when we come to the discussion of interim banned we may pick up the situation where we have a real strong hunch that this is something that if we have a little more data we would probably recommend being banned but we don't have enough data yet. So I think it would dilute the importance of our ban recommendation if we do it on a guess. That's what the interim category is for in my mind. It would be accomplished the same thing but it would be a declaration that we didn't have as much comfort in banning this one as we did another one where we had sufficient data to make it clear that that's what the decision was. Chris did you have another? No. Can I add something here? I think your second point response to the key to this is that it's considered relevant for humans that's concerned for human safety is plausible. Can I suggest to specify this a little since we're talking about phthalates so this means the phthalate syndrome in relevant animal models. So the are all of or parts of the phthalate syndrome or elements of the phthalate syndrome shown to be induced by the phthalating question in relevant well-conducted animal studies. Do you need to be asked this subject? Because there are going to be other syndromes or effects of what you want to consider. Do you make it that narrow or are you limiting sort of limiting our decision making? Yeah, no I don't mean it as an exclusive criteria but just to specify this. It raises an interesting thought that if we had a substitute or a phthalate that was very weak in terms of its causing any of the phthalate syndrome but it was a repeated with found to be a hepatic carcinogen. Yes, good point. We couldn't really afford to be silent on that just because it didn't cause hypospadies. Let me do something that I apologize I should have done earlier. Phil, did you get a copy of the e-nail that has this in it? Yes, I have it in front of me. Oh good. I wanted you to have that too. Other discussion? I think the point for making all the different criteria and in a sense they all are important in each one of these related things and I think the idea of the hazard index is the way I've always do this is that it raises your level of concern. It's not a number that I would want to benchmark for a ban or not a ban. It's just something that says okay there's a level of concern. In fact that's the way it's used. It's basically used as an indicator. And so therefore that is not the only thing that we can base our decision on. In fact it shouldn't be. But the rest of these bullets are all just as important in fact some are more important than others. At least in my mind it's in fact known to cause human health effects. Well that's level one. It's not like the way you deal with carcinogen. Known to human health effects, suspected human health effects, etc. etc. These all fit within that category. I'm sure you base some of your thoughts about this on that point when you develop them. So I look at this as sort of like the weight of evidence on the effects and the exposure side coming together to make a decision. It's neither one or the other and it's not just one of the variables. It's a host of things where we actually use our best judgment. I mean that's the way I look at it. They're all relevant. Thank you Paul. Mike a question for you. Okay. And this is partly what authority you have and maybe it's semantic to some extent. But again it comes to my reluctance of using more band as opposed to restrict. Would there be a circumstance where we might recommend that there would be a restriction and for some chemicals it might be 100% the equivalent of a band. But in another case it might be a restriction to a particular concentration in products which isn't a band. I think the whole range of risk mitigation activities, risk reduction activities is on the table except for one because it's a children's product. We can't just put a label on it. Right. But other than that everything is on the table. So you could say you know less than a certain percent or you could say you know you essentially can't use it which you know you'd have to come up with some detection limit or something. But and also whatever we're doing it's it applies to a specific products or glass of products so it's not a blanket thing and we typically don't even use the word band because it's not a we wouldn't ban you know we're banning the use of a chemical in particular cases. But we haven't talked about for example we're stricking it to a tenth of a percent. It's well it's well the current ban the ban that we have now on children's products specifies .1% and that's essentially it's a ban but that's a practical sort of detection limit and you know we don't worry about trace trace amounts and so on. So if so that's essentially we're saying you can't use those chemicals in those products. So what I'm asking is if we use the word ban are we inappropriately restricting the choices that CPSC has. I don't I don't think so I think as long as we're clear what we mean the lawyers and the commissioners can worry about the wording. Because if we kind of volunteered to begin to talk about restrictions instead of a ban. Well that's okay in fact I think the word that word I think the language in the statute says something about restricting you know it's not necessarily a ban and I think we as long as we're clear what we mean we are not being asked to come up with a concentration in products that we consider to be safe. Well you could but we could I mean we're not you don't have to know if we don't get that far we would not have failed. Right. And in fact for the mouthing at least most people have abandoned the idea of setting a concentration. Yeah. Because the migration isn't necessarily predictable from the concentration. Yeah. Well if we use the word restriction it doesn't mean that we're limited to what's out there today. Right. We're talking about something less than what's today we're just not specified. Absolutely. Well along those lines what you've suggested Michael is the notion that there may be classes of products we may say should have not like things that have teaching potential type of type activity associated with the word kids will titrate this material from the product. So those maybe one class that you can consider not this restriction of banning because of the probability if you find that there's a reasonable amount of titration that can occur among a normal or even a child can lead to high exposures where they'll say there may be some products where you would not find TV that may actually Michael would be outside of that boundary. Is that what you're suggesting? Well I'm I'm saying if that's appropriate if you know the idea is to address whatever risk there is. Got it. All right. So there's another thing concentration and also banning based upon product type and use. There might be another criteria. So the discussion about children's choice makes me think that you know the concern I also have is to pregnant women when it's when it talks in the description here of child care articles and then later on I mean it's written in a kind of a confusing way it brings up pregnant women in a lower place but whatever we could do for protection there as well would be helpful and important. For protection of the unborn or protection of the woman. For protection of the unborn. I'd say that's fair. That should be part of the game plan too. So it's not just a child's toy. Well I'm just using an example but I would not exclude if I'm absolutely right Chris that should be part of the constellation of products if you'd say would either fall under direct observation or a ban or a restriction a little bit more difficult. You're talking about adult use of products which is very varied. What is but we should assume that for example cosmetics or health care products that would be used on an adult pregnant female we shouldn't assume that the percent is a barrier to prevent exposure of the fetus. Some should be that it passes across the placenta at a level that is representative of what's in the blood. The biggest issues for them that would be obviously dermal exposure. But we have to consider the time concentration which one could be a significant contribution. Sure. Just by the way they the statute used the term banned hazardous substance what that means is a product that doesn't pass or doesn't meet a regulation. So it doesn't mean the chemicals necessarily banned it means that product is banned for because it doesn't meet some standard whether it's a concentration the type of chemical the the migration whatever the standard is that's that's all that means. I mean it's banned for use in that another product. What means that product is should be would be recalled or taken off the market until it's been recycled into something else that's more appropriate. That's helpful. Thank you. I think this was a rich discussion. Other comments or questions? Phil anything from you on this? Well I'm listening and several things have come up. One is one of your criteria levels of human exposure are high enough to cause adverse effects in humans. Isn't that informed by the hazard index? I understand that if it's greater than one there's some there's some individuals in the population that may have received a dose of combination of phthalates that could be a toxic. So if that's if I'm right on that then level of human exposure high enough to cause adverse effects in humans for example an HI equal to or greater than one. But that HI is a sum total of the roots. Yes. And so therefore you can't ascribe that to any one product. That's a problem I'm having with the entire discussion. How can we talk about individual phthalate when we know from bio monitoring data that people are exposed to virtually all of them? Well the point is combined exposure that's really important if we believe that human exposures can be toxic whereas the individual components by themselves would not be. Well yesterday we pointed out in a discussion that we can't we can't do we can't describe the sources of all exposure to phthalates. What we're limited here is our ability to quantify a range of concentrations that are appropriate or associated with one particular class. And what we can do by difference or by differential analysis is determine based upon what we learn if the hazard index for a particular class of chemicals I mean a class of products is relatively low then we have to make some judgments as to whether or not that is a significant contributor or not based upon judgment. We can't you know you're trying to put on to this process an analysis that we don't have enough data to understand which is basically more more or less diet which has very little to do I think at this point to the toy question that we're dealing with. It has a hazard issue but it's it's not directly under the purview of what we're doing. Phil I think your point your point is valid and this last point can be interpreted in many ways I think but your interpretation I will definitely agree with in along the lines of hazard index exceeding one or but again I have similar problems with this similar to the hazard index discussion so I think this this alone or this despite I'm not sure this is a useful criterion to decide on a ban we we again let me reiterate we have other charges and we have to look at exposures we're supposed to look at safe levels and try and derive them etc etc that's all that's all details in the charge so we have to do something about it but it's quite a different question as to whether these give useful criteria for deciding on so I would have a problem with that last point do you feel Andrea said is the human exposure high enough to cause every health effect would you suspect so I would maybe that the hazard index would be through the roof yes sure but that's so therefore because the hazard index goes through the roof it's not it's not a criterion for deciding on a ban you know right the example of DPP DPP is currently not relevant in terms of much in terms of relevant human exposures and definitely a level of human exposure of DPP are not high enough currently to cause adverse effects so therefore would you say let's not ban it this is nonsense no nonsense we have to be very careful for example with DPP because we know it has a certain toxicological effect profile and we would not want to see DPP in children's toys definitely not but in present time it's not exactly so therefore there's no index there's no relevance of the hazard index again we get back to the fact that forget the hazard index I don't know why you keep returning because we're using totally irrelevant to this discussion we're using it as a basis for some of the work we're doing so therefore yes if we ignore it then we're gonna come back and people say why do we do it we're using it in response to point number one and two right yeah but we discussed yesterday that these we have to answer all these Charlie points one through two that's what we're supposed to do but it's quite a different question in what situation you want to decide on a ban right in what I thought but this we have to derive specific separate criteria which do not necessarily have anything to do with the hazard and I agree with that and that's why I'm saying that they have the index for something that's not in toys already it's not relevant yeah it's it's it's it's not even it's not even worth even discussing exactly well that's not under dispute anymore where I think we're past that point yes I agree but the last the last point down here which is number the dot the levels of extreme exposure high enough that may be relevant for certain other chemicals and it's part of the mix of discussion that we have about sure particular agents in terms of others it may not be part of the mix because we won't want to introduce them anyway so therefore it is just a number of different criteria and we're not going to settle on one to be the main driver in all cases back in some cases it may not be a driver at all that's what I'm saying about the hazard index just as well as this one so we have to use the best time for anything else before we move on to the interim band consideration let's expand the thing yeah just a comment or question it's a different direction it's not one of the six ballots it's DEP is that something that discuss at all or how will that end up in our report or would is it not relevant because for DEP you actually have kind of a flip problem or not problem but your DI is high I mean it's one of the highest exposures for phthalates but based on the animal data you know there's there's it's not anti-antigenic but there is some human data you know limited human data the swan study with any general distance and one or two other studies so I just wanted to it's not one of the six phthalates that are listed in this legislation but just wanted to put it on the table to remind us to either discuss it and dismiss it or continue to discuss it in today and in future meetings number one says consider all of the potential health effects of the full range of phthalates which means which I interpret to mean that we would have to consider DEP we haven't constructed parking lot on paper like somebody else did in a previous meeting but we need to be sure to keep these nuggets in our own personal parking lot so that we don't lose them but thanks for bringing up again okay let's expand the consideration to the interim band situation which I've defined as being similar to the situation which we would discuss and except one or more of the criteria has not been fully met this reasonable to expect with more laboratory effort in more effort in the laboratory or in the field that results will be available to determine if the substance should or should not be banned and restricted and I gave a couple of examples of the situation where there the evidence might be insufficient right now to talk about bad but there are also components of concern that suggest that we wouldn't put it in the category of no concern so responses to animal tests or research are assumed to be predictive of toxicity in humans for this particular chemical but further research is needed to be certain to be more certain that such research or to be more certain of the fact that it applies to humans and such research can be conducted in a time-lapse manner so we're not holding up a decision here for 20 years to develop some new technology to be able to answer this question the the answers are in sight somebody can do this work technically and it can be done from the standpoint of being able to get information so that would be one example where we need we're uncertain about the application of the animal data to humans another one would be where perhaps animal data are all insufficient but additional survey samples to further determine human exposure are needed and can again can be obtained in a timely manner so before we have maybe a few pieces of information that don't seem to fit together very well for human exposure and we need more to know what's really true before we overreact in either a ban or nothing so we decided to give more samples more data better characterize human exposure to able to do a better risk assessment so those would be two examples then there are perhaps better ones where we might conclude that an interim ban is appropriate so it in fact creates a ban or restriction but it puts a mark on it that we do this recognizing that there are some uncertainties that need to be resolved how does how does our discussion in the first hour fit in with this question just a question be the situation I think we're facing with the IDP and the NOP is less so with the IDP but very much so with the NOP appropriate toxicological data are actually totally absent how does that fit in so you're looking at structure activity relationship and predicting that this molecule is very similar to one that we know a lot about we would we would fully expect we need to discuss this yes so would so the first bullet point here would that capture that situation I think not quite it should be if we want to have that included this change people are inclusive we would be remiss if we ignored it I think as a group of people who have been picked to deal with this if we ignore what all of our friends who know about metabolism and toxicity already know we would be criticized for having ignored something that was obvious to a lot of our colleagues on the other hand there will be other people who say you made a decision based on nothing no hard evidence just gut feel so how can we do better than just gut feel the interim the designation of an interim ban doesn't mean things go on as usual that implements a ban or structure activity relationships are another indicator it's the first level of concern the interim ban is the first level of concern we don't know enough and so we need more data and if all the support for that is structure activity data we basically are still in the position of an interim ban I think because the fact that that is the first indication of the fact that there may impact the effects that people want to discount disprove that won't do diligence to do the research so that it doesn't exist I would think that that would be something to be on the front burner of anyone who is a producing this particular product so in the meantime with the absence of data to disprove the ban and with structure activity data being an indicator in the EPA he seems to be with talks 21 you'll be more structure activity data to at least give us an indication to whether or not something toxic or not I see no way in which we can avoid using that information I agree if we don't before silent on it we're giving the pass to a decision to collect no data by manufacturers by whoever has been involved in producing that product and has chosen so far not to collect data on it we're saying that's okay by not saying anything by not saying that ban should continue or be implemented an interim ban by avoiding the notion of the situation where we have a gut feel that this chemical to be treated even though there are very little data on this chemical it's so similar to one that we know a lot about that we shouldn't just ignore it if we ignore it we're giving a pass to the manufacturers and the toy manufacturers who probably know exactly the same thing and have decided not to do anything about it because in most cases that would be a conscious decision isn't that it never occurred to them Mike a little history would be helpful to me the history of what's happened to interim bans and what does it take to reverse one and don't let it that way it's just the history of interim bans in the CPSC well I don't I'm not aware that we've had any interim bans before before this so there there is no history the only other interim ban item in the European Union had had interim a series of interim bans for the phallides which they eventually make permanent that's it I don't think we've ever done well that's it I don't think we've ever done well there you know there with the phallides we did do that's one point manufacturers agreed to take DINP out of certain products voluntarily while we considered while the previous chap considered the issue and when it was over and the chap said that you know under though for that product and DINP by itself was not a hazard to consumers it didn't affect the product that you know DINP never went back into those products so they just moved on but I'm assuming that the fact that there are interim banned phallides right now that we're being asked to review right doesn't dictate doesn't limit the choices that we have been making in recommendation at this point it doesn't mean that we automatically have to ban them oh no not not in a way I mean that's what one big purpose of the chap is whether to continue the interim ban okay in the reason well in the I think the logic behind the interim ban is that the data were not clear as they were for the other the three permanently banned ones so our choices are no different than if the interim ban hadn't been put there we were starting to know I'm not sure we have resolved your good question about the SAR situation being a sufficient driver to make a decision other thoughts on that it depends on the detailed analysis but I thought see that these are the issues we have to face total absence of adequate data animal data the majority of the country's so this is the world living but what may be a position that we can take on this that would be defendable is that structure activity relationship data may be sufficient to drive a decision and because we only have the SAR data doesn't mean that we are precluded from making the decision that's close ability considerations etc. etc. have to come in there to bridge certain data gaps yeah is it fair for us I mean I put the same here so is it fair for me to expect that the answer to the uncertainty can be attained in a timely manner so they don't get trapped into a situation where we made it we have given the main recommendation that this is interim with the prospect that the answer is not in sight because of technical difficulties or some of the reason you have to have a GCMS that nobody has designed yet in order to do the analytical work and we know that that takes 10 20 years to shake that down before you have to have been wrong with each other bill do you have thoughts about the interim ban discussion I read the 40 page or 60 page document from ExxonMobil well not page by page I can't speak for everybody but yes I read through a lot of them they're arguing I think that at least two of the three on the interim ban list should be removed from it yeah that is no teach okay yes I think that you know we have to either using these criteria that brands come up with or others at some point go family by family and come to some decisions oh yes and it'll be based on individuals and it'll be based on the composite exposure right you're right that's that is a step down the road yeah but hopefully if we have this discussion now we won't have these discussions when we're in that process of looking at an individual chemical or combinations I suspect that the discussions that we're going to have on specific chemicals while these are I think a good set of criteria to start with the discussions that will have will generate others oh there's no doubt about that if these are so generic that they didn't that we didn't come up with exceptions later on they probably wouldn't be very useful so that there'll be we will have to reinvent some new things again we'll have to invent some new things as we go based on the data yeah but hopefully this will start as a foundation so that we don't have to go back to the foundation every time well maybe we're brus I guess the the same way I brought make sure that we didn't lose sight of DEP also making sure we don't lose sight of some of the alternatives which are also written into the legislation to consider alternatives for which we may not have any data or very very little data so just keep that in our sights as well thank you and we're going to come back for discussion at the end of this about those chemical sports startable data so right okay let's let's talk about whether or not we need to have criteria for no action or whether that's just a default that if you can't recommend a band or an interim band without further discussion doesn't automatically fall into no action or do we have some requirements for a no action decision and one of those might be that the hazard index should be less than one so that's the error correct that there adequate studies of characterized toxicity in animals as well as in oil doing by this I mean it's a well-designed study you have those response you have identification of target organs and you have an identification of the target response in those organs and you have no way and all of it suggests that either by mode of action or by level of exposure required to cause some effect this is the chemical that we're not particularly concerned about is that a requirement or do we not be silent on that and an adequate exposure survey data exists to confirm that human exposures are not high enough to raise concern about human exposure and adverse effects in humans there may be the other considerations here if we I guess what I'm asking is do it does a chemical fall into the no action category just because we have to put it some place or are there requirements for being a no action kind of a camera can I just ask what Sashley is meant by no action I'm not not entirely clear about it for example it there are three permanently banter planets we are supposed to consider those we may come to a conclusion no action necessary meaning ban should stay permanent yeah or do you mean no action there's some phallite we think it doesn't fall into the structure activity realm close that caused the phallite syndrome therefore no action meaning yeah use it this is I think this needs to be spent I think we're being asked to identify whether a given chemical should be banned interim ban or no ban so no action no actually maybe may not be the right word because I think the grants is right if something is permanent ban we don't want to bring that back on the table and I'm assuming that by no action means that we leave it as in the band category the band designation you know we take no action to change it from that was what I had in mind but this one that's not reflected here that maybe there should be another right here something it's already banned we will not be recommending to delete it from the no ban category but we have we have to indicate that we had an active review of those things that were banned or in remband to make a decision whether that should be changed from that so we didn't ignore those just because there was a decision already made we clearly have been asked to review but I think address is correct that the criteria here sort of suggest we're talking only about things that are okay so this it's no further action doesn't make much sense okay so you better to say criteria for no change from current regulatory steps okay yeah yeah but then what you listed doesn't quite fit that either I agree maybe we need we should call it what you just said criteria for no change in regulatory status and then additional criteria for for no ban or right for want of a better word but what was written here I think would fit better on criteria for no ban okay that's a good observation now do we even need to have a category criteria for no ban that's a default position and we could leave it at that because if it takes an action to either put an interim ban designation under a ban that's the action you know action is to leave it as it was yes we have on our list DPP DPP and I think we've added DIDP or DIDP sorry what criteria are we going to be asked to evaluate those three they're not bad they're not an interim ban are we actually supposed to do anything about well our charts as we're supposed to consider all fallowings and we've limited ourselves to those three additional fallowings plus the fallowings alternatives I assume we have to come up with a recommendation on each of those as well is that true Mike you know I all the fallowings are on the table excuse me all the fallowings are on the table I mean we the chap is free to recommend taking action on any other thallate or thallate substitute yeah that's correct it says on the C yeah it doesn't necessarily mean you have to go down a list and say yes no maybe but but it's certainly part of the charge yeah that's absolutely right it says here the report to the Commission shall make recommendations to the Commission regarding any thallates or combination of thallates in addition to those identified in subsection a well that's very clear so we do need a category criteria for you know not to ban yeah so yeah yeah I just point out I mean I think this is a very important point and it gets to the whole you know structure of statistical analysis in the you assume the null hypothesis and look for evidence of departure are we gonna assume something safe unless we find evidence toxicity are we going to follow a precautionary principle and the same that we need to have evidence you know of quote safety maybe we can narrow the discussion on the criteria for no ban a little bit by taking away those chemicals with no data let's jump to the last category because that will take a lot we couldn't recommend what we made a structure activity relationship consider an action on one of those but for the most part these will be chemicals that we don't have good structure activity basis for making the decision we just are no data it may be it there may be no exposure data there may be no animal data there may be neither so well what I said here is simply that kind of us for which little little toxicity or human exposure data exists remain on the list of chemicals for which inadequate data are available to determine risk to humans so I don't know that we can say anything so that then is a fourth category well that's the last one you had yeah because you're not you're not putting it in the no ban category that's correct so I just wanted to mention that as another category and now back into those chemicals for which we have read we have reason to be concerned because of the volume of production or the structure activity relationship that was to be suggestive of some biological activity or some other factor that would cause us to look at greater detail on this particular chemical which there probably is little or no data but we're going to look at it to identify those that either have sufficient animal and human exposure data to say that there's there's enough here that suggests there is no exposure of concern and the biological properties are such that it doesn't raise a trigger so we're gonna leave that chemical in a no ban status there are data that we've looked at and we have decided there is no basis for recommending a ban so that's where those chemicals go as to distinguish them from those for which there are no data but this should be restricted to I understand this as having that we have to restrict ourselves to children's toy and child care so that's but that's another limiting criteria then because not all salates I guess I have a likely to turn up in terms of toys or child care articles stop correct hold on but that goes against what we talked about with pregnant women exposure to pregnant women well same things be certain products that are associated with that just not to talk to me talk toys or chocolate products but here are other products that are used for other purposes and have no possibility categories and I think that's correct we have to learn ourselves to have a degree of responsibility I'm not sure we have to limit ourselves but that's definitely what we have to address I just prior well I guess okay we don't have to in terms of discussion but in terms of making recommendations we have to learn ourselves and I have to say I mean you know from a public health perspective lack of data does not mean safety correct and to allow for chemicals that are in wide use to be in wide use without any data to support you know reasonable safety criteria is the problem I know that I'm jumping into the frying pan by saying that but Chris that's that's why there's a don't want to make sure there was that fourth category because you're not putting it in the no-bam category because you don't have the data to suggest that it's toxic this is a category is just saying we don't know anything about it you don't know if it's safe but the actions what I'm concerned about is that the action is going to be just let it go and I worry about that well we haven't talked about that no weather that would be your okay I don't think we have right we've just talked about defining a fourth category we haven't determined well that question is what action we need to do we have any basis for making the next or on the flip side do we have any basis for not making well I'm saying is why it's a mechanical we have no basis for making an action I'm making right basically right if you don't do anything you've done something right but if you do something you've done something and yeah that's something that's credible and can be held up with challenge and when there's no data challenge will be very substantial but can I therefore suggest a simplification so we need criteria for a band we need criteria for an intermediate band can I suggest that we abandon these criteria for no action I just noticed again and reminded myself that we're supposed to do a de novo analysis so it would it make sense to leave this out and then have the third criteria on the criteria for well not not recommending a ban or regulatory action or something like that could be formulated and more brilliant by I'm trying to catch where you're heading because we have two category yeah no ban intermediate ban and then no regulatory action but we still need that fourth category we won't have data to make that oh yes and no data so we can be on the scope of what we can do without data and then like second thoughts about the phrase no data because there are chemicals out there that have a trivial amount of data that are totally insufficient to make a decision but there are no data well there's not sufficient sufficient data yeah for one of the other three categories so I would just change that to the chemicals with inadequate data instead of no data yeah thank you so slow more liberal yeah but still doesn't satisfy Chris because if things we can't do right because we don't have information but Chris is right this if we identify one of those is one of the 50,000 or so chemicals in commerce who is there no data that's it that was a struggle we had with within the National Toxicology Program because there was an expectation that the NTP was going to shorten that list there's no single organization in the world that can sufficiently work on a list of 50 to 65,000 chemicals so that it ends up being a prioritization process if we identify chemicals again structurally that we think are so important that they shouldn't be ignored then we can make recommendations in the report that are certain chemicals that warrant follow-up and be specific about the basis for us saying that and what we would recommend be done is it human exposure data is it more tox data is it both is it not toxicology data itself is it motive action data so we can make those recommendations but then you're raising the point Andrea so whether or not we should in fact not identify criteria for no regulatory action in the sense of not moving any time 18 or out of the categories where they are placed at the moment I think that's not that's very confusing so I would suggest to leave this out and not consider it with the justification that we're supposed to do the novel to the creations so what we'll have countless we'll make recommendations for a band or interim band yeah we will we will try to get recognition for a group of chemicals for which they are inadequate data and we'll be essentially silent on all the rest so there will be some chemicals that have enough data to judge the toxicity and the human exposure but they don't warrant there is no need for a band of any kind so I default or silent on those is that the position that we want to take is that what you're suggesting well I agree with the with the former categories which you which you but I'm not sure about I think we need a bit more thought about it may I mean when there's no data you can't this is a real or if there is inadequate data that's a real dilemma you know the both positions they're not difficult to maintain the position to do to file into regulatory action simply because inadequate data of that is difficult to maintain as well as the one that says don't do anything because that raises fears like Chris is just we need a bit more thought about that we can do that that's this can be a conclusion from today I guess my my thought is the category of chemicals on which there are no data make me nervous it would be nice so the flip side of that is to recognize those organizations that have collected the data and just because they don't indicate a yellow or red flag doesn't mean we should ignore we should recognize that there are chemicals out there where there are adequate data and there's no concern in the same way that we're going to highlight chemical the category of chemicals for which there are no data and we don't know the level of concern be nice to recognize those institutions those companies those manufacturers a bit the bulk and invested money and collected the data to confirm that there is no particular action needed here be nice to recognize there might be because that's the model we'd like to see followed up so category three and four basically come down to data that's been collected but there's not adequate information to make any action data was the situation with no data any substantial amount collected to be considered data where there's no action for a no a no no a use a decision can be made so you know three categories and each one there's more the farther and farther to get away from data for more fuzzy any decision to be made would be and that would tend to make me want feel that you know we just have to make a statement that in those cases it's inadequate we can't make a decision doesn't mean it's you know doing bad or ugly it's just the fact that somewhere along life I would like to preserve our ability to pull that chemical out that all we know is the structure and our no data to pull it out and I like it I don't want to put that in an untouchable category that's the trust sophisticated enough to capture that as being sorry to pull this ground again then but how many categories do we have well I'm I'm not sure well you have the the ones for for the ban intermediate then the ones where we acknowledge no fears or concerns are raised and then the fourth pin for chemicals you know adequate I think you know I know anybody disagree with that yes but I'd like to put that I'd like but no adequate data shouldn't be a place where people want to be right yeah and I don't know just by saying no adequate date it seems to me it's sort of a let them go with it and again public help I don't I don't really like that so they in the report we can make comment on that yeah yeah discuss it you know so wouldn't just end up that they're there without any discussion about difficult things of ending up in that but the action is what I'm knowing yeah what it what are we gonna say about it well just I don't know what we're going to say about it but there are at least two actions that well three actions that can happen one of them is that we bring it to the attention of regulators FDA and EPA that here's a category of chemicals that you ought to be concerned about because there are no data and you have to be concerned of those about those for which we recommend to ban or interim ban that requires immediate attention on your part but don't ignore those that are in that category where there are no data because we don't know where they belong until we have more data so that the regulators need to pay attention to that and we can highlight that we can then you have the categories of organizations that can collect data so that might be CEC it might be NTP it might be NIH NSF there are a variety of organizations that can fund research to help shorten that list then you have the watchdogs who are looking for that kind of a list to get media attention to hey look at how many chemicals we have in commerce on which there are no data and the regulators are doing nothing so those those are the outlets I think for the information in industry itself I mean the industry knows this list better than we do but you're right that's another that's the target here is to get people to step up to the line and say well we'll do something about it or we or they could be put into the intermediate yeah I think they would be hard to defend and an unnecessary burden to the economy at this time when we're already struggling so you're right but I would not encourage that but we could call them you you could call them instead of the chemical chemicals with an adequate data chemicals where more data are needed make it a positive certain we can do that there are these all chemicals that are used currently in children's products and some of the alternatives here some of the ones were just inadequate data yeah so that leads us to say more strongly that they are used in products can be two exposures among these two sets of groups and that is in common upon us to make sure that people are protected to their for adequate data needs to be collected we just can't put our heads in the sand I think that's a little bit more strength because if it isn't using the products of concern then we then do diligence by saying that their own products out there to use it we don't have enough data and I think Mike's point is the data should be collected. I would assume that some of those chemicals are there because of the performance that they bring to the product others are there because they follow along with other chemicals that are there because of their performance and they're just there not intentionally headed that they are sorted out they're not cleaned out removed. Where they have a useful purpose and be in common to demonstrate that they have a close heart. So we I think we've clarified that we have four categories. Phil what do you think of that? I'm still confused but I think it's maybe the early morning in the lack of caffeine. Well we can take care of the caffeine we can't take care of the early morning anymore but let's take a 15 minute break and think about this and then come back after that. We'll give you a call in 15 minutes. Let's reconvene just thinking of how we want to use our time the rest of the morning. What I would recommend is that we continue this discussion. I think the more we talk about it the more we sort it out and get things sorted straight. Phil has a couple of questions for us to continue to discuss. I would suggest that we plan to wind up this discussion by 12. It gives us from 12 to 1 to talk about what other assignments need to be made and I think the discussion about the date for the next time will be relatively brief but it would be done by 1 o'clock and not break for lunch. You can do whatever you want to check for that. Phil if you want to open the discussion of a couple of points of concern that you have then we can continue that discussion. I need clarification on several issues. One is are we going to apply the criteria that we've been talking about this morning? My understanding is that we were going to restrict our discussions to the three randomly banned, the three interim banned, four additional ballots not banned by CPSC i.e. Diamethyl, Diethyl, Dipentyl and DIVP and then six alternatives. And if I listen to the discussion it seems at times that we were going to go well beyond that. I think we need to come to a decision. Are we going to stick with these 16 or are we going to go beyond that? Let me just give you my other area of concern and that has to do with the hazard index which is one of the criteria that we may or may not be using. My understanding is that we don't, and I may be wrong on this, we don't have hazard indices for each individual ballot by the analysis that Chris and Holger did, but we have a hazard index for seven ballots together. If that's the case then how do we use hazard index in any event when we're talking about a specific ballot and whether it needs to be banned, not banned or put on an interim ban? And the other issue I have is if we use these criteria that we were talking about this morning, for example to criteria that has to be meant to ban something, don't we by definition, if we don't fulfill any of those, that we would not ban something? If it has an index below one, if there were no responses in key toxicity studies considered relevant for humans, if there were no responses that could be seen in humans that had a serious health effect, etc., then wouldn't we by definition not ban them? So the third category, criteria for no ban, really are the converse of the criteria for ban them? Those are my three issues. Let's start with the first one. What are the categories that we're going to work out? Well the charge is slightly ambivalent there. And under number B it speaks of to complete an examination of the full range of ballots that are used in products for children, etc., etc. On the other hand later on under number C report and shall make recommendations to the Commission regarding any phthalates for combinations in addition to those identified in subsection A. So I'm afraid we're grappling with a very badly drafted piece of legislation here. That's our dilemma. And I think that's why in earlier discussions we said that there was a rationale for identifying these 16 chemicals and there was a rationale for not worrying about a lot of those beyond those 16 because of the lack of data. So my understanding was that we were going to focus on those 16 and if there were others that we wanted to specifically reach out and say something about, we would. But otherwise we would collectively say that these are the ones that we focused our efforts on in this review and we recognize that there are hundreds of other chemicals that are beyond that that we didn't look at in any detail and to justify why we did that. I personally would be very happy with restricting it to the 16 we discussed earlier. The question is whether we are pulling short of the charge of what we're supposed to do. Maybe we need a little help with interpreting this from Mike. Well, I think that the charge says a full range of phthalates. That in itself is not a hard number and I think like all aspects of this, it's a broad charge and you should do what you reasonably can. As far as the entire scope of phthalates goes, we've identified I think about 30 and we're going to have tox reviews of all of those. Many of them are data poor. I would like to, I know we're getting far along in the process, but I would like to maybe categorize them somehow so that they're a little bit easier for the chap to think about in terms of health effects. You know, categorizing by structure and so on into groups that might make it easier to get a handle on. And of course as far as the phthalate syndrome goes, we have a pretty good idea of what the structure-activity relationship is. So we know what to suspect, although who knows there could be some surprises, but I think we have a pretty good handle on that. As far as the substitutes goes, I mean, you could go on forever. I think the number we have is, in my mind, it adequately addresses the potential substitutes reasonably. Mike, I think what we need in your assessment of phthalates and alternatives is production levels, uses, if they're used in products that humans are exposed to, that's a consideration we need to take into account. So that kind of information I think would be very helpful for us, at least for me. Yeah, I think that would be very helpful and we've started it, but we need to get that moving. But could we as Chap not make an informed decision and say we focus now on those 16 phthalates? We can justify this, I think we should, in the report, by restricting ourselves to these 16, but I think it is very plausible, very justifiable, but could we not do this? I think we've already made that decision in earlier meetings. I thought so as well, but the discussion this morning sort of led me to blame that maybe we haven't. So the question is whether we want to change that decision that we made earlier, and I don't see any heads nodding in the direction that would suggest that we ought to change it. So, soon we're going to continue with this group of 16 as the highest priority. Holger, has Di-Pentals been on the list? Holger, I can't hear you. Yeah, I thought it was whispering. Holger asked if Di-Pentals on the list and I thought it was, but I think it's one where we're still waiting for the... Is it one we're still waiting for? Phil says it's on the list. Oh, okay. Good. We made a wise decision then. Well, for me, I'd like to clarify what's actually on the list, but maybe we could do that by email. Yes. When we talk about assignments, that's one that I'm going to come back to. So, we're done with the discussion of the list. Okay, what about the HI's on the individual phthalates? There is no such thing as an HI on an individual phthalate. It's then called hazikoscient or unusual. Yeah. I don't know whether that terrifies your question, Phil, but... How do you apply an HI then to an individual phthalate, which is what we can ask to do? No. When we talk about DVB and whether it should remain in the band, we're going to use the criteria on Byrne's list. How do we use the HI information that we have on phthalates, not just DVB? This may be a misunderstanding. HI, by definition, always means that you're dealing with several, with a sum of hazikoscient. So, that may be a misunderstanding. And also, the other point was, how can an HI be operated for phthalates where they have no data about phthalates? Of course, it can't. And I don't think that Chris and Hulk have done that. But I think the HI where you're summing one thing is a hazikoscient. So, we could think of that as a general... Yeah. Right. So, in that regard, Phil, the work that Holger and I have done to date, we focus on the combinations. But we have talked about producing maybe some plots of the distributions that we see for the hazard quotient, I guess, with reference values for the reference doses from various sources on the same plot. And we've talked about maybe having that in an earlier chapter and not in the combination hazard index part. So, we are trying to address that. We haven't discussed it maybe when you've been online. Yeah. So, what you're doing or what you're saying is that instead of using the HI when we talk about individual chemicals, we would use the hazard quotient for that chemical. Yeah. That's correct. That's good. So, we need to modify the criteria then. Yes, I agree. So... As I said earlier, I think the hazard index really informs us about the last dot on the criteria for ban. I mean, levels of humans' exposure are high enough to cause adverse effects in humans. To my mind, that's what the hazard index doesn't do. In other words, if it's over one, we have reason to suspect there could be an adverse effect in humans. Is that not right? Yes, that could be so. But before we, again, reiterate, we have to remind ourselves that under point B in the law, B point number two, it says, consider potential health effects of each of these phthalates, both in isolation and in combination with other phthalates. So, that we have to do, and the hazard index approach may be helpful in addressing this part of the charge. But as I suggested yesterday, so the charge clearly says we have to do something like that. We have to consider this. So, we are going on the hazard index considerations are helpful there. But that, in my mind, has to be separated from any question relating to criteria for justifying or otherwise a ban. You see, so we have to do hazard index or consideration of combination effects anyway. But that, I think, is separate from anything relating to recommending a ban or otherwise, which we also have to do. It's a first order. It's a first order worth of information, and anything else beyond that is more important. Basically, it tells us whether we raise our antenna or we don't. Yeah. But that brings us to another point that I would like some clarification on from the committee. If you take the biomonitoring data at face value, what it tells you is that humans are exposed to phthalates. It doesn't tell you where they come from. Correct. Absolutely. That's what we've been saying today. Yeah. But so, how can we restrict ourselves in our analysis of whether to ban something only based on information related to its presence in toys, or cosmetics that pregnant women might be exposed to, and ignore all other modes of exposure? I don't see how we can do this. Well, that's where the work that we're doing on exposure characterization comes in. We do estimates of the amount of daily intake for the different types of products, and the activities surrounding those products that would lead to the bioaccumulation of those materials in comparison to the overall body burden of the individual chemicals for all phthalates that are in the environment. All you can do there is to a relative ranking in whether or not... I understand that that's an important thing to do, especially if you want to put in place restrictions. So, you say, we know that exposure occurs through house dust, so everybody has to vacuum their house every day to reduce exposure. Or, more importantly, that we know that the exposure potential for using certain kind of menics with phthalates in it are high to find a replacement. That, I think, is a more appropriate way to look at the standpoint of the charge that we have. That's an example. But my point is that despite all that, we already know from bio-monitoring data that we are exposed to a whole range of phthalates. And I think to consider whether or not to ban something without taking that into account, which I think the hazard index nicely does, unless I misunderstand, I think we're missing the boat. I think we are going to take that. I think part of our discussion yesterday, maybe you missed it, in the morning, indicated that we are going to take into account the fact that there's a constellation of other potential roots of exposure and sources of exposure that has to be considered beyond what we can do with our limited ability within the charge of this committee. And not just saying that in isolation we solve the world's problem. I understand that, but what I'm getting at is how do we apply that to our decisions about whether we're going to ban or not ban or whatever, a particular valley. I'm confused as to how that's going to be done. And maybe that won't fall out as we use these criteria and discuss DVP based on these criteria. Where would it fall? Would it be banned? Would it be an interim ban or what? Maybe that will fall out and I'll understand it. But right now I don't understand how we are going to apply these criteria to individual chemicals when we know that people are exposed to probably all of these or most of these. I think we'll have to just note that it's your problem and it's basically a problem that we all have, I think, in some degree, but we just have to live within the charge that we're dealt with. At least that's my opinion. I have the same conundrum you do, but I think the only thing we can do is just, I think Andreas has said quite clearly a number of times today, we have a limited vehicle to operate with in terms of banning, meaning children's toys and products that can be used by pregnant women and let's do the best we can with that and use that as a basis for people to consider for other types of materials and sources. I think you come to different conclusions if you limit yourself because if you say that exposures that are relevant to CPSC do not rise to a level of concern when we know that taking an aggregate from all exposures that they would rise to a level of concern, I don't see how we can do that. Am I making myself clear? No, I don't. Look, we do this with every other chemical that I've ever dealt with. Banning, where do you make, where do you put your axi and how do you impact accordingly? It would lead to as many sources, benzene as many sources, you have different regulations for different agencies that can control the emissions or the banning of lead or benzene. You have to work from what your agency or your legislative mandate is. You're going beyond that. All you can do is recommend that there's a whole bunch of other stuff out there and you have to consider it. I just don't, I mean I've done this before and that's the only way you can work. But I think... Mike, is that hero? You agree with that? Yes, yes, I mean that's the system that we have. You know, the charge goes well beyond our jurisdiction but we have to, you know, in the end the recommendations are going to be related only to consumer products and not sources beyond that. We're considering the exposures from the other sources. Okay, so let me pose it this way. If you know that in the products that you can regulate, DDP, just for example, is followed by our analysis not to be a particular problem for humans based on exposure, based on whatever. But you know that children are exposed to DDP by a variety of other amounts of exposure where when you add those in, they're at a level of concern. Would you not ban DDP because in the products you regulate, it doesn't rise to a level of concern? I think that is within the CHAP's purview to recommend to ban or not ban based on that. And it's also the Commission ultimately would decide whether the portion that comes from children's products warrants a ban or a regulation or not. In a case where, you know, if we were looking at lead or even some other chemical where there's a significant background exposure, we consider that background exposure or we can in setting any kind of a regulation. This is a little bit, this is kind of stretching that situation because the quote-unquote background might be greater than the product specific exposures. But, you know, this is what we are going to do and the CHAP will make its recommendations based on public health. The Commission will make a decision based on public health as well as the regulatory framework. And then we know that other agencies who have authority over other products will be looking at the CHAP report. In fact, there are several programs at EPA who are already working on Valleys. So, you know, I think that the CHAP's goal is first to say this is what we know about the risks and what's causing them. This is number two, this is what the Commission we recommend to the Commission. And then beyond that, you know, I don't think the CHAP report is going to fall on deaf ears. I think that EPA at least and maybe other agencies will be involved. Phil, in my opinion you are expressing a dilemma I'm grappling with as well, I have been. The dilemma is this, your example is very good with DVP. There could be a situation where, say, the amount coming out of child care products or children's toys is not very large. And yet there is background exposure from other sources. Looking at background exposure, we might come to a conclusion we are now concerned. Looking at what's coming out of child care products and children's toys, we might conclude, well, very little irrelevant. Therefore, to resolve this dilemma, it is practice in other areas of chemical regulation. For example, in the labelling arena, when you label chemical hazards, to not consider exposures. Exposures do not enter into these considerations at all. What is solely important is to judge when the chemical question has a profile of toxic effects that give rise to concern and then they are regulated on that basis. And I think we should adhere to this, there is precedent for this and stick to that. And that would resolve a couple of dilemmas and focus the situation. Okay, that clarifies things for me, thank you. So what I meant is all these pieces of law classification, labelling, etc., etc. They never ever do exposure considerations enter, whether you want to, for example, classify a chemical as carcinogenic. It's solely based on tests, clearly described toxicological assets. Except in the US. It's absolutely wrong, you're absolutely wrong. Smoking, secondhand smoke, you're absolutely wrong in that. Well, it's not chemical in the sense that you... We have labels on cigarettes, I mean, my goodness, we do it based upon exposure as well as toxicity. I don't think smoking falls under the remit of this CLP regulation, which is a worldwide piece, which every country... Well, the Americans have to adhere to that as well. This was negotiated at UN level. So, I mean, smoking may be a special case, but let's not complicate that, it matters. If you want to look at a chemical called benzene, it is very clear, it is a carcinogen. And you classify it, label it, etc., as such, or chromate or whatever you want to say. And that's solely based on the outcome of toxicological tests. Mike, was there something else you were going to talk about? I mean, this is another dilemma. Europe, the globally harmonized system, have labeling that is at least primarily based on the hazard, not the risk. In the U.S., and especially consumer products, everything is risk-based. So, you know, we're still... I don't know which way we're going to go in the future if it's going to be more toward a hazard-based or not. But I know that there is a provision in the GHS for risk-based label. Yeah, for certain cases, yes. But all I'm saying, I mean, we're not proposing to revolutionize globally harmonized systems or the CLP or whatever. We are just dividing, we're looking around for what other people do and what is useful for the task at hand. And while I can only repeat myself, that's my proposal, I think it's logical. So exposure considerations should not enter this. I mean, there's no need for the panel to go on. There's no need to hazard in risk. We don't need anything. I mean, if you're basing it on low-antoxicity, then a lot of the work we're doing, we don't need to do it. No, no, no, no, no. I repeat, look at the charge. There are all these point points which we also have to address. For these, we need the hazard index. For these, we need the exposure considerations, et cetera, et cetera. We're banning material. We are also expecting to do this and put it aside and just do that. I don't think that would apply. I don't think that would apply. That's why this law is written the way it is. Yeah, I mean, we cannot ignore the charge here. We have to address these points. I think the bottom line is by addressing those points, it puts a lot of information on the table and we're going to account for all of that information and then make a decision. And especially recognizing that exposure changes when some chemicals are banned and others are allowed or whatever, exposure changes so that cannot maybe be completely foreseen. So to base things solely on risk is unpredictable. So going back and looking at hazard information is valuable. So, you know, I think we're getting to the point where we're saying black and white and it's really a lot of things together that are going to be put in. And that's what Burns List has provided, sort of a wide description. I think there's a lot of shade to grade. We just have to, we have to walk through. I think the point was maybe before we have to walk through this example and see where it leads us. That's the better way of looking at it because we don't know what we're going to say in the end until we see what the data shows. I think what is least useful is for us to get one word answered to a question about this and that's why I mentioned earlier about the textual description and for some of them I'm sure we would emphasize hazard more than anything. In other words, we might emphasize exposure more than anything. So I think in the context of textual description we will focus on risk and hazard because that would be the best way to describe power concerns and it may also be most useful in the future. Question. In terms of applying your criteria to the 16 chemicals, how are we going to do that? Are you and I going to do that and then send it out to the committee for comment or are we each going to do it separately and then fuse them together? What's the process? My suggestion would be that each of us does this and perhaps in the next meeting we would spend a lot of time comparing notes, comparing thoughts. What drove us to say this or that about each chemical, combinations, whatever it is that we want to focus on. So I think that has to be a committee discussion to derive that and I'm not sure that I want my own opinion to either accept or reject. I think it's best that we each have the opportunity. We all come to this from a slightly different leaning. I think it's best that we all do it individually and then talk about it. Other thoughts about that? The next meeting I think I would say that we could get more specifics in terms of the toxicology chapter so that we can base from that writing. Whatever is the right time. That's how we do it. Two tools we need. In the dilemma with the hazard index and the hazard quotient so the hazard index might be above one and the hazard quotient for the individual is below one definitely below one. So we will have this consistent in the end that might have to look at the hazard as it is and the risk. Russ, are you okay with this approach? What are their concerns or details? I think the criteria served a purpose this morning. I think we've gotten a lot of good discussion. I will revisit this and try to recast this to reflect the conversation that we had this morning and put a preamble to it to give it a little better context. And again, not that we're going to do anything other than just read it and use it to gel things in our own minds and so that we weren't in a consistent manner. But there isn't anything in this set of criteria that we can revisit as we need to, case by case. But I'll take that on as one of the assignments. Another consideration about the no data concept I would think that in many cases there are data it's a question of what's available to us and what's public because I'm assuming that there are a lot of data in regulatory agencies in the U.S. and outside of the U.S. that we don't access in a literature search but it doesn't mean there aren't any data. It just means that there's information out there that we can't access. Unless you get special permission from a manufacturer through an agency to be able to have access to that information. Mike, would that correctly characterize what we would find in a literature search? Yes, yes. There are data that are available, data that are not available. Yeah. So the term no data isn't necessarily accurate. It just means no data available to us through a literature search. If we are done with this, we should quit before we undo something. Maybe we could clarify what our tasks will be between now and the next meeting. Yes, and let's go on to the topic of assignments. And it might be good to go back and look at the outline that we have that's very early in this notebook and make a list of the things that we didn't have on the outline. We already made some corrections to it earlier. Excuse me, what do we need to have homework done between now and the next meeting? So we have what we need. And I guess we should talk a little bit more about what do we expect to have in hand for the next meeting? Well, I'm going to write up the results of an update of literature on the mixture effects of phthalates in animals and also combination effects of phthalates with other animals. I think there was a table that was sent around. I haven't studied it yet that had RFDs from various sources. Did you send that out, Mike? Yeah. And I'm not sure if we need additional pieces to that or if we think that, did you look at our homework? Yeah. Well, it's a list of all the published regulatory agency reference doses, ADIs. For how many chemicals? For a handful of phthalates, maybe half a dozen. I mean, the ones where people have bothered to issue those. Okay. So with that, I hope we can extend our cases to include maybe not just anti-androgenicity activity, but whatever the guidelines are based on, the references are based on by maybe the EU and the EPA. Yeah. Now, the EPA ones are probably out of date or maybe out of date. They will have new ones, draft new ones in the fall. But anyway, if they look like they're way different, it's probably just because they're old, if they're different from everybody else's. But also, if you're going to look at individual chemicals or if you're going to look at DDP or a phthalate that's not anti-androgenic, you probably would look at the most sensitive endpoint, which is something else. And Chris, it's my intention to develop our fees for developmental toxicology for each of the ones that I can. So that would be helpful maybe to add to this table. Do you have a time frame in mind, Phil, that it would be? I should be able to get that done, you know, at least by the end of the next month. So that should give us time then to go ahead and expand our cases. I think we should work on this together, Phil. You should check the vendors we use and double check them. You should check whether our case one approach it. The one basically based on Andrea's work is OK. Or if maybe case two with the Earl Grace data is OK. Right. You know, you don't, obviously the chap can derive its own ADIs. You don't have to use, you know, EPAs or anybody else's. And our charge is to do this gainable would probably would be a good idea for us to derive these ourselves as well. Yeah, actually our case two approach is a gainable approach based on the presentations from Earl Grace or Foster and also preliminary data. So that's really the noble approach. OK, another assignment that we agreed to for some of us was to come up with summary tables of the information from our sections that will detail into what some of the rest of you are working on so that we can go back and forth between there so that that's maybe that's you, Russ and Phil and me in particular. The three of us. We will have new literature reviews on literature reviews on chemicals that we haven't seen before coming from Versa. And when would you expect those, Mike? We hope to have drafts by the end of April. Yeah, we could send you the drafts as they come in. OK. Walter? Personally, we'll have to work on the individual relates risk assessment with the data intakes related to the TDI's RFE. So we'll do, we split our cumulative approach into the single tellings that most of the data basically is there. OK. It'll be a noble approach to, based on the individual RFD speed it does from current data. Are we going to actually get estimates of exposure for things that we don't have biomonitoring data for? For the full 16 or 17, whatever the number was, list? Depends upon the data that's available. I mean, it all depends upon what we have in terms of the product. Formulations and whether or not we have data used substantially in terms of looking at titration or what would happen when you apply it. Sure. If it's available, we can get it. I think the answer is for some you'll get pretty good data. For others, you may get a limited range of scenarios. You know, I'm thinking the substitutes. I'm thinking in terms of just the products that, you know, we have data on the children's products that CPSC tested. I don't know. Is there a need to go beyond that? I don't know. So it may be difficult to get total daily and take estimates for some. Yeah. And then as you go down the list of phthalates, you're going to get fewer and fewer data of any kind. Are we interested in trying to approach, you know, the substitution effect to try to look at exposure predictions as some chemicals go out of the market? Others are used? We'll be able to get some. We'll be able to get, if they're comparable products, we should be able to do comparative analysis in the previous valuing with the substitutes. If we have the data, we can do comparative analysis using the same basic calculations of exposure. So, but it sounds like that this timeframe of this is not going to be between now and the next meeting. That you guys are... We're supposed to... The data acquisition process, which Mike and I outlined, because it is substantial, hopefully be done by the end of May. And you and I are meeting with, hopefully, Mount Blobber and three of us will go over how the exposure sets will be done in the beginning of June. And then from then on, I gave a cranking of the estimates. That's where I think that's where we are. Because it is a tight consuming process, and even if they... I think they have a reasonable timeline based upon what we know will be a difficult task. We have some now, but as I said yesterday, we want more. That, I think, is a reasonable timeline. So I would assume, for the standpoint of having data available, Mike would figure we end up in the middle of July once we get our act together. I would hope so. Yeah. So the comparison to the biomonitoring results and sort of combining the two together for maybe additional chemicals, that's further down in the summer, fall, we're not going to be doing that. I think as we get data, we can actually give you information. And the more, you might say, the higher tiered stuff, the more it's possible. And then as other things come out, we'll give it to you. We'll work on the top six first and then go from there. Or at least a draft or, you know. No, I don't want to leave you guys hanging until full. I would be unfortunate. Where we are. Any other pieces that we talked about filling in, what I have right now for assignments? Andreas will be working on the literature review of the animal evidence of the effects of combinations. Phil and Russ and I will be working on summary tables for our areas. New literature reviews are going to be coming from CPSC that will drive further of the same thing that we've been doing with just our more chemicals. Lists of updates of RFDs and generation of new RFDs by Chris and Holger working with, working with Phil. Holger and Chris doing more hazard index evaluations in the meantime and on individual line groups. Mike, one thing that I still think is needed is a list of chemicals that we have now agreed upon with their molecular weights and with their cache numbers. We really want to have just one such list in the report. Yeah, and I think with the understanding that everything on that list, you know, maybe it doesn't show up in biomonitoring or some, you know, or you might not find exposure data. I mean, we will each address those chemicals to the, you know, everybody will address those chemicals as, you know, the best they can. I mean, if it's not in the EPI studies, then you can't address it. But we need to know that there are no EPI studies out of it. So if we don't, we're not silent on it, there's nothing there. We need to know that there is nothing there for that endpoint. Okay, and then one more thing, the one that Paul talked about last, Paul and Mike working on continuing with the exposure data. So I think those are the assignments. And if I look forward three months to what we get from those assignments, we're not doing anything new in a revolutionary sense that we haven't done before, but we're filling in. And we're adding pieces as we go to what we've already begun as a format for the report. And I would expect that we would spend a day and a half next time going in more detail over the materials that we have in the report and less time talking about the overall approach that we're going to use to do this. Next time we'll be more detail on the actual contents of the report and then the discussions that come out of that. Now, we need to talk about dates for a meeting in the last two weeks of July. And one thing that we talked about that I'm not sure we've gotten in front of you yet is the desire then to begin to talk about the next meeting with the next four meetings, not dates for the other three. But if we have a meeting sometime in the first two weeks of July, then the next meeting could be in October. And then the meeting after that would be January, February, time frame. And then the meeting after that would be April. So just to block out what we're going to do for the next year so that we can begin to pencil in times for meetings beyond the next one, that's what we're looking at. And each next time we'll have to talk about specific dates for the October meeting. But if somebody is going, knows now that they'll be going all of October, out of pocket, out of all of October, it would be helpful to know that now. I'll be out of town in Europe in the second half of October. Second half of October, so we're out in the first half of October. But for now, let's try to get a date or a meeting in the second two weeks of July. The first two. I'm sorry, the last two weeks of July. There's a National Academy of Sciences meeting on Mixtures, the 27th and the 28th. Meet before. 25th, 26th. Look for me. Look for me. We're talking about the 25th and 26th of July. Of July. It's okay with me. That's a Monday and a Tuesday. Yeah. Yeah. Oh, that's okay with me. It works. Okay. Let's say July 25th and 26th. It's photocopying. Mike, is that okay? It's okay for a year? Yeah. It's helpful to have everybody here first thing. Yeah. Monday morning. I think I'd be able to couple hours and start on the meeting. But if people can't be here, that's different. So it sounds like we're okay for July 25th and 26th. And I think it would be feel to try to set dates for October that would be out. But if you can, you know, like we already know that the second two weeks in October are a problem for Paul. I'm here on 21st, 22nd, anyway for this international toxicology of mixtures meeting. So. October. In October, yeah. So it would suit me well to combine this. So if we met on the 18th and the 19th of October? Perfect. I can't. I have a new meeting. Otherwise, we're into a weekend. What about to do the 24th and the 19th? In Europe. In Europe? Mm-hmm. Yes. I'm in Europe for about the 16th and the 21st. Well, if you're not here for the, if we looked at the 24th and 25th, you're not here any longer. Well, we may not be able to match up with your meeting. And the 17th and 18th doesn't work either? No. I have an American Society of Reproducted Medicine from the 15th and 19th. What about some two days of the week of the 10th of October? It should work. The only thing I teach in the law, so I just have to. I don't know what my schedule is. I could teach Tuesdays, Thursdays, but not every four. Not every five. But I could chat. I'll get that. Or I have the syllabus. Okay. I'll check that too. Phil, are you available on the week of the 10th of October? Yeah. My teaching is only Wednesday and Friday, but I can work around that. 10th of October. That's a holiday. Yeah. When I get a fine to figure out when the holiday is. Columbus days. This is the 10th. Yeah. So that would be... 12th of the 13th. I just have to check my teaching schedule. I don't know. I don't like your condition. You have a conflict? Yeah. On the 12th and 13th? 13th, 14th. And Monday is a holiday? Mm-hmm. So, 17th, 18th of October was out? Yeah. Mm-hmm. Yeah. I assume that September is cutting it too close? Mm-hmm. Ready? Of course we could have done that. That means we're into November. The first week in October? Not yet. The 10th is bad. The 10th is bad for me. The 10th is bad. Yeah, I think that week is for us, first of all. I'm available the first week in October. October 6th, 7th. Or October 6th and 7th would be about 12th. 7th is not allowed to fly. 7th is what? No, I think 6th. Yeah. The 10th to 6th. October 5th and 6th? The 10th is bad for me. October 5th is bad for me. 3rd and 4th? What's the least bad? I mean, I know Paul can't make 24th, 25th. But who else can make 24th, 25th? October? Yeah. Is the ICS conference in Baltimore from the 23rd to the 27th? Yeah, another one. And who are they? So you're going? I'm going definitely. I can't be in Europe. There isn't time for it. Who again couldn't make it before, say, any day between 17th off October 20th? I never told you. I mean, I can't. I reproduced in Madison meeting from the 15th through the 19th. It's terrible. What I would suggest is that we collect information from your calendars for October in the first week of November. Yeah. And we may have to decide what is the best time or we can get everybody for one. Yeah. Could you send us a spreadsheet to wrap the guy in the mic? Sure. So we'll do from October, we'll do October, November? Yeah. What about the first week of November? The 31st is bad for me. But other than that. Yeah, 31st, I can't die then. Well, the 31st of October. Yeah. But later that week would be fine. The other days in the first week of November, the latter part of it would be reasonable. Would be, yeah, test at 5 a.m. It's good or bad. It's good. That's reasonable. The 3rd and 4th of November? Yeah. That's just not, yeah. Just asking. Oh my God. Does that agree? I don't know. Yeah, let's take this quickly. Is it a miracle? Is that okay with you? It's good for me. Let's mark down the 3rd and 4th of November. Good for you. I'll have to just make sure with teaching. Yeah. I'm not Thursday, but I know the 4th is definitely good. Shall we pass it to you? Yeah. All right. Think it in on your computer. Permanently. Yeah, look. It's helpful. Should we drive for more? No. No, I don't think so. We'll save that phone for next time. Three things that I had in mind for this morning. Do I have time before? Anything else you want to bring up? Bill, anything from you? Okay. Mike, anything from your side? No, I think we're okay. I assume Lisa has talked to you about it. About whatever travel vouchers you need, whatever you need to do. Other than that, we're good. Did she give you anything? I'll check with her. No. She hasn't said anything about travel vouchers. Just travel to the airport. Yeah. I'll make sure there isn't anything else. Well, thank you. There's nothing else. Thank you, Byrne, for filling in. Thank you all for coming. Bill? Yes? Did you do anything after the meeting? You're breaking up all of you after the meeting? Yes, please. Yes, I will. Well, I guess we're adjourned. Thank you all. Thank you.