 Okay, welcome back Let me just Remind everyone to sign the attendance sheet outside and The meeting is being webcast and it is being recorded this afternoon We're I guess going to continue with our discussion of the pieces of the chap report and Right first we're going to talk about the exposure assessment and That the exposure scenarios and I guess we'll start with a presentation from Surge Dasgupta from Versar. Thanks Mike Good afternoon everybody My name is Serge Dasgupta I'm an environmental engineer at Versar Incorporated and I'm here today with my division director David Boddmer who's sitting out there and The presentation that I'm going to do today is Going to include a basic overview of The steps that Versar has done to Calculate scenario-based Aggregate human exposures to phthalates all right I'm going to talk about the objectives and then Dev a little bit into the overall background Then move on to the methodology that we have used for this particular task I'm going to show you some Excel Workbooks, which you know will give you guys an idea of some of the preliminary results That we have so far And then finally we can talk about the next steps of the future course of action So the overall objective of this task is for us to Determine or to calculate scenario-based Human exposures to a variety of phthalates What makes this process complex is that it's truly a multi-dimensional issue because you have a variety of phthalates these phthalates are present in a variety of media and We have different exposure routes So to capture, you know the relationship that exists between all these and To look at how the exposure varies between different populations is definitely a challenge and that is what we are Trying to achieve over here The way we are going ahead with this is is what we call, you know, we are focusing on the forward method Where we look at, you know, the Concentrations and the exposure factors put them in in an equation and come up with an exposure estimate as opposed to the backward method which is trying to You know Measure the amount of phthalates present present in in blood and urine so on and so forth In the background, I'm going to talk about some of the exposure routes that we have looked into And how these relate to phthalates present in the different media The list of phthalates that we have focused our research on so far the different subpopulations that we are dealing with and and a few sentences about general data requirements So this figure out here kind of gives you a Big picture of of the different Exposure routes that we have come across so far Dealing with this task as we know the three main routes are inhalation dermal and oral but between them you also have certain sub Subgroups or sub, you know exposure routes if you might call it so and The next figure kind of gives you an idea of how these are related to the different media Before I get into the details, I would just like to say that this is an evolving process We are finding out more about the complex relationships between the different media that the phthalates are present in and the exposure Out so this is not, you know the complete thing. This is just a A picture of what we have found so far. We are still doing the research and this is going to get You know corrected as and when we find out more information But just just to give you an idea For example under inhalation, you know, we've we've seen that a variety of media would contribute to Phthalate human exposures personal care products environmental sources like dust soil Water and of course the use of household products and and and the list kind of goes on As and when we try to look at a particular exposure route We do research and we determine that you know the data comes from a variety of media And so the idea is to compile all that and then come up with a single exposure route for a particular given You know route media combination Some basic guidelines These are the list of eight phthalates that we have focused on The population groups the idea was to first focus on pregnant women and women of childbearing age Some of the results that I'm going to discuss today are are are only going to be for this subpopulation The next steps of course are going to focus on infants children and then adults We decided to come up with a qualitative estimate of the quality of the data in other words classified as high medium and low and This is based on some basic guidelines and and I will talk a little more about that in in the subsequent slides As far as statistics are concerned What we've observed is we have a variety of Concentration data for a particular phthalate in a particular media So the idea here is to come up with the mean as well as the 90th percentile value For those concentrations and then combine it with the exposure factors to come up with exposure estimates Moving on to the methodology as as I mentioned sometime back the idea is to use the forward method To calculate aggregate human exposures to phthalates So this task can clearly be divided into two groups One is the group that focuses on compiling concentrations phthalate concentrations and the other that focuses on obtaining the exposure factors As far as concentrations go our efforts have mainly included, you know, we've received a lot of data from CPSE We've also looked at we've obtained the data from A detailed report that we submitted to CPSE back in February of 2009 And we've also been doing some additional literature search As far as explosive exposure factors again, we've received some data from CPSE and Most of the concentration factors that we hope to find would be in the exposure factors handbook that where SAR has compiled for EPA and Of course additional literature research for example outstanding papers like warm-up. Really it has a lot of useful information Where I'm sorry I think where SAR was Involved in this task a couple of years back where we looked at exposure factors For a variety of populations, you know infants children women and we came up with Factors that were all compiled in a handbook and this is I believe it has yet to be peer reviewed But it's you know available in the website EPA website And I believe the the version is 2009. Is that right? Okay. Okay. Okay Sorry, but what is it? Oh It it basically contains the the factors Exposure to humans by how much area you breathe how much water yeah, yeah, okay examples All right, so it could be things like skin surface here exposed skin surface area the number of times You know a particular product is used What what percentage of the population you know would be exposed to that thing the fraction of that particular chemical You know absorbed a fraction exposed those those sort of things how much food you eat exactly Consumers non-consumers Yeah, and there's the children's exposure factors handbook. Yeah a separate handbook for And this the 2009 is is an update. I mean it's There was at least one prior addition maybe two 97 was is the latest 90 is the finalized version before this one. Yeah, and there was one in the I believe in the 80s, okay so basically what it provides for for all of us is is information that since we don't have individuals who have basically Had exposure assessments done for phthalates provides data to take you from source human receptor What the exposures could be based upon inhalation dermal uptake? ingestion and then calculate a an exposure For these media and then use daily intake, you know by intake rates to figure out a daily intake value Which can be comparable to what you're doing and you take it by this different media or different routes And you can basically sum up whether it's from from ingestion and ingestion of food versus inhalation So you come up with an intake value that is accumulated I think you should have to find what a aggregate exposure is it's aggregating all the exposures across different routes That can enter the body and then you have measured or Estimated values for each one of those routes to compare against the total versus compare against what you come up with in a biomarker So just a point of Education so all those things have distributions to them. So are you summing the median? Are you summing extreme values? Do you do both? But I forgot what we rely What we agreed upon was to use the the mean and the 90th percentile values for the concentrations only as far as the exposure factors go We are norm. We are primarily going to focus on the mean values But why the mean and not the geometric mean since you would expect skewed distribution and why the 90th instead of the 99th? The exposure as you know is like an art more than a science You know and a lot of times that I Think we strive for something called a high-end high-end of exposures Which is defined as between the 90th and 100 percentile some people like to try to get it what the 95th is I think it's more of an art typically when you have Exposure factors, and then you have exposure media and then you have multiple pathways You really it's it's your opinion as to what is a true high-end, you know the real population not the hypothetical or theoretical upper bound So typically what they do is they they choose maybe like a high end with regard to exposure media But then take average concentrations, and that's the art of getting at a high end of an expose, but it's it's To answer your questions probably no, you know, there's no proven rule of thumb is to the best answer It's more of an art because you go to the extreme by saying highest Concentration highest of this highest of that highest of that and you're up with a person who never existed I'd before they were born used to they used to do that and then there was a push in the community to try to get at the real population Yeah, I think that's usually a combination of some mid-range central tendency values with some high-end and and we all sort of agree That's the best way to go And actually thought we were going to use a high-end concentration See what that does and then In another Calculation look at a high-end frequency of use or that sort of thing. So we're going to have Both the two high-end values calculated by different means Different methods Yeah, no, no, and in in fact, I mean when we said well mean, I mean we We meant an average value because Depending on on the studies People may only report a mean or a geometric mean or Or a median. So it we were using average as a generic measurement of central tendency um Yeah, but yeah, that's a good point, but When we started researching the exposure factors, we realized that in some cases It's very difficult to come up with a single number. Sometimes the number is there. Sometimes we had to kind of aggregate itself like for example Use of a lotion We had values for face for hands for legs So in some cases we had to come up with you know a combined number So in those cases they themselves represent the the higher end Um, just make sure you document all this. Yes. Yes. I'm I'm I'm going to show you some of the Spreadsheets which you will see that it's all document well documented and and if you put it to what you've been using, you know, you use the biomarker data, which is usually a point estimate You know, it's it's the same sort of thing. There's a little bit of artwork Science to try to come up with a daily intake okay, um Coming back to the the the data quality Again, this is something that is not really set in stone. We are This is an evolving process, but in general What we decided to do was Focus mainly on us data and data that you know has been Compiled in the last 10 years or so and that would be classified as high quality If for some reason that data is missing we would then go and try and obtain european data Generally the idea would be to obtain data from peer reviewed journal articles that would again qualify as high quality And in some cases the numbers might be really low For example, you know, we just have one or two values for a particular phthalate found in a particular media That could mean two things one is the data could be sparse or limited Or it could also mean that really that particular phthalate is not present in that media So we are going to make that judgment And we will document that Moving on now to Some of the the preliminary results As I mentioned earlier our our primary goal was to first focus on The subpopulation which was pregnant women and women of childbearing age Within that we focused on three specific exposure routes That would be inhalation Dermal cosmetics mainly personal care products And direct ingestion which is mainly you know food and beverages So the way we uh did this task was for each General exposure route We have three spreadsheets the first spreadsheet Has concentrations concentration data only and it provides details of you know All the the data and I will be showing you examples of you know these spreadsheets that we've put together The second would be exposure factors and as paul had mentioned sometime back the way we've compiled it is For each exposure factor that we have come up with we have a justification Or our comments as to what our rationale was to come up with those numbers And finally the third spreadsheet You know combines these concentrations with these factors Plugs it in an equation and then comes up with an aggregate Exposure number or estimate um From here i'm actually going to exit this presentation and then open up some of the the spreadsheets Yes, yes, yes, I have them here uh what i'm first going to show you is um The spreadsheet where we have compiled all the concentrations And again, this is not complete This is just you know has a good good amount of data, but we are obviously you know adding to it so The way the data is arranged is you have Valates the different exposure routes you have a general media and then you have a specific media Uh, the specific media goes into the actual the actual media there there, you know the concentration was found this kind of Gets into a little little bit of detail You have uh the the population now remember in some cases It clearly mentions that the data was collected for that population group In other cases it doesn't mention anything So we are just going to assume that that you know, you know exists um You have a column for data qualifier, which you know some of the studies mentions What the data is if it's mean or a maximum or minimum whatever we tried to document that Um, these are the concentration values These were the units that they were listed in in the articles or the documents that we looked at Some of them mentioned the number of uh, you know readings or the records It gives us uh the location Have the the source And then we have uh the conversion factor because the idea is to Get all the concentrations in in a single unit so that it can be aggregated or combined and then used in the equation So we have conversion factors and we have notes in some cases as to you know, how we converted the units from you know Um one unit to the other these are the new concentration values the new units And then we have some additional comments Uh, the last column is is data quality Which um, you know, we really haven't uh completed because you know, once we look at the data, we you know Have to make some judgment calls and and decide How to classify the data But uh, this is really in it's it's almost like in the form of a database So if you use filters in excel for example, if you want to look at One particular phthalate the EHP You can see that this is available In the following exposure routes or rather, you know, humans could be exposed to this particular chemical In all these different ways Among this if you want to you know, look at say for example Inhalation Then you see that You know, these are all the different things where DEHP would be available Uh and humans could be exposed to it through inhalation so This really gives you You know the big picture thing, but you can really drill down into the details using filters and it could give you specific answers What we did from here was to split this data according to exposure routes so in today in today's presentation, I have uh ingestion direct which is nothing but food and beverages And then we have uh dermal cosmetics and then we have inhalation. So we split the data And then combined it with some of the exposure routes. So this is I'm sorry, go ahead clarifying question. So I'm Maybe because I'm not seeing all the way across a row, but when you have multiple like you had Relation household dust multiple times It could be is it different kinds of household dust? Yes different sources location. Yes different data sources Or it could be the same paper, but it could be collected at you know different locations in the u.s So, but at the end of the day, are you going to come up with a single? Yes That way you were talking about the 90th percentile of the yes average of whatever That household dust was across whatever locations and whatever correct The idea the idea is to combine these values For one particular phthalate for a particular media So in this case Based on the question that you asked what we would do is we would take all the dehp values For inhalation For household dust indoor And we would come up with the mean Of those numbers as well as the 90th percentile And then we would use those numbers as You know to calculate exposure estimates That is just from concentration these values And then do you just do you differentiate between a woman a pregnant of childbearing Age and then also pregnant women or do you put them together? Well Yeah, as of now we have combined them. I think the the reason being that at this level you Can't find much In terms of data to that distinguish between the two I mean maybe inhalation rates and body weights But You know other than that The concentrations are the same and so on yes and the factors are not specific for pregnant. Yeah, and yeah the factors Aren't specific enough. I mean there are some research papers, you know where they have only looked at pregnant women And they have calculated concentrations. So that's clear cut But for the most part what they do is they just measure phthalate levels in in different media And and the assumption is that All Everybody's going to be exposed. But do you use that as kind of a tier where the top tier is if if there's data available For pregnant women and that's the values you would choose if not then you would use Well Because well the thing is that so far there is I think we have just come across just one or two studies Where you know the data is only for pregnant women. So it's included over here But you know the calculations also include all the other concentrations So, I mean we can we can you know categorize it Um, it would just be a matter of you know, selecting a subset from this and just saying that you know, this is Really really specific because even the concentrations are specific only to pregnant women Um, and and the thing is it would be easy to do that because I have that listed as the comments As in this was collected only for pregnant women So it would be easy to do that in the future Can I ask a question from from all I know um concentration data In media like this are not normally distributed. They're skewed, but I notice you use averages Often you have bimodal distributions even Could you comment on that? What we have done so far is um, we have tried to compile data from a variety of sources And within that source Sometimes they list all the values or sometimes they just have one number So the for to make it simple the assumption is let's go with you know the 50th percentile or the or the mean And you know if there are specific studies, which give us you know more detailed data statistics Then we will look into that Because we wanted to you know Not get bogged down with details When it comes to one or two studies because really there are very few studies that provide those that kind of detail The idea was to focus on big picture Um But there any I have a question too in terms of individual getting at that mean Some studies have large n some have very small and did you treat each study? As an equal in other words, did you do it on a uh a sample basis or did you derive your means on a study basis? um in some cases No, we we treated everything as equal in other words The mean of study means Or the mean in other words if one study had large n n equals 100 Did that study overwhelm everything else all samples treated equally? No, not in what we have compiled mean of study means. Yes. Yes. Yes And and that's a good point you raise because you know, we came across that where some studies have one right there 120 homes Versus one home versus, you know Yeah, so the 120 home study was basically treated equally to the study had one home. Yes. Yes There's there's arguments on both sides. We when we did a pre-pa we did mean of study means So we didn't want one study to overwhelm everything One other thing that we came across was um in case, you know If the mean was not specifically mentioned What we did was if we had like min and max values we included those So the idea would be that, you know We still have some, you know, representative numbers You know, that's it's a tough call because some people will report You know 100 measurements in the same room in the same house and You know that 101. Well, they're all in Cape Cod. So Should that be Given that much more weight than the rest of the country, you know, I I don't know Right, right Next document that I'm going to show you is um an example of the exposure factors And I'm going to select say the dermal cosmetics um, so the way we have it here is We have Different phthalates and for each phthalate we have specific media And what we did was we collected uh These are the exposure factors for example, I'm going to just go through them mass applied and we have, you know A brief explanation of how we got to that value The skin surface area that that particular product has applied and this is this is all for women pregnant women and women of Childbearing age. I think in the exposure factors handbook. They have a particular um age Um, and then the fraction absorbed Um fraction exposed And then the the mean body weight And there is one other thing that we came across which actually was not part of the original thing And that is the fraction of the phthalate available in the product That's something which you know was not initially Um part of the the equation we we put it in here But I guess we can talk about it a little later because If this is factored into the equation it would make a Uh a big difference to to the final estimates um Again, this is a sort of thing that we only came across for you know these cosmetics or personal care products We don't have those numbers for some of the other media that we focused on so For all the other media the exposure factors really are independent of the phthalate, you know, it's like But in this case The factors vary from phthalate to phthalate and that's mainly because of this number Of these numbers over here in this column so Another comment those that for skin applied you also have an absorption for a fraction Whereas for inhalation And oral I guess you're assuming 100 absorbed Uh, yes So that's sort of crossing the skin boundary is also Dermal is different than others And which skin Looking around facial well, it depends on the the media right for example Like for example Not immediate the source. Okay. Okay media it means Soil water food, but those are sources All right, so you start with nail polish. Okay, that's the fraction Is the mass applied? Okay Uh, this is the skin surface area, you know, it's obtained from that particular study. How much is absorbed? 25 percent Warmest study And is that the only one? Yes. Yes. This is if if we have warmth over there That's just because we could not come, you know Find that number either in the exposure factors or the the research that we've done so far Fraction looking at absorption. So you actually will come up with a Kilograms per kilograms per day Depending upon how many times you apply nail polish, whether it's once twice or whatever Then the fraction absorbed which is I mean the fraction exposed. That's the fraction of the population And um, this we obtained from one of the Articles that we came across But these these numbers are based on A woman using these products not a not a professional who That's right. That's right. Yes. And that's what this number is. So the assumption is Whatever, uh, you know 10 percent Of, you know, of only so what if we had a population which I think we discussed at our last meeting of Women who are I mean in sahir salons They're going to have a heck of a lot more exposure to the stuff than anyone else They'll have eight hours a day. Correct. So how do we factor that in as a highly exposed group and they will be normally women of childbearing age So that I think that's a population we have to consider To me what it is It's effects a child. I mean a child. It doesn't matter if it's occupational or a incidental Or community That into the discussion me not to say you'll have to do some calculates because that will be a high-end group Well, no, we did we did talk about that and you know, we said that for the most part. We're not looking at occupational But that's one exception one that we would look at I think we had discussed that at our at the may Meaning, yeah, basically the confluence of a high-end risk group and concentrations okay, and The next one that I'm going to pull up is The spreadsheet where you will see how the concentrations get combined. Can I just ask another? I'm sorry. Absolutely Like a clarifying question. So it seems to me there's a there's a Level I'm not used to this exposure so inhalation Our absorption those things per person, but then the whole idea about behavior Is it is another distribution? So Is this is this layered on top of so here's the absorption rate the whatever, you know for this kind of behavior now. Here's another kind of behavior is Are you going to talk about the behavior part of this? These things could It's not a typical thing that's in in the exposure factors handbook. They have Let's have those distributions How many times you touch? I mean how frequently you do so and if you don't you have to find and you look for particular studies They how frequently a woman Puts on her cosmetics during the day. All those things are part of exposure factors All of those things are incorporated here. Well, I don't know how many but quite a few and if it's not We can always adjust it later on based upon what we find in the literature So what we do a lot now with cosmetics is a big issue right now because With nanoparticles nanoparticle exposures through cosmetics is a big deal Um, and we're trying to figure out things like what frequency women which women applies it Reapplies it during a day two three four times a day and how much So it's a similar a similar phenomenon I think the I think you're what you're getting at maybe not but another layer of what you're getting at is You have to define your exposed individuals, right? Like a woman of childbearing age and for her you will you know determine inhalation exposure And food exposure And nail polish, you know, you have to lay out more you have to define your exposed individual and what Pathways you're going to consider for that individual and then add them up and then get a grand total I mean, that's also part of what he's doing. You kind of skipped over that Assumption that we are defining. I assume you're defining x number of Individuals that you're modeling You know, you have I guess you mentioned children in there and you and women of childbearing age and maybe a general adult or something For each of those there's a number of pathways For each pathway, it's like average exposure factors combined with high-end media, you know, there's a whole there's a whole Cerebral layers to think about for for comparison. How does it get the distribution in there? I mean, so you say do you actually make assumptions about okay five percent of women wear a lot of makeup Well, I think it depends what he's doing. It's also depends on how he's structuring it You could say that a woman who uses nail polish on on this day And maybe you're not I don't know what they're doing, but maybe they're not Saying over an average over a whole population includes five percent who use and 95 who don't use He might just be saying a nail polish a woman who uses nail polish That's it So you decide let's the next discussion is how frequently or how concerned are we If we may not be concerned if it's point one percent of population We may be concerned if it's, you know, turns out to be a high exposure and it's 20 percent, you know, that's the Discussion number two that's down the line But I again, I don't know how I structure. Yes, it's part of the process and I think as you as they present their results the exposure scenario maybe better than that Will be weighed out rather clearly for the 95 90th percentile in the 50th percentile You'll have a lot of data Those that there will be a description of those kinds of assumptions those kinds of distributions that you assumed and all of that Yes, um for each as I mentioned sometime back for each of the factors, you know, we have Um, actually this one is like for example deodorant. This is the assumption so much is used You know so many times a day. So that's how we come up with, you know, this particular mass Um, and there are other examples Those are for users, correct? Or is that over Is that the average including users and non users? No, no, that's that's users for users. Yeah for users But then we also use a number which says the fraction of the population exposed you are coming up ultimately with an average including users and non users over the population Well, this No, because it gets multiplied by that factor, right of only the that percent of the population is using it, right? So wouldn't it be just for that population? You have to describe what you're using it for that percentage of the population that is using it you say that The percentage of the population to use it is x and this is what it comes up with if they don't use it Well, they don't get exposed Think if you leave out that Fraction of population exposed if you leave that out You're modeling only users Put it in all of a sudden now you're averaging the you're modeling the average person In other words, let's say you're fraction using as point one If you multiply your number by point one what you're doing is an average including one person who use it and nine who didn't May I ask what the I mean in real life either you use it or or you don't and you get exposed or you don't what then is the benefit of modeling the average of Often essentially binary thing because your biomarker data has no discrimination between users no users either Biomarker data is probably is Yeah, because you don't know what they were exposed to all you know is you have a biomarker level we only look at the user and we may say well g whiz is an awfully high number or maybe an awfully low number When you take into account the total population which would be more representative Of what you would get from the anhanes data or something of that sort Because there's no discrimination in that On users could you have no idea? Don't take that kind of information At least we want to understand what the high end is just in case there are people who are You know and since we're trying to look at this in the standpoint of risk We have to look at the users as being part of the example when you want to compare it to the Daily intake that you get from biomarker data unless it's from the same group users There's going to be a dichotomy between a and b and I think we have to be able to recognize that You know you have to put in a total population to compare it to a non discriminatory biomarker data set I you know I think Our intention is to start with this this average Person average for that population then Once we have that it's easy to go back and do these what if Things uh, you know to the extent that we have the time and energy to do that because they're At some point I think we're going to have to calculate how many parameters Go into this and it's going to be a big number and we can't Look at all the permutations I think the most important way to differentiate that is this is an aggregate exposure. So therefore you have to Disaggregate it first and say which ones of which of these Exposure roots are important and which ones are not and then you can go and look at the extremes And see them work there. Don't start with everything say. Oh, well gee whiz, you know most Maybe inhalation turns out to be almost nothing If that's the case, well, you don't go worry about the extremes if If ingestion turns out to be something well, then you can go look at the extremes and look at that in a logical way And you can vary vice versa and if it's a case of users versus non users whatever that fraction is if it's a small number If it's point one, you know That all you got to do is move the decibel plate place and you'll see what the Dose is for the users only. I mean it's We we got to start somewhere and Something similar to that is, you know, what I showed sometime back was that column which has Data which says this percentage of the product has this phthalate like for example deodorants if it says only 40 percent of You know the deodorants that have been measured or whatever have phthalates then how do we You know address that because I mean everything, you know, even if you assume everything else makes sense um Do we multiply that final exposure number by point four or Depends on what you're trying to compare it to again if we're looking at biomarker data. Yeah But if you're not What's a different story again, you gotta be careful What we want to use it for comparisons part of our objective here is to compare it with the Intakes that are estimated based upon the biomarker data So when you think of that that you have to think about well If in fact most of your data is taken from large-scale studies. Is that correct chris? Yeah, I'm in hains and then from the data shaman swan. So therefore you're looking at Population based studies and you're not looking at users That's so that's one example where you have to be careful of that's why we said you look at the mean How to look at an overall population distribution? then If we want to look at the extremes because we will know there will be users out there, then we have to look at them separately That's the way I'm looking at that because this is a model for what we're going to do with the toy Toys are a big issue in their own right because each toy is different and you'll have on users and Odd way like melding all the time versus no melding at all. You know the Intensive is the fact that the tails are going to be So what you're suggesting is almost like a tiered approach. This is like a tiered Yeah, a screening level assessment where we weed out, you know, the really critical ones and then do like a detailed analysis That's what we were discussing but I think putting it in this forum now each other's these Wise it becomes totally impossible to do Mainly yeah I have another point I would like to remind ourselves of the presentation tom berg gave to us the silver book presentation talking about uncertainties and Uncertainty factors and so on so currently what I see the the median and the 90th percentile is only Content driven it's driven by the content in the product but I am and a lot of factors are related to it, but these Real these factors are numbers Numbers without uncertainties So I would be interested in What is the uncertainty behind these numbers like How much dust is actually ingested? Can be the range? What is the assumption behind it that you say out of One milligram of dust I inhale or I ingest this that amount So I would be interested in the uncertainties behind these factors Which we assume as one number nothing more Um to answer that question I I can say that the numbers that we've used from the exposure factors handbook a lot of those details are provided in those and and I can you know I don't have the a copy of the you know factors handbook, but but it really details It provides a detailed description of you know, what assumptions were there what the You know ranges of numbers are and and that sort of a thing as far as you know The numbers which we've obtained from other sources Um, yeah, that's that's something we would probably have to look at But we talking about uncertainty or variability Because I think we're talking what you're talking about there right now is variability because those are real numbers Let's say they have the range of ingestion of dirt by kids All right, what they do is have a range of numbers That are the median and the high and the low end distribution of how kids In just soil But that does not account for the uncertainty In the individual estimates, I don't think we'll ever going to get those But we will be able at least get the range of variability Because each time you're asking a question you're going back a father and father into the database And you know, it's like within Haynes. What's the variability versus? What's the uncertainty in the measurements? We don't know You know, it's hard when you start taking Data and you're moving farther and farther away from the source of the data So let's either call it variability on or uncertainty in the end. It doesn't matter Right the factors you use Are they mean factors? Are they the 95th percentile from this variability? So these factors where Where are they? They're mainly the means the averages. Yes What would you like to see included? The final numbers you'd like to know what the the variability is in some of the factors for the ones with the crucial Scenarios that are completed and reported Do you want to have those not the screening level? But At a much higher tier Like I'm doing with chris It's easy if you have the the formula and the numbers you can play around with the number So I would like to have some Guess on on the variability of of the outcome So that would be interesting not only the median and the the 90th percentile based on the content of delays in in the In the sources, but also the variability or the uncertainty in in the exposure routes But in the cases where there are multiple measurements, could it be a weighted sum instead of just A weighted average instead of a just a straight out average of things that would account for the uncertainty of some of the numbers some numbers are more When that's available, I don't know how often it would be available If it is, you know, we would try our best to come up with a reasonable estimate like I can I can give you an example here I mean for example the mass Mass ingested for milk These are some of the estimates that we have, you know, we have different age groups And we have different grams per day of consumption These are single numbers, which I believe would be the means for those ranges so again We have documented that but we have just used one number But if we were to go and try and find out, you know ranges between each subpopulation for one category only Really really challenging And I think I think you have to I think what you're going to have to do is you're going to have to do the screening and then Based upon the screening results, if there's anything that shows up as being very very important Then we may want to go back and do some variability on the ones that are really important because again some of this stuff is going to just be hero it's just when you have something that's Apparently very high. Let's say the phthalates beverages are very high Well, you don't want to just leave that you want to say, well, what's the range of not only you want to You just don't want to know Who does drink certain beverages and don't but what the range of concentrations could be in those beverages Because at least they'll give you a fair idea as to how I think that's the best approach I mean I over there I mean I can definitely guarantee that if you look at this spreadsheet You will at least get an idea of you know, where the data has come from and Generally what it looks like but then to get the specifics we would have to refer to you know, either the handbook The handbook has you know, some of that but uh, for example, if it was obtained from A journal article, you know, the article might not have that information If it had we would have you know, tried to at least put some notes or comments in our spreadsheet Our sheets will be tables Uh, well more like yeah, appendix Yeah Yeah But uh, I think our approach to variability was to look at average and night Average values and then 90th percentile of the concentration in the medium and 90th percentile of Uh a use factor like frequency, you know, how often you use makeup or how much you use or something like that and I mean that's What we decided to do Really good idea. What's going on biggest challenge is going to be for kids toys Not product use by adults There you're dealing with Behavioral issues being very very apparent You know, whether it's touching or whether it's mouthing Sucking all those issues in kids So are these factors incorporated in this handbook too? Mouthing sucking. Yeah That's the fact that's the children's handbook, which I think is already out, correct? The children's handbook is incredible. I mean they've done a very good job of Accumulating all the data on children's activities Over the last 10 15 years Study so that's I'd say that's a very robust data set But Mike, let me come back again to what you said So you introduced the second variable So one variable is the the content of delays in the products and the second variable is the the use characteristics but We still have a lot of factors here related to other issues like How much dust is ingested? What is the resorption rate from the dust? All the dermal issues with the cosmetics The data is very weak there So I would prefer to on some points like dermal resorption of delays and dust ingestion have some Impression on what is the certainty or uncertainty of these factors that you assume Just to get an idea. I think that's fine, but I think the first thing Some of these Trivial Yeah, but that depends on the uncertainty No, in some ways it's the uncertainty On the concentrations in the media and the frequency of use or pick up So so many things will flow out some of them will be very very highly variable and you're right We have to do it, but you have to just have a triage or else Those are nuts But exactly as you said, but if we assume a factor very small It falls out of the calculation per se Who tells us that it's too small or too high? So I would like to see Why we kick this out because we assume it is too small Because that's a factor you made up not made up, but A factor you somehow came to so I would like to see the rationale behind This factor and the uncertainty behind this factor Because it's way more than just looking at what's the content of delays in the products and what's the use of the delays It's Much more the basic data I'm interested in How much is that weighted by day time of the day And the events that occurred prior to that day when that value was taken So we have to take all these things and realize there's going to be a large degree of uncertainty on both sides. So we don't go We don't go health or scouter in either Exactly at the point we want to compare the data the bio monitoring data and the Potion scenario data And see whether the results are in accordance Or comparable Because bio monitoring data Population but in terms of use and individually so the extremes Then be able to use that to say well What how does this compare to the 90th percentile of the bio monitoring day? Which could be some of those people who are in the extreme or it may not be Yeah, but the mean we are looking here is this is an assumption out of many factors And I at least would like to see the factors behind this mean Agreed And what might be the uncertainty behind this mean as As you said the bio monitoring data has some uncertainty some major uncertainty I think we should be aware of Another thing is that that's been over that's been done in a literature Catherine Clark's published now twice one one's coming out And we're doing it as well when you take the mean of your adult Which has all the pathways and get a mean intake Of phthalate then look at like NHANES and take your central tendency be a median And work backwards and get an intake and you compare the two total intakes It actually is kind of remarkable how similar they turn out to be So once you get there Then you say okay. Well now maybe we have something to work with let's see You know if we have that 90th percentile on food or 90th, you know the heavy makeup user or something I mean you're never going to be able to probably verify That if you will but when you do those Central tendency calculations both on NHANES and on your forward calculation scenario It's kind of remarkable how close they've come up And that gives you some evidence Problem with the exposure factors in the forward is that you have 25 different things to get worried about Whereas in NHANES, you know, you have the one bio monitoring And then maybe creatinine or something else to worry about so it looks intimidating When you have lots of pathways and each one has like four factors in it. So What you're saying is then from your from your experience is that even in the face of these sorts of uncertainties When you play around with that you may be within an order of magnitude. Oh, it's it is it is and and what's also interesting is that things Different researchers come up with similar findings like food dominates dehp And you've done that with fasting studies and you've done that with the forward based calculations When you've included dehp in air and in dust and so on and they fall out and all of a sudden The few studies with food it shows to dominate So some there's some similarity start coming through and different researchers Look at the same thing mostly looking at central tendency because you're right You do you do get lost In the fact that there are several pathways and each pathway has three so You start picking you start wondering about certainty and variability and which ones you pick So you stick with central tendency on both ends and they seem to match and they seem to show some interesting things And once you get at that point, that's when you can go back and do what if scenarios and take a closer look and Which ones dominate and how do we feel about that pathway and the factors that went into it and what can we do with it? And so on Is that sort of qualitative evaluation going to be part of Part of this Right up or is it going to just be the numbers? No, it has to be part of the write-up I mean when they write this up, they have to explain Each one of the scenarios and then within that there's going to be a bunch of Qualifying statements and also reasons why we get where we did No, it's not going to be just a bunch of numbers that that would be illogical But also the the evaluation of It is making sense because these numbers are similar to what these people got. I mean that sort of qualitative Evaluation if their numbers are there then it's we can do it, but they're not you can't there's always a first for some of this I mean, this is all built upon years of experience with EPA has had with risk assessment on these Aggregate exposure issues lead is being a classic example and pesticides being the second classic example Where they've been very successful in terms of being able to say, oh gee whiz, you know, now we've done x y and z Q is the only one that's left With respect to lead it was basically the elimination of lead from gasoline within five years the blood levels Went down to virtually zero why it happened all the source was going there for what was left It was either paint or road dust that would became the two dominant sources And so therefore you really had a good understanding of what was causing the blood lead to be so high Same thing with pesticides the pesticide exposures have changed dramatically in the last 20 years Why because the manufacturers have changed from broadcast spraying to cracking crevice to designer pesticides And because of those things the different influence from the different routes of exposure change where we now today look mostly at silly ways of applying pesticides versus pesticides that are in Food as residuals as being major sources. It depends upon where you know It's it's good. It's very very well designed and uh Approaches so it's it's not this is not the first time it's been done. It's been successfully done before It's just a matter of how you Slice it to make it come out and give you a reasonable understanding of the situation Here in phthalates we have a lot the biggest problem we have is we don't know all the routes We have no clue I mean we've glossed over the root of adult toys which uh It becomes an example of something that where we have to have cpsc do some Studies And what and then we yeah, what's the fraction of population that uses them? So those are issues that we um And we don't have answers to but clearly these are Things that we can be left as open question When we look in paraway that the influence of particular Sources as well as routes of exposure and as well as contact frequencies and use frequencies So it was all fit in Sorry No, thank you I took over one other thing my understanding from uh, you know The last chap on phthalates you you did the investigations on the birth case scenarios like mouthing and chewing So how does fit does that fit into now with this approach here? Because this is in my understanding not a worst case approach this way So how would The data from here be comparable with with the older data Based on worst case assumptions on chewing and mouthing habits of children You should also be able to model it from this data if you look at the upper percentiles So this would be one way I would like to have these models being calibrated You can not only calibrated to the mean but also to the upper percentiles So I think this would be a perfect approach to to show it via this model I'm not sure what you mean by the 90th percentile concentration And then possibly the 90th percentiles of certain other issues exactly if you can give us a good example that you want put in there for calibration purposes Like like like the the model you used you said that the the children Might be chewing two hours on this and think thing might contain 40 percent of the phthalate So you should be able to to calibrate it this way Well, at least see what the comparability is and whether or not the original calculation was reasonable exactly too far off on the end So this might be valuable information. I think it's a very very good idea to add that one One point in or at least some examples for calibration and I I assume that might Very good point. How about medications as a source? I have that you you've included that okay. Yes. Yes for dibutyl and diethyl You do um The data that we obtained We got it from cpc, which I think was from fda And what they had was they had different drugs. They did not have the names. They just named it as a bcd correct correct And they had the amount Of phthalate that was ingested when you have that particular drug across different populations So we use that number I'm going to open up this spreadsheet which has concentrations for Direct ingestion. There are some of the numbers have The populations mentioned over here Yeah, that would be under the comments. Yeah. Yeah. Yeah 60 67 milligrams per day Yes, okay and and We did not we wanted to group everything as drugs. So we are going to get one number But if you want to go back you can see how we've obtained it these are the classifications So again coming back to what you know We suggested if we want to go back and maybe look at drugs in particular And try to you know sub-categorize them based on you know, the users we can easily do that right now We just have one number. I mean two numbers the mean and the ninth percentile and that would be Combining all these together Doesn't matter you take up you take a hundred percent We tested it it's absorbed hundred percent The late they are Our plan was to calculate an internal dose. So the only adjustment For the dermal absorption In a way, you're assuming a hundred percent Ashton dose Well We did come across a number in warmoth and we've documented it here. What's that? This is for the fraction of soft the drugs 60 percent You want to make it Taking it as one for the time being but we've also made a comment saying that It seemed trying to get up this hard closer Well, it a it's Pretty high and be We're comparing to animal most for the most part to animal oral Doses Well, I mean you've talked about we're not talking about absorption of the drug We're talking about absorption of the phthalate and the drug Yeah, yeah There are uncertainties there Analysis Yeah Yeah But then It's very interesting because now we are right talking about what I pointed out. We should talk about The variability behind these factors But with the medications we can be pretty sure there's a study from 2009 Investigating butyl phthalate in medication 17 volunteers and the resort dose was 78 percent So we can roughly assume it's 80 percent, which is right the high rather high Number and this is my experience from my studies that uh, very high percentage of the dose is really What what was that study? 17 volunteers in chesting diputyl phthalate containing medication I can give it to you. Okay. Okay Yeah, I would definitely like to have a look at that data Published 2009 in tox letters The last thing that I would like to show you all is, um You know the spreadsheet which does the final calculations where we come up with the final estimates I'm going to use the cosmetics as an example. Um, what you will see over here is So we have values Uh, that we collect as far as concentration go and then we also have exposure factors Well for them to come together, you know, you need to Have data for a particular phthalate in that particular source So what you see over here is um These are the phthalates and these are their sources And so these combinations we have calculated the exposures because we have valid data for both concentrations as well as exposure factors So it kind of tells you over here the number of data points we had and this is only for concentration We have the average numbers over here and the the 90th percentiles And then we have the exposure factors that we've used And then these would be Um, the average and the 90th percentile exposure estimates for those phthalates and those media And so straight away you can see let's see these two numbers I and that would be in lotion DEP and and fragrances I'm I'm showing you these because I've kind of gone through the estimates and these are the relatively high numbers The numbers in food as well as inhalation are pretty low. If you're going to do comparability between three you have, um, milligrams Square centimeters per kilogram per day. So is it basically the total number of milligrams? Times the total number of square centimeters. So basically it's the total number of milligrams or it's multiplied Yeah, but that would mean that's that would be All the way to the end I think you take the centimeter square out because the other part is Milligrams per square centimeter times square centimeters. So it's just milligrams per kilogram per day Go away to the end last number Basically milligrams per kilogram per day because you've taken Kilograms per square centimeter and multiplied by square centimeter Concentration is milligrams per per meter cube. How could it be? Actually, it's not square. Yeah. Yeah. I'm sorry. This is So you you have a calculation error Yeah, no, it's a unit zero. It's it's no, it's just a typo the concentrate the the units are correct Hold on. Let me just back up Excuse No, the the how do you get milligrams per cubic meter? No, that's what I'm saying Yeah, the it's just a typo. I'll tell you what I think the units that I have Can't be per cubic No, it's it's it's milligrams per grams. It's That's what the concentration is So that's the concentration of the phthalate found in that particular You know cosmetic product. Yeah, but you have the applied surface So that This would be I just want to make sure your final units Of your final column are correct the way the way units are listed in the final column Seems a little weird the final the last column milligrams slash centimeters squared. I'm not sure what that you those units mean Dermal exposure should be It's times milligrams times centimeter squared divided by kilogram day You're gonna have an absorption coefficient. Yeah, it can't be that way. I don't I don't understand It's usually milligrams per kilogram per day. Yeah, that's that's those milligrams slash centimeters squared The the equations that be That we got from cpsc were exactly in these units That doesn't make any sense because if you're gonna compare it it's coming up per kilogram per day So to get to the point according to Your units there we now need to Multiply these numbers by the surface area to which this stuff is applied to get An exposure in milligram per kilogram and day. Correct. No, I believe you have to divide it because this number has already been Multiplied by this number, which is the skin surface area Then that's confusing then that really the unit should be milligram You have a You have a number of milligrams applied per surface area on the skin Cosmetic multiplied the total by the total number of surface that's been Covered and then you're going to have an now leave milligrams and you have to multiply it by the fraction of the absorbed To come up with milligrams per kilogram per day There's something wrong here We also have a mass over here We also have a mass the mass is just basically the mass is basically multiplied by the surface area To just go again to the numbers Right, so we're really talking if I read this correctly now we're talking What one milligram per kilogram and day from On average the third from the bottom Um, yeah fragrances uh-huh d. E. P But do I read this correctly? Yeah, because it's direct contact and it's got a lot of not a mass. I mean Normally Inhalation is very very small Are we surprised by that chris? I'm not surprised Okay, can you show us an example with a non d. E. P. Thalete? d. E. H. P Or butyl d. B. P. Yeah Sounds reasonable to to me and dr. Koch That doesn't mean anything, but yes professor court can come Is that just that's total Is that dermal inhalation or total? No, this is just uh dermal. Okay particular You know thalete I can I can show you um Let's see Some ingestion numbers We have a lot of categories for for food But these numbers are generally Very low Yeah, could we just for another check look at a um Look at a thalete where experts mostly via food to get an d. H. P. It's a good example I'm pointing out what what you estimate as the total exposure via food to d. H. P But this is food for an average 60 kilogram weighing us citizen Well, this number is based on a particular age. I think a weight. I think it's uh, let me see. Let me go back The weight that we used was 71.5 Kilograms yes And uh, that's a bit obese really That's that's the number that we obtained from the Is this 10 year old children or what? No, no, no, this is only uh the pregnant um, so d. E. H. P as obtained from uh data collected from grains These would be the the numbers in terms of milligrams per kilograms day per day Well, yeah, we're gonna come up with a daily Exposure for for food I mean we could separate food and drinks if you want, but Well, that's the the challenge in this is is Yeah So right now we have it all, you know separated, but we can easily combine it Right, right. Sorry. Can we have a look again at the unit? Just what would you? Yeah, yeah, this is uh Again, the I don't think this Yeah, the the unit was it was meant for inhalation. I think I I did not change it, but uh I go back to the concentrations And select um gestion direct Concentration units are milligrams per grams That's what we you know It really intact that would be the factors Gestion direct explosive exposure factors, right? This is these are the no, no, this is the Just the factors One, yeah Earlier you were highlighting on grains and it didn't indicate something is a miss that we have to work on because Your exposure for grains Over there was like 0.2 And the actual total exposure DEHP is like three micrograms 0.00 Three but your numbers you can just arrow down and see them you at 0.2 milligrams, so there's something Amiss Want to arrow down and see? Yeah, I know that was one of the high numbers. It's and it's not correct The total you know Even at the high end by you know using in hangs biomonitoring And and all the science shows that DEHP exposures No more than 0.01 Milligrams per kilogram per day 10 micrograms per kilogram per day you have Like 200 to 700 micrograms No, no, this is not micrograms. This is milligrams. I know But 0.2 milligrams is 200 micrograms. Yeah. Yeah. So your your numbers are wrong somewhere for food grains The others look in the reasonable range something something's awry with that with that row Okay Yeah, and You know if I go back to my last slide, it's like, you know, we've been looking at a lot of data Right, we have yet to kind of take a step back Well, that's that's sort of the benefit of looking at it from both ways you do reality checks And immediately my eye caught my eye caught that number because I know that number's not right And also hope we're looking at each other Some's not right The final numbers The final exposure numbers I can actually do this Um, okay Could you not add them up and then we have an idea? Yeah, if you add them up, it's going to be driven by food grains Right now we just you know kept it separate so that you know, we can see You know what the different categories are but yes, it would be very simple just you know aggregated or just add it up We're in the mood to fiddle with the data Could you could you add up the the median levels here for the food stuff? Just add it up. Just sum it up But again, I think what he said was right Yeah, yeah, yeah, this is the sum 0.4 400 micrograms per kilogram per day, which is which we know is not sorry But as you say in your defense, you know, you're counting You're counting various food items multiple times. So you would have to weigh So we can't just add up Oh, and this also includes some other things like, you know dust How's the dust? It's not no, it's not just food, right? It was oral intake Oral intake Except the ones with toys crawling on the floor Just to wrap up. Do you have have you done it to the point where you have any Go for a daily intake for any of the phthalates No, no, we haven't started aggregate. No Just started, you know getting to this and it's been really really challenging. So we haven't gone to the next step But but the fact is we're going to tell us about where you're going which you haven't done yet Are you going to be back when we return in An hour do you want to Go back to the slides I Yeah, I just have one slide really. Okay too much. I mean All I was going to say is that, you know I was going to take down the the suggestions that you know Y'all had and then incorporated in whatever we've done so far. But the next step of course would be You know to focus on children um And of course do more literature search to come up with more concentrations as well as exposure factors And um, you know do a thorough qaqc, which is something that you know, we haven't really done so much Um Then I hear you're just continuing The only thing would be that you know when we finish it Uh, there might be a possibility that you know down the line, we might get some additional data sources. Yeah, that's fine. Yeah Young children, which you'll be doing now. Okay. Thank you. Thanks for coming Do we want to talk about a time frame then I mean Not a lot but maybe a little bit on the spot I mean do we have a sense of I mean our time frame is To get some of this uh as soon as possible. But the question is when I guess Do you have a sense of when you might have a um A set of data for Women of childbearing age a set of exposures Um, if we go with the the current concentrations that we have collected so far, which I think it's probably around 800 records or something um, we Are almost through with the exposure factors for the other routes So I would think that we would have a complete data set for pregnant women. Maybe Two weeks add another week to that three weeks When we look at the concentration, it's really all all the the thalates And you know, we always get some additional data We haven't really put it in the equation if you want you can still take a look but it should have all the eight thalates Yes, yes. Yes the final numbers that we are going to get are going to be You know per thalate per source Yeah, and it's it's not going to be um Like the n-hane state, I mean it's going to be an average of the what eight thalates an average in the 90th percentile value for each one of those it's not going to be actual exposures on individuals like you have But we're going to we're going to be able to see exposure daily intake in the 90th percentile, right? And the cumulative exposure to The cumulative exposure, how how would you calculate that then add up the nine? Like we did we we had You know like you calculated 95th percentile So we that that we're not going to have But what we can do is is calculate the hazard index for You know by adding up the average Exposures for all the thalates at the median level But right also add up the 95th or the 90th percentile. We can we can do that. Yeah It would be another approach than we did because we Didn't add up the individual 95th percentiles. We looked at each individual that added up the thalates here. We would add up the upper ranges of yeah, yeah, we can't do we can't do that in your way is the ideal way Our way would be an overestimate Yeah, I just wanted to point it out. Yeah If there are no more comments, it's uh jern we'll return in 20 minutes okay, what I'd like to do For the rest of of today is talk about scheduling Our next meeting beyond the November 3rd meeting In order for us to to do that. I I think it Behooves us to take some time To talk about what we're going to do Between when we leave here and when we reconvene November 3rd and 4th what we hope to accomplish At the November 3rd and 4th meeting and what we want to do to prepare for that meeting So we have some specific goals in mind And whether we want to have conference call or calls What kind of work products we want to have completed at what time so Let's begin that discussion So we've got a meeting scheduled for November 3rd and 4th At that point I will Along with with mike will put together a complete Draft of our document with all the the parts that that I have at the moment And Then when I get more input before the November 3rd meeting I will update that so we will have an updated version um, I think Bern you're pretty close to having a Fairly complete draft of your section, correct? Well, I've got based on the cd that we got now. There's another 10 chemicals to look at but What I understand correctly they are chemicals for which there is not a large volume of data So that will not be a major process to read the rest of those and get them converted into an abstract and Onto a table didn't we didn't we get a cd? Your cd has a Eight more talks reviews. It includes diso butyl dphp and you know some of the other ones we're interested in But we're not going beyond the The um Ones that we have already talked about Right, right, right. Oh, well, then I don't well why why do we have well it includes those eight include I think are let me find my It includes the ones that you're that are um explicitly We're explicitly discussing so um For completeness Well, they're there because we're supposed to look at quote-unquote all phthalates I don't think anyone said, you know, but what The final ones include dimethyl Diethyl this is the final eight di iso butyl and i'm looking at tab three Uh cyclohexyl iso heptyl iso octyl dphp and some Mixed years c9 to 11 di on desol and di tri desol and so I the I think the the first seven of those anyway are are explicitly in either the biomonitoring part or the Exposure scenarios part Well, I think the one The different the difference was the cyclohexyl there just was no exposure data. Yeah I'll review those eight and have a summary statement about them but the question that I have coming back I mean this this morning we were thinking that the getting the versar data and getting it available to To work with the hazard index evaluation was a Uh, maybe a slower slower step in the train here But we know not we know more now than we did this morning so what Based on what we heard about the versar data How What does that affect our thoughts about scheduling now? What can we be have done by november now that we know A little more firmly when new information is coming I'm I'm I'm I'm confused now about I thought we had decided specifically on which phthalates we were going to be Focusing on and we seem to have changed that and in terms of the hazard index analysis, which is one of the major propellers of what Is going to lead to our recommendation um A lot of Those 10 on this new on tab three Don't appear So I guess I don't think we have any intention of adding those to to that hazard index analysis So but in in the spirit of What mike said about looking more broadly at the phthalates I think now that we have these in hand I would spend A day or whatever the time is to go through them and summarize them and see if there are any surprises there Okay, that would cause us concern Do that for their developmental talks as well You want me to look at both? No, I mean I would do I would do okay So then we'll at least have that part behind us even though it doesn't Draw more exposure data or a more hazard index evaluation We'll at least be able to say that yes, we did look more broadly than the 14 that we were looking at specifically for regulatory decisions But what I was getting at in my other part of my comment was now that we Are more sure that the verse our data are going to be coming More quickly than we might have thought What impact does that make on the hazard index evaluation with having the exposure scenario data right behind it? Does it allow us to for sure be able to have a meeting in November and talk about these two in a fairly final stage I I think christen holger's Contribution is really going to drive the next meeting And would it be helpful then to have a conference call of an hour or two sometime in Late september to be able to to Keep things on track and make sure that Both of these parts and the rest of us move Simultaneously so that by november we have it we have it all in hand So that would be my proposal for what might come in before the November meeting And so the goal would be by that conference call to have a pretty final draft Of of this hazard index section Maybe that's being too optimistic at least by the end of september Have a fairly good feel where the eight Valides that we're looking at fit in terms of exposure scenarios with respect to what You will be doing in terms of evaluating them for daily intake from the biomarker and doing it. We may not have a report You may not have a finalized report, but you at least will know where where you've set Some of that's going to depend on when I can get tables for you. Yes Yes, absolutely. Well, we We should have tables well before november. Yes Well based on what versar said They should be able to provide something within three weeks to a month. Right that that was the first Population women of childbearing right age and then at least gives Chris something to yeah, and then actually they should be Essentially done by october right With data then their actual, you know, the written report take will take a little longer So Of the of the ones that they remain the most important ones are the young children The children and the women of childbearing age last pregnant women They're going to do adults, but that to me is a lower priority Correct So, um, yeah, so the two main ones for them to focus on are those two groups first And then tidy up with the adults That holger and chris can finish their job Brett saying this but We don't have to necessarily match all of those cases Right in the sense of I I had assumed and That include in the hazard index pregnant women From in hanes and from the shana swan pre post natal and infants But the children that that we actually had done earlier I removed just because it seemed to me that wasn't the focus of what the consumer products I think we have young children and Children and the children and in hanes was you know, six to 12 and 12 to 18 Or in the yeah, but the exposure work we're doing right now has to include the young children young children We've got the infant zero to three that's that's what we're gonna and I think that's what we're gonna be including but the older children Six to 18 if I mean that doesn't seem to me seem bulky to me when I was putting all of it bulky, I mean, how do you mean bulky? All of that all of the work for that Six to 18 children that didn't seem to me The point of what we were getting to so it just seemed Like it's true. Well, that's true. I mean if you think it needs to be well, we wrote into the For the exposures that verse ours doing we said zero to three And then three to 12 where you know, the the mothers would be the first priority Infants zero to three second And then the other you know children three to 12 and adults are are a lower priority The other two are the main priorities. Yeah Children chapter do we need to have all of those cases? No, no, no It's it depends on what you Have data to do support In the reality is that it's First two groups. Yeah, are the most important anyway Yeah, do we have are we gonna have to include those? I mean, I don't remember me being very, um Adamant about the older groups. I mean, I wrote I wrote it in for really for completeness Okay, so that may not be part of the final report because it may not be because it's just a lot of information That may not have any relevance Chris so basically what you'll get is what you need Basically, what you'll get is what you need Okay Because the rest of the analyses are being done for completion's sake and they may not even be in the appendix of the final report because In a sense, they're going to deflect from what we're our charges At least they'll have it for future reference for other things they want to do Correct Correct and okay, by the way, I mean, they're doing all that work Might as well get it done might as well do the whole thing, but these are This is what I put together a while back and I believe these are the Valights of interest to the panel and I didn't get any comments Saying to the contrary These are the 14 that I was talking about this morning We're doing eight in the exposure assessment. We're doing eight in the exposure assessment And one we couldn't do because there's no data And if you look on this list, they're there Either because they're in the cpsia. They're in the biomonitoring data Uh, or they're known, you know, the the pentel is there because it's known to induce the phthalate syndrome that list Workbook in in in the book in tab Was it five Tap five at the end of tap five those tables are These are the ones that I highlighted in green on the tables Highlighted the light green all the way the light green all the way across So um back to your suggestion the end of september for a Conference school I think it'd be cool good So let me just be a little more specific. So I need to to give you some No wells on the developmental talks If I did that and versard Got the information to you by the end of august or at least september Would you be prepared to have a conference call the middle of september? so Yeah, I mean so what I'd like to the so that gets back to the reproductive and developmental Talks, you know, yeah, we'll we'll sort that out. So when you say you're gonna give me developmental Yeah, it's sorted out. Yes. So there'll be one k. You guys will define. Yep a case The reference dose is for a case Yes That'll be good. So if you give me that by did you say the end of august and the versar Data and the versar data mainly what we all do is just plot it without Like reference lines I would say we first look at the data check it double check it and then But in terms of what we'll do, you know, there's a lot of discussion about it, but in terms of some work done between On the conference call Essentially see is it in the ballpark Right, so do we want to have a conference call on the 15th of september? That's a thursday I can do the 21st And we've got the issue of time During the day as well Has to be morning. I think To accommodate Our european colleagues I can I can get up fairly early. So we're talking about so 21st of September it's a wednesday Actually correction, uh, you can take a pic 19th or 20th That's better And he's a 20th either one works for me. It's better for me 20th Russ, okay September 20th What time do you think then I guess we'll leave it up to mike to figure out A time based on all the different time zones last time We started at noon eastern time That That would make it I think 9 a.m. Mind. I was I was earlier than that my time because I remember I had to get up Okay, is that yeah, I know you're thinking about the let the last chat meeting where you had to get up Okay, so so that's 9 a.m. My time. Okay And if it's not we can always schedule another one you can start 11 30. Is it okay with with you and he 8 30 is fine with me Starting at 11 30 Got it. Okay That'll be on the 20th And then I'd like to have a date certain when each of us will have Updates again on our individual work products And I'd like that to be Before we meet so that each of us has Time to provide feedback To all the other authors so that we don't spend time at the meeting Trying to Read through a long document So What about October the middle of october having Updates on our work products That's only a couple weeks Weeks The expectation is we would have our updates emailed to mike and michael then forum to all of us We will then read them and provide feedback prior to the meeting And we can discuss issues at the meeting I would think that the the major item for discussion at the november 3rd and 4th meeting will be Again exposure be basically you Will have given you all the data and be matter It'll be combined. It can buy. Yes back and combined and now Back and forth Hopefully we'll begin to develop that part of your document that is now blank September 20th That's when updates of our sections are due They're cool or How far can we get in the November meeting on a discussion of recommendations? The preliminary discussion of recommendations That's That's going to I think flow from the discussion that we have But I think that should be that must be the aim for the November meeting At least we'll have some arguments No, no arguments Complete agreement Total agreement a loving instead For example, if we just if we have discussion about data and process on the third Commit all of the fourth to our preliminary discussion of recommendations So that's reasonable so that we don't put it on a back burner but And I think another issue that we would want to address at that meeting Would be the the other sections of of the Report that we haven't yet started I have a suggestion on that line Phil we have this tour so page Description that we develop back in july About what we thought at that time would be the contents of the final report Could we get a copy of that so that we could look at that either yet this afternoon? Come in and look copy on the screen. I think we have we have that under tab eight We have it Because mine mine is too mine is within the entire yeah It's in tab It's also in tab four I think we should review that one more time to see if there are parts in here that we don't think Now fit the structure of the report or if there are some that we missed that we would need to add in there So that we make sure we have a complete list and assignments for the report Everybody go to tab four. Let's let's go through that at this point I mean the one the first part is the executive summary that that's something that that bern and I have agreed to To write and then with the input from from the committee And and obviously that's going to be driven. That'd be something that's written fairly late in in the program introduction and background that's Well on underway An exposure scenario that's underway with paul Do we have why don't we have it twice? What's that ground just going to be a short statement and then The actual result be in the Because you have it twice. What what do we have twice? I think the second I think the second one is where it's combined with the biomonitoring and and So on the first one is in the introduction of background, but that's not the result Where is it fit? Sorry, I still don't know what where what you're talking about. There's what fit you have in the Section which is the report correct? Under you have introduction and background All right, then under that there's a place in a subheading human exposure scenarios, correct? Then He goes out there a whole bunch of detailed subsections under exposure scenarios I don't understand where that fits to begin with because it's a subjection of human exposure and then we come back to risk assessment and scenario-based exposures comes back again. Why is First why is human exposure scenarios a category that is above toxicology of phthalates, which I think is And then the other one is under risk assessment. You have exposure Scenario-based exposure is the second time By these by the way this thing is set up Toxicology be its own heading If we if we could go to tab eight. I I don't know I don't think this this Organization is what we've settled on. I think tab eight is Yeah, what we settled on no because a table eight has fate and transport and I said that Dealing with that in this report That that may be I thought we had eliminated that and we were back to the other one Okay, I'm confused Here we have charge to the chap regulatory history. I think that's Mike has done that. Yes, and human exposure environmental fate I think is whatever it is that you're going to put down in exposure scenarios or whatever it is that you Are going to have text about I'm confused because human exposure is above it with Why don't we separate it this way? Internal exposure issues, which is basically The biomonitor results then you have the external exposure issues, which is basically what we're doing now Okay, because that's the forward versus the backwards the back end is biomonitoring the front end is the other way We're doing it. Can we not call it human exposure then section a source modeling, which is what you do It's actually be receptor and then receptor to exposure Which is yeah, and then and then biomonitoring. Yeah, let's do it that way instead of having to sit I think I like that idea. Okay, so under human exposure you're going to do one is source to human Receptor and the other ones from human receptor back to wherever Which is basically biomonitoring. How do you want to describe that over? Good title for that. Think about it. It'll be to think about it. So then we'll cross out environmental faith, right? Yeah, because that has nothing to do with what we're And then you should add epi After the human exposure epidemiology So the new D is human epi Yeah We kicked out D environmental faith and the new D is Human epidemiology, right? That works out Isn't that number three under human exposure? No Oh human exposure has one in two one in two and then D is separate section separate section toxicology before the human Because we'll need to draw upon it Like they're going to explain the phthalate syndrome And I'm not going to really in the human section. I'm going to refer to it and try to Draw parallels between what you see in the human data and you can have toxicology after exposure and then have epi after toxicology That makes sense. Yeah, as long as epi follows the toxicology Now in the The biomonitoring part they're integrating the exposure and the risk Calculations essentially so I'm wondering if Now oh, it's it's only biomonitoring nothing to do with risk at this point Even the the hazard index. No that comes like that comes later Can I make suggestions that we discussed this morning where to put the metabolism stuff? I think in order to bring the Biomonitoring bit to life or yeah, well the biomonitoring would need information on metabolism, wouldn't it? Should we not stick it somewhere before? Wasn't the bi when you look at the biomonitoring in terms of a hazard index? That's when it needs Apples the other one you're just presenting I'm confused I would say the validity of biomarkers has something to do with knowledge on human metabolism Yeah, okay So for me metabolism is part of the biomonitoring section The issue I had with with Russ was the comparison between animals and humans So that's another issue. So in my part human biomonitoring. I will focus on human metabolism and the validity of The biomarkers I use Or we use in urine Russ we might think about Some passages in your chapter about the comparison between animal models animal metabolism Yeah, I was I was mostly commenting. I think on metabolism differences within animal species potentially explaining Differences between the rat model mormocet, etc and less so between The animal species and human Would we not need A separate section on species differences as part of the big toxicology part and then we could slip it in there Yeah, okay. Does that make sense Phil? I'm sorry. I was looking ahead. So so was I I was looking ahead to the toxicology part and my proposal is to Make a new subsection there after everything. We could call it species differences and in that context deal with both the toxicodynamic aspects of species differences, but also with The differences in metabolism as far as I understand You know inform the differences in in toxicodynamics Does that you're gonna write that? No, I'm not I'm sorry. I shouldn't have said anything I'm just proposing this I'm not expert there There's species differences. Tell me again what you're what you're referring to And the species differences we need to deal with the question You know what there are obviously differences Between the rat the mouse the mormocet That needs to be described I've covered that That is right. You've already covered this. What am I talking about? I'm lapsing here. I'm really I'm jet-like, but as part of this we could that's my proposal we could put Again metabolism, but this time in in animals In just briefly like russ suggested in order to see To what degree it informs these species differences Could be a half a page or a page. It's I don't think you need a lot And hold on in the biomonitoring you're gonna to write about and comment on the use of some of the metabolites as Biomonitoring for the diaster and how some Are minor metabolites and others may not Fully capture the exposure specifically thinking about some of the earlier diisodontal metabolites It will compile some introductory remarks on why do we do biomonitoring in urine and not in blood What is the matrix of biomonitoring? And then of course what is the choice of biomarkers valid biomarkers? I want to make it make this as short and general as possible Because I could write books about that And probably doesn't If you could turn to page 36 under tab eight Where I have number two human and hauser I'm proposing to make that section e epidemiology hauser Then there are subsections in that you can modify as you Get in terms of subsections. So I don't know we came up with those. I'm not sure um Then the number three That should be now. I think F talked about selection of toxicity endpoints and sensitive life stages basis for prediction of human risk I'm still I was given that assignment, but I'm still not sure what Go in there I'll talk. I'll discuss that with burn So then we go to the next section, which is risk assessment of exposure to phthalates So individual and cumulative exposure Andreas your section would part of it would go there There's also section c other anthra androgens You can either divide it up or or not Yeah, can I suggest to change that first of all, uh, you know the all of a sudden the um lettering changes from abcd E f to roman numerals. So but that's a minor thing Can I propose a new section g simply called something like Experimental results phthalate mixtures So we have the the empirical the experimental studies in one in one section and then So this would we could strike out this point number a individual and cumulative exposures with My name behind it Move that and make this a section g But in entitled something like experimental Experimental evidence mixture effects. I'll invent a nicer title include phthalates and anti androgens. Yeah We're going to strike then a would also strike b Because most probably Of the late substitutes will be discussed by you with the tox data And as there is no exposure data I have problems to make a risk assessment So in the end we'll just stick with the tox data that's there And there's nothing to discuss With the epi there's there's no epi. Okay Just another suggestion concerning the other anti androgen to make it more logical Can I propose to include that as a subsection of toxicity? That's Your chapter feel I'm sorry again. I was thinking of something else. No, I'm the focus now the The toxicity Effects for other anti androgens can we put this under your section toxicity of phthalates? That would sit there a lot more logically than under mixtures Yeah, but I can I can write something briefly That'll be good because I'm that's not something I'm at all familiar with It doesn't have to be an exhaustive review, but just some stuff Okay To back up a second for the phthalate substitutes we have data We can make exposure estimates for children's toys Um, I don't know about anything else, but we can can do that I think we have data for that Then again, it wouldn't be in my field of expertise. I wouldn't mind doing it together with paul Yeah, well, well I think we should leave it in and Doesn't necessarily have to be you Are we now in the risk assessment chapter deep deep deep You Wouldn't it make sense to begin this with the usual classical approach? Everyone loves so very march and everyone's very familiar with i.e. chemical by chemical That could then Provide the basis for Doing the cumulative. Oh, yeah Yeah, two risk assessment. You want to start off with chemical by chemical B would be cumulative Okay, we've got biomonitoring data. Is that going to be Something needs to stand alone. That's how we described it before or is that going to be in corp? Aren't we just doing now a risk assessment? Yeah, we take the results from What holger and chris have done validated by the exposure to serenarios and yeah, absolutely Yeah, which is the adi and then calculator risk. So I think the biomonitoring d by monitoring Data corp Doesn't sit there very well. It has been dealt with already or should a scenario based experience has been dealt with too. Yeah So where is the biomonitoring data been dealt with in chapter way back Way back at the beginning And under human exposure a was Yes, you're right. Yep, right Because we already done those so then we have The hazard index calculations hazard in this approach But I before we go there because hazard in there are various different approaches possible For doing cumulative risk assessment and I think we would have to justify why we went for the hazard index This requires a little overview of what could be done in cumulative risk assessment and then Focusing in on on hazard index and if my if my esteemed colleagues to my left Would agree I can volunteer writing this blood The three way of results of the hazard index evaluation Poor impact of variabilities and uncertainties. That's we started a parking lot this These and that's probably going to expand You have discussion conclusions and recommendations and that's going to be I think those sections At this point unless you think otherwise bern we're going to have to leave until after the Third disc meeting thank you summary. Um, normally. Yeah Yes Based on this discussion, I will put together a revision of this outline and send it around and And please then revise that based on your understandings and we'll come to a Final consensus An ultimate final And eventually an ultimate Okay so then We need to talk about So we have a pretty good idea of where we're going to be at the end of the member third and fourth When do we want to meet? Subsequent to that meeting Somewhere warm. How about bermuda? I don't know if that's Burn it bern has made the argument to me that Having three months between meetings is too long. We kind of Three months. I don't have to do anything for a while. I can put it off and all of a sudden it's two weeks and Before the meeting and you haven't done anything so And plus we're really bumping up against our Our deadline which may be firmer than we thought But we're going to we're going to develop those at the november third and fourth meeting And so we're going to then chew on those after we leave Discuss those again in the conference call That would force us to work our way through the full range of recommendations in november So that we would see them all in context By early december and we would still Have a meeting in january february timeframe That would at that point we would be depending on ppsc staff to pull together A text of all the pieces that we've given them and make a report on it Is that right mike that would be our first shot at a draft report Yeah, well when so that would be for january february, of sure And the April meeting would be a final review and and kind of giving final approval Of the recommendations and revising whatever text we need to go with that Okay, so we're talking about there's a proposal to have a conference call in december That's a good idea Availabilities we're coming down to a last chance of having anybody come and Speak to us if we want If there are other speakers that we want to have brought in we about have to plug it in now That was what we were going to Do at the november third and fourth meeting right? Should they if we want more information should they not be invited for the november meeting? Yes, I think so Yeah, I agree with the timing, but I really don't want to take a half day or so for outside speakers If if we could compress that So that we still have plenty of time to hear the business that we need to from our own Liberations, that's fine if we can do that But I think for what we have in mind half a day should do it we're talking about m and url and paul and Richard and there's also the option of Having a three rather than two-day meeting in november from europe be lucky if I get here on time on the third We're gonna have more talks. I I I I tend to object to that. I I'd rather keep us to our business and get it done I just don't see where it's gonna be Observation we need we need clarification on the species difference issue. That's pretty important and we still need another clarification from cpsc about whether or not we can have a meeting after april Because if we if we could slip that one if we could request to have permission for one more meeting after april Then we could have a half day To listen and still get our work done But wouldn't it be better then? I mean I appreciate paul you You're coming back from europe It wouldn't be better than to in november have a three-day meeting Ultimately more effective, isn't it? I think that you need to have the species differences you would need You would be here for the important parts Relate to your input All right, so let's get back to then the the conference call in in december um What about the 12th? It's a monday monday the 12th. What is november? Monday the 12th of december two three and four Not sure What a little day I could probably make the 12th. Do we start early on the second or is it uh? Ain't we talking about the second of november You know would that make a difference for travel reasons for you guys probably wouldn't Not for me Yeah, or hoger and andreas. It wouldn't make a difference either if if we then could fly back Say friday night that would be good Half day at the back end Yeah, well, I mean friday is not a full day, but we can make it you know leave it noon or whatever All of lights are up from three two seven three two nine. That's okay Okay, so we're all on board with I have a student committee meeting on the second from 12 30 to two, but I think I could move it given How far out we are So we'll have a full day the second and third And when would you want would you want to have the speakers start in the morning now? That's a miss Morning of the second if you know that's compatible with their schedules. That's another issue Hopefully this far out that won't be a problem, but And now we we've got on the table a proposal for december 12th for a conference call Fine with me 1130 again 830 my time Okay How long would that be? I would think You think burn an hour So Based on that scheduling the next meeting And we may get an answer tomorrow on these Cpsc Deadline of april Get a firm answer Either way, then we'll have to work around that again Should we schedule the meeting for I mean I think I mean I'm wondering even if we do some form of peer review if we couldn't Still make the deadline That was the essence of the discussion that paul and I had this morning that this this Isn't a global review of the whole document by peers. It's a focused review by a small number of risk assessment Types to look at whether or not the bigger picture fits together and was Interested in relaying that message back Guys, do you have problems with that because I think that's a little bit less cumbersome and It was with the critical issue Putting it all together because you weren't involved this morning. You were out of the room when we start talking about the Of the type of peer review I think I was there maybe Maybe I was invisible, but really I was there Maybe you were I have no problem. I have no problem with that whatsoever Okay, if if let's let's talk about a january meeting and first of all what we would accomplish at that meeting Um snow Yeah Big time temperature may have been 101 two days ago, but it's going to be so we're going to be facing that possibility in february and march so I think burn's plan was that by January february we'll be talking about we'll be on be beyond the basics and the results and we'll be talking about the the recommendations and discussion and all that stuff Yeah, because at the conference call we were going to be dealing with recommendations and And so that the january meeting I think would really be focusing on finalizing those correct burn if if we Get permission and decide to have this peer review. When are we going? When will be initiated at what stage after the december 12th meeting After the december 12th conference call could we have enough of a draft report to give To these three or four reviewers otherwise we have to Have our final evaluation of the report In this january meeting right and then put it out for peer review I think that would be reasonable and then whatever length of time it takes That peer review to be completed and get the comments back to us. That's when we would have the last meeting to look at our final report again in the context of reviewers comments And make recommendations for how to make that final revision And that would be our last meeting What about a meeting the second week of january 9th 10th 5th 12th 13th Pardon not a good week and we're pushing ourselves In terms of getting that report to the external reviewers A lot of deadlines That's the 16th That's a hard week to start up of classes again Not an easy week that for you Well, what pencil it in see how it goes 19th and 20th january 19th. It's a long way away for a two-day meeting here in person purposes to get the Purposes to get the final report at a stage where you can send it out to peer reviews The prospect of having the last meeting in april to Make whatever Accommodations revisions we want to make as a group to the final report based on the report from other comments from the reviewers At that point we'll discuss, you know, how long we want to give the external reviewers. Yeah Do their job That will allow us to do our remaining job and That will depend on whether we have an extension or not right, but don't we want to have the importance? Yes in time for Yeah, and that's going to depend on whether we get an extension or not I'm just guessing what we're going to get out of this review But my guess would be that they would probably not Take us on in terms of our recommendations I would be surprised if they would second guess our recommendation for an interim ban or restriction or something They're more I mean if we ask them to to review how well the pieces fit together They're probably not going to say you shouldn't demand that fell out They're more likely to focus their comments on how how we Rationalized our decisions and I think that's what we want. Well, I think as we said this morning, we want to get some very Very specific questions to ask them. Yeah, so we are dealing with the issues that we need to have Looked at in terms of integration and in terms of the our recommendations or our recommendations Now they could say that the basis for Based upon what they saw in the risk assessment Or the hazard analysis may have a flaw in it. We should go back and review it And in that case we go back and review and then it's our decision as to whether or not we modify our conclusions and recommendations I think what we're looking to make sure they they look and make sure that what we've done is appropriate To lead the conclusions that we got but not the recommendations that we make Hey mike you I think we've we've got the way forward planned. Yeah. Yeah, I think we have a good plan And we'll try to get more Try to get an answer before we By tomorrow, hopefully As to whether or not an extension might be possible If your general counsel Wants to talk to us I would suggest that we should be available for your general counsel. Yeah. Well, yeah. Yeah, I think she knows that Yep Any other Comments questions If not, I move we adjourn for today and Return tomorrow at nine nine o'clock tomorrow or Okay