### 202-234-4433 Neal R. Gross & Co., Inc. Page 1 U.S. ENVIRONMENTAL PROTECTION AGENCY + + + + + CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE

LEAD REVIEW PANEL

+ + + + +

PUBLIC MEETING

+ + + + + WEDNESDAY, JULY 20, 2011 + + + + + The meeting convened in Salon BCD of the Marriott at Research Triangle Park, 4700 Guardian Drive, Durham, North Carolina, at 9:00 a.m., H. Christopher Frey, Chair, presiding.

CASAC LEAD REVIEW PANEL MEMBERS PRESENT: H. CHRISTOPHER FREY, Chair GEORGE A. ALLEN

HERBERT ALLEN DEBORAH CORY-SLECHTA CLIFF DAVIDSON PHILIP E. GOODRUM SEAN HAYS PHILIP HOPKE CHRIS JOHNSON

SUSAN KORRICK MICHAEL KOSNETT ROMAN LANNO RICHARD L. POIROT JOEL POUNDS MICHAEL RABINOWITZ WILLIAM STUBBLEFIELD

IAN von LINDERN GAIL WASSERMAN MICHAEL WEITZMAN

### 202-234-4433 Neal R. Gross & Co., Inc. Page 2

U.S. ENVIRONMENTAL PROTECTION AGENCY STAFF

PRESENT:

AARON YEOW, Designated Federal Officer

VANESSA VU, Director, SAB Staff Office

ELLEN KIRRANE

JOHN J. VANDENBERG

### 202-234-4433 Neal R. Gross & Co., Inc. Page 3 C-O-N-T-E-N-T-S Convene and Welcome 5 Introductions of Panel Members, Purpose of Meeting, Agenda Review 10 EPA Presentation on the Lead Integrated Science Assessment 22

Public Comment 52 Charge Question 1 Causal Framework/Study Selection 63 Charge Question 3 Ambient Lead 96 Charge Question 4 Exposure, Toxicokinetics, and Biomarkers 152 4a - Exposure and Toxicokinetics 152 4a - Biological Markers 168 4a - Empirical Modeling 223 Charge Question 5 Integrated Health Effects of Lead Exposure 231

5a & 5e - Modes of Action and Dose Response 231 5b & 5c - Health Endpoints 241 5d - Integration of Epidemiological and Toxicological Evidence 251 Charge Question 7 Ecological Effects of Lead 282 Charge Question 6 Susceptible Populations and Life Stages 334

### 202-234-4433 Neal R. Gross & Co., Inc. Page 4

C-O-N-T-E-N-T-S

Charge Question 2 Integrative Health and Ecological Effects

Overview 352

Summary and Action Items 390

Adjournment 396

### 202-234-4433 Neal R. Gross & Co., Inc. Page 5 1 P-R-O-C-E-E-D-I-N-G-S

2 9:00 a.m. 3 MR. YEOW: Good morning, I'm Aaron 4 Yeow, the Designated Federal Officer for the 5 Clean Air Scientific Advisory Committee and 6 Lead Review Panel. 7 I'd like to convene this public 8 meeting of the panel and to open the meeting 9 with a short statement. 10 The panel's meeting today and 11 tomorrow to conduct a peer review of EPA's 12 Integrated Science Assessment for Lead and a 13 consultation on EPA's Lead Risk and Exposure 14 Assessment Planning Document. 15 CASAC is a federal advisory 16 committee and by EPA policy, its meetings and 17 deliberations are held as public meetings that 18 meet the requirements of the Federal Advisory 19 Committee Act, also known as FACA. 20 Through their charter CASAC, the 21 panel's empowered by law to provide advice to 22 the administrator. Consistent with the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 6 1 requirements of FACA and with EPA policy, the 2 deliberations of the panel are conducted in 3 public at meetings for which advance public 4 notice is given. 5 The discussions and substantive 6 deliberations of the panel, its interactions 7 with the public and the agency are conducted 8 in sessions where I, as the DFO, am present to 9 ensure that the requirements of FACA are met. 10 This includes the requirements for 11 open meetings, for maintaining records of 12 deliberations of the panel, making available 13 to the public summaries of meetings and 14 providing opportunities for public comment. 15 We have received one set of 16 written public comments which has been 17 distributed to the panel and has been posted 18 on our website. And we also have one 19 registered public speaker for the ISA

20 document. 21 Minutes of this meeting are being 22 taken to summarize discussions and action

### 202-234-4433 Neal R. Gross & Co., Inc. Page 7 1 items in accordance with the requirements 2 under FACA. These minutes will be certified 3 by the panel chair once completed. 4 I want to remind all in attendance 5 today of the status of the panel's compliance 6 with federal ethics laws. The SAB Staff 7 Office has determined that there are no issues 8 with conflict of interest or appearance of a 9 lack of impartiality for any of the advisory 10 panel members participating in this review. 11 I'd also like to note at this time 12 that Dr. Richard Canfield was not able to make 13 it at the last minute due to a family 14 emergency. 15 I'd now like to turn the meeting 16 over to Dr. Vanessa Vu, Director of the SAB 17 Staff Office, and then over to Dr. Chris Frey, 18 Chair of the CASAC Lead Review Panel. 19 DR. VU: Good morning. I'm 20 Vanessa Vu. I'm the Staff Director of the EPA 21 Science Advisory Board. I'd take this 22 opportunity to welcome everyone to the public

### 202-234-4433 Neal R. Gross & Co., Inc. Page 8 1 meeting of the Clean Air Scientific Advisory 2 Committee Lead Review Panel. 3 I want to thank Dr. Chris Frey, 4 and members of this distinguished CASAC panel, 5 members of this panel for your committed 6 public service to EPA. 7 As Aaron has indicated, you'll be 8 asked to provide review comments on the 9 agency's document on the Integrated Science 10 Assessment of Lead, and tomorrow you'll be 11 conducting a consultation regarding the 12 agency's document regarding the scope and 13 method plan for the exposure and risk

14 assessment. 15 As part of the ongoing review of 16 the lead, you will be asked to provide 17 independent advice to the administrator 18 through the charter CASAC, and your report 19 will be considered by the charter CASAC for 20 approval before we transmit to the 21 administrator. 22 As Aaron has mentioned, that we do

### 202-234-4433 Neal R. Gross & Co., Inc. Page 9 1 receive public comments. I ask that you 2 consider public comments, both written and 3 oral comments as part of your discussion 4 deliberation and your preparation of your 5 report. 6 I'd like to acknowledge and thank 7 members of the EPA Office of Research and 8 Development National Center for Environmental 9 Assessment, headed by Dr. John Vandenberg, who 10 will be here today to be part of the, give 11 presentation about the ISA, and his staff will 12 also respond to any clarification questions 13 you might have on the ISA. 14 And tomorrow you'll be joined by 15 Dr. Bryan Hubbell, from the Air office, the 16 Air Quality Planning and Standards Office, 17 OAQPS, will be here to talk about the scope of 18 the risk and exposure scoping plan. 19 Finally, I want to thank Aaron 20 Yeow, who's the Designated Federal Officer for 21 this panel, and all members of my staff and 22 contractor personnel for making this meeting

### 202-234-4433 Neal R. Gross & Co., Inc. Page 10 1 happen. 2 So with that I'd like to turn the 3 meeting over to Dr. Chris Frey. 4 DR. FREY: Thank you, Vanessa. 5 Good morning, and welcome to Research Triangle 6 Park on this nice, warm day. 7 Welcome to members of the panel

8 and to the EPA staff and to members of the 9 public. 10 We'll begin with a round of 11 introduction of panel members, and then I'll 12 briefly talk about the purpose of the meeting 13 today and then review the agenda. 14 I am Chris Frey. I am a professor 15 of Environmental Engineering at North Carolina 16 State, and I'm serving as Chair of the Lead 17 Review Panel and I'm also on the statutory

18 CASAC. 19 What I would like to do is start 20 with Dr. Allen, and if we could just go around 21 the table and please introduce yourself and 22 your affiliation.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 11 1 Dr. Allen? 2 DR. FREY: Oh, Herb Allen. We 3 have two Dr. Allens, sorry. 4 MR. ALLEN: Only one, actually.

5 DR. ALLEN: I'm Herb Allen. I'm 6 from the University of Delaware Department of 7 Civil and Environmental Engineering. 8 DR. FREY: Oh, and please, yes, 9 please use the microphone. Thank you. 10 DR. ALLEN: Got to do this again? 11 I'm Herb Allen. I'm from the University of 12 Delaware Department of Civil and Environmental 13 Engineering. 14 DR. LANNO: I'm Roman Lanno, Ohio 15 State University Department of Evolution, 16 Ecology and Organismal Biology. 17 DR. JOHNSON: I'm Chris Johnson. 18 I'm currently Chair of the Department of Civil 19 and Environmental Engineering at Syracuse 20 University.

21 DR. POUNDS: I'm Joel Pounds from 22 the Pacific Northwest National Laboratory.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 12 1 DR. GOODRUM: I'm Philip Goodrum 2 with ERM in Syracuse, New York. 3 DR. HAYS: Sean Hays with Summit 4 Toxicology in Allenspark, Colorado. 5 DR. KOSNETT: I'm Michael Kosnett. 6 I'm in the Division of Clinical Pharmacology 7 and Toxicology at the University of Colorado 8 School of Medicine, and also the Department of 9 Environmental and Occupational Health at the 10 new Colorado School of Public Health. 11 DR. WEITZMAN: And I'm Michael 12 Weitzman. I'm a professor of pediatric 13 psychiatry, and environmental health at the 14 New York University School of Medicine.

15 DR. CORY-SLECHTA: I'm Deborah 16 Cory-Slechta from the University of Rochester 17 medical school. 18 MR. ALLEN: I'm Mr. George Allen, 19 as opposed to Dr. Allen. That's how you tell 20 us apart. And I'm from NESCAUM, which is a 21 multi-state organization based in Boston that 22 works with the eight northeast states.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 13 1 DR. HOPKE: I'm Phil Hopke. I'm 2 the Director of the Institute for a 3 Sustainable Environment at Clarkson 4 University. 5 MR. POIROT: I'm Rich Poirot. I'm 6 with the Vermont Department of Environmental 7 Conservation. 8 DR. KORRICK: I'm Susan Korrick. 9 I'm at Harvard Medical School. 10 DR. WASSERMAN: Gail Wasserman in 11 child psychiatry at Columbia Medical School. 12 DR. von LINDERN: Ian von Lindern 13 with TerraGraphics Environmental Engineering 14 in Moscow, Idaho. 15 DR. RABINOWITZ: I'm Michael 16 Rabinowitz. I'm a retired isotope geochemist. 17 DR. DAVIDSON: Cliff Davidson, in 18 Civil and Environmental Engineering at 19 Syracuse University. 20 DR. STUBBLEFIELD: Bill 21 Stubblefield, Oregon State University in the 22 Department of Environmental and Molecular

### 202-234-4433 Neal R. Gross & Co., Inc. Page 14 1 Toxicology. 2 DR. FREY: Okay. Well, great. 3 Thank you, and thanks to all the panel members 4 for agreeing to serve on this review panel. 5 This is a multi-year adventure that we're 6 setting out on and your service is greatly 7 appreciated by EPA and it's an important 8 public service to the nation to provide 9 scientific advice regarding the development of 10 National Ambient Air Quality Standards. 11 There was an ulterior motive in 12 this, which was to practice using the 13 microphones. And when you make comments 14 during the discussions, please remember to use 15 the microphone so that you can be heard by all 16 in the room, and if we have anyone on the 17 phone so they'll be able to hear what you're 18 saying. 19 And just a reminder, if you have 20 any cell phones, please mute those. 21 So Vanessa mentioned the purpose 22 of this meeting but just to reiterate, CASAC

### 202-234-4433 Neal R. Gross & Co., Inc. Page 15 1 has essentially a mandate consistent with the 2 Clean Air Act to provide independent advice to 3 the EPA administrator regarding the technical 4 basis for EPA's National Ambient Air Quality

5 Standards. 6 And so today we're going to be 7 focusing on providing that advice in relation 8 to the scientific basis for the National 9 Ambient Air Quality Standard for Lead. 10 The document we're reviewing today 11 is called the Integrated Science Assessment. 12 And this is EPA's effort to compile all of the 13 relevant science that will then be the 14 foundation for whatever decision making is to 15 come in the subsequent months and years as we 16 go through this review process. 17 And just to quote from a memo that 18 the National Center for Environmental 19 Assessment sent to this panel, "The ISA is 20 intended to accurately reflect the latest 21 scientific knowledge useful in indicating the 22 kind and extent of identifiable effects on

### 202-234-4433 Neal R. Gross & Co., Inc. Page 16 1 public health, which may be expected from the 2 presence of a pollutant in ambient air." 3 And of course, we're addressing 4 not just public health effects in the 5 deliberations today, but also what are known 6 as "welfare effects" or secondary effects. So 7 those are other effects that can include 8 ecological effects, for example. 9 So that's our charge, our broad 10 charge for today. And we have specific 11 questions that have been posed to us by EPA 12 that we will answer as we go through the day. 13 What I would like to do is then 14 review the agenda which you should have in 15 front of you. 16 And our next segment will be a 17 presentation by EPA on the Integrated Science 18 Assessment for Lead, followed by public 19 comments. And we have as I understand, one 20 public speaker. 21 Depending on the timing we might 22 take a break at that point. We'll then come

### 202-234-4433 Neal R. Gross & Co., Inc. Page 17 1 and discuss the charge questions. The first 2 charge question has to do with the causal 3 framework and criteria for study selection for 4 studies considered in the ISA. 5 And for each charge question we 6 have lead discussants. So for example, for 7 Charge Question 1, Dr. Kosnett and Dr. 8 Davidson are the lead discussants. 9 Among the lead discussants we've 10 designated I guess a lead, lead discussant, 11 And that person with the asterisk on the 12 agenda for a charge question is the one who 13 we're asking to be responsible for developing 14 the consensus written response to that charge 15 question. 16 For many of the charge questions 17 there's maybe two discussants, sometimes 18 there's three, sometimes there's five, just 19 depending on the scope of the charge question 20 and the panel member expertise related to that 21 question. 22 Just to reiterate, the outcome of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 18 1 this meeting will be kind of three parts. One 2 is a letter to the administrator that contains 3 the high level comments, consensus comments 4 from the panel in about a two-page format.

5 Then there'll be an attachment 6 that contains the consensus response to each 7 charge question, and so that part's going to 8 rely very heavily on the lead, lead 9 discussants drafting the written response to 10 those charge questions. 11 And then the third part is the 12 individual member comments. Most of you have 13 submitted individual comments prior to the 14 meeting. You are welcome to revise those 15 comments, and Aaron Yeow and I, later will 16 give you a deadline for submitting those 17 revised individual comments. 18 What I would like is for the lead, 19 lead discussants today to, at the end of the 20 discussion of each charge question to be 21 prepared to just reflect on what they think 22 the key points are in answering the charge

### 202-234-4433 Neal R. Gross & Co., Inc. Page 19 1 question. That'll help us reach consensus or 2 understand what our consensus is. 3 What I'd like ideally by the end 4 of the day today, is that we have a pretty 5 clear idea of what it is we're going to say to 6 EPA in answering the charge questions. 7 That'll also help me quite a bit in 8 formulating the letter to the administrator. 9 Let me just pause for a minute and 10 ask, are there any panel member questions 11 about that process? Okay. 12 All right, so returning to the 13 agenda, we'll first talk about Charge Question 14 1. We're going to skip Charge Question 2 and 15 save that for later, because that has to do 16 with the integrative summary in the ISA and it

17 would seem to make sense to come back to that 18 after we've considered all the constituent 19 parts of the ISA. 20 So we'll go from Charge Question 1 21 to Charge Question 3. Mr. George Allen and 22 Mr. Rich Poirot are the lead, lead discussants

### 202-234-4433 Neal R. Gross & Co., Inc. Page 20 1 on Charge Question 3, so they jointly will 2 share responsibility for drafting the 3 consensus report for that charge question, 4 with the input of Drs. Davidson, Hopke and

5 Johnson. 6 As we go into Charge Question 4 7 that has subparts to it, so we've split it out 8 into an Exposure and Toxicokinetics part, a 9 Biological marker part and Empirical Modeling 10 part, and the discussants are indicated in the 11 agenda. 12 Charge Question 5 is also 13 subdivided into three parts. This is on the 14 top of the second page of the agenda. Modes 15 of Action and Dose-Response is one part, 16 Health Endpoints, and then Integration of 17 Epidemiological and Toxicological Evidence is

18 the last one. 19 Charge Question 7 is on Ecological 20 Effects of Lead, and we have a number of 21 experts in that area who will respond. 22 Charge Question 6 is on

### 202-234-4433 Neal R. Gross & Co., Inc. Page 21 1 Susceptible Populations and Life Stages, and 2 then we'll come to the Integrative summary 3 related to Charge Question 2. 4 For each charge question, I'll 5 first recognize the lead discussants in order 6 of the lead, lead discussants and then the 7 lead discussants, and then I'll open it up to 8 anyone on the panel who wants to provide 9 input. 10 What I'd like to do is, if you 11 would like to be recognized to speak, I'll 12 scan the room. If you want to put your 13 placard on end to indicate you want to speak, 14 that's fine, or just get my attention. 15 I will keep a speakers list, and 16 we'll start with that process and see how it 17 works. If there's a topic under discussion 18 where you really want to respond to that 19 topic, I don't know if there's a good way to 20 indicate that. Maybe just wave your arms 21 frantically and then I'll know that you want 22 to get in on that part of the discussion, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 22 1 we'll just try to manage that the best we can. 2 But otherwise, I'll generally recognize people 3 in the order that I notice that they've 4 indicated they want to speak. 5 With that I think that's all I 6 need to say at the moment. Anything else from 7 the DFO? Okay. 8 All right, so with that I would 9 like to invite the U.S. Environmental 10 Protection Agency to go ahead and present on 11 the Integrated Science Assessment, and I guess 12 I'll turn it over to Dr. Vandenberg. Thank 13 you. 14 DR. VANDENBERG: Okay. Thank you 15 very much, Dr. Frey. I would like to welcome 16 the panel on behalf of the EPA and the 17 National Center for Environmental Assessment. 18 We very much appreciate the time 19 you have committed to review the draft 20 document now and in subsequent draft when we 21 consider your comments, and the time you've 22 taken to come here today and enjoy this nice,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 23 1 balmy weather we have outside. 2 So I'd also like to welcome the 3 SAB staff and the members of the public that

4 are here. 5 We also are joined by a number of 6 the authors of the draft, and that's the NCEA 7 staff that are along the wall and in the back

8 as well as a number of ORISE fellows and 9 contractors. So welcome to all of you. We 10 appreciate your time and energy today as we 11 review this draft. 12 I'm going to provide a little bit 13 of context and then turn to Ellen Kirrane, who 14 is the overall Chemical Manager for the Lead 15 Integrated Science Assessment. 16 And then she'll be followed by 17 Debra Walsh, who is at the front with me as 18 well, who will discuss the Health and 19 Environmental Research Online system that you 20 have access to and how that works and is 21 intended as a support system for the review, 22 and also providing public access to the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 24 1 information that's used in the assessment. 2 Importantly, this is an Integrated 3 Science Assessment, which is different from 4 previous documents on lead which were called 5 Air Quality Criteria documents. 6 About three years ago, at the 7 direction of EPA upper management, we moved to 8 change the way we were structuring these 9 documents to try to have them be more focused 10 on the most policy relevant science and have 11 them be really more integrative and focused on 12 the information that is most important to 13 consider in setting the National Ambient Air 14 Quality Standards. 15 So we changed the title and we 16 also changed the document quite a bit. We've 17 constructed in the first couple chapters, 18 information on a framework that we use and 19 then we apply that framework in Chapter 2. 20 And then the following chapters actually 21 provide the scientific review of the different 22 studies that were considered.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 25 1 One of the things that I'd like to 2 communicate is that we've, now this is our 3 fourth assessment, fourth or fifth assessment 4 now that we've applied the new framing of the 5 Integrated Science Assessments to, and we're 6 continuing to evolve these documents. 7 And we very much benefit from the 8 input from CASAC. We've applied it to 9 particulate matter, to the NOx, SOx eco 10 assessment that was done some years ago to 11 carbon monoxide, and most recently to the

12 ozone assessment. 13 As a result of that we continually 14 get new ideas and new perspectives on how to 15 continually improve the document and we 16 certainly welcome your input on that. That's 17 the purpose of part of these charge questions, 18 is to give us ideas on how we might focus

19 that. 20 We are now awaiting the comments 21 from CASAC on the ozone first draft, so we're 22 just staggered a little bit here with the Lead

### 202-234-4433 Neal R. Gross & Co., Inc. Page 26 1 ISA following the Ozone ISA. And there's been 2 a lot of really important and helpful comments 3 on the ozone document that we're benefiting 4 from and kind of we're waiting for the final

5 letter from CASAC. 6 But one of the considerations 7 there that that panel has made is to do some 8 structural changes to the front of the 9 document where we look at the Introduction and 10 the Integrative summary as Chapters 1 and 2 in 11 the document that you have. 12 And we're looking at ways to 13 better frame that to be a little bit more 14 focused and integrative right up front. So 15 we're continuing to evolve this and certainly 16 welcome the Lead Panel input on it as well. 17 So what I'd like to do is just 18 review briefly the process that we use. On 19 this slide which you see to the top left is a 20 workshop on science policy issues. 21 This is where we benefit from the 22 prior review and the development of new

### 202-234-4433 Neal R. Gross & Co., Inc. Page 27 1 science that has occurred since that time. 2 And we bring in a number of experts and the 3 public are invited as well, to share their 4 views on what most important science issues 5 are that remain for us to consider and to

6 focus on. 7 That goes into an integrated 8 review plan that then goes through formal 9 CASAC consultation and public comment. Again 10 I think you've all seen that. That helps us 11 make sure the document is structured around 12 the most important issues. 13 Flowing from that plan are 14 actually two different documents. The 15 Integrated Science Assessment, which we're 16 reviewing today, and then the Risk and 17 Exposure Assessment plan, which is what will 18 be discussed tomorrow, ideas about that. 19 And again, CASAC involvement and 20 they're, ultimately information is flowing 21 into the policy assessment that is then, that 22 is actually developed by our colleagues in the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 28 1 Office of Air Quality Planning and Standards, 2 and that goes forward into the decision making 3 and support for the administrator's decisions 4 on what to do in terms of proposing standards. 5 Again, public review and comment, and then 6 finally, a final rule making that will occur. 7 This process takes a number of 8 years to go through, and so on the next slide 9 what you see is, the schedule for this review 10 is we are at the July 20-21st timeframe, the 11 highlighted bar here, and the first draft is 12 being reviewed today. 13 As you see, our second draft is 14 anticipated for December of this year. So 15 upon your considered comments and review and 16 comments back to the administrator, we'll 17 revise the document and provide it again with 18 ample opportunity for your second review as 19 well as for public comment. 20 Our goal is to finish the document 21 in the late winter or early spring of 2012, 22 and thereby that sets the stage for again the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 29 1 subsequent steps which is the Risk and 2 Exposure Assessment if it's warranted, and 3 decisions made to proceed with that. Finally, 4 the policy assessment and rule making. 5 So we have matched up these 6 meetings to optimize your time and energy. 7 And so as you see by the bar to the far right, 8 the meeting today is both to discuss the first 9 draft ISA as well as the planning document for 10 the Risk and Exposure Assessment, and then 11 subsequently in the February, March timeframe 12 is to, just the next steps of that process. 13 So the goal here is rule making 14 that will finish up late in 2014, and we are 15 very much again recognizing the several year 16 effort that it will take on your part to 17 contribute to this overall process. So thank 18 you again for your time. 19 I very much want to acknowledge and 20 extend my personal appreciation to the Lead 21 ISA team. And what you see again is a number 22 of the authors here in the room as well as

### 202-234-4433 Neal R. Gross & Co., Inc. Page 30 1 external authors, experts that we bring in to 2 help us as we frame certain issues that are 3 very important for this Integrated Science

4 Assessment. 5 So with that what I'd like to do is 6 turn to the team leader which is Ellen 7 Kirrane, who will walk through an overview of 8 the ISA and in particular, the charge 9 questions for your discussion today. 10 DR. KIRRANE: Thank you. This 11 slide shows the structure of the ISA. You've 12 seen the charge questions, and as you know 13 there's a general charge that addresses the

14 document as a whole and there are also 15 specific charge questions that are linked to 16 each chapter of the ISA. 17 I'm going to go through the charge 18 questions, and there are a lot of words on the 19 slide, so we've used the blue text and the 20 underline to highlight key phrases that we've 21 just selected to focus the presentation. 22 So for the general charge what

### 202-234-4433 Neal R. Gross & Co., Inc. Page 31 1 we're doing, we're aiming to present the most 2 policy relevant science, and we're building on 3 the findings from the 2006 Air Quality 4 document and also including new science. 5 It's our intention though to retain 6 adequate discussion of older studies that 7 remain the definitive works or may be open to 8 reinterpretation, so we're requesting comments 9 on how well we achieve that goal. 10 Turning to the next slide, the 11 specific charge for Chapter 1. The selection 12 criteria used to identify studies for 13 inclusion in the ISA are described in Chapter 14 1 of the document. We're requesting comment 15 on whether these selection criteria were 16 applied appropriately and consistently. 17 We've considered studies that are 18 approximately within one order of magnitude of 19 the current exposure levels, and we've 20 included some occupational studies. 21 And the example that we have 22 parenthetically in the charge question

### 202-234-4433 Neal R. Gross & Co., Inc. Page 32 1 addresses the extent to which, or requests 2 comment on how well we have consistently 3 incorporated those occupational studies across 4 endpoints. 5 This charge question also addresses 6 HERO, which will be discussed later in the 7 presentation. 8 So the slide for Chapter 2, the 9 specific charge, Chapter 2 is an integrative 10 summary of the ISA. We're requesting comment 11 on whether it's a useful summary and whether 12 it's effectively conveying the needed 13 information. 14 Also we are asking if the framework 15 for causal determination is appropriately 16 applied for both the health and the ecological 17 endpoints. 18 We noticed or observed a 19 substantial overlap between ecological and 20 health endpoints, and we've also observed that 21 the health and ecological effects are mediated 22 through interconnected modes of action.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 33 1 So we found an opportunity for 2 integration there and we are requesting 3 comment on whether this particular approach is 4 useful and effective. 5 And we've included some slides 6 from, just for a content to the ISA just as 7 examples. This is the framework of causal 8 determination that is described in detail in 9 Chapter 1 of the document. We evaluate the10 weight of the evidence and apply this five11 level framework. 12 This is a table that appears in the 13 document in Chapter 2. It's adapted from 14 Table 2.5. And it's a summary of the causal 15 determinations for both health and ecological 16 effects. The health effects, as you can see 17 causal determinations were made for all of the 18 outcomes evaluated except for cancer, where a 19 likely causal relationship was determined. 20 You can see the overlap between the 21 human health and ecological causal 22 determinations here.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 34 1 Towards the end of the slide where 2 we start with bioaccumulation there are no 3 causal determinations for the health outcomes 4 and those, for those outcomes. But we do note 5 that there is evidence from the health studies 6 that support and supplement the evidence and 7 the ecological literature base. 8 The next slide addresses the 9 specific charge for Chapter 3. Chapter 3 10 provides a wide range of information to inform 11 both exposure and health sections of the ISA. 12 And we're requesting comments on whether the 13 information is conveyed appropriately and 14 appropriately characterized. 15 The information included is lead 16 source characteristics, fate and transport, 17 lead monitoring, spatial and temporal 18 patterns. 19 And specifically we are requesting 20 comment on the relationship between ambient 21 air concentrations and concentrations of lead 22 in other media, and whether we have done an

### 202-234-4433 Neal R. Gross & Co., Inc. Page 35 1 adequate job to characterize those 2 relationships. 3 The specific charge for Chapter 4 4 is here. Chapter 4 covers lead exposure,5 toxicokinetics and biomarkers. It's a three6 part question and Part A is on this slide. 7 We are requesting comments on how 8 well the choice and emphasis of topics in the 9 chapter provide a useful context for human 10 health effects of lead in the ISA as well as 11 whether the ISA adequately describes 12 imbalances air related and non-air related 13 pathways of lead exposure. 14 Parts B and C are on this slide 15 also addressing Chapter 4, how well does this 16 section reflect the current state of the 17 knowledge of lead biomarkers and their 18 interpretation as it relates to both exposure

19 and dose? 20 And Part C, does the section 21 accurately reflect what is known about air 22 lead/blood lead relationships? And I've

### 202-234-4433 Neal R. Gross & Co., Inc. Page 36 1 included a table that we've adapted from the 2 ISA here. This is Table 2.7 in Chapter 2 of

3 the document. 4 The relationship between blood and 5 air lead was very important in the 2008 NAAQS 6 consideration because it allowed the 7 relationship between what's in the blood and 8 what's in the air to be characterized. 9 We have here the studies of 10 children that supply this relationship, and in 11 the far right column we have the slope. And 12 the slope, the units are in micrograms per 13 deciliter of blood per unit of air and 14 micrograms per cubic meter. 15 And for nonlinear models the nature 16 of the slope depends on where we are in the 17 distribution of air concentrations. 18 So we have computed the slopes, if 19 you look at the footnote, at 0.15 micrograms 20 per cubic meter as well as 1 microgram per 21 cubic meter for those nonlinear models. And 22 there's a difference, because the log log

### 202-234-4433 Neal R. Gross & Co., Inc. Page 37 1 models have a larger slope at the lower 2 concentrations and log linear models have a 3 smaller slope at the lower concentrations. 4 And something in terms of 5 interpreting those slopes, in the third bullet 6 we were just pointing out that the 7 concentrations range at which the slopes were 8 derived vary quite a bit, and some are very

9 low. 10 And in the case of Brunekreef the 11 range is 0.2 to 10 micrograms per cubic meter, 12 so in that case it's outside the range of 0.15 13 where we're deriving this slope. 14 Chapter 5 of the document presents 15 the health effects of lead. The evidence is 16 organized by health effect category then 17 endpoint and scientific discipline. 18 And Part A of this question, and 19 this is a five-part question, we are asking 20 about the mode of action and to what extent 21 are the discussion and integration of the 22 potential modes of action underlying the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 38 1 health effects of lead presented accurately 2 and in sufficient detail. 3 Mode of action is presented at the 4 beginning of Chapter 5 and then linked to 5 subsequent health effects later in the

6 document. 7 We do this because many modes of 8 action are common across health effects and we 9 find that this organizational scheme helps us 10 eliminate some redundancy in the document. So 11 basically is this effective, is this approach 12 effective? 13 This is a figure that appears in 14 the document. It's showing the lead-induced 15 events upstream from the observed health 16 effects, and you can see that there are 17 multiple modes of action responsible for the

18 health effects. 19 Altered ion status is the major 20 unifying mode of action, and it's the theme 21 around which the chapter was organized. 22 The second part, Part B, is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 39 1 requesting comment on the clarity and 2 effectiveness of the figures and tables in the 3 document. We're trying to accomplish quite a 4 bit in a snapshot in those figures, and I have 5 a few examples. 6 This is a figure that appears in 7 Chapter 2 of the document. It's the lowest 8 blood lead levels at which health effects are 9 substantiated. 10 As I'm sure you know, we've 11 determined causality depending on the larger 12 health effect category. 13 And this is a table that breaks it 14 down by endpoint and links those endpoints to 15 blood lead levels that that endpoint is well 16 substantiated. So does this type of figure 17 help convey useful information? 18 This is another example of a figure 19 from the ISA. It appears in Chapter 5 of the 20 document. It's a figure of full-scale IQ in 21 children, and the studies are organized by

22 mean blood lead level.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 40 1 The change of an IQ is standardized 2 at 1 microgram per deciliter of blood, and 3 some of the models are nonlinear so the change 4 in IQ also similar to the slopes for the air 5 to blood relationships. The slopes in these 6 studies also depend on where in the 7 distribution of blood lead level you are. So 8 again, these are standardized at 1 microgram 9 per cubic meter. 10 There are columns for the timing of 11 blood measurement, mean blood lead level from 12 the study as well as age of the children. 13 Continuing with the third part of 14 Chapter 5 charge question, should discussions 15 of specific endpoints be expanded to provide 16 a more comprehensive assessment? 17 Part D asks specifically if the 18 integration of the epidemiologic and the 19 toxicological evidence is accurate and well 20 characterized. 21 We have a figure in, it appears in 22 both Chapter 2 and Chapter 5 of the document

### 202-234-4433 Neal R. Gross & Co., Inc. Page 41 1 that is an example of one approach for 2 integrating the document. This figure is 3 meant to, in sort of a snapshot, show the 4 consistency between the toxicology and the 5 epidemiology for parallel endpoints. 6 The purple is epidemiologic 7 findings, and the toxicological findings are 8 in green. And you can also see in this figure 9 the consistency and coherence with the modes 10 of action at the bottom of the period leading 11 all the way up to more downstream effects, 12 learning, memory, behavior, mood disorders and 13 motor function. 14 So this is one example of how we 15 are integrating the findings, and it was the 16 concepts that I just mentioned are important 17 in our causal determinations. 18 The last part of Chapter 5 we are 19 asking for comment on the extent to which the 20 expanded discussion of the concentration 21 response function and the shape of the 22 function is consistent and informative.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 42 1 And that discussion appears in 2 Chapter 2 of the document and is also expanded 3 upon in Chapter 5. 4 So moving on to the specific charge 5 for Chapter 6. We have several key phrases 6 underlined here. Are the characteristics 7 included within the broad susceptibility 8 categories appropriate and consistent with the 9 definitions? 10 Are there key susceptibility 11 factors that were not included and need to be 12 added? Is it appropriate to include material 13 on susceptibility factors related to exposure

14 and dose as well as effect of factors that 15 modify the associations between lead and

16 health outcomes? 17 The definition of susceptibility is 18 listed here. And this is the definition that 19 we currently use. It's in the document. 20 CASAC has been discussing this definition as 21 part of the ozone review. We expect to make 22 some refinements based on that review of the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 43 1 definition that we're using. 2 Right now it's an all-encompassing 3 definition and it's designed so that we don't 4 need to distinguish between the different 5 terms like susceptible, vulnerable, at risk 6 and sensitive.

7 We chose an umbrella term because 8 it's very often difficult to categorize the 9 factors into those terms. So we opted for

10 that umbrella term. 11 This is the listing of susceptible 12 populations and lifestages identified in the

13 document. 14 The charge question also mentions 15 that susceptibility to lead is discussed in 16 other parts of the document, not just in 17 Chapter 6. 18 So we're also requesting feedback 19 under this charge question on whether other 20 sections of the document adequately cover and 21 appropriately distinguish lifestage dependent 22 differences, specifically the differences

### 202-234-4433 Neal R. Gross & Co., Inc. Page 44 1 between children and adults as they relate to 2 the effects of lead in the mode of action 3 section, for example, the exposure section, 4 toxicokinetics sections. 5 The last set of charge questions 6 relates to Chapter 7. Chapter 7 is the 7 ecological effects chapter. Several new 8 approaches were tried in this chapter. 9 In addition to considering effects 10 of lead in terrestrial and aquatic systems,

11 the eco team took a look across taxa at 12 endpoints such as neurobehavior, development 13 and reproduction. 14 Where appropriate toxicological 15 evidence was used to support findings of the 16 effects of lead in those terrestrial and 17 aquatic systems. Bioaccumulation was 18 considered as an effect, as it affects 19 ecosystem services. 20 Causal determinations at the 21 species level were considered when evaluating 22 causality at the community or ecosystem scale.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 45 1 And the impacts to ecosystem services, the 2 benefits people obtain from ecosystems were 3 evaluated in this assessment. 4 This is a slide, the mode of action 5 slide you've seen before. This is the slide 6 that shows a table showing the shared modes of 7 action between the health and evidence in 8 biota.

9 These are the health effects that 10 are common to both human health and ecosystems 11 and the causal determinations are also 12 included here. These are the ecosystem 13 effects for which we did not do a causal 14 determination for health effects, but as I 15 mentioned before some of the evidence in the 16 health literature does support these causal 17 determinations as well. 18 And finally, for the specific 19 charge on Chapter 7, has the ISA adequately 20 characterized the available information on the 21 relationship between lead exposure and the 22 effects of individual organisms and ecosystems

### 202-234-4433 Neal R. Gross & Co., Inc. Page 46 1 as well as the range of exposure 2 concentrations for the specific endpoints? 3 So with that I'd like to turn it 4 over to Debra Walsh to discuss HERO. 5 MS. WALSH: Good morning. HERO, 6 Health and Environmental Research Online, so 7 this is a system that we've been developing 8 for several years now. Actually we started 9 HERO when we started changing from the Air 10 Quality Criteria document into the Integrated 11 Science Assessment. 12 And it's been an evolving system 13 that we really try to provide an agile 14 environment so that we develop something, we 15 try it, we use it, if it works we keep it. If 16 it doesn't work we try to change it and make 17 it a useful tool not only to the researcher 18 but also as a way of providing some 19 transparency to the stakeholders and to the 20 public. 21 So here you see two websites. The 22 first one is HERO Net, and this is the tool

### 202-234-4433 Neal R. Gross & Co., Inc. Page 47 1 that we use to facilitate assessment 2 development. This has been primarily used for 3 NCEA and partners. And partners we look at 4 certainly in this for the ISAs is OAQPS. 5 So they have been in HERO Net. It 6 allows them access to some different tools 7 than you will see actually at the public 8 website, which is just epa.gov/hero, that we 9 use to provide transparency to stakeholders 10 and public. 11 All right. So this is the public 12 page for HERO and it gives you some general 13 information about the database and some menus 14 where you can get some additional information 15 on other pages. 16 This is what the public page would 17 look like for the Integrated Science

18 Assessments as well as the IRIS assessments 19 that we do in other parts of NCEA. 20 At the first tab under the 21 Integrated Science Assessments for the air 22 pollutants you see lead.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 48 1 And we now provide not only the 2 references for the, that were actually cited 3 in the document, we've done that back to PM I 4 think was the first one where we actually, you 5 could see the document and you could actually 6 see all the references as a bibliography if 7 you wanted to print that off and export that

8 to use those references. 9 But we're also providing the 10 references that were considered. And we did 11 that first for ozone, which was the previous 12 one to lead, and then I'm going to show you 13 where it's a little bit different in how we're 14 providing those references that are 15 considered. 16 This is the HERO Net page. So if 17 you look on the menu far on the left, you'll 18 see the same kinds of things that you would on 19 the public side where we can provide the 20 abstract, the citation and information on how 21 to get the article. 22 Down at the bottom of that white

### 202-234-4433 Neal R. Gross & Co., Inc. Page 49 1 bar there in the middle you'll see some 2 different tools like LitSearch, LitBrowser, 3 LitReporter and Screener and LitCiter, and 4 those are the internal tools we use in 5 assessment development.

6 Now we have as of ozone entered 7 CASAC, so all of the panel members here should 8 be entered into HERO Net. So you would see 9 this exact page if you go to epa.gov/heronet 10 so you would now have access to see the same 11 kinds of things that we have as tools in 12 developing the assessment. 13 So this is the PM document. This 14 was the first ISA that we actually used the 15 tool we call LitCiter, one of the modules, to 16 hyperlink the reference inside the document. 17 So if you would look at that number 18 that's underlined and in blue, we've changed 19 that now with the lead ISA. But you would 20 click on that link if you were reading the 21 document, and that HERO ID's a unique number

22 to that reference.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 50 1 And this is a Word plugin that we 2 use that's very much cite while you write.

3 It's now based off of EndNote. And then the 4 reference is available to the public where 5 they can not only see the citation but 6 actually read the abstract. 7 Now this is the lead landing page. 8 This is different. This is a new, as I've 9 mentioned earlier we're trying to really 10 incorporate whatever we can in feedback from 11 the public and from CASAC to try to provide 12 more transparency to how we develop our

13 documents. 14 So for lead you would not only see 15 the references cited but those that were 16 considered, and we've organized them by 17 filters you can see over on the right, by 18 discipline and subject matter. 19 And as we're moving forward to NOx, 20 which will be the next ISA we're working on, 21 we're trying to provide even more information 22 to the public and to CASAC, and we're using

### 202-234-4433 Neal R. Gross & Co., Inc. Page 51 1 LitReporter. 2 So our plans as we're developing 3 that ISA is to have in addition to the actual 4 reference, to have some specific information 5 that would pull out about that material that 6 would be available for review. 7 This is a start toward our ultimate 8 goal which is a LitExtractor where we would 9 actually pull the data out of the papers and 10 into this relational database that you could 11 query, export and then do analysis on actual

12 numbers. 13 So that's the introduction to HERO. 14 I'll be happy to take any questions. And we 15 really would like for you to use the database. 16 We really want your feedback, so if you have 17 any difficulties at all. 18 I know there were a couple members, 19 I think we resolved that so feel free to 20 contact us. We really want it to be a tool 21 for you to use in your review of the ISA. 22 DR. VANDENBERG: Dr. Frey, back to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 52 1 you. 2 DR. FREY: Okay, well thank you. 3 Do the panel members have any questions of 4 clarification at this point? I don't see any. 5 Thank you. Thank you very much. 6 I think at this point we will go to 7 the public comment session, and I understand 8 we have one speaker registered. Craig 9 Boreiko, and is that correct? 10 DR. BOREIKO: Boreiko. 11 DR. FREY: Boreiko. Okay, so we 12 can offer you five minutes.

13 DR. BOREIKO: Sure. 14 DR. FREY: Strictly enforced, and 15 are you ready? If you're ready you may begin. 16 DR. BOREIKO: My name is Craig 17 Boreiko. I'm Director of Science Programs 18 with the International Lead Zinc Research 19 Organization, a couple exits west on the I-40 20 is where we're based. 21 I'm basically here one, because I'm 22 a glutton for punishment and two, we are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 53 1 supported by the industry and that includes 2 the Association of Battery Recyclers, who have 3 independently filed comments, and the 4 International Lead Association, which is

5 London based. 6 Copies of my comments are available 7 including an annotated version with references 8 and what have you. 9 I've been through the ISA, granted 10 perhaps not as in depth as I would have liked 11 to have gone through it, but did find it to 12 deviate from previous criteria documents in a 13 number of significant ways, some good, some

14 I'm not so sure about. 15 The preface on the issues of 16 causality and how one determines causality I 17 found to be valuable and interesting. And 18 given the pressure the agency has been under 19 for a number of quarters on its risk 20 assessment procedures, I can understand the 21 inclusion of such a section. 22 I did find it difficult to evaluate

### 202-234-4433 Neal R. Gross & Co., Inc. Page 54 1 because it seems to have lowered the terms of 2 engagement if you will or criteria for 3 causality, but very difficult to evaluate when 4 placed within the context of lead where you 5 can pretty much say anything you want about 6 lead that's bad and people are going to say 7 yes, okay, that's true. 8 The task was made doubly difficult 9 by the fact that even though causality 10 criteria are put forward in the document, I 11 did not find that they were rigorously applied 12 in a number of instances within the body of 13 the ISA itself. And I'll just give a couple 14 of examples of that. 15 Confounder and co-exposures, we all 16 know that they are important in the 17 consideration of environmental neurotoxicants. 18 This is particularly important for 19 lead, where lead is really a signature marker 20 if you will for socioeconomic disadvantage and 21 adverse living circumstances, what have you. 22 Scant attention is paid by the ISA

### 202-234-4433 Neal R. Gross & Co., Inc. Page 55 1 to the causality guidelines with respect to 2 confounders that appear to influence the 3 outcome of lead epidemiology studies, and this 4 includes some of the newer papers that have 5 come out that have defined confounder of 6 Surkan and what have you that we know are 7 important in lead/child development studies, 8 and yet up to this point in time have not been 9 considered by most investigators. 10 Gulson published a paper that 11 produced a firestorm of response a few years 12 back, talking about other environmental 13 neurotoxicants that might be present in 14 influencing the outcome of lead/development 15 studies. 16 The paper's not mentioned and 17 neither is the literature that documents the 18 impact of other neurotoxicants that have an 19 adverse impact upon child development. 20 I mention that only because while 21 the lead literature does not pay attention to 22 those environmental toxicants, those

### 202-234-4433 Neal R. Gross & Co., Inc. Page 56 1 environmental toxicants are conducting their 2 studies and correcting for the effects of

3 lead. 4 The ISA does achieve a consistent 5 narrative voice. At some points I found it 6 did so by neglecting or in some cases 7 essentially misrepresenting some of the 8 studies that it was discussing. 9 Table 2.2, you've got a discussion 10 of the effects of lead on end-of-grade testing 11 by Miranda. The ISA will give a page or two 12 of discussion of that paper. 13 DR. FREY: Thirty seconds. 14 DR. BOREIKO: Thirty seconds. And 15 then essentially give passing mention to a 16 paper by Chandramouli et al. and say in a 17 sentence or two and they fundamentally found 18 the same thing. 19 Actually read the paper and they 20 say yes, there are effects under ten, and oh 21 by the way there's a threshold at five. That 22 study comes from the ALSPAC study that the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 57 1 U.K. government runs with some frequency. 2 I'll just make one final comment on 3 issue of quantitative emissions. You've got 4 an estimate of 1,200 tons of anthropogenic 5 emissions. I did some quick comparisons. I 6 know the numbers are difficult to come up 7 with, but what are the estimates of natural 8 emissions to the atmosphere? 9 Well, in '89, Nriagu was estimating 10 about 12,000 tons or about ten times the 11 amount globally, so U.S. 1,200 tons, probably 12 about equivalent to what you would expect from 13 natural emissions. More recently, Richardson 14 et al. estimated North American natural 15 atmospheric emissions to be 36,000 tons, 16 considerably larger. 17 I guess my main point is, is that 18 current anthropogenic emissions are 19 quantitatively probably about the same if not 20 less than those that are coming from natural 21 emission sources. It causes me to wonder 22 whether further reductions in anthropogenic

### 202-234-4433 Neal R. Gross & Co., Inc. Page 58 1 emissions are likely to yield measurable 2 public health or environmental benefits. 3 Thank you. 4 DR. FREY: Okay, thank you very 5 much. Are there any questions of 6 clarification from the panel? 7 Yes, Dr. von Lindern? 8 DR. von LINDERN: Craig, you said 9 you submitted comments. 10 DR. BOREIKO: Yes, they are 11 available. I have copies with me and they're 12 on the CASAC website. 13 (Off microphone discussion) 14 DR. FREY: Yes, Dr. Weitzman? 15 DR. WEITZMAN: May I ask you to 16 repeat or clarify a comment that lead being a 17 marker for other types of socioeconomic 18 disadvantage so that I might respond 19 appropriately? 20 DR. BOREIKO: I would say to the 21 child development community at large lead 22 serves as a marker for socioeconomic

### 202-234-4433 Neal R. Gross & Co., Inc. Page 59 1 disadvantage. Lead exposure is -- I should 2 say invariably you oftentimes find that 3 socioeconomic exposure is associated with risk 4 factors for lead exposure as well as other 5 social and other factors that have adverse 6 impacts upon child development. 7 DR. WEITZMAN: So may I respond to

8 that? 9 DR. FREY: I think if it's in the 10 spirit of clarification. If it's more 11 deliberation then I think we could reserve 12 that for the later discussion. 13 DR. WEITZMAN: No, I think it's 14 clarification. 15 DR. FREY: Okay. 16 DR. WEITZMAN: I think if you look 17 at the recent CDC publications you'll find 18 that that's an antiquated statement. That in 19 the United States at this particular point a 20 lot of the racial economic differences have 21 gone away. 22 I'd also like to point out two

### 202-234-4433 Neal R. Gross & Co., Inc. Page 60 1 other points, which is that there is a fairly 2 robust literature looking at middle class 3 children and a related literature that looks 4 at the multiplicative effect if you will of 5 lead when it's combined with socioeconomic 6 disadvantage. 7 And I take great issue with the 8 statement that the lead literature doesn't try 9 to control for confounders. And there are any 10 number of studies that form the central opus 11 upon which we understand lead's effects and 12 the population basis on children that control 13 for as many as a dozen different confounders. 14 DR. BOREIKO: I would be in 15 complete agreement with you there. I would 16 say that there is not systematic treatment of 17 that issue within the ISA, and that is where 18 I have problems, because that was stressed as 19 being very important within the context of 20 establishing causality. 21 Within the context of the ISA they 22 acknowledge confounding but they do not

### 202-234-4433 Neal R. Gross & Co., Inc. Page 61 1 subject it to the sort of systematic analysis 2 and treatment that you have suggested is 3 necessary and I would agree. 4 DR. FREY: Okay, yes?

5 DR. LANNO: Just a comment on the 6 anthropogenic versus natural lead emissions. 7 You mentioned that the natural lead emissions 8 are about ten-fold higher, is that correct? 9 Am I interpreting that correctly? 10 DR. BOREIKO: I'm flashing back to 11 '89 and the classic Nriagu paper where global 12 emissions, I want to say global emissions 13 were, natural emissions were estimated to be 14 ten times higher. But that's global. You

15 have to scale down to the U.S. 16 The only other more recent

17 reference I was aware of was one that came 18 from Canada, a geological survey, which was 19 about 36,000 tons for North America including 20 Canada, Mexico.

21 DR. LANNO: Am I that clear 22 understanding that you said that reducing the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 62 1 anthropogenic emissions may not make that much 2 of a difference in global scale or U.S. scale

3 overall? 4 DR. BOREIKO: If those estimates of 5 natural emissions are correct, yes. 6 DR. LANNO: And I guess if it's 7 general distribution I might agree with you, 8 but I think that if we look at localized 9 inputs there may be situations where -- 10 DR. BOREIKO: Point sources, sure. 11 And constraints of time were such that I 12 didn't get into it, but you really don't find 13 within the ISA, at least I didn't see within 14 the ISA the establishment of a, what is the 15 contribution of air lead to current blood lead 16 or to the health impacts that we are concerned 17 with? 18 Monitoring data from the U.S. is 19 largely nonexistent for most counties. Most 20 air monitoring stations really belong as 21 relics in the Smithsonian Institute as opposed 22 to where they are.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 63 1 We have a hard time relating air 2 lead with any accuracy to current blood leads. 3 DR. LANNO: Okay, thanks. 4 DR. FREY: Okay, thank you. 5 Well, we're a little bit ahead of 6 schedule, and I would propose that we just 7 move forward to discussing Charge Question 1 8 and then take our break after that discussion. 9 And our lead discussants on Charge Question 1 10 are Drs. Kosnett and Davidson. 11 So Dr. Kosnett, the floor is yours.

12 DR. KOSNETT: I felt that the 13 criteria of using, or concentrating on 14 epidemiological studies that were within one 15 order of magnitude at the general population 16 blood lead range is reasonable. 17 I mean if we consider that based on 18 the latest NHANES analyses, the 95th 19 percentile is approximately 4.2 or right 20 around there micrograms per deciliter. That 21 means we're looking at literature that has 22 considered human exposures associated with

### 202-234-4433 Neal R. Gross & Co., Inc. Page 64 1 blood lead concentrations up to about 40, you 2 know, give or take a few points. 3 And I think that that's certainly 4 reasonable for a document that intends to 5 focus on environmental as opposed to 6 occupational lead exposure, and I thought that 7 that was reasonably applied and consistently 8 applied throughout. 9 The charge also asks us about the 10 HERO system. I thought it was great and I 11 enjoyed using it. I think it's a tremendously 12 helpful public resource to have that. 13 We really weren't asked to, the 14 charge question and I read it, didn't ask us 15 specifically to say what we think about the 16 framework for causal analysis and weight of 17 the evidence, right, I mean that was my 18 understanding. But I mean I thought it was 19 nice to see it in there and how it was laid 20 out and, you know, the explanations of Sir 21 Bradford Hill's criteria and how they apply. 22 I think as we get into further

### 202-234-4433 Neal R. Gross & Co., Inc. Page 65 1 point, discussion points on how those were 2 applied and how transparent the causation 3 analysis was for various endpoints, I'll have 4 more comments. But since I don't think those 5 were covered in specifically Charge 1, I can 6 be brief and end there. 7 DR. FREY: Okay, great. 8 Dr. Davidson? 9 DR. DAVIDSON: I agree with Dr. 10 Kosnett. I think that Chapter 1 had a certain 11 consistency and that the criteria of 12 considering studies within one order of 13 magnitude of the current exposure is

14 reasonable. 15 I also liked the HERO network. I 16 thought that it worked very well. And I have 17 a number of typographical suggestions and some 18 editorial suggestions. 19 One specific comment in terms of 20 making the document shorter, there is a short 21 section that deals with human exposure in 22 controlled chamber studies, and my suggestion

### 202-234-4433 Neal R. Gross & Co., Inc. Page 66 1 would be that that paragraph might not need to 2 be included since as the document points out, 3 lead exposures are not done in chamber 4 studies. Except for that I have no other

5 comments. 6 DR. FREY: Okay. Other members of 7 the panel? Dr. Hopke? 8 DR. HOPKE: Okay. I'd like to be 9 a bit of an iconoclast here. And one of the 10 questions is, why do we still need lead as a 11 criteria pollutant? 12 You know, we could ban leaded 13 avgas, take the wheel weights off of cars and 14 now we're down to primary and secondary 15 nonferrous metal smelters which could be 16 handled under Section 109 given the fact that 17 lead is a hazardous material. 18 And so I think there still needs to 19 be some, there needs to be at least some 20 rationale to me as to why we can't declare 21 victory and move on and look at potentially 22 other criteria pollutant, things that should

### 202-234-4433 Neal R. Gross & Co., Inc. Page 67 1 become criteria pollutants because they're 2 much more widespread and likely to have much 3 more of a problem. 4 Not that lead is not still a 5 problem, but there are better ways to deal 6 with it. There may be better ways to deal 7 with it than as a criteria pollutant. And, 8 you know, at least some rationale in there for 9 why this continues to be needed as a criteria 10 pollutant I think would be very helpful to all

11 of us. 12 DR. FREY: Okay, thank you. 13 Dr. von Lindern? 14 DR. von LINDERN: Well, I'll be the 15 guy from the other side. I have problems with 16 the ISA process, and maybe this is the right 17 place to bring that up. I don't know. 18 But this limitation on looking at 19 only one order of magnitude with regard to 20 exposure excludes 90 percent of the world. 21 There are high exposures going on in the rest 22 of the world, and I don't see any of that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 68 1 information ever reaching the policy decision 2 makers through the ISA process. 3 Also there's very, very little 4 exposure in this entire document. In fact, I 5 think the conclusion that it's leading to is 6 that there's really no need to redo the risk

7 assessment because there's no new data. 8 What in that ISA process then 9 information is going to get to the 10 administrator to make a policy decision if

11 there's no new work done? 12 So we have a great literature 13 review. We have a fantastic literature review 14 on health and environmental effects, but we 15 have no information on exposure and we have no 16 information on what's going on with lead in

17 the rest of the world. 18 Much of which is happening because 19 of U.S. policy. We have sent our problems 20 overseas and I don't see anything in this 21 document that informs the administrator 22 eventually of that problem.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 69 1 So I'm going to throw these arrows 2 at this agency for the next four years, and 3 I'm hoping that it hits somewhere within the 4 science and policy people because it seems to 5 be avoided in this first step. 6 DR. FREY: Yes, I guess I'll just 7 make a comment that, you know, in some sense 8 we're a bit constrained under the framework of 9 NAAQS which may or may not be amenable to 10 addressing some of the issues that you're 11 raising. 12 I think Dr. Hopke's point is 13 probably something that has to be borne in 14 mind as we go through this process, probably 15 not something that this panel can decide. 16 Maybe the panel at some junctures can make 17 recommendations as it sees fit based on 18 science. 19 But yes, Dr. Vandenberg, I think 20 you wanted to comment? 21 DR. VANDENBERG: I'd just like to 22 clarify again, one of the first slides that I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 70 1 showed had the process of the different, in 2 some sense the different pieces of the 3 process. And the exposure assessment and risk 4 evaluation if it's decided to be pursued is 5 actually in the companion document to the

6 ISAs. 7 The ISAs typically do not include 8 the consideration of what either measured or 9 projected human exposures are given the 10 current sources and distribution of sources, 11 so that's really brought into the risk and 12 exposure assessment which is what you'll be 13 discussing tomorrow. 14 So I can appreciate your concern 15 saying well, where is that? Well, that's 16 actually in the companion document that's 17 developed by our colleagues in the Office of 18 Air Quality Planning and Standards, and that's 19 partly because the monitoring system for 20 ambient air quality monitoring is organized by 21 the states with EPA support and so that's 22 where that data is obtained is evaluated.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 71 1 And then the different options for 2 policy to look at the potential benefits for, 3 or the effects on risk with different policy 4 options is actually evaluated by again the 5 risk and exposure assessment and feeding into 6 the policy assessment. 7 So there's a set of really three 8 different potential documents here that 9 together form the basis for the 10 administrator's, supporting the 11 administrator's decision. And so perhaps that 12 speaks to some of your concern, where is that 13 information? 14 DR. von LINDERN: That helps but it

15 makes me nervous. 16 DR. VANDENBERG: Hopefully you'll

17 be calm tomorrow. 18 DR. von LINDERN: I should say, I 19 was on the first CASAC in 1975, and I've been 20 on it all along. We used to see all of this 21 information developed up front.

22 So the fact that I don't see the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 72 1 exposure-relevant information that's going to 2 be required to make eventual policy decisions, 3 is that something we didn't look at 4 intentionally in this document because 5 somebody else is going to look at it later?

6 Is that the case? 7 DR. VANDENBERG: Could you repeat 8 that? That last part?

9 DR. von LINDERN: We don't see the 10 information that used to be developed in the 11 Air Quality Criteria documents with respect to 12 exposure, with respect to lead in commerce, 13 with respect to use, with respect to lifecycle 14 in the country, all of those factors that get 15 developed into developing rational policy. 16 All of which seem to be unknown and much of 17 which would be relevant to Dr. Hopke's 18 question. 19 How much lead is used in the U.S., 20 where's it going and what are the policy 21 implications that the agency will make that 22 will influence that? We don't seem to know

### 202-234-4433 Neal R. Gross & Co., Inc. Page 73 1 anything about that according to this ISA.

2 Is that because we haven't looked? 3 Is it because there is no data? Or is OAQPS 4 going to look later? 5 DR. VANDENBERG: Well, again to 6 clarify, as you look to the discussion 7 tomorrow about the risk and exposure plan, 8 what you'll see is the development of 9 information that is the companion to this, the 10 Integrated Science Assessment, again leading 11 to the policy assessment document. 12 So I don't know, we've got folks 13 and they're all shaking their heads yes, 14 that's right, over there. So I don't know if 15 anybody else wants to comment.

16 We do have our -- 17 DR. FREY: Well, I think John maybe 18 is, I understand the question. It's a 19 question about the scope of the ISA and was 20 there a decision to not, I guess, do more on 21 quantifying the sources of lead and the 22 exposures related to lead as part of the ISA.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 74 1 And if that's the case then I guess 2 I think what I'm hearing you say is the 3 implications, it's assumed that will be 4 addressed in the REA. 5 DR. VANDENBERG: And the policy

6 assessments. 7 DR. FREY: So I guess clarifying -- 8 DR. VANDENBERG: Yes, so that when 9 we develop the plan, the plan for this entire 10 set of documents and analyses that was kind of 11 what we're doing, is we're laying out the 12 pieces and the plan to that. 13 So I see Dierdre would like to 14 comment as well. If I might get Dierdre to 15 comment, Dr. Frey? 16 DR. FREY: Sure, yes. 17 DR. VANDENBERG: Dierdre, go ahead. 18 There's a microphone over there. 19 DR. MURPHY: I'm Dierdre Murphy 20 with the Office of Air Quality Planning and 21 Standards, the lead on the review for that 22 office.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 75 1 And I just wanted to say that of 2 course there is an exposure section to the ISA 3 which does include discussion of emissions and 4 the current air monitoring information. 5 So I think there is actually, my 6 sense of course is that there is an intent 7 that the ISA does tee up the information we 8 have with regard to emissions of lead in the 9 U.S. with regard to air concentrations that we 10 currently have accessible to us in the U.S. as 11 well as the literature. 12 What is in the literature in terms 13 of published studies on exposures, and the ISA 14 makes a point of saying that they're 15 considering exposures not just from air lead 16 because sometimes that's hard to tease out of 17 some of the studies, but that is described in

18 the ISA. 19 And so that information is all of 20 what we consider in terms of us in the Air 21 office in thinking about what usefulness would 22 come from doing quantitative analyses, which

### 202-234-4433 Neal R. Gross & Co., Inc. Page 76 1 is part of the discussion for tomorrow in 2 terms of potential for doing updates to 3 exposure assessments and risk assessments, and 4 then all of it of course gets considered in 5 the policy assessment. So hopefully that's

6 useful. 7 DR. FREY: Yes, I wonder if some of 8 this could be deferred to when we talk about 9 Chapter 3, because that chapter does address 10 at least nominally some of the issues of the 11 sources and the concentrations. 12 But yes, Dr. Allen? 13 DR. ALLEN: If you want, it's on 14 that topic. I'll hold it if you want me to or 15 ask it now, your choice. 16 DR. FREY: I'll defer to you 17 because I don't know what you're going to say.

18 DR. ALLEN: A lot of the 19 information is on general background 20 concentrations of lead in the air. 21 And what about if I own a house 22 that is located right at the fence line at

### 202-234-4433 Neal R. Gross & Co., Inc. Page 77 1 Teterboro Airport, God forbid, or if I own a 2 house in the Coeur d'Alene mining area? 3 What are the dust exposures? What 4 are the ambient air lead exposures to those 5 smaller populations as opposed to what we see 6 in these more global assessments? Is that 7 being looked at and considered? 8 DR. FREY: Well, it sounds like 9 that's an REA question, but I guess to the 10 extent in say Chapter 4 that deals with 11 exposure that the scientific basis for that is 12 discussed adequately or not, and it's probably 13 something we could talk about today. 14 DR. ALLEN: I think those people 15 are getting a dose. 16 DR. FREY: So, you know, Chapter 3 17 deals with the source to concentration, 18 Chapter 4 includes exposure. So maybe we can 19 come back to some of these issues at that 20 point. 21 I think was there another comment 22 from this side of the room? Did I miss

### 202-234-4433 Neal R. Gross & Co., Inc. Page 78 1 anybody? So any other discussions on Charge 2 Question 1? 3 Yes, Rich? 4 MR. POIROT: I just had a, this is 5 more of a question really where it asks to 6 comment on the HERO system. 7 And one question was whether the 8 references cited in this current ISA are the 9 only lead-related references or whether the 10 HERO system would be intended to encompass all 11 of the references from previous CDs for lead, 12 for example, and whether they were organized, 13 you know, in a consistent way. 14 MS. WALSH: So certainly some of 15 those references from previous, like the other 16 Air Quality Criteria documents, you would find 17 some of those references there, and some of 18 those may also be cited in actually this

19 document. 20 But on the lead landing page that 21 I had that screen shot of, is our attempt to 22 try to in a more systematic way organize the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 79 1 references that were, if you would, reviewed 2 for this Integrated Science Assessment, 3 because not all references reviewed were 4 actually cited in the document. 5 So this is a part of our 6 transparency that's trying to show that we did 7 look at more than what was just actually cited 8 in the document. 9 And in that landing page as opposed 10 to if you went and looked at ozone, for 11 instance, the one previously, it was not 12 organized in such a systematic way. 13 So there you can look and see by 14 effects, by disciplines, those kinds of 15 things. And we're really interested in your 16 feedback on that. And if I didn't say that 17 when I gave my little presentation, we really, 18 really want your feedback. 19 And one of the differences here for 20 CASAC, for ozone and now for lead is that you 21 actually have access to the manuscripts. So 22 if you click on that link you can actually see

### 202-234-4433 Neal R. Gross & Co., Inc. Page 80 1 the paper that we cited and look at that 2 information. 3 We provide that to this review 4 panel because we consider you in that partner 5 group as we develop and move forward with our

6 ISA. 7 Clearly we can't provide that to 8 the public for copyright issues. That's the 9 difference. That's one of the primary 10 differences between HERONet and HERO. 11 But you should be able to click on 12 that link and whereas in the screen shot it 13 had the number, you would just click on the 14 citation. We tried to get rid of that number 15 for lead. Again that was a new thing to lead 16 this time. 17 MR. POIROT: Yes, I mean it seems 18 like it's going to be a very useful system, 19 and some of your summary slides that you 20 showed earlier were kind of the first time I 21 had any idea that, you know, that was the 22 scope and the depth and breadth.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 81 1 But anyway the idea though of 2 providing links to all the citations and 3 previous documents I think is going to become, 4 is important and becomes increasingly 5 important especially since these ISAs are 6 supposed to just tell what's new. 7 And if we're trying to briefly 8 summarize what was the state of the scientific 9 understanding prior to the new ISA simply by 10 reflecting back to the previous one, if the 11 previous one was only what was new, it's kind 12 of a spiral that goes in the wrong direction. 13 So building in all of the 14 references upon which the basic level of 15 understanding of lead in the atmosphere and 16 its associated effects would I think be a good 17 idea. 18 MS. WALSH: That's a great comment. 19 Thank you. 20 DR. FREY: Yes, Dr. Allen? 21 DR. ALLEN: One thing that was very 22 hard in the ISA was the fact that it jumped in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 82 1 at 2006 with not even a paragraph at the 2 beginning of the section to tell me what you 3 consider the important information to be prior 4 to that. In other words, you know, in the 5 previous documents. 6 And what really would have been 7 exceedingly helpful to me would be to know or 8 to have a summary of where the position was 9 and why and therefore how this new information 10 really is new and useful to me. 11 You know, it's a great literature 12 review overall, but it's so highly restricted 13 in it's timescope that I would have to take 14 the previous documents, cut them apart and 15 paste it all together to have an integrated 16 view. 17 DR. FREY: Okay, other comments on 18 Charge Question 1? 19 Dr. Kosnett, would you be able to 20 take a stab at summarizing what you've heard 21 as the consensus on this charge, or the key 22 points?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 83 1 DR. KOSNETT: Yes, I think there

2 were a lot of comments that weren't based on 3 the charge though. 4 DR. FREY: Sure, yes, and I think 5 that's true. So I think you can edit the 6 discussion to what was responding to the 7 Charge Question. 8 DR. KOSNETT: Well, I think most 9 people were happy with, I think there's 10 consensus. Most people were happy with the 11 discussion of the articles that were within 12 the order of magnitude. 13 I respect Ian's comments about the 14 value of looking at those larger ones. But 15 Ian, maybe help me. Do you think those higher 16 studies will assist EPA in assessing a 17 potential revision of the National Ambient Air 18 Quality Standard? 19 DR. von LINDERN: I see my problem 20 is with the process, because I see that this 21 process confines the information that's going 22 to move forward as opposed to the former

### 202-234-4433 Neal R. Gross & Co., Inc. Page 84 1 documents, which were inclusive of almost 2 everything that was known about lead out

3 there. 4 Now it's down to, what's the new 5 stuff that was known about lead in the last 6 two years that might change our particular 7 policy decision that we made last time? I 8 have problems with that. 9 I think a broader view should be 10 moving through the agency that the old 11 criteria documents used to reflect. 12 And confining it to only U.S. 13 exposures only based on new information that's 14 coming from the peer review literature pretty 15 much predetermines that we're not going to do 16 anything about lead in the next two years 17 because there's not new information out there 18 to redo these analyses. 19 DR. KOSNETT: So you're saying as 20 a valuable scientific document that is useful 21 worldwide it's good to include studies that -- 22 DR. von LINDERN: Certainly.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 85 1 DR. KOSNETT: But you're not 2 disagreeing that in terms of the way the 3 policy is focused on the question of the 4 ambient air quality standards in the United 5 States that those studies are helpful?

6 DR. von LINDERN: I can see that 7 this process moves forward to help EPA answer 8 this particular question. This process does 9 not replace the information that was formerly 10 provided in the old process to the agency to 11 conduct policy. And I don't know if that's 12 happening anywhere else in the agency or if 13 it's just being forgotten. 14 DR. FREY: Yes, I think though the 15 issues you raised are, in fact, constraints on 16 this process. 17 That this is a process leading 18 toward a, informing the administrator on a 19 decision whether to retain or revise the 20 existing NAAQS, and if revising it inform 21 based on scientific information so that she 22 could take that into account in making a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 86 1 decision to revise. 2 So the context is not a broader one 3 as you point out. I think that is just simply 4 a constraint of what our mandate is. Not sure 5 what else to say. 6 I think Vanessa would like to add 7 something. 8 DR. VU: Well, previously the CASAC 9 has discussed about the scope and size of the 10 AQCD, the ambient criteria document. 11 And CASAC has engaged with the 12 agency in revising the process to recommend 13 the agency to develop an ISA, and Integrated 14 Science Assessment, shorter document, more 15 synthesis of what we have new. 16 Now I understand, I hear a lot of 17 comments about what's in the various chapters 18 on exposure and emission, et cetera. 19 As I think Dr. Frey has discussed, 20 you know, you can comments of the adequacy of 21 these chapters with intent of covering what is 22 the agency's plan to cover to inform the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 87 1 decisions with regard to ambient air quality 2 monitoring, standards. Ambient air quality 3 standards, sorry. Excuse me. 4 So the CASAC has agreed and support 5 the agency this process of develop ISA, the 6 risk and exposure assessment followed by the 7 policy assessment which used to be a staff 8 paper. 9 So we went through all that and, 10 you know, just when we started this new 11 process with PM and then now with ozone, now 12 with lead, we all agreed to this process. 13 So any scientific question you have 14 about the scope of the document and the 15 content is welcome, but I just want to make 16 sure that you all that process have been 17 engaged with CASAC and CASAC is pretty much is 18 support this process. 19 So I'm just going to let John, you 20 know, clarify anything I didn't say 21 appropriately. 22 DR. VANDENBERG: No, I don't have

### 202-234-4433 Neal R. Gross & Co., Inc. Page 88 1 anything to add. I think that's the point, is 2 that part of this planning process is to lay 3 out the pieces and actually to add more focus 4 and that's partly the EPA's desire. 5 But also CASAC's comments in the6 past have been to focus on the most policy7 relevant information, with that policy being 8 the information that'll support the decision 9 to retain or revise the standard. 10 So I certainly respect the concern 11 that the former Air Quality Criteria documents 12 were more, perhaps viewed as more complete or 13 included other information, but that was also 14 viewed as somewhat of an impediment to the 15 overall goals of trying to be able to be a 16 focused timely manner. 17 DR. FREY: Yes, Dr. Wasserman? 18 DR. WASSERMAN: I just wonder 19 whether it perhaps wouldn't be helpful in this 20 document then to make that explicit and to 21 say, you know, there is a whole lot of 22 information about higher levels of exposure

### 202-234-4433 Neal R. Gross & Co., Inc. Page 89 1 that may be important for the science of 2 understanding this, but that's really not what 3 -- see, I think there's a, we have a misnomer 4 here for calling this an Integrated Science

5 Assessment. 6 It does seem as though it should be 7 the last word of everything you'd ever want to 8 know about lead. And if it can't be, and I 9 reflect that it, that's really maybe too 10 broad, then at least to parse it down and say, 11 we're going to focus here, and there is a

12 whole lot of other stuff we can't look at

13 there. 14 DR. FREY: Okay. Well, yes, that 15 may be a fairly easy thing for EPA to just 16 give a little context. 17 You know, I'm not, I'm an engineer 18 so I'm not a health effects expert and I'm 19 just struggling with, you know, if there was 20 a recommendation from this panel to EPA to 21 look at studies at much higher exposure 22 levels, would that inform judgments about

### 202-234-4433 Neal R. Gross & Co., Inc. Page 90 1 things like mode of action or other factors 2 that aren't informed by narrowing the focus to 3 within order of magnitude? 4 I mean if there was some scientific 5 rationale that would be helpful elsewhere in 6 the document, you know, maybe that would be a 7 way of coaching that particular recommendation 8 if that's a recommendation the panel wants to

9 make. 10 But I think what I heard is, you 11 know, that at least a few discussants were 12 pretty happy with the roughly order of 13 magnitude range of the study selection 14 criteria and that the main motivation for 15 looking at higher exposure levels was that 16 that had some relevance to situations perhaps 17 in other countries but may not be that useful 18 to the standard process here in the United 19 States as, you know, given where we are now. 20 And if that's the case then I think 21 that's just information. In context probably 22 not that critical to the ISA. And I'm not the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 91 1 one who can make that judgment because I'm not 2 a health effects expert. 3 I guess you want to address this 4 point? 5 DR. ROSS: Can I follow up on that?

6 DR. FREY: Yes.

7 DR. ROSS: One of the bases that 8 we've used for that sort of bounding for the 9 higher concentration studies has been and is 10 for other pollutants to is the -- I'm Mary 11 Ross. I'm the first level supervisor for this 12 group, sorry. Has been the concept that at 13 the higher concentrations you may have a 14 different mode of action. They may not be 15 exactly on the same path. 16 So I would actually, that's 17 something we're seeking advice on from the 18 health experts is, does it make sense to focus 19 on the concentrations at tox studies that are 20 relevant to the epi study exposure levels, or 21 do the higher concentration studies inform 22 what's happening at lower concentrations too?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 92 1 So that's a question we'd be 2 interested in your thoughts on.

3 DR. FREY: Dr. Goodrum? 4 DR. GOODRUM: Yes, I think Ian's 5 suggestion goes beyond, you know, the 6 consideration of studies that evaluated high 7 level exposure from the point of view of high

8 blood leads. 9 I think the recommendation is more 10 of a can we continue the knowledge base that 11 we have through our successive documents in a 12 way that allows us to address more 13 specifically some of the questions that we 14 have currently? I think we all recognize that 15 teasing out air as a contributor to multiple 16 exposure pathway risk assessment is pretty 17 challenging. 18 I think understanding source 19 contributions and maintaining some synopsis of 20 what those data are and how those change over 21 time can be helpful. I would find that 22 helpful.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 93 1 And I think one thing that I'm 2 hearing is that this document is large already 3 and we only have limited time and resources to 4 continue to synthesize information. I guess 5 I would just encourage consideration of moving 6 further towards, you know, electronic 7 repositories. 8 And I'll just give the ITRC as one 9 example, the Interstate Technical Regulatory 10 Council, which develops technical regulatory 11 guidance documents. And they are moving 12 towards electronic postings of those documents 13 with hyperlinks between sections, moving away 14 from paper documents. 15 So I think, you know, especially 16 with the HERO platform and EPA's move to 17 provide more information electronically, that 18 I think we have an opportunity to listen 19 pretty closely with Ian's suggestion as to 20 carry forward some of the information from 21 previous assessments. I'd like to just make 22 that suggestion.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 94 1 DR. FREY: Okay, let me maybe 2 reflect a little bit on what we've discussed. 3 I think by and large that my impression that 4 the panel is more or less happy with the one 5 order of magnitude selection criteria. 6 However, I think we can revisit 7 this through the day. I think as we go 8 through the other charge questions to the 9 extent that issues come up where it would make 10 sense to look at studies beyond that criteria 11 that we could modify, you know, this position 12 on Charge Question 1. 13 It seems like informing that 14 further would really be contingent on what 15 we're going to say for some of the other 16 charge questions. So I guess my thought right 17 now is we may have said about all we can say 18 right now on Charge Question 1. 19 We can revisit it toward the end of 20 the day if it seems like we've learned 21 something from the discussion that would bring 22 us beyond what seems like, you know, the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 95 1 general comfort level with the plus or minus 2 order of magnitude. 3 Seems like there were positive

4 comments on HERO. There were even comments 5 toward going to more computerized hyperlink 6 documents rather than paper documents. 7 And anything else significant we 8 might want to say on Charge Question 1 at this 9 point? 10 If not, I would propose we go ahead

11 and take our break now. And we were 12 originally going to have a 15-minute break so 13 we'll go ahead and do that. That means we 14 come back at 10:50, and we will then start on 15 Charge Question 3. 16 (Whereupon, the foregoing matter

17 went off the record at 10:37 a.m. 18 and resumed at 10:51 a.m.) 19 DR. FREY: We're going to 20 reconvene. We're now 15 seconds behind

21 schedule. 22 All right. Our next order of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 96 1 business is discussion of Charge Question 3, 2 and our discussants include George Allen, Rich 3 Poirot, Cliff Davidson, Phil Hopke and Chris 4 Johnson, and we'll begin with George Allen. 5 MR. ALLEN: Thanks, Chris. Some 6 general comments that the document is well 7 written, it's certainly comprehensive and very 8 detailed. 9 But as was recently discussed with 10 the ozone ISA, it may be too comprehensive in 11 some areas, and at a thousand some-odd pages 12 might benefit from some edits to reduce the 13 overall length and improve the focus and 14 specifically on Chapter 3. These comments are 15 addressed in that context and may also apply 16 elsewhere, I don't know. 17 DR. FREY: George, could you maybe 18 move a little closer to the mic? 19 MR. ALLEN: Well, okay. I can be 20 loud, although I seem to have a -- oh, okay. 21 Let's see, where was I? It's tough 22 to say where to cut. That's a question we'll

### 202-234-4433 Neal R. Gross & Co., Inc. Page 97 1 probably revisit. But I think it's probably, 2 to make it a little bit better read, the 3 length right now is excessive. 4 Moving on from that topic, those of 5 you who know me and what I do probably know 6 what's coming next. A notable omission in 7 Section 3.4.1 is, there's no discussion of 8 current work currently being done by EPA at 9 ORD, but a different part of ORD, to develop 10 a better, not a better HiVol, a better big 11 part of an uber-coarse sampler like greater 12 than PM10 but something that's more robust 13 than the HiVol. 14 The section does discuss the 15 limitations of the current FRM HiVol sampler, 16 which dates back to the '40s. It's getting 17 quite old with essentially no changes. 18 But the section doesn't suggest 19 anything better other than PM10, which that 20 discussion occurred in the last round of the 21 lead NAAQS review, and we stayed with the 22 HiVol as the FRM because there wasn't anything

### 202-234-4433 Neal R. Gross & Co., Inc. Page 98 1 waiting in the wings to take its place. 2 I hope we don't go down that same 3 path this time that when we get to that point 4 that ORD will have characterized some thing, 5 and there is some thing in mind that would 6 with some discussion obviously hopefully be 7 acceptable to this panel as a replacement for 8 the HiVol as the lead FRM sampler. 9 DR. RICHMOND-BRYANT: I'm sorry, I 10 just want to make a quick comment just to 11 maintain the context of the ISA. 12 I agree that all of the things that 13 you're mentioning are very important 14 developments in the future, but we're somewhat 15 limited in our scope to review what is in the 16 peer review literature, what is in the public 17 domain of the things that are available and 18 what their limitations as well as benefits

19 are. 20 So while those are important 21 developments, it was just somewhat outside of 22 the scope of the work that we present for the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 99 1 ISA. So just to kind of keep that in context 2 that we're limited to review what's in the 3 peer review literature. Thank you. 4 MR. ALLEN: Yes, there is limited 5 literature on this issue about using other 6 inlets that exist that could be referenced. 7 I could make a point or two that --

8 DR. RICHMOND-BRYANT: That would be 9 terrific. 10 MR. ALLEN: -- actually I think I 11 did in our previous meeting a few months ago. 12 All right, I won't go on to that, 13 but at what point in the process would that be 14 appropriate to raise? If not in the ISA, 15 would it be in the policy assessment document

16 or -- 17 DR. RICHMOND-BRYANT: My colleagues 18 in OAQPS may speak more succinctly to that, 19 but there is a separate monitoring of 20 implementation process that goes on. So that 21 might be a more appropriate venue. 22 MR. ALLEN: Implementation not in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 100 1 the context of post-NAAQS but in the NAAQS 2 review process? 3 DR. RICHMOND-BRYANT: I'm sorry. 4 Could you repeat that? 5 MR. ALLEN: Implementation I 6 usually think of as after the NAAQS has been 7 issued, but are you talking that 8 implementation or some other implementation 9 that's within the NAAQS process? 10 DR. RICHMOND-BRYANT: It's outside 11 of the ISA review. Later on in the process 12 there might be separate deliberations over how 13 the monitoring to show compliance with the 14 NAAQS is implemented and that's just outside

15 of what we do for the ISA. 16 DR. FREY: Yes, I guess I'd like to 17 just bring us back to the panel discussion. 18 And I think questions about the 19 scientific merit of high volume sampling 20 versus scientific merit of others seem 21 appropriate, but I guess I'd like to go ahead 22 and continue with Mr. Allen's comments.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 101 1 I think the question of how to 2 interpret that for revision of the ISA to the 3 second draft is something that, you know, you 4 can consider in receiving the comments, but I 5 think this is an issue that's come up time and 6 time again. 7 And, you know, the panel has some 8 expertise I think to provide some information 9 that could expand the literature search, maybe 10 the scientific basis for it in the context of

11 the ISA. 12 But this also would translate that 13 into, well, it certainly would have 14 implications for I think the policy assessment 15 and something that the panel probably would 16 need feedback from EPA as we go forward on, 17 you know, what if anything the agency can do. 18 And I think we've seen this with 19 other NAAQS reviews where there's questions 20 about the monitoring network and how that ties 21 into evolution of the monitoring network. 22 So I think rather than having a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 102 1 meta-level discussion about whether or not to 2 talk about it, let's just go ahead and hear 3 the comment and then we'll deal with it as 4 appropriate. 5 MR. ALLEN: Okay. You know, my 6 biggest concern is at some point during this 7 process, not after it because the FRM is part 8 of the NAAQS, when they issue the NAAQS they 9 say, this is the method, I want to make sure 10 that this does get addressed. You know, 11 that'll come up later in the comments. 12 But moving on from that, another 13 area of concern that isn't really addressed by 14 the ISA is discussion of lead in both wildfire 15 and residential space heating related wood

16 smoke. 17 There certainly is lead in wood 18 smoke just as there's sulphate and mercury. 19 And we have valley towns where wood smoke 20 concentrations really can be quite high 21 periodically during the winter. This is 22 probably their primary air exposure pathway

### 202-234-4433 Neal R. Gross & Co., Inc. Page 103 1 for new lead. 2 On Page 3-102, it does note that 3 fine lead is fairly soluble. I don't know to 4 what extent that's true for wood smoke lead, 5 but that's why you'd expect it in general to 6 be present in the wood in uptake by the tree 7 or possibly through the leaves. 8 A few specific comments, Section 3- 9 2, Pages 14, Lines 14, 16, about the 2008 NEI 10 Lead Inventory Reports, general aviation 11 aircraft is about half of all lead emissions. 12 But the question here I think is 13 the question, how much of that is relative to 14 human exposure? And it's probably a lot less 15 since most of these emissions are at altitude 16 and their in the fine mode and they may 17 deposit as wet deposition mercury or they may 18 deposit outside the U.S. 19 So I'd like to see that comment 20 refined, because as it stands right now it's 21 to me a somewhat misleading or unclear. It's 22 a stunning number and it's technically

### 202-234-4433 Neal R. Gross & Co., Inc. Page 104 1 probably true, but I don't think it reflects 2 the relevant exposure, human exposure. It's 3 certainly not air pathways. 4 I do, as a footnote, fully support 5 phase out of lead in avgas, but I'm not 6 convinced that avgas lead is a significant 7 human exposure at least in the context of the 8 current NAAQS or this NAAQS review. 9 Of Section 3.4, Lines 8 and 15 and 10 16, where it talks about the Herculaneum 11 primary lead smelter in Missouri which is the 12 largest single point lead source in the 13 country, it may or may not be worth noting and 14 it may or may not be new information to EPA or 15 this part of EPA I should say that that source 16 is closing by the end of 2013. 17 There is a consent order and it's 18 driven primarily by SO2 but also by lead, and 19 that's sooner than the binding 2016 date. 20 They went ahead and decided, we've had enough. 21 And I want to stress here that this 22 closing would really present an incredibly

### 202-234-4433 Neal R. Gross & Co., Inc. Page 105 1 rare opportunity to study the changes in soil 2 lead as well as the effects potentially on 3 vegetation. 4 Over time you're going to turn that 5 switch and that source is going to go off. 6 And there's a lot of uncertainty as to what 7 happens to lead in the soil that's discussed 8 in this chapter. A lot of pages are devoted

9 to that. 10 So this is a rare opportunity to 11 learn more, although it certainly cites 12 specific and soil varies widely from place to 13 place, but I don't think you'll ever have a 14 chance like this to do a longer term study 15 after you throw that switch. 16 So it's not really an 17 accountability study, but it certainly would 18 be a study of opportunity. And I would 19 encourage EPA, not necessarily ORD but EPA as 20 a whole, to develop funding for an extramural 21 study or perhaps studies maybe through the 22 STAR program, and to start before the smelter

### 202-234-4433 Neal R. Gross & Co., Inc. Page 106 1 shuts down for a number of reasons. 2 Because there will be clean-up 3 efforts and so on and so forth but if you get 4 in there after the fact -- you really want to 5 start, people, because this is a major 6 opportunity to really advance our knowledge of 7 lead in the soil and what happens to it. 8 Its fate, essentially, how long 9 does it persist? And that question comes up 10 later in the REA as one of the uncertainties.

11 Some other near road sources. I 12 don't think it's noted in the ISA what that 13 lead wheel weights have been banned in seven 14 states or more. And my understanding, and I 15 may be wrong on this, but EPA is planning an 16 NPRM next year in 2012 to ban them on a 17 national scale. 18 I would need to confirm that, but 19 that was what I got from poking around. And 20 that's probably worth mentioning, because 21 certainly they're one of the largest sources 22 of near roadway lead currently out there. And

### 202-234-4433 Neal R. Gross & Co., Inc. Page 107 1 once they're banned, their use will drop very 2 rapidly and again things, that's a very big 3 change. 4 Also especially in the post-lead 5 wheel weight era, which is potentially coming 6 soon, I found very little quantitative 7 information about lead in tires. It is there, 8 but I couldn't find any clear literature that 9 said, you know, so many -- it's not large, but 10 there's a lot of tire dust. 11 (Off microphone discussion) 12 MR. ALLEN: Yes, but it would be, 13 obviously be in the coarse or uber-coarse mode 14 but, and I'm not talking about bologna skins 15 here, I'm talking about tire particles that 16 get re-enchained and blown off to the side of

17 the road. 18 So in the absence of lead wheel 19 weights that might be, even though it's small 20 there's a massive tonnage of tire wear on the 21 road, so it might be the next important thing 22 as you drill down and get rid of the more

### 202-234-4433 Neal R. Gross & Co., Inc. Page 108 1 obvious solid chunks of lead on the roadway. 2 This comes up also in, that was in 3 3.2.5. It also comes up again or perhaps 4 should come up again in Page 3-69, Lines 8 to 5 14. So that's a topic there. 6 I believe those are the major 7 points that I want to make, and at this point 8 pass it back to Chris. Thank you. 9 DR. FREY: Okay. Well, thank you, 10 George. Rich? 11 MR. POIROT: Thanks. I agree with 12 nearly all the points George raised. The 13 first part of the charge question had to do 14 with, to what extent are the atmospheric 15 science and air quality analyses presented in 16 Chapter 3 clearly conveyed and appropriately 17 characterized? 18 And this is sort of a very general 19 commentary on the process, but I kind of 20 wanted to follow up on something that Herb 21 Allen mentioned earlier in the context I think 22 of the Chapter 1.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 109 1 It's very difficult I think to just 2 tell the story about what's new since the last 3 review cycle. It's impossible really without 4 first stating what has been the current state 5 of the scientific understanding up to this 6 point.

7 And I know and Vanessa's talked 8 about how well we've decided that we should 9 focus on what's new, but I think it's really 10 more a matter of degree.

11 It wouldn't take that much to 12 provide a clear summary statement in each 13 section. This is the current state of the 14 scientific understanding as has been 15 identified in previous review cycles. 16 A summarization, and then talk 17 about what's new, and that gives you a better 18 way to put those new papers in context. Are 19 they really relevant? Do they change the way 20 we're thinking about anything? 21 So I think to me that was 22 especially notable in parts of Chapter 3 where

### 202-234-4433 Neal R. Gross & Co., Inc. Page 110 1 the authors stuck in some cases very strictly 2 to the assignment of just tell what's new 3 almost to a fault where, you know, most of 4 what we know is actually what's old and what 5 we knew before five years ago. 6 And this is going to become more 7 important as these ISAs cycle through more 8 rapidly. If we define the state of the 9 previous understanding as what was stated in 10 the previous ISA, and if that itself is only 11 a five-year update then we're going to be in

12 trouble. 13 So anyway that was just something 14 that I think in certain sections of the 15 chapter, jumped out at me, and I'm not a fan 16 of the only what's new approach. 17 The second part of the charge 18 question related to the information regarding 19 lead source characteristics, fate and 20 transport of lead, lead monitoring, spatial, 21 temporal patterns of lead concentrations in 22 the air and non-air media, are they accurate,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 111 1 complete and relevant to the review of the 2 NAAQS. 3 I agree with George that this was 4 a very thorough discussion within the 5 constraints of, you know, emphasizing what's 6 new. And so I thought that was all rather

7 well done. 8 There to me are some lingering 9 issues with emissions inventory. During the 10 last lead review cycle, the inventory changed 11 during the course of that review process such12 that the largest source categories flip13 flopped back and forth. 14 So at any rate, there seemed to be 15 some inconsistencies particularly in the, what 16 fraction of the total is emitted by aviation 17 fuel. From the last review was apparently 18 less than ten percent of the total, to now 19 it's half the total. 20 Well, is that because everything 21 else has been reduced so substantially within 22 that recent, that five-year period? Or is it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 112 1 because of just differences in the inventory 2 methodologies, which I suspect probably some 3 of the latter was contributing. 4 And just to make that clear would 5 be useful rather than simply presenting the 6 numbers from the previous assessment, in this 7 one and showing how they differ. 8 One of the things that I think is 9 especially difficult to do in many cases is to 10 really relate the concentrations of lead in 11 all these different and other environmental 12 media to concentrations of lead in the ambient 13 air. 14 And I don't think that's the fault 15 of the reviewer, of the authors. I think 16 largely the literature often doesn't really 17 make those connections in a way that we can 18 say yes, the concentrations of lead in soil 19 are expected to change with this slope as a 20 function of changes of lead concentrations in 21 the air. So that's an inherently weak point, 22 but I think you've done about as well as you

### 202-234-4433 Neal R. Gross & Co., Inc. Page 113 1 could have. 2 Let's see, I guess my one major 3 point that I wanted to raise has to do with 4 some of the information mostly presented in 5 the appendix to the chapter, which generally 6 was quite helpful and very detailed, showing 7 the difference of lead concentrations and8 different particle size measurements from co9 located measurements of lead in TSP, PM10 and

10 PM2.5. 11 And one thing I wanted to comment 12 there on is that in the previous lead review 13 cycle a similar kind of a comparison was made 14 especially between lead in PM10 and TSP, in a 15 memo by Mark Schmidt and Kevin Cavender, which 16 included many of the same comparative sites 17 and datasets that were finished then and 18 haven't been expanded now as have been 19 included in the current analysis.

20 And some of the answers were 21 different in the current appendix than they 22 were in that previous memo. It just kind of,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 114 1 I don't know why I even thought to check that. 2 It's just that some of the numbers surprised 3 me and then looking back I saw that they were 4 different. 5 Part of that difference I think is 6 due to you used a different correlation metric 7 this time around, is Spearman's rho I think, 8 whereas they had used an r-squared. 9 But I guess I expected, maybe we've 10 got good statisticians in the room, I expected 11 the r-squared to be a more stringent number.

12 PARTICIPANT: We won't comment on

13 that.

14 MR. POIROT: And then the other one 15 was the average ratio of the lead in the 16 different size samples, PM10 to TSP lead. 17 That metric appears to be the same in the two 18 analyses, but the answers are different in 19 many cases. 20 So just raises a something to 21 double check. I'm sure there's an explanation 22 that I'd be curious to know, you know, maybe

### 202-234-4433 Neal R. Gross & Co., Inc. Page 115 1 the method was a little different or something 2 along those lines. 3 But here's the main point and then 4 I'll shut up. To me there was a very 5 disturbing member of totally illogical results 6 in this comparison. Almost 20 percent of the 7 sites comparing PM10 lead to TSP lead found

8 more PM10 lead than TSP lead. 9 And somewhat more disturbing, 10 almost 20 percent of the sites comparing PM2.5

11 lead to TSP lead found more PM2.5 lead than 12 TSP lead. And almost 40 percent of the sites 13 comparing 2.5 lead to 10 lead found more 2.5

14 lead than 10 lead. 15 Rather than illuminating our 16 knowledge of what's the size distribution of 17 lead, this is telling me we've got some really 18 bad quality lead measurement data out there. 19 And it really kind of surprised me. I thought 20 we knew how to do this better, but I guess we

21 don't. 22 PARTICIPANT: But we do. They just

### 202-234-4433 Neal R. Gross & Co., Inc. Page 116 1 didn't do it right. 2 MR. POIROT: And Phil will add to 3 this in a minute. So it made me want to ask 4 at least for some additional information when 5 you make these comparisons of the different 6 sampling and analytical and extraction methods 7 that are typically used for these different 8 programs. 9 I know there's a wide variety out 10 there but, for example, most of the PM2.5 lead 11 is going to probably be XRF data. 12 (Off microphone discussion) 13 MR. POIROT: Oh, okay. And so 14 those methods would be useful along with, now 15 I'm wanting to see a lot more of the accuracy 16 and precision data from the different 17 measurements. I think that would be helpful. 18 So that was the one major thing 19 that jumped out at me that I thought deserved 20 comment. All the rest of my comments are all 21 fairly minor points. 22 DR. FREY: Okay. Thank you, Rich.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 117 1 John, you want to clarify? 2 DR. VANDENBERG: Yes, just a point 3 on that last point that you made. I think 4 it's a very good point about the 5 identification of the methods that we're 6 using, and that may help clarify that. 7 Jenn, did you have a comment? 8 DR. RICHMOND-BRYANT: I just wanted 9 to say after that, because I saw Mr. Curtis'

10 comments as well as a few of the other 11 panelists, and that issue came up in 12 particular a couple of times. 13 So a couple things we'll be doing 14 are, as you point out, to clarify the accuracy 15 and precision of the data and where possible 16 to clarify the methodology by which it was 17 obtained. 18 But we also dug back into the data 19 and found that several of those sites where 20 there were higher ratios had data below the 21 method detection limit. 22 And so I think we're going to be

### 202-234-4433 Neal R. Gross & Co., Inc. Page 118 1 probably casting a different filter before we 2 present those data so that we're a little bit 3 more targeted in what we present next time. 4 So we will certainly state clearly how we 5 choose to present what we do. 6 But we'll also be a lot more careful in the 7 next review of presenting data that are below 8 the method detection limit, because you're in 9 the white noise range where some of those 10 ratios were presented and were very high. 11 Thank you. 12 DR. FREY: Okay, next is Dr. Cliff 13 Davidson. 14 DR. DAVIDSON: Thanks, Chris. 15 So I had a few comments that were along the 16 lines of what we just heard from George Allen 17 and Rich Poirot and I won't, therefore, go in

18 to those. 19 Let me mention a couple of other 20 things. One is, there is a section on 21 deposited lead near roadways. 22 This is at 3.2.2.6, and there's a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 119 1 discussion there of the only study in the 2 literature that tried to quantify how much 3 airborne lead is from resuspended soil that 4 was contaminated from all those decades of 5 leaded gasoline use. 6 And the paper used a mass balance 7 method and came up with the conclusion that 8 the lion's share of the airborne lead is -- 9 this is in Los Angeles and this was back in I 10 think 2001 is when the data were used, 2001,

11 2002. 12 The lion's share of that airborne 13 lead is from resuspended soil, and the number 14 given was around 90 percent but that was just 15 a rough estimate. 16 The ISA basically says that this 17 number was not valid and cites -- yes, that's 18 actually the paragraph I'm talking about. 19 Says that that number, 90 percent, was not 20 valid and therefore will not be used in the

21 current assessment. 22 And I just wanted to make the point

### 202-234-4433 Neal R. Gross & Co., Inc. Page 120 1 that that's only a rough estimate, and rather 2 than making a statement that the paper isn't 3 valid, it might be better just to say this is 4 a rough estimate and the results suggest that 5 resuspended lead near the roadside could be 6 very important. 7 I think that would be a better way 8 to handle it because, unfortunately, this is 9 the only study in the literature that attempts 10 to do this. 11 I'll mention just one other point, 12 is that throughout the chapter there are 13 several places where dry deposition is viewed 14 as kind of an ultimate sink for lead. 15 That once the lead dry deposits 16 it's essentially out of the atmosphere and 17 therefore it, you know, it may get on food 18 that people eat or perhaps children will 19 ingest it because of hand to mouth activities

20 and so forth. 21 But essentially that's viewed as a 22 sink where exposure can happen a different

### 202-234-4433 Neal R. Gross & Co., Inc. Page 121 1 way. And I think the truth of the matter is 2 that a lot of the lead that dry deposits 3 subsequently gets resuspended and then it 4 deposits again and then it gets resuspended 5 again. 6 And so I think rather than viewing 7 lead depositing as an ultimate sink, I think 8 it might be better to view that lead as moving 9 through a complex system in different forms. 10 And therefore it could be subject 11 to causing exposure from the air subsequently 12 or from being deposited on the surface. 13 So okay, those are my only 14 comments. There are a few more issues that 15 are in my written report but they're fairly 16 minor. 17 DR. FREY: Okay, thank you, Cliff. 18 Phil Hopke? 19 DR. HOPKE: Okay, several things. 20 I'd like to echo George's comment that this 21 looks much more like a criteria document than

22 ISA.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 122 1 I think with some judicious use of 2 appendices one could substantially reduce the 3 volume of Chapter 3 and make it much more 4 readable in terms of really providing an 5 integrated synthesis of the information rather 6 than again as comprehensive a review as -- you 7 know, again it harkened me back to the good 8 old days of criteria documents and I had hoped 9 we were past that. 10 Second, you comment about long 11 range transport of lead bearing particles, but 12 there's no effort to actually analyze the data 13 that are available. 14 There are data available and there 15 are reports particularly Liu et al., in JGR in 16 2003 or '04, I give the reference, in which, 17 you know, there is an effort to extract an 18 Asian dust signature from Lassen volcano and 19 Crater Lake National Parks. 20 And there's no indication that that 21 signature is enriched in lead. It was 22 certainly enriched in sulphur, but not

### 202-234-4433 Neal R. Gross & Co., Inc. Page 123 1 enriched in lead. 2 And so I think we need to be 3 careful, and I'll raise the three most dreaded 4 words in this whole discussion, Policy 5 Relevant Background. 6 If we're going to start getting 7 into Policy Relevant Background, which is 8 really what you're laying the basis for here, 9 you really need to have somebody take a look 10 at those improved sites along the mountain 11 ranges in the West and really see whether 12 there's a basis for saying that there is a 13 significant increment of additional lead 14 coming with respect to the Asian dust 15 transport that's coming from the Pacific Rim. 16 I'm having problems with my 17 computer so I can't actually read my comments, 18 but I was rather appalled to see the use of 19 the Spearman ranked correlation. 20 I don't see how that informs 21 anything in this case and, in fact, simply 22 having things line up in the same order really

### 202-234-4433 Neal R. Gross & Co., Inc. Page 124 1 doesn't tell us a lot about this kind of data. 2 And so Pearson correlation is 3 really the approach you should be using, and 4 if all you're trying to do is jack up the 5 apparent correlation coefficients by using 6 Spearman, that's really providing a false 7 representation of what's going on. 8 It was my impression that much of 9 that PM lead data was XRF, and I'm still very

10 concerned about the fact that PM10 and TSP 11 data are probably not being particle size

12 corrected. 13 And in both cases, and particularly 14 with TSP, you have attenuation by the 15 collected particulate matter that's going to 16 lead to substantial underestimates of the lead 17 in the more coarse fractions, because the 18 penetrability of the induced x-ray is small 19 compared to the range in the collected 20 particulate matter. 21 And so I think again there needs to 22 be very careful scrutiny and judicious choice

### 202-234-4433 Neal R. Gross & Co., Inc. Page 125 1 of those data that are analyzed by methods 2 other than XRF in order to start informing us 3 appropriately of the PM10 to 2.5, TSP to 2.5 4 ratios. 5 I mean we really need to decide 6 whether we really need TSP or not. Even with 7 the new TSP heads that are available out 8 there, they're not well characterized. 9 They have not been wind tunnel 10 tested particularly. They are at least wind 11 speed or wind direction independent, but I'm 12 not sure that they're wind speed independent. 13 That's, be very unlikely given the design. 14 And there still is going to be an 15 effective cutoff just as there is an effective

16 cutoff for TSP. 17 So, you know, one of the key 18 questions and something that I think you ought 19 to at least explicitly address, is the 20 question of the industrial hygiene definition 21 of inhalable particulate matter. 22 If what we're really interested in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 126 1 is accumulation of lead in the nasal cavity 2 and then uptake into the GI tract, it's 3 inhalable particles and that inhalable 4 particle curve that maybe we should be trying 5 to mimic in the sampler.

6 And there needs to be at least some 7 discussion somewhere in this document of, you 8 know, inhalable versus respirable versus et 9 cetera, because I think we're not really 10 adequately addressing the question of why we 11 want to look at TSP versus PM10 and get at 12 where our appropriate ultimate exposure metric 13 needs to be when we come up with an indicator 14 for a NAAQS. 15 DR. FREY: Okay. Thank you, Phil. 16 Dr. Chris Johnson? 17 DR. JOHNSON: Okay, thank you. I 18 thought the chapter was generally pretty well 19 written. I have some similar concerns about 20 its length. But a couple general comments. 21 On the atmospheric side, the data 22 for the lead concentrations in air came from

### 202-234-4433 Neal R. Gross & Co., Inc. Page 127 1 four different networks which were set up for 2 different purposes.

3 And at least as far as I could 4 tell, none of them are particularly well 5 suited for the assessment of whether existing 6 or future NAAQS for lead is attained. 7 So if not in this assessment, 8 perhaps by the time of the next NAAQS review 9 it would be useful to have some kind of a 10 network that was capable of assessing whether 11 or not this attainment was occurring. 12 George and Phil and Rich have all 13 talked a little bit about the particulate 14 matter data, and it sounds like there's going 15 to be an attempt to try to work with those 16 data to understand it better. 17 The section that follows that 18 section is a literature review of studies in 19 which you've tried to look at these particle 20 size distributions. You know, there are 21 plenty of studies in that section. 22 Maybe it's best to leave this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 128 1 particular analysis out and just rely on the 2 literature for that part of the assessment. 3 The sections talking about 4 different spatial and temporal patterns of 5 lead in various environmental media I thought 6 were, well, I wondered if they were as 7 complete as they could be. 8 In the case of the soil studies, 9 the section on soil studies had some very 10 interesting material on urban and suburban 11 soils, smelter impacted soils, soils affected 12 by lead shot. 13 There weren't any studies cited of 14 more pristine environments like forest soils. 15 There are a couple of studies which I put in 16 my comments that might be discussed there. 17 The section on lead in rain, the 18 only information cited there are from a couple 19 of studies in Canada and Europe on temporal 20 patterns in lead and rain, which just made me

21 wonder. 22 Is there no one in the United

### 202-234-4433 Neal R. Gross & Co., Inc. Page 129 1 States that's monitoring lead in rainfall 2 somewhere? And if there are people who are 3 monitoring lead in rainfall it would seem that 4 that data, some of those data might be in here

5 now. 6 The document does try to look at 7 studies that have been published since 2005, 8 and so maybe there haven't been things 9 published. But still it seemed to be a pretty 10 important omission. 11 And then also the section on 12 natural waters. Actually it only talks about 13 one study, one paper, which is a study from 14 Ontario, in Canada. And again it made me 15 wonder, is no one doing any monitoring on lead 16 in lakes and streams in the United States? 17 It seemed to be that there ought to 18 be some information out there on temporal, if 19 not spatial patterns because there's not a lot 20 of studies, at least temporal patterns and 21 concentrations in some natural waters. 22 One of the charge questions says,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 130 1 does the ISA adequately characterize the 2 available evidence on the relationship between 3 ambient air and lead in various environmental 4 media? 5 As I think Rich maybe -- I can't 6 remember -- mentioned, it's a tough question. 7 I mean it's tough. 8 I work a lot with soils, for 9 example, and it's, you know, it's tough to 10 imagine how you would relate ambient air to 11 soil, lead in ambient air to lead in soil, and 12 whether those relationships, even if they 13 existed, would be useful for prediction and 14 that sort of thing. 15 But, you know, having said that 16 there isn't a lot of information in here about 17 relationships between lead in ambient air and 18 lead in water, lead in rain. Lead in rain, 19 you'd think you could be able to that, lead in 20 soil, et cetera. 21 I guess a couple more comments. 22 The talk about lead solubility in the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 131 1 atmosphere in particular, one thing that, you 2 know, is also true. It's a good news story. 3 Acid rain especially in the Northeast and 4 Midwest is going down, down, down. 5 And, you know, you would think that 6 with the pH of moisture and precipitation in 7 the atmosphere increasing that would affect 8 the solubility of lead and therefore might 9 affect deposition through a pH effect. 10 I don't know if people have studied 11 that but it certainly could be modeled and 12 that could make a difference in terms of the 13 lead deposition. 14 And I guess I'll finish with a 15 comment on Figure 3-19. I don't know if we 16 can get that up on the screen. That's on Page

17 374. 18 This is a section in which the 19 document tries to look at seasonal variations 20 in lead TSP, and the document says that -- see 21 if I can find it here. 22 The document says that "the average

### 202-234-4433 Neal R. Gross & Co., Inc. Page 132 1 of lead concentrations over all monitoring 2 sites is higher in fall and lower in winter 3 than in other seasons." 4 (Off microphone discussion) 5 DR. JOHNSON: Thank you very much, 6 by the way. There you go. 7 So the text says that the average 8 lead concentrations are higher in fall, lower 9 in winter than in other seasons. 10 Box plots are hard to, I mean 11 they're hard to interpret for patterns and 12 what not, but it seems to me like spring is 13 highest, maybe fall is next and then winter 14 and then summer, at least looking at the stars

15 on there. 16 But in any event, whatever the 17 pattern is, were there any statistical 18 analysis used to try to verify or to get a 19 level of confidence in a conclusion based on 20 this study and then looking at this seasonal 21 pattern and the data? 22 Maybe they were referring to other

### 202-234-4433 Neal R. Gross & Co., Inc. Page 133 1 figures, I don't know. But the other figures 2 at least at a glance that followed this also 3 seem to show similar patterns or non-patterns. 4 Anyway I think that, I also have a 5 number of comments that the group can look at 6 but I think that's all I really want to say

7 here. Thanks. 8 DR. FREY: Okay, thank you. 9 I'd like to I guess ask George and 10 Rich if they could reflect on -- or I guess 11 actually before I do that I should ask, I 12 should invite the other panel members to make

13 comments.

14 So are there comments from other 15 panel members on Charge Question 3? Yes, go

16 ahead. 17 DR. GOODRUM: Just one discussion 18 point. I think Dr. Hopke mentioned his 19 reservations about switching from Pearson to 20 Spearman. 21 And just have to say that I'm a big 22 fan of Spearman rank and Kendall tau, the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 134 1 other non-parametric methods, because they're 2 less sensitive to outliers in your para

3 dataset. 4 And I guess through exploratory 5 data analysis we maybe wouldn't rely totally 6 on a Spearman rank coefficient or the square 7 of that. We'd also look at the graphic. So 8 we'd look at both the visual inspection and 9 the statistical result. 10 But the use of Spearman rank is 11 pretty well established with environmental 12 data, and primarily because of its benefit for 13 being less sensitive to the outliers in your

14 data. 15 DR. FREY: Okay, thank you.

16 Yes?

17 DR. RABINOWITZ: If I could make a

18 comment on a comment? 19 DR. FREY: Absolutely. 20 DR. RABINOWITZ: Thank you. I very 21 much appreciated George Allen's comments about 22 trying to learn more about the residence time

### 202-234-4433 Neal R. Gross & Co., Inc. Page 135 1 of lead in soil. It's a challenging problem, 2 and of course there is this opportunity you 3 mentioned. 4 And I'd just like to comment and 5 suggest that there are other opportunities out 6 there. And for instance, we've closed any

7 number of smelters and we know when those

8 smelters were closed. 9 We know they're in different 10 climates, which may affect different soil 11 types, may affect residence time. 12 Indiana, for instance, in the '70s 13 and '80s there are any number of toxic waste 14 sites where they measured exact soil levels 15 and they know to within a foot where they took 16 that soil sample. In Indiana there are many 17 sites like that. Just to name one state. 18 There's also many in Utah, and you 19 could think of other states too, where people 20 have -- or the other side of Missouri. 21 Over in Joplin, what's left of it, 22 there used to be a large smelter. They knew

### 202-234-4433 Neal R. Gross & Co., Inc. Page 136 1 exactly when it closed down. They knew 2 exactly how much soil was in it. 3 Already decades have passed since 4 those values were taken, so you have a chance 5 to see what may have happened in the meantime. 6 So it's a good idea. Hope you have 7 better luck funding then I did. 8 DR. FREY: Yes, I think there's a -

9 -

10 DR. RABINOWITZ: Excuse me. If I 11 may add, there's also roads that have closed 12 too. Highways that have shut down abruptly. 13 They know when it happened. Thank you. 14 DR. FREY: Yes, I think these are 15 good suggestions. The challenges that, if 16 these are really aimed at recommending future 17 studies then it doesn't quite help EPA in 18 revising the ISA. 19 But I think they are good things to 20 pass along to EPA, and I think as George 21 mentioned, you know, maybe it's useful for, 22 you know, the STAR grants program or ORD to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 137 1 keep these in mind. 2 DR. RABINOWITZ: Thank you. 3 DR. FREY: So yes, with I guess a 4 lot of the NAAQS reviews we tend to have kind 5 of a catch-all of things we'd like to 6 recommend to see done in the future, and this 7 certainly would be in that category. 8 Although I guess maybe part of what 9 you might be saying is that there's an 10 opportunity to mine some data, existing data, 11 to look at some of the issues that the ISA is 12 trying to address. 13 Or do you think that's such a 14 substantial effort that that's not something 15 that can be done by a second draft ISA? 16 DR. RABINOWITZ: No, it's just to 17 the future sometime. But I have other written 18 comments, which I'm sure you've all read all 19 of everybody's written comments. 20 That's why I mentioned this in the 21 meeting. It's more a question of resampling. 22 DR. FREY: Okay. Other panel

### 202-234-4433 Neal R. Gross & Co., Inc. Page 138 1 member comments on Charge Question 3? 2 Well, then can I put George and 3 Rich on the spot to kind of synthesize what 4 you saw as maybe the top three to five points 5 that came out of panel member input? 6 MR. ALLEN: Thanks, Chris.

7 DR. FREY: You're welcome. 8 MR. ALLEN: The top three to five 9 off the top of my mind here. What pops out, 10 Phil's comments about dry deposition and that 11 you should have ultimate atmosphere at the 12 sinks. That's probably true for fine mode and 13 most likely not true for coarse mode. So 14 maybe there's a mode dependency upon, I'm sure 15 there's a mode dependency there. 16 Phil also noted issues with self 17 absorption with heavily loaded large particle 18 lead XRF analysis.

19 I don't know how much of the 20 network data, and there are several different 21 networks, how much of it is XRF and how much 22 of it is the various other back end analyses

### 202-234-4433 Neal R. Gross & Co., Inc. Page 139 1 that would not have that issue. I don't have 2 a handle on that so I don't know how big a 3 problem it is. 4 (Off microphone discussion) 5 MR. ALLEN: Right, right. I mean 6 I think for the most part, the other non-XRF 7 techniques are probably pretty decent in 8 getting all the lead, whereas we know -- 9 probably. Can I get a "probably" from you, 10 Phil? 11 Whereas, we know XRF, if it's 12 heavily loaded with big particles does have a 13 problem. And we don't know if it's been done, 14 corrections have been done properly. So 15 that's a big piece. 16 Let's see. Not to reiterate Rich's 17 comments or mine, because we know what they

18 are. 19 DR. FREY: Well, you've already 20 given two, so you only have -- 21 MR. ALLEN: I have one more, okay. 22 Network, suitability of the network, Chris

### 202-234-4433 Neal R. Gross & Co., Inc. Page 140 1 mentioned that. That's a good question. I 2 mean we're in a resource-constrained world.

3 We do have more of a network now as 4 a result of the last NAAQS, maybe a better

5 network. It'll never be what we want or what 6 we need, so here we have the art of 7 compromise. 8 But, you know, we are, presently we 9 have a source-oriented network and then a 10 generic and core urban and a little bit of 11 rural, which is maybe all we can do and maybe 12 it's good enough.

13 We'd love to have more source14 oriented data. We're data starved for near 15 source data. But I don't, unfortunately, I 16 don't see those changing. 17 I guess that's my three. There's 18 a few others. Lead in rain, can I say that? 19 Okay, thanks. 20 DR. FREY: Okay. Rich? Anything 21 else you saw as jumping out as a high level 22 point that we --

### 202-234-4433 Neal R. Gross & Co., Inc. Page 141 1 MR. POIROT: I felt like we, again 2 the discrepancies in the recorded lead 3 measurements from the different size 4 distributions was just something we should 5 have to size. 6 And also sounds like something EPA 7 was already on the track to look at carefully. 8 But to me that's quite important. You know, 9 and I think we just keep assuming that yes, we 10 ought to know how to measure lead. 11 But this has come up too many times 12 where, you know, and lead is sort of unique. 13 In the sense of all the criteria pollutants 14 it's the one that becomes dependent on each 15 analytical laboratory in each of the different

16 states. 17 There are so many equivalent

18 methods that are out there that are 19 permissible. So I think it really, you know, 20 is something that we could emphasize a little 21 bit, but they're good. 22 Phil also had raised a point about

### 202-234-4433 Neal R. Gross & Co., Inc. Page 142 1 Asian contributions, and I think I had noted 2 that in some of the written comments of

3 others. 4 It seems like something that's, a 5 closer look at it is quite doable from the 6 perspective of existing datasets. So maybe 7 that's something that could just be clarified. 8 I don't know if it's a major point, but I 9 think it's quite doable. 10 DR. FREY: Okay. 11 MR. POIROT: Somebody like Phil can

12 do that. 13 DR. FREY: All right. Any last 14 thoughts on Charge Question 3 before we press 15 on? I think we've covered the terrain there

16 for the moment. 17 So we're still ahead of lunch. I 18 think we ought to press on with our next 19 charge question, which is 4a, and see where we 20 are at noon, whether we want to finish up that 21 discussion or just break at noon for lunch. 22 So we'll see how the discussion

### 202-234-4433 Neal R. Gross & Co., Inc. Page 143 1 goes on, at least on 4a. And for that charge 2 question the lead discussant is Dr. von 3 Lindern, and then the other discussants are 4 Drs. Goodrum and Hopke. 5 So Dr. von Lindern, the floor is 6 yours. 7 DR. von LINDERN: Well, I'm over 8 here struggling with whether to make this 9 short or long. Lunch has something to do with

10 that. 11 DR. FREY: Yes, how popular do you

12 want to be? 13 DR. von LINDERN: Most of my 14 concerns seem to be rendered irrelevant by the 15 process eliminating those things that I'm 16 concerned about here for consideration. 17 So if I stick to the charge 18 question and just answer that it'll be short. 19 If I get to put my complaints out it will be 20 longer. 21 So I think Chapter 4 itself was 22 pretty well put together. I think it answers

### 202-234-4433 Neal R. Gross & Co., Inc. Page 144 1 the questions adequately. I'll just briefly 2 go through that. 3 There is an early discussion in 4 that chapter about the effects of the phase 5 down from, in air lead levels. I think that's 6 good, but I see this entire document 7 attributes most of the success in reducing air 8 lead levels to the phase down. 9 There were, in fact, much larger, 10 and reductions in the magnitude of exposures 11 around the stationary sources in the country 12 and much greater drops in blood leads amongst 13 the population surrounding those stationary 14 sources. That seems to have been forgotten, 15 and it would be good to remind ourselves of

16 that. 17 There is a discussion of indoor and 18 outdoor exposures in there. Every time we 19 have one of these meetings somebody says 20 outdoor's greater, and then the next meeting 21 somebody says indoor's greater, and it's gone 22 on that way for years.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 145 1 It seems that those are site 2 specific conditions and it could be either way 3 and maybe we should just acknowledge that. 4 And then the remainder of this 5 section goes through other media. I think 6 part of what's missing there is, and we've 7 heard it a number of times here, only looking 8 at new information. 9 A little summary at the beginning 10 about how much media concentrations have 11 changed over the years would be helpful I 12 think. 13 We have seen large reductions in 14 these other media concentrations throughout 15 the country, and it would be good to give that 16 the same amount of attention that we give to 17 air. 18 And then moving on to the portion 19 about pathways and does the ISA adequately20 describe the balance of air related and non21 air related pathways. 22 There are many pathway specific

### 202-234-4433 Neal R. Gross & Co., Inc. Page 146 1 exposures to children and to adults that vary 2 considerably due to a lot of other factors, 3 lifestyle, behavioral, cultural factors. And 4 in different situations, one pathway or 5 another can be dominate. 6 And I think as we're moving into 7 other populations rather than these North 8 American and European studies that all of this 9 is based on, we're finding that other pathways 10 are more important and that there are a number 11 of ways in which the intake and uptake can 12 vary significantly. 13 And maybe we're becoming too myopic 14 about the populations that all of this history 15 has been based on and maybe should discuss a 16 little bit more how these various pathways 17 influence intake and uptake and the other 18 socioeconomic, ethnic and behavioral factors 19 that can influence that. I don't know that 20 there's good treatment of that there. 21 And I think this might be 22 particularly important when we begin to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 147 1 consider some of the susceptible populations 2 later on, particularly immigrant populations 3 that are bringing some other habits and 4 behaviors with them that could be important in

5 that factor. 6 Those are my main comments with 7 respect to the question. Now if I can 8 complain, which requires me going back to 9 Section 3. If we are, and maybe I'm just dead 10 wrong on this, I don't understand. 11 But if this is the information that 12 is going to be used to provide the basic data 13 for an exposure assessment to go into the 14 policy document that's going to end up with 15 the administrator, it is woefully inadequate. 16 If there are other opportunities to 17 bring other data and information into this 18 process later on maybe it's going to work. 19 And that's where my primary confusion is. 20 There is in Chapter 3, absolutely 21 no information whatsoever about the role of 22 lead in U.S. commerce, the production of lead

### 202-234-4433 Neal R. Gross & Co., Inc. Page 148 1 in the United States, the uses of lead in the 2 United States, the distribution of that lead, 3 where's it being disposed, where it's ending 4 up. Is it being shipped overseas? None of 5 that is in here. 6 Is that going to be developed 7 somewhere else or is it going to be ignored in 8 the policy determinations? That's a big 9 question for me. 10 Next, with regard to the ambient 11 data, we've just had a discussion about, this 12 document has done a good job of summarizing 13 the ambient data that's out there. 14 But nobody points out that that 15 ambient data is woefully inadequate in telling 16 us whether we're in compliance with the NAAQS 17 in the country, where the exposures are at, 18 what the concentrations are around key 19 populations. 20 It seems as if we don't know that. 21 Is that something that's going to be developed 22 later or are we saying now that we don't know?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 149 1 In the last document, this is 2 another consideration of the only looking at

3 new data. In the last round we concluded that 4 there wasn't sufficient data out there to 5 evaluate this question, and it was a big 6 inadequacy in the document. 7 And it seems that the obligation 8 was on the agency to develop that information 9 in the last three to four years. That seems

10 to have not been done. 11 And we're going to come to the 12 conclusion that there isn't sufficient data to 13 conduct an adequate risk assessment, so we're 14 going to go back to doing pilot modeling. 15 I don't think that message was 16 delivered here at all that we don't have a 17 good handle on the ambient concentrations out

18 there. 19 We don't have a good monitoring 20 system for it yet, but is this process just 21 going to conclude that then we don't need to 22 look at it, we can stick with the same

### 202-234-4433 Neal R. Gross & Co., Inc. Page 150 1 information? 2 That's difficult for me to 3 understand, how the agency is dealing with 4 that. And that should be pretty close to 12,

5 so I'll cut off there. 6 DR. FREY: Okay. Actually we're 7 still ahead of 12. It's about 10 of. 8 Well, thank you for the comments. 9 So I think some of what you said actually 10 touched on Chapter 3 and may be something that 11 George and Rich may want to consider in 12 developing the summary. 13 And Phil, yes, do you want to

14 comment? 15 DR. HOPKE: Yes, I mean I think you 16 have to understand how criteria pollutants are 17 regulated. The key is that these are from a 18 variety of sources giving rise to general 19 exposures. 20 The specificity of where lead comes 21 from and how it's used really comes into play 22 when people start to develop state

### 202-234-4433 Neal R. Gross & Co., Inc. Page 151 1 implementation plans. And so it's not clear 2 that we should be getting into that level of 3 detail in the Integrated Science Assessment. 4 Now again, what Chapter 3 tries to 5 do is portray a picture of the concentrations, 6 and then Chapter 4 should explain how it moves 7 those concentrations to estimate the basis for 8 moving those to exposures, whereas, the 9 exposures themselves would be then calculated 10 in the exposure and risk assessment later. 11 So we have to be careful as to just 12 what parts of the process each of these things 13 is trying to achieve. 14 DR. FREY: Okay. Well, let's 15 continue then on Charge Question 4a with Dr.

16 Goodrum. 17 DR. GOODRUM: I'm going to try to 18 keep my comments short as well. I focused 19 more on 4c, which is a subset of 4. So 20 specifically to the questions in the charge, 21 the organization and the content I thought was 22 logical.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 152 1 The amount of information that was 2 spent on revisiting exposure in biokinetics 3 and the empirical information that allows us 4 to relate biomarkers to estimates of exposure 5 I thought were appropriate and matched the 6 charge in terms of trying to introduce the new 7 literature and information that was available. 8 I do think I'd like to echo what 9 Ian said in terms of helping the reader out 10 with some short synopsis of what's known to 11 date on changes over time in certain exposure 12 media. 13 And just one example would be 14 looking at the background documents in support 15 of IEUBK for dietary exposure and just tracing 16 over time FDA's data and estimates of average 17 daily intake through the diet pathway. 18 That's pretty well established and 19 well vetted analysis and could be captured in 20 a succinct way. And along those lines, I 21 think there's an opportunity maybe in this 22 chapter, to start to guide the reader a little

### 202-234-4433 Neal R. Gross & Co., Inc. Page 153 1 bit more. 2 Because we're moving from exposure 3 into more of the modeling and the use of 4 empirical data, is to try to frame the 5 discussion in terms of what empirical 6 information is there to inform estimates of 7 background, so for populations that are not 8 near a smelter or near some active source. 9 But we're talking about background 10 levels. The types of discussions that would 11 accompany evaluations of the NHANES blood lead 12 data, for example. 13 The structured mechanistic models 14 provide one point of view on the relative 15 contribution of air to both the outdoor and 16 indoor reservoirs and just through direct 17 inhalation. 18 I think it would be interesting to 19 start to set the stage for, you know, if we're 20 going to use those models. 21 And on the one hand, to help inform 22 the risk assessment down the road and the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 154 1 policy, how do those assumptions that are 2 built into that model now line up with the 3 data that we have from the multivariate 4 analyses where we've tried to tease apart the 5 relative contribution of air to some of the 6 other pathways? 7 So we have an opportunity here to 8 maybe revisit a verification of the 9 contribution of air. 10 I've used the IEUBK model quite a 11 bit, but more for Superfund site assessments 12 where air is not the driver, and here we have 13 the opposite focus where we're trying to 14 understand to what extent air is the driver. 15 And so I think it behooves us to 16 revisit this question of air contributions to 17 soil and dust and connecting empirical data 18 with the modeling assumptions. 19 DR. FREY: Okay, thank you. 20 Let's see, Phil? 21 DR. HOPKE: Yes, I thought this 22 chapter was in reasonably good, part of it I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 155 1 could follow which was 4-1, which is what I 2 was asked to do. However, there's no 3 discussion of exposure models. 4 And EPA has put considerable effort 5 into coming up with TRIM, which I was under 6 the impression was now available. 7 And, you know, so the question is, 8 how do you put these pieces together? And it 9 seems like the science of the exposure 10 modeling should be included in here because 11 there's got to be some way to put those pieces 12 together when you move on from here to the 13 exposure and health risk assessment. 14 Lead is different than most of the 15 other criteria pollutants because we are 16 worried about multiple pathways. 17 And therefore, how you, what the 18 state of the science on modeling those various 19 pathways as well as elucidating what those 20 pathways are, are both important to providing 21 the basis for the next step forward. 22 And I didn't see any of that in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 156 1 here. I mean I assume that there's going to2 be some sort of exposure modeling, multi3 pathway exposure modeling. 4 It's certainly going to be needed 5 in the next step, and the basis for that 6 should be here in the ISA. 7 The other major thing that I saw 8 missing was that, you know, obviously several 9 years ago we had the major episode of the 10 Chinese lead-painted toys and that was not 11 included in Table 4-6. 12 And given that this led to 13 substantial action by other regulatory 14 agencies in the United States, you know, it 15 doesn't have anything bearing on the air 16 quality standard, but in terms of you've got 17 other sources of lead mentioned in here, 18 that's certainly an incident of sufficient 19 magnitude that it warrants incorporation into

20 Table 4-6. 21 DR. FREY: Okay. Other comments on 22 specifically Charge Question 4a?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 157 1 Yes, Dr. Kosnett? 2 DR. KOSNETT: Well, I'm inclined to 3 look now and see whether my comments were just 4 specifically to 4a. Actually more on 4b. So 5 I spoke too soon. 6 DR. FREY: Okay. All right, other

7 comments on 4a? 8 Okay, Dr. von Lindern, would you 9 want to take a stab at maybe what are the top 10 two or three main points that come out of 11 this? 12 DR. von LINDERN: Maybe you don't 13 want me, right? I would like to ask EPA a 14 question first to help me -- 15 DR. FREY: Okay. Sure, that's 16 fine. 17 DR. von LINDERN: -- in that 18 regard. I don't see in Sections 3 and 4, a 19 conclusionary nature like there was in the 20 health chapters with regard to causality. 21 And if I were drawing a conclusion 22 with regard to Chapter 3 and 4 in terms of, is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 158 1 there an adequate database presented in this 2 document to support exposure analysis, I would 3 have to say no. 4 But is that important to this 5 document? And it harkens back to another 6 thing that happened in the last review that's 7 not happened here, is the professional trade 8 literature available to help develop that 9 exposure information? 10 Because that's where it's at. It's 11 not in these peer reviewed journals. And if 12 the agency is going to do a credible job at 13 some time, they're going to have to access 14 that data. Does that happen later in this 15 process or are we going to live with what's

16 there now? 17 DR. FREY: Well, if you're asking 18 me, I don't know all the answers to that. But 19 I guess one distinction that tomorrow we will 20 review the scope and methods plan for the risk 21 and exposure assessment. 22 And I think the question about

### 202-234-4433 Neal R. Gross & Co., Inc. Page 159 1 trade literature as it pertains to the REA 2 would be something we could talk about

3 tomorrow. 4 But I guess the trade literature as 5 it pertains to the ISA is something we could 6 certainly ask the folks here at the front of 7 the room about today. 8 And I don't know if, John, maybe 9 you want to comment on that? 10 DR. von LINDERN: It's not trade, 11 it's trade but it's EPA's files. They can 12 look in their own files and they can find this 13 information. Will they do that? 14 DR. FREY: You're saying literature 15 that's not, it's not peer reviewed journal 16 papers. It's things other than that. 17 DR. VANDENBERG: Yes, that's an 18 important clarification, what you meant by 19 trade literature versus what information's 20 available to the agency, we do consider that. 21 So maybe you can clarify what you 22 meant. Maybe you just did. Is that what you

### 202-234-4433 Neal R. Gross & Co., Inc. Page 160 1 meant, is what EPA has in terms of the 2 monitoring data, the data that's available to 3 us through either EPA's files or NHANES or 4 other collaborations? Is that what you're 5 referring to? 6 DR. von LINDERN: And in the other 7 programs in EPA. There's lots of exposure 8 information, that hundreds of sites in this 9 country that can inform this document with 10 regard to exposures out there, but it's not 11 included at this point. 12 This is where I'm confused. If 13 this is really a literature review of the peer 14 reviewed literature, then I think it should 15 conclude that in the peer reviewed literature 16 there's not sufficient exposure information to 17 go forward. 18 But there is sufficient exposure 19 information somewhere else. Is the agency 20 going to access that later? 21 DR. VANDENBERG: I'd like to say I

22 have the answer to that because we do focus on

### 202-234-4433 Neal R. Gross & Co., Inc. Page 161 1 the peer reviewed literature, and then data 2 that's available to EPA such as through the 3 Ambient Air Quality Monitoring System that's 4 used that's reflected here in the data that 5 you were saying earlier. 6 But in terms of the data that might 7 be available to our other program offices, we 8 may or may not be bringing that in in the 9 manner that you're referring to here. 10 And so I think that may be a 11 comment we certainly would welcome, but I 12 don't have a particular good answer for you 13 right now, I'm afraid. 14 I'll look to my colleagues here. 15 I don't know, Mary, if you have any comment

16 about that? 17 (Off microphone discussion) 18 DR. VANDENBERG: Yes, are you 19 talking about the Superfund sites? As an 20 example of that.

21 DR. von LINDERN: Yes. 22 DR. VANDENBERG: Yes, we can look

### 202-234-4433 Neal R. Gross & Co., Inc. Page 162 1 into it. 2 DR. von LINDERN: So now I'll try 3 and answer your question. 4 DR. FREY: I'm sorry? 5 DR. von LINDERN: I'll try and say

6 what the concern -- 7 DR. FREY: Okay. 8 DR. von LINDERN: Actually, no 9 particular order, but maybe some additional 10 discussion about modeling because, and the 11 science of modeling. 12 I think some additional discussion 13 of the significance of different exposure 14 parameters with regard to the peculiarities of 15 different subpopulations that we're likely to 16 see, more history about the media 17 concentrations. 18 Well, and then my pet peeve. It 19 wasn't all gas. There were a lot of smelters

20 that were closed too. So that should be 21 included in the discussion of lowered 22 exposures over the years.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 163 1 I would like to suggest that there 2 be more conclusions drawn in Chapters 3 and 4, 3 more similar to the health sections, and those 4 conclusions drawn with regard to the adequacy 5 of the databases as they're presented to 6 support further analyses. 7 And particularly those databases 8 that really it's the responsibility of EPA to 9 collect and develop those. But I'll take 10 advice from my fellow members on whether we 11 should put that sort of thing in the 12 recommendation or not. 13 DR. FREY: Yes, I think as I 14 mentioned, you know, I think almost every 15 panel gets into a territory that has to do 16 with recommending what EPA should do to get

17 more or better data. 18 And that's sort of a different 19 flavor of recommendation than commenting on 20 the ISA and how, you know, how should EPA 21 revise for the second draft ISA. 22 So I think we can certainly compile

### 202-234-4433 Neal R. Gross & Co., Inc. Page 164 1 some of those thoughts and think of a way that 2 we might pass that along to EPA, but it's sort 3 of a different kind of an animal in that 4 regard. 5 Phil? 6 DR. HOPKE: Again, once upon a time 7 us old-timers remember we used to come up with

8 research needs assessments after each round. 9 But those disappeared because they always 10 turned into massive laundry lists instead of 11 targeted priorities. 12 DR. FREY: Yes, and I think we did 13 something like that with PM in the recent 14 review, and so I don't think it's totally gone 15 away. 16 DR. VU: Last year at one of the 17 meeting with CASAC, I forgot which panel it 18 was. I think it was ozone. No, it wasn't 19 ozone, it was PM I think, or the year before. 20 But we did discuss with, I did have 21 a discussion with ORD about doing some kind of 22 a meeting with CASAC to look at the specific

### 202-234-4433 Neal R. Gross & Co., Inc. Page 165 1 research needs for the air pollution NAAQS 2 program. 3 So I'll continue to talk with them 4 about it, but I know these are some of the 5 urging needs that from CASAC's trying to help 6 the agency prioritize some of the key data 7 gaps, that you all would like to see. 8 So I will keep you informed where 9 that is, okay. I know Dan is busy so we'll

10 see where we are.

11 DR. von LINDERN: Can I make one 12 clarification? 13 DR. FREY: Sure, go ahead. 14 DR. von LINDERN: Although I'm all 15 for lead research, I'm not advocating 16 additional lead research. 17 I'm trying to point out that this 18 information that is necessary to move forward 19 has traditionally been collected by EPA as 20 part of their statutory responsibilities. 21 That has not happened in the last few years. 22 And as a result, that database is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 166 1 not available. Not because the research 2 hasn't been done and isn't in the peer 3 reviewed literature. It's because the 4 monitoring has not been done. 5 And that isn't research monitoring, 6 that is monitoring to help characterize the 7 extent of exposure in the United States. That

8 doesn't seem to be there. 9 Perhaps it's available in some of 10 the other venues in EPA. I don't know whether 11 this group is attempting to look for that. 12 That's the question. 13 DR. FREY: Okay. All right, just 14 mindful of the time and lunch. So any last 15 thoughts on 4a before we break for lunch? 16 Okay, so I think we'll go ahead and17 take a, I think we were scheduled for a one18 hour lunch. So we'll go ahead and do one hour 19 for lunch. Let's just say that we'll 20 reconvene at 1:15, and enjoy your lunch. 21 (Whereupon, the foregoing matter 22 went off the record at 12:10 p.m.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 167 1 and resumed at 1:15 p.m.) 2 DR. FREY: Our next agenda item is 3 to discuss Charge Question 4b. 4b is on the 4 topic of biological markers. 5 And I think we'll go ahead and do 6 Charge Question 4b, and then we might come 7 back for a few minutes to -- EPA has some 8 clarifications they want to provide on the 9 process. 10 But we'll do that I guess after 4b, 11 would that be okay? Or are you ready now? 12 DR. VANDENBERG: We can do it any 13 time I think. 14 DR. FREY: Okay. Well, if you're 15 ready now then maybe this is a good time. 16 So yes, we thought we would take a 17 minute and just offer some clarifications 18 since some of the questions, or comments we've 19 been hearing kind of touch on the interface 20 between the Integrated Science Assessment and 21 the risk and exposure assessment. 22 And EPA can help clarify some of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 168 1 those distinctions and some of the other 2 issues that have come up. 3 So, John? 4 DR. VANDENBERG: Thank you, Dr. 5 Frey. Just again for clarification. I'm 6 joined here by Dierdre Murphy, who's with the 7 Office of Air Quality Planning and Standards. 8 And Dierdre will be one of the 9 point persons tomorrow when we're talking 10 about the risk and exposure assessment, but 11 OAQPS also deals with the policy assessment. 12 And again the research and 13 development wing of EPA tends to support the 14 discussion and the consideration of science as 15 we go into those next stages in that overall 16 flow chart that I was talking about. 17 But I thought it would be helpful 18 to just sort of step back and talk about the 19 different pieces of all of the assessment 20 activities that are going on to support the 21 decision making. 22 And then also speak as Dr. Hopke

### 202-234-4433 Neal R. Gross & Co., Inc. Page 169 1 did, that some considerations come in quite a 2 bit later in terms of state implementation 3 planning where things like economic impacts 4 are considered. 5 That's not considered in the 6 standard setting process, but it is considered 7 when it comes to the states developing plans

8 to meet the standard. And that's where 9 economic impacts would play a role. 10 And issues like how is lead used in 11 commerce or how is it, you know, influencing 12 other things, that's a separate step from the 13 process that we're involved with right now. 14 So just to sort of set the stage 15 is, a few years ago when we were struggling 16 with a lot of the Air Quality Criteria 17 documents, one of the struggles we had was the 18 scope of them became ever larger.

19 And so there was a sense of almost 20 crisis in the program is that we needed to 21 really recognize that the purpose of the 22 Integrated Science Assessment is to support

### 202-234-4433 Neal R. Gross & Co., Inc. Page 170 1 the standard setting process. 2 In addition, it directly supports 3 the risk and exposures assessment work and 4 ultimately the policy assessment that the Air 5 office is charged with developing. 6 So if you think about these pieces, 7 one of the things that we're trying to do is 8 to focus on the information that is most 9 informative, most policy relevant to the 10 standard setting process. 11 And through that process of 12 interactions with different CASAC committees, 13 we've kind of developed this existing document 14 that you have now. 15 And as I mentioned in my opening 16 comments, we're continuing to improve the 17 document to try to add more analysis, more 18 interpretation, more focus. 19 More user friendly in some ways by 20 adding figures and tables and information that 21 helps the audience, and of course there's a 22 lot of audiences here to understand the nature

### 202-234-4433 Neal R. Gross & Co., Inc. Page 171 1 of information and how ultimately that helps 2 the administrator in setting the standards. 3 So when you consider that, one of 4 the things that we have focused on is the 5 information that is most relevant to the 6 standard setting itself. 7 And some of the questions that were 8 being discussed a little bit before the break 9 related to datasets that might be viewed as 10 somewhat outside of that. And one of the 11 things we're struggling with, and it would be 12 useful to get the comments from CASAC members, 13 is how that information might help inform 14 either the interpretation of the science or 15 its application perhaps subsequently in the 16 risk and exposure assessment and policy

17 assessment. 18 So we're trying to sort of process 19 some of that earlier discussion to make sure 20 that we understand the points being made. 21 And with that I'm going to ask 22 Dierdre if she wanted to add anything to it as

### 202-234-4433 Neal R. Gross & Co., Inc. Page 172 1 well, because part of it is the information 2 that we tend to present in the ISAs is the 3 empirical data. It's a lot of information on 4 the data that's available. 5 And in terms of projections, in 6 terms of modeling, in terms of looking at 7 different policy options, that's where the Air 8 office comes in. 9 So would you like to add anything

10 to that? 11 DR. MURPHY: Yes, I'll just add, 12 because I was reflecting on that conversation 13 over lunch as well. And I think another piece 14 to clarify is something that was talked about 15 earlier. 16 That the mode of the ISA is sort of 17 an update mode. And that to the extent it 18 does not pull in previously assessed and 19 considered information, that information is 20 still available to the agency for our use.

21 And so as John alluded to we have

22 some downstream documents from the ISA. We

### 202-234-4433 Neal R. Gross & Co., Inc. Page 173 1 consider whether or not we're going to do a 2 new risk and exposure assessment. 3 And that's a topic of conversation 4 tomorrow where we have an REA planning 5 document which was intended to evaluate, what 6 is the newly available information and does 7 that lead us to conclude that an updated risk 8 assessment is warranted? 9 We did a complex one in the last 10 review. The results of that analysis are 11 still available to us to consider in this 12 review as is all of the information that was 13 assessed in previous CDs, the Criteria 14 Documents, in addition to what's assessed with 15 this criteria document.

16 And when we come to the next 17 document, which is the policy assessment 18 document, that's where it all comes together. 19 Because we, you know, OAQPS then say okay, 20 there are a couple of key questions for us. 21 Does the newly available evidence 22 call into question the adequacy of the current

### 202-234-4433 Neal R. Gross & Co., Inc. Page 174 1 standards? That's kind of an overarching 2 question for us. And so, you know, we look 3 at, okay, what's new and how does that fit 4 into what we knew before? 5 Does it cause us to change our 6 conclusions about things which are important 7 with the regard to the protectiveness and the 8 adequacy of the current standards? 9 And so I think just keeping in mind 10 that although the ISA strives to be 11 streamlined, we in EPA still reach back for 12 all the pieces of information that support 13 that from previous reviews. And we'll pull 14 that out as appropriate in the policy

15 assessment. 16 The other piece of information that 17 I think was touched on was different types of 18 data sets and whether or not they would be 19 appropriate to be talked about in the ISA or 20 in other documents. 21 And to the extent they are data 22 sets and can be mined for relationships and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 175 1 things like that, they can be touched on in 2 any of these documents. 3 In terms of one example of a 4 relationship I recall being essential in the 5 assessment that we did in the last go around, 6 the exposure risk assessment is we had some 7 Housing and Urban Development databases on 8 dust lead and housing age in different cities. 9 And we used that to help us 10 understand background concentrations of dust 11 lead to feed some modeling we did to project 12 changes in air lead, changes in dust lead that 13 were important to exposure modeling. 14 So we did draw on existing data 15 sets that either were published in agency 16 reports, either our agency or other agencies. 17 We worked with some Superfund data near the 18 primary smelter site that we had, because that 19 helped us work on relationships between dust 20 lead and air lead. 21 So there are different places where 22 those types of data can be used throughout the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 176 1 review process. 2 DR. VANDENBERG: So the point is, 3 I guess we wanted to just give an opportunity 4 for any other questions or discussions to us 5 in terms of how this process, where we are in 6 the process.7 And again it's a multi-year, multi8 step process. And try to put sort of an 9 understanding around this document that you're 10 commenting on today and the document being 11 reviewed tomorrow. 12 And then again you all are going to 13 be with us for years, so I want to make sure 14 we're all on the same page, okay? 15 DR. FREY: Okay, any questions by 16 members of the panel? EPA? Everything's

17 clear. 18 DR. VANDENBERG: Good. Well, thank 19 you for the opportunity to clarify. 20 DR. FREY: Okay, sure. Well, thank 21 you for the clarification. Okay, well, with 22 that let's pick up where we left off, which is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 177 1 to start on Charge Question 4b on biological

2 markers. 3 And our discussants are Drs. 4 Pounds, Hays and Korrick. And Dr. Pounds, the 5 floor is yours. 6 DR. POUNDS: Thank you. So I 7 talked briefly with my codiscussants at lunch, 8 Susan Korrick and Sean Hays, and I regret to 9 inform you that you'll probably not be 10 entertained by bloody intellectual combat 11 complete with prisoners and body counts, 12 although it's always dangerous to 13 underestimate the provocative abilities of Ian 14 or the two Michaels.

15 It seems that most of our comments 16 are related to the charge of identification of 17 topics that require additional or clarifying 18 discussions, and of which collectively we have 19 five or six. 20 I think they often come under the 21 context of putting the new data in context, as 22 has been discussed with the previous chapters.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 178 1 The perspective, for example, 2 clarification, Section 4.2.1, which is on 3 absorption, defines the terms absorption, 4 bioavailability and bioaccessibility. 5 And it gives the definitions of 6 absorption and bioavailability that do not 7 make these terms very distinct. And I think 8 just, you know, invokes some confusion later 9 in the chapter. 10 The chapter defines absorption as 11 referring to the fraction of lead absorbed 12 from the respiratory or gastrointestinal 13 tract, while bioavailability refers to the 14 amount of lead ingested or inhaled that enters 15 systemic circulation. 16 So it's not clear whether it's the 17 units, fraction versus amount, or whether it's 18 absorbed in systemic circulation or not that 19 distinguishes these two terms. 20 The ambiguity is furthered by the 21 apparent interchangeable use of these two 22 terms in different parts of the chapter. And

### 202-234-4433 Neal R. Gross & Co., Inc. Page 179 1 I suspect that most of the inconsistent use 2 results from carryover from the authors' usage 3 in the original paper. 4 So I'd suggest that these 5 definitions be revisited and that the entire 6 ISA document be reviewed to ensure the 7 consistent use of the clarified definitions

8 across the document. 9 In a similar vein, Section 4.3 and 10 elsewhere, defines the definition and 11 application and limits of biomarkers. This 12 section really should be expanded and carried 13 into, you know, 4.7.3. 14 That is to say that the section 15 would be well served by defining the 16 distinction between validation and application 17 of biomarkers for exposure, body burden, dose 18 and risk, which are kind of the general 19 categories of biomarkers.

20 It's clear from the text that the 21 ISA recognizes that lead biomarkers are not 22 equally valid when applied to different

### 202-234-4433 Neal R. Gross & Co., Inc. Page 180 1 exposure scenarios, and have actually done a 2 very nice job of illustrating that. 3 But it's easy for all of us to use 4 and interpret biomarkers in a facile manner 5 without really communicating the biomarker for 6 what, and the limitations of the biomarker for 7 that particular purpose. 8 This chapter contains cogent, but 9 really scattered throughout it, discussion 10 related to this issue.

11 And because blood lead and bone 12 lead are used for risk assessment and risk 13 management, I suggest that it's important to 14 bring this discussion up to the front of the 15 Section 4 and include it in the summary, as 16 well as to review the remaining parts of the 17 ISA to ensure consistent use of these terms. 18 I have a couple other additions, 19 but I, make sure that other people have a

20 chance to -- Susan? 21 (Off microphone discussion) 22 DR. POUNDS: Do you want to talk

### 202-234-4433 Neal R. Gross & Co., Inc. Page 181 1 about the uncertainties of the bone lead

2 measurement? 3 DR. FREY: Well, you're welcome to 4 go next if you're ready to go. 5 DR. KORRICK: Were you done? Is

6 that -- 7 DR. POUNDS: I've got a couple 8 more, but I'll pass, unless we've got time. 9 DR. KORRICK: Oh, okay. So yes, so 10 I actually, I apologize, Joel. I did have a 11 few things when I went back and looked at my 12 notes that were perhaps a little more 13 controversial. 14 And I think my, I focused my review 15 on Section 4.3 where I think that the section 16 does reflect current knowledge, and that the 17 focus is appropriate in terms of blood and

18 bone lead. 19 But I think I had one question 20 which perhaps the EPA or others could help me 21 understand, which is that it seemed as if this 22 section relied pretty heavily on the ICRP lead

### 202-234-4433 Neal R. Gross & Co., Inc. Page 182 1 kinetics, biokinetics model to demonstrate 2 relationships among different biomarkers. 3 And I suppose, I'm not a modeler, 4 so I suppose it's useful for demonstrating 5 some theoretical relationships. But I found 6 it a little difficult to understand the 7 context in which those models are relevant to 8 interpretation of the health effects 9 literature. 10 For example, there's a model in 11 there that suggests that with a short term 12 lead exposure, blood lead returns to baseline 13 levels even though body burdens go up, which 14 probably is not what you would necessarily see 15 in the epidemiologic literature. 16 And there are other parts of the 17 report that talk about the challenge of 18 looking at blood leads in older adults, which 19 likely reflect a combination of recent 20 exposures as well as long term body burdens. 21 And that's not really reflective in 22 some of these models. And I have a hard time

### 202-234-4433 Neal R. Gross & Co., Inc. Page 183 1 understanding how these models help inform 2 interpretation of the relationship of these 3 biomarkers to health outcomes in the real

4 world. 5 And I wondered why there wasn't 6 more in this section that looked at available 7 data demonstrating relationships among 8 biomarkers in a biologically relevant context. 9 In other words, in an epi context 10 or in human populations as opposed to in the 11 modeling. 12 So I may be missing something, but 13 I found it hard to see the role of these 14 descriptors and wondered why other kinds of 15 descriptions were seemingly lacking in the 16 section. 17 So I don't know if that's something 18 that you all want to address, or am I, I'm 19 probably not understanding the basic issue. 20 DR. POUNDS: Susan, what model 21 specifically -- 22 DR. KORRICK: Well, it's the ICRP,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 184 1 the International Commission on Radiological 2 Protection. A lot of the information in 3 Section 4.3 related to relationships among 4 biomarkers is based on this theoretical model 5 as opposed to based on empirically observed 6 data. And I have a little problem with that. 7 DR. VANDENBERG: Would you like to 8 -- yes. 9 DR. FREY: Yes, if you have some 10 clarification that would help. 11 DR. STANEK: Well, a couple of 12 comments I guess. So we attempted in the 13 kinetic section to present empirical data, and 14 then in Section, I think was it 4.3? 15 DR. KORRICK: Yes, it's 4.3. 16 DR. STANEK: Yes, we went into the 17 more modeling. So we tried to present both 18 the data that we had available on kinetics in 19 the chapter as well as using the models just 20 to present the data both ways, because there 21 are some areas where we don't have data, 22 empirical data, and so we relied on the models

### 202-234-4433 Neal R. Gross & Co., Inc. Page 185 1 more.

2 Just more to look at the 3 relationships between how lead moves 4 throughout the body as opposed to linking it 5 specifically to health effects. 6 DR. KORRICK: But I guess where the 7 models seemed to predict things that aren't 8 confirmed in the empirical observational data, 9 would it possible to have some acknowledgment 10 of that in this section? 11 You know, I think, again I admit 12 I'm not a modeler, but I think there are 13 limitations to these models probably in terms 14 of assumptions. 15 And the empirical data that are 16 available suggests to me that some of these 17 models are not necessarily applicable to a lot 18 of real work. So some sort of acknowledgment

19 of that. 20 Maybe that's in there, but I felt 21 like I didn't get a sense that the limitations 22 and roles of these models was very well

### 202-234-4433 Neal R. Gross & Co., Inc. Page 186 1 delineated. 2 DR. STANEK: We tried to outline 3 that at the beginning of that section, but 4 maybe we didn't do a very good job. So if you 5 can provide us specific examples where these 6 models are not doing a good job. 7 DR. KORRICK: But even Figure 4.10, 8 the upper panel sort of implies that, you 9 know, you get a lead exposure and then your 10 blood leads normalize back to where you 11 started. This is on Page 449. 12 And in adults that's probably, I 13 mean it's probably not how it works based on 14 real-world observational data.15 DR. HAYS: Do you know of real16 world observational data that shows that?

17 DR. KORRICK: That shows that? 18 Well, I mean I think it -- 19 DR. HAYS: That shows the opposite 20 of this? 21 DR. KORRICK: Not the opposite, but 22 in general if you get an exposure over a five-

### 202-234-4433 Neal R. Gross & Co., Inc. Page 187 1 year period, depending on the nature of the 2 exposure, your blood lead may, especially in 3 an adult, your blood lead may be higher at the 4 end of the period. 5 It will necessarily, because you're 6 going to, there's going to be some equilibrium 7 between blood and bone compartments which will 8 reflect the increase in body burden that's 9 been accrued over that intervening time. And 10 this model suggests that that doesn't go on. 11 I mean I think the reason I'm 12 pointing that out as an example is elsewhere 13 in this document there's a lot of discussion 14 about the difficulty of interpreting blood 15 leads in adults because they reflect body

16 burdens and bone stores. 17 And if we're going to, and I think 18 that's a reasonable issue. And if that's an 19 important issue in understanding the health 20 effects studies in adults, then to have a 21 model in the document that sort of implies 22 that's not what happens seems a little

### 202-234-4433 Neal R. Gross & Co., Inc. Page 188 1 contradictory. 2 And for purposes of internal 3 consistency, I think it's important to make 4 sure that the ways in which we're thinking 5 about these biomarkers, whether it's through 6 modeling or empiric evidence, are consistent 7 so that there's a body of sort of paradigms 8 for thinking about exposure and interpreting 9 exposure measures in the health literature. 10 I don't know if that makes sense. 11 DR. POUNDS: I think in these 12 figures as was well with some of the others, 13 when there's a change, in this case, the blood 14 that's -- I'm sorry, the leads that's input to 15 the model drops to zero. All right. 16 That what that means is the 17 epidemiologists don't do that kind of 18 experiment. 19 DR. KORRICK: So it's not real. I 20 mean it's not how people really expose. 21 DR. POUNDS: It's trying to show 22 the relationships. It's not trying to, in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 189 1 this particular instance I think, it's not 2 trying to model real-life scenarios. 3 DR. KORRICK: So how does this then 4 help us with the task of the ISA? Maybe 5 that's too broad a question, but I just kind 6 of lost track of where this actually fits into 7 figuring out how to understand. 8 DR. FREY: Let me see if I can 9 maybe summarize or focus a little bit. It 10 seems like the, if I understand the comment 11 you have, it seems to be in part what I'm 12 hearing is a preference for using empirical 13 data where it's available. 14 And then if there's some reason why 15 EPA felt the model was a more valuable way of 16 generating insight on the one hand, to make 17 more clear why that was better than using 18 empirical data, or maybe there wasn't 19 empirical data. 20 But then I think a related issue 21 is, how valid is the model? How's it been 22 evaluated or validated for these applications?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 190 1 And then a third thing I think I heard was, 2 the case studies being used with the models 3 may or may not represent perhaps a realistic 4 scenario. 5 But maybe that's intentional 6 because they're trying to tease out a specific 7 kind of interaction, and maybe that's not 8 clear. So are those kind of -- 9 DR. KORRICK: Yes, you said it much 10 better than I did. 11 DR. FREY: Okay. 12 DR. KORRICK: Thank you. 13 DR. FREY: So I think, and that's 14 probably just feedback for EPA that they could 15 either clarify it and, you know, address those 16 kind of, those three points. 17 DR. KORRICK: I mean I think these 18 are important issues because they're really 19 important to how we interpret the epidemiology 20 in ways that allow us to understand exposure 21 risks. So I think it's not a minor issue. 22 I think the other, I had mostly

### 202-234-4433 Neal R. Gross & Co., Inc. Page 191 1 more minor comments. I think that in the 2 Section 4.3 there's some reference to the 3 previous Air Quality Criteria document showing 4 information about measurement error in bone

5 lead. 6 And I think it would be helpful to 7 at least repeat some summary data related to 8 that, since bone lead is definitely measured 9 with a fair amount of error depending on the 10 nature of the population being assessed. 11 And I think that becomes an 12 important consideration when interpreting the 13 health effects literature. And I think the 14 other, these are again more minor comments. 15 There was a discussion about 16 challenges in bone lead measurements because 17 they're normalized to bone mineral content,

18 and that adds a source of error. 19 I think that the physicists that 20 I've talked to about this would say it doesn't 21 add error so much as it, in the context of low 22 bone mineral content, it increases measurement

### 202-234-4433 Neal R. Gross & Co., Inc. Page 192 1 uncertainty because you're just basically 2 generating less data to estimate exposure. 3 So I think that's a slightly 4 different take on it, and I think it is 5 important to acknowledge as part of the sort 6 of QA/QC parameters around some of these 7 different biomarkers that for bone lead in 8 particular, variations in bone status can 9 impact measurements. 10 And I think that relates to my 11 final point, which is that I think there's a 12 fair amount of sexual dimorphism in lead's 13 effects both in terms of biokinetics as well 14 as health effects, which is not as 15 consistently addressed in this document as I 16 think it should be.

17 And that relates both to the nature 18 of bone lead measures in women versus men are 19 quite different, and also that in Section 4.3 20 there's some description of the age 21 relationship, the relationship of age with 22 bone lead that uses the Normative Aging Study,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 193 1 which is obviously a very important study 2 that's contributed a lot to our understanding 3 of the field. 4 But it needs to be acknowledged 5 that the Normative Aging Study is all male, 6 and what we know about the relationship of 7 bone lead to age in women is probably quite 8 different. 9 And so I think it's important that 10 there be, and this is one example, but I think 11 this happens in other parts of the manuscript 12 as well, or the final document, that being 13 sure that the limitations of the information 14 that are being presented are explicitly 15 acknowledged. 16 And that in this case that 17 limitations of information that's 18 predominantly or exclusively in a male 19 population, and the NAS is cited a lot in the 20 document, may or may not apply to women which 21 represent a big portion of the population, and 22 that that needs to be at least acknowledged.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 194 1 There may not be as much data in 2 women, but I think the data that we have 3 suggests that there are going to be 4 differences, and that that's an important part 5 of understanding the health literature that's 6 not as clear as it could be. 7 So that was my comment. 8 DR. FREY: Okay, thank you. Great. 9 Dr. Hays? 10 DR. HAYS: Thank you. So Joel, 11 I'll give you the, what was the term, 12 controversy, that you thought we'd be lacking 13 in this section, or in this charge question. 14 I'll preface my comments by saying 15 that I actually lobbied Aaron pretty hard to 16 let me out of this review. And he was a 17 convincing persuader to make me stay in, 18 because when I thought about this review I 19 thought, what could possibly be new since we 20 just finished the last lead CASAC? 21 So actually I like the organization 22 of the ISA and the fact that you're just

### 202-234-4433 Neal R. Gross & Co., Inc. Page 195 1 dealing with what information is new, and in 2 particular Chapter 4 is really good with 3 respect to that. 4 Having said that, when I started 5 reading the section on lead biomarkers I 6 thought well, now what could be new in the 7 lead biomarkers world that could be needing to 8 be added to this ISA document to let us know 9 what is new and important to consider for the 10 next, starting the next NAAQS? 11 As I started getting through it I 12 actually started to think, see what I thought 13 the motivation behind putting this section in

14 was. 15 And that is, in the last NAAQS 16 review, terms about blood leads being used 17 like concurrent, lifetime average, integrated, 18 lifetime maximum, dose measures, all of these 19 were kind of being thrown out there with I 20 thought little understanding of what they 21 actually meant. 22 So I actually liked the section and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 196 1 I actually like these graphs -- Susan, sorry 2 to contradict you on this -- because it helps 3 to show those relationships between lifetime 4 maximum, concurrent, integrated exposures, 5 blood versus bone and such like that. 6 So I thought it was actually a good 7 exercise, and I think I saw what the 8 motivation for adding it was in terms of 9 helping the epidemiology community to 10 understand kinetics, how bone and blood 11 interplay, how they would interplay with 12 respect to short term exposures over time. 13 And one of the other things that I 14 think we in the epidemiology and risk 15 assessment community have been pretty poor in 16 understanding is intraindividual variability 17 and lifetime profiles of exposures. 18 We're starting to understand that 19 a little bit with respect to short-lived 20 compounds like phthalates. We know that 21 within an individual your levels can vary by 22 a thousand-fold in a day, in an individual.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 197 1 Something like dioxin that has a 2 half-life of ten years, you don't expect that 3 kind of variation. What you have now is going 4 to be what you have in ten years pretty much. 5 Lead is in there in between. You 6 would expect some intraindividual variability 7 over time on the time scale of months to 8 years. 9 And so I think having these kinds 10 of graphs help the epidemiologists and the 11 risk assessment community appreciate that fact 12 that hey, we may be having short term 13 exposures here and that will impact our blood

14 lead levels and our bone lead levels and that 15 those interplay between the two needs to be

16 understood. 17 So actually I liked their section 18 and I liked the graphs and I liked the use of 19 the biokinetic models to help convey that 20 concept. And that's it for my comments. 21 DR. POUNDS: That's controversial? 22 (Laughter.)

### 202-234-4433 Neal R. Gross & Co., Inc. Page 198 1 DR. HAYS: Well, sorry. I like to 2 contradict Susan. 3 DR. KORRICK: Put that way it's 4 fine. I think it's just important, I think 5 there should be some mention of where modeling 6 diverges from empiric data and what that 7 implies. 8 I think it needs to be a little 9 more explicitly reviewed. 10 DR. FREY: All right. Well, I know 11 Dr. Weitzman has been eager to make a comment,

12 and then Dr. Kosnett. 13 DR. WEITZMAN: I just have one I 14 think quick comment, which is variation on the 15 point that you raised. I just point out that 16 we have the same problem in assessing lifetime 17 exposure in children.

18 And whether or not a current 19 biomarker reflects a current exposure or 20 earlier exposure, that same issue applies 21 whether it's in research and regulation or in 22 the care of individual kids.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 199 1 DR. KOSNETT: Thanks. I wanted to 2 offer a few comments on this section about 3 biomarkers. And I'm still going through 4 Chapter 4, so I will have additional comments 5 at some points. 6 But, you know, in Chapter 2, which 7 is a summary which summarized some of Chapter 8 4, there is a statement in there and it said, 9 and I'll read it, it's on line 22. 10 It says, "Blood lead in adults is 11 typically more an index of recent exposures 12 then body burden." And I disagree with that 13 statement because I think that, well it 14 certainly needs qualification, let's put it 15 that way. 16 Because in a lot of the key studies 17 that have looked at the impact of long-term 18 cumulative lead exposure and its implications 19 for adults from environmental settings, like 20 the Normative Aging Study and the Baltimore 21 Memory Study are two, the blood lead 22 concentrations in those subjects were averaged

### 202-234-4433 Neal R. Gross & Co., Inc. Page 200 1 about five. Five micrograms per deciliter. 2 They were people in their 50's to 80's, let's 3 say. 4 And at the same time that those 5 people had blood leads of five on average, the 6 teenagers in the same point had blood leads 7 around one. If you look at, you know, the

8 NHANES Data. 9 And, you know, most and if you look 10 at current environmental exposure to the 11 general population, most of it is coming from 12 food and water. That's actually shown in 13 Table 4-1, which I'll also comment on. 14 So you have teenagers, you know, 15 eating more than anybody and -- well, most 16 people. Maybe not these days. Teenagers 17 certainly on a body weight basis, let's put it 18 that way, seem to consume the most and drink 19 the most. And, you know, their blood leads 20 are one-fourth the values of people who are in 21 their 50's, 60's and 70's, at least there's 22 some suggestion.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 201 1 Some of the studies might be 2 different. The bottom line is, those blood 3 leads in those adults are not reflecting 4 contemporary exposure. They're reflecting the 5 accumulated body burden of lead that came from 6 these folks, who are in their 50's, 60's, and 7 70's who grew up and spent most of their lives 8 prior to the dramatic decline in lead exposure 9 that occurred in the 1980s. 10 Now the implication for this, for 11 the document is very, very substantial. And 12 this goes on to some comments I have on 13 Chapter 5. Because in a lot of places, in 14 discussing the health effects, it implies that 15 blood leads in the range of, you know, two, or 16 three, or four are associated with like renal 17 outcomes, or cardiovascular outcomes, or a 18 number of things. 19 And that is, yes, in that 20 population that was studied at that time, 21 there was associations between the blood lead, 22 but it doesn't reflect their long-term

### 202-234-4433 Neal R. Gross & Co., Inc. Page 202 1 cumulative exposure, which was much higher 2 because most of these folks spent, had lead 3 exposure in the ten to 20 range, or ten to 25 4 range. 5 So anyway, I think that this 6 statement and to the extent that it's 7 reflected elsewhere in Chapter 4, and I don't 8 have the page number, I'm going to have to -- 9 it really, I would suggest it be revised to 10 acknowledge the fact that actually in adults 11 today, you're blood lead is highly dependent 12 on your age, and that is highly dependent on 13 your past cumulative lead exposure. 14 And so I think, to say that blood 15 lead just reflects recent exposure is a 16 mistake, with all due respect. 17 Okay, and then with respect to the 18 biomarker issue, another -- I also want along 19 the lines of what Susan was saying about the 20 models. If you turn to that model, Page 4-49, 21 you know, it shows a very, it depicts a very 22 rapid decline in blood lead.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 203 1 And there's a statement on Page 4- 2 48 that says, "Based on this hypothetical 3 simulation, a blood lead concentration 4 measured one year following cessation of a 5 period of increased lead uptake, which show 6 little or no appreciable change from prior to 7 the exposure event. Whereas the body burden 8 would remain elevated." 9 That, you know, may be potentially 10 true to this isolated inputs to this model, 11 but I tell you, there was, you know, there was 12 a three-fold increase, or a four-fold increase 13 in blood lead between ages 30 to 50, going 14 from two to eight. 15 And then you say within a year it 16 goes back to two, I can not really -- I'm very 17 troubled by that observation. Because I can 18 tell you that if we put, you know, for people 19 in the workforce who had levels in ten to 15 20 range of blood lead, or 20 range, and they 21 worked for 30 years at that level, they are 22 not going to have the same blood lead a year

### 202-234-4433 Neal R. Gross & Co., Inc. Page 204 1 later as people who never worked. 2 So maybe this is a -- this rapid 3 decline only applies with blood leads going to 4 two to eight, but as a general statement to 5 have the narrative suggest that within a year, 6 after 30 years of exposure, your blood lead is 7 the same as it was before your exposure, even 8 when that exposure increased by a magnitude of 9 three or four-fold, is just not what we see,

10 and not what we observed. Go ahead. 11 DR. WEITZMAN: Let me see if I can 12 clarify what you just said. But you describe 13 data that you're familiar with from workers 14 who have been exposed for 20 to 30 years. And 15 in that case their body burden's quite huge, 16 and so you wouldn't expect them to come back 17 down to baseline really rapidly.18 And what this is, is a very short19 term exposure of less than five years. 20 DR. KOSNETT: No, it's 20 years. 21 DR. WEITZMAN: No. This is the, oh 22 right.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 205 1 DR. KOSNETT: It's 20 years. 2 DR. WEITZMAN: Okay, got you, 3 sorry, never mind. My bad. 4 DR. KOSNETT: Okay. I mean it 5 might be -- this simulation may show that if 6 you only go from two to eight, maybe there's 7 not enough.

8 But I don't want the take-home 9 message of the document to be that your blood 10 lead falls within a year to baseline, to how 11 it was after 20 years of higher exposure. 12 Because I know a lot of settings where that's 13 not the case. And I think you -- 14 DR. KORRICK: That's exactly what 15 I was trying to say as well. 16 DR. KOSNETT: Okay. And I had a 17 couple of comments on 4C, but I'll, those are 18 my comments on 4. 19 DR. FREY: Okay. All right, great, 20 well thank you. Other comments on 4B? Okay. 21 Well I think we -- maybe I can take a little 22 crack at what at what I think I heard.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 206 1 I think Dr. Pounds has some 2 comments about terminology and the need for 3 consistency in the use of that terminology, 4 which seems like an important point that needs 5 to carry forward. 6 And we had a lot of discussion 7 about the modeling, and we just touched on it 8 again, so that's clearly an important theme 9 and response to charge question, 4 b. 10 I think there were also some 11 comments about differences by gender and age 12 that might need more discussion in terms of 13 biomarkers. 14 Are there other key points that the 15 discussants, just want to make sure kind of in 16 the high level summary, does that capture most 17 of it or are there other things you think are 18 kind of the top level key points for EPA. 19 DR. KORRICK: Did you mention 20 measurement error, or do you think that's not

21 as -- 22 DR. FREY: Certainly, that's what

### 202-234-4433 Neal R. Gross & Co., Inc. Page 207 1 I wrote down too. So measurement errors as 2 well. Okay. Well it seems like we've 3 probably addressed that for the moment. So 4 why don't we move on then to -- I don't have 5 my agenda in front of me, 4 c. 6 So 4 c, is Dr. Goodrum, Dr. Hays, 7 and Dr. Pounds, and we'll start with Dr. 8 Goodrum. And this is on empirical modeling. 9 DR. GOODRUM: Thank you. So this 10 Section 4.5.1, was air lead, blood lead 11 relationships. It's about eight ages, and it 12 introduces about eight studies I think, I 13 count here for child populations, and one for

14 adult. 15 And I had some specific questions 16 and then a suggestion overall for how to maybe 17 reframe this section. Overall I thought it 18 was really useful the way the Table was put 19 together and there were brief discussions that 20 accompanied each of the sections. 21 Where I think the reader may pause 22 a little bit is in understanding the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 208 1 significance of the slope factors that are 2 presented, which is really what the goal I 3 think is here, of laying out what each of the 4 studies might support in terms of blood lead, 5 air lead ratio, and why those might differ. 6 And to explain a little bit about, 7 to at least introduce the idea that there are 8 difference mathematical models that are used, 9 and that might explain in part some of the 10 differences. 11 So I think all of those concepts 12 came across well, but just a few specifics. 13 It actually starts off by reviewing a 14 Brunekreef, et al. '84, document which was a 15 review document of other studies. 16 And does so to introduce or give an 17 opportunity to introduce a calculation of a 18 slope factor. So I think that's helpful. 19 There is one typographical error which is 20 important, because it may carry through this 21 Section, would be worth doing some just double 22 checking.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 209 1 On Page 479 in that first 2 paragraph, it talks about what the slope 3 factor might be a you move from an air 4 concentration of .15 to 1.5 micrograms per 5 cubic meter. 6 When in fact the study really gives 7 that example with 0.5 to 1.5. And of course 8 that will make a big difference in terms of 9 trying to reproduce that number. It's not 10 reproducible at .15, so I'm quite sure that 11 was not intended. 12 The table itself I think would 13 benefit by reorienting it, landscape and then 14 expanding just a bit the descriptions of the 15 models. Right now there's a lot of 16 information packed into the third column on 17 Model Description. 18 But it's actually missing two 19 pieces of information that I would look for in 20 order to reproduce some results. And that 21 would just simply be the parameters that go 22 along with the model.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 210 1 So for example, if you have a log 2 log fit, you'd be looking for both the slope 3 and the intercept. So if you orient it 4 landscape you'll have a little more room. I 5 know you're probably down to about 7 point

6 font here. 7 The other thing that I thought 8 would be worth revisiting is the very last 9 column which is important, because it's the 10 summary information that's being provided that 11 the reader's being pointed to. 12 And this is, you know, look at the 13 range of slope factors that are generated 14 across these studies, and also understand that 15 that slope factor may vary in these non-linear 16 models depending on where you're looking at in 17 the change of errors. That's a very important 18 concept. 19 I actually couldn't reproduce 20 though some of these numbers the way they were 21 presented. So I believe the footnotes right 22 now say that, at a specific concentration of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 211 1 .15 and one microgram per cubic meter, this is 2 what the slope factor would be. 3 But just as an example of 4 Brunekreef, you actually need to present some 5 interval, I think change in order to describe 6 what that slope factor is. So I wasn't able 7 to reproduce any of those numbers, or trace 8 them back to the original citations. 9 The overall suggestion that I would 10 have, just thinking about how might use this 11 information, then moving forward. So we 12 understand that because of the complexities 13 and the different studies, they measure 14 populations that had different blood lead 15 levels, and different air lead levels, 16 particularly acknowledging that the air lead 17 levels that the models were developed from 18 only in just a few cases overlap even the 19 existing standard of .15. 20 So we're really talking about a 21 series of models and slope factors for which 22 there mainly developed on kind of the upper

### 202-234-4433 Neal R. Gross & Co., Inc. Page 212 1 end of what the air concentrations going to 2 be, and that has implications for the slope

3 factors. 4 So to avoid I think what is 5 ultimately a trap, because of the limitations 6 and the available data of declaring all of 7 these slope factors to be uncertain, would be 8 to recast this section as, you know, here's 9 supporting information that gives a variety of 10 slope factors. They're going to differ for 11 these different reasons and we understand 12 that. But for decision making it helpful to 13 understand that if you slope factors fall 14 within a certain range, that has implications 15 for what the change in the geometric mean and 16 geometric standard deviation blood lead would

17 be. 18 So I put together just a few 19 graphics to illustrate that. And I have one 20 multimedia presentation here. Okay, so just 21 three graphics. So I thought I would just 22 spend a minute, because these are in my

### 202-234-4433 Neal R. Gross & Co., Inc. Page 213 1 comments in case they're not clear what I was 2 trying to suggest. 3 So on the x-axis here, this is just 4 again those series of slope factors. I chose 5 just to from one to nine. Some of those slope 6 factors go even higher. So this would be the 7 change in blood lead that you would expect per 8 increment or per one microgram per cubic meter 9 change in the air standard. 10 So if we think about the fact that 11 we're at .15 right now, of course we can't 12 change by one, we're going to change by some 13 small increment of one, so it's helpful to 14 recognize that as we evaluate potential 15 alternative standards. 16 Maybe more conservative standards 17 going from .15 and in this case to .10, this 18 is what the implication would be based on 19 these different slope factors. 20 And so the y-axis just tells you of 21 the blood lead distribution statistics. 22 You've got two lines here assuming it's log

### 202-234-4433 Neal R. Gross & Co., Inc. Page 214 1 normal with a GSD of 1.6, the slope factors 2 will translate into a incremental change in 3 your geometric mean below .5 micrograms per 4 deciliter, and then at the 95th percentile 5 below one. So that maybe helpful to

6 understand. 7 And then you can do the same 8 exercise again for alternative metrics. So if 9 you can go down to Figures 2 and 3. 10 So Figure 2 is the exact same 11 exercise, but this time going from .15 to .05, 12 and you can see now we've got a slightly 13 larger change that we're asking you to 14 evaluate. And the corresponding changes in 15 blood lead get higher. 16 And then I just ran one more going 17 from .5 to .015, so in order of magnitude18 difference. So just for clarification, the y19 axis isn't the predicted blood lead 20 distribution, it's just the change that we 21 would expect given the slope of the 22 empirically derived slope factors that fall

### 202-234-4433 Neal R. Gross & Co., Inc. Page 215 1 within these ranges. 2 This would be the change in the 3 geometric mean above and beyond baseline, 4 above and beyond the other contributions. So 5 this may, to the extent that these models are 6 predictive and, you know, you need to look at 7 the R-squares, and understand sample size and 8 all of those things. 9 This gives you some way of kind of 10 framing, you know, how these data, and then as 11 additional reviews happen, as you collect more 12 data down the road, it may or may not fall 13 within these ranges. 14 DR. KOSNETT: So this is in 15 children? 16 DR. GOODRUM: This is, well you 17 could look at alternative slope factors for 18 adults and run the same exercise. 19 DR. KOSNETT: Yes, but this is in 20 children using IUK? 21 DR. GOODRUM: No, this is just 22 simply using the assumption of a log normal

### 202-234-4433 Neal R. Gross & Co., Inc. Page 216 1 distribution. 2 DR. KOSNETT: Oh, yes, got you. 3 DR. GOODRUM: Yes. So with an 4 incremental, because what we have with this 5 slope factors tells us that an incremental 6 change in air lead corresponds to an 7 incremental change in blood lead. 8 DR. KOSNETT: Right. I got you. 9 DR. GOODRUM: The other point as I 10 was trying to put this exercise together, 11 you'll see, I assume that the ratio that was 12 referred to here was the geometric mean. And 13 that's worth clarifying. 14 And you can get wrapped around the 15 x a little bit as you take log tranforms on 16 what actually, when you back-transform, you're 17 getting the ratio of. Is it the ratio of the 18 geometric mean? Or is it the ratio of the 19 arithmetic mean blood lead. And so I don't 20 have anything definitive to say because I 21 didn't seriously investigate each of the 22 primary studies.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 217 1 But I would just encourage you to 2 go back and really make clear whether you're 3 talking about the ratio based on the change in 4 the geometric mean or the arithmetic mean, 5 because of course that has implications for 6 these hypothetical log normal distributions. 7 And it's probably worth even having 8 a description, a section short enough you 9 could have a paragraph description just 10 pointing out that in some cases, these studies 11 may be more representative of an predicted 12 arithmetic mean change in the population 13 rather than geometric mean change. And Chris, 14 I think that's it. 15 DR. FREY: Okay. Great, thank you 16 very much. Let's see Dr. Hays. 17 DR. HAYS: I actually like Section 18 4.5, it was nice to see more blood versus air 19 correlations. In that last NAAQS, we kind of, 20 instead of like in the 11th hour switched to 21 the empirical model over the IEUBK model, and 22 I think we had one may slope factor, maybe two

### 202-234-4433 Neal R. Gross & Co., Inc. Page 218 1 that we relied on. So it was nice to see more 2 put into this document. 3 What I'd like to see is how the 4 results from these other slope factors compare 5 to the one that was relied upon for the last 6 NAAQS to see how that difference might be 7 between the previous approach and these

8 models. 9 The other thing that struck me was 10 that, what would be very helpful is to take 11 Table 4-11, and convert it into a figure in 12 which you plot the slopes of these lines, 13 blood lead versus air lead, and only show the 14 line for which the air concentrations were 15 valid for that study. 16 And show how they all compare 17 across each other on a linear linear scale, on 18 a log log scale, on a log linear scale, 19 however you want to do it. I know it's hard 20 because they're going to be all over the 21 place. 22 But show what air ranges their

### 202-234-4433 Neal R. Gross & Co., Inc. Page 219 1 relevant for, their applicable for, because 2 these kinds of correlations really start 3 getting wacky on the tails. And when you 4 start trying to extrapolate, especially down 5 to these lower regions, a lot of these 6 correlations are not valid. 7 And so, you know, make that 8 apparent through a figure to show where 9 they're applicable for and where they're not. 10 And it may be that none of them are applicable 11 for the range at which we're considering for 12 the NAAQS here between .15 and 1.5. But that 13 needs to be made very apparent and 14 transparent. 15 The other thing is you could code 16 those by the factors that Phil mentioned. For 17 instance, whether the ambient air was a 18 function of the exposure type, like was it a 19 smelter community? Was it a urban community? 20 Was it a gasoline phaseout population study? 21 All of those are going to have very 22 different exposure characteristics and that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 220 1 may help explain the difference between them. 2 And the particle size for the air sample 3 collections because that definitely would have 4 an impact as well. 5 I had another comment on an earlier 6 section of Chapter 4, and maybe I should've 7 said something in the discussion of 4 a. 8 But one of the things I've been 9 frustrated by in the last NAAQS and this NAAQS 10 as well, or this discussion as well is that 11 it's not east to tell from these exposure 12 chapters how much of a role air plays in the 13 given blood lead levels that we're 14 experiencing in the U.S. today. 15 What is it contributing? Is it 16 five percent, is it 30 percent, is it 50 17 percent, is it 70 percent, what is it? 18 You know, I'd love to see a pie 19 chart that says for a given blood lead of one 20 micrograms per deciliter, five percent is due 21 to air, 30 percent is due to diet, 40 percent 22 is due to water, whatever that is, I'd love to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 221 1 see that. 2 And how does that change as a 3 function of blood lead. And maybe that's too 4 simplistic. And I know it's hard because lead 5 is such a multimedia contaminant and, you 6 know, I'm going to be with Philip on this one. 7 You know, maybe lead doesn't need 8 to be in the NAAQS anymore, because it's just 9 so multimedia and I think air is playing such 10 a minor role now. 11 But I'd love to see that in this 12 exposure chapter. What role does air play for 13 the given blood leads we're experiencing, and 14 as a function of blood leads. 15 Is it that the higher exposure kids 16 that have, or adults that have leads of five, 17 that all of sudden air's becoming a more 18 important player there. 19 Or is it the opposite, that it 20 really has no role whatsoever at those higher 21 levels. Is it all just dust, or diet at that 22 level. So that's it, that's my comments.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 222 1 DR. FREY: Okay, thank you. Dr.

2 Pounds? 3 DR. POUNDS: This was an easy 4 section to read like the rest of Chapter 4, 5 and my comments are editorial. 6 DR. FREY: Okay. All right, great. 7 Well then that opens us up to other members of 8 the panel on Charge Question 4c. Yes, Dr.

9 Kosnett? 10 DR. KOSNETT: I had a question or 11 a comment on the section about the air 12 lead/blood lead relationships, you know, which 13 is really very critical to this whole 14 exercise. 15 And when I read the summary in this 16 section, which I guess is on, what page is 17 that on? Well the page that summarizes the 18 relationships between blood lead and air lead. 19 Maybe it was --

20 PARTICIPANT: It's towards the

21 back. 22 DR. KOSNETT: Yes, it's on Page 4-

### 202-234-4433 Neal R. Gross & Co., Inc. Page 223 1 97.

2 PARTICIPANT: Yes. 3 DR. KOSNETT: I think it would be 4 helpful for the EPA for this section, to try 5 to do a more critical analysis of which of 6 these slopes, bears the most evidence, you 7 know, or what's most relevant to the levels 8 that we're facing. 9 Because Phil, what you just showed, 10 now I understand it. I was off on -- I don't 11 know why I missed that first point, but now I 12 see what you said. I mean you really 13 basically showed how for a different magnitude 14 of air reduction, you'll get a change in blood

15 lead. 16 And depending on the slope, there's 17 a substantial difference. So the key question 18 that emerges, which is the right slope? 19 DR. GOODRUM: Or what range of 20 slopes are represented. 21 DR. KOSNETT: Or which range of 22 slopes are representative, and I hope, I don't

### 202-234-4433 Neal R. Gross & Co., Inc. Page 224 1 know the answer to that. 2 But I hope if you can potentially 3 take this Section 4-7.4 which is on 4-97, it 4 doesn't really give me, you know, when you're 5 finished reading that you don't come away with 6 an opinion as to what, it's not like a 7 critical analysis of what do you think. And 8 to the extent you can help us with that, I 9 think that is very important. 10 You know, you say that some of the 11 differences might reflect model selection by 12 the investigators. Maybe you can run 13 different models and diagnostics, you've got 14 the world's expert over here, Dr. Rothenberg 15 (phonetic) on that, on looking at models and 16 diagnostics, and things like that. It would 17 be helpful to do that. 18 Then I had another question and it 19 kind of, or a point, it kind of follows what 20 Sean just said, and that is, the issue of the 21 contribution of air lead to food. 22 You know, I was really struck, it's

### 202-234-4433 Neal R. Gross & Co., Inc. Page 225 1 very interesting when you look at Table 4-1, 2 can you put that up? It's on Page 4, is it 4- 3 4? Yes, Page 4-4. If you can put it on that, 4 oh, I don't know. 5 If you look at the relationship 6 between, it's a table that's interesting 7 because it basically shows the contributions 8 to humans of lead from various sources. 9 And I don't know, I'm curious if 10 this is the best data and the most recent data 11 that exists. It very well may be. I mean I 12 know that back in the 80s, the average blood 13 lead estimate in the United States was quite 14 a bit higher than about ten, I guess I think 15 closer to 30, or 40, or 50, in that range. 16 But what you see here is that by 17 far, by far for the average person, I'm not 18 talking about a child living in a, you know, 19 with leaden dust, but by far for the average 20 person, it's dominated by lead in food and 21 beverage intake. It's estimated to be ten 22 micrograms per day.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 226 1 If you look at the air levels 2 there, at the top and you multiply them by, 3 like an adult breathing in 20 cubic meters a 4 day, that's about right, right? You know, you 5 get .3 micrograms, or point, yes about .3 6 micrograms at the medium, or .4 micrograms, 7 compared to ten micrograms in food and diet. 8 So diet, it's like extremely 9 important. So the question that emerges, how 10 did that lead get into the food and beverages, 11 you know? 12 And some of that is probably a 13 consequence of the fact that air lead, you 14 know, gets into the ground and into the food 15 supply ultimately. And long-term will 16 influence, you know, what that number is. 17 And I'm just curious, and I don't 18 know that the document really addresses this 19 or answers it, but I think it has policy 20 implications. 21 If the average person is getting 22 about ten micrograms a day, ten to 12

### 202-234-4433 Neal R. Gross & Co., Inc. Page 227 1 micrograms a day, let's say, or ten micrograms 2 a day. And the average blood lead in the 3 United States now is about 1.5 micrograms per 4 deciliter. 5 If we cut our air lead emissions 6 any further or we change the standard, will 7 that number go down? This is the kind of 8 thing that you were raising Sean. 9 Because that number, that ten is 10 what's driving most of the blood lead in the 11 United States today for the average American. 12 And I'm just curious, how much 13 would that number go down, even if it's not in 14 the short-term, but if it's in the long-term. 15 Now I notice tomorrow we're talking about the 16 modeling with recent lead and then past lead. 17 And unfortunately for the various 18 limitations, you don't look, you just 19 consider, you don't consider the effect of air 20 on food and water, you consider that 21 background. 22 And we're not modeling that in our

### 202-234-4433 Neal R. Gross & Co., Inc. Page 228 1 exercises. And I understand the difficulty, 2 at least in the short run. But I'm just 3 wondering in the long run, if anything we do 4 to air going to change that ten. 5 Because that ten micrograms a day 6 is what's keeping most of us with a blood 7 lead, well those of us under 50 maybe. The 8 younger people among us are keeping the blood 9 leads of, you know, one to two. 10 And until we lower that ten, we're 11 not going to get much lower than that. And 12 I'm just wondering, does air have an influence 13 on that. And I don't know the answer, and I 14 wish the document could shed light on that to 15 a certain extent. Because I think that from 16 a policy perspective, that's a very important 17 question. That was my comment. 18 DR. FREY: Okay, great. Other 19 comments on 4c, or 4 more generally? Okay. 20 DR. von LINDERN: This has helped me 21 to organize some of my thoughts. I thought 22 those were great comments.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 229 1 DR. FREY: Can you use the 2 microphone, please? 3 DR. von LINDERN: The pie chart 4 part though, that is going to vary by every 5 situation in the country as to how much is 6 relative to air, relative to the other 7 sources. And the food certainly plays into it 8 big. 9 I guess part of what bothers me is 10 we don't know what those situations are in the 11 country. We're going to model a few of them 12 in this risk assessment process, but how do 13 those apply across the U.S. 14 So I'd love to see what you want 15 Sean, but I think we can only get it probably 16 from these modeling exercises, and they're 17 hypothetical. And we do have a major data gap 18 in how applicable are those hypothetical 19 situations we're going to model to the overall 20 situation in the country. 21 And then the one other thing you 22 have to throw in is that it's not only by

### 202-234-4433 Neal R. Gross & Co., Inc. Page 230 1 site, but it's by population. Because there 2 may be specific populations that have 3 different ingestion patterns that will 4 influence that as well. 5 DR. FREY: Okay. Just looking at 6 the clock we're a little bit behind schedule. 7 So I would propose to move onto the next set 8 of Charge questions on number 5. 9 And there are five subparts which 10 we've grouped into three categories. The 11 first category is 5a and 5e, which relates to 12 modes of action and dose response, and those 13 seem somewhat related to group them together. 14 So the discussants for that are Dr. 15 Cory-Slechta, and Dr. Hays, and of course, Dr. 16 Canfield couldn't be here, and he was another 17 one of the assigned discussants. So I'd like 18 to turn the floor over to Dr. Cory-Slechta on

19 5a and 5e. 20 DR. CORY-SLECHTA: Okay. I'm going 21 to make some comments first about the mode of 22 action, which I thought was a great addition

### 202-234-4433 Neal R. Gross & Co., Inc. Page 231 1 to the document. And I thought it was 2 generally pretty clearly written. I have a 3 few specific things I think need to be talked

4 about. 5 One are studies on oxidative 6 stress, and these are cited throughout the 7 document and they're cited in the mode of 8 action. Unfortunately, the studies aren't 9 really described in enough detail, at least to 10 the reader to come to the conclusion that 11 you're really reducing or reversing oxidative

12 stress. 13 Because one of the things that 14 could be going on and is not really discussed 15 in this section, is whether or not the agents 16 that are being given, and I don't know what 17 the time frames of all of these were, what the 18 specific design was. Are they altering 19 toxicokinetics? 20 So to me if something is simply 21 blocking the uptake of lead, and thereby, 22 reducing the level of oxidative stress, that's

### 202-234-4433 Neal R. Gross & Co., Inc. Page 232 1 just changing the dose of lead so to speak. 2 I don't consider that to be 3 essentially a mechanistic study showing 4 oxidative stress is reversing an effect. And 5 there are lots and lots of descriptions of 6 studies in there that I couldn't interpret as 7 necessarily reversing oxidative stress. 8 Because the designs are not spelled 9 out enough. If you've given lead exposure, 10 generated oxidative stress, and then give 11 something that reduces it that's one design

12 where I can see that. 13 But unless you can show me that it 14 didn't change the uptake, or the blood lead, 15 or the brain lead concentration, I don't 16 necessarily know that it was working by 17 reducing oxidative stress, per se, as opposed 18 to having a toxicokenetic influence. 19 So I think you have to be careful 20 about how you interpret that kind of data, 21 unless you look at the specific design. 22 One of the other things that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 233 1 troubled me reading this was there's a lot of 2 studies of in vitro lead exposures, which 3 clearly have their place. But there's lots, 4 and lots of descriptors in there of levels, 5 concentrations used with the phrase, "as low 6 as," and then saying things like one 7 micromolar, or five micromolar. I don't think 8 we even considered one micromolar to be low, 9 and even cases where it says, as low as five, 10 just kind of like, no. 11 So I would suggest deleting those 12 because they're not considered low. Or at 13 least deleting those and maybe putting them in 14 some kind of context. 15 So I think what's really hard, 16 especially for somebody who doesn't know that 17 literature, is to try to relate in vitro 18 exposures to in vivo, what is that? Can you 19 provide some kind of a scale? 20 And I say this recognizing that 21 these are really supportive more than anything 22 else. But they feature prominently in the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 234 1 mode of action section. So I think that 2 deserves some consideration. 3 I think one thing that doesn't 4 belong in this document, and I think we'd all 5 agree is never going to happen, there are 6 statements made and they're not necessarily in 7 the mode of action, they're in other sections

8 as well. 9 Based on biochemical changes, I 10 think one of them related to synaptic 11 plasticity, I can't remember what. Suggesting 12 that as I remember, glutamatergic angonist, or 13 antagonist, or something might be used 14 therapeutically for lead. 15 I can't imagine anybody would ever 16 think about using compounds like that in low 17 blood lead levels, not even maybe high blood 18 lead levels. And I just don't think they 19 belong in the document. 20 So I think anything therapeutically 21 that's based on some biochemical or molecular 22 site, and come back and talk about kelation,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 235 1 probably doesn't belong in the document. 2 Kelation is a different issue. Which actually 3 isn't talked about all that much, but I'm not 4 sure that it belongs here anyway. So those 5 will be my statements about the mode of 6 action. 7 With respect to the dose response, 8 I think the non-linear nature has clearly been 9 supported by a lot of additional data that has 10 come out since 2006. I don't have any quibble 11 with that.

12 In reference to some comments that 13 were made earlier in the day, it's clear that 14 not all studies are going to be able to 15 demonstrate that non-linearity. Because first 16 of all, they're going to have very different 17 power in terms of detecting effects. 18 And secondly, one thing that kind 19 of gets left off the table here, they use 20 different endpoints. And those endpoints 21 differ in their sensitivity and ability to 22 pick up those kinds of effects.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 236 1 So, you know, even something like 2 IQ. If you have an average IQ in a population 3 that's 70 or 75, how much lower can you go as 4 opposed to starting out at 90 or 100. So you 5 already have a floor effect. 6 But I think we need to remember 7 that not every study is going to have the 8 ability to detect those kinds of effects. So 9 for 5a and e, I'll stop there. 10 DR. FREY: Okay, thank you. Let's 11 see, Dr. Hays? 12 DR. HAYS: My comments are pretty 13 brief on these two Charge questions. With 14 respect to the mode of action question, unlike 15 Chapter 4, this chapter kind of seemed to 16 review the scope of the world with respect to 17 mode of action. 18 And I didn't get a good 19 understanding as to why that was necessary, as 20 opposed to what was just new. Maybe you had 21 objectives that just weren't spelled out 22 clearly.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 237 1 In particular, Table 5-2. If you 2 look at that table, one of the things that 3 struck me is that, I don't know if you can 4 bring that up?

5 PARTICIPANT: 541.

6 DR. HAYS: 541?

7 PARTICIPANT: Yes. 8 DR. HAYS: Thank you. Let me get 9 there myself. It appears from this table that 10 all effects associated with lead, ranging from 11 altered ion status to cell death and 12 genotoxicity are equally potent. Are equally 13 potent. And I don't think we think that from 14 the toxicology perspective. 15 Not all those are equally potent 16 outcomes associated with lead toxicity, so I 17 think this Table is pretty misleading. You 18 need to include more information if you want 19 to try to compare the potencies of these 20 various endpoints. 21 (Off the record comments.) 22 With respect to the non-linear

### 202-234-4433 Neal R. Gross & Co., Inc. Page 238 1 section, I actually really liked this section. 2 The discussion about the dose response 3 relationship between blood lead and IQ deficit 4 in children. 5 And in particular, Lanphear Study, 6 and debating whether it was log linear or 7 linear linear or piecewise linear, was a big 8 debate in the last NAAQS. And so I think this 9 section actually helped me because I was one 10 of the doubters of that log linear dose 11 response relationship. 12 And so having other lines of 13 evidence that could help explain that 14 relationship was helpful for me, so I 15 appreciated that and I liked that section. 16 That's it for my comments. 17 DR. FREY: Yes, go ahead. 18 DR. CORY-SLECHTA: I just want to 19 follow-up on one thing I think Sean just said, 20 and this belongs in the section on integration 21 as well. But one of the things I always 22 struggle with because I do both human and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 239 1 animal work is the human folks are always 2 looking for some direct correlation in the 3 animal literature of a non-linear slope, to 4 what you see in humans. 5 But physiology doesn't work that 6 way as we all know. And I think it would be 7 really useful to in fact, state that. That, 8 you know, we have huge amounts of evidence of 9 non-linear dose effect curves in the tox 10 literature. 11 There not necessarily going to look 12 exactly like the non-linear slope in IQ. 13 Because they don't directly translate, and 14 they wouldn't reflect human physiology if they 15 did. 16 So I think it would be really 17 useful to put that in there, and maybe start 18 getting this point across. 19 DR. FREY: Great, thank you. I'm 20 tempted to maybe just go forward with the lead 21 discussants on all subparts of 5, and then 22 come back to the panel. Would anyone object

### 202-234-4433 Neal R. Gross & Co., Inc. Page 240 1 to that? I think it might -- 2 DR. CORY-SLECHTA: Well then do you 3 want us to go through? I have comments. Do 4 you want us to just go through them? 5 DR. FREY: Well I'm mindful that 6 we're a bit behind schedule. So what I want 7 to do is go with the lead discussants on 5b 8 and 5c, and then on 5d, and then we can come 9 back and discuss anything we didn't otherwise 10 catch. So on 5b, and 5c, Doctors Kosnett, and

11 Wasserman. Dr. Kosnett? 12 DR. KOSNETT: One of the key 13 Charges to 5b is, does the ISA adequately 14 describe the evidence with regard to the range 15 of exposure concentrations, and/or blood or 16 bone levels associated with the identified 17 endpoints. All right. 18 And I think that the document, in 19 some places doesn't do that adequately. For 20 the reason being, that it attributes certain 21 blood lead concentrations less than five, 22 maybe on the order of two or three blood lead

### 202-234-4433 Neal R. Gross & Co., Inc. Page 241 1 concentrations, two micrograms or whatever, to 2 being sufficient to cause some of the 3 endpoints that have been observed based on 4 certain studies. 5 Let me be more specific. There's 6 evidence in certain studies, like some of the 7 NHANES studies that if you have a blood lead 8 going from two, to three, to four, like Dr. 9 Muntner's studies, that you increase 10 cardiovascular mortality. 11 Okay, that's observed yes, in that 12 study but the implication that if you just had 13 for your whole life a blood lead concentration 14 that went from two to four, that you would 15 have, you know, 20 or 30 percent increase in 16 cardiovascular mortality can't be devined from 17 Muntner's studies because those are conducted 18 in people who are middle-aged to older for the 19 most part. I mean if the NHANES, you realize 20 the NHANES population, half of them were born 21 before 1950, in the NHANES database. 22 So these people may have blood lead

### 202-234-4433 Neal R. Gross & Co., Inc. Page 242 1 concentrations of two, or three, or four now,

2 but that doesn't mean that a blood lead 3 concentration of two, or three, or four is 4 sufficient to have caused them to have this 5 increase in mortality. And I think the 6 document would benefit by highlighting that. 7 Similar thing occurs in the renal 8 section as well. And it applies basically to 9 almost the endpoints as they apply to adults.

10 Because a lot of the effects that have 11 occurred that we're witnessing in adults, are 12 associated with cumulative lead exposure, that 13 includes substantially higher blood leads. 14 Even not withstanding the fact that right now

15 the blood leads are low. 16 I think that was recognized well in 17 the document we're going to talk about 18 tomorrow. But I don't think it was as clearly 19 specified or spelled out in this chapter. 20 And, you know, if you look at the 21 tables, some of the tables, you know, talk 22 about changes in blood pressure, or changes in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 243 1 renal function at, you know, one microgram per 2 deciliter. 3 But the problem with that is the 4 data don't show that if you just had exposure 5 that can find you to having blood leads of one 6 or two, that you would see those effects. 7 I hope I'm not repeating myself, 8 but I think is a major concern that I had with 9 respect to how the range of effects were 10 presented. 11 DR. FREY: Okay. Was that it for

12 5? 13 DR. KOSNETT: For 5b, yes. 14 DR. FREY: Okay, and 5c? I think 15 we're talking about 5b and c. Did you have

16 comments on c? 17 DR. KOSNETT: Should we expand the 18 endpoints? No, I think you covered the 19 waterfront on the endpoints. 20 DR. FREY: All right, Dr.

21 Wasserman? 22 DR. WASSERMAN: I'm speaking mostly

### 202-234-4433 Neal R. Gross & Co., Inc. Page 244 1 about the effects on neurocognitive outcomes, 2 but I think this is true of other outcomes. 3 Throughout this chapter it's not 4 really clear what the clinical significance of 5 the effect sizes that we're talking about 6 might be. And this is really the case for, 7 certainly clearly the case for the -- like the 8 IQ effects. 9 If we're talking about a point or 10 a half a point, or a third of a point, that's 11 something that's really just not going to be 12 of any -- much clinical significance.

13 So we need to have some sense of 14 how much of an effect, whether it's in the 15 renal system or the neurocognitive system, is 16 meaningful from a clinical standpoint. 17 If you keep in mind, maybe some 18 discussion then of the metrics of IQ 19 assessment is important to keep in mind if 20 you've got a standard error of measurement and 21 an IQ test of five points. 22 Which means if I assessed the same

### 202-234-4433 Neal R. Gross & Co., Inc. Page 245 1 child twice over two days with the same, 2 pretty much the same test, and the same child, 3 and the same investigator, I could get a score 4 that's five points different. 5 So it means that the one or two 6 point difference is not really discernable in 7 terms of walking around skills that we would 8 see in a child. 9 And I think while we can identify 10 yes, there is this effect, if you're going to 11 translate this into policy, ultimately what is 12 the added value of reductions down at this 13 level, has to be taken into some 14 consideration. 15 And I think there's some mention 16 here in this section, but it gets more 17 specifically, the case with some of the other 18 documents that spin off this Chapter 5, when 19 we're talking about points lost being a half 20 an IQ point. 21 I mean as a psychologist I will 22 tell you that it makes my skin crawl. There

### 202-234-4433 Neal R. Gross & Co., Inc. Page 246 1 is no such thing as a half a point, a third of 2 point being lost, it doesn't get measured that 3 way. 4 I think that also the presentation 5 here, because there are so many health 6 outcomes, and I think certainly I wouldn't 7 want to expand their range. 8 I would really like to see some 9 cross-talk increased in terms of, these are 10 all presented as though we have sort of 30 11 independent outcomes. And the outcomes are 12 quite related in some regard.

13 And I'm not sure I understand how 14 they would be, but some discussion perhaps of 15 how we go from ion transfer differences to 16 then IQ points, would be useful. Or how the 17 cardiovascular effects might also reflect or 18 be captured by further downstream behavioral 19 and intellectual functions, would be useful. 20 And as a smaller note, even when 21 we're talking about the cognitive functions, 22 again, they're all presented as though they're

### 202-234-4433 Neal R. Gross & Co., Inc. Page 247 1 at the same level. And some of these 2 obviously interrelate. 3 So that if we know we're going to 4 see a compromised intellectual function, if we 5 know we're going to see behavioral 6 disturbance, it should come as no surprise 7 that we're going to see academic difficulties 8 or grade achievement difficulties. 9 So these things all interrelate 10 with each other in some ways that really would 11 be useful to be described. 12 I think that it's important to, 13 where we know that there's things that need to 14 be, that there are confounders of the IQ 15 outcome -- the exposure outcome relationship. 16 It would be nice to be more consistent about 17 describing what those are, so that in some 18 instances the behavioral literature is 19 discussed and it's not clear to me whether or 20 not all of these papers are adjusting for 21 other things that might be important in that 22 relationship.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 248 1 Probably we don't want to mention 2 every single thing that everybody ever has 3 adjusted for, but some description of what 4 those might be, or what key features should 5 need to be held aside when looking at that 6 outcome, might be useful. So that the reader 7 can better evaluate the quality of all of 8 these things as they interrelate. 9 I have a semantic disagreement with 10 the use of the term neurological to describe 11 this entire section. These are really not 12 neurologic outcomes or they are, but they're 13 not only neurologic outcomes. 14 They really are nervous system, 15 central peripheral nervous system outcomes. 16 Most of us don't publish in neurological 17 journals. These are neurobehavioral, 18 neuropsychological, neurocognitive, they're 19 more functional than they are structural. And 20 I know that's a carryover from earlier 21 documents, but these really are not, that's 22 just jarring me to read.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 249 1 Again, there's lots of examples of 2 places where I think the document would be 3 helpful in providing cross-talk. For example 4 the behavioral effects seem to be in one 5 domain for children, and a totally different 6 domain for adults. What does that mean? 7 Kids with increased blood leads 8 typically show increased, what we call 9 externalizing disorders, like acting out, 10 oppositional, impulsive behavior. Adults with 11 elevated levels, the most consistent report is 12 for mood disturbance and depression. 13 How is that possible? I can 14 speculate, but it might be at least important 15 to document or to say to the reader, we don't 16 know how we get from a to b, but effects are 17 very different across the lifespan. I think 18 it's important to make note of that. 19 What else? Let's see. Oh that, 20 the table that talks about specific indices of 21 cognitive function. There's my point that 22 many of these things are the components for

### 202-234-4433 Neal R. Gross & Co., Inc. Page 250 1 the underlying substrate of what's there when 2 we look at IQ. 3 But also included in that table are 4 the studies of infant developmental outcomes, 5 the Bayley's Scores, which really aren't, 6 we're talking apples and oranges here. 7 These are not specific functions in 8 infants, they are sort of the developmental 9 equivalent of an IQ, but scaled down to 10 babies. So they don't really map really well 11 onto the other elements that are in that 12 table, Table 5-4. 13 And we know that early 14 developmental scores are far less stable over 15 time in terms of measuring IQ, so it's not a 16 surprise that the effect sizes look a little 17 bit different when we look at the Bayley's 18 scores then other indices of cognitive 19 function. 20 So again, I would be happy of there 21 was some way to have greater cross-talk to 22 explain how we get this wide range of, either

### 202-234-4433 Neal R. Gross & Co., Inc. Page 251 1 the nervous system outcomes, or to go from one 2 kind of outcome to another, if that's 3 possible. And I had some specific comments, 4 but those are probably easier dealt with else 5 wise. 6 DR. FREY: Okay, great, thank you. 7 All right, let's go to 5d. And for this, the8 lead discussants are Doctors Korrick, Cory9 Slechta, and Kosnett. So, start with Dr. 10 Korrick. 11 DR. KORRICK: Okay. I think 12 there's probably going to be some overlap in 13 this Section with the previous Charge 14 Question. 15 So I think, I'll focus I guess on 16 the balance between the toxicologic and 17 epidemiologic literature. And I think as a 18 sort of epiphenomenon, making sure that both 19 streams of knowledge are optimally presented. 20 I think it's very important to 21 they're being well integrated. And I have 22 some general comments on that issue and then

### 202-234-4433 Neal R. Gross & Co., Inc. Page 252 1 some specific comments from my written 2 submission that I won't go into. 3 But I think, depending on the 4 particular health measure that's being looked 5 at in this section, I think some sections are 6 better than others at identifying and 7 prioritizing studies.

8 So there's a lot of tables that 9 indicate a long laundry list of studies in a 10 particular area and affect estimates. But the 11 text isn't always very helpful in 12 prioritizing, and I think that's an important 13 piece that needs to be in this Section. 14 Some of those studies have design 15 limitations that are pretty substantial, and 16 some are just inherently probably more 17 valuable, of longitudinal studies probably 18 better off than a case-control study, which is 19 better off than a case series. 20 And some studies can be better at 21 controlling for confounding than others. And 22 I think that degree of analysis in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 253 1 interpreting the literature is not 2 consistently represented in this Section. 3 And it's critical, because before 4 you can make inferences from this long laundry 5 list of studies, you need to be able to tease 6 out which information you think should be 7 given more weight, and understanding the 8 underlying conclusion. 9 And I think that's missing in a lot 10 of cases. And actually, specifically saying 11 that, you know, that the interpretation of 12 this body of literature is the following based 13 on the weight that we give to studies that we 14 feel are more robust. So that's one issue 15 that I think needs to be cleaned up a little 16 bit. 17 And then also I think sort in 18 keeping with that and apropos of my earlier 19 comments, oftentimes it looks as if there are 20 a large number of studies on a particular 21 topic, when in fact, a substantial portion of 22 what's presented is variations on analyses in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 254 1 one particular population. 2 Again, the Normative Aging Study is 3 a good example, or NHANES where most of our 4 knowledge on a particular area comes really 5 from only two types of studies. 6 And although, those studies have 7 done a lot of good work, again, I think 8 interpreting findings and interpreting the 9 weight of evidence, it's important to keep in 10 mind if evidence is coming from a relatively 11 limited set of studies, because that impacts 12 implications that can be made about robustness 13 and reproducibility. 14 And I think, so in terms of the 15 animal data, I'm not obviously an animal 16 person, but I think there are ways in which 17 analogous issues with presentation of 18 toxicologic data, both in vitro models as well 19 as animal models, that would help make the two 20 data streams more cohesive. 21 For example, I appreciate that the 22 way that animal dosing is done is very

### 202-234-4433 Neal R. Gross & Co., Inc. Page 255 1 different than the way humans are typically 2 exposed. But where the animal dosing 3 component of an experiment can be explained in 4 a context that helps figure out how to relate 5 it to humans would be useful. 6 So for example, there are studies 7 in the neurological outcomes section that 8 expose animals to lead through direct 9 hippocampal injection. Well, you know, that's 10 really the interesting from perhaps a 11 mechanistic point of view, but it probably has 12 very little relationship to human exposure, if 13 not, you know, very limited. 14 And so how to interpret that as 15 this sort of evidence of neurologic effects 16 that help us understand health effects in 17 humans, is very problematic for me. And I 18 think there needs to be more critical 19 acknowledgment of that in the summaries of the 20 toxicological literature. 21 When you have direct hippocampal 22 injection, this may or may not be that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 256 1 relevant to our understanding of human studies 2 and not, you know, others who are animals, 3 experts I'll defer to, but I have a little 4 trouble with that. 5 I think the other thing that 6 happens is that the form of lead in the animal 7 studies seems to me potentially relevant, and 8 it's not discussed. 9 And again, I don't know if this is 10 not something that's typically done in animal 11 studies, but there are studies in the cancer 12 outcome section where lead chromate was used. 13 And sure enough they saw cancer, but it was 14 probably related to the chromate. 15 And so I think, really thinking a 16 little more comprehensively about what we do 17 in animal studies, and what works and doesn't 18 work in terms of understanding human risk, 19 could improve the integration between the two

20 data streams a lot. 21 And sort of in keeping with that, 22 I think there are a number of sections in this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 257 1 Chapter in which there's a lot of information 2 about in vitro mechanistic studies, which is 3 very interesting. 4 And there are some section in which 5 in vitro findings are not consistent with in 6 vivo models, and there's no -- there was 7 rarely an acknowledgment of the fact that you 8 may see differences in an in vitro and an in 9 vivo model because they're very different

10 models. 11 And the implications of that were 12 not very explicitly acknowledged. And again, 13 I think that's really important to then 14 applying that information and integrating it 15 with the human data. 16 And I think the other thing along 17 that line is that, some of the animal studies 18 had outcomes, I realize you can't get complete 19 parity between outcomes in a rodent and 20 outcomes in humans. But I think it takes a 21 lot of work and it's worth the effort to try 22 to figure out where there are homologies is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 258 1 between what's being done in animals and 2 what's being done in humans. 3 And I didn't see that happening in 4 a lot of the sections. So in the neurologic 5 section there's a description of a rotarod

6 task and a rodent. And I'm not sure what that 7 means for humans if it's related to 8 Parkinson's Disease.

9 I mean I'm not sure what that 10 means, and it would have been helpful for me 11 as a non-animal person to have a better sense 12 of how important that might be in a human 13 setting. 14 I think the last sort of main issue 15 was, and this sort of gets back to my previous 16 comments about sexual dimorphism in both 17 toxicokinetics and toxicity is that, I think 18 one of the challenges in this chapter is how 19 to identify meaningful susceptibility factors. 20 And by meaningful I guess I mean 21 factors that would really impact how you think 22 about a risk assessment and populations that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 259 1 are at risk that need special protection. 2 And I think there are a number of 3 susceptibility factors that are looked at both 4 in the animal models and in the human data. 5 But it strikes me they're a little bit 6 arbitrary at times. 7 And I guess the, and I admit to 8 some personal bias, but I think for example, 9 the genotyping data is very interesting, but 10 whether that really helps you identify 11 susceptible populations in a meaningful way, 12 I'm skeptical about. 13 And I think that there's very 14 little on sex or other susceptibility factors 15 which I think are probably more meaningful in 16 this document. 17 So I think there's a little bit of 18 an imbalance with the overrepresentation of 19 susceptibility factors that are of 20 intellectual interest, but may not have a lot 21 of practical applications, and it 22 underrepresents other factors that may be more

### 202-234-4433 Neal R. Gross & Co., Inc. Page 260 1 immediately relevant to a risk assessment 2 process. 3 And then I guess I have a couple, 4 or not a couple, I have a number of very 5 specific comments, which I think I'll just 6 leave for my written comment. 7 DR. FREY: Okay, well, great. 8 Thank you, Dr. Korrick. Dr. Cory-Slechta? 9 DR. CORY-SLECHTA: So while I agree 10 with a lot of Susan's points, I don't 11 necessarily agree with the fact that you can't 12 have parity between human and animal studies. 13 And I in fact I think we've made -- 14 DR. KORRICK: Like I said, it's 15 just hard. 16 DR. CORY-SLECHTA: Right, we've 17 made a lot of progress I think also in moving 18 beyond IQ in the last five or six years. 19 First of all, IQ scores don't capture all of 20 what's captured by the word behavior, nor does 21 behavior capture everything that's in an IQ. 22 So if you do a correlation between

### 202-234-4433 Neal R. Gross & Co., Inc. Page 261 1 IQ tests and other behavioral measures, you 2 don't see always very good correspondence. So 3 they capture different things. 4 So I think it would have been 5 possible in the integration section actually 6 to capture a lot of what are some of the 7 demonstrated parities now in the animal and 8 the human literature. 9 So for example, I know that in, you 10 know, we published in 2004 from the Rochester 11 Cohort, very explicit data on measures of 12 memory and learning and attention using the 13 CANTAB test in the Rochester Cohort. 14 These are basically the same 15 measures we actually use in animal studies. 16 So there are very direct correspondences and 17 ways to integrate. 18 Another one I would point out is 19 the work, we've been doing work on stress. 20 And one of the things we know that lead does 21 is it basically breaks down the negative 22 feedback system for stress.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 262 1 Well Gump's studies in children has 2 showed exactly the same thing. There is a 3 slower deceleration, if you will, of the 4 cortisol response after a stress exposure in 5 kids. 6 Attention is another one, and I 7 think the Chapter doesn't break this out well 8 enough in terms of the neurobehavioral

9 outcomes. 10 There have been very, attention is 11 another behavioral construct and it means many 12 different things, and people have begun to 13 break down those different kinds of attention 14 deficits, and look at them both in the human 15 and in the animal studies, and there are some 16 very interesting correspondences in things 17 like impulsivity, self control, whatever you 18 want to call it. 19 Another one where I think sort of 20 got short shrift on the human side, and not, 21 maybe got passing reference on the animal 22 side, and is referred to really as auditory

### 202-234-4433 Neal R. Gross & Co., Inc. Page 263 1 acuity, is the auditory brainstem evoked 2 response. 3 And this is something that 4 certainly affects auditory acuity, but we also 5 know that when you get changes in some of the 6 peaks of these measures, they relate back to 7 morphological changes and changes in synaptic 8 function and plasticity. 9 So they have very significant 10 implications. These are seen across the 11 animal and human literature, so I think 12 there's some very specific examples that could 13 be put into that section that indeed can 14 integrate it better. And in fact, they show 15 up at very similar blood lead concentrations. 16 One other thing, I thought, just 17 sort of going back to the health thing, the 18 toxicological section at least on the, what's 19 called the neurologic side, but I would agree 20 that is absolutely the wrong term, is kind of 21 disorganized. 22 It separates out Morris water

### 202-234-4433 Neal R. Gross & Co., Inc. Page 264 1 mazes, as if somehow those were separate. Now 2 that's just a measure of learning, and it 3 doesn't matter whether I put the animal in a 4 water maze, or an operant chamber, or anything 5 else, it's how I arrange the reinforcement 6 contingencies in the environment, not whether 7 it's in a pool or an operant chamber. 8 And again, here I thought attention 9 could have been broken out, both in the human 10 and the animal literature, and memory 11 separately. 12 So there seems to be some confusion 13 in terms of the tox chapter on, you know, 14 what's what. So there's a section I think 15 called Response Inhibition, which could've 16 been in a section on attention with a much 17 more in-depth assessment of attention deficits 18 as we know them and what comprises them. 19 Just one other thing, there is 20 mentioned, and this comes back to vulnerable 21 populations of stress. And I think we have to 22 be a little careful about that, because one of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 265 1 the things we also know from the stress 2 literature is that high levels of stress can 3 be bad, but high levels of stress can also be 4 good. 5 And they can induce what we call 6 resilience, and in fact there is an animal and 7 a human literature on resilience, and I think 8 if you think about it in terms of your own 9 kids, if they don't experience disappointment 10 once in a while in life, they don't tend to do 11 quite as well. 12 And I think we're beginning to 13 understand that as well. So I think we have 14 to be a little careful about how you cite 15 stress. It's not just a unitary kind of 16 phenomenon. 17 DR. FREY: Great, thank you. Yes, 18 that reminds me there was a, I think a story 19 on ABC News before Father's Day about fathers 20 horsing around with their kids, and that that 21 taught them to deal with frustration. 22 And, you know, when a dad grabs a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 266 1 kid and has them punch themselves in the head, 2 and so I don't know if that's consistent with 3 the, you know, it's like, yes, you must deal 4 with this kind of stress. All right, Dr.

5 Kosnett? 6 DR. KOSNETT: I wanted, let me 7 offer just a few comments on the toxicological 8 integration, the integration on the 9 toxicological data with the epidemiological 10 data. And then I want to just take a moment 11 or two to discuss a concern I had just with 12 the whole approach in Chapter 5 on causal

13 assessment. 14 With respect to the discussion of 15 the toxicological data, I wanted to make a 16 suggestion that you parse out or separate out 17 animal and toxicological studies where the 18 dose is relevant to the low levels of human 19 exposure that we're seeing today. 20 You know, if you consider that if

21 we're concerned about blood leads between one 22 to ten micrograms per deciliter, generally

### 202-234-4433 Neal R. Gross & Co., Inc. Page 267 1 speaking plasma lead is about one percent of 2 that, okay? And if you convert that into 3 concentration ranges that would be active at 4 a cellular basis, it's about .5 to five an 5 animal. 6 And why am I concerned with plasma 7 lead? Well plasma lead is, theoretically at 8 least the form of lead that's distributed in 9 the blood stream that's available for uptake 10 into the brain, into the kidney, into the 11 heart, into the vascular endothelium, and the 12 other endpoints. 13 There are, you know, many studies 14 that are discussed in this document that talk 15 about micromolar range, and not nanomolar 16 range, and I think we ought to focus on what 17 can be gleaned from studies that particularly 18 have concentrations that are relevant. The 19 same thing -- 20 PARTICIPANT: When you're done, 21 I've got a rebuttal. 22 DR. KOSNETT: Okay. All right,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 268 1 that's fine, that's fine. And, you know, some 2 of the doses, you know, of animals exposed in 3 diet to 100 parts per million, which is 100 4 milligrams a liter or 100,000 micrograms per 5 liter. 6 A couple of months ago we were on 7 a panel talking about lead and water, and we 8 were talking about ten micrograms per liter of 9 concern, you know, so some of these levels 10 were extraordinarily high, the animal studies 11 were extraordinarily high. 12 Not to say that they were that 13 value, but let's try to focus on the doses

14 that are relevant to the low level human 15 exposures that are particularly of concern 16 with respect to the ambient air quality

17 standard. 18 The other thing has to do with the 19 temporal pattern. If you look at a lot of the 20 human health effects, like cardiovascular, 21 let's talk about blood pressure which is a key

22 concern.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 269 1 Whatever the mechanism that's 2 active in humans to cause them to develop 3 elevated blood pressure, it's not a short-term 4 pharmacological effect. I mean we don't see, 5 for example lead exposed children develop high 6 blood pressure. 7 If you look at the studies, it's 8 not there. And if you look at adult studies 9 to the extent that they exist, you know, and 10 just from basic -- well my personal 11 observations or whatever, is people who begin 12 work in a lead factory don't become, their 13 blood leads might go up in two or three 14 months, their blood pressure doesn't go up. 15 It's not a short-term pharmacologic 16 action. The mechanism of action that is 17 causing some of the cardiovascular effects of 18 lead, and possibly also the renal effects and 19 the neurodegenerative effects, is probably an 20 insidious process or process that has a long 21 latency. 22 And it may be associated with, you

### 202-234-4433 Neal R. Gross & Co., Inc. Page 270 1 know, oxidative stress on certain organs and 2 how they are remodeled. It may have something 3 to do with epigenetic variability and that 4 could even explain how maybe early life 5 exposures. 6 But whatever, let's try if we can 7 to focus on the toxicological mechanisms from 8 the literature that are consistent with a 9 disease process that would be insidious, in 10 other words, slowly occurring over a number of 11 years or have a long latency. 12 Because in terms of the low level 13 effects of lead that we're dealing with, in 14 humans, that's probably what we're 15 confronting. 16 And then I wanted to just say a few

17 words about the causal assessments that are 18 made in this document. You know, Chapter 1 19 had a nice table on Page 1-25, about the 20 weight of evidence for causal determination. 21 And it sets forth, you know, five different 22 levels. Causal relationship, likely to be a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 271 1 causal relationship, suggestive of a causal 2 relationship, inadequate to infer a causal 3 relationship, or not likely to be. 4 And I would make a request or a 5 suggestion that in Chapter 5, that there is a 6 more transparent and rigorous application of 7 how you decided on causal relationships. It 8 was somewhat troubling to me to see on the 9 Table 2-, can someone put up Table 2-26? 10 No, Table 2-3, excuse me, 2-3 on 11 Page 2-26. And the same thing -- my comments 12 would also apply to Table 2-2. But what you 13 notice is that you have, can you, someone's 14 trying to do that? Okay. 15 If you notice on, you know, they're 16 at five micrograms per deciliter. There is a 17 number of different endpoints in adults that 18 are all -- these are all accepted as being 19 causal at that low level of exposure, at least 20 it's implicit in this document. And that if 21 you had someone who was -- exposure occurred 22 under five micrograms per deciliter, they

### 202-234-4433 Neal R. Gross & Co., Inc. Page 272 1 would have those effects. 2 And, you know, really there are no 3 human studies, and no animal studies either, 4 that show that if you just confine an animal 5 or a human to a blood pressure under five, 6 that they would develop adverse cardiovascular 7 effects, or develop renal damage, or develop 8 decrements in cognitive function, if you're an

9 adult. 10 Those studies either haven't been 11 done, and I'm not saying that it might not 12 happen, but the data doesn't show that. And 13 I think, you know, particularly with the renal 14 endpoints, there's the whole issue of reverse 15 causation has not been adequately resolved. 16 It's an unresolved issue to the 17 extent to which renal insufficiency causes an 18 elevated serum creatinine, I mean to the 19 extent that an elevated serum creatinine that 20 reflects renal insufficiency causes you to 21 have an elevated blood lead as opposed to an 22 elevated blood lead causing that has not been

### 202-234-4433 Neal R. Gross & Co., Inc. Page 273 1 really fully sorted out. 2 And I could go into more details 3 about the renal literature and the studies by 4 you, and Lynn, and colleagues, but we would be 5 here for a long time. 6 DR. GOODRUM: Michael, you're 7 proposing a ranking scheme that kind of 8 mirrors what was in the weight of evidence? 9 DR. KOSNETT: I think -- right -- 10 I think that it -- and also what the document 11 does, is it just lumps, it says, there's 12 evidence for a causal relationship of lead 13 with neurological endpoints. 14 If you turn to the previous table, 15 can you turn to Table 2-, yes. Okay, so at 16 five you have ADHD there with children next to 17 decrements in full-scale IQ. 18 I think I agree that there's a 19 considerable amount of evidence that's 20 coherent with the toxicological literature, 21 that has mechanistic explanations of multiple 22 investigators, across multiple studies of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 274 1 different types about lead affecting IQ in 2 children at low levels. 3 Okay, even down at five. But the 4 data for ADHD is not on the same grounds, on 5 the same footing at this point. It's more 6 preliminary. I mean some of the key studies 7 acknowledge the fact that they haven't been 8 able to control for parental ADHD. 9 And in a disease that is 75 percent 10 or more genetically inherited, that's a very 11 critical thing to control for, parental ADHD. 12 So there's not really a -- this 13 document really doesn't parse out or examine 14 the way I think it could. Where do we, how do 15 we establish causality? And does ADHD really 16 belong on an equal footing with IQ loss, in 17 establishing causation at lead levels less 18 than five. 19 I mean and the causation issue is 20 of course, the issue of does it cause it at 21 any dose, and would it cause it at these low 22 doses. If you go through the entire document

### 202-234-4433 Neal R. Gross & Co., Inc. Page 275 1 on all the endpoints, that's of concern. 2 I mean a lot, and I hope that in 3 the next round, that could be given more 4 attention. And in fact, in describing the 5 studies I think it would be helpful if there 6 was an extra column that said basically, the 7 strengths and limitations of all the studies. 8 You know, you have a lot of tables 9 that put forward, you know, summarize the 10 evidence from various studies, but there's not 11 a column in there about limitations of those 12 studies, or relative strength of those 13 studies, or which are the key studies that 14 ultimately get us to this point of saying 15 whether it's causal, or just suggestive. 16 DR. FREY: Okay, great, thanks. 17 Let's see, we're a little behind schedule. I 18 do want to make sure we have an opportunity 19 for whatever further discussion we need to 20 have on Charge Questions 5.

21 We also need to take our break 22 fairly soon, and we still have three more

### 202-234-4433 Neal R. Gross & Co., Inc. Page 276 1 Charge Questions to go. So having said that, 2 is there anyone who wants to say anything more 3 on any of the 5a through e questions? Dr.

4 Pounds? 5 DR. POUNDS: I'll make it quick. 6 I agree with both Debra and Michael that it's 7 very important to evaluate the experimental 8 design of in vitro experiments to determine 9 their relevance for elucidating to mode of 10 action.

11 But I would want to make sure that 12 EPA, and Michael, and Debra, realize that the 13 simplest and most direct way to do this is 14 just to compare, is to convert the media 15 concentration of the cell culture media to 16 it's blood lead equivalent. 17 But that's absolutely indefensible 18 and inappropriate, even though it's easily 19 done. We know from autopsy studies, animal 20 studies, and dare I say it, biokinetic 21 simulations, that a given blood lead 22 concentration can result in wildly different

### 202-234-4433 Neal R. Gross & Co., Inc. Page 277 1 tissue lead concentrations. 2 So the matter of evaluating these 3 in culture -- cell culture experiments is not, 4 how does the culture medium equate to blood 5 lead, but it's how does cell culture, how does 6 the cell lead equate to the lead content of 7 the tissues that's being studied. 8 That studying neurons, then the wet 9 weight of lead in the cell culture should be 10 in the range of tissue lead concentrations 11 from brain. You're not going to find those 12 data very often, but I would argue that those 13 are one, there's others, but that's one of the 14 primary criteria by which you should evaluate 15 in vitro studies. 16 DR. FREY: Okay. Other comments on 17 health effects? Do you have a question? 18 DR. KORRICK: I just wanted to 19 follow-up on one of Gail's comments that, 20 especially for a metric like IQ, it's useful 21 to have information about it's clinical 22 relevance, and that a one point change in IQ

### 202-234-4433 Neal R. Gross & Co., Inc. Page 278 1 is clearly not going to be clinically relevant 2 for an individual child. 3 And I think that's a good point, 4 but I think there's a complimentary approach 5 in the context of population studies and 6 population risk. 7 And I think the classic example was 8 Herb Needleman's explanation of, you know, 9 like this, so this dent in lead in studies 10 where if you shift population IQs by small 11 amounts, you can impact the tails of the 12 distribution disproportionately and have a 13 larger proportion of kids with either very 14 low, or fewer kids with gifted IQs so that on 15 a population level small changes in a mean 16 indicator for a particular continuous health 17 measure can have an impact, even though on an 18 individual level, there's not a clinical 19 interpretation of it. 20 So, I mean I think that's the 21 classic perspective that we usually take 22 around these kinds of measures. And it's true

### 202-234-4433 Neal R. Gross & Co., Inc. Page 279 1 for the blood pressure measurements as much as 2 it is for the IQ. 3 You're talking about a point 4 difference in systolic blood pressure being 5 related to a microgram per deciliter of blood 6 lead, which has no clinical relevance. 7 But on a population basis looking 8 at the distribution of blood pressure on the 9 population, that can shift blood pressures in 10 a way that disproportionately increases the 11 number of people who would meet clinical 12 criteria for hypertension and be at risk for 13 all sorts of cardiovascular disease related to

14 that. 15 DR. WASSERMAN: I'm sorry I have to 16 respond. 17 DR. FREY: Go ahead, sure. 18 DR. WASSERMAN: The shifting of 19 population means in IQ, is to really not based 20 on much of anything. 21 All of the prospective studies 22 which really contribute to the Lanphear meta

### 202-234-4433 Neal R. Gross & Co., Inc. Page 280 1 analysis, and really most of the work done 2 even before that, removed kids from 3 investigation who were very low functioning, 4 or who had other high risk conditions, which 5 would've contributed to IQ. 6 So for various reasons, kids with 7 genetic anomalies or other health conditions, 8 so we really don't know, and maybe this is a 9 question for the sort of susceptibility, 10 vulnerability portion of the analysis. 11 We don't really know what the lead 12 effect is on otherwise very low functioning 13 children. So we don't know if a kid has an IQ 14 of 50, and we then expose that child to a high 15 level of lead, whether you will have the same, 16 or greater, or none, or what kind of impact, 17 on his function. 18 DR. KORRICK: Yes, I mean I think, 19 that you're right, and it's conceivable that 20 those susceptibility factor, Deb said, you 21 know, there's a floor effect and, you know, 22 blah, blah, blah.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 281 1 But I think just in terms of the 2 mathematics of the distribution of a 3 biological property in the population, you can 4 model shifts in the mean of the population, 5 assuming a particular distribution which will 6 vary depending on the health outcome. 7 And you'll see changes in the 8 proportion of the population, it's a little, 9 it's different than saying what the outcome 10 specific effect of the exposure is, it's 11 looking at the effect of the exposure on a 12 distribution of outcomes. 13 DR. WASSERMAN: But you don't have 14 any data at that point, to say that's what the 15 shape of the distribution would look like to 16 shift that population. 17 DR. FREY: Okay. I think we're 18 heading toward a break unless there's any 19 other Chapter 5 comments. If not, since we're 20 behind, let's just take a ten minute break. 21 Let's come back at I guess 3:25, and we've got 22 three more questions to go through, so be

### 202-234-4433 Neal R. Gross & Co., Inc. Page 282 1 ready to go. 2 (Whereupon, the foregoing matter 3 went off the record at 3:14 p.m. and resumed 4 at 3:25 p.m.) 5 DR. FREY: Okay. Well, let's see 6 who is here and who's on the next Charge 7 Question. So we wanted to move toward a 8 discussion on Charge Question 7, which is on 9 ecological effects. 10 I think there was some lingering 11 issues about our health effects discussion 12 just a minute ago about changes in IQ, and 13 partly in the context that the last review by 14 a CASAC and EPA reached a conclusion that a 15 change of, I guess a population change of two 16 IQ points was of public health significance. 17 I'm not sure that what I heard, and 18 I guess the two people involved in that 19 discussion aren't in the room at the moment.

20 But I don't know that what I heard was 21 inconsistent with that. 22 I think we were talking about half

### 202-234-4433 Neal R. Gross & Co., Inc. Page 283 1 an IQ point, as opposed to two IQ points. But 2 that may be something we need to come back to 3 and just clarify whether we're reversing what 4 CASAC had been saying, which I don't think we

5 mean to do.

6 DR. WEITZMAN: I have a sense that 7 we're going to say the same things. 8 DR. FREY: Okay. 9 DR. WEITZMAN: But, what I took 10 away from what Gail was saying, was a focus on 11 half an IQ point in an individual child, as 12 opposed to a population basis. 13 DR. FREY: Okay. 14 DR. WEITZMAN: And I think that 15 many people avoid then on changes as low as an 16 IQ point on a population basis of having 17 difference in measurable outcomes of function. 18 DR. WASSERMAN: I'm sorry, I missed 19 what you said. 20 DR. FREY: Well what we're talking 21 about is the last review for the lead 22 standard, led to a more or less a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 284 1 recommendation that a two percentage point 2 change in IQ was a -- 3 DR. WEITZMAN: Two points. 4 DR. FREY: Two IQ points was of --

5 DR. WEITZMAN: Or one.

6 DR. FREY: Or one was of 7 significance, and we had some debate about 8 half a point being perhaps for an individual 9 child not significant clinically. 10 And I think it's an important point 11 as a panel that we clarify the distinction 12 between a clinical outcome for an individual 13 child, versus a population metric of some 14 kind, whether it's an average, or a median, 15 and that, I guess clarify that there is a 16 distinction there. 17 DR. WASSERMAN: I think there's a 18 distinction between statistical significance, 19 clinical significance, and perhaps public 20 health significance, and it would be useful to 21 define what those are. 22 DR. FREY: Well the public health

### 202-234-4433 Neal R. Gross & Co., Inc. Page 285 1 aspect is ultimately a judgment. I mean the 2 whole standard setting process ultimately 3 becomes a judgment of the administrator based 4 on input from the staff and from CASAC, and 5 from the public. 6 So it's probably not purely a 7 scientific question, it's an interpretation, 8 and it's also a value judgment in that sense.

9 Yes? 10 DR. KOSNETT: Forgive me if someone 11 else said this earlier. But, you know, when 12 you identify a small change in any, you know, 13 one to two micrograms, excuse me one to two IQ 14 points, or one millimeter, or two millimeter 15 systolic blood pressure changes, bear in mind, 16 that emerges from the population. 17 There are some people who have a 18 substantially higher impact, and some people 19 probably don't have any impact. I mean that 20 could happen. 21 So, you know, on average though, if 22 you see those even small effects across a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 286 1 population, that infers that there are some 2 people who are substantially more exposed, and 3 that's a reason to take action. 4 And, you know, the other thing 5 about the ambient air quality standard that's 6 important to bear in mind, is that it's 7 supposed to account for not only vulnerable 8 populations, but to have then a margin of 9 safety. 10 DR. FREY: Right. 11 DR. KOSNETT: Associated with it 12 too, and a lot of times in lead we don't even 13 allow traditionally the margins of safety that 14 are incorporated into regulations for a lot of

15 other substances. 16 So when we bear that in mind, I 17 think there is a public health concern for one 18 to two micrograms per deciliter, excuse me, 19 one or two IQ points, or one millimeter, two 20 millimeter systolic blood pressure. 21 DR. FREY: Okay. Well that may be 22 all that we need to say on that at the moment.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 287 1 I just wanted to clarify that a little bit. 2 Let's go onto Charge Question 7. 3 PARTICIPANT: Do you want to skip

4 6? 5 (Off microphone comments) 6 DR. FREY: Well we have, yes in the 7 agenda -- 8 PARTICIPANT: We got eco first. 9 DR. FREY: In the, well I have on10 the agenda, Charge Question 7, is not the eco11 effects. 12 PARTICIPANT: Yes it is. 13 DR. FREY: That is the eco-effects. 14 Okay, so the next set of discussants are Drs. 15 Stubblefield, Herb Allen, Chris Johnson, and 16 Dr. Lanno. And we'll start with Dr. 17 Stubblefield. 18 DR. STUBBLEFIELD: Let me get 19 myself organized here for a second. All 20 right. I will go through the Charge Questions 21 as addressed, and we'll characterize my 22 comments at this point, and then I will leave

### 202-234-4433 Neal R. Gross & Co., Inc. Page 288 1 it to each of my compadres here to make their

2 comments. 3 I think that I need to start by 4 saying that I think that Section 7 was an 5 extremely well written, well organized 6 document. It certainly covered an awful lot 7 of information in a very short period of time, 8 and it was quite readable, and excellent in 9 all of those categories. 10 I will say a couple of things. 11 There's some questions about the desire to 12 stick to 2006 and later data. Clearly that is 13 what was done, that was clearly the charge 14 that was written into the approach that was

15 taken. 16 I think that we need to be mindful 17 that this 2006 number, I gather derives from 18 the previous air review document, and that 19 relied on other criteria, and numbers, and 20 data that proceeded that. 21 But if you look back at the genesis 22 of some of those numbers, like if you're

### 202-234-4433 Neal R. Gross & Co., Inc. Page 289 1 relying on what are quality criteria derived 2 values, and those summarizations for the data 3 evaluation, you're really looking at 1985 4 science, you're not looking at anything newer

5 than that. 6 If you're considering the soils 7 effect data, you're really relying on 2003 and 8 older data. And because of that I think that 9 it's very important that we go back and pick 10 up some of the newer information, or at least 11 include that in our summary of the, when 12 addressing the potential effects 13 concentrations. 14 There's also a question about the 15 availability and the use of some additional 16 data that were not included in the document. 17 And that's deriving predominantly from the 18 fact that most of the data that is, well in 19 fact all of the data that's in there is 20 limited to the peer reviewed literature. 21 And there is a substantial body of 22 information that's been generated over the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 290 1 last five to six years, that have been driven 2 by the European REACH Regulations. 3 And that has resulted in really 4 pushing forward an awful lot of new 5 information, new empirical data that, if we're 6 going to do the best job we can, we should 7 include that information. 8 Now I know that, it's my 9 understanding that there was a call for data 10 that it went up with the announcement that 11 this work was going to go ahead. 12 And my understanding is that the 13 industry had recommended at that point in time 14 to, or at least acknowledged that they had 15 that data, and that they would make that data 16 available at the time of the REACH 17 registrations. 18 And my understanding is that that 19 has occurred at the end of last year, and so 20 all of that information should be available. 21 And I know that you can search the European 22 Chemical Agency's website and you can get

### 202-234-4433 Neal R. Gross & Co., Inc. Page 291 1 direct access to summarizations of all of the 2 data that has been generated. 3 While we were sitting here earlier 4 today, I actually pulled that document up and 5 went back and looked at the information that 6 was available in there, just as a cursory 7 example. 8 And of the data that were listed in 9 those tables for example, if you're just 10 looking at say invertebrates, aquatic 11 invertebrates for example, there was an 12 additional 26 tests, with at least six 13 additional species, that were all included in 14 the post, as part of the REACH generation 15 process. So there's a substantial database 16 that we really should take into consideration. 17 As far as the organization of the 18 document goes, I felt that it was quite well 19 organized. I liked the separation of the 20 terrestrial and the aquatic effects. I like 21 the segregation on the basis of endpoints. 22 I would suggest that there be, at

### 202-234-4433 Neal R. Gross & Co., Inc. Page 292 1 least in the aquatic area, well, I guess, yes, 2 in only the aquatic area, that we would 3 separate marine and freshwater data. There is 4 a clear difference in lead speciation in the 5 marine system versus the freshwater system. 6 The sensitivity of the organisms 7 are reflected as a part of that, and any of us 8 that have ever put lead chloride into water 9 and found out that it didn't immediately go 10 into solution, has learned that lesson. So I 11 would make that recommendation. 12 Moving along in the charge 13 questions here. The second one that we were 14 to address was, is it appropriate to derive a 15 causal determination for bioaccumulation and 16 its effect on ecosystem services. 17 I'm not going to go into a lot of 18 detail on this, because I know Dr. Allen has 19 a substantial series of comments about this. 20 I'll just say that bioaccumulation, 21 bioconcentration should not necessarily be 22 thought of as an adverse or toxic effect.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 293 1 Bioaccumulation as a result of 2 environmental exposures can result in an 3 adverse effect to an organism or to the 4 consumer of that organism, but only if 5 concentrations actually reach a site of action 6 in that organism. And so that has to be taken 7 into consideration, and so I'll leave 8 additional comments on that topic to Dr.

9 Allen. 10 To go on, has the ISA adequately 11 characterized available information between 12 lead exposures and effects on individual 13 organisms. Here I've already highlighted the 14 fact that there's additional data that should 15 be taken into consideration. 16 I believe, I think that the way one 17 should move forward on presenting that kind of 18 data is probably in the form of species 19 sensitivity distributions. It allows us the 20 opportunity to present an array of data and we 21 can highlight in such a presentation new data

22 versus old data.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 294 1 Frankly if you look at the old 2 data, most of the old data would not be 3 acceptable by today's standards in terms of

4 how we evaluate data. 5 For example, much of the data that 6 was included for example in the original Water 7 Quality criteria, was based on nominal 8 concentrations as opposed to measured 9 concentrations. And by today's scientific 10 standards, those data wouldn't even be 11 accepted. They would be rejected out of hand. 12 So I think it's important we take that into 13 consideration. 14 Subject areas that should be added 15 and expanded, or removed. This one is an 16 interesting question and I think we need to 17 give some consideration to it. 18 There is a substantial amount of 19 the text that is related to physiological 20 stress, or immunological effects, or 21 neurobehavioral effects in this document. 22 And traditionally the EPA has

### 202-234-4433 Neal R. Gross & Co., Inc. Page 295 1 always taken a position when dealing with 2 ecological endpoints, that we look at 3 predominantly effects on populations and 4 communities, as opposed to individuals per se. 5 By taking the, and unless you can 6 make a direct correlation between those

7 measurements and the effects on the 8 population, or the effects on the community, 9 then it's, you're basically changing the 10 paradigm that the Agency has taken with regard 11 to how one considers those data. 12 And it wasn't clear in the text, or 13 the subsequent evaluation of how that is going 14 to be done, or if it's going to be done. 15 If you decide that you are going to 16 continue with the typical EPA evaluation on 17 endpoints, that is to focus on endpoints 18 related to survival, growth, and reproduction, 19 then my suggestion would be to then take the 20 rest of that information and move it into an 21 appendix, or something of that nature, that 22 would allow you to reduce the volume of the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 296 1 document. So I'll leave that one there. 2 Questions about soils, I know Roman 3 is going to, Dr. Lanno's going to make some 4 comments on that topic, so I will leave it at 5 that. I will just say that it would be my 6 recommendation that you focus your efforts on 7 natural soils, as opposed to artificial soils. 8 And the issue of how one would go 9 about presenting data associated with 10 environmental parameters. We've made a major 11 point, and I think that it's worth commenting12 on specifically, is that the question of bio13 availability is really the state of the 14 science today with metals. 15 You've seen this in the development 16 of the Terrestrial Biotic Ligand Models. 17 You've seen it in the Aquatic Biotic Ligand 18 Models. And so therefore, it is extremely 19 important that that information be taken into 20 consideration in any type of an evaluation. 21 And the way that is probably most 22 easy to present that kind of data in a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 297 1 document such as this, is to present the data 2 as adapted for a range of conditions. 3 So for example, if we know for a 4 fact that things like calcium concentration, 5 magnesium concentration, pH, and dissolved 6 organic carbon, all affect the toxicity of the 7 material, then what you do is you present a 8 range of calculations reflecting toxicity over 9 the range of conditions that exist throughout 10 the United States. 11 So cover tenth percentile DOC, 90th 12 percentile DOC, et cetera, et cetera, and 13 present the data in that fashion. Therefore, 14 the reader gets an idea of what the conditions 15 are throughout the U.S., and what the effect 16 of those individual parameters are. 17 So that covers I think the charge 18 questions, or at least my comments on the 19 charge questions. But there's one more issue 20 that I'd like to raise very briefly that 21 wasn't posed as a charge question. 22 And that's the issue of causal

### 202-234-4433 Neal R. Gross & Co., Inc. Page 298 1 determination. There is a section at the end 2 of Section 7 that goes into detail on reaching 3 conclusions with regard to whether a causal 4 relationship has been shown or not. 5 And so when I first looked at that, 6 I started asking myself, what is that really 7 getting at? And I went back to Chapter 1 and 8 read the description of the weight of evidence 9 for causal determination. 10 And the thing that grabbed me was 11 the very first sentence under a causal 12 relationship says in Table 1.2, it say, 13 "Evidence of sufficient," speak Bill, 14 "Evidence is sufficient to conclude that there 15 is a causal relationship with relative 16 pollutant exposures." 17 And that's the part that got me, 18 "with relevant pollutant exposures," because 19 I don't think that that's addressed adequately 20 throughout the document. 21 If you are just looking at lead 22 concentrations and/or whether data exists to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 299 1 show that, you know, lead can be causally 2 related to mortality. Well, you know, that 3 can be shown on so many levels, you know, 4 during hunting season, ask the ducks, they're 5 pretty sure there's a causal relationship. 6 But when we start looking at some 7 of these other factors, like effects on 8 growth, effects on, you know, 9 bioconcentration, which I disagree with, I 10 mean but, all of those documents, you've 11 concluded that there is a causal relationship. 12 And I don't disagree that 13 concentrations can cause these effects. I 14 mean it's shown in the literature, but as to 15 whether it meets the standard of relevant 16 environmental exposures is the question that

17 I have. 18 I mean basically what you're doing 19 is you're doing a risk assessment as you move 20 forward with that and you have to adequately 21 address exposures in any risk assessment. And 22 so, well I'll just leave it at that.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 300 1 DR. FREY: Thank you. Dr. Herb

2 Allen? 3 DR. ALLEN: I guess I'd like to 4 start off and say, you know, it's in many ways 5 a tremendous document. I looked at this 6 things and said, my god, I have 115 pages to 7 read, yes. And so I started wading through 8 them and found that they were exceedingly well 9 written, that the articles -- and there were 10 lots of articles -- were well summarized, not 11 critically but they were well summarized. 12 They reflected what the author's said, as 13 opposed to a critical evaluation, I'll talk 14 about that in a second. 15 So I thought all of that was very 16 good. The thing that I said this morning 17 still holds. When I read each one of these 18 sections, I didn't know what the contribution 19 of those two or three or six new papers were 20 to helping you make decisions. 21 Because I didn't know what you 22 thought the state of science was at the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 301 1 beginning of the period, and that -- how this 2 modified it. 3 You know, they're great studies, 4 but did they really provide important 5 information. They provided information, but 6 did they provide important information for a 7 rulemaking process? And that really is a key 8 thing. 9 I'm going to hold my comments to 10 two topics. And the first of these is 11 something that's at the bottom of Page 7-9, 12 and that talks about a sequential extraction 13 procedure was employed by Ettler, et. al14 (2005), to determine the relative bio15 availability of different lead fractions 16 present in soil collected from a mining 17 smelting area in the Czech Republic. 18 I said great, you know, I'm highly 19 biased. I hate to have to tell you this, I 20 think that sequential extraction procedures 21 stink. I don't think they're that good, but 22 it's polite company.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 302 1 So I have real problems with 2 sequential extraction procedures, but here I 3 read the sentence, and it said, my god, these 4 things really provide useful information.

5 I've never seen that. 6 So I went into this paper, which 7 incidentally the HERO system, you people are 8 my hero. The HERO system is great. You get 9 kudos for that, click on it, up pops the 10 paper. I can go into the library at the 11 university, I can get that paper. 12 But I can't get most of the book 13 chapters and reports, and those really were 14 helpful. So the system really does provide 15 somebody like me with a great deal of help. 16 And boy, I don't know that I would've gotten 17 all of the things that I wanted without it. 18 At any rate, back to the sequential 19 extraction procedure. In sequential 20 extractions, what you do is you take the 21 sample, you shake it up with a witch's brew, 22 or, you know, out pops metal, or you analyze

### 202-234-4433 Neal R. Gross & Co., Inc. Page 303 1 this, and now you have a number. 2 Well, I took freshman Chemistry and 3 I took a few more chemistry courses after 4 that, and it said if I really want to 5 understand partitioning, I need to have two 6 numbers. One is a capacity and the other one 7 is an intensity. 8 And if I do one extraction, I can 9 only get one number, and there's no way to get

10 two numbers out of one measurement. That was 11 my fifth grade arithmetic teacher told me 12 this, you know, and I paid attention in that 13 class when I wasn't sleeping. 14 So this was my problem in going in, 15 so I really was delighted to find that you 16 actually found this to be useful because you 17 wrote the documents. So I went in and I read 18 the paper. 19 And I got quite surprised. 20 Determine the relative bio-availability.21 Well, I know how to determine relative bio22 availability, we do it in the laboratory all

### 202-234-4433 Neal R. Gross & Co., Inc. Page 304 1 the time. 2 You know, something dies, something 3 doesn't grow as well, something goes funny, 4 you know, something happens. So I read this 5 paper and I looked and I looked and I looked, 6 and you know what I didn't find: any organism. 7 Nothing was ever exposed. Tell me 8 how do I determine bio-availability without a 9 bio. This was nothing more than one more of 10 a great litany of papers which have used the 11 same technique, which have said, gee, if it's 12 in the first extractant, you know, it's more 13 bio-available than in the second extractant, 14 and that's more bio-available than the third

15 extractant. 16 Or have I ever seen that proven? 17 No, not once. Now why do I spend the time 18 doing this? Is it because this is so 19 important? No, it's because as I read the 20 whole document, this is what I see to a large 21 extent in the document. 22 You are citing what the authors

### 202-234-4433 Neal R. Gross & Co., Inc. Page 305 1 say, as opposed to having critically looked at 2 the information and assessed the information 3 scientifically, independently, completely 4 independently of what the authors claimed, or 5 the reviewers. 6 Being a journal editor, you know, 7 I can tell you there are excellent reviews, 8 and there are some reviews that I simply mark 9 never ask this reviewer to look at anything of 10 mine again. 11 So these things go on. It is, I 12 think your job, not just to say what is in the 13 literature, but actually to evaluate the 14 literature, and say not, this is a new paper 15 since 2006, but this is a useful paper since 16 2006. That's point one. 17 Point two. Later on and throughout 18 this whole thing, we run into BCF, 19 bioconcentration factors, and then I won't 20 steal what Dr. Lanno was going to tell you, so 21 I'll simply leave it very generic as 22 bioconcentration factors.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 306 1 I have been very interested in 2 bioconcentration factors. In, oh 1995 or 3 1996, Peter Chapman and I got together at a 4 meeting, you know, we were dealing with, among 5 other things, bioconcentration. 6 And bioconcentration factors are 7 exceedingly useful. They are exceedingly 8 useful in a regulatory framework. They were 9 developed to deal with DDT. Lead is not DDT. 10 DDT and its related compounds have 11 the same property with regard to bio 12 concentration factor. That is, that the 13 concentration in the organism, divided by the 14 concentration in the water, is a constant, 15 roughly. 16 You know, I mean you have to do a 17 little bit of modification to make it true 18 these days, but basically that's what it's all 19 about. Now that's important because if I know 20 the concentration of the organism, I know what 21 the concentration of the water is. 22 If I know what the concentration of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 307 1 the water, I can tell you what's present in 2 the organism. They're related by this 3 constant. The BCF, wonderful concept. 4 I'm old enough to remember back in 5 the old Great Lakes data days when we started 6 with DDT in fish, we had no idea what was in 7 the water, because nobody had an analytical 8 method that could measure DDT in the water. 9 But what we did know was that it 10 was directly related, and so we knew that if 11 we had a fish with a higher concentration than 12 another fish, it had been exposed to a higher 13 concentration in the water. 14 And if you did some mapping you 15 could say, gee, there's a contamination area 16 over here relative to here, you know, things 17 like this. So it is actually a very useful 18 thing. 19 Now we come to, you know, use of 20 BCFs in this document dealing with lead, and 21 this is not true. You know, back to the '96 22 story, Peter and I said, you know, we ought to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 308 1 put together a little paper that deals with 2 why BCFs are not useful for metals. And we'll 3 put this in as a review paper in Environmental 4 Science and Technology. 5 So Environmental Science and 6 Technology says if you want to write a little 7 review paper for us, send us a paragraph and 8 we'll tell you whether we want it or not. 9 So we wrote them a paragraph and 10 they said, ridiculous, nobody in their right 11 mind would do BCFs for metals. We don't want 12 the paper. 1996, not 2011. Nobody would do 13 this. 14 We wrote back to them, we said, 15 sorry, there's this organization called EPA. 16 There are these Europeans, they all use BCFs. 17 They said, what, they're completely nuts. 18 Write the paper. The paper's in ES&T, it's 19 cited in here. 20 Since then, it does the graph and 21 it does the graph correctly, but with a very 22 limited set of data, and I forget which metal

### 202-234-4433 Neal R. Gross & Co., Inc. Page 309 1 we used, but since then, a group got together 2 and they went through all of the literature 3 which was available for metals, and that paper 4 is cited in my review. 5 And what they did was they put 6 together the BCF concentration relationships 7 for metals. Now if metals are like DDT, if 8 you made these graphs, the line would have a 9 slope of zero. They don't. They virtually 10 all have a slope, and the slope is negative. 11 That is the higher the aquatic 12 concentration, the lower the BCF. Now the 13 policy implications of this are tremendous. 14 If you want to lower BCFs, get rid of these 15 stupid controls that we have on systems and 16 start dumping metals into the environment,

17 we'll lower the BCF. 18 So if you want to make BCFs, you 19 know, the policy, then boy, put more metals

20 out there. That'll lower the numbers. A few 21 organisms might die, you know, but what the 22 heck, the BCFs will be lower on the whole,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 310 1 right. 2 So this is the problem. It just 3 isn't useful, it's the wrong parameter. Now 4 does EPA know that? Oh yes, EPA knows that. 5 EPA put together a policy document out of the 6 risk assessment forum called Framework for 7 Metals Risk Assessment. 8 And I suggest, and I suggested out 9 of the last consultation on this, that that 10 document be used. The ARRA Office was 11 involved in putting together, ORD was involved 12 in putting together, everybody was involved in 13 putting together. It went through the Agency. 14 This says BCFs aren't useful. Your 15 document says, gee, here are BCFS, here in

16 wonderful numbers. I don't know what to do 17 with them. With that, I should shut up. 18 DR. FREY: Thank you. Dr. Johnson?

19 DR. JOHNSON: That's a hard act to 20 follow. I'll be brief. One of the Charge 21 Questions was, is it appropriate to derive a 22 causal determination for bioaccumulation as it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 311 1 affects ecosystem services. 2 It's already been alluded to, and 3 from what I can gather, Roman's going to talk 4 a little bit more about this too. But of 5 course, it is a tricky question because 6 bioaccumulation, and this is even mentioned in 7 the document, is an ecosystem service, as one 8 of the services that ecosystems provides, the

9 removal of these metals. 10 So you get into this logic where 11 reducing the amount of the metals in the 12 environment actually reduces the value of the 13 ecosystem service, because there's less metal 14 being removed. 15 So my answer to this question, is 16 this Charge Question, is that it probably is 17 not appropriate to, you know, derive this 18 causal determination between bioaccumulation, 19 as it affects ecosystem services. 20 And that kind of goes to the end of 21 the chapter in which, as Bill mentioned, these 22 have these causality determinations. And one

### 202-234-4433 Neal R. Gross & Co., Inc. Page 312 1 of them was that there is a causal 2 relationship between lead exposures and 3 bioaccumulation of lead that affects ecosystem 4 services. 5 First of all, having just said that 6 I don't think it makes sense to connect those 7 two. Okay, well if you do connect them, I 8 don't think the case was made in the document 9 that there is a causal relationship between 10 lead exposures and bioaccumulation. 11 And secondly, I wouldn't agree that 12 there's evidence that any such bioaccumulation 13 actually had a substantial impact on ecosystem 14 services, the services that ecosystems 15 provide. So I guess I would disagree with the 16 conclusion that's made in that particular

17 case. 18 The other causal determinations 19 with the caveat of what Bill said about the, 20 what were the environmental levels, that 21 phrase, I was okay with those. 22 Another Charge Question was, are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 313 1 there subject areas that should be added, 2 expanded upon, shorten or removed. I agree 3 with Bill that keeping the terrestrial and 4 aquatic systems separate makes a lot of sense. 5 It really helped me read it, to get 6 through it. But the one thing you lose there 7 is you lose, excuse me, you lose any 8 discussion of the connectivity of aquatic and 9 terrestrial systems. 10 And so in freshwater systems in 11 particular, the loadings of metals that come 12 into those systems largely come from the 13 terrestrial environment and there really is 14 not any discussion in Chapter 7 of those sort 15 of watershed-nature linkages of those 16 environments. I think that's a pretty 17 important omission. 18 A relatively small comment to -- a 19 lot of discussion in the chapter talks about 20 aging of lead in soils. It's not really, the, 21 excuse me, the definition of aging is 22 basically leeching following initial influx,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 314 1 but also binding and complexation. 2 It's a very confusing definition. 3 I think most people reading it would have a 4 gut feeling of what it means, but it's really 5 not much of a precise definition. 6 Leeching is a physical process. 7 Complexation and binding are chemical 8 processes. So this idea of aging isn't really 9 aging, it's more physical/chemical 10 transformation of the lead in the soil. 11 The points that are made are fine, 12 but maybe aging isn't quite the right term to 13 use, and maybe it would help readers if 14 another term were developed. 15 And then the last thing I'd say is 16 that I was very disappointed in both these 17 terrestrial and the aquatic ecosystem 18 sections, with the discussions of critical

19 loads. 20 In both cases, what the document 21 said is, well, you know, nobody's really 22 published anything on critical loads in the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 315 1 last five years, so I guess it's not 2 important. I guess we don't really need to 3 talk about it. 4 The fact that people haven't 5 published a lot on critical loads doesn't 6 necessarily mean that we are not in a better 7 position to use critical loads analysis to 8 look at some of these question. 9 We have a lot more, well a lot 10 more, there's more data out there. There are 11 more studies that can be used to support a 12 critical loads type analysis. And I thought 13 that the document kind of punted on that, when 14 they probably could've been a little bit more 15 productive. So, I'll stop there. 16 DR. FREY: Okay, thank you. Yes, 17 I think the term aging gets used in other -- 18 for other pollutants too. Maybe it's sort of 19 a popular term, but maybe not so precise. Dr.

20 Lanno? 21 DR. LANNO: I would like to concur 22 with the other panel members and say it was a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 316 1 well written document, and covered a lot of 2 ground. 3 And I think that the biggest 4 problem I really had with it was linking the 5 context and relevance of exposures that were 6 being made in vitro and lab systems to, but we7 could use, actually call, you know, policy8 relevant data. And so I'll talk a little bit 9 more about that in a second. 10 But I'll skip right down to the 11 Charge Question, are there any other subject 12 areas that should be expanded upon, shortened 13 or removed. And Bill covered quite nicely all14 the factors that could affect the bio15 availability of metals in lead and soils. 16 And it's a very complex system. 17 And there's a really nice schematic in the 18 Metals Risk Assessment Framework that captures 19 the interaction between chemical and metals 20 external to the organism, interacting with 21 environmental matrix, interaction with the 22 membranes, and kind of what happens once they

### 202-234-4433 Neal R. Gross & Co., Inc. Page 317 1 get inside the organism. 2 And that might be something that 3 would be useful to incorporate as kind of a 4 summary or introductory diagram or figure when 5 you start talking about bio-availability. 6 I guess this another editorial 7 thing, if you call these editorial. You 8 provided a nice little summary of background 9 levels of aquatic levels of lead, and there's 10 nothing for soils.

11 Now another U.S. EPA document on 12 the Eco-SSL, Ecological Soil Screening Level, 13 guidance for developing Eco-SSLs. If you go 14 to the lead document, they have a nice little 15 diagram of background lead concentrations in 16 the U.S. that might be useful to orient the 17 reader to what's background, what a dose might 18 actually be, a represent -- what a high dose 19 would represent. 20 And along with that the Biotic 21 Ligand Model that we talk about and this is 22 quite complex, and there's some great diagrams

### 202-234-4433 Neal R. Gross & Co., Inc. Page 318 1 that can show, provide a visual for that as 2 well. So, you know, a really good point of 3 talking that you can use to distinguish 4 between various factors that are affecting 5 metal speciation. 6 Along the lines of 7 bioconcentration, I'm following up with what 8 Dr. Allen said here. Throughout the document 9 I find that the terms bioaccumulation and 10 bioconcentration are being used 11 interchangeably. And there are very, very 12 definite definitions, that they are different. 13 And with bioconcentration being 14 solely uptake from water and often an artifact 15 of lab situations, where you test in the lab 16 and it was designed for organic compounds, 17 like Dr. Allen mentioned, so it's got 18 different implications. 19 Bioaccumulation factor would 20 involved anything that is in contact with 21 something that you're not sure where the metal 22 is coming from, so the diet. So it could be

### 202-234-4433 Neal R. Gross & Co., Inc. Page 319 1 ingestion of soil or sediment. So sediment 2 and soil tests would involve bioaccumulation

3 factor. 4 And we see the same thing with 5 bioaccumulation factors in soil, they will 6 decrease with the concentration of lead in the 7 soil, metal in the soil. 8 Nominal concentrations, done that. 9 And I'd like to address the comment, or the 10 Charge Question about, if the ISA was expanded 11 to consider dose response in terrestrial 12 systems, should we limit data to field soils? 13 And I'd say absolutely. Natural 14 soils are the only way to go. We 15 unfortunately, have this substrate that we use 16 for testing organisms called the OECD 17 Artificial Soil, which as any soil scientist 18 will tell you, it's not soil. It may be 19 closer to dirt, Herb, than soil. 20 But it's not a soil. It's a test 21 substrate. And it doesn't really have any 22 relevance if we're supposed to derive any kind

### 202-234-4433 Neal R. Gross & Co., Inc. Page 320 1 of guidance with respect to natural soils. 2 It has it's function as a medium 3 that you can use to test proof of principle 4 concepts of exposure to certain elements, and 5 even that's arguable, or certain compounds, 6 some people won't use it at all. But it can 7 be used in that context. 8 And so I don't really think it's 9 appropriate, you know, we have to be careful. 10 We call soils as well and how we sample them. 11 There's a lot of guidance out there that 12 involves how to go out and take soil samples 13 in the field. 14 You know, removing the organic 15 thatch and what horizons you're going to use 16 and define those. So there's quite a bit of 17 data available on how to do that in the soil 18 science literature that could be referred to. 19 The other thing is, you know, for, 20 if we're going to develop guidance for plants, 21 hydroponic testing probably is not as useful 22 as full soil, natural soil tests, or

### 202-234-4433 Neal R. Gross & Co., Inc. Page 321 1 artificial soil tests. 2 For many organisms, their 3 physiology changes when not in contact with a 4 substrate. That goes for aquatic sediment 5 organisms as well as terrestrial soil 6 invertebrates, as well as plants. You know, 7 plants may not have as much in the way of root 8 hair, so that changes the whole uptake surface 9 that's available for interacting with metals 10 in the medium. 11 So soils are the way to go natural. 12 Soils that are prepared and sampled, that's a 13 different story, but let's just say artificial 14 soils are not good, and natural soils are the 15 way to go. 16 Throughout the text there's again 17 this idea of relevance and context. 18 Statements like, accumulated significant 19 amounts of metal, or metal significantly 20 increased, or detected at elevated levels, 21 without the context of where you're comparing 22 it to a control. Is it the background levels?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 322 1 What's the comparison being made to? 2 So it's a little bit, I understand 3 that maybe we make the assumption that, you 4 know, if we have a series of concentrations, 5 we're going to, you know, compare our 6 exposures to a zero concentration. But is 7 that zero/zero, or is it a background level of

8 metal? 9 You know, so the context has to be 10 set in a way that we understand what the, you 11 know, the relevance of that effect we see in 12 terms of the increase of the parameter we're 13 measuring. 14 My final comment is basically 15 related to assessing these primary literature 16 documents, and what kind of quality assurance, 17 quality control, are we going to use to assess

18 whether or not the document and the data 19 within the document are actually useful for 20 developing any kind of assessment with respect 21 to lead in soils. 22 So there is an example for instance

### 202-234-4433 Neal R. Gross & Co., Inc. Page 323 1 of an I think it was a nematode experiments, 2 when they have I think it was exposed in agar, 3 and they had some molar value of lead 4 exposure, and looking at defects in 5 development and behavioral aspects of the

6 nematode. 7 And I'm thinking, okay, so how do 8 we relate that to population level effects. 9 It's possible, but it's an in vitro test from 10 a plate where you're exposing them in 11 solution, with no soil, and so how do we get 12 to the nematodes that actually live in the 13 soil. Same species, but, you know, different 14 test media. 15 And so we have to remember that, in 16 working with organisms as Bill said, we're 17 interested in community and population 18 effects, but not just structure, the function

19 as well. 20 And that's something that, you 21 know, we have organisms that people don't care 22 about. You know, who cares if worms get

### 202-234-4433 Neal R. Gross & Co., Inc. Page 324 1 cancer, maybe the fisherman do if they can't, 2 well even if they got cancer, you can take 3 them fishing I guess. 4 But, you know, the bottom line is 5 that they're performing a function out there. 6 They're turning over soil. They're ingesting 7 soil and organic carbon, and well then carbon 8 cycling as our collembola, as are bacteria. 9 And within that whole community, 10 there's this term called dysfunctional 11 redundancy, were often interested in just, is 12 the carbon cycled, and we don't care what 13 cycles it. So we have to remember that 14 context as well. It's, you know, not just the 15 organism. 16 So for bacterial tests in soil, we 17 will be looking at, you know, nitrification 18 processes and such that are important in 19 supporting all the ecosystem services that we

20 have. 21 So I think, you know, from that 22 context, let's try to make sure we use the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 325 1 right studies to describe what it is that we 2 want to do within policy development, make 3 them policy-relevant. 4 So there are a number of questions, 5 and it was a great guidance and again, 6 presented in the Eco-SSL document, as to what 7 are good studies to use from the primary 8 literature if we're doing this. So if you can 9 refer that document, that would be a good 10 place to start. 11 DR. FREY: All right, thank you. 12 Other comments on Chapter 7 and the Charge 13 Question for Chapter 7? Yes, Dr. Kosnett? 14 DR. KOSNETT: I had a question and 15 then a comment. And maybe, Roman, you can 16 answer this question about aging of lead in 17 soils. I mean I saw that there was a 18 discussion in there that aging tended to 19 increase lead's interaction with organic 20 material in the soil, and render it more 21 immobile. 22 And I just had a question about

### 202-234-4433 Neal R. Gross & Co., Inc. Page 326 1 aging of other mineral deposits of lead. Like 2 is it the case though, that when you have mine 3 tailings, like lead sulphide, and it gets 4 weathered, it becomes a sulphate or perhaps 5 even a carbonate, and becomes more mobile. Is

6 that correct?

7 DR. ALLEN: That's correct.

8 DR. KOSNETT: And should that be 9 reflected in here somewhere, I don't know. I 10 mean that might apply just to tailings, but I 11 didn't, when I read that I was just a little

12 confused because I had heard that. 13 DR. ALLEN: It applies not just to 14 tailings, but also to rice paddies. It 15 applies to reservoirs. Sulphide oxidation is 16 a well known phenomenon. 17 DR. KOSNETT: And that's considered 18 aging? That -- 19 DR. ALLEN: That is, that certainly 20 is one aging and it does not make things less 21 mobile, but makes them more mobile. So, what 22 is observed in adding metals to soil are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 327 1 generally from spiking experiments is that, 2 without leeching, even without leeching, so 3 that we don't have a mass-balance problem. 4 That with time, the assessibility 5 as a very general term, becomes less. And 6 this is due to physical/chemical changes, 7 reactions that are slow on the time scale of 8 these kind of observations, which are days to 9 months to years. 10 DR. KOSNETT: Okay so if I, perhaps 11 if I, and just to simplify it, is it possible 12 to say then, that when lead's already soluble, 13 in a soluble form, and it sits and ages in the 14 soil, it binds to organic materials and 15 becomes more immobile. 16 But if you start with a lead 17 sulphide, and you, like in tailings, and it 18 gets weathered, then there might be a period 19 of increased mobility?

20 DR. ALLEN: Yes. 21 DR. KOSNETT: Is that a way to put 22 it all together?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 328 1 DR. ALLEN: That's exactly what 2 will happen. Like we've done some recent 3 experiments in the laboratory not with lead 4 sulphide, but with another tailing, and that's 5 exactly what happens in the system.

6 DR. KOSNETT: And then I had one 7 other comment. And this was actually a 8 comment similar to one that I made earlier 9 this spring about the issue of commenting and 10 mentioning the extraordinary lead burden of 11 raptors that occurs in various parts of the 12 United States. 13 Now, you know, that is a 14 consequence of the use of lead ammunition. 15 And in the initial planning document it said 16 that the document won't consider the extent to 17 which ammunition contributes to the food 18 chain, and lead body burden of wildlife, 19 because that's not a source relative to 20 consideration of air-related lead. 21 But we do note that the document in 22 many other places considers background lead.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 329 1 And especially in the human section, you know, 2 we have a document on air lead, but we're 3 talking about contribution of paint and other 4 sources as it contributes to background. 5 And I think it would be, I would 6 like to make a request again, and I don't know 7 if there's a consensus or support for this, 8 but I hope there might be, that in order to 9 fully assess the impact of cumulative lead 10 from all sources including airway, pathways, 11 or air-related pathways, it's worth noting in 12 as comprehensive a document as this ISA is, of 13 that fact that, of all the wildlife out there, 14 probably the most highly impacted by lead are 15 the predatory birds, or the raptors. 16 You know, there was a study in 2009 17 in the Yellowstone ecosystem of 63 bald eagles 18 and golden eagles. And the median blood lead 19 concentration in those eagles were 41 20 micrograms per deciliter. And they're our 21 national bird, as an aside. 22 But, you know, so I just think that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 330 1 I would like to make a request and if people 2 agree, there's a consensus that at least there 3 be mention in here of that impact, of that 4 extraordinary background, because I don't 5 think there's any other animal, group of 6 animals that have that much lead. Does anyone 7 disagree with that? 8 DR. CORY-SLECHTA: So avians have 9 a nucleated red blood cell, so they bind lead 10 differently. They have higher blood leads 11 because of that. So I'm not sure you can 12 compare them directly to mammalian red blood 13 cell binding. 14 DR. KOSNETT: Do they have that? I 15 mean other birds don't have that -- 16 DR. CORY-SLECHTA: No, mammalians

17 don't. 18 DR. KOSNETT: -- it's the eagles, 19 the predatory birds. 20 DR. CORY-SLECHTA: But still I'm 21 not sure what that means relative to what we 22 think of in terms of mammalian blood lead

### 202-234-4433 Neal R. Gross & Co., Inc. Page 331 1 concentrations. I don't know how those curves 2 intersect, or where they intersect. 3 DR. KOSNETT: And that's a good, 4 that's an interesting point and I respect 5 that. But I'm just saying that this document 6 doesn't mention the extraordinary occurrence 7 of high lead levels in predatory birds as a 8 consequence of, probably of ammunition to a 9 certain extent. And I just want it to be 10 mentioned. I would like to request it be 11 mentioned. 12 DR. FREY: Well it seems like, yes, 13 reasonable enough to mention it, and mention 14 the different, I guess the different way lead 15 binds in avians. And I'm not sure if the 16 health implications are that well known, or 17 the species survival, or growth effects. 18 DR. KOSNETT: When, you know, and 19 I don't want to belabor this point, but when 20 it does come to things like the California 21 Condor and eagles and all that, there have

22 been a lot of adverse health effects

### 202-234-4433 Neal R. Gross & Co., Inc. Page 332 1 documented at the high levels that are being

2 seen. 3 DR. FREY: But I think if that's in 4 the context of exposure to lead ammunition, it 5 seems like something that could be noted, but, 6 unless it's important to a background7 characterization because there might be a non8 linearity in a response function, then how far 9 the EPA needs to go with that is I think maybe 10 not very far. 11 DR. KOSNETT: Yes, I don't think to 12 the extent that it contributes to background 13 and there's a desire to capture parts of 14 terrestrial organisms that have particularly 15 high backgrounds, I think is, it might be 16 worth mentioning. 17 DR. FREY: Okay. Okay, sounds fair 18 enough. I think we need to move on unless 19 there's a burning issue on ecological effects. 20 We'll go to Charge Question 6, which is on 21 susceptible populations and life-stages.

22 We're at about 4:20. I do want to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 333 1 try to adjourn by 5:30. And we have this 2 Charge Question and then Charge Question 2, 3 which is on the integrative summary. 4 So in making your comments, if you 5 might just keep in mind, you know, your 6 written comments will be part of what goes to 7 EPA. I think the focus here would be on, you 8 know, the significant comments that we all 9 need to hear, and EPA needs to hear. 10 But anything that's sort of 11 detailed maybe you can reserve that just for 12 your written comments. Yes, Dr. Hopke? 13 DR. HOPKE: And the lead discussant 14 should be pulling together all of the comments 15 from all of the people to make an integrated 16 consensus report. 17 DR. FREY: Sure, that's right. 18 Yes, and that's a good reminder. I mentioned 19 this at the beginning that the lead 20 discussants should be identifying the key 21 points that would go in the Summary Consensus 22 Response to the Charge Questions.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 334 1 I would like the lead discussants 2 to draft something by this evening so that 3 this could get emailed to me, so that I can 4 bring something back tomorrow. 5 We might not spend a lot of time 6 talking about it, but I'd want at least a 7 preliminary idea of where we are in answering 8 the Charge Questions. 9 And I've been taking a lot of 10 notes, so I have some idea, I think of what 11 our answers are, but I really want to get the 12 input from the lead discussants. So just keep 13 that in mind. That applies to about a dozen 14 of you who have a little bit of homework for 15 tonight. 16 Okay, let's go ahead and get into 17 Charge Question 6. This is Doctors Weitzman, 18 Cory-Slechta and Wasserman. And let's start 19 with Dr. Weitzman. 20 DR. WEITZMAN: I thought that this 21 was an important, kind of well-crafted 22 chapter. I did have a number of concrete

### 202-234-4433 Neal R. Gross & Co., Inc. Page 335 1 issues with it, and then suggestions. 2 Beginning with the title. So it 3 does deal with susceptibility and it does deal 4 with age as one of the characteristics that 5 lead tracks with, but there are a whole host 6 of other things that are discussed in this 7 chapter as well, such as where do you live, 8 nutritional status, and so it really is not 9 exactly capturing what the chapter's about. 10 So the chapter's division deals with 11 susceptibility to exposure and absorption of 12 lead as one part of it. And the other is 13 susceptibility to adverse consequences given 14 a certain exposure. 15 And I like that a great deal, but 16 I think that it was difficult for the people 17 who wrote this to stick to it. And so I kept 18 on getting confused because, in different 19 sections, the authors actually had things 20 mixed up. 21 So for example, underneath the 22 effects in nutrition, there's some discussion

### 202-234-4433 Neal R. Gross & Co., Inc. Page 336 1 of nutritional consequences of different lead 2 levels. But there's virtually nothing 3 discussed about nutrition as it leads to 4 absorption of lead, or to behaviors that 5 might, like pica that might increase it. 6 But I won't waste a lot of time on 7 this because I actually have, and what I've 8 written, specific pages of numbers where 9 things appear. 10 A generic issue was raised for me 11 in this chapter in that, repeatedly in the 12 chapter, there was mention, and in other parts 13 of the report, this was discussed in more 14 detail. 15 And I think it would make it a lot 16 easier if either the page references, or 17 hyperlinks were provided to those areas where 18 that was discussed. 19 And this is a variation on 20 something that several people have brought up, 21 including the gentleman who spoke this morning 22 representing the public, was now the member of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 337 1 the board, which is that, in the Effects 2 section, there are a fair number of variables 3 that are mentioned that are supported by one 4 or at most two studies. And for example, the 5 study on ADHD being heightened amongst 6 children who have secondhand smoke exposure,

7 and leads as well. 8 That's one study from NHANES. It's 9 cross-sectional. So that really we need to be 10 very careful in any way suggesting that there 11 are causal inferences here. 12 This is something, in fact this 13 chapter more than any other part of this 14 report for me, I found myself wanting to write 15 laundry lists of unanswered questions about 16 susceptibility. So that's what kept on coming 17 up for me. 18 There are a number of medical 19 mistakes in what's written. So for example, 20 in speaking about weight and blood lead and 21 renal function, so a BMRI of 25, and I'll give 22 you more examples, is not being obese, that's

### 202-234-4433 Neal R. Gross & Co., Inc. Page 338 1 overweight. 2 So there are a number referring to 3 people with diabetes as diabetics is now in 4 the medical community seen as something that's 5 impolite. You don't define somebody in terms 6 of a characteristic that they have. People 7 are more than the sum of their disease, and 8 that appears in a number of places here. 9 As relates to susceptibility to 10 lead exposure, I thought that there were a 11 number of things that, and it may be my bias 12 given what I count, my professional 13 background, but housing is extremely important 14 to children or to individuals' blood leads. 15 And it may or may not directly 16 affect them via exposures inside the house. 17 So many of the things that we're discussing in 18 terms of ambient lead may be a consequence of 19 deteriorating exterior paint. 20 And HUD and the National Center for 21 Healthy Housing, has mapped using geographic 22 information systems, extremely well those

### 202-234-4433 Neal R. Gross & Co., Inc. Page 339 1 parts of the country that have older houses or 2 don't have replaced windows. 3 And I think that if the point of 4 this is to be encyclopedic about the knowledge 5 that we currently have about exposure and 6 consequences, to me it doesn't make sense to 7 ignore housing, or urban/rural residence, or 8 proximity to -- it came up today, somewhat 9 jocularly about proximity to an airport, so 10 there are many sources that we know that there 11 are ways in which you could highlight children 12 as being exposed. 13 Again, I'm slipping over into what 14 isn't known, when you said, Michael, that 75 15 percent of ADHD is associated with genetics. 16 It's 75 percent of it runs in families. All 17 right, so you have parents who have it. 18 So it may be that having a parent 19 who has ADHD enhances the likelihood that, 20 given a specific exposure to lead, that you're 21 going to develop it as well. So yes, there's 22 a genetic basis to ADHD. There's a genetic

### 202-234-4433 Neal R. Gross & Co., Inc. Page 340 1 basis to absorption of lead. And I didn't 2 think that that kind of thing was discussed 3 well enough. 4 I mentioned the nutrition. There 5 was an extensive literature, at least on iron, 6 there's a much more rudimentary literature on 7 calcium and fat intake and children's 8 absorption of lead although, if you look at 9 the pediatric literature, people speak as if 10 it's a given, the calcium metabolism. 11 And calcium metabolism again, I 12 don't know that it belongs in this document. 13 But Vitamin D receptor genes have been shown 14 to be associated with lividity of absorption

15 of lead. 16 Part of the obesity epidemic is 17 that at least serologically, that very 18 substantial parts of the population now are 19 measurably Vitamin D-deficient. Although, 20 that raises all sorts of biologic questions. 21 If Vitamin D, which is a fat 22 soluble vitamin, is in cells, does that mean

### 202-234-4433 Neal R. Gross & Co., Inc. Page 341 1 that it's unavailable to function in terms of 2 its other functions? That is a whole emerging 3 literature. 4 But I don't know how exactly how 5 they're related to this, other than that we 6 know that lead is intimately tied to bone 7 metabolism, as is calcium and Vitamin D. 8 So I have a number of other things, 9 but I think I'll save that for the summary 10 that I'll put together. 11 DR. FREY: Okay, great, thank you. 12 Dr. Cory-Slechta? 13 DR. CORY-SLECHTA: Well, I had some 14 very specific things, to some extent I take 15 exception to, or maybe think we ought to 16 consider a little more critically, that show 17 up in the susceptible populations. 18 There is significant discussion in 19 there, as well as other parts of the document 20 amount gene/environment interactions. And 21 there's never in any place in the document any 22 indication of the magnitude of those effects.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 342 1 So this has come up peripherally 2 before, but, you know, are we talking about a 3 one percent or a two percent change, how 4 important are these as susceptibility factors? 5 Are they really, even, you know, a 6 beta coefficient doesn't really tell me 7 anything. If I'm talking about, are they 8 really changes of biological meaning in terms 9 of susceptibility, I can't tell from the 10 document. And a lot of what I see in the 11 literature doesn't suggest to me that they are 12 necessarily all that critical. 13 I think another thing that tends to 14 give over-sold has become dogma in the 15 literature more than anything else is that 16 early development is the most vulnerable 17 period. 18 And there clearly are, if we think 19 about things like toxicokinetics, that there 20 is greater vulnerability early on, but I would 21 suggest there is a significant database to 22 show that later periods in life generate lots

### 202-234-4433 Neal R. Gross & Co., Inc. Page 343 1 of adverse health effects. 2 You know, there's a huge rodent 3 literature showing exposures that don't even 4 start until, you know, adolescence or later, 5 can have great effects. The greatest effects 6 on LTP, which is the underlying physiological 7 substrate for learning, occur post-weaning in

8 rodent models. 9 So I think we tend to oversell it. 10 We state it. We don't put references in. And 11 I would note in the document, it's stated 12 several times with no references whatsoever. 13 So I think we tend to give it 14 greater emphasis than it deserves. Even some 15 of the longitudinal cross-sectional studies 16 where effects later in life were being 17 attributed to blood leads at two years, are 18 being reinterpreted because current blood lead 19 at seven, eight, nine, ten, 15 years old, is 20 as good or not better predictors. 21 So I think that needs more careful 22 thought than to just throw those old phrases

### 202-234-4433 Neal R. Gross & Co., Inc. Page 344 1 back out there. 2 And I want to come back to this, 3 two other issues. One is the importance of 4 gender. It just strikes me as just 5 extraordinary that, with all the literature on 6 lead, it's probably been studied more than any 7 other environmental chemical, we know almost 8 nothing about gender. 9 If the animal studies tell us 10 anything, we almost never see the same effects 11 in males and females. We never put them 12 together. They're always divergent. 13 So let me give you a little 14 example. We know that blood leads always tend 15 to be slightly higher in males than females. 16 We don't really know why. 17 So if you're thinking about the 18 distribution and the non-linearity of the 19 dose/effect curve, where presumably there 20 would be a greater number of girls because 21 the blood leads are lower, maybe in fact girls 22 are more sensitive.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 345 1 So the need to stop statistically 2 controlling out the effects of gender and to 3 look at those modifiers, and I think gender's 4 gotten far too little attention. 5 One thing that does come up in the 6 document, and I think is going to be important 7 in the future is the potential for epigenetic 8 changes and I think what they suggest in terms 9 of susceptibility, is the role of the maternal 10 and the paternal contribution to what those 11 might be later in life. 12 And I would also agree with the 13 comments about nutrition. And I think if 14 we're going to talk at all therapeutically, 15 most of those early studies were not done in 16 a way in populations where you could actually 17 determine how useful iron supplementation or 18 calcium supplementation were. 19 But again, I think that's something 20 that deserves a little bit more attention. So 21 those are my comments. Thanks. 22 DR. FREY: Great. Thank you very

### 202-234-4433 Neal R. Gross & Co., Inc. Page 346 1 much. Next is Dr. Wasserman. 2 DR. WASSERMAN: I would agree with3 those comments. This chapter's a real hodge4 podge of effects. And effect modifiers that 5 appear in a single study to me, should be very 6 suspect until -- I mean on the one hand we 7 have studies of IQ and lead, and there's like 8 hundreds and thousands of papers and then we 9 have like one study that finds something. 10 And there has to be some way of 11 saying there are 45 of these, but only two of 12 these, and they shouldn't all be presented 13 with a similar level of, gee, this is new and 14 interesting. 15 In fact the table that's in this 16 chapter, the Table 6-3 that lists all the 17 possible modifying factors, for almost all of 18 them the authors rightly conclude that more 19 evidence is warranted. 20 So I think that's the general 21 conclusion. But maybe it could be shrunken 22 down or integrated somehow better.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 347 1 DR. FREY: So maybe a general 2 warning, unless otherwise noted, more evidence 3 is needed or something like that. 4 DR. WASSERMAN: Exactly. 5 DR. FREY: Okay. 6 DR. WASSERMAN: Here's a list of 7 things for which we, that might be 8 interesting, but, gee, we'd like more. 9 DR. FREY: Right, okay. Was that 10 it? Those are your comments?

11 DR. WASSERMAN: Yes. 12 DR. FREY: Okay. I'm sorry someone 13 raised their hand. Yes, go ahead? 14 DR. WEITZMAN: Okay, but only in a 15 more general way on this topic. 16 DR. FREY: Okay. Well, I think all 17 the lead discussants have spoken. 18 DR. WEITZMAN: May I just? 19 DR. FREY: Yes, go ahead, and then.

20 DR. WEITZMAN: It relates to what 21 Debbie said. 22 DR. FREY: Okay, sure.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 348 1 DR. WEITZMAN: I won't belabor it. 2 You know, there's a much more extensive human 3 epidemiologic literature on IQ than many other 4 subtle but serious, you know, cognitive

5 decrements. 6 And what Debbie was pointing out 7 about, what we call critical windows of time, 8 and people will frequently talk about lead not 9 having a single biologic signature. It may 10 very well in part be due to different timing 11 of exposure. So you may have different 12 effects. And you may be susceptible to 13 different types of effects at different times. 14 DR. WASSSERMAN: Especially since 15 so many neurodevelopmental functions can't be 16 measured reliably, you can't even find 17 differences until adolescence. So if we're 18 not looking and because this document would 19 suggest, why even bother looking at

20 adolescence. 21 And other parts of these other 22 documents would suggest that the older people

### 202-234-4433 Neal R. Gross & Co., Inc. Page 349 1 get, the harder it is to even quantify what 2 their exposure is. But again would say, let's 3 not even go look there. But there's many 4 things that you can't even identify until you

5 look there. 6 DR. FREY: Okay. Yes, go ahead. 7 DR. RABINOWITZ: Well, if I could 8 just, I suppose, share a bias I have with you 9 all. And that is, I know a lot, year by year 10 more and more work is being done on 11 susceptibility in subpopulations, and it's 12 very important to find out who's the most 13 vulnerable to protect them. 14 Mostly we learn a lot about 15 mechanisms. However, the biggest predictor of 16 lead's effect on a person are not these 17 details about the person, but how much lead 18 there is. 19 And I'm afraid that we only have so 20 much emphasis to go around, only almost 21 resources to go around. And I don't want to 22 lose sight of the major factor that is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 350 1 affecting people's ill effects from lead is 2 how much lead is there, rather than some other 3 factor that modifies the effect. 4 DR. FREY: Sure, yes. 5 DR. CORY-SLECHTA: I think well, 6 no, I just think there's a different 7 interpretation of effect modifications, so, 8 and I'm very acutely aware of this is that, 9 lead may have effects at far lower levels in 10 the presence of some modifier, than it does 11 without that same context. And therefore, you 12 know, it can change essentially what we're 13 talking about as effective levels, and that's 14 not just for lead, it's for an toxicant. 15 So it may be that lead has effects 16 at one microgram instead of ten micrograms if 17 it's in the presence of insufficient iron 18 status or something like that. So I think 19 it's not just where the money goes, but, you 20 know, when we're talking about, more about the 21 risk assessment, per se. 22 DR. FREY: Phil, did you want to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 351 1 add something? 2 DR. GOODRUM: Yes, I'm just hoping 3 Michael can help me out here a little bit, 4 because I think I understand what you're 5 saying is that, you know, it's the mass. It's

6 the dose. 7 But I think in terms of setting 8 standards, you know, all things being equal, 9 and in other words, all populations being 10 exposed equally, is there an unequal response 11 due to differences in susceptibility. So I'm 12 just struggling a little bit with your point 13 on it's the quantity that is really the 14 driver. 15 DR. RABINOWITZ: Well, maybe I 16 didn't express it well or maybe I'm wrong. 17 But I think that the, one of the major drivers 18 of lead toxicity is how much lead's in the 19 environment. 20 Now I know our task is to protect 21 the most vulnerable among us, and for that 22 it's good that we go through all these other

### 202-234-4433 Neal R. Gross & Co., Inc. Page 352 1 exercises. 2 But I just wanted to have a naive 3 reader take away from this big fat document, 4 that what's important is how much lead is in 5 the environment, as well as these other

6 factors. 7 DR. GOODRUM: But it's the standard 8 setting that kind of influences how much lead 9 gets in the environment, so where we set that 10 standard, it's like a bad calculation, you

11 know. 12 DR. RABINOWITZ: To protect the

13 most vulnerable. 14 DR. FREY: Okay, any other burning 15 issues on Charge Question 6? Going once, 16 going twice, okay. Let's go to Charge 17 Question 2. 18 So this is the integrative health 19 and ecological effects overview. And now that 20 we've covered everything, we can, I guess, 21 focus on the integration aspects of Chapter 2. 22 And we have, let's see, one, two,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 353 1 three, four, five, six, seven, eight 2 discussants on this. So just keep in mind 3 that we probably have about 40 minutes on 4 this, at most. So 40 divided by eight is 5 five, right. So five minutes or less per 6 person. The lead discussants will start with 7 Dr. Davidson. 8 DR. DAVIDSON: Okay, thanks. 9 Thanks very much, Chris. Basically I felt 10 that Chapter 2 was probably the most difficult 11 chapter to write. And I also think that it 12 may end up being the most problematic. 13 Although, I think that there is a 14 lot of positive to say, is that it's a 15 tremendous synthesis of information, and that 16 synthesis that has parts that are well 17 presented. 18 The main overall problem that I 19 have with Chapter 2 is that it is, I guess, 20 not consistent in terms of both the content 21 that it has, and also inconsistent in terms of 22 how it references the other chapters.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 354 1 The content is a problem because 2 it's pretty clear that there are value 3 judgments being made here about, what is 4 important enough to include in Chapter 2, and 5 what is not sufficiently important, so you 6 just basically leave it in the rest of the 7 chapters without bringing it to bear in 8 Chapter 2. 9 And that's a very difficult thing 10 to do, and I'm not sure that everybody would 11 agree with the judgments that were made on 12 what to include in Chapter 2, versus what to

13 leave out. 14 When I read through Chapter 2, 15 there are certain areas where that I feel are 16 well written, but I want to get more 17 information on it. And so therefore, I would 18 like to know where it is in the rest of the 19 document that I can go in order to get that 20 more information, the more detailed 21 information. 22 Some sections like, a notable one

### 202-234-4433 Neal R. Gross & Co., Inc. Page 355 1 is, let me see here, Section 2.8.4.1, on 2 Exposure of Children, has lots of detail with 3 regard to where it is later in the document 4 that I can go and look this up.

5 Now there's a trade off here 6 between having so many citations to the later 7 chapters, that it almost ends up being 8 difficult to read. 9 On the other hand, the good thing 10 about it is that any detail that I want in 11 that Section 2.8.4.1, I know exactly where to 12 go to get more information. So there's a 13 little bit of a trade-off here between making 14 it easy to read and making it easy reference. 15 Conversely to this particular 16 section, there are several other sections 17 where the reader does not know where to go in 18 the rest of the document to find the 19 information. 20 And then there are some sections 21 where the content is not very thorough, and in 22 addition, there are not a whole lot of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 356 1 citations to the other chapters. So, you 2 know, kind of the bottom line here is 3 consistency all the way through. That's all

4 I have. 5 DR. FREY: Okay, thank you. Great.

6 Dr. Wasserman? 7 DR. WASSERMAN: I think as I 8 understood what was, that this is a summary, 9 but I also remember reading in Chapter 1, that 10 the first task is to determine causation and 11 then only if there's causation determined, 12 then to look at the magnitude of causation. 13 Because there's very little 14 reference in this Chapter 2, again to effect 15 sizes. But I'm not sure whether that's, that 16 may be because of this framework of, here 17 we're going to talk about causality, and then 18 later we'll talk about the magnitude. 19 On the other hand, so that would be 20 a plus for having this organizational 21 framework. This is just causation, amount of 22 causation.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 357 1 My concern would be that most 2 practitioners are going to read Chapter 2, and 3 no much else in this document. So I think it 4 really behooves us to have this to be as solid 5 as possible. 6 So it might be useful then to weave 7 in some aspect of clinical significance to 8 these effects that are mentioned here. Aside 9 from that, my points about Chapter 5 in terms 10 of the nomenclature, and some of the other 11 ways of considering things, so it all applied 12 to discussion here. 13 I like very much the framework of 14 saying, you know, this is a strong effect, 15 this is a minuscule effect, that's really very 16 helpful. That's a very nice rubric to carry

17 forward. 18 My concerns have to do primarily 19 with the fact that many people are just going 20 to stop here. And so is that, do you have in 21 here what you want to have in here. 22 DR. FREY: Okay, thank you. Next

### 202-234-4433 Neal R. Gross & Co., Inc. Page 358 1 is Dr. Herb Allen.

2 DR. ALLEN: I echo what Dr. 3 Davidson said on having a link in some way to 4 the more detailed information in other 5 chapters. 6 It certainly would help. It should 7 not be the reader's responsibility to try and 8 find where the information is that supports 9 the one or two sentences. And I think there 10 are a number of ways that can get handled. 11 A couple of, I have a number of 12 comments, but I'll give you only a couple. 13 The correlation of lead with zinc, bromine, 14 copper, and potassium from around the airports 15 was absolutely fascinating. 16 But, you know, shouldn't that be 17 followed up. If airplane fuel makes up 49 18 percent of the lead, then there have to be 19 very, very strong correlations of potassium in 20 that fuel, compared to potassium from other

21 sources. 22 And my guess is, that isn't true.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 359 1 My guess is that some of these correlations 2 are completely spurious. And again, that was 3 my point of, I think that you need to take a 4 deeper look at the information, other than 5 simply reporting what is said. 6 And I haven't gone through that 7 analysis myself, but that's simply a guess. 8 I think the copper, and others come from other 9 places. Bromine probably does come from the 10 fuel in the absence of significant signatures 11 from sea spray, which will overshadow it.

12 You use an LC50 as a measure to 13 compare environmental concentrations. I would 14 suggest that an LC50 probably, I'll defer to 15 my biologist friends, but killing half the 16 population is probably not a good idea. 17 You know, even as a chemist, I see 18 that. So if you're going to use a comparison 19 to an effects concentration, I'd pick an LC5 20 or an LC10, as being the kind of a number that 21 you might get away with, without raising 22 everybody's hackles, you know, in the process.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 360 1 One more on where I think you need 2 to be careful on taking data from the 3 literature. And that is, if I can find my own 4 comments. You have on Page 40, a discussion 5 of sediments, let me read you the one sentence 6 here, sediments are one of the things I happen 7 to have done some work on in my life. 8 "Since the 2006 lead AQCD, there is 9 further evidence for the effects of lead in 10 sediment associated communities, exposure to 11 three levels of sediment lead contamination," 12 and it gives the levels, "eye on a microcosmic 13 experiment, significantly reduced nematode 14 diversity and resulted in performing of 15 restructuring."

16 It had effects. So I looked at the 17 study, the first thing they did was to silt 18 the sediments and oxidize them. These aren't 19 sediments anymore, they're laboratory 20 manipulated former environmental sediments. 21 And how to relate this to what's 22 going on in the environment, I don't know.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 361 1 There isn't any sulphide left. You got rid of 2 it all. So it's modified and these effects 3 are not what you would see in the environment 4 and certainly not at these concentrations. 5 So I, you know, again I think you 6 need to really delve into what the studies 7 actually did, and then whether these data can 8 actually be used to draw these kind of 9 conclusions. 10 Or whether there might be 11 artifacts, and there's nothing wrong with the 12 study. I mean, you know, they did this, they 13 found this, those are the effects they found. 14 It's now taking this and trying to extrapolate 15 it and use this as saying, ah, ah ah, look at 16 this, you know, that's the problem. With 17 that, I be quiet. 18 DR. FREY: Okay, thank you. Dr. 19 Korrick?

20 DR. KORRICK: So I don't have a lot 21 to add, just two comments. I think that 22 because this is the section that maybe people

### 202-234-4433 Neal R. Gross & Co., Inc. Page 362 1 will start with, as integrating, that it's 2 important to set a tone of sort of, clear 3 thinking in this section. 4 And there are a number of examples 5 which I'll send in with my written comments 6 that that doesn't appear to be the case, I'll 7 give one that I found particularly confusing 8 on Page 11. 9 Which says, studies of adults 10 without occupational lead exposure have not 11 provided consistent evidence for associations 12 between blood lead and neurological effects, 13 I'm paraphrasing, has cognitive reserve may 14 compensate for the effects of lead. 15 Compensatory mechanisms may become 16 less affective with age, explaining the 17 consistent associations between measures of 18 accumulative lead exposure and neurocognitive 19 deficits. 20 So I found that logic a little hard 21 to understand. It somehow implies that bone 22 lead measures are done in a different age

### 202-234-4433 Neal R. Gross & Co., Inc. Page 363 1 distribution than blood lead, which is not 2 really the case. 3 So there are a number of examples 4 where, in summarizing sort of the overview of 5 what's in the document, the logic gets a 6 little bit perverted, and I think it is 7 important to sort of go back and do a quality 8 of thought check, and make sure that what's in 9 there really makes sense. It may be cutting 10 and pasting, I don't know what happened. 11 And my only other comment is, I 12 didn't realize until looking at this section, 13 that growth was never covered in the human 14 health review although, it's covered in the 15 ecology review. 16 And I wondered why that was. There 17 are studies, old but studies looking at 18 stature and lead, especially in childhood 19 growth charts that see lead-related decrements 20 in childhood stature, which I think are 21 interesting and mechanistically tie into some 22 of what's thought to be lead's effect on bone.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 364 1 And I wondered if that was a 2 conscious choice, or an oversight. Because 3 seeing the information in the ecology and 4 realizing it was absent from the human review, 5 I thought was sort of an unusual omission. 6 And maybe because it's old data, it 7 wasn't included. But I wondered if anybody 8 could comment on that? So those are my two. 9 (Off microphone comment.) 10 DR. KORRICK: Yes, so maybe the 11 chapter, the miscellaneous outcomes, growth is 12 in there, okay. So it should just come 13 forward in Chapter 2. I didn't see it, but. 14 DR. FREY: Okay, thank you. Dr.

15 Lanno? 16 DR. LANNO: I think it's really 17 interesting to see the comparison of these 18 toxicities, modes of toxic action across all 19 the different groups. And along with that 20 comes, from my perspective, it's how do we 21 compare these? 22 And if we do, we have to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 365 1 standardize the units. And this is kind of 2 something that got under my craw a little bit 3 was, you know, if we're going to express 4 exposure dose, let's be consistent with it. 5 And I take you to maybe to Table 2- 6 6 there. And it was really, really 7 interesting because I'd never done much work 8 with the human parameters. But it sticks in 9 my mind, micrograms per deciliter is the blood 10 value. So as soon as we talked about birds at 11 41, I'm going, okay, that means something. 12 But if you look at the other, the 13 exposure dose column in that table. You've 14 got picomolar, nanomolar, micromolar, and part 15 per million. 16 And first of all, part per million 17 is not even an exposure dose. I mean, let's 18 at least put SI units and go to milligrams per 19 liter, or something like that for that. 20 And then I said, okay, well here's 21 a good chance to use HERO, so let's go and 22 look in the database and see what this part

### 202-234-4433 Neal R. Gross & Co., Inc. Page 366 1 per million actually was in. 2 And so, if I go to this table here, 3 I'm going to this table here, okay. So it was 4 the studies of the second last line there, 5 endocrine disruption, and it states the dose 6 is 20 part per million acute, and there's two 7 references given. 8 And I went to one of them, and one 9 of them was actually the experiment that that 10 value came from, and it was in drinking water. 11 So then I went to the other one, 12 and it was in some other medium. None of 13 these are in air, so it's not really clear to

14 me. I mean we talk about context and 15 relevance again, so drinking water and an 16 effect, and then the other one was an in vitro

17 test and an effect. 18 And again, I think we really have 19 to be careful, if like as Dr. Wasserman 20 mentioned, if this is the only chapter 21 somebody is going to read, we have to be very 22 careful of the context of the exposure doses

### 202-234-4433 Neal R. Gross & Co., Inc. Page 367 1 as you express them in this chapter. 2 And I would suggest that, you know, 3 at least SI units, molar is best because 4 you're not dealing with a massive chemical, a 5 massive lead at the site of toxic actions, the 6 number of moles of the element at the site of 7 toxic action, interact with the biological 8 molecules. So, molar might be the best way to 9 express it, but at least SI units. 10 And one last comments, I see that 11 we go from human to ecological, and then we've 12 got all these great summary tables for the 13 human section. And we don't have those great 14 summary tables for the ecological section. 15 It'd be nice to have them if we could. 16 And in the ecological section you 17 tend to forget to include references, so 18 people can go to the paper where the data 19 might have been presented. And there's very 20 few measures of exposure dose that are 21 presented in the ecological section. 22 So I think maybe we're getting the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 368 1 short shrift there in the ecological section, 2 in terms of the interpretations. So maybe 3 that would be something to look at when you go 4 through it again. 5 DR. FREY: Okay, thanks. Dr. 6 Rabinowitz? 7 DR. RABINOWITZ: Okay. In the 8 interest of time, I'll try and be a little 9 brief. Of course I know everybody reads 10 carefully everything I type, so I'll try and 11 talk here instead about substantive things

12 more. 13 And it was irresistible to try and 14 compare the welfare system, the ecosystem with 15 the humans, and the question is, it's just 16 irresistible, I'm glad you did it, the 17 question is doing it right. 18 And it's a matter of aligning the, 19 so the doses and exposures are all kind of 20 correspond. There's hazards in doing this, 21 but they all become apparent to you and you'll 22 highlight it for us.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 369 1 I guess my main concern has to do 2 with causality. And a lot of that really 3 appears first in the document, back in Chapter 4 1, and on Page 19. But with your indulgence, 5 could I address it here? 6 And I just, let me find my -- I 7 guess it has to do with, let me just find 8 myself here, excuse me. It has to do with 9 whether lead is the independent risk factor, 10 maybe I can just read what I wrote here. 11 I wish efforts could be made to 12 show the extent or strength of confounding, in 13 the context of the effect size for lead. And14 for the whole model's predictive power, the R15 squared. 16 The presentation the researchers 17 they cite, and the journal reviewers they must 18 satisfy, seem content to show that lead as a 19 non-zero coefficient in multiple regression

20 models. 21 For example, and for children, and 22 the mental performance. But because of the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 370 1 extent of the confounding, this is different 2 than showing that lead is an independent risk

3 factor. 4 And these other risk factors often 5 share considerable variants with lead, 6 particularly in some of the high risk 7 populations, lead exposure and other risk 8 factors coexist. 9 The relative size of this non-zero 10 coefficient, the size of the lead effect, 11 should be shown in terms of the total model, 12 R-squared, the goodness of fit, some measure

13 that. 14 How good is the model's fit and 15 does adding a lead term improve the model's 16 goodness of fit, having nested models. I'm 17 not a statistician, but when people tried to 18 teach me things, they thought that I would be 19 part of the standard. 20 Is to see if you add lead to a 21 model, does it improve the model's goodness of 22 fit, to show a model with a lead term, without

### 202-234-4433 Neal R. Gross & Co., Inc. Page 371 1 a lead term, don't just satisfy us, and show

2 a non-zero lead term. 3 I would like to see just lead 4 improved the model's goodness of fit. Do the 5 other coefficients of the other risk factors 6 change significantly. 7 Those are the types of things I'd 8 like to see when people say that lead is a 9 risk factor, especially these low levels. My 10 concern really is that these increasingly low 11 levels and, you know, I've been at this long 12 enough, I think that everything now is low

13 level. 14 Where lead effects are small, blood 15 lead can still be measured relatively 16 accurately, usually to at least two 17 significant figures. 18 Where other stronger variables such 19 as maternal education, the richness of a 20 child's home environment, it's hard to measure 21 it to two significant figures. And also, 22 they've often entered it to the models as

### 202-234-4433 Neal R. Gross & Co., Inc. Page 372 1 broad categorical variables where lead is 2 allowed to be a continuous variable. 3 So for these reasons, I'm sorry, 4 but I still remain skeptical that at these 5 rather low levels, the effects that are 6 attributed to lead are fully caused by lead. 7 And besides that, there's a few 8 other comments I have mostly about, well I 9 just, how some tables could be made better, 10 some things could be made better. 11 The work that Arthur Chamberlain 12 did, that you report here, that fell into the 13 chapter of ethyl lead, by the time he burned 14 and exposed it to people, it's really 15 inorganic lead, so maybe that needed to be 16 shifted. Things like that, so thank you. 17 DR. FREY: Okay, thank you. Next, 18 Dr. von Lindern? 19 DR. von LINDERN: Thank you. I have 20 the distinction of having stood between us at 21 lunch, and now -- 22 (Laughter)

### 202-234-4433 Neal R. Gross & Co., Inc. Page 373 1 DR. FREY: We planned carefully. 2 DR. von LINDERN: So I'll hold it 3 to two main comments. One, I really liked 4 this chapter and I think it was a courageous 5 presentation. 6 And in, kind of, the history of 7 these documents and this process, I think it's 8 an important event because you are trying, for 9 the first time to bring the ecological and 10 human health material together, and I think

11 that's an advancement for EPA and for the 12 science. 13 That being said, you're bringing 14 two disciplines that haven't greatly 15 cooperated over the years together, and 16 they're both not going to like it. So you're 17 going to get a lot of criticism there, but 18 that should be constructive criticism that 19 should be a starting point for building this 20 as a process in EPA, so I commend you for

21 that. 22 I think it was excellently edited.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 374 1 It was a good read. And I'm not used to 2 giving these many compliments, so now I'll 3 move to the other part. 4 And this isn't a criticism of the 5 chapter so much, as it is perhaps the status 6 of knowledge right now, or what information 7 was sought, only for 72 pages of this chapter 8 address exposure. 9 But exposure is a critical part of 10 doing the overall job here, and doing the risk 11 assessment that we'll discuss tomorrow. And 12 is that because we haven't looked at that 13 information or is that because there's no new 14 information, or is that because there's no 15 information about contemporary exposures in 16 the country. 17 So I beat that horse one more time, 18 and then I yield. Thank you. 19 DR. FREY: Okay, thank you. Is 20 there a question on this point, or?

21 DR. CORY-SLECHTA: It was on 22 Michael Rabinowitz's comment.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 375 1 DR. FREY: Okay. All right, why 2 don't you go ahead then? 3 DR. CORY-SLECHTA: Well, I guess 4 I'd like us to sort of consider the opposite 5 point of view, and Michael, and I would argue 6 some of the same things that David Bellinger 7 has argued. That in many of these 8 epidemiological studies, we completely

9 overcontrol. 10 So for example, if I go to the

11 Rochester Cohort database and I look at the 12 correlations between virtually, mother's IQ, 13 income, home score, you name it, they are so 14 highly correlated, they essentially all boil

15 down to one. 16 And yet we throw every single one 17 of those into every study, and we do it not 18 for a good biological rationale, we do because 19 everyone else did it, or it won't get 20 published if we don't put it in. 21 But I would argue that we probably 22 don't really appreciate the magnitude of the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 376 1 effect because we're so extensively over 2 controlling for all of the other things we 3 think are out there, that are all highly 4 related and boil down probably to SES. 5 DR. RABINOWITZ: I find myself 6 agreeing with you, that these are really all 7 wrapped up in some way, and that's why I think 8 it would be better for the reader to see it 9 with and without lead, and they can see the 10 extent of this confounding. Maybe it's over 11 controlled, you know. 12 DR. CORY-SLECHTA: Nobody presents 13 the correlations between all the other 14 covariants, that's the big, so.

15 DR. RABINOWITZ: Would nested 16 models help you in that circumstance?

17 DR. CORY-SLECHTA: What?

18 DR. RABINOWITZ: Would nested 19 models help you in that circumstance to

20 understand? 21 DR. CORY-SLECHTA: Yes, and no. 22 There would be several ways to look at it I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 377 1 think. 2 DR. FREY: Okay. Dr. Weitzman? 3 DR. WEITZMAN: So I agree with much 4 of what's been discussed. I think that it's 5 really a remarkably well put together

6 document. 7 I think there's a metaphysical 8 question that has to be answered, which is, 9 whether it's a summary, it's an executive 10 summary that comes up front, or it's something 11 that comes later, and how one structures an 12 executive summary is often different than the 13 closing chapter or concluding chapter, in a 14 volume of this size. 15 I think that this would be a great 16 place to try new technological efforts since 17 this is going to be online to link people to 18 the myriad places where this heroic effort has 19 been undertaken to summarize a truly 20 voluminous literature. 21 So I do think that there are ways 22 to do that. And the only concrete objection

### 202-234-4433 Neal R. Gross & Co., Inc. Page 378 1 that I had, I'm not sure that it applies to 2 both volumes that you provided to us, but it 3 certainly applies to Chapter 2. 4 There's one sentence that says that 5 there are studies that show associations 6 between lead in paint, and children's blood 7 lead levels. So I understand that the purview 8 of this exercise doesn't focus on paint or 9 children's homes. 10 But somehow it seems to do a 11 disservice to the most ubiquitous 12 environmental problem that confronts children, 13 namely lead, to have just one sentence that 14 says there's an association that's been shown. 15 So, yes there are multiple, 16 multiple, this is a multimedia exposure 17 problem, but it somehow seems disingenuous to 18 have that one sentence as enough. 19 DR. FREY: Okay. Any other 20 comments on Chapter 2? Rich? 21 MR. POIROT: I just wanted to echo 22 Ian's point about how useful I thought it was

### 202-234-4433 Neal R. Gross & Co., Inc. Page 379 1 to really try to put the health and 2 environmental effects together. 3 You know, if for no other reason 4 then, you know, some of you may know, I've 5 been on a campaign for many years to try to 6 get the Agency to consider having separate 7 secondary standards for pollutants. 8 And in some cases, those have been 9 very well justified. But conversely, 10 secondary standards are almost always set 11 equal to the primary standards, even when 12 there's no justification whatsoever for doing

13 that. 14 You know, the most recent example 15 I think would be the secondary Sox NOx, now 16 we're going to have secondary standards for 17 NO2, I don't know. At any rate, I think that 18 this will really put you in a much better 19 position to draw those links and to establish 20 secondary standards that are justified, which 21 I think would be important.

22 CHIARMAN FREY: I wanted to make

### 202-234-4433 Neal R. Gross & Co., Inc. Page 380 1 one comment and then, so I guess on the one 2 hand I was almost thinking we wouldn't have a 3 comment about where Chapter 2 was. 4 But it's kind of funny because I 5 guess, I don't know how many of us are also on 6 the ozone panel, there was big discussion on 7 the ozone panel about this issue for that ISA. 8 And what I am sensing from the 9 relative lack of commentary about it is, and 10 I guess a lot of positive comments about this 11 ISA's Chapter 2 is that, and maybe I'm over 12 interpreting. 13 But there was I think a general 14 comfort level with Chapter 2, where it was, 15 and kind of the general scope but, you know, 16 taking into account some of the comments we've 17 heard about need for consistent, kind of level 18 of detail and referencing to other parts of 19 the document, and then of technical issues

20 here and there. 21 But I think the question of 22 whether, you know, this is an executive

### 202-234-4433 Neal R. Gross & Co., Inc. Page 381 1 summary, is it a summary, should it come early 2 or later in the document, inevitably comes up 3 I think for every ISA, for every criteria 4 pollutant review. 5 And I think, I guess I'm wondering 6 if anyone feels strongly that Chapter 2 needs 7 to be other than where it is, and kind of 8 other than what it is. 9 You know, I think there's some 10 value for the reader to have that early in the 11 document before you might, I guess get up the 12 courage to go look at Chapter 5, which is it's 13 own -- yes, and energy. 14 I guess I just want to get a sense, 15 because I think EPA would appreciate the 16 feedback and maybe the feedback from this 17 panel will be different than other panels, 18 which is fine. 19 DR. GOODRUM: I'll just quickly 20 respond that I think if it's -- well, where it 21 is, it's a good preview, especially given most 22 of the chapters have, there's an attempt to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 382 1 have a mini summary at the end of the chapters 2 anyway, so I don't feel a need for an overall 3 document executive summary. 4 DR. FREY: Okay. Yes, Cliff? 5 DR. DAVIDSON: Yes, I guess I agree 6 with that, but I think when I hear the words 7 executive summary, I think about, you know, a 8 small bite size piece that I can look at. And 9 Chapter 2 will never be a bite size piece, 10 it'll be voluminous in its own right. 11 But obviously, much shorter than 12 the whole rest of the document. So I kind of 13 like where it is as well, because I don't 14 think it looks like an executive summary. 15 DR. FREY: Yes, I think one other 16 aspect that maybe was more evident in this ISA 17 than in other pollutants, is the integrative 18 aspect, and particularly the human and eco, I 19 think as some people have already pointed out, 20 a nice improvement. 21 So I just wanted to echo some of 22 that for EPA's benefit because I think,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 383 1 certainly there's some things to revise there, 2 but by and large, it seems to be about where 3 it needs to be. And probably about the length 4 it has to be. 5 You know, I don't think an 6 executive summary is probably even realistic 7 for this document. Any other, I guess Dr. 8 Kosnett, you had something you wanted to tell

9 us. 10 DR. KOSNETT: Earlier when I had 11 made some comments about Chapter 5, I also 12 mentioned my concerns about the application of 13 the causal framework, and certainly that gets 14 recapitulated and summarized in Chapter 2. 15 So I hope that, to the extent

16 there's consensus that those concerns would be 17 raised in the comments on Chapter 2. 18 DR. FREY: Okay. Are we about out 19 of steam, from the panel? Anything else on 20 Chapter 2? If not, John, you have a -- 21 DR. VANDENBERG: I very much 22 appreciate the discussion about Chapter 2, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 384 1 again as you mentioned Chris, there was quite 2 a discussion about this with those on it. 3 We've been fortunate in that we've 4 got a pretty dynamic process. We can change 5 things, and so we consider all the detailed 6 comments as was asked, or a comment made 7 earlier, but we also consider the big picture, 8 kind of structural things. 9 And so, if you'll allow us, what I 10 might ask is for Mary Ross to share some of 11 thinking that's been going into what we've 12 been reacting to from the comments on the 13 ozone document, is that may help you get some 14 sense of the direction that we're going, and 15 it's some of the reframing of things. 16 And part of that I think is a 17 reflection of, even the sense here, is this an 18 executive summary, is this an integrated 19 overview, is this redundant, is it different, 20 what is it? 21 And so we're trying to rethink that 22 and think of what's the most effective way for

### 202-234-4433 Neal R. Gross & Co., Inc. Page 385 1 us to communicate to perhaps a variety of 2 audiences. 3 And there are a variety of 4 audiences clearly, you know, different 5 audiences have different needs for 6 information. So if you'll give us just a 7 second, let me ask Mary to give her thoughts

8 on that. 9 DR. FREY: Yes, just I guess one 10 little comment about the ozone. My 11 recollection of the response to the relevant 12 charge questionnaire, was that that panel 13 actually didn't really have a consensus as to 14 what that Chapter 2 should be. 15 And among the opinions in that 16 panel were, comfort with kind of where it was, 17 which was analogous to what we're seeing here, 18 but yes, it would be interesting to hear, you 19 know, what your thoughts are moving forward. 20 DR. ROSS: Yes, because we heard 21 various executive summary, put it at the end. 22 And so one of the things we've considered, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 386 1 others actually independently have said, why 2 is this Chapter 2? 3 So we have considered merging 4 Chapters 1 and 2 into an over arching summary 5 that comes up front that's more than an 6 executive summary. 7 We might add then your snapshot, if 8 needed, for a long chapter. But we take a lot 9 of what's Chapter 1 and put it into two other 10 places. 11 And those would be a preface that 12 include the history of the pollutant, the 13 history of the NAAQS review, and the 14 legislative background that are specific to 15 that pollutant that are useful information, 16 but you don't necessarily have to read it to 17 get into the health and eco effects. 18 So that would be a preface that 19 would include what is now legislative and 20 historical information. And move the 21 causality framework into a preamble, since 22 that is actually applied across pollutants.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 387 1 Not unlike what's done for IARC, 2 for those of you familiar with the IARC 3 process. So then that would still be 4 available electronically, but it actually 5 diminishes Chapter 1 to about four or five 6 pages, that is specific to the pollutant. 7 This is lead. This is the standard 8 for lead. These are the policy relevant 9 questions. These are the literatures. The 10 parameters that would play a role in 11 developing this document, that lead right into 12 what is now Chapter 2. 13 We were going to test run that for 14 ozone. I guess we can ask you feedback on 15 whether you thought that would be useful here. 16 Then Chapter 1 and 2 would become one thing at 17 the beginning of the document. 18 DR. FREY: Okay. 19 DR. VANDENBERG: So I think the 20 point is that we're actively thinking this 21 through, and trying to think of different ways 22 to frame it that would be as affective as

### 202-234-4433 Neal R. Gross & Co., Inc. Page 388 1 possible, so your comments are very much

2 welcome. 3 DR. FREY: Yes, Dr. Wasserman? 4 DR. WASSERMAN: I think that if you 5 want to put the causal framework, like the 6 logic of the framework separate from the 7 results, that might work well. 8 But I actually like having your 9 causal determination as a separate piece, not 10 merged in with the history and the act and all 11 the legislative stuff, but just the 12 determination that this is a level one, and 13 this is a level four, and there's strong 14 evidence here. I like those things, gold 15 boxes that you can put something in. 16 DR. ROSS: And I'm sorry, I 17 misspoke, so the legislative, the history 18 would be in a preface, but all of the causal 19 determinations and the discussion of it would 20 remain. But the general structure of the 21 framework, the Hill criteria, and the things 22 would be in a side document that, since that's

### 202-234-4433 Neal R. Gross & Co., Inc. Page 389 1 sort of the basis for determining it. But 2 definitely what's in Chapter 2 would stay in 3 the document. If that's, perhaps I -- 4 DR. WASSERMAN: I just didn't want 5 to have that causal, your possible conclusions 6 merged in with the history of -- 7 DR. ROSS: No, that wasn't what we 8 intended. We were trying to get them farther 9 apart.

10 DR. WASSERMAN: Yes. 11 DR. FREY: Well I think the lack of 12 the vehement opposition might be interpreted 13 as implicit support. I mean it sounds like 14 something worthwhile to experiment with. 15 And yes, I think the generic causal 16 framework that's in Chapter 1, you know, that17 appears in every ISA, and making that a stand18 alone document that is consistent has a lot of 19 benefit. 20 But then as, I think you alluded to 21 some interpretation relative to each pollutant 22 is still useful, but that would still be in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 390 1 this new Chapter 1, so that sounds fine. 2 Okay, well I think we've gotten 3 through a day of charge questions on the ISA. 4 So I think we're at the point in the agenda 5 that is labeled Summary and Action Items. 6 I think given the time, I do want 7 to adjourn at 5:30 and it's 5:22 now, so I 8 don't want to try to do a summary right now. 9 What I would like to do is just 10 remind the lead discussants if they could 11 please put together, whether you do it in 12 bullet form or paragraph form is fine, I'm 13 mainly interested in the content of what you 14 think the key consensus points are for your 15 charge question, and email that to me and 16 Aaron, preferably if you can by, not later 17 than 10 o'clock tonight. 18 I'd like to have a chance to take 19 a look through that. I would like possibly 20 tomorrow morning to just spend a little bit of 21 time reviewing that, because I think whatever 22 we can do face to face here, could save us a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 391 1 lot time in a teleconference later on. 2 And we will have to have a 3 teleconference to follow on, to review, you 4 know, the full draft of the letter to the 5 administrator, the response to charge 6 questions for this review of the ISA. 7 So the more we do to kind of put 8 that in, at least content before we adjourn 9 from this meeting in our TP, the better. Yes? 10 (Off microphone comment.) 11 DR. FREY: Yes, I'll get to that. 12 Are there any questions about what I'm asking 13 in terms of the response on the charge 14 questions? Does that seem clear? Everyone 15 know who they are, who's, I made a list. 16 It includes Drs. Kosnett, George 17 Allen, Rich Poirot, von Lindern, Pounds, 18 Goodrum, Cory-Slechta, Korrick, Stubblefield. 19 I can't read my writing. Wait, now I should 20 be able to figure out who that is. 21 PARTICIPANT: Everyone with an 22 asterisk.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 392 1 DR. FREY: Everyone with an 2 asterisk. Let's see Stubblefield, Weitzman, 3 that's what I couldn't read, Davidson and 4 Wasserman. Yes, so all of you are on the hook 5 for homework assignment. 6 But all of your co-discussants 7 should please make, if you haven't already 8 provided your written comments, or if you 9 revised your written comments, please get that 10 to your lead discussant on each of the charge 11 questions your on, and that'll help them write 12 the summary. 13 Tomorrow we start at 8:30 sharp. 14 We will have a presentation from Brian Hubble 15 and others from EPA's Office of Air Quality 16 Planning and Standards on the exposure and 17 risk assessment scope and methods plan. 18 Do we have any public comments? 19 Right now, we don't have any signed up. So 20 then we'll have discussions on health risk 21 issues, and welfare risk issues related to 22 that scope and methods plan.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 393 1 And that will be a consultation so 2 we do not need to present, or produce a 3 consensus report. So our work tomorrow's a 4 little bit, maybe more straightforward in that 5 regard. 6 I saw a list of all the airline 7 departure times. I think 99 percent of us are 8 here until at least noon, maybe one exception, 9 and I think may of you had flights around 2:30

10 or so. 11 So we're scheduled to go until 12 12:30 tomorrow, and as I said, you know, if we 13 can I do want to use some time tomorrow 14 morning to look over the Response to Charge 15 Questions. 16 So if I can get your input tonight, 17 if things go well, maybe we'll have a rough 18 draft of the content of the Response to Charge 19 Questions that we can hand out first thing

20 tomorrow. 21 You could take a quick look at it 22 when you come in, and if there are any content

### 202-234-4433 Neal R. Gross & Co., Inc. Page 394 1 issues there, we can try to address that. We 2 don't need to do all the wordsmithing. Yes? 3 (Off microphone question.) 4 DR. FREY: For tomorrow's ERA, if 5 you have pre-meeting comments, you can submit 6 those. There's no other specific homework for 7 the REA. Any other questions? Anything from? 8 I guess John, and did we meet your needs, or 9 do you have any last questions, things that 10 you were hoping to hear that you didn't hear

11 about? 12 DR. VANDENBERG: No, I would just 13 like to extend my great appreciation. This 14 has been very, very helpful. We appreciate 15 the time and energy, and we will very much 16 appreciate your written comments as well. We 17 do go through them very carefully. So thank 18 you, really thank you very much from all of

19 us. 20 DR. FREY: Yes, actually maybe 21 along that line, there was in the 22 administrative meeting, there was some, I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 395 1 think new members who were asking, what 2 happens to our comments? 3 And I assured the panel that EPA 4 does take them very seriously, and certainly 5 anything that we put in the letter to the 6 administrator, or in the Consensus Response to 7 the Charge Questions, I think EPA has a pretty 8 high burden either to respond to those or come 9 back with a pretty good reason why it wasn't 10 possible to do that. 11 And then also, that EPA does look 12 through all the individual member comments, 13 and I think that's a fair statement.

14 DR. VANDENBERG: That's correct. 15 DR. FREY: Okay. Yes? 16 DR. GOODRUM: A question, if we 17 included some charts along with our text 18 comments, would you like us to attach Excel 19 files? 20 DR. VANDENBERG: If you attach the 21 chart that you generated?

22 DR. GOODRUM: Yes.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 396 1 DR. VANDENBERG: Or a chart that 2 you lifted from part of -- 3 DR. GOODRUM: Yes, as part of our 4 notes. If we generated charts to explain a 5 concept? 6 DR. VANDENBERG: No, I don't --

7 DR. GOODRUM: No?

8 DR. ROSS: I don't know that we 9 need the Excel file unless you wanted us to do 10 something with it. But I mean the 11 presentation. 12 DR. FREY: Okay. Well, I think 13 with that we're going to finish early. It's 14 5:28, and we're adjourned. 15 MR. YEOW: We can be adjourned. 16 (Whereupon, the above-entitled 17 matter went off the record at 5:29 p.m.)

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26:10 31:11,14 33:9 36:20 40:2,8 63:7,9 65:5,10 78:2 82:18 94:12 94:18 95:8 108:22 270:18 298:7 356:9 369:4 386:4 386:9 387:5,16 389:16 390:1 1,200 57:4,11 1-25 270:19 1.2 298:12 1.5 209:4,7 219:12

227:3 1.6 214:1 1:15 166:20 167:1 10 3:4 37:11 115:13

115:14 150:7 213:17 390:17 10:37 95:17 10:50 95:14 10:51 95:18 100 236:4 268:3,3 100,000 268:4 109 66:16 11 362:8 11th 217:20 115 300:6 12 150:4,7 226:22 12,000 57:10 12:10 166:22 12:30 393:12 14 103:9,9 108:5 15 95:20 104:9

203:19 209:4,10 211:1,19 213:11 213:17 214:11 219:12 343:19 15-minute 95:12 152 3:12,13 16 103:9 104:10 168 3:14 19 369:4 1950 241:21 1975 71:19 1980s 201:9 1985 289:3 1995 306:2 1996 306:3 308:12 2 24:12 19:14 21:3

24:19 26:10 32:8 32:9 33:13 36:2 39:7 40:22 42:2 103:9 199:6 214:9 214:10 271:9 273:15 333:2 352:17,21 353:10 353:19 354:4,8,12 354:14 356:14 357:2 364:13 365:5 378:3,20 380:3,11,14 381:6 382:9 383:14,17 383:20,22 385:14 386:2,4 387:12,16 389:2 2-2 271:12 2-26 271:9,11 2-3 271:10,10 2.2 56:9 2.5 33:14 115:13,13 125:3,3 2.7 36:2 2.8.4.1 355:1,11 2:30 393:9 20 1:9 115:6,10

202:3 203:20 204:14,20 205:1 205:11 226:3 241:15 366:6 20-21st28:10 2001 119:10,10 2002 119:11 2003 122:16 289:7 2004 261:10 2005 129:7 301:14 2006 31:3 82:1

235:10 288:12,17 305:15,16 360:8 2008 36:5 103:9 2009 329:16 2011 1:9 308:12 2012 28:21 106:16 2013 104:16 2014 29:14 2016 104:19 22 3:5 199:9 223 3:15 231 3:17,19 241 3:20 25 202:3 337:21 251 3:22 26 291:12 282 3:23 3 3 3:9 19:21 20:1

34:9,9 76:9 77:16 95:15 96:1,14 103:8 108:16 109:22 122:3 133:15 138:1 142:14 147:9,20 150:10 151:4 157:18,22 163:2 214:9 226:5,5 3-102 103:2 3-19 131:15 3-69 108:4 3.2.2.6 118:22 3.2.5 108:3 3.4 104:9 3.4.1 97:7 3:14 282:3 3:25 281:21 282:4 30 203:13,21 204:6

204:14 220:16,21 225:15 241:15 246:10 334 3:25 3524:14 36,000 57:15 61:19 374 131:17 3904:17 3964:19 4 4 3:11 20:6 35:3,4

35:15 77:10,18 143:21 151:6,19 157:18,22 163:2 180:15 195:2 199:4,8 202:7 203:1 205:18 206:9 207:5,6 220:6,7 222:4,22 225:2,2,3 226:6 228:19 236:15 4a 3:13,14,15 142:19 143:1 151:15 156:22 157:4,7 166:15 4b 157:4 167:3,3,6 167:10 177:1 205:20 4c 151:19 205:17

222:8 228:19 4-1 155:1 200:13 225:1 4-11 218:11 4-4 225:3 4-49 202:20 4-6 156:11,20 4-7.4 224:3 4-97 224:3 4.10 186:7 4.2 63:19 4.2.1 178:2 4.3 179:9 181:15 184:3,14,15 191:2 192:19 4.5 217:18 4.5.1 207:10 4.7.3 179:13 4:20 332:22 40 64:1 115:12

220:21 225:15 353:3,4 360:4 40s 97:16 41 329:19 365:11 449 186:11 45 346:11 4700 1:12 479 209:1 48 203:2 49 358:17 5 5 3:2,16 20:12

37:14 38:4 39:19 40:14,22 41:18 42:3 201:13 214:3 214:17 230:8 239:21 243:12 245:18 266:12 267:4 271:5 275:20 281:19 357:9 381:12 383:11 5a 3:18 230:11,19

236:9 276:3 5b 3:20 240:7,10,13

243:13,15 5c 3:20 240:8,10

243:14

### 202-234-4433 Neal R. Gross & Co., Inc. Page 449 5d 3:21 240:8 251:7 5e 3:18 230:11,19 5-2 237:1 5-4 250:12 5:22 390:7 5:28 396:14 5:29 396:17 5:30 333:1 390:7 50 203:13 220:16

225:15 228:7 280:14 50's 200:2,21 201:6 52 3:6 541 237:5,6 6 6 3:25 20:22 42:5

43:17 287:4 332:20 334:17 352:15 365:6 6-3 346:16 60's 200:21 201:6 63 3:8 329:17 7 7 3:23 20:19 44:6,6

45:19 210:5 282:8 287:2,10 288:4 298:2 313:14 325:12,13 7-9 301:11 70 220:17 236:3 70s 135:12 70's 200:21 201:7 72 374:7 75 236:3 274:9

339:14,16 8 8 104:9 108:4 8:30 392:13 80s 135:13 225:12 80's 200:2 84 208:14 89 57:9 61:11 9 9:00 1:13 5:2 90 67:20 119:14,19 236:4 90th 297:11 95th 63:18 214:4 96 3:10 307:21 97 223:1 99 393:7NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. (202) 234-4433 WASHINGTON, D.C. 20005-3701 www.nealrgross.com C E R T I F I C A T E

This is to certify that the foregoing transcript

In the matter of:

Before:

Date:

Place:

was duly recorded and accurately transcribed under my direction; further, that said transcript is a true and accurate record of the proceedings.

----------------------- Court Reporter 450

Clean Air Scientific Advisory Committee Lead Review Panel

EPA

07-20-11

Durham, NC