DR. KATHLEEN GILBERT:  That's a good question.  I'm not sure.  I mean, you could make the argument that something occurred during that chronic 70-day exposure that made the uterine wall less habitable for the pups.  You can't necessarily say that that was the one short window during gestation that caused it.  But whether it's going to make it more or less sensitive, I am not sure.
                  It could be argued that they're using it as more conservative, and I think they're probably right.  So, they're using it as, let's be on the safe side and use this as their study to use to devise these numbers from.  And I think that's probably okay.  I just want to acknowledge the fact that it's not clear-cut science.
                  DR. KENNETH PORTIER:  Any other comments?  You guys are happy with that?  Just checking.  Dr. Willett?  You know, your body language like this tells me, I don't want to say anything.
                  DR. CATHERINE WILLETT:  Actually, the thing I wanted to comment on was, why not use the neuro?  The neuro for the non-cancer, it was included as a consideration.  But I also think that -- and maybe for short-term -- in the human occupational studies, they wouldn't necessarily have seen the reproductive effects because they weren't looking for it.  So, it doesn't mean they're not there.
                  DR. HENRY ANDERSON:  To me, that issue would be, is the neuro result in a less conservative or less protective number than using the reproductive?  And I would say, okay, the reproductive gives some added security and it's the same as -- you use a chronic study when you have a lot of more acute studies, and then make the assumption that there could be smaller windows in there, and things mixed into the chronic studies.
                  So, I would just like to be assured that, if the decision was you'd use the reproductive one, because it's a more cautious, protective number, that's hard to argue that, well, let's be cautious.  But if it ends up with a less protective number than if go through using the neuro data, then I'm not sure which of those is more protective if that's the decision, as we want to pick the study that results in the most protective approach for acute exposures as opposed to which actually is the strongest or most relevant.
                  DR. KENNETH PORTIER:  I'm not sure I heard a recommendation come on it.  I heard comment on it.  Dr. Gilbert, is that correct?
                  DR. HENRY ANDERSON:  Oh, my recommendation would be to do the analysis on multiple endpoints or at least one other endpoint to see what the result would be.  And then, if the decision is you want to go with the one that's most protective, then do that, rather than just say, well, this one using a chronic are anticipated to be more protective.  But I would like to actually see that to be the case.
                  DR. KENNETH PORTIER:  Yes, Dr. Gilbert?
                  DR. KATHLEEN GILBERT:  I don't really have any recommendations.  And they did a good a job explaining that they knew this wasn't completely accurate, but they thought it was more health protective, so they were going with this study.  So, I don't really have a recommendation.
                  DR. KENNETH PORTIER:  Dr. Anderson, on page 171, Table 3.1, there are a lot of developmental studies that they analyzed and presented points of departure from other than just the WILs post-implantation result.  That just happened to be the one that produced the lowest POD.  But your point is that there is no -- well, there are four nervous system studies that are analyzed.
                  DR. HENRY ANDERSON:  I was just looking at the summary tables.
                  DR. KENNETH PORTIER:  But none of that analysis was done on epidemiology data.  It's all done on animal data, obviously.
                  DR. HENRY ANDERSON:  No, no.  I agree.  And it's true.  They say there are no studies of reproductive exposure in humans, but there's quite a bit of neurologic studies, which, again, some of the exposures appeared to be relatively low.  Now, again, some of the criticism of those studies as well are used as time-weighted average and there could be peak exposures in there.  Well, that's true of all of the studies where you use a time-weighted average.
                  So, that's kind of why I take a greater interest on neurologic animal studies being consistent with the human experience, simply because we don't have reproductive studies.  And in most instances, reproductive outcomes are, in fact, more protective.
                  DR. KENNETH PORTIER:  Dr. Vorhees?
                  DR. CHARLES VORHEES:  Well, for this, they do cite human data for neurological effects down to very low doses, down to 0.07 ppm.  And normally, you would use human data in preference to animal data.  But you then say that there are methodological limitations to these studies, and then I presume that that's the reason that they were not used.
                  Now, I didn't go in to look in detail of what the deficiencies in those studies were.  But I presume they were pretty serious, or you would have deferred to the human data over the animal data.  Is that correct?
                  DR. STAN BARONE, JR.:  This is Stan Barone.  That is correct.  Again, the Chinese worker studies had some methodological concerns that were called out and explained in the systematic review data quality evaluations.  We also received significant public comments about the use of those studies in our prior assessment as well.  There's a lack of blinding of the physicians who are doing the testing.  There's, again, from the description of the studies, the methodologies submitted inappropriate aspects to the testing.
                  There's probably something significant there, but to say that they're ready for dose response, we did not choose to use them for dose response.  They're a part of the hazard ID weight of evidence.  And again, we fell back on the animal studies where we could actually do dose response and felt we had more confidence.  If you look within, for the developmental effects and the neuro effects in the animal studies, we're basically talking about within the order of magnitude for those effects.  We're not talking about several orders of magnitude.
                  So, they are close to one another, but we appreciate your comments.  We recognize that using this developmental outcome following a repeated exposure has some controversy around it.
                  DR. KENNETH PORTIER:  Dr. Davies?
                  DR. HOLLY DAVIES:  This is Dr. Davies.  I wanted to speak to the question then the suggestion to use other endpoints for the acute.  On page 145, EPA refers to their Guidelines of Developmental Toxicity Risk Assessment and explains that the reason they were using the developmental endpoint is because of the critical windows of fetal development and that that was appropriate to use the developmental endpoint for the acute because the one exposure, and that wouldn't be appropriate for the other endpoints.
                  DR. KENNETH PORTIER:  Dr. Anderson, did you want to comment?
                  DR. HENRY ANDERSON:  Oh.  Again, yes, they're close.  But that doesn't say which is more than the other.  There's a lot of comparative language used without -- and the quantifier we're seeing, it could be, if that's the case when you analyze it, then say that and that just further supports the choice of the reproductive outcome.  And I'm not against using that; I'm simply saying there's a lot of other data there that I wasn't overly convinced of the reasoning for not at least using that.
                  Now, I can understand the human epidemiology data that typically, in studies like this at least, one of the criticisms was they don't describe the selection process.  Well, you can't particularly randomize workers.  But there were a number of concerns.  There always are with these types of studies that do an observational type of study.  But whether those are fatal flaws or not, I would tend to argue with.  But I'm not against using the reproductive study.
                  Just, my sense would be, I would like to have seen a little more review of alternative.  Maybe it's all there and, given all the pages that are there, I misinterpreted, or I didn't read it as carefully as I should have.  But I just felt the neuro disease -- again, that's what's been seen in the people.
                  DR. KENNETH PORTIER:  Okay.  Before we leave this question, I just wanted to make sure everyone was happy with the selection of the uncertainty factors in all cases and a total uncertainty factor of 100 was used.  I didn't really hear anybody commenting one way or the other.  It seemed pretty standard to me, but I wondered.  There didn't seem to be any reason to go higher or lower.
                  Okay. Question 6.2.
                  DR. KATHERINE ANITOLE:  6.2; please comment on the assumptions, strengths, and weaknesses of the MOE approaches used to estimate the non-cancer risks to consumers following acute inhalation exposures to 1-BP, including the MOEs presented in the document.  Specifically, please suggest alternative data that could be used.  Please comment on the selection of uncertainty factor values in deriving the benchmark MOE for acute inhalation exposures.
                  DR. KENNETH PORTIER:  Dr. Davies.
                  DR. HOLLY DAVIES:  I thought we were doing 6.3.
                  DR. KENNETH PORTIER:  We'll get to 6.3.
                  DR. HOLLY DAVIES:  Kathleen, did you want to do them together?
                  DR. KATHLEEN GILBERT:  Sure.
                  DR. HOLLY DAVIES:  Or it's fine with me, whichever we'd prefer.
                  DR. KATHERINE ANITOLE:  If that's okay, we might as well do 6.3 now.
                  DR. KENNETH PORTIER:  Well, please read 6.3 into the docket, and then you guys can discuss it how you want to.
                  DR. KATHERINE ANITOLE:  Question 6.3; please comment on the assumptions, strengths, and weaknesses of the MOE approaches used to estimate the non-cancer risks to workers and occupational non-users following chronic inhalation exposures to 1-BP, including the MOEs presented in the document.  Please comment on the selection of uncertainty factor values in deriving the benchmark MOE for chronic inhalation exposures.
                  DR. KENNETH PORTIER:  Dr. Gilbert.
                  DR. KATHLEEN GILBERT:  Well, there's not really much to add here.  Once again, they're using the WIL study for many of these.  And as far as chronic exposure goes, it would be hard to argue that they would not be appropriate.  They're using obviously the same uncertainty factors and all the other parameters.  So, I don't really have any kind of problems with this question.  I don't have any suggestions either.
                  DR. KENNETH PORTIER:  Dr. Anderson, did you want to add anything?  6.3?
                  DR. HENRY ANDERSON:  No, I don't think so.
                  DR. KENNETH PORTIER:  Does anyone else want to comment on 6.3?  It seemed pretty straightforward.  Yes, Dr. Barton?
                  DR. CHARLES BARTON:  I just wanted to bring up again that the exposure model for consumers, the way that it was used in the consumer exposure model, evaporation wasn't taken into consideration.  Whereas, for the workers, the fraction that's absorbed does.  So, two different models are being used, one for workers, one for consumers.
                  It just appears a little strange why one was chosen for each.  May be best if it's explained why one was chosen.  For example, why was this one chosen for consumers?  And giving a rationale behind different inputs on why these are best would go long ways in allowing the reader to see what is occurring and allow more transparency.  Because now we're having to assume the assumptions that are being made.  Thank you.
                  DR. KATHLEEN GILBERT:  I just think that's a good point.
                  DR. KENNETH PORTIER:  Thank you, Dr. Gilbert.  Any additional comments on 6.3?  Then let's go to 6.2.  Dr. Davies.
                  DR. HOLLY DAVIES:  So, since it's already been read in, I want to make the point just that the MOE, of course, is dependent on all the uncertainties in estimates of consumer exposure that are going to be in Question 6.5 and in the human health hazards.  So, all the uncertainties and the assumptions and strengths and weaknesses that we've talked about in different parts.
                  I thought there was really a nice explanation in the risk characterization section on page 251 on the uncertainty factors.  It laid out what all the uncertainty factors were, although it kind of directed back to Table 3.1 that Kathleen mentioned before.  So, for each specific ones, I was surprised to see that they were all the same.  I was expecting to see different ones picked for different reasons, but they were all 100.
                  I didn't have any comments as to why they shouldn't be 100.  And it sounds like nobody else has a comment on that either, but maybe they do for consumers.  I was taking Chuck's comment on the consumers modeling for this one also.  And then Table 26, it was very nice to have all of the MOEs for the consumers.  I didn't have that much for this question, if anyone else has anything.
                  DR. HENRY ANDERSON:  I don't.
                  DR. HOLLY DAVIES:  One more thing.  One thing I did really like in comparison to 2016, is how there's so many endpoints.  Because in the draft risk assessment, there was just the one endpoint for non-cancer, just developmental.  So, here, it's nice to see all the endpoints of the points of departure that were done for multiple endpoints and to see them from line-up.  It gives that nice weight of evidence that it's not just reliant on one point of departure from one study, and to see that weight there is really nice.
                  DR. KENNETH PORTIER:  Any additional comments?  Dr. Anderson?  Dr. Cory-Slechta?
                  DR. HENRY ANDERSON:  No.  I like that table that had them all as well.
                  DR. ISAAC PESSAH:  This is Isaac.  It was very helpful.
                  DR. KENNETH PORTIER:  I think they like this section.  That was good.  It's wonderful when you have data.  You know?
                  DR. STAN BARONE, JR.:  Yes.
                  DR. KENNETH PORTIER:  Any additional comments?  Let's move onto 6.4.
                  DR. KATHERINE ANITOLE:  Question 6.4; please comment on the assumptions, strengths, and weaknesses of the approach used to estimate extra lifetime cancer risks to workers, which EPA derived from an inhalation unit risk based on lung tumors in female mice for estimating incremental or extra individual lifetime cancer risks.
                  DR. KENNETH PORTIER:  I'm looking at Dr. Gilbert.
                  DR. KATHLEEN GILBERT:  Okay.  Once again, I hope some other people can chime in on this.  I don't really have that many suggestions or issues with this.  The calculations and the parameters they used seemed appropriate.  The cancer risk estimates for acute inhalation were not derived as we've talked about before, but the chronic exposure ones seemed fine.  The uncertainty factors, again, seem appropriate.
                  The data for the lung tumors was based on a combined incidence of alveolar adenoma or carcinoma in female mice and was selected for derivation of the inhalation unit risk and the dermal slope factor.  They used multi-stage modeling as well as the averaging, the frequentist.  I know some people like the Bayesian especially, so they used that model as well to determine the BMCL ATC values for both the 40-hour work week and 24 hours per day.
                  The BMCL ATC values represented 95 percent lower confidence limit estimate of the occupational exposure concentration expected to produce a one in ten or one in a thousand lifetime extra or added risk of lung cancer was used.  Although not directly comparable due to different BMR values, they produced IUR for both the 40-hour week and 24-hour exposure models that were similar.
                  The values selected as a POD for the inhalation unit risk and dermal slope factors were thought to be protective of more sensitive individuals, which is always good.  Of course, the MOA of 1-BP is not known.  Therefore, the inhalation unit risk and dermal slope factors were calculated using a default linear approach, which seems appropriate.
                  Since the IURs and dermal slope factors calculated by all three modeling approaches were similar, the model averaging can be used to determine that model uncertainty was not significantly impacting the IUR or the slope factor.  So, that means that the slope factor determined using the multi-stage modeling was consistent with EPA guidelines for cancer risk assessment.  Additional high confidence in the IUR or dermal slope because they were based on high quality animal data.
                  So, basically, I think it sounded really good and I didn't have any issues or recommendations for this section.
                  DR. KENNETH PORTIER:  Dr. Anderson, do you want to comment?
                  DR. HENRY ANDERSON:  Why do we always start at the top of the alphabet?  Yeah, I just have a question here.  Let's use this cancer risk only to workers who are -- in all the others, it includes occupational non-users.  I'm assuming they're not omitting the question about exposure and cancer risk to occupational non-users.  It's in the document, but I was curious that it wasn't part of this particular question.
                  The only other thing, I don't know where it fits, but it's come up a couple of times before.  That's the integration of the inhalational exposure and the skin exposure to a data integration into a whole list, like risk to the individual, rather than just parse the risks by skin or by inhalation.  So, somewhere, I think that combined exposure and then what are the risks of the combined exposure should be in this document somewhere.  So, that would be a recommendation.
                  DR. KENNETH PORTIER:  Dr. Anderson, I'm looking at Figure 4-1 on page 230 where it just displays the cancer risk estimates for the occupational users.  That kind of combined the dermal inhalation risk.  Would you do that for all of these or only for the ones that have the lowest risk, like the import worker or the disposal worker?
                  I'm just trying to figure out whether this recommendation is a global one.  I mean, most of these already show significant risk just from inhalation.  So, to my way of thinking, this would be maybe an added analysis that might be done for those that are a marginal low risk and that that dermal might put them over a 1 times 10 to the 5 or 1 times 10 to the -6 threshold.  Does that make sense?
                  DR. HENRY ANDERSON:  Yeah.  I think part of the discussion earlier was if the inhalational exposure is not terribly high, then the contribution of skin was up.  It becomes more significant where they have a high exposure and the skin gives the marginal addition to it.  I just would like to have it at least discussed.
                  It doesn't necessarily have to be calculated for all of them, but it could be, is it important?  And when is it important to consider the two together?  Because again, somewhere, I would again suggest having a discussion of mitigation impacts rather than, in many of these tables, having the respirator use and the glove use right in the table with the others.  It seems to me the issue here for TSCA is, is the environment the worker is in hazardous or not?  Then, if it is hazardous, what can be done?
                  Certainly, recognizing the impact of if respirators are used, being positive, I think that's very important.  But it almost here implies that the environment is somebody wearing a respirator when, in fact, what's in the air, not necessarily what the person is inhaling, is the target here.
                  So, I don't know whether the combined -- how much difference that would make.  I mean, if it's already excessive, then that's fine.  But it does help if you're going to say, well, how are we going to control this exposure in the workplace?  Is it more important to spend your money on a respirator program or buying expensive impervious gloves for everybody?  Or if you'd like to do them both.  That's really my issue about having somewhere in here how these two interact.
                  DR. KENNETH PORTIER:  Dr. Blystone?
                  DR. SHERI BLYSTONE:  I'm on a different topic.  Sorry.
                  DR. KENNETH PORTIER:  Okay.  I think Dr. Barone wanted to comment on that.
                  DR. STAN BARONE, JR.:  I wanted to get some clarification, because I heard two things and I'm not sure I understood the two issues that Dr. Anderson was raising.  One, I think, he was raising issues about occupational non-users.  Again, our assumption is occupational non-users are not using PPE, whether it's inhalation or dermal.  And there are risks for occupational non-users.
                  We're showing the impact on the risk estimates for inhalation APF reduction for the workers for each of the scenarios.  And then, the protection factor, if it's appropriate for dermal.  The second part of the question, I think you were talking about aggregate of the dermal exposure and the inhalation exposure.
                  DR. HENRY ANDERSON:  Yeah.
                  DR. STAN BARONE, JR.:  And if you have some suggestions on how you think we should do that, we would much appreciate what approach you're proposing.
                  DR. HENRY ANDERSON:  I'm not sure I have a method.  What I would do is talk to NIOSH experts or others that are doing that.  For instance, you do biomarker measurements.  That really is an integrated exposure of the two.  How you can calculate the exposures, you're already calculating the skin exposure based on what's in the air measurements.  You have a relationship there and that is somewhat proportionate.  So, I think you can sum up what the exposure would be.  But that's probably an approach that could be used.
                  DR. STAN BARONE, JR.:  We're still not clear on how to make that actionable.  We struggle with this, Dr. Anderson.  Without a PBPK model to do the aggregation, we're really struggling.  So, if you have some other approach that we don't know about, we'd appreciate it.
                  DR. HENRY ANDERSON:  You've got to remember, I'm a physician and my job is diagnosing and treating ailments and looking at the exposures of the individuals.  Therefore, I look at the aggregate exposure of the individual and then try to parse out where those exposures are coming from.
                  DR. STAN BARONE, JR.:  I totally get it.
                  DR. HENRY ANDERSON:  I'm just saying that I don't see that when you break out the various routes of exposure and treat them independently.  You know?  You may have missed a totality.  Or maybe you can ignore the skin, and with a high inhalational exposure, the skin is not going to really contribute much to the aggregate exposure.  In my practice with clinicians, I don't use models to do those or the PBPK kind of things.
                  So, you'd have to ask somebody with that expertise how you can do that versus a simply additive kind of approach.  I'm just recommending that you'd take a look at that.  If it can't be done, then simply put that in the document.  We explored doing this and we can't come up with a way to do it.
                  DR. KENNETH PORTIER:  I think what we've identified is another methodological gap.  We've identified data gaps.  This is more of a methodological gap and one that we can possibly at least point out.  It's something that might need to be discussed in Section 4.3.1 on uncertainties of the occupational exposure assessment, something that, in a sense, hasn't been discussed that's integrating this inhalation and dermal.
                  I understand what Dr. Barone is saying about without having a PBPK model, it's hard to integrate those two sources of exposure into some kind of endpoint that utilizes both of those.  I hadn't thought that far.  I'm glad you mentioned that.  I was thinking, well, just add them up.  It doesn't work that way, does it?  It's not that simple.  So, Dr. Gilbert, maybe make a point to get that in there, okay?  Now, Dr. Blystone, another topic related.
                  DR. SHERI BLYSTONE:  Yeah.  It is a different topic, but a question to the rest of the panel members, really.  In thinking back to some of the conversations from yesterday, I understood that the mouse model may not be the most relevant to humans for carcinogenicity.  If we're using that here, the question was, does that add any uncertainty in this part of the report?  If so, was that adequately captured?
                  DR. KENNETH PORTIER:  So you're thinking in terms of the uncertainty factors and whether 100 was adequate?  Is that part of what you're talking about?
                  DR. SHERI BLYSTONE:  I mean, if they're using that model to derive their additional analysis of risk, there's some question about whether that model is appropriate to humans.  If that uncertainty mattered here, I'm not sure.  I'm asking the question.  And if that answer is yes, then was that adequately addressed in the report?  Because I don't remember anything particularly around that here.
                  DR. KATHLEEN GILBERT:  Well, I guess the issue of whether mouse studies are relevant for human or how relevant they are to human comes up all the time.  I'm pretty sure they address that uncertainty factor as part of their calculations.
                  DR. KENNETH PORTIER:  Any additional comments related to estimation of extra lifetime cancer risk to workers?  Okay, Dr. Gilbert, I guess you've got something to write here.
                  DR. HENRY ANDERSON:  I'm not saying --
                  DR. KENNETH PORTIER:  Hello?
                  DR. HENRY ANDERSON:  I said I'm sorry I couldn't be more specific, and clear.
                  DR. KENNETH PORTIER:  No, but I think you raised a good point that needed to be discussed.  It ties into our discussion yesterday and it kind of identifies a method gap that we at least can point out.  It's not actionable on EPA's part today, but part of our task, as a committee, is to identify these things, get them documented.
                  So, who knows?  Somebody may look at that, some smart academic may read this report and say, I know how to do this without a PBPK model.  Dr. Schlenk's shaking his head, no, that isn't going to happen.  Okay.
                  DR. HENRY ANDERSON:  Well, kind of the issue is if you're making a determine of unreasonable or reasonable risk, and you're saying in manufacturing there's no reasonable risks for those workers, doing a sum may make a difference.
                  DR. KENNETH PORTIER:  Okay.  Question 6.5.
                  DR. KATHERINE ANITOLE:  Question 6.5; please comment on whether the risk characterization has adequately described the assumptions, uncertainties, and data limitations in the methodology used to assess risks from 1-BP. Please comment on whether this information and the risk conclusions are presented in a logical, transparent manner and provide suggestions that could increase clarity in the risk characterization.
                  DR. KENNETH PORTIER:  Dr. Davies.
                  DR. HOLLY DAVIES:  This is a really big question that spans all of the risk assessment.  So, as I was going over the 14 pages of assumptions and uncertainties for all of them, it just seemed like -- this was in my preamble -- we've gone through a lot of this with the other risk assessments, pieces.  This question, it seems hard to answer for me having not dug deeply into these.  Not everyone who was assigned this question had dug into all of those, and I didn't copy down everyone's comments, even though I was trying to.
                  So, we're going to need help from the rest of the committee on this.  I'm trying to put all of my clarity questions in Question 8 on my list for Michael for that, so some of these might overlap a little bit.  So I'm really not sure how to write this up.  Because I think some of these are in the other questions, and I'm not sure how to present this.  But I'm going to start.  Also, I got some comments from other committee members, but I didn't get them early enough to integrate.  So, this isn't as smooth as I would like.
                  I'm going to start with some other general questions.  Uncertainties and occupational exposure modeling and confidence -- it's nice that they explained the confidence.  That went through, and it was very qualitative.  More than one person had this comment that the qualitative confidence was good, whether it was high or medium, but it wasn't really clear because we weren't quite sure yet for what was high and what was medium.
                  So, it was nice to have the qualitative discussion, but there was no quantification or even criteria around when it was high and when it was medium.  When I went through, I didn't write down which of these were actually in here and which of them I added because they weren't in here.  And then I'll add other ones that I don't have in here.
                  One of the uncertainties that I had seen was in the amounts manufactured, imported, and released that we've discussed before.  Also, the list of other occupational uses on page 100 that are not quantified.  One of the key uncertainties that they identified was whether they actually correctly identified the potentially exposed and susceptible subpopulations, which will be the next question, 6.6.
                  I think there's a lot of uncertainties on number of workers in all of these.  I know I haven't had time to really delve into that.  Especially the ONUs, the exposures variable, and the studies don't stay where they are.  And the HHE is not typical exposure.  These are all things that the report mentions that are really good.
                  Issues that we've brought up about the post engineering controls when they look at that.  We've brought up issues on whether that's described, whether there's data for that, personal protective equipment.  All the models that they used, two issues -- that they were not scored for quality in the systematic review, and the other issue is the current criteria are so weak it wouldn't have helped because they would have all just scored high.
                  An issue that I have not brought up before but that I've been thinking about is, at least in King County -- because I know the age of all the dry-cleaning equipment in King County -- many of the dry-cleaning machines are old, past their expected lifetime and they're more likely to be leaking.  If that's representative of other areas in the country, there could also be another exposure because there'd be more leaking.
                  Of course, balanced on that is, as you know, 1-BP is not used very much.  In fact, it might not be used at all in King County.  But the age of the machines would be more leaking, balanced with this isn't very commonly used in dry cleaning.
                  I do know that we have not seen 1-BP used as a spot cleaner in King County.  So that assumption in the draft risk assessment that it's not used much is supported by what we see in King County while we're inventorying all the spot cleaners used in dry cleaners.
                  Questions that have come up on the Westat Survey that been brought up about the age, the survey we have.  We've brought up uncertainties around consumer products.  I haven't been able to find any evidence of consumer uses.  This has been brought up by some other people also.  Issues around whether the consumer uses are really industrial uses, and then, of course, the fact that consumers sometimes use products that aren't consumer products.  They go out and buy industrial products and bring them home and use them.
                  One thing that's in the document is EPA refers to the SDSs as high degree of confidence, which I would definitely disagree with.  I don't have any confidence in information that I've gotten off of SDSs.  So, I wouldn't put that as a high confidence for that information.  I usually found information on SDS is not so reliable.  The phrase I really liked about the modeling inputs for the consumer exposure was that they were well established and commonly used.  They're what we normally use for risk assessment.  There's other things in all these pages about modeling and risk assessment has all the normal caveats about risk assessment.
                  One question I was actually wondering though, while I've just dissed SDS information, I was wondering -- SDSs do often have data about acute aquatic toxicity, and if some of the industrial products are high levels of 1-BP -- if there was data there about acute aquatic toxicity.  Something I thought earlier, this is on the cancer MOA that has been brought up again multiple times on that issue.  Dr. Eastmond brought up that ECA had determined the non-mutagenic MOA; and looking at the ECA that that was actually the registrants that had brought that up.  I just wanted to make that point, minor point.
                  DR. DAVID EASTMOND:  But they agreed to it.
                  DR. HOLLY DAVIES:  Some things, I'm not as familiar with.  The factors that were used in the environmental risk assessment, it always seems odd to me that you have to just divide by 5 here and divide by 10 here and call it good.  I think that would be, again, the well-established and commonly used.  Another question, the physiochemical properties and environmental fate characteristics that hasn't been brought up, they seem fairly good.  We don't have a lot of monitoring, but the characteristics don't seem like we would find it.
                  So, is that enough information to go forward?  That's kind of a question for the committee.  What kind of precedent are we setting?  Let me see if I can find others.  And Mark sent me some stuff that I find hard to understand.  Other things that came up with just more explanation that came up in the previous questions around weight of evidence decision makings and choosing the studies that were used for the point of departure.  And then Mark said he liked the Bayesian models.
                  Mark Johnson had to leave early, and he sent me something and it's kind of mixed in with some of the other things because, as I said, these are also mixed in with the other questions.  So, I think he had also brought some of these up earlier.  He liked the Bayesian model approaches.  I think that's the comment he most wanted me to make.  So, with that, I will leave it open to the rest.
                  DR. KENNETH PORTIER:  Dr. Anderson?
                  DR. HENRY ANDERSON:  Okay.  I would say, assumptions that were made are clearly stated.  Where I would say there is a problem is the uncertainties and the reliability of those assumptions are not clearly laid out.  Where again, not to beat a dead horse too much, but the full issue of respirator use, the assumption of 100 percent use, I have no confidence that that's the case, or similarly, that the expensive impervious gloves would also be used.
                  So, while it's stated that you have the risk as respiratory protection is not used, it would be very helpful either to have it as a separate section to talk about the benefits of use of mitigation opportunities.  Again, the data limitations, EPA provides no data on respirator use.  There is some observational data that respirators weren't used, whether they would be used now or not.  There's really no data on that.
                  Again, I would say the assumptions are clearly stated.  But why one would assume 100 percent use of protective equipment, the same as would go for engineering controls.  I think there's been plenty of discussion about all equipment that isn't quite so effective.  When they replace it with better equipment, the old equipment gets shipped to another user, so exposures (inaudible).
                  Again, I would just raise the issue about assumption of 100 percent respirator use.  And not only that, but that they are in fact effective to the stated protection factor.  I think it was read out in one of the public written comments that with respirators, especially when you have cartridge respirators, they would be the ones you'd use in this instance that you could get breakthrough in the cartridge and not realize that.
                  So, the effectiveness will actually deliver the level of protection that you're assuming.  You have a compound, and you're assuming it is 100 percent effective up to that level and that everybody is using them continuously.  I think those are unrealistic real-world expectations.  That probably needs to be stated somewhere.
                  One way to approach that, as I've said, recommendation would be to, I think, not get rid of that information in the report, but have it as a separate section on the impact of mitigation efforts.  Because I think it's very important.  So, have that information that, when this exposure environment is hazardous, some type of mitigation effort, such as respirators or gloves, needs to be implemented.
                  DR. KENNETH PORTIER:  Dr. Sheela, did you want to add comments?
                  DR. SHEELA SATHYANARAYANA:  No.  I agree with everything that's been said this far.  And I thought, overall, the descriptions were pretty transparent.  And then the few issues that are there have been brought up.
                  DR. KENNETH PORTIER:  This is Ken Portier.  When I looked at this question, I guess I thought this was more the 30 thousand-foot view rather than the detailed view.  So, if I could rephrase, it would say, please comment on whether the risk characterization in the document as presented on pages 188-253 adequately describes the assumptions, et cetera.
                  I looked at this and I said, if I can go to a particular table, Table 4.6, and look at a number, can I trace it back?  Can I trace back the point of departure?  Can I trace back the exposure?  Can I come up with the same number?  Are there discussions about uncertainties and assumptions on each of those components in the document?  And I couldn't find any places where we didn't have that.
                  Now, I agree that sometimes we don't agree with their assumptions.  We don't agree with their uncertainties.  But in terms of what they've written here and kind of linked together as a logical presentation on risk characterization, I had no problems with it.  To me, that's the answer to this question.
                  We've already pointed out a lot of deficiencies in the pieces that go into this.  This is the question of, when EPA put it together in the document, is something missing?  Or can something be better clarified?  And I guess that was the way I was looking at the question.  Dr. Eastmond?
                  DR. DAVID EASTMOND:  Just to clarify, Holly is correct.  The information I found was on ECA website.  But the ECA information on the ECA website is largely put in by the applicants.  Because they tried to flip the burden of proof, so the registrants had to evaluate the studies and make their own assessment.  And then, periodically, it gets evaluated by ECA itself.  But there's no evidence that ECA actually reviewed these.  So, just to clarify that.  Sorry I misled people.
                  DR. HOLLY DAVIES:  I had thought earlier you had been -- because you talked about the WHO model, the World Health Organization model.  But I had thought you'd also just meant that -- we'll talk about it later.
                  DR. DAVID EASTMOND:  On that one -- the WHO model, I was chair of that committee.  So, I'm pretty familiar with it.  That's the guideline.
                  MR. ALAN KAUFMAN:  Yeah, this is Al Kaufman.  I think we had already decided that it was kind of a judgement call and you could kind of go either way, depending on which way you looked at the data.
                  DR. KENNETH PORTIER:  Dr. Blystone.
                  DR. SHERI BLYSTONE:  I just feel the need to comment on safety data sheets since it was brought up.  Certainly, under OSHA, any hazardous ingredient in a product must be disclosed.  Most often, that is in ranges.  And I think that's the data we were talking about here was whether or not it's in a product and how much.
                  It's probably going to be reported in ranges.  It is hazardous, so it will be reported over 0.1 percent because it's a carcinogen.  Those ranges will be -- and if you take the high-end value, it's going to be overly conservative for that.  So, I think there's limited ability there to claim trade secrecy for ingredients.  That is possible from that percentage.  But I think the information on the safety data sheets and hazardous ingredients is pretty straightforward.
                  Your question about the eco tox, the aquatic toxicity -- of course, under OSHA, they will defer to EPA for aquatic tox.  So, we are not, in the United States, required to classify for environmental hazards.  However, many companies do.  And they put the information in Section 12, like you said.  So, they would classify for GHS hazard aquatic.  And most likely, those people are going to go and look at publicly available data like the ECA database and use that information to write their classifications.  So, it's unlikely that there's no data somehow hiding in a safety data sheet.
                  DR. HOLLY DAVIES:  I did just want to say, whenever I've worked with companies on specific products, we have often gone to the SDSs and worked with the company and found they're not actually correct with what's in the product.  And it's been an out of date SDS or the SDS isn't totally correct, so they're not as good as the scientific paper.  If I was ranking things on high, medium, low, I wouldn't put them up there without a peer review journal from sources of information.
                  DR. SHERI BLYSTONE:  But a useful source, I wouldn't call it unacceptable.
                  DR. HOLLY DAVIES:  Well, I think if it were identifying that 1-Bromopropane was in the product on an SDS that that would be fairly reliable.
                  MR. ALAN KAUFMAN:  This is Al Kaufman.  Listening to the conversation between the two of you, it sort of triggered a thought.  I wonder if this rises to the level of requiring hazard labeling under the Federal Hazardous Substances Act for consumer products.  That might be something we want to think about as well.
                  DR. HOLLY DAVIES:  I also wanted to clarify, when I said earlier something about not having seen 1-BP in consumer products, that I actually went out and searched for it.  I have actually searched all of my usual places where I find data on consumer products and didn't find it.  So, it's not just that I didn't see it presented here.  It was that I went and looked myself in my usual places and didn't find any additional data.  After actively searching, I didn't find it either.
                  DR. KENNETH PORTIER:  I was looking for it in nonflammable hairsprays.  But I couldn't find it.
                  DR. HOLLY DAVIES:  I didn't look in my basement, but I was looking more like in the Nordic databases and the SPIN database and other places more like that.
                  DR. KENNETH PORTIER:  Go back to Question 6.5.  Again, I really do think this was a 20 thousand-foot question because I think it's key for this document.  If this section is not logical, not transparent, then the next section where EPA goes to its risk determination doesn't follow logically and transparently.
                  So, I just really want to make sure you guys are comfortable with this risk characterization section, at least on the human health.  We had a conversation on the eco risk characterization yesterday, but at least on the human health.  Mr. Kaufman?
                  MR. ALAN KAUFMAN:  Is the question, are we comfortable with how it was explained?  Or are we comfortable with -- do we agree with it?  Because I think you nailed it when you said we may disagree with the characterization, but in general, it was very well explained as to how they got where they got.
                  DR. KENNETH PORTIER:  In previous questions, we have identified issues with uncertainties and assumptions and models and data gaps.  So, given our answer to the previous questions, the way they presented the risk characterization here.  Does that look okay?  Not necessarily every number we agree to.  That's not what I think they're asking us.  They're asking us whether this way we presented it.  Logically, I think of it as linking backwards from these particular tables to the hazard and exposure discussions, so that it comes together logically at this point.
                  DR. HOLLY DAVIES:  This is Holly Davies.  After this, there was all the pages of the assumptions and key sources of uncertainty.  So, I still think it's -- when you're saying the 20 thousand view, I didn't think it was just linking the tables in there.
                  DR. KENNETH PORTIER:  So, you're saying, I want to add something to that section, right?  For clarification.
                  DR. HOLLY DAVIES:  No, no, no.  I'm still saying that this section should be reflective of everything is what I was seeing the question as.
                  DR. KENNETH PORTIER:  To me, it's integrated.  You know?  They looked at a whole bunch of conditions of use and they did a whole bunch of scenarios, and then they kind of came down to one number which is going to be the number on which they're going to base their risk determination.  And the question is, have they made the case down to that number?  Is that case followed logically?  That's the point I'm asking to get a feel for the panel.  Dr. Barone, am I reading this question correctly?
                  DR. STAN BARONE, JR.:  You are.  That is the intent of the question.  That's what the intent of the risk characterization is.  Have we integrated the information, told you what the risk drivers are, made it clear how we got to those decisions?  And I think you have pointed out some areas where we could be more transparent, some areas where we might consider alternatives.
                  But for the most part, other than our prior discussion about a summary table of all the risks, which we did not have time to implement into this particular effort, I hope you will see that in the very near future in some of our upcoming assessments which will also be addressing this particular question.  Go ahead.
                  DR. HOLLY DAVIES:  This is where I didn't know if this is this question or it goes into Question 8.  Because, for me, it was really weird to see this whole section with everything together rather than see them integrated into each part, if that makes sense, to have all the assumptions separated out into one section.  Cathy knows what I'm saying.
                  DR. CATHERINE WILLETT:  Yeah.  I was going to mention that, but I guess it goes in Section 8.
                  DR. HOLLY DAVIES:  Question 8.
                  DR. CATHERINE WILLETT:  But trying to review the section is really difficult, because you have to keep flipping back and forth.  You know?  So, I had all my piles all over the place because there's a table in one section, then you have to look at a table in another section, then you have to go to the appendices.  I mean, I know it's really hard to organize this complexity of information in a way that always makes sense.
                  But I think maybe, by putting these discussions at the end, like in the presentation, that was really great because you had all the information about a certain kind of exposure in one place.  You went through it all at once.  Of course, this is all trial and error trying to get it to be great.  But maybe that organization might.  But I guess this is Question 8, right?  Can I bring up a couple other things while I'm talking?  Okay.
                  DR. KENNETH PORTIER:  I just want to clarify.  Dr. Davies, one of the things that you're pointing out is Section 4.3, Assumptions and Key Sources of Uncertainty.  They've kind of integrated that.  And that didn't make much sense to you.  You're kind of saying, well, why didn't we have that under each table?
                  DR. HOLLY DAVIES:  Well, reading through that, it was just part of everything.  And I think a lot of it is in here, and maybe it's duplicated.  It could totally be duplicated so that people who like it in see it in, and people who like it out have it out.  Because some people like it both ways.
                  DR. KENNETH PORTIER:  Yeah.  You see, as I was thinking about your comment, I'm thinking, well, if I'm looking at one of these tables and there's a number, it would be nice to be able to click that number, go back to the previous exposure or hazard table, look at that number in that context, look at the uncertainties and discussion there.  Why do I have this global uncertainties and discussion when you do the risk characterization?  I guess I haven't read that chapter, that section, clear enough to see what its purpose is.
                  DR. HOLLY DAVIES:  I read it because I thought that's what this question was about.  Here we have all the uncertainties, assumptions and uncertainties for everything.  It did adequately describe it.  And it was, in general, really well done.  As you said, it has nice qualitative, but also integrated in here was a lot of this.  I, of course, don't need the hyperlinks as much because I print things out like a dinosaur.  And different people are going to want, but other people do what the hyperlinks and different styles.
                  DR. KENNETH PORTIER:  I think it does bring the question though.  What is the purpose of Section 4.2?  What are you really trying to accomplish there?  Because it's very repetitive.
                  DR. HOLLY DAVIES:  Section 4.2 or 4.3?
                  DR. KENNETH PORTIER:  4.3, the assumptions and uncertainties section.
                  DR. HOLLY DAVIES:  Which goes to question 8.
                  DR. KENNETH PORTIER:  I'm sorry.  4.3.
                  DR. HOLLY DAVIES:  It goes to Michael tomorrow.
                  DR. KENNETH PORTIER:  Okay.  But the whole point is, if that confused you, that's a point that you need to bring up.  Why was this here when we've had all this distilled discussion in the hazard section, and in the exposure section where you've had all this discussion about uncertainties and assumptions there?  What is the point of trying to integrate and squeeze that down?  Now I see where you were coming from.  I just wasn't sure where you were coming from with your comments.  Dr. Barone?
                  DR. STAN BARONE, JR.:  If I may, again, this is something we struggle with too.  As a risk assessor and a team lead looking across these assessments, one of the challenges you see when you're reading a lot of these documents is risk assessors will just create laundry lists of all the uncertainties.  And at the end of the day, it's like, oh, wow.  What really matters?  So, what we're trying to get to in this section and the risk characterization, what matters?
                  From your sensitivity analysis, which of these uncertainties or which of these limitations, what of these strengths, what matters?  Versus back in the exposure section or in the hazard section where it seems like there's just a listing of uncertainties.  So, we're really trying to bring this together.
                  Again, I think some of this conversation actually helped solidifying how we should ask this question more clearly.  But that's the goal.  That's what we're trying to get to, is have we really outlined the key uncertainties, the key limitations?  What is overestimating or underestimating, impacting the risk estimation process?  That's our goal.
                  I think the latter questions where we actually moved them from the beginning really talk about the linkages between exposure, fate, the uncertainties, and all the prior sections, and bringing those forward.  Are they being captured?  Are they being captured in the supplemental information?  Are they being captured in the appendix and being brought into the body of the assessment?
                  We've had some challenges with that, and you've called those out in previous assessments.  So, those are two different dimensions to the same problem.  Again, I think you guys have been struggling with that and giving us some good input.  I do have a few clarifying comments or questions.  I'll come to those.
                  DR. KENNETH PORTIER:  Go.
                  DR. EDWARD PERKINS:  I figure I'll have to say something.
                  DR. KENNETH PORTIER:  Yeah.
                  DR. EDWARD PERKINS:  I totally agree with what you're saying.  I think that's the way I viewed it, but I noticed there was often a lot of uncertainties associated with each calculation in the earlier sections.  But they weren't really described what the potential impact of tweaking that would be, overrepresenting and underrepresenting.  You noticed a lot of that when we were talking about different areas, how it might affect it.
                  But I did notice in this section of the 4.3 it was really talking about potential impacts of those different things.  It was a little easier to see how the different elements would affect the overall risk assessments.  I think that was valuable right there.  It might do, to even clarify it farther, to highlight that a bit more.  Just bold out something simple like that or just highlight it.  Because there is a lot of text.  But I thought it was very useful and well explained.
                  DR. KENNETH PORTIER:  Something you said came to mind.  Key uncertainties, key assumptions.  And to me, it's almost like each table needs two bullets: key uncertainty, key assumption.  What do we think is the most uncertain about the numbers that are in Table 4-53?  To me, that's probably more useful to somebody who's reading this than going to Section 4.3 and reading a global summary.
                  I don't know if anybody's going to try to take these 53 tables and do a gestalt feeling for that, and then think in terms of global uncertainties.  They're going to look at numbers and say, why should I not trust this number?  Or what do I need to know as I assess that number?  That would be my feeling.
                  DR. HOLLY DAVIES:  This is Holly Davies.  I appreciate that in the consumer exposures when I was looking at those models.  It said, these parameters are what affect the outcome the most.  And it was good to have that in -- I can't remember if it was in the body or the appendix.  But as I was looking at those, it was good to have that and to see which would affect it the most, and that's why you were varying those.
                  Because I actually found things in here that I hadn't seen, like on the potentially exposed and susceptible subpopulations, right?  I thought I had seen everything you had written about that, and then I found new stuff.  I was like, oh, look at that, I missed this.  Because it was kind of tucked.  But that's that style.  And again, some people are going to be like, did EPA look at the uncertainties?  I want a chapter just on uncertainties.  And they wouldn't see it if you integrate it.
                  DR. KENNETH PORTIER:  This is Ken Portier.  To me, the uncertainties and assumptions were part of the context for each of those tables.  And to separate them out and have a discussion in a whole separate chapter kind of disengages that content.  It's like taking the metadata from your data set and putting it over here.  Here's the data.  Oh, if you want the metadata, here it is.  But to me, this table means very little unless I know something about assumptions and uncertainties.
                  But I was willing to link back and look at the numbers and see the previous discussion.  But it's fair for us to ask EPA to find the one key assumption, the one key uncertainty for each of these tables and highlight that for us as either a footnote or a part of each of those -- they're each a sub-sub-section of their own.  Right?  There's a lot of tables in this chapter.  By the way, I really do like figures 4-2 and 4-1.  Those are cool.  Whoever did those, good job.
                  UNIDENTIFIED FEMALE:  What figures is it?
                  DR. KENNETH PORTIER:  4-1 and 4-2, the central tendency inhalation cancer risk estimates with the nice, bright, red line where you could look down.  I mean, the only suggestion I would make is rank them from the most to the least, so people can say what's the most important one that I need to worry about?  But that's a minor thing.
                  Gosh, what is this section number here?  <IP_ADDRESS>.  So, you might have a discussion in each of those ".2.2.2" sections.  But that Section 4.3 just didn't catch my attention when I read it.  But obviously, it caught Dr. Davies' attention.  So, it had some value.
                  DR. HENRY ANDERSON:  It was very helpful to have the color specifics in the risk section.
                  DR. KENNETH PORTIER:  Any additional comments before we go onto 6.6?  Oh, I'm sorry.  Dr Doucette.
                  DR. BILL DOUCETTE:  Bill Doucette again.  I'm not sure it belongs here.  I guess it does, because of the way the discussion went.  But I know there was a comment across the table about how much nicer it was for the introductory presentation, how well organized it was.  And I really appreciated at the end of each one of the sections, because you have to break this document into readable sections, where they went through and talked about essentially the strengths and limitations within that section.
                  I missed the second get-together, but the first get-together with PV29, that was also brought up how much clearer that arrangement was in the slide presentation than it was in the format.  And I don't know if that's the appropriate model.  Again, I think that's open for discussion.  But I like the fact, at the end of each section or the beginning of each section to warn me what I'm looking for, that I have that table of strengths and limitations.
                  I found that more useful to me than a long summary of trying to put everything all together.  And that's just my opinion.  I'm not sure everybody else feels the same way.  But I think the consensus is that the summary presentation that you folks give is really very helpful.  And maybe that's the format for the document.
                  DR. KENNETH PORTIER:  Dr. Barone?
                  DR. STAN BARONE, JR.:  This may sound pedantic, but with the risk evaluation rule, we're actually asked to specifically call out in the risk characterization assumptions, uncertainties, and data limitations.  So, you can imagine why we have a template and an outline that actually has specific sections, just like we have an aggregate/PESS section in the risk characterization now.  There's a logic to this.
                  I do appreciate and we definitely are in the process of adaption to your comments about the format.  We're also discussing, now, the template for the next 20.  So, stay tuned.  I think some of your comments and, again, lessons learned will be incorporated into that.  I have a couple of clarifying points.
                  DR. KENNETH PORTIER:  Let me address that.  One second.  We'll push back just a little bit.  So, while you have to have a Section 4.3, it doesn't have to be a reiteration of a lot of what we've covered before.  It could be much more of a global summary, a narrative about what we think is really the critical things that's going on here.  And the way I read this section right now, it's a lot more repetitive of what we've seen before.  So, maybe our recommendation is to think about distilling it a little bit more than it's currently distilled.
                  DR. STAN BARONE, JR.:  Thank you for that.  Yes, exactly.  And that is the goal.  Again, the instructions to our teams are to make it more of an integrative section.  Again, you'll see the more we're including sensitivity analysis and uncertainty analysis, it becomes a more integrative section.  Again, that's where we're trying to head.  I think you've already commented about the improvements.  Hopefully successive approximations.  We'll get there.
                  One of the couple of clarifying issues on comments that were made, SDSs -- going back to the safety data sheets -- are not a source for our eco tox evaluations.  We're not using those for eco tox evaluations.  In fact, trying to figure out what eco tox study was actually being cited or referred to in an SDS is more than a trivial challenge.
                  On the models, there seems to be confusion about systematic review of models.  With Section 26-H, when we talk about data quality and the quality of the science, it's peer review and/or systematic review.  It doesn't have to be both.  In fact, many of our models are not going to be appropriate for systematic review.  The inputs and the science that goes into the models, but really the models are peer reviewed.  And we use peer review, like you all, in what we're doing here to get at the evaluation and validation of the models, not systematic review.
                  So, I think interpreting that every model has to go through systematic review, it's just a different process.  It's for a different kind of product, so I want to be clear about that.  Then there was some discussion about the ECA database and the ECA information.  I want to underscore the issue that it is the sponsor's information.  ECA does a quality review.  Their cap is 5 percent.  Their data quality is capped at 5 percent of that information that's submitted.  They would like to do more.  But they're basically only able to check up to 5 percent.  They don't have the capacity to check more than that, but that is where they stop.
                  So, they're not going into every file, every study, or every dossier to review that for quality, which is different than our requirements.  We're sort of in a different place statutorily as far as data quality review.  Just the facts.
                  DR. KENNETH PORTIER:  Dr. Doucette?
                  DR. BILL DOUCETTE:  Bill Doucette.  Sorry.  Just a follow-up clarification.  So, in terms of the models, for example, the EPI Suite values that you gave in the physical/chemical properties, for example.  You rank them as high, and that was exclusively because we had the peer review for that particular model.
                  DR. STAN BARONE, JR.:  That's right.
                  DR. BILL DOUCETTE:  Okay.
                  DR. STAN BARONE, JR.:  That's right, and those particular values are within the model applicability domain.  Again, there are certain data quality criteria, but essentially because of the peer review value of the model and the model's output.  There are cases where we're using models and we're stretching the models.  We may be at the limits of the applicability domain and we're going to tell you, in many cases, where we get to those cases.
                  DR. KENNETH PORTIER:  Any additional comment on 6.5?  We have a second mid-afternoon break scheduled, but we really only have one more question to address.  So, I'm going to look at the panel and see.  Do you want to take a break?  Or do you want to just soldier on?
                  UNIDENTIFIED FEMALE:  Soldier on.
                  DR. KENNETH PORTIER:  Soldier on.  Okay.  Please read question 6.6.  Bill, put your flag down.
                  DR. KATHERINE ANITOLE:  Question 6.6; please comment on whether the risk characterization has adequately identified and characterized the "potentially exposed or susceptible subpopulations" -- PESS -- based on a thorough review of the reasonably available 1-BP exposure and health effects information on both potentially exposed and biologically susceptible subpopulations.
                  DR. KENNETH PORTIER:  Dr. Davies?
                  DR. HOLLY DAVIES:  I just noted that this was new to TSCA and was updated in 2016.  This was put in in several places, including in Section 6, for these risk evaluations to include these populations and these determinations.  And it had a definition of what that means, including infants, children, pregnant women, workers, and the elderly, but not a great definition.  EPA's working, as with so many of these, exactly how to do this.
                  I wanted to acknowledge there are several challenges in identifying and characterizing the potentially exposed or susceptible populations, including the lack of definitions in TSCA and the lack of data on these groups required under TSCA.  Also, clearly, if EPA included everyone possible from the definition in TSCA, then everyone would be included.  Because if you include children, reproductive-age adults, and the elderly, well, we've really just now included everyone.  So, that wouldn't work.
                  I think the goal is to identify which subpopulations are likely to be more effected by this chemical and address that risk.  Ideally, one would take into account both intrinsic factors such as age, genetics, and disease, and external factors such as poverty, racism, and exposure to other chemicals.  Some communities have different exposures, not just higher exposures, such as tribal members.  And children are particularly vulnerable because they take in more air and water per kilogram of bodyweight.  They're still developing, and they interact with items differently than adults do.  In addition to protect potentially exposed or susceptible subpopulations, the aggregate exposure should be estimated.
                  In this document, again -- we've mentioned this a couple times -- in the presentation we had the first day, the slide had a nice summary of this.  But in the draft risk evaluation, I found kind of skipping through.  Like, a little bit here and a little bit here and a little bit there.  And it was harder to pull it together.  EPA listed what they did to assess exposure for workers and consumers by age group to break it down into reproductive age that we've talked about before, and children were included as bystanders, but not in the occupational.  We've had this discussion before.
                  EPA noted the importance of acute exposure and the critical window of fetal development but didn't mention that as a potentially susceptible subpopulation.  On the example of the genetic polymorphisms in CYP2E1, expression that had been linked to alter disease susceptibility is a great example of an intrinsic factor that's a susceptible subpopulation.  Unfortunately, there's not a lot of data as to how many people there are and who they are.  But that is a really good example of a susceptible subpopulation that they noted.
                  There was a section in that section that we just talked about on the last question that says EPA identifies the following as PESS.  But I had missed the first several times on the run through, because it was tucked in there, and the aggregate and sentinel exposures.
                  So, my suggestions were that this would be improved by putting it all in one place with a more clear statement of, these were the groups that were identified.  Because TSCA does say it's identified by the administrator.  This is what was identified, and here it was addressed more like slide 78 in the presentation.
                  And then, even if EPA does not intend to address the risk to TSCA, which is another conversation we've had before, the aggregate exposure should be estimated to fully characterize the risk so that we know, what is the full risk that this subpopulation is getting?  Even if it's going to be addressed through the Clean Air Act or RCRA, or some other law, what is the full aggregate exposure that the subpopulation is getting?  And if the data is missing for these subpopulations, appropriate uncertainty factors a protective defaults can be used to be protective.
                  The other comment I had gotten for susceptible subpopulations was for consumer uses and actually on a cleaner for implantable prosthetic devices and that being a, perhaps, susceptible subpopulation, a population that would be more exposed to this although we don't have estimates on the size of that subpopulation.
                  DR. KENNETH PORTIER:  Thank you, Dr. Davies.  Dr. Anderson?
                  DR. HENRY ANDERSON:  Well, I think I've said most of my points.  I think it would be helpful if they summarize what are the groups upfront.  It seems, throughout the document, exposed or susceptible populations, at times, are not the same.  So, that's one of the issues that just makes the document longer if you have to list a long set of individuals.
                  The other group that has not taken mention in these is individuals with chronic diseases, and I would just use the general term "chronic diseases" rather than go through people with neurologic disorders or diabetes or hypertension.  Some of these compounds, those individuals are particularly sensitive to them, especially in the workplace.  I would just add chronic diseases.
                  DR. KENNETH PORTIER:  I don't have anyone else listed as a discussant on this question.  But is there anyone -- oh, Dr. Blando.  Good.
                  DR. JAMES BLANDO:  It's Jim Blando.  I just want to quickly mention, I have the same thought that Holly did about this definition which I read for what a PESS population is.  But, especially being hired in the general population, it seems to me that our discussion of the HAP petition for people who, for example, live in co-located buildings with industrial operations, it would strike me that they would meet that definition of PESS.
                  So, although I know they're not included in this risk assessment, it strikes me, as Holly had mentioned, that those folks would meet that definition.  That's just the comment I would make.
                  DR. HENRY ANDERSON:  Yeah.  That would hold for neighborhood people as well.
                  DR. KENNETH PORTIER:  Dr. Anderson, we didn't catch the beginning of that.  Could you say that a little --
                  DR. HENRY ANDERSON:  That would probably also pertain to people living in the neighborhood as a potentially exposed group.
                  DR. HOLLY DAVIES:  Yes.  And they also (inaudible) fence line.
                  DR. KENNETH PORTIER:  Dr. Cobb, and then Dr. Barton.
                  DR. GEORGE COBB:  I thought about introducing this earlier.  In poking around the Albemarle website the other day, looking for some of their data, it seems that 1-BP is marketed as a cleaner for implantable prosthetics.  And I don't know if that's been assessed at all, which will maybe throw a real curve ball at you.
                  MR. ALAN KAUFMAN:  Can somebody explain what an implantable prosthetic is?
                  DR. GEORGE COBB:  I'm going with a hip or a knee replacement.  It may be something different.  But it says, on the website, implantable prosthetic devices.
                  MR. ALAN KAUFMAN:  But once you've implanted it, you wouldn't continue to clean it.
                  DR. SHERI BLYSTONE:  It also would be regulated by FDA in that case.  But it probably had the similar scenario to decreasing in general.
                  DR. GEORGE COBB:  Well, it's still potentially an exposure to a population that would be at risk.
                  DR. HENRY ANDERSON:  It would be impregnated into the hard plastics.
                  DR. GEORGE COBB:  Excuse me.  George Cobb again.  Not a population that would be at risk, a population that may be susceptible because they're undergoing, most likely, a surgical procedure.
                  DR. SHERI BLYSTONE:  I can't imagine it's still on the prosthetic when it gets implanted.
                  DR. KENNETH PORTIER:  Dr. Barton.
                  DR. CHARLES BARTON:  Thank you.  The lung cancer endpoint risk assessments were based upon a decrease in live litter sizes in the rats, and it was thought to occur from exposures possibly varying between ovulation to implantation.  It's not known whether it was exposure to the males or the females or if it really was.  In a way, it hasn't really been demonstrated if it wasn't really a developmental effect where that started initiating with the same number of implants.  But they did not stay.  They died away as simple multicellular fetuses.
                  If that's the case, the developing fetus would be a susceptible subpopulation.  As it's written, if we go along with it's actually effects on the F-zero generation, then the susceptible subpopulation would really be males and females of reproductive age.  As it is, what's been written really hasn't made a strong enough argument to say that it's actually a reproductive effect and not effects directly on the fetus.  Thank you.
                  DR. KENNETH PORTIER:  This is Ken Portier.  Dr. Davies, something you said just kind of got me looking at the outline again.  You're right; in Chapter 2, susceptible population is a main heading, all caps.  Then you get to Section 3, and it's four levels down under dose response.  And then level 4, now it's a third level.  So, I think you need to kind of take a step back and look at your outline and decide if this is going to be a major 2.2, 3.2, 4.2 kind of heading and integrate all that stuff.
                  I understand why, for example, you have that susceptible population might be a subsection on dose response.  But for emphasis and for the reasons that EPA indicated that it's called out specifically in the TSCA regulations, you may want to consider, in the general format, pulling that up to a main subheading and just do your integration that way.  Any other comments?  Dr. Gilbert.
                  DR. KATHLEEN GILBERT:  I just want to say, I understand this kind of characterization is really difficult.  But as far as the potentially exposed population, once again, it comes down to this unresolved issue as whether or not we have a baseline exposure and majority of people, including pregnant women, which, once again, as Chuck would say, is putting fetuses at risk.
                  So, until we resolve that, do we have to consider this as a baseline exposure that would have to be added into other kinds of exposure for the risk characterization?
                  DR. KENNETH PORTIER:  This is Ken Portier.  You bring up a good point.  I just zipped back to Section 2.2 and there's no discussion of that, the biomonitoring implications for susceptible populations at the exposure section.  So, we probably should make a recommendation somewhere that they include that.  And we may have done that yesterday.  I have all of yesterday integrated.
                  But those of you who had sections on that exposure might want to think about how we might want to incorporate a recommendation, put something like that.  Section 2.2 of the discussion, susceptible populations exposures and indications thereof.  Any additional comments on Question 6.6?  Dr. Barone, questions?  Issues?
                  DR. STAN BARONE, JR.:  Just some clarifications.  TSCA, again, focuses on conditions of use.  So, it's not the broad rush of everything in the population.  It's about the conditions of use.  And we have divided up industrial/commercial general population and consumers into the three human health receptor subpopulations.  Within those are additional susceptible populations and potentially exposed.
                  So, to the degree you all can provide us comments about those linkages and where we might be lacking on those linkages, we've tried to make clear we do not expect children or infants to be affected by all these conditions of use.  We've tried to be clear about when we do think children -- I'm using children as an example -- will be affected by the conditions of use, and then what context, in an acute or in a chronic scenario.
                  Your comments that you provide will provide us with impetus to look further or expand those context of acute versus chronic if chronic gets expanded.  I think we talked about at least one condition today where consideration for a chronic exposure or subchronic exposure might be expanded.
                  There's another context for susceptibility -- Dr. Davies and others have brought this up -- and that is preexisting disease.  Dr. Anderson brought this up too.  If you have additional information that's relevant to 1-BP exposure, that would increase the variability in response or increase the vulnerability of the subpopulation, whether it's workers, consumers, or others.  Because, a preexisting disease, we very much would like to include that.
                  We did that in our prior assessments, HBCD and fatty liver disease and metabolic disorders.  If there's specific information here or that we're missing that -- Dr. Eastmond's waving his hand -- it would be really helpful to get that kind of additional information incorporated into the evaluation.
                  DR. KENNETH PORTIER:  Dr. Barton, and then Dr. Eastmond.
                  DR. CHARLES BARTON:  Thank you.  Since it appears that cytochrome P450 2E1 is embogged, and it could increase toxicity and you mentioned underlying diseases, alcoholics could be a susceptible subpopulation.  It's estimated that between 10 to 15 percent of the population have alcohol abuse disorder, according to DSM-IV or whatever they're out with now.  Thank you.
                  DR. STAN BARONE, JR.:  We did call that out to some extent.  If you have additional information please, be free in advising us.
                  DR. CHARLES BARTON: I did appreciate that it was called out, but I've never seen that category of the population that's considered a susceptible subpopulation.  But there would be.
                  DR. STAN BARONE, JR.:  If I can mention, you did bring it up in the document, although it's more indirect.  Because you said that those exposed to solvents -- alcohol, ethanol, or drugs -- would be at higher risk of cancer.  But it wasn't directly linked to the 1-Bromopropane.
                  The other thing is, as mentioned, CYP2E1 is inducible.  And in alcoholics, it's believed to have higher levels that make them at higher risk.  It's also altered in diabetics and some other ones.  If you want, I can provide some information on that because it's under a variety of different controls within the body and those could influence susceptibility.
                  DR. STAN BARONE, JR.:  The more that you can help us define the range of variability and response -- actually, you laugh.  But this becomes important information later on when we enter into cases where we do impact assessment, qualitatively and quantitatively.  This is the assessment phase.  If we move into another phase, this data serves as the foundation for that further assessment work.
                  So, the more that we can build that scientific foundation, the references, the data, the understanding of those impacts, the easier that effort is later on, which is not a trivial issue if you've gone through rulemaking before.
                  DR. KENNETH PORTIER:  This is Ken Portier.  Before we go on, Dr. Bennett, on discussions on Question 3, I just realized that in Section 2.2, which is the potentially exposed or susceptible subpopulations, there's really no reference to the eight consumer uses at all.  It's all about workers and there's nothing about consumer uses, and I kind of missed that.  The question was not asked, and we didn't notice it.
                  But coming out of this conversation, I think we really should add something, somewhere in 3.1, 3.3, where we mention the fact that susceptible populations for consumer conditions of use are not addressed at all in that section.
                  DR. STEVEN BENNETT:  I did mention that in passing yesterday, but I don't think you really got the full emphasis of where it was lacking or where it should be incorporated into it.  But yeah, I completely agree that there should be an expansion within that earlier chapter to incorporate those, if that is the case.
                  DR. STAN BARONE, JR.:  That will probably come up in Question 7 tomorrow.
                  DR. HOLLY DAVIES:  Ken, what were you suggesting for the consumer uses?  Were you suggesting that we put it in our answer?
                  DR. KENNETH PORTIER:  No.  I'm saying, in our discussion on Question 3, which was about consumer conditions of use which is Chapter 2 in the document, that Section 2.4 has no mention of consumer conditions of use and susceptible subpopulations.
                  DR. HOLLY DAVIES:  I guess I was specifically not mentioning it, because I knew this question was coming up.  And I like the idea of putting it in one place and not having it spread in multiple places.
                  DR. KENNETH PORTIER:  I'm an in-the-moment kind of person when I'm over here, so I wasn't looking at tomorrow.  I was looking at today.
                  DR. HOLLY DAVIES:  So, we can do it either way.  That was just my thought process.
                  DR. KENNETH PORTIER:  No, no.  We'll bring it up again tomorrow.
                  DR. KENNETH PORTIER:  It'll come up.  Yeah.
                  DR. STEVEN BENNETT:  This is Steve Bennett.  I think my recommendation is to incorporate, into the earlier section on the consumer use, the exposures in there and the incorporation of it.  In the PESS issues, that would be identified within the consumer uses that are in there.  And then in this section, there will be, whether that works into the risk consideration.  So, pair the two others.  It'll be two separate entities but two different considerations.
                  DR. HOLLY DAVIES:  I'll send you my notes.
                  DR. STEVEN BENNETT:  Thank you.
                  DR. KENNETH PORTIER:  Okay.  Dr. Blystone?
                  DR. SHERI BLYSTONE:  This is probably more on the Question 8 thing, but to satisfy both -- and I think, Dr. Portier, you mentioned maybe condensing things -- there's an opportunity there to hyperlink back to the other section do you don't have to repeat it.
                  DR. KENNETH PORTIER:  I think we've kind of worked all of Question 6 over pretty good.  I have us being right at 4:00.  And given that the panel was not quite ready to proceed with questions 7 and 8, I'm looking to the panel to end an hour early today and start again tomorrow morning at 9:00 and tackle the two questions.  I think it's a pretty good bet on our part that we will be done by noon tomorrow.  I think we'll be able to cover the two questions in three hours.
                  That's my hope and my goal.  And I expect Question 7 people to work hard this evening because they've asked for this dispensation.  I'm going to expect a wonderful presentation in the morning.  Thank you.  With this, we'll end for today.
                   (MEETING ADJOURNED FOR THE DAY)
                        OPENING OF THE MEETING - DAY 3

                  DR. KENNETH PORTIER:  Good morning.  Welcome to Day 3 of this meeting of the Science Advisory Committee under TSCA, and we're going to continue our discussion of the EPA questions.

                        FOLLOW UP FROM THE PREVIOUS DAY

                  DR. KENNETH PORTIER:  I wanted to open this morning's discussion to see if there was anything left over from yesterday that someone wants to bring up.  We need final discussion, final comments on Questions 1 through 6.  Dr. Eastmond.
                  DR. DAVID EASTMOND:  I just want to make a correction, I guess.  The three target sites are -- two of them are clearly at the site of exposure and one in the large intestine.  Because this is an inhalation exposure, it's going to be more indirect.  You can have it through grooming or something but, it's not a direct site anyway unless you clarify that.  I realized that in the middle of the night.
                  DR. KENNETH PORTIER:  Anyone else?  So we're going to move onto the general risk characterization questions, Question 7.  And I'm going to ask that 7.1, 2, and 3 be read in together, and then we'll take 7.4 separately because 1, 2, and 3 kind of go together as a group.  And I'm told that the group responding to this have their act together, and they really want to really jump into it.

                               CHARGE QUESTION 7

                  DR. KATHERINE ANITOLE:  Question 7. General Risk Characterization.  This question pertains to Sections 4.1, 4.2, and 4.3 of the Draft Risk Evaluation.  EPA concluded that 1-BP does not present an unreasonable risk of injury to the environment under the conditions of use.  EPA concluded that 1-BP presents an unreasonable risk of injury to human health under the conditions of use.
                  Question 7.1 Please comment on the objectivity of the underlying data used to support the risk characterizations and the sensitivity of EPA's conclusions to analytic assumptions.
                  Question 7.2 Please comment on the characterization of uncertainties and assumptions including whether EPA has presented a clear explanation of underlying assumptions, accurate contextualization of uncertainties and, as appropriate, the probabilities associated with both optimistic and pessimistic projections, including best-case and worst-case scenarios.
                  Question 7.3 Please provide information on additional uncertainties and assumptions that EPA has not adequately presented.
                  DR. KENNETH PORTIER:  Thank you, Dr. Anitole.  The lead for the discussion is Dr. Cobb.
                  DR. GEORGE COBB:  Thank you.  First of all, I'd like to say that the things that I'm reading into the record and, when I indicate that there's more to come from other discussants, those have had broad consensus among the discussants, and we're trying to do this for efficiency so that you know who to direct questions to if there are any, hopefully.  And pardon me, I'm largely going to read this, so here we go.
                  The panel commends the Agency staff who are working directly on completing these complex risk assessments.  The 1-BP assessment has many attributes that present improvements from previous TSCA assessments that have been reviewed by this committee.  The panel appreciates these refinements.  The panel has specific comments, many of which were noted in-depth in responses to Questions 1 and 6.  We're not going to verbalize them here today, at least not all of them.
                  Related to the specific questions, the discussants found it quite difficult to follow the exclusion criteria that significantly winnowed the available literature to a small percentage of studies that were utilized for the assessment.  This limits the panel's ability to make an informed assessment of the objectivity used to retain or exclude the data.  And this exclusion criteria produced no or limited data -- for instance, an N of 2 for environmental exposures -- and cascaded into really large uncertainties in the environmental exposures.  No reproductive or developmental data were included in the environmental exposures.
                  Techniques to include more data by lowering weighting for existing studies that might be of lower quality could be valuable for inclusion in the TSCA risk determinations.
                  We also observed that the process for winnowing the papers to a single or a small key number of studies may be appropriate for cancer endpoints in the human health risk assessment, but it is inappropriate for environmental assessments where a robust data set is needed to get species distribution analyses or species sensitivity analyses.  And that may have led to some of the tension in the discussions about some of these processes.
                  Although it's understood that the Agency intended to be protective, the decision to use a single high-quality study for the dose-response non-cancer and cancer hazard evaluations may give us a false sense of precision.  Although we understand that is protective, and maybe that uncertainty can be clarified in the document.
                  Also the diminution in scope between 2016 and 2019 doesn't instill confidence in objectivity.
                  The 1-BP assessment includes a statement on page 246 that the model surface water concentrations represent a high-end estimate of exposure interval or a pulse exposure and there's no evidence to indicate that this is a high-end exposure.  1-BP's concentration in surface water were from a single reported release from a single site, and that release is three times ten to the minus fourth percent of all of the 1-BP used in the U.S. in a single year.  So it's hard to say that that's a high-end estimate.  And there are ways that you couldn't but do a high-end estimate.  They simply haven't been done.
                  There are gaps in the human health risk exposure assessment, and a quantified sensitivity analysis could help with these gaps.  There are also gaps in the consumer product exposure section that could be used to better describe uncertainties there.
                  The panel concurred that the data supporting the finding of unreasonable risk for consumers and in occupational users was justified.
                  Also the Agency states that benchmark MOEs were exceeded by several orders of magnitude, and that's not true in all cases, so there's several places where we've identified.  Please go back and redo that again.
                  There are also areas where Dr. Perkins is going to address some of these topics.  I'm getting ready to just read off the topics.  He's going to address these later in more detail: sensitivity of human health conclusions to analytic assumptions, the assumption in age and length of exposure, and the possible underrepresentation of exposure.
                  Assumption of nontarget exposures leading to uncertainties surrounding aggregate exposures and assumptions that little BP will enter the soil subsurface doesn't have any data to back that up.
                  So, going on, there are instances where the wording the agency uses implies more rigor or more confidence in the data then is justified.  We're not going to go through all of those but several of those are pointed out in our writeup.  Just for an example, the Agency states that, because of uncertainties inherent in deriving risk quotients, the values are protective so that the risk estimate can state with a high degree of confidence that risk quotients less than one are not an ecological risk and can be screened out for further analysis.  That statement is actually incorrect; the uncertainties make it less likely because the uncertainties are so high, and there's more to come on that particular topic in just a second.
                  The consumer uses associated with uncertainties need some refinement in Section 3.  I think we mentioned that just a second before.
                  The consumer product data are old and the leaking household containers have not been considered, and we realize that you were just informed about the leaking containers in this meeting.  Probabilities of differing human health exposure scenarios were well characterized with the exception of the assumed emission rates for occupational exposures perhaps being inaccurate.
                  The draft evaluation focuses on the major exposed population and defines the limits of populations at greatest risk by estimating high-end exposures.  To these major populations, EPA does mention other populations such as pregnant women or people with other alleles for the CYP2E.  That may make these populations more susceptible to the effects of 1-BP, but the Agency used a blanket uncertainty factor of ten to protect these populations.  And references to support the biological significance to this should be provided or some discussion of uncertainty provided.
                  We talked about modes of action.  There was a section on uncertainties and confidence at the end of each section that qualitatively describe them, but it wasn't clear why some of these were high confidence and some were medium confidence, and that should be clarified.
                  Also the use of models, some of which were probabilistic and some of which were deterministic, is sometimes unclear and confusing, and that could be improved.
                  And there's also an uncertainty about the number of workers that were exposed or at least the precision with which those data are reported.
                  The aspects of adjustment factors in the environmental exposures that require attention -- and it's specifically related to Question 4 and perhaps this should have come up after Question 4 but -- I didn't get these references all pulled together in the information ferreted out until it was too late for that.  So, in Kienzler et al. in 2017 -- and we realize this after your risk assessment was done -- they pretty clearly demonstrated that acute-to-chronic ratios for single species of fish require an acute-to-chronic ratio of a hundred to protect 90 percent of the organisms.  So that acute-to-chronic ratio of ten is probably too low.  So the suggestion is to use that paper, and others that may differ somewhat, to use an acute-to-chronic ratio that approaches a hundred and then use an adjustment factor for inter-species sensitivity perhaps of 5X as was done in the acute study.  And that's the suggestion there.
                  Also, on 187, the report states that the lower bound of toxicity for ECHA studies was used; that's not correct.  The assessment uses the lower of two fish studies, but, if you've got an N of two, just choosing the lower mean is not the lower bound.  The lower bound of that study that was chosen is quite a bit lower in concentration than what is used in the assessment, and this all goes into the uncertainty.  And the panel recommends that the Agency evaluate uncertainties in data sets and ascribe these adjustment factors and uncertainty factors within the numerical assessments of hazard and then discuss the uncertainties in this section around those adjustment factors.
                  Generally, the panel agreed that uncertainty analysis would benefit from inclusion of more discussion on biomarkers and nonspecificity of the assessment endpoints and inclusion of rigorous treatment of uncertainty for the amount of BP that's moving into the environment.  And that concludes all of 1, 2, and 3.
                  DR. KENNETH PORTIER:  Dr. Cobb, this is Ken Portier.  I just want a clarification.  You mentioned diminution in scope 2016 to 2019.  Is that in the environmental risk or is that in general?  I think you needed to expand on that a little bit more.
                  DR. GEORGE COBB:  So, I believe we heard that the scope of the previous document included some air exposures and/or some general population exposures, and that's what that was referring to.  And I do not believe it was referenced to the environmental.
                  DR. KENNETH PORTIER:  Okay.  You said something about human health quantified sensitivity analysis.  Can you expand with that?  I was trying to figure out what that --
                  DR. GEORGE COBB:  Okay.  That was not my comment.
                  DR. KENNETH PORTIER:  I know.
                  DR. GEORGE COBB:  Can you tell me where it was?
                  DR. KENNETH PORTIER:  It was right after diminution in scope.
                  DR. GEORGE COBB:  All right.  Let's get to it.
                  DR. KENNETH PORTIER:  Probably in the next section.
                  DR. GEORGE COBB:  All right.
                  DR. KENNETH PORTIER:  I was trying to figure out --
                  DR. GEORGE COBB:  Data gaps in human health exposures assessment, that was, I think, Dr. Davies, that was your comment on data gaps in human health exposures without quantified sensitivity analysis makes it difficult to understand the gaps in the effects in the results.
                  DR. KENNETH PORTIER:  Dr. Davies.
                  DR. HOLLY DAVIES:  This is, I think, partly from putting our notes and putting them together.  I think the data gaps I was referring to, I think, were general data gaps.  I don't know if -- I don't think I had human health exposures specifically.  I think Dr. Cobb might have added that.  I think I was pointing that we had data gaps that were important, but we don't know how important all the data gaps are.  So I don't think I was specifically talking about -- because some of them were -- one of them that comes to mind is, as we've talked about, with the lack of mass balance; we don't know what we're missing in some of the other data gaps.
                  DR. KENNETH PORTIER:  This is Ken Portier, so I think it would help if we had a little bit more specificity on that con- --
                  DR. HOLLY DAVIES:  On some of those.
                  DR. KENNETH PORTIER:  And then the last thing where I have a question -- assumed emission rates for population exposure.  I didn't quite understand the context of that and that was toward the end of your comments.  I just wanted to make sure I was hearing everything correctly.  There's a lot of stuff in there.  There's something right after the old consumer product data.  You were talking about --
                  DR. HOLLY DAVIES:  Sorry.  I'm trying to catch up to Ken who's trying to catch up to George.  So I mentioned the data gaps, but then the next comment was mine which was appreciating in the consumer exposures that sometimes we have to move forward with some of the data gaps that we can't just say we don't know enough.  We can't do anything.  And that was just one example of making estimates that are good if not perfect.  That was mine.  So what was your other question?  I don't know.
                  DR. GEORGE COBB:  Ken, this is George.  Is it where we're talking about the probabilities of different human exposures being well characterized with the exception that it's assumed emission rates for occupational exposure may be inaccurate?  Is that what you referred to?
                  DR. KENNETH PORTIER:  Yeah, that was it.  So say that again.  I just wanted to make sure because I think that was kind of an important statement.
                  DR. GEORGE COBB:  So it's probabilities of differing human health exposure scenarios were well characterized with the exception that assumed emission rates for occupational exposure may be inaccurate and, therefore, have produced release rates that underestimate actual releases.  I'll apologies; that was not my comment.  I believe that was either Dr. Cory-Slechta's or Dr. Willett's, but I'm not sure.
                  DR. KENNETH PORTIER:  Dr. Cory-Slechta, I think you're next on the list of discussants.  Do you want to add?
                  DR. DEBORAH CORY-SLECHTA:  It's hard to hear on the phone because somebody's typing, and so I couldn't hear what Dr. Cobb just said.
                  DR. KENNETH PORTIER:  So this is Dr. Portier.  I asked him about the statement on the probability of defined human health exposures was well with the exception that the assumed emission rates might be underestimated for population exposure, and I think he said that might have come from your notes.  And I wondered if you could expand on that.
                  DR. DEBORAH CORY-SLECHTA:  I'm not sure if I did, but I'm wondering if it's the comment that I had about the fact that these ONUs may not really be distinct from workers particularly in a lot of the smaller dry-cleaning operations and that I think that distinction in a way is potentially artificial and overstated.
                  DR. KENNETH PORTIER:  Okay.  Do you have any additional comments to add to the Section 7.1, 2, 3 questions?
                  DR. DEBORAH CORY-SLECHTA:  No, I don't.
                  DR. KENNETH PORTIER:  Thank you.  Dr. Davies.
                  DR. HOLLY DAVIES:  No.  I think Dr. Cobb captured the comments for these sections.
                  DR. KENNETH PORTIER:  Dr. Perkins, you indicated you had supplemental discussion.
                  DR. EDWARD PERKINS:  Most of my stuff was recapping things that were discussed in Questions 1 through 6 such as accounting for actual respirator use.  There was discussions on how people may not be actually using the respirators that they think they might be using, and the quality of respirators may be a lot lower than we're thinking.
                  The idea of combining dermal exposure with inhalation or that some of the procedures during occupation, people might have two different types of occupational exposures simultaneously, so that created a lot of uncertainty and then discussion on application of age adjustment factors and how that there may be daycares or children in the area.
                  Then pretty much a number of other things that were talked about created a lot of uncertainty to greater or lesser degrees.  Dr. Cobb talked about the general topic.  Most of the specifics have already been discussed in other questions.  I'll expand upon that in the written element.
                  DR. KENNETH PORTIER:  Thank you.  Dr. Willett.
                  DR. CATHERINE WILLETT:  I think Dr. Cobb captured everything under those three that I had.
                  DR. KENNETH PORTIER:  So we'll come back to Dr. Cobb.  I should open it up to any additional comments, but I'm going to ask Dr. Cobb at the end to kind of point out what recommendations might have come out of this discussion because I'm not sure I heard recommendations specifically.  I heard a lot of good comments but recommendations.  Dr. Blando.
                  DR. JAMES BLANDO:  This is Jim Blando.  Just one other uncertainty, I know Dr. Cobb mentioned something about the estimation of the number of workers exposed.  One other additional uncertainty that might be worth noting in the report, although I don't know that there's any recommendation of what you can do about it, is just the difficulty in predicting future worker populations because, as any economists would probably tell you, that's almost impossible to predict but that might be worthwhile just making a mental note that although you predict the number of workers or you might say there's only a certain number of shops or places that use this, it's really hard to predict in the future what that future demand might be.  Again, I don't know what you can do about that other than just make a mental note that that's something to think about when you're trying to predict impacts.
                  DR. KENNETH PORTIER:  I know in the past the panel's always been worried about future consumer use and the impact of this assessment on driving or depressing future consumer use.  I was talking to someone this morning who said, well, the industry says the future for 1-bromopropane is bright for consumer products.  And I'm like, okay.  How do we incorporate that into this?  We don't.
                  UNIDENTIFIED MALE:  Maybe we should.
                  DR. KENNETH PORTIER:  Yeah, but where do we get that information and how do we quantify that to a point that really helps EPA?  I think we all agree that's an uncertainty, but it's not necessarily a quantifiable one at this point.  But it's always a concern.  Any additional comments?  Dr. Cobb, can you identify any specific recommendations that came out of that?
                  DR. GEORGE COBB:  This is part of the challenge we had because this question -- and you even alluded to it this morning -- how is this question different than some of the underlying questions for the previous six?  So a lot of the suggestions are probably called out in the first six responses, the responses for the first six questions.  The things that I can kind of grab onto to right now is, make it clearer how the data assemblage, data exclusion, data retention was done.  I know that's kind of a mammoth task.  That gives people a better sense of the objectivity and trying to include data that is useful even though it might not pass every single one of the criteria and maybe use a weighting scheme in there.  And I'm not even sure we got to that.  That might be in 7.4 even.
                  And then making sure that uncertainty factors or adjustment factors are appropriate for the data set.  For instance, if you've got an N of two for the universal data that's available, there's a lot of uncertainty about that data and having the right adjustment factors or uncertainty factors in those sections in the numerical hazard quotients can help.  Most of the things I brought up are things that could be improved in the report, the different ways that the uncertainties aren't as well-specified, and if you would like, we can try to be specific on where in the document that those improvements could be made.
                  DR. KENNETH PORTIER:  Any additional comments?  I was looking at Question 7.1 and thinking about sensitivity and trying to figure out, is there anything else they could do especially on a quantification sensitivity analysis?  But I can't think of anything especially on the human health hazard assessment.  Then using the model averaging approach kind of was part of a sensitivity analysis and so they've done that.  Other than actually quantifying the assumptions and trying to do some more, I just can't think of anything to add to that.  Dr. Kissel.
                  DR. JOHN KISSEL:  I've been trying to figure out where exactly this fits, and maybe it was supposed on 6.5.  There seems to me there's a lot of overlap between these sections that we're discussing.  But I asked early on in the -- it was either under Question 2 or 3 about how some of the dermal modeling was done.  And I finally had a chance last night to go find P_DER2b and look at it and put it in a spreadsheet and do some calculations, and it is structurally incorrect.  So all of the results that are generated by P_DER2b are incorrect and do not reflect the assumption, so we're not talking about just I'm arguing about what assumptions you're making about the exposure parameters.
                  As you're using it, you're using the density which is the concentration of the pure compound as the driving force with a permeability coefficient that applies to application in an aqueous vehicle, and so there's a partitioning problem there that is not included.  The consequence of that is that fluxes of up to 13 milligrams per square centimeter per hour are predicted which are 13 times higher than the max fluxes experimentally determined by Frasch and another 30-fold higher than the max flux that you would get if you took that aqueous vehicle permeability coefficient and multiplied by the solubility.
                  So it's likely that the dermal estimates calculated using P_DER2b are overestimates given the stated assumptions.  It doesn't mean that they're actually overestimates because the stated assumptions can be wrong, but the calculation on the basis of the stated assumptions is leading to too high of a number.
                  Are we in the right place for this?
                  DR. KENNETH PORTIER:  Yes.  We can always move it back to 6.5 when we write the minutes, but it's good to capture this at this point.
                  DR. JOHN KISSEL:  Okay.  There's also some confusing stuff.  In the consumer exposure model user's guide on page 67, there's language which explicitly states that P_DER2b doesn't use load, so it's just calculating from some mystery material that's somehow out there and actual loading doesn't come into play.  But, in the tables which describe the assumptions for the various consumer exposure scenarios, there actually are numbers about amount of load.  And I don't know whether those are just stuck in the table and not used or whether there's some disconnect there, but I couldn't figure that out.  So that's not clear to me.
                  This is a minor point, but in the description of P_DER2b -- I really don't like that acronym but -- P_DER2b says to select a surface area in a bodyweight ratio which is one of the exposure factors that's in there, go to Table B2 in the appendixes to the user's guide of the consumer exposure model.
                  DR. HOLLY DAVIES:  Can I just ask one quick question?  Is the dermal model that was used just for consumer use or was it the dermal model used for occupational?
                  DR. JOHN KISSEL:  P_DER2b is the permeability model that's used for the consumer case.
                  DR. HOLLY DAVIES:  Okay.
                  DR. JOHN KISSEL:  The occupational stuff used to fix fractional absorption.  So the appendix says, go look in Table B3, and it's actually in Table B2, so I had to hunt around for that.
                  Now, if I could say something a little more general about the -- so many people, mostly toxicologists, said, we really don't like flipping back and forth between permeability models and fixed fraction absorption models.  And, although I don't like fixed fraction absorption models, I'm not so sensitive about that if you do both of them at will.  If the predicted outcome is a reasonable result, then I don't care how you got there quite so much.  The mere fact that they're different doesn't bug me quite that much.
                  But, generally, fixed fraction absorption models are not well-grounded in physics because they only apply -- whatever fixed fraction that you observed experimentally only applies to those experimental conditions.  And, once you extrapolate to some other condition, it's not a physical constant.  It's not like molecular weight.  And so you can't just go off to anywhere else in the world and say, oh, we were always going to get 0.0016 fraction of the material absorbed, so that basically doesn't make any sense.  This is a pretty volatile compound, and so the competition between volatility and absorption is important.  I do think that the way the experiments were done were under higher-velocity conditions -- wind speed -- and, therefore, more rapid evaporation when you would see in a normal case.
                  And so, therefore, I think there's a good chance that the dermal exposures are underestimated, and, actually, there's a second reason for that as well.  Whereas, the consumer exposures overstate the actual -- the intended exposure.  Now, in that world, there's how much stuff do people actually come into contact with?  And I don't think we have a very good handle on that, so there's always a possibility that you're overestimating from an underestimating starting point.  So you might be getting to not an unreasonable result.  I can't really say.  Without biomarker data to back up what's going on, then you don't really know whether you're making a good estimate or not.
                  The other piece -- and there was some confusion about this because I brought up that, if you put on respiratory protection then you can't necessarily neglect direct dermal uptake from vapor.  And that's not in here anywhere. I don't know if Dr. Anderson's is on the phone, but in his comments, I've detected some confusion about how the dermal absorption stuff is being done.  And the dermal absorption that's presumed is exposure to liquid, and nowhere in this document is there any exposure to vapor.
                  And I did a back-of-the-envelope calculation using the slope factor of the 0.006 milligram per kilogram per day extrapolated inhalation to dermal slope factor for carcinogenicity.  And my back-of-the-envelope calculation is that via vapor alone at 20 parts per million ambient, you've got about a 10 to the minus 3 lifetime excess cancer risk; and that's not in here anywhere.
                  Potentially, the dermal vapor uptake is not negligible for this compound.  And that's based upon -- if I had done that calculation two weeks ago based upon the max flux estimated from water solubility and epoxy-type permeability coefficient, I wouldn't conclude that.  But I've adjusted that calculation for the observed experimental fluxes shown by Frasch, and those numbers are much bigger.  And when you plug in those potential max fluxes, then the reduced flux at something less than saturation in the air and it's a lot less than saturation.  So you're at 20 parts per million, and saturation's about 200 thousand parts per million.  But you're involving two square meters of a human being when you're doing vapor uptake.  So it turns out that I think direct dermal vapor uptake is not negligible, and that's not in here anywhere.
                  DR. HENRY ANDERSON:  I'd say thank you very much.  You're right; I was confused.  I didn't realize it was liquid that the estimate was done on, so thank you very much.
                  DR. JOHN KISSEL:  In the last part here, I was a little confused by the conversation yesterday about we can't do aggregate risk because we don't have a PBPK model.  I understand that, if you're trying to match biomarker data to inputs and you have to work backward, then you need a PBPK model to do that.  But my experience with EPA risk assessments is that pathways get added together, and aggregate doses are then multiplied by a slope factor.  And that's been happening in the Superfund world for decades, and so I don't understand why it can't be done here.  It may be a little imprecise if you're taking gross systemic absorption from dermal and one and adding it to ingestion because of the liver first-pass phenomenon.  But, in this case, ingestion isn't really in the mix, and I don't understand why we can't add systemic dose from dermal and systemic dose from inhalation and estimate it a total risk.  So that's more of a comment than a question.
                  I guess, something else that I would add is that what I've discovered is that not just what somebody has done for this particular risk assessment but the actual -- the text in the published consumer exposure model user's guide is incorrect and misleading, and that's a problem going forward.  And, if P_DER2b is wrong and there's a possibility that everything's in there are wrong also, other dermal models are wrong also.
                  It's a fairly common mistake to think that once you've calculated a permeability coefficient -- and some of the people that produced them are not very helpful and the work is taken from Wiltenburg's (phonetic) website and it's not at all clear.  He doesn't point out that he's produced an estimate for an aqueous vehicle; it's not clear there.  But you can't take a permeability coefficient for an aqueous vehicle and apply it to a mixture of any other kind than an aqueous vehicle, and I see this in the literature all the time.  It's not like EPA has done something that is particularly odd here.
                  But working in the dermal risk world, this is a really common mistake.  The problem here is that it's embedded in an EPA document, and that's actually been embedded in prior EPA documents that I have criticized.  But at some point, you need to hire a team of dermal people that actually know what they're doing and work on your protocols because I'm going to be saying this at every one of these meetings is that the way you're doing dermal is not correct.
                  DR. KENNETH PORTIER:  Dr. Kissel, can you add in a reference for that aggregate risk.  You mentioned the Superfund document.
                  DR. JOHN KISSEL:  Well, it's probably in regs which is the standard document.  I'd have to go look, but I'm sure I've seen that many times.  In many EPA documents that multipathway -- if you have exposure via ingestion of food, ingestion of dirt, ingestion of water, they'll get added together ultimately.  And you don't have to isolate all that so that we can't do aggregate because it came in a different vehicle or it came from a different route.  That's not historically how EPA has operated.
                  DR. KENNETH PORTIER:  I think Dr. Cobb and then Dr. Davies.  Dr. Cobb.
                  DR. GEORGE COBB:  Thank you.  I really have a question.  So your assessment was the error in the P-DER2b model overestimated the exposure by dermal uptake.  Is that correct?
                  DR. JOHN KISSEL:  P_DER2b is exposure to product, and I think it's overestimating because the driving force is the density and not the aqueous solubility.  So, if you have pure compound -- thermodynamically, at least theoretically, with damage to barrier function, things can change.  But, theoretically, exposure to pure solvent is the same thing as exposure to saturated liquid.
                  So, if you had pure solvent on your skin, then you could take an aqueous vehicle permeability coefficient multiplied by the aqueous solubility and that would give you an estimate of what the max flux that you would expect.  Now, in this case, that estimate, that traditional estimate of max flux, is much lower than what was actually observed in the Frasch experiments.  I mentioned this last time; you're making estimates based upon physical/chemical parameters and those things can be off by one and half logs which is what we have here, and so that number can be wrong.  But, with respect to intention, the consumer thing is too high.  Now it's possible that there's other errors build in there that that overestimate actually isn't all that awful, but that's a different issue.  And that's not error at all.  I'm not asserting that the air is overestimated because the air is not even considered.  So it's by definition underestimated.
                  DR. KENNETH PORTIER:  Dr. Davies.
                  DR. HOLLY DAVIES:  So having John dig into that model just brings up another issue that I want to mention some point explicitly on some of these models that were used here that we didn't dig into that seemed reasonable for this use that I didn't want to make it seem like we were kind of peer reviewing them for all uses or blessing them in some way more than we are because we haven't really dug into them.  And I just wanted to make sure when we write up our report or the way it comes that it's qualified in how they were used or that they were being used for this.  And maybe that goes in Question 7 with the characterization of uncertainties and assumptions.  And it's also kind of how they get peer reviewed and what constitutes peer review because we haven't -- because I think John's the only one who really tried to run any of these and dig into it and only the dermal one.
                  DR. KENNETH PORTIER:  I would say things like the BMD package.  It's pretty standard, and they put that right.
                  DR. HOLLY DAVIES:  I saw in the EPI Suite.
                  DR. KENNETH PORTIER:  But in some of the --
                  DR. HOLLY DAVIES:  Right.  Some of them are well established.
                  DR. KENNETH PORTIER:  Yeah.  The one like the unloading model that I questioned earlier on.  I was like, I wanted to kind of dig into it, but I had a hard time getting down to the actual details of the model.  And I think we recorded that a couple of days ago.  Any additional comments?  Oh, Dr. Blando.
                  DR. JAMES BLANDO:  When I read this question, I was thinking more of sort of global statement that I felt like we were being asked to make.  So I'm going to make my global statement that, after reviewing this and spending a few days talking about a lot of the subtle details that are really important and really and crucial for EPA to consider to improve the assessment, I just wanted to make the statement that for me, personally, as a member on this committee as a scientist working in this field that I did feel that this risk assessment was objective and is a quality product, and that as a public health professional, I would feel comfortable utilizing this document to make decisions.  And I just felt -- that's what I thought we were being asked for to confirm that, and, in my personal opinion, I just wanted to confirm that.  That's not to say it can't be improved.  It's not to say that all the very important suggestions that have been here in the last few days that EPA really does need to consider, but I just wanted to affirm that I think this an objective and quality product.
                  DR. KENNETH PORTIER:  I think that's a good lead into Question 7.4 because I have a feeling that's what 7.4 is asking us.  So why don't we go ahead and read 7.4 in.
                  MS. TAMUE GIBSON:  Dr. Barone.
                  DR. KENNETH PORTIER:  Yeah, okay, before we read it --
                  DR. STAN BARONE, JR.:  I'd like to get some clarifications first.  I just want to be sure we understood things correctly, and I want to make sure we get the feedback in the report so that to really make these recommendations or what I'm hearing as nascent recommendations actionable.
                  I do appreciate Dr. Blando's comments.  Sometimes I think the committee has really great ideas and has criticism, but sometimes these criticisms can be interpreted by others as showstoppers.  And so we really need to know when things are showstoppers or prioritize what these efforts could actually entail because some decision-makers would use some critiques as, oh, you can't make any decisions.  Oh, you can't do anything with this.  So that's why I'm drilling down a little bit, so I want to preface my comments or my questions.
                  So I heard the comments about occupational emissions as being incorrect, and it wasn't really clear.  When I hear occupational emissions or occupational emission rates, that's a big deal for our modeling efforts.  So I need a little bit more information about what you think is wrong with our assumptions or the data that we're using for occupational emissions.
                  DR. KENNETH PORTIER:  This is Ken Portier.  I didn't quite hear that and that's why I asked the clarifying question because I think what they were saying was, and if I get my notes right, that general population exposures -- and maybe you're talking about indoor air consumer use exposures -- might not have been properly estimated, and I'll ask Dr. Cobb to clarify.
                  DR. GEORGE COBB:  Again, that was asked earlier and I appreciate the question and I was kind of the scribe here.  That was from one of the other discussants, and I'm not sure which discussant that came from.
                  DR. KENNETH PORTIER:  Can you read that section again?
                  DR. GEORGE COBB:  What I'm reading here is probabilities -- and, Stan, correct me if I'm wrong with this what you're getting to -- differing exposure scenarios were well characterized with the exception that the assumed emission rates for occupational exposures may be inaccurate.  Is that what -- and lead to an underestimate of actual risk.  I'm struggling to find out who sent me that comment.
                  UNIDENTIFIED MALE:  That may have been Cory-Slechta.  Yes, Cory-Slechta.
                  DR. HOLLY DAVIES:  Yeah, I checked my notes, and I don't see it in my notes.  It doesn't sound like me, and I didn't accidentally send it.
                  DR. STAN BARONE, JR.:  So, if you can figure out what the basis for that is, we would like to be able to correct that because that, at least from our vernacular, that's a big deal.
                  DR. GEORGE COBB:  Understood and actually you can't see it, but I have that italicized, or actually bolded, in something that I need to go back and clarify.
                  DR. STAN BARONE, JR.:  Okay.  And, again, emission rates for general population, general population wasn't assessed here.  We scoped that out for regulatory Nexis reasons.  There was also mention of ADAFs again in Dr. Perkins's comments.  And, again, we are not looking at daycare and adjacent buildings.  ADAFs only apply to a mutagenic mode of action.
                  So, again, depending upon the recommendations of the committee, and then what we decide to do, we sort of need to have that ground tree thing of, you know, when do apply ADAFs and when don't you apply.  You don't apply ADAFs for every carcinogen.  It's only with a mutagenic mode of action; and it's only for children's exposure from 0 to 16.  It's not for gestational exposures.  We do not have guidance for gestational exposures, unlike Cal. EPA.
                  So I just wanted to put that out there.  The comments on P_DER2b, again, the more that can be detailed out in the recommendations, the more actionable that will be for us.  And we do have ongoing work on dermal modeling.  And, again, this has been brought up several times, so we're working fast to try to resolve some of these issues.  But the more detailed comments -- and we've yet to get a report from the committee.  As soon as we get a report from the committee, we hope that we can come back and talk to you next time about the specifics in the report and have revised estimates based upon our ongoing work.  So this is a sort of moving target we recognize, but we really need the committee's input on this very important issue.
                  DR. KENNETH PORTIER:  Oh, Dr. Blando.
                  DR. JAMES BLANDO:  This is Jim Blando.  What I thought I heard, just to clarify regarding occupational exposures, was the comment that Dr. Cory-Slechta made on the phone which was her concern about the occupational emissions was that for small shops, small operations, the distinction between an ONU and a worker is not that clear, and that perhaps it's too artificial, and that maybe an ONU and a worker that distinction between their exposure concentrations because it's not that distinct and that maybe their ONUs and worker exposure should be.  So that's what I thought I heard, but she's on the phone, so she can clarify if that's what she meant.  That's what I heard.  That's what I thought I heard.
                  DR. DEBORAH CORY-SLECHTA:  Yes, that's what you heard.