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

OZONE REVIEW PANEL

+ + + + +

PUBLIC MEETING

+ + + + + THURSDAY, MAY 19, 2011 + + + + + The meeting convened, in the Chancellor's Ballroom of the Carolina Inn, 211 Pittsboro Street, Chapel Hill, North Carolina, at 8:30 a.m., Jonathan Samet, CASAC Chair, presiding.

CASAC MEMBERS PRESENT:

JONATHAN M. SAMET, CHAIR

GEORGE A. ALLEN JOSEPH D. BRAIN H. CHRISTOPHER FREY* ARMISTEAD (TED) RUSSELL HELEN SUH KATHLEEN WEATHERS*

PANEL MEMBERS PRESENT:

ED AVOL JOHN BAILAR MICHELLE BELL DAVID CHOCK WILLIAM MICHAEL FOSTER

JUDITH GRAHAM DAVID GRANTZ JACK HARKEMA

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DANIEL JACOB

STEVEN KLEEBERGER

FREDERICK J. MILLER

HOWARD NEUFELD

JAMES ULTMAN

SVERRE VEDAL*

PETER WOODBURY

SCIENCE ADVISORY BOARD STAFF: HOLLY STALLWORTH, DESIGNATED FEDERAL OFFICER

*Participating via telephone

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Call to order 8 Dr. Holly Stallworth Designated Federal Officer SAB Staff Office

Introduction of Panel Members 11

Review of Agenda 14 Dr. Jonathan Samet CASAC Chair

Presentation on the Ozone Integrated 18 Science Assessment (ISA)

Dr. John Vandenberg 18

Ms. Lydia Wegman 22

Questions and Comments 29

Dr. Jim Brown 37

Questions and Comments 50 Ms. Debra Walsh 52 Questions and Comments 61

Public Comments 66 Dr. Allen S. Lefohn 67 ASL Associates Helen, Montana

Questions and Comments 73

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Public Comments (Continued)

Dr. Julie Goodman 78 Gradient Corporation Cambridge, Massachusetts Representing the American Petroleum Institute

Questions and Comments 86

Mr. George Wolff 89 Air Improvement Resource, Inc. Representing the Utility Air Regulatory Group

Ms. Sam Oltmans 99 Boulder, Colorado

Discussion of Charge Questions 102

Framework for Causal Determination 103 (Question 2)

Dr. John Bailar 103

Dr. Sverre Vedal 107

Dr. Howard Neufeld 114 Dr. Jonathan M. Samet 116 Discussion 118

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Atmospheric Chemistry and 127 Ambient Concentrations Question 4 Dr. Ted Russell 127 Mr. George Allen 132 Dr. Daniel Jacob 144

Discussion 155

Environmental Effects 166 Question 10

Dr. Kathleen Weathers 166 Dr. David Grantz 168 Dr. Howard Neufeld 176 Discussion 182

Climate Change and UV-B Effects 198 Question 11

Dr. Howard Neufeld 198

Dr. Peter Woodbury 199

Dr. Daniel Jacob 203

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Exposure 210 Question 5

Mr. Ed Avol 210

Dr. Chris Frey 215

Dr. David Chock 218

Discussion 221 Dosimetry and Mode of Action 237 Question 6

Dr. Fred Miller 237

Dr. Joseph Brain 251 Dr. Jack Harkema 256 Dr. James Ultman 264 Discussion 274

Health Effects of Short-Term 283 Exposure (Question 7) Dr. W. Michael Foster 283 Dr. James Ultman 287

Dr. John Bailar 293

Dr. Judith Graham 296 Discussion 306

### 202-234-4433 Neal R. Gross & Co., Inc. Page 7 C-O-N-T-E-N-T-S (CONTINUED) Health Effects of Long-Term 319 Exposure (Question 8)

Dr. Michelle Bell 319 Dr. John Bailar 229 Dr. Judith Graham 331 Discussion 336

Susceptible Populations 343 (Question 9) Dr. Steven Kleeberger 343 Dr. Fred Miller 348

Discussion 352

Integrative Summary 372 (Question 3) Dr. Helen Suh 372 Dr. Christopher Frey 380

Dr. Howard Neufeld 382

Discussion 386

Length of Document 407

(Question 1)

Dr. Judith Graham 407 Dr. Michelle Bell 411 Discussion 418

Administrative Matters 424

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2 8:30 a.m. 3 DR. STALLWORTH: Good morning. 4 I would like to go ahead and get

5 started. 6 I want to thank everyone for 7 coming. 8 I am Holly Stallworth. 9 How is the audio here? 10 I am the Designated Federal 11 Officer for the Clean Air Scientific Advisory 12 Committee. And as always, I need to open the 13 meeting with a short statement. 14 CASAC is a federal advisory 15 committee, and by EPA policy, its meetings and 16 deliberations are held as public meetings that 17 meet the requirements of the Federal Advisory 18 Committee Act. 19 CASAC is chartered by law to 20 provide advice to the Administrator. 21 Consistent with the requirements 22 of FACA and with EPA policy, the deliberations

### 202-234-4433 Neal R. Gross & Co., Inc. Page 9 1 are CASAC are conducted in public at meetings 2 for which advanced public notice is given. 3 The discussions and substantive deliberations 4 of the panel, its interactions with the public 5 and the agency are conducted in sessions where 6 I, as the Designated Federal Officer, am 7 present to ensure that the requirements of 8 FACA are met. And this includes the 9 requirements for open meetings, for 10 maintaining records of deliberations, for 11 making available public summaries of meetings, 12 and providing opportunities for public

13 comment. 14 I will be checking the minutes of 15 the meeting to summarize the discussion and 16 action items. These minutes will be certified 17 by our Panel Chair, Dr. Samet, once completed, 18 and posted on our website. 19 Finally, I would like to comment 20 on the status of this Committee's compliance 21 with federal ethics laws. The SAB Staff 22 Office has reviewed information relevant to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 10 1 conflict of interest and appearance of a lack 2 of partiality, and appropriate balance and 3 breadth of expertise, knowledge, and 4 experience needed to address the charge, and 5 determined there are no conflict-of-interest 6 or appearance of lack-of-partiality issues for 7 any of the members participating. 8 Before I turn the meeting over to 9 Dr. Samet, I want to see if there is anybody 10 on the phone. 11 At some point, Sverre Vedal should 12 be calling in as well. 13 Chris Frey had the flu. He was 14 unsure if he would -- 15 DR. FREY: Holly, this is Chris 16 Frey. I'm on the phone. 17 DR. STALLWORTH: Oh, great. Good, 18 good, good. 19 I think I am forgetting something. 20 Oh, my Director, Dr. Vanessa Vu, is unable to 21 be here today. She sends her regrets. 22 I am going to turn the meeting

### 202-234-4433 Neal R. Gross & Co., Inc. Page 11 1 over to Dr. Samet. 2 DR. SAMET: Okay. Good morning. 3 Good morning, everyone, and welcome, I guess, 4 to what will be the first of multiple meetings 5 of this panel. So, we will have the 6 opportunity to spend a lot of time together, 7 I suspect, in North Carolina reviewing 8 documents over the cycle of this. 9 Let me start. First, I will ask 10 the panel to introduce themselves, and, then, 11 we will come back to the agenda. 12 So, again, I am Jon Samet, Chair 13 of CASAC, pulmonary physician and 14 epidemiologist from the University of Southern 15 California. 16 DR. GRAHAM: Judy Graham, 17 independent consultant, with a background in 18 inhalation toxicology and exposure. 19 DR. MILLER: Fred Miller, 20 independent consultant; background dosimetry, 21 inhalation toxicology, extrapolation modeling. 22 DR. GRANTZ: David Grantz. I am a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 12 1 plant physiologist from the University of 2 California at Riverside.

3 DR. HARKEMA: I'm Jack Harkema 4 from Michigan State University, a pathologist 5 and inhalation toxicologist. 6 DR. JACOB: I am Daniel Jacob, 7 atmospheric chemist at Harvard University. 8 DR. KLEEBERGER: Steve Kleeberger 9 from the Laboratory of Respiratory Biology at 10 NIEHS. My background is in environmental 11 physiology and genetics of susceptibility to 12 air pollutants.

13 DR. NEUFELD: I'm Howard Neufeld 14 from Appalachia State University, and I am a 15 plant ecophysiologist.

16 DR. RUSSELL: Ted Russell at 17 Georgia Tech. I am an environmental engineer.

18 DR. SUH: Helen Suh from NORC at 19 the University of Chicago. I am an exposure 20 assessment, environmental health scientist. 21 DR. ULTMAN: Jim Ultman, Penn 22 State University. I am a biomedical engineer.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 13 1 DR. WOODBURY: Peter Woodbury from 2 Cornell University. I do ecosystem modeling, 3 agriculture and forestry. 4 MR. ALLEN: George Allen from 5 NESCAUM in Boston. Measurement methods, 6 monitoring, exposure assessment. 7 MR. AVOL: Ed Avol, University of 8 Southern California. Exposure assessment and

9 health effects research. 10 DR. BAILAR: John Bailar, retired 11 from the University of Chicago, and now 12 scholar-in-residence at the National 13 Academies. I am a physician, a statistician, 14 and epidemiologist. 15 DR. BELL: Hi. I'm Michelle Bell 16 from Yale University at the Environment 17 School, with joint appointments at the School 18 of Public Health and, also, the Environmental 19 Engineering Program. And I do epidemiology of 20 air pollution and human health. 21 DR. BRAIN: Joe Brain in Boston at 22 the Harvard School of Public Health. I am a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 14 1 lung biologist and inhalation toxicologist. 2 DR. CHOCK: David Chock, 3 independent consultant, environmental 4 scientist. 5 DR. FOSTER: Mike Foster, 6 Professor of Medicine at Duke University 7 Medical Center. Expertise in pulmonary 8 physiology. 9 DR. SAMET: Thanks. As you can 10 see, it takes a village to review the Ozone

11 ISA. 12 (Laughter.) 13 So, let's just spend a moment on 14 the agenda. Of course, we are going to begin

15 and hear about the ISA from the EPA team that 16 has put it together. 17 We will have comments from the 18 public. Then, we are going to go on and move 19 through the discussion of the charge 20 questions. 21 I want to thank everybody for the 22 work that has been done in advance and the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 15 1 comments that have been submitted. And we are 2 on our way towards getting the job of review

3 done. 4 Our goal in these discussions will 5 be really to go over the key points, the 6 points that really the Committee needs to 7 discuss. I think we will try to avoid more 8 minor points of discussion and wordsmithing,

9 and so on. 10 So, this is an opportunity to go 11 through the lead discussants and, then, have 12 others join in. And by the end of the day, we 13 will want to have a plan for drafting our 14 response. What are the key points that will 15 go into overall letter and, then, the charge 16 questions. 17 Again, for those of you who are 18 new to this, which is perhaps some of you, 19 what we have been doing is writing a letter to 20 the Administrator that really summarizes the 21 main overall points about the document and 22 highlights those aspects of our responses to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 16 1 the charge questions that we think are most 2 critical. 3 So, we have been writing, roughly, 4 a two-page, single-spaced letter, then 5 accompanied by our Committee's responses to 6 the charge questions. And, then, your 7 individual comments are appended as well. 8 So, there are three things, then. 9 There is our summary letter to the 10 Administrator, the roughly two pages, 11 highlighting key points. There are our, 12 essentially, consensus responses to the charge 13 questions and, then, the individual responses. 14 And what we will do is, after the 15 meeting, we will complete the drafting of the 16 responses to the charge questions, we will 17 look at the letter via teleconference, and 18 come to completion of that. And so, that will 19 take probably, roughly, a month after this. 20 Now tomorrow there's the review of 21 the two scopes and methods plans for the 22 health risk and exposure assessment and the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 17 1 welfare risk and exposure assessment. And 2 there will be discussion of those, and that is 3 a consultation. Yes, that is a consultation. 4 So, it does not come with charge questions, 5 and we just provide our guidance to the 6 agency. 7 So, I think that is sort of a 8 quick review. And again, for those of you who 9 have been with the process in the past, and I 10 think we will hear about this from the agency. 11 We have now this change from what you will 12 remember from the old days of the criteria 13 document staff paper to the new ISA risk and 14 exposure assessment analysis and the policy 15 document. So, I suspect you are going to take 16 us through all of that. 17 So, I think if along the way there 18 are any questions about process, and anybody 19 wants clarification, let me know. But any 20 immediate questions or comments? 21 (No response.) 22 Okay. Good. Then, let me turn

### 202-234-4433 Neal R. Gross & Co., Inc. Page 18 1 things over, I guess. John? 2 DR. VANDENBERG: I'm trying to get 3 used to the technology here. 4 My name is John Vandenberg, and I 5 would like to welcome the Committee and 6 indicate our great appreciation for the time 7 today and tomorrow, as well as for the next 8 couple of years. I think, as Dr. Samet 9 pointed out, this is a fairly elaborate and 10 extremely important process, and we greatly 11 value your input, both your comments today and 12 tomorrow as well as your written comments now 13 and subsequently. It is a great opportunity 14 for us to benefit from your perspectives. 15 I am joined this morning by Lydia 16 Wegman, who is a colleague at OAQPS, the 17 policy office in the Health and Environmental 18 Impacts Division. She will be speaking about 19 the policy aspects of risk and exposure 20 assessment, policy assessment, and, 21 importantly, about the reconsideration. 22 We think it is important that we

### 202-234-4433 Neal R. Gross & Co., Inc. Page 19 1 provide some context this morning for the 2 panel to understand the different pieces that 3 are coming together here, so there is no 4 confusion. We certainly welcome any questions 5 or clarifications. 6 Jim Brown will, then, go through 7 the charge questions and very briefly 8 summarize some of the nature of the 9 information that is in the different chapters, 10 just setting up for the discussion later 11 today. 12 And, then, Debra Walsh, my 13 colleague here, will also be speaking about 14 the Health and Environmental Research Online 15 system. This is an important new development 16 that we have been bringing online over the 17 last couple of years that will continue to 18 evolve over the next several years. And we 19 want to make sure that the panel understands 20 the capabilities of that and how that will 21 help support your review steps. 22 We are also joined this morning by

### 202-234-4433 Neal R. Gross & Co., Inc. Page 20 1 our staff in the back. A number of EPA staff 2 are here. I am very proud of this group of 3 people, and they are listening with great 4 interest to your comments about the various 5 chapters that they have been contributing to. 6 So, we are going to be very brief 7 on this because we think we need to get right 8 into the discussion. The various parts of the 9 process are shown here. 10 We began by having a workshop and, 11 then, we have developed an integrated review 12 plan. And the point of today's discussion is 13 really regarding the integrated science 14 assessment and, then, for tomorrow the 15 consultation on the risk and exposure

16 assessment. 17 Ultimately, these will flow 18 together with CASAC and public input -- and 19 again, we very much appreciate the public 20 comments -- flowing into the policy 21 assessment, which then goes through a series 22 of meetings and decision points, including the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 21 1 agency decisions on proposed standards, 2 followed by the agency decisions, again, after 3 public comment, on the final standards. And 4 that will take course, over the next couple of 5 years. 6 In terms of the integrated review 7 plan, what we have done in the last several 8 years is recognized the benefit of having a 9 coherent program plan that cuts across both 10 the science and the policy. We bring that 11 together in our integrated review plan, which 12 lays out the schedule which we will show you 13 in a moment, highlights sort of the process 14 for conducting a review of the CASAC meetings, 15 the development of key policy-relevant issues 16 that tend to be very important to how we form 17 and narrow down some of the areas of emphasis 18 in the ISA. 19 And, then, that flows into the 20 ISA, which again, is intended as a concise21 evaluation and synthesis of the most policy22 relevant science. Our emphasis is to identify

### 202-234-4433 Neal R. Gross & Co., Inc. Page 22 1 the world science and bring that to bear and 2 draw conclusions from that, as well as 3 highlighting the strengths and uncertainties 4 of the evidence. It is the foundation for the 5 risk and exposure assessment as well as the 6 policy assessment and the agency decisions. 7 Again, underscoring the sort of 8 process that we have got here, we have a 9 companion group. I will turn now to Lydia 10 Wegman to pick it up from there. 11 So, Lydia? 12 MS. WEGMAN: I want to add my

13 thanks to Jon. 14 Again, my name is Lydia Wegman. I 15 am the Director of the Health and 16 Environmental Impacts Division in the Office 17 of Air Quality Planning and Standards, which 18 is part of the Office of Air and Radiation at 19 EPA. And it is my Division that takes on 20 these next two pieces that we have up here. 21 But I just want to say thank you 22 again for all the time you have put into

### 202-234-4433 Neal R. Gross & Co., Inc. Page 23 1 reviewing the documents to date. And as you 2 will see when I walk through the schedule, we 3 are really looking at about another three 4 years from to when we get to a final standard. 5 And your work is going to be invaluable as we 6 move forward on this review and the many 7 documents that you will be reviewing and 8 providing comments on. When I go through the 9 schedule, you will see the points where we 10 anticipate your review. 11 Once the integrated science 12 assessment is done, and I shouldn't say "once 13 it's done", in concert with the development of 14 the integrated science assessment, my office 15 works on the risk and exposure assessment. 16 Today you will be giving us comments and 17 consulting with us on the plan for the risk 18 and exposure assessment. So, that will be the 19 scope and methods document, which you have 20 already reviewed. And, then, the document 21 itself will provide a presentation of the 22 results and observations and uncertainties

### 202-234-4433 Neal R. Gross & Co., Inc. Page 24 1 that will help inform the policy assessment. 2 The next document is called the 3 policy assessment. It used to be called the 4 staff paper, as John said. And the policy 5 assessment is a document that integrates the 6 science and the risk and exposure assessment 7 and provides options for the Administrator to 8 consider in setting the standard. 9 I want to emphasize here that, in 10 addition to providing us advice on science and 11 the technical assessments, we seek your advice 12 on the standards themselves. We are asking 13 for your help to integrate the science, the 14 risk and exposure assessments, to come up with 15 policy options for the Administrator to 16 consider. 17 The Administrator makes the 18 decision, but your advice on what options she 19 could consider and what options are supported 20 by the science and risk and exposure 21 assessments is critical to her review.

22 We have a recent court case

### 202-234-4433 Neal R. Gross & Co., Inc. Page 25 1 involving our particulate matter standard 2 which observed that we had not followed the 3 advice of CASAC and that we had failed to 4 provide an adequate explanation for our 5 decision not to follow the advice of CASAC. 6 So, I want to emphasize to you how important 7 your advice is to the agency in thinking about 8 these issues. It is important for the 9 Administrator's consideration, and it is 10 important from the standpoint of the Clean Air 11 Act and the courts which review our actions on

12 these rules. 13 So, let me walk through quickly 14 the schedule, as we see it. I won't go 15 through every single date. 16 But the first slide here are the 17 completed elements. It took us some time, but 18 we did actually ultimately issue a final 19 integrated review plan for this review. That 20 is the third from the bottom where it says 21 "final IRP released". It was released in 22 April, very shortly after we got out, after

### 202-234-4433 Neal R. Gross & Co., Inc. Page 26 1 John and his folks got out the first draft of

2 the ISA. 3 As you know, we have got the scope 4 and methods plan. 5 Today's CASAC meeting is the first 6 of many. This shows you what we anticipate 7 for the next three years, roughly. There will 8 be a second external review draft of the ISA 9 coming in September, followed by our first 10 draft of the risk and exposure assessment, 11 which will build on the ISA, in October. 12 Then, we hope to have a meeting with you in 13 November of this year to go over both of these

14 documents. 15 Then, the final integrated science 16 assessment in February of next year. Then, 17 our second draft of the risk and exposure 18 assessment and a first draft of the policy 19 assessment. And all of those will be -- well, 20 actually, I'm sorry, the second draft of the 21 risk and exposure assessment and the first 22 draft policy assessment will be coming in July

### 202-234-4433 Neal R. Gross & Co., Inc. Page 27 1 of next year. 2 So, then, we will have the final 3 risk and exposure assessment and the second 4 draft of the policy assessment. And you will 5 be reviewing the second draft of the policy 6 assessment in December/January of 2013, 7 December 2012, January 2013. 8 The final policy assessment in 9 March of 2013, and, then, we hope to have a 10 proposed rule out by September of 2013 and a 11 final rule by June of 2014. So, that is the 12 three-year schedule as we envision it right

13 now. 14 You will note that this is not 15 following the five-year schedule precisely. 16 We last issued an ozone standard in March of 17 2008. Normally, we would have expected to 18 conclude this review by, roughly, March of 19 2013, but the Administrator of EPA made a 20 decision to reconsider the March 2008 21 standard. And that has led to some delay in 22 our moving forward on this review.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 28 1 We proposed revisions to the March 2 2008 standard. The March 2008 standard, as I 3 think you all well know, was set at 0.075 4 parts per million. And in January of 2010, 5 consistent with the advice we have gotten from 6 CASAC many times, we did, in fact, propose to 7 set the standard within a range of .060 to 8 .070 parts per million. 9 And we also proposed to set a 10 distinct cumulative secondary standard within 11 the range of 7 to 15 parts per million hours. 12 That is using the W126 form. 13 As many of you know, we sought 14 additional advice from CASAC in early 2011, 15 and we got that advice, reiterating again 16 their recommendation for .060 to .070 parts 17 per million. 18 And we have indicated to the U.S. 19 Court of Appeals for the District of Columbia 20 Circuit that we plan to issue a final rule on 21 the reconsideration by July 29th of this year. 22 So, that is activity going on in parallel with

### 202-234-4433 Neal R. Gross & Co., Inc. Page 29 1 this review. We just wanted to make sure you 2 understood the nature of the two actions. 3 So, that is it, and I will see if 4 there are any questions. Then, I will turn it

5 over to James Brown. 6 Yes, Fred? 7 DR. MILLER: Lydia, how does your 8 schedule change if Obama isn't reelected? 9 (Laughter.) 10 MS. WEGMAN: No comment, Fred. 11 DR. MILLER: I just thought we

12 should set the tone here. 13 DR. SAMET: It might be useful, 14 Lydia, for you or John maybe to describe in 15 what way these new sets of documents differ 16 from the old or are intended to review. What 17 is the difference between an ISA and a 18 criteria document? 19 MS. WEGMAN: Yes, I am going to

20 let John take that one. 21 DR. VANDENBERG: I think it was in 22 2008 we derived a new process. The idea was

### 202-234-4433 Neal R. Gross & Co., Inc. Page 30 1 to move away from the encyclopedia-type air 2 quality criteria document, which I think for 3 ozone the last time was about 2,000 pages, and 4 have a more integrated and effective document. 5 Part of the key difference here is 6 that we created, as documented in Chapter 1, 7 a new framework for how we are considering 8 information in terms of deriving causality 9 determinations. And so, in the former 10 document, the air quality criteria documents, 11 you wouldn't see a consistent manner in which 12 we evaluated the evidence. We weren't as

13 clear about that. 14 So, part of what we have done in 15 the new document is present the framework and 16 the approaches that we are using to derive 17 causality evaluations in Chapter 1. 18 In Chapter 2 -- this is also a new 19 difference -- we have brought a lot of the 20 findings forward just to kind of highlight the 21 major findings that, then, are supported by 22 the subsequent chapters. And so, there has

### 202-234-4433 Neal R. Gross & Co., Inc. Page 31 1 been a restructuring of the document, a change 2 in the way we have framed it in terms of the 3 framework that we are using and the derivation 4 of these causality statements. 5 And the way we are presenting the 6 results has changed quite a bit as well. We 7 are adding more tables, more figures. 8 Importantly, again now, we are also using the 9 Health and Environmental Research Online 10 system to augment what is in the paper copy, 11 if you will. 12 So, we have a much more 13 comprehensive, but also more focused approach 14 here in the integrated science assessments. 15 So, that is this change. 16 As Jim Brown will show in a few 17 minutes, we are also trying to highlight the 18 basis from the older studies, whether it is 19 the 2006 air quality criteria document or even 20 earlier ones, and bring some of them, the most 21 pertinent findings forward into this document, 22 to provide that larger context for the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 32 1 totality of the evidence that we are 2 considering in this document. 3 So, it represents, for some of you 4 who have been familiar with the old air 5 quality criteria documents, they were much 6 longer and much more, you know, study, study, 7 study, study. And we are attempting to 8 continually move towards a more integrated 9 synthesis and actually change the documents. 10 And we welcome suggestions on how to make it 11 more effective because we find that, being in 12 a more dynamic or flexible approach to this, 13 that it has certain advantages to all of us. 14 So, is that speaking to your 15 question?

16 DR. SAMET: Yes. Thanks.

17 Yes?

18 DR. JACOB: I don't understand how 19 this ozone reconsideration proposal, does this 20 short circuit the formal revision of the 21 standard, which I understand is going to take 22 three years? Is this because this argues that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 33 1 a 2008 NAAQS was wrongly set? 2 MS. WEGMAN: Yes, it does not 3 short circuit it. These are two parallel 4 actions. One is a reconsideration. 5 And I should have noted this. The 6 reconsideration of the March 2008 standard is 7 based on the record for that review. So, we 8 didn't consider any new science. ORD did do 9 a provisional assessment of the new science to 10 ensure that there wasn't something that 11 materially changed the conclusions of the 12 scientific assessment for that March 2008 13 review. But we are looking only at the 14 scientific record and the entire record from 15 the March 2008 review for the reconsideration. 16 This is the next formal review, 17 the formal statutory five-year review of the 18 ozone standard. And so, it is somewhat 19 confusing, but they are moving forward in 20 parallel.

21 DR. SAMET: Just as a further 22 comment, you won't be aware, Daniel, but CASAC

### 202-234-4433 Neal R. Gross & Co., Inc. Page 34 1 did comment quite recently on the 2 reconsideration. I think it was roughly 3 several months ago that we held --

4 MS. WEGMAN: Yes. 5 DR. SAMET: -- two lengthy 6 teleconferences. We heard from many public 7 commenters and again provided guidance to the 8 Administrator on the record as it had been 9 compiled up through 2006 in support of the 10 prior revision, the 2008 NAAQS. So, if you 11 are interested, there is a letter posted that 12 you can take a look at. 13 MS. WEGMAN: Yes. Does that help, 14 Daniel?

15 DR. JACOB: Yes. 16 MS. WEGMAN: Okay.

17 DR. SAMET: Howard? 18 DR. NEUFELD: Can you hear me now?

19 MS. WEGMAN: Yes. 20 DR. NEUFELD: Given the extended 21 length of time for the process, what is the 22 protocol or provisions if significant new

### 202-234-4433 Neal R. Gross & Co., Inc. Page 35 1 findings come out, say, in the last two, two 2 and a half years of the process, that could 3 have an impact, say, on what your decision is?

4 DR. VANDENBERG: What we have done 5 is we certainly have found that the science is 6 changing. We have two rounds, if you will, 7 two documents here on the integrated science 8 assessments that we will be deriving. We can 9 bring new science into that, and we will try 10 to identify in a sense a deadline for 11 consideration of new studies that are coming 12 into the next document. 13 In the past, we have found CASAC 14 making recommendations to us to bring even 15 newer studies into the final document, and we 16 have done that in the past, based on a 17 recommendation from CASAC. 18 In addition, depending upon the 19 time it takes to move it into the policy, we 20 have done a provisional assessment in the past 21 of the new science to see if it will 22 materially change the conclusions that are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 36 1 represented in the ISA. We do that to the 2 benefit of the Administrator. So, that is 3 kind of a catchup at the very end, just to 4 make sure, is there anything out there that 5 the Administrator needs to be aware of prior 6 to making a final decision. 7 DR. SAMET: I think just as a 8 further comment, there has been an effort to 9 assure that these documents represent 10 systematic reviews where there is a clear date 11 up to which evidence is accumulated. And I 12 think as one goes beyond that point, this 13 discussion has come up many times and the 14 concern about potential selectivity in picking 15 one or another documents for consideration 16 becomes a critical matter. 17 So, if there are one or more key 18 studies, they might be brought forward, but 19 there is not an effort to continually update 20 the full systematic review. I think it is 21 simply not feasible. 22 MS. WEGMAN: Yes, and I will just

### 202-234-4433 Neal R. Gross & Co., Inc. Page 37 1 note the Clean Air Act does provide for review 2 and revision, if appropriate, of these 3 standards every five years. So, there is a 4 recognition that new science will come along 5 toward the end of one review that will have to 6 come into consideration in the next review. 7 DR. SAMET: David? 8 DR. CHOCK: Just as a point of 9 clarification, the .06 to .07, I guess you 10 mean the fourth highest value in three years, 11 is that correct? 12 MS. WEGMAN: Yes, it is the fourth 13 highest maximum with an average of three 14 years, that's right, yes. 15 DR. SAMET: Okay, why don't we

16 move ahead? 17 DR. VANDENBERG: So, I think at 18 this point we will turn to Jim Brown to 19 provide the context for this review. 20 Jim? 21 DR. BROWN: I would just like to 22 follow up on the comment about when is the cut

### 202-234-4433 Neal R. Gross & Co., Inc. Page 38 1 point for the science going into these 2 reviews. For the February/March 2006 air 3 quality criteria document, we had a number of 4 2006 epidemiological studies and I think two 5 controlled human exposure studies that were 6 added to that review. Following the second 7 external review draft, those were added to the 8 document, either because CASAC specifically 9 asked that they be included or public comments 10 pointed out new publications that were in 11 press and that should be included in the 12 review. 13 So, this is an evolving document, 14 the one that we are about to talk about today. 15 The comments that we receive from you, the 16 comments that we receive from the public, we 17 do our best to respond to and incorporate in 18 relevant information. 19 So, on this first slide that I was 20 going to start with, it is just the chapters 21 in this first ISA. I felt pretty good about 22 where we were now with putting together this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 39 1 rather large document. I admit that, after 2 looking at slide 6, we have got a long ways 3 ahead of us to get to the end of this review, 4 and that is scary to me. But this is where we 5 are at this point. 6 So, on this slide, if you look 7 starting at the third chapter, we have 8 atmospheric sciences. You will see that we 9 also consider exposure, dosimetry, mode of10 action. We look at health effects of short11 and long-term exposures, effects on 12 vegetation, and we also look at climate and

13 UV-B effects. 14 So, much like the backgrounds of 15 this Committee, we have a very diverse 16 background of individuals that have 17 contributed to this document. Later today, 18 when we go through the charge questions, we 19 will have people coming up to the table and 20 here that may help respond to questions or 21 provide clarifications to the Committee, if 22 those are desired.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 40 1 Now I am going to go ahead and 2 start going through the charge questions 3 quickly. Those relate back to the chapters 4 that I just showed you on slide 8. We have 5 charge questions specifically related to each 6 chapter. 7 This one, however, the very first 8 charge question relates to the entire 9 document. As John mentioned, there is a lot 10 of information. We have a lot of old 11 information that was very relevant to this 12 review and new literature. 13 With this copious amount of 14 research, we have tried to focus on what we 15 consider to be the most policy-relevant 16 information. So, some of the studies that may 17 have been included in old reviews, some 18 sections that were included in old reviews are 19 not included in this document. And we need 20 some guidance perhaps on what should be added21 or removed even to make it more policy22 relevant and not such a large document.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 41 1 Moving to the next two charge 2 questions, well, the first chapter presents 3 the framework. We would like your opinion on 4 whether we have applied that appropriately for 5 this Ozone ISA. 6 And Chapter 2 provides an 7 integrated synthesis of our review and shows 8 you all of our causal determinations. And 9 again, we would ask if those were 10 appropriately applied. 11 So, on the topic of the causal 12 determination, it is a five-tiered assessment. 13 We could move all the way from discerning that 14 there is likely, well, that there is a causal 15 relationship between an exposure to ozone and 16 a given health effect down to it not being 17 likely that there is a causal relationship. 18 On slide 13, this just overviews 19 some of the causal determinations that were 20 arrived at in our 2006 review and now our 21 conclusions in the 2011 ISA. This is for 22 human health effects from short- and long-term

### 202-234-4433 Neal R. Gross & Co., Inc. Page 42 1 exposures. 2 On the top half of the slide, for 3 the short-term exposures, we don't really have 4 any change in what we concluded from the last 5 review. 6 On the bottom half of the slide, 7 we have long-term exposures being considered, 8 and we do have some new determinations there 9 that we would like the Committee's opinions

10 on. 11 We also have present causal 12 determinations. And on this slide, I have 13 just highlighted some of those for the 14 ecological systems effects and effects on 15 vegetation. Those range from likely causal to

16 causal. 17 Moving on to more specific 18 chapters, Chapter 3 is overviewed in charge 19 question 4. This overviews the atmospheric 20 sciences. And so, what we would like there 21 and what we have sought to provide is a useful 22 context and insights into the evaluation of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 43 1 human health effects on vegetation, 2 ecosystems, and climates. Did this chapter 3 support materials that we present later? 4 I have highlighted, I forgot to 5 mention to you there is highlighting on this 6 on some of these slides. And that is just to 7 emphasize some of the key points, at least as

8 I see them. 9 On this one, I have highlighted 10 4B. That is looking at policy-relevant 11 background. That becomes very important later 12 in the risk assessment in discerning the 13 effects due to human emissions on the ozone

14 levels. 15 And I think I will stop there and 16 move on to the next slide, which actually says 17 that. What is PRB? Well, PRB is the ozone 18 concentrations that would exist in the absence 19 of manmade emissions from the U.S., Canada, 20 and Mexico. So, North American emissions. 21 Well, PRB is not directly

22 measurable because we have those manmade

### 202-234-4433 Neal R. Gross & Co., Inc. Page 44 1 emissions. And so, we have to model PRB. 2 We present some simulations in our 3 current assessment. We are continuing to work 4 on this. I mentioned that the document is 5 evolving. This is something that we are 6 working on for our second draft. We are7 trying to look at a finer resolution, a half8 degree by two-thirds of a degree resolution 9 for North America nested in a 2-by-2.5 degree 10 resolution for a global model. On this plot, 11 the color is just illustrating the pressure. 12 But, with regard to this model, 13 and it is done by GEOS-Chem, and GEOS-Chem 14 considers or looks at ozone levels, NOx, 15 volatile organic compounds, and aerosol 16 chemistry. It is looking at 48 vertical 17 levels. I am sure if I continue on, I will 18 get something mixed up there, and so I won't. 19 (Laughter.) 20 But that is why we have 21 atmospheric scientists here for later in the 22 discussion today, when we do talk about the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 45 1 atmospheric chemistry and policy-relevant 2 background. 3 But we are working currently on 4 producing simulations for the years 2006 5 through 2008 to include in our second draft, 6 as opposed to what we have currently is a 1- 7 degree-by-1-degree resolution for North 8 America, which is roughly 100 kilometers, I 9 believe, by 100 kilometers. 10 Moving on to charge questions 5 11 and 6, this is looking at Chapters 4 and 5, 12 where we look at human exposures to ozone. 13 And those are intended, again, to help us 14 understand and interpret some of the findings 15 in the epidemiological studies. Have we done 16 that appropriately and does it actually help 17 in the assessment of those epi studies? 18 Chapter 5, looking at dosimetry 19 and mode of actions, well, we look at 20 dosimetry to help us understand differences in 21 the dose received between individuals and 22 species. We look at modes of action to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 46 1 support the biological plausibility in the 2 epidemiological studies or observed in those 3 epidemiological studies. 4 Chapter 6, charge question 7 on 5 slide 19, you can see why I underlined key 6 phrases. This is looking at or discussing the 7 short-term effects of ozone exposure on human

8 health. 9 This is one of the chapters where 10 it really became apparent to me that we were 11 trying to balance out this old information 12 that we presented in former ISAs with some of 13 the newer information. Have we pulled in some 14 of the old, most relevant information? And 15 have we used toxicology adequately to support 16 the plausibility of those observations that we 17 are now seeing in some of the new 18 epidemiological studies? 19 Charge question 8 looks at, again, 20 human health effects, but now from long-term 21 exposures to ozone. I would like to slow down 22 on this slide for just a second to emphasize

### 202-234-4433 Neal R. Gross & Co., Inc. Page 47 1 that we are looking at what I see as important 2 new findings. Specifically, we are looking at 3 the effects on new-onset asthma in children. 4 We are looking at first childhood asthma 5 hospital admissions, increased asthma 6 severity, school absences. Children is what 7 I am emphasizing there. 8 And when I move a few slides later 9 and look at susceptibility, did we actually 10 present the susceptible groups appropriately? 11 Especially children and asthmatics were two of 12 the large groups. 13 On slide 21, this is just included 14 to illustrate the large spectrum of evidence 15 that we are considering when we look at the 16 short-term and long-term human health effects. 17 What is circled on this slide is mainly what 18 is new to this review, as in what we did not 19 have in the 2006 air quality criteria

20 document. 21 What is new? Again, as I 22 emphasized, I guess five out of those six

### 202-234-4433 Neal R. Gross & Co., Inc. Page 48 1 circles relate to long-term exposures. As far 2 as the short-term exposures, we have 3 additional evidence of effects going down to 4 lower levels of exposure, that being 60 ppb in 5 some of the controlled human exposure studies. 6 I told you I would get to 7 susceptibility. That is our charge question 8 9. And these are just some of the different 9 characteristics that we looked at on slide 23 10 in considering the susceptibility. 11 Susceptibility is pulled together 12 out of our entire review. We have tried to 13 take the observations that we are seeing in 14 all the epidemiological studies and the 15 controlled human exposure studies and in the 16 tox studies that are presented in the earlier 17 chapters and pull those together into our 18 susceptibility chapter. 19 Moving on to our last two charge 20 questions on slide 24 -- I am getting tired 21 now from going through all of these that you 22 all are going to give us input on -- charge

### 202-234-4433 Neal R. Gross & Co., Inc. Page 49 1 question 10 is looking at the effects on 2 vegetation and ecosystems. Charge question 11 3 is looking at the effects on climate and UV-B. 4 There is a lot of information that is 5 presented in those chapters, especially 6 Chapter 9. 7 This is just a snapshot on slide 8 25 of some of that evidence. On slide 25, 9 this is the effects of ozone on plant growth. 10 In the leftmost panel, you will 11 see some plans for comparison to those in the 12 middle panel. Underneath each of those panels 13 is the cumulative weighted seasonal exposure 14 of those plants based on a W126 that was 15 presented in Chapter 9 and was also proposed 16 in the ozone reconsideration for the form of

17 our current standard. 18 Looking at the righthand panel, 19 that is just illustrating, if you couldn't see 20 it from the pictures, the actual loss in the 21 biomass as a function of the exposure 22 concentration.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 50 1 I would like to emphasize, 2 however, that this is a sensitive species. 3 The cottonwood is not necessarily 4 representative of an average. It is a 5 sensitive species. 6 Lastly, this is just an overview 7 of the effects of ozone on climate. On the 8 third row down there, tropospheric ozone has 9 a positive radiating force on the climate. 10 And with that very quick overview 11 of some of the stuff that we have in this 12 document, I would like to move over to Debra 13 Walsh to discuss HERO. 14 DR. VANDENBERG: Would this be a 15 point for any questions or clarifications for 16 Jim? 17 DR. MILLER: Jim, why are you 18 willing to dismiss the cottonwood as a 19 sensitive species, but children we are 20 bringing in through the front door? I don't 21 see the connection there that you should say 22 that one is in an area, because of its eco or

### 202-234-4433 Neal R. Gross & Co., Inc. Page 51 1 welfare, that, therefore, we are not going to 2 go with the most sensitive as opposed to the 3 health we are. Is that a charge of the Clean 4 Air Act or is that a policy already coming 5 into play? 6 DR. BROWN: Actually, I emphasized 7 that that is a sensitive species a little bit 8 because I believe the lower end of our 9 proposed range now was 7 ppm hours. I do see 10 effects on this slide. Actually, that is why 11 I went ahead and pulled this slide in. But I 12 was pointing out that that is not 13 representative of all species. 14 If we only looked at the 15 cottonwoods, there are clearly effects at the 16 7 ppm hours. And so, I was just trying to -- 17 DR. VANDENBERG: It also isn't 18 dismissing this at all I think. It is just to 19 illustrate it, just to make a point. 20 DR. BROWN: I am sure we will come 21 back to this, as we plough through.

22 DR. VANDENBERG: Yes.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 52 1 DR. SAMET: Other questions or 2 clarifications? 3 (No response.) 4 Okay. 5 MS. WALSH: So, John has already 6 spoken about HERO, Health and Environmental 7 Research Online. So, HERO was a part of this 8 change in process when we were trying to 9 gather our information and use technology to 10 help us in the thousands of references that we 11 consider and, also, cite in our documents. 12 HERO is actually two parts. One 13 is the actual database that provides the 14 transparency to the stakeholders and the 15 public. And you can see that at epa.gov/hero. 16 The other piece is HERO Net. This 17 is the internal part of the HERO system that 18 we use, actually, to develop our assessments. 19 It provides a way to be sustainable in these 20 large documents that we produce, and so many 21 of them in such a quick time. 22 The reason that we are trying to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 53 1 provide some extra slides here is because we 2 are really interested, and we don't have a 3 charge question on HERO, not that that is 4 appropriate, but I am very interested in your 5 input and your comments. 6 HERO is a very dynamic and agile 7 system. We have the developers for HERO as 8 federal staff. We listen to comments, what 9 works with the staff, what doesn't, public 10 commenters as well. We get a lot of comments

11 on the database. 12 We are using the information to 13 try to make it better. We deploy often. We 14 change. What works we keep; what doesn't work 15 we try to change. 16 I have already spoken to a few 17 CASAC members. If you are having trouble with 18 HERO, getting into HERO, please reach out to 19 us. We want you to be able to use this and 20 for it to be a resource for you. 21 This panel is the first one that 22 we have actually put in as reviewers into HERO

### 202-234-4433 Neal R. Gross & Co., Inc. Page 54 1 Net. And we will show you a little bit later 2 what is different about that. 3 So, this is the public page. PM 4 was the first integrated science assessment 5 that we used HERO to put those blue links that 6 you see in the document. It takes you, when 7 you click on that link, if you are on the web, 8 it takes you to the HERO database. This is 9 just a screenshot. 10 This is the bottom part of that 11 first page. You can see, and I apologize for 12 the fonts here. It is a screenshot. So, the 13 resolution is not great. But you can see here 14 the integrated science assessments. If you 15 click on those tabs, you could actually see

16 the assessment.

17 You can see all the references 18 that are actually used and cited in the 19 document. You could export a bibliography of 20 that, if you wanted to. 21 When you look at the bottom part, 22 HERO was first developed for the ISAs, but we

### 202-234-4433 Neal R. Gross & Co., Inc. Page 55 1 are very quickly trying to integrate this 2 system into our IRIS assessments that we do in

3 NCEA as well. 4 This is HERO Net. So, this is 5 what we use. It has some tools. If you look 6 at the top part above that line, that is very

7 much the same as the HERO database that the 8 public has access to. Below that line, you 9 will see where, instead of just search HERO, 10 the literature search. We have a federated 11 search that we use where we link in all of the 12 subscriptions and databases that EPA 13 subscribes to, as well as all the ones that 14 NCEA actually buys subscriptions to. 15 And instead of in the past, some 16 of you maybe can relate to this, where you 17 would have a journal with a routing slip, and 18 you would pass it around to people's offices. 19 And after you finish, you pass it to your next 20 person. We now have ours electronically into 21 the literature search where the staff can do 22 that online. LitBrowser, LitCiter, these are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 56 1 all different tools that we use at different 2 parts of the assessment. 3 So, this was a page out of the PM 4 document. It was the first -- I think it was 5 the final, where we used LitCiter, which is 6 one of our tools. We actually link in the 7 reference into the assessment. 8 So, if you click on that link, we 9 have a HERO ID that is a unique number. That 10 helps us a lot in keeping our references 11 straight. As you can imagine, trying to 12 manage in some of our assessments 3,000-4,000 13 references, it was a challenge for us. So, 14 this helps us moving away from a paper-based 15 way. 16 You click on that. It goes to the 17 HERO ID, in this case. And this is what you 18 would see. So, the public sees this as well. 19 So, it is the abstract in most 20 cases, if we have that; the relevant metadata 21 that would be there on the citation. You 22 can't see it, at the bottom, where that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 57 1 reference was cited. As you can imagine, some 2 of our references are cited in numerous ISAs. 3 All of that is listed there. So, you would be

4 able to see that. 5 And at the very bottom, that is 6 not captured here -- I apologize -- is 7 actually the DOI. So, the public could click 8 on that and take them to where they can get 9 that paper. A lot of papers we cite are in 10 Open Source. If you have a subscription to 11 that journal, you can get that with your own 12 password. And if you wanted to pay for that, 13 you could, or know how to go find that. 14 For ozone, we tried to, in being 15 responsive to not just what we had in-house, 16 but to now in transparency provide this to the 17 public, are actually the papers that we 18 considered but didn't actually cite in the

19 document. 20 So, in each of the chapters in 21 this first draft of the Ozone ISA, you will 22 see a link that takes you to this landing

### 202-234-4433 Neal R. Gross & Co., Inc. Page 58 1 page. And when you click on this link, then 2 you will be able to go and see all the 3 references that were considered. You can, 4 then, select a box and go look at the

5 abstract. 6 We changed this. The Ozone ISA 7 was released in March, early March. And we 8 just in early May posted the Lead ISA. And in 9 that, we have changed, in that short period of 10 time -- as I mentioned earlier, HERO is a 11 really agile, evolving system. We get 12 comments and we try to change that. 13 So, on the Lead landing page for 14 whoever goes and looks at the Lead ISA that is 15 up, posted now on the web, you are able to go 16 to the link in that and see here the 17 references are actually not only listed, you 18 can see the ones that were cited as well as 19 considered. And there are actually some 20 filters here so you can look at discipline or

21 outcomes. 22 Where we are moving forward, ozone

### 202-234-4433 Neal R. Gross & Co., Inc. Page 59 1 was the first ISA we did not have the 2 supporting material that we called annexes, 3 which was a lot of detailed tables with 4 information, that our goal as we move forward 5 with HERO is to put that type of information, 6 actually the numbers, into HERO in a module we 7 call LitExtractor, where you would be able to 8 query and run a report and get that 9 information out to how you would like to look

10 at that. 11 That is a big undertaking, as 12 anyone here can imagine. We have done 13 different trials with that, and we are trying 14 to get that as soon as we can. 15 But, in the process, to go between 16 the paper Annex tables and before we can get 17 the full LitExtractor deployed, we are doing 18 what is called this LitReporter. So, this is 19 what we are proposing to do for the NOx ISA, 20 which is the next pollutant that we will

21 start. 22 And it is going to have a list of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 60 1 the references and the different metadata that 2 you would pull out of that paper, as well as 3 findings field that will, then, point you to 4 the actual table or figure where some of that 5 information is actually at. 6 This is just a screenshot of our 7 beginning thinking about NOx. We are really 8 trying, as we move forward, to be in a more 9 systematic way to capture what we are 10 evaluating and how we are providing access to

11 that. 12 And then this is just the meeting 13 agenda, how we guide the rest of the day, 14 looking at the charge questions, and our time. 15 So, I would welcome any comments, 16 and would please encourage, we want you to use 17 HERO. We want you to use HERO Net. If you 18 have any difficulties -- I know a letter was 19 sent out. So, please feel free to call us in 20 that information, and we will walk you through 21 that. I am here all day and tomorrow. You 22 know, catch me in the hall. I want to do

### 202-234-4433 Neal R. Gross & Co., Inc. Page 61 1 whatever I can to make this work for you.

2 DR. SAMET: Fred? 3 DR. MILLER: Debra, this is "one 4 giant step," a Neil Armstrong analogy, for 5 ISAs. I mean it is a tremendous step forward 6 for the agency in being able to assimilate 7 this information. 8 I had one quick question about, if 9 we are discussing today papers that we think 10 should be added in that, how is the process 11 where you now take it off of a considered 12 list, and is that something that has to 13 actually be done manually with each one? Or 14 how can you make this job doable on those 15 kinds of refinements? 16 MS. WALSH: So, it is a matter of 17 changing a tag of how that would move. That 18 is not an issue. 19 One of the things, not to

20 elaborate about HERO because I know we are 21 kind of running short on time, but, as we were 22 just speaking earlier, some of the comments

### 202-234-4433 Neal R. Gross & Co., Inc. Page 62 1 about trying to capture those new studies that 2 are coming out and trying to look in a way to 3 keep up with the literature, you know, we are 4 really working with HERO, particularly in this 5 new literature searching that we are doing 6 with the discovery service. 7 We had had a federated service 8 earlier that we had subscribed and built, very 9 similar to what you have at universities, how 10 you can look at multiple databases 11 simultaneously and then remove duplicates and 12 those kinds of things. EPA is working toward 13 that. HERO kind of got in front of that 14 because we are the largest user probably, at 15 least in our facility, of literature like 16 this. 17 We had moved from reams of paper, 18 as we were talking to someone earlier, paper 19 references to get that to an electronic way, 20 where you don't go to a library as such to 21 pull that information. 22 We are really trying for HERO to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 63 1 be an evergreen system where there's constant 2 searches being run. So, the staff is going to 3 have that popping up to them in a way that is 4 whatever we decide is appropriate, weekly, 5 monthly, whatever those studies would show up.

6 DR. SAMET: Howard? 7 DR. NEUFELD: You mentioned that 8 you can find out which document a reference is 9 cited in. Can you also get it down to the 10 page and line number, so you could see where 11 all the -- like if one article is cited 10 12 times in the ISA, you could find out exactly 13 where it was cited in the document? 14 MS. WALSH: No. That's a good 15 question, but, no. We haven't moved to that 16 yet. 17 DR. VANDENBERG: But you can put 18 in, like Adobe, you can put in a search 19 defined field --

20 MS. WALSH: Yes. 21 DR. VANDENBERG: -- and it will 22 roar through it and find all those places for

### 202-234-4433 Neal R. Gross & Co., Inc. Page 64 1 you. That is using an Adobe feature, not a

2 HERO feature. 3 MS. WALSH: But at the moment you 4 can't do that, but you will be able to as we 5 build more in our LitReporter module. This is 6 a relational database, an Oracle relational 7 database, where you will be able to run 8 standard queries as we build that in reports 9 and actually build your own. So, you would be 10 able to see how many ISAs this particular 11 paper was cited in, rather than trying to 12 click through that yourself. To go to the 13 actual page number, we haven't looked at 14 trying to add that kind of information. 15 DR. SAMET: Judy? 16 DR. GRAHAM: What you are doing is 17 just amazing, just amazing. A suggestion. 18 MS. WALSH: Okay.

19 DR. GRAHAM: You talked about what 20 you are going to do for the NOx document. And 21 the impression I got is you are going to use 22 this system to create tables.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 65 1 Given the massive amount of work 2 involved, and at least in my mind the vast 3 importance of tables, it just might be a good 4 idea if you had, let's say, a couple of drafts 5 that you shot out to CASAC, to avoid having to 6 redo things later. 7 MS. WALSH: Absolutely. That is 8 why we are putting you in HERO Net. The 9 general public is not in HERO Net. I mean how 10 we have tried to be very careful, because we 11 are very concerned about copyright and not 12 infringing upon that, but as you look at how 13 we are interpreting the copyright law, it is 14 that it is for researchers. 15 And so, our team, our research 16 team, certainly had included OAQPS, not just 17 NCEA, and those other collaborators that work 18 closely with us on some of our projects we put 19 in there. And this is the first time we have 20 expanded with ozone and to include the 21 reviewers in the CASAC panel as part of our 22 partners working with us. And we think that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 66 1 is appropriate, to put you in HERO Net. 2 DR. SAMET: Okay. Let me check 3 this. Anyone on the phone want to ask a 4 question? I have been ignoring you. Out of 5 sight, out of mind. 6 (No response.) 7 Okay. All right. Any other 8 questions for EPA, for the staff, before we 9 move on to the public comments? 10 (No response.) 11 Great. I am sure we will have 12 many questions later in the day. 13 Okay. Thank you. 14 So, we will move on, then, to a 15 public comment period. And I have four public 16 commenters listed, two of whom will be on by 17 phone. 18 Just as a reminder, you have been 19 allocated five minutes for your public 20 comments. I am holding my trusty stopwatch in 21 hand. I will give you a warning when you have 22 30 seconds left. And I do ask that, when you

### 202-234-4433 Neal R. Gross & Co., Inc. Page 67 1 have completed your five minutes, when I say 2 your five minutes are up, please to end. 3 And for the panel members, if you 4 have questions, clarifying questions or 5 whatever, we will take those right after each 6 of the public commenters. 7 So, let me begin. Our first 8 public commenter is Sam Oltmans from Boulder,

9 Colorado. 10 Let's see, are you on the phone? 11 (No response.) 12 Okay. Then, we will move on to 13 our next public commenter, Allen Lefohn. 14 DR. LEFOHN: Where would you like

15 me? 16 DR. SAMET: There is a spot right 17 up there for public comment. 18 DR. LEFOHN: All right. We're 19 good. I was going to say, do you want me to

20 talk about W-126? 21 Good morning. 22 Let me get my thing going.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 68 1 My name is Allen Lefohn. I am 2 from Montana. I would like to focus on PRB 3 this morning. 4 PRB concentrations we are talking 5 about should be characterized as hourly 6 average concentrations, is my opinion. PRB's 7 temporal characterization should reflect the 8 way in which it is to be applied in various 9 policy aspects, the requirements for one-hour 10 PRB inputting to the risk analysis, based on 11 controlled human laboratory and vegetation 12 studies. 13 By characterizing PRB as hourly 14 average concentrations versus, let's say, 15 multi-month-type averages, I believe it is 16 more meaningful for a comparison with 17 empirical data, such as from Trinidad Head, 18 California, where they can be performed. And 19 Trinidad Head is a site that experiences PRB 20 conditions many times during the springtime. 21 At Trinidad Head, California, the 22 range of maximality concentrations for the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 69 1 month of April over the period is 54 to 65 2 ppb. Generally, during April through May, the 3 monthly mean of the daily maximum eight-hour 4 average is approximately 45, with the number 5 of hourly average concentrations greater than 6 or equal to 50 ppb for April varying from 30 7 to 187. Daily eight-hour average 8 concentrations greater than or equal to 50 are 9 observed on a regular basis during the 10 springtime. 11 Seasonal preference for enhanced 12 ozone concentrations, that is greater than or 13 equal to 50 ppb for Denali, Glacier, 14 Yellowstone, and Voyageurs, reference size 15 during the springtime. 16 And important contributor to PRB, 17 sufficient evidence exists to illustrate that 18 stratosphere to tropospheric transport 19 processes contribute to background ozone20 concentrations at the surface of both high21 and low-elevation monitoring sites. The key 22 question is, how frequently do they

### 202-234-4433 Neal R. Gross & Co., Inc. Page 70 1 contribute? 2 Current estimates of the 3 stratospheric contribution is being performed 4 by our research team. The team consists of 5 Lefohn, Wernli, Shadwick, Limbach, Oltmans, 6 and Shapiro. 7 The trajectory model, LAGRANTO is 8 used to identify days when STT-S enhances 9 hourly average concentrations greater than or 10 equal to 50 ppb. An example of the frequency 11 of STT-S events for a high-elevation site, 12 which we consider to be the gold standard, 13 meaning this is a site that we believe is 14 being enhanced by the stratosphere very 15 frequently, again, April and May predominate 16 for 2006, 2007, and 2008. 17 For a low-elevation site in 18 Chittenden County, Vermont, again, April and 19 May predominate, but there is variability from 20 year to year that occurs. 21 This statistically-significant 22 relationship between STT-S and ozone hourly

### 202-234-4433 Neal R. Gross & Co., Inc. Page 71 1 average concentrations greater than or equal 2 to 50 ppb for the 2006-to-2008 period for 3 Yellowstone, it shows March through August for 4 2006; March through September 2007; March 5 through July 2008. The numbers in parentheses 6 reflect the number of days that STT 7 contributed to the enhancement. 8 For Chittenden County, again, 9 because of the variability that exists, April 10 2006, 19 days; April 2008 and May 2008, 20 and 11 17. We had no relationship during 2007. 12 Statistically-significant 13 relationships between STT-S and ozone greater 14 than or equal to 50, additional sites that we 15 examined for Cheeka Peak; Trinidad Head; 16 Denali; Glacier; Burke County, North Dakota; 17 Voyageurs; Crandon in Wisconsin; Presque Isle 18 in Maine, and Washington County, Maine, all 19 showed statistically-significant relationships 20 in these early elevations on the right. 21 When statistically coincidences 22 occurred at the high-elevation site, the daily

### 202-234-4433 Neal R. Gross & Co., Inc. Page 72 1 maximum hourly springtime averages were 2 usually in the 60-to-70-ppb range, the maximum 3 daily eight-hour in the 50 to 65. At many of 4 the lower-elevation sites, the daily maximum 5 hourly average concentrations were mostly in 6 the 50 to 65, and the daily eight hour, 50 to

7 62. 8 Concluding remarks: the frequency 9 of SST-S events is greater at higher elevation 10 than at lower elevation sites, but both are 11 frequent during the springtime. And 12 statistically-significant relationships are 13 observed between SST-S and daily maximum 14 hourly averages in concentrations greater than 15 or equal to 50 -- 16 DR. SAMET: Thirty seconds. 17 DR. LEFOHN: -- at both high- and 18 low-elevation sites during the springtime and 19 sometimes during the summertime. 20 Final remark: besides being 21 important for determining the emission 22 reductions required for attaining an ozone

### 202-234-4433 Neal R. Gross & Co., Inc. Page 73 1 standard, the level of PRB also affects the 2 risk estimates. PRB ozone concentrations 3 should be characterized as hourly average 4 concentrations because of import requirements 5 associated with the risk analysis, 6 methodologies for controlled human laboratory, 7 and vegetation studies. 8 Thank you. 9 DR. SAMET: Thank you. 10 You had barely a second left. 11 Very good. 12 (Laughter.) 13 One question: it sounds like you 14 have an ongoing program of research. Could 15 you say what are you doing and who is funding 16 it? 17 DR. LEFOHN: Okay. The API is 18 funding this research. The API also funded my 19 research for the AOT 90 adjusted for the human 20 health that we came out with last year with 21 Milan Hazucha and Dr. Adams, Drs. Hazucha, 22 Adams, and Chadwick, and W126 they also

### 202-234-4433 Neal R. Gross & Co., Inc. Page 74 1 funded. 2 DR. SAMET: Okay. Thank you. 3 DR. LEFOHN: Thank you. 4 But can I also add one quick point 5 to your question? It is ongoing, and there 6 are 12 sites where we looked at it, phase 2. 7 We have now looked at 36 sites over the 2006- 8 to-2008 period. 9 DR. SAMET: Okay. Thank you. 10 Other questions?

11 DR. MILLER: I have one. 12 DR. SAMET: Yes, Fred? Fred?

13 DR. MILLER: You talked about 14 hourly averaging, and the EPA presentation

15 referred to the fact that the PRBs would be 16 modeled. Is there any difficult from your 17 perspective that this could, in fact, move 18 over? Because my own feeling would be that 19 you would be doing a cumulative, weighted 20 average moving with time through the year, not 21 just making it seasonal. And I think the 22 computational power is there to do it.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 75 1 So, I am curious what you are 2 meaning, if there is a difference on how it 3 could be implemented or not from your 4 recommendation. 5 DR. LEFOHN: Well, let me see if I 6 said that right. The input last time, and I 7 think the recommendation this time in the 8 risk, is for hourly average concentrations to 9 go into the risk for some of the analysis, for 10 the W126 and for the personal exposure part of 11 the human health risk. 12 Last time, what was done was that 13 they used the diurnal patterns. On page 2-55 14 of the staff paper, it says we provided, we, 15 EPA, provided the diurnal patterns, the one 16 o'clock average, the two o'clock average, the 17 three o'clock average, for April through 18 September. There was a problem with that, in 19 my opinion. 20 And that problem was where we talk 21 about PRB being a range of 15 to 35 ppb in the 22 last criteria document, when that diurnal

### 202-234-4433 Neal R. Gross & Co., Inc. Page 76 1 pattern was averaged, it was really 15 to 25 2 ppb. Occasionally, it reached 30 and 35. But 3 it was the smoothing of use of the monthly 4 diurnal pattern. 5 As far as how the model goes and 6 such like that, Daniel Jacob and I have had 7 conversations on this and such. And I am sure 8 that he will be able to expand on that. 9 DR. SAMET: Daniel? 10 DR. JACOB: I can expand and 11 follow up as a question to Allen. Yes. Okay. 12 So, right now, the model POD calculations, as 13 described in the ISA, are based on the MDA and 14 the AR daily maximum averages. And the model 15 can capture a very large fraction of a 16 variability that you describe, except at the 17 very, very high extremes. Like the models 18 cannot get 100 ppb at Yellowstone. But, aside 19 from that, the models can get really all the 20 variability stretching to 70-75 parts per 21 billion. 22 And my question to you is, what do

### 202-234-4433 Neal R. Gross & Co., Inc. Page 77 1 we gain by going from this capture of the 2 diurnal variation of the PRB, day-to-day 3 variation of the PRB, to going to the hourly 4 variability, which the models I think would 5 have a harder time capturing? 6 DR. LEFOHN: Well, I am not sure 7 the models are capturing it that well. For 8 example, at Trinidad Head, if someone were to 9 take -- and I have not seen -- I guess I have 10 looked at some of the 2001 maps in the ISA. 11 It shows, I don't know, 20 to 35 ppb. But 12 those are average. Those are two-month 13 averages for the springtime, April and May. 14 So, my point is, No. 1, for the 15 W126, I believe the hourly average 16 concentrations are going to be required in 17 there of PRB. The eight-hour daily max that 18 is in the appendix and such like that is a 19 good start at being able to compare against 20 the empirical data that are seen, PRB 21 conditions. 22 Trinidad Head is a very good site.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 78 1 We think we are seeing stratospheric 2 contribution or we believe we are seeing3 stratospheric contribution at the low4 elevation sites. I believe using some of the 5 information there of higher resolution, and 6 not the multi-month-type averages, begins to 7 get at the contribution of the stratosphere at 8 the lower-elevation sites, which is very, very 9 important. 10 DR. SAMET: Okay. Any other 11 clarifying questions? 12 (No response.) 13 Okay. Thank you. 14 DR. LEFOHN: And Sam Oltmans may 15 be available. He was supposed to be. 16 DR. SAMET: Okay. That's fine. I 17 will come back to him and see if he is 18 available. 19 Okay. Our next presenter is Julie 20 Goodman from Gradient Corporation, on behalf 21 of the American Petroleum Institute. 22 Julie?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 79 1 DR. GOODMAN: Thank you for the 2 opportunity to -- 3 DR. SAMET: Why don't you wait? 4 Do you have slides?

5 DR. GOODMAN: I do not. 6 DR. SAMET: Oh, you do not? Okay.

7 Go ahead then. 8 DR. GOODMAN: Are you going to 9 start the timer over? 10 (Laughter.) 11 DR. SAMET: Go for it.

12 DR. GOODMAN: Thanks for the 13 opportunity to speak today. 14 The ISA does not provide evidence 15 to support a lower ozone NAAQS than the 16 current primary standard. The weight of 17 evidence from controlled human exposure 18 studies indicates that there are no effects on 19 lung function associated with ozone exposures 20 below 72 ppb, and this is consistent with 21 biological data that support a threshold 22 mechanism of action.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 80 1 Group mean changes in FEV1 were 2 statistically-significant, although not 3 clinically-relevant, in only one of four 4 studies examining 60 ppb. So, one must 5 conclude this association cannot be 6 interpreted as causal.

7 Now much has been made of the 8 Adams 2006 study, which indicated that 9 controlled exposure to 60 ppb ozone did not 10 result in a statistically-significant group 11 mean change in FEV1. And I have previously 12 provided comments to CASAC on the 13 inappropriate re-analysis of Adams by Brown, 14 et al., in 2008. 15 This re-analysis resulted in a 16 statistically-significant group mean decrement 17 in FEV1 at 60 ppb, but this can be attributed 18 to the majority of the data being selectively 19 omitted from the analysis.

20 EPA has not addressed another re21 analysis of the Adams 2006 data by Nicholas 22 2007, nor an analysis of five controlled human

### 202-234-4433 Neal R. Gross & Co., Inc. Page 81 1 exposure studies, including Adams 2006, by 2 Lefohn in 2010, who just spoke. Both of these3 analyses did not find a statistically4 significant group mean FEV1 decrement with 5 exposure to 60 ppb ozone.6 EPA has given no scientifically7 acceptable justification for relying on the 8 Brown analysis over the original analyses 9 conducted by Adams or those of Nicholas or 10 Lefohn, which used methods that are more 11 appropriate for the study design and indicated 12 there is no association between exposure to 60 13 ppb ozone and lung function decrements. In 14 the ISA, EPA should recognize and give greater 15 weight to analyses using these methods.

16 The most recent controlled human 17 exposure study by Kim, et al., in 2011, 18 measured FEV1 at several time points during 19 the exposure period, but only analyzed the 20 data from the pre- and post-exposure time 21 points, an approach that is likely to have led 22 to false-positive results.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 82 1 Also, while the authors reported a 2 statistically-significant group mean change in 3 FEV1 after 6.6 hours of exposure to 60 ppb 4 ozone, the lung function effects were not 5 adverse, according to broadly-recognized 6 clinical guidelines. The available evidence 7 indicates that adverse lung function effects 8 are only observed at controlled ozone 9 exposures of at least 88 ppb. 10 But, regardless of the statistical 11 method used, EPA should acknowledge that it 12 cannot be determined whether any large 13 decrements in lung function in particular 14 individuals in these exposure studies are 15 representative of a generalized effect of 16 ozone exposure. These studies were not 17 designed to determine whether effects in 18 individual subjects are attributable to ozone 19 and should not be re-analyzed or interpreted 20 as such in the ISA. 21 In addition, one cannot determine 22 whether there would be a population shift in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 83 1 FEV1 decrements based on the small number of 2 individuals in the controlled exposure 3 studies. Using the results of these studies 4 to make broad conclusions about large 5 populations is at variance with the criteria 6 of the American Thoracic Society, which draw 7 a clear distinction between small changes in 8 lung function in individuals from exposure9 studies and small, but statistically10 significant reductions in lung function of a 11 population, as derived from observational 12 epidemiology studies.

13 EPA has also not addressed how the 14 controlled exposure studies, as well as other 15 biological data, indicate a threshold mode of 16 action for the effects of ozone on lung 17 function. For example, it has been shown that 18 antioxidants react with ozone in a time- and 19 concentration-dependent manner in the 20 respiratory tract, and it is only when these

21 defenses are saturated that ozone can cause

22 adverse effects. EPA should address these

### 202-234-4433 Neal R. Gross & Co., Inc. Page 84 1 data, as well as the clear evidence for a 2 threshold from the controlled exposure 3 studies, in the ISA. 4 Now, moving on to the 5 observational epidemiology data, EPA does not 6 document its methods and criteria for 7 identifying the studies to be reviewed. This 8 results in a lack of transparency in the 9 assessment, as it is unclear how many studies 10 with null results may have been omitted from 11 the evaluation. 12 In addition, the ISA does not 13 sufficiently describe EPA's methods for 14 evaluating the strengths and limitations of 15 the selected studies, which leads to an 16 inconsistent evaluation of individual studies. 17 EPA emphasizes positive associations, whether 18 they are statistically-significant or not, and 19 often discounts null results. 20 Furthermore, there is no clear 21 framework presented for evaluating the weight 22 of evidence in establishing causation, which

### 202-234-4433 Neal R. Gross & Co., Inc. Page 85 1 leads to inconsistent and often ad-hoc 2 approaches to hazard identification. 3 Finally, the ISA does not define 4 the concept of consistency of findings within 5 and among studies, leading to conclusions 6 about causation that appear to be based on a 7 subjective view of the overall data. 8 As I pointed out in my written 9 comments, these points are consistent with 10 those of a Committee assembled by the National 11 Research Council of the National Academy of 12 Sciences, who reviewed EPA's draft IRIS 13 assessment for formaldehyde. They noted that 14 other NRC committees have identified -- 15 DR. SAMET: Thirty seconds. 16 DR. GOODMAN: -- the same issues 17 in a number of EPA's IRIS assessments over the

18 last decade.19 In closing, a scientifically20 rigorous analysis did not support a causal 21 relationship between ozone exposure and health 22 outcomes evaluated in the ISA at exposure

### 202-234-4433 Neal R. Gross & Co., Inc. Page 86 1 levels below the current NAAQS. 2 DR. SAMET: Okay. Thank you. 3 I do have to point out, as Chair 4 of the Committee that reviewed the IRIS 5 formaldehyde assessment, that, in fact, in 6 Chapter 7, the process of the ISA, and so on, 7 is actually highlighted as one that 8 represented a major shift in how the agency 9 was conducting its reviews that had led to a 10 greater transparency. So, I believe that 11 needs to be made clear in your appendix, which 12 does draw on that document, Chapter 7, that, 13 in fact, there was additional material related 14 specifically to this process.

15 Others? Fred?

16 DR. MILLER: Your statement 17 relative to the Kim study and the fact that 18 they analyzed at this end of the six hour, 19 leading to a false-positive, is beyond 20 credulence. That study had adequate 21 statistical power compared to any other 22 clinical study at the 60 part per billion.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 87 1 And moreover, when you are looking at the 2 decrement, you would have also seen a 3 significant time trend. So, it is beyond me 4 how you can claim that that would lead to a 5 false-positive. 6 DR. GOODMAN: Because when Kim did 7 the analysis, they didn't account for all of 8 the time points that they looked at. They 9 only --

10 DR. MILLER: That doesn't matter. 11 The point is that the overall trend and the 12 time period that they were comparing in their 13 hypothesis relative to the other extended 14 exposures was the final point, and it is valid 15 statistically. 16 I have a doctorate in statistics, 17 and I can tell you I looked at the Brown 18 analysis and they did acceptable statistical 19 evaluations. There are different ways to 20 analyze data depending on what your hypothesis 21 is. 22 DR. GOODMAN: I think that you

### 202-234-4433 Neal R. Gross & Co., Inc. Page 88 1 have to consider that several other people2 have done statistically/scientifically3 appropriate analyses which I would argue are 4 more appropriate than the Brown analysis, and 5 they found no statistical association. And 6 there is really no argument to discount those, 7 first of all. 8 And, second of all, you need to 9 consider that, even if it is statistically 10 significant, the decrements are so small, they 11 are not clinically-relevant. 12 DR. SAMET: Well, we will return 13 to these issues when we look at that chapter. 14 Other questions? 15 (No response.) 16 Okay. Thank you, Julie. 17 Next, George Wolff. George, are 18 you on the phone? 19 MR. WOLFF: Yes, I am, Jon. 20 DR. SAMET: Okay. So, next we 21 will hear from George Wolff, Air Improvement 22 Resource, Inc., on behalf of the Utility Air

### 202-234-4433 Neal R. Gross & Co., Inc. Page 89 1 Regulatory Group. 2 George, anytime, please. 3 DR. STALLWORTH: I would like to 4 say that George's slides are on the CASAC 5 website, if you want to follow along on your 6 laptop. 7 DR. SAMET: Okay. Are they going

8 to be shown?

9 DR. STALLWORTH: No.

10 DR. SAMET: We don't have them

11 here. 12 Okay. Okay, fine. George, go 13 ahead anytime. 14 MR. WOLFF: Thank you. 15 In the REA health plan, EPA 16 states, and quote: "We will likely consider 17 several different background definitions, U.S. 18 background, North American background, and 19 natural background." I strongly endorse EPA 20 considering different backgrounds. 21 The EPA modeling plan includes the 22 GEOS-Chem modeling system, which will be run

### 202-234-4433 Neal R. Gross & Co., Inc. Page 90 1 using emissions and meteorology for three 2 annual periods, 2006 to 2008. The GEOS-Chem 3 model will be run using two nested grids. The 4 outer grid will be global in extent to utilize 5 the grid resolution of 2 degrees by 2.5 6 degrees. The inner grid will be centered over 7 North America and use a horizontal resolution 8 of .5 to .67 degrees, and four scenarios will 9 be modeled. These are welcome improvements to 10 the previous ISA. 11 Different background scenarios 12 that are proposed by EPA: first, the base 13 case simulation will be completed using all 14 global, anthropogenic, and natural emissions. 15 A model performance evaluation will be 16 completed for this scenario. 17 Second, U.S. anthropogenic 18 emissions of NOx, non-methane VOC, and CO are 19 set to zero. All anthropogenic emissions 20 outside the U.S. are maintained at the current

21 level. 22 And, third, U.S., Canadian, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 91 1 Mexican anthropogenic emissions are set to

2 zero. 3 And, fourth, all global 4 anthropogenic emissions are set to zero. 5 However, as I will show shortly, 6 these scenarios address the wrong questions. 7 I applaud this four-tiered 8 approach because GEOS-Chem runs used by EPA in 9 its 2007 risk assessment significantly 10 underestimated PRB because it underestimated 11 the stratospheric and tropospheric 12 contributions. It underestimated natural NOx 13 emissions. It underestimated Asia-Pacific NOx 14 emissions. It used outdated chemistry and 15 physics. The grid resolution was too coarse. 16 And monthly means of the diurnal PRB profiles 17 are inappropriate to use for a max that is 18 based on the three-year mean of the fourth 19 highest eight-hour value. 20 However, I feel the definition of 21 PRB is also inappropriate. EPA assumes that 22 it has the power to control emissions in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 92 1 Mexico and Canada. By not including these 2 emissions in PRB, EPA assumes a treaty could 3 eliminate it. It penalizes states that must 4 come up with additional control measures to 5 compensate for Mexican and/or Canadian 6 emissions. EPA needs to redefine PRB to 7 include emissions from all foreign countries, 8 including Canada and Mexico. 9 EPA is asking the models the wrong 10 question. EPA is asking, what would the ozone 11 be in the U.S. if the U.S. had no 12 anthropogenic emissions? This is a 13 meaningless question. The answer has no 14 relevance to control strategies. It has no 15 relevance to risk assessment. It answers 16 questions about a fictitious atmosphere. 17 The correct question to ask is, 18 what are the contributions from sources that 19 EPA has no control over? There are two ways 20 to answer this question. 21 First, you can use GEOS-Chem, run

22 a base case. The second run would zero-out

### 202-234-4433 Neal R. Gross & Co., Inc. Page 93 1 natural emissions and get the natural 2 background. 3 Third would be zero-out natural 4 and foreign anthropogenic emissions, and 5 subtracting this from the base case, you would 6 get the revised PRB. 7 And fourth, zero-out Mexican and 8 Canadian anthropogenic emissions, and 9 subtracting that from the base case, you would 10 get the Canadian and Mexican contribution. 11 You could also do this using a 12 combination of CAMx and GEOS-Chem where the 13 GEOS would compute boundary conditions and 14 CAMx would be used for proportion. 15 Finally, my recommendation: PRB 16 should be redefined to include Canadian and 17 Mexican anthropogenic contributions. I 18 support EPA's new modeling effort with the 19 modeling -- 20 DR. SAMET: Thirty seconds. 21 MR. WOLFF: -- emission scenarios. 22 Emission scenarios should be modified so that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 94 1 all U.S. anthropogenic emissions are included 2 in all scenarios. 3 I strongly support a rigorous 4 model performance evaluation on the base case, 5 and the ISA should be revised to include the 6 modeling plan. 7 Thank you. 8 DR. SAMET: Okay. Thank you. 9 Questions? 10 (No response.) 11 Okay. I guess not. 12 Thank you, George. 13 Let me check, is Sam Oltmans on 14 the phone? 15 DR. OLTMANS: Yes, I am. 16 DR. SAMET: Okay. Let's see, do 17 you have slides?

18 DR. OLTMANS: I do. 19 DR. SAMET: Let's see, Holly, do

20 we have them?

21 DR. STALLWORTH: We don't have 22 them loaded on the laptop.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 95 1 DR. SAMET: I'm sorry, I guess we 2 don't have your slides available. 3 DR. OLTMANS: I was told they were 4 at least loaded onto the website. 5 DR. SAMET: Loaded on the website. 6 Okay. 7 Why don't you go ahead, then? 8 DR. OLTMANS: Okay. My name is 9 Sam Oltmans. I am a recently-retired research 10 scientist with the NOAA Research Laboratory in 11 Boulder, Colorado. These comments are being 12 provided by me as a private individual. 13 A significant portion of my 14 research career has been devoted to measuring 15 and understanding background ozone in the 16 atmosphere. 17 Next slide. 18 Although a policy-relevant 19 background is not a directly-measured 20 quantity, I believe it is very important to 21 make measurements of what I will term 22 "background ozone", not only as a validation

### 202-234-4433 Neal R. Gross & Co., Inc. Page 96 1 tool for models, but, also, as a quantity that 2 can be directly compared with measurements 3 made at locations that must meet air quality 4 compliance requirements. 5 I established the Ozonesonde 6 Program at Trinidad Head in 1997 and the 7 surface ozone-monitoring program at this site 8 in 2002 for the express purpose of measuring 9 baseline ozone entering the West Coast of the10 U.S. As I will discuss later, the relatively11 remote exposed location at Trinidad Head is a 12 well-located site for measuring and 13 understanding background ozone. 14 Skip to slide 4. 15 I have published several papers 16 describing tropospheric ozone at this site, 17 focusing on the representativeness of the 18 ozone measurements and characterizing the 19 ozone background entering the West Coast of 20 the U.S., and understanding the processes that 21 contribute to this background ozone signal. 22 In the spring, Trinidad Head

### 202-234-4433 Neal R. Gross & Co., Inc. Page 97 1 consistently sees ozone mixing ratios greater 2 than 50 ppb, an April average of over 45 ppb, 3 and a range of maximum hourly averages between 4 54 and 65 ppb. At the top of the boundary 5 layer, based on the Ozonesonde data at 6 approximately 2 kilometers, average ozone 7 mixing ratios are 50 ppb in both the spring

8 and the summer. 9 Next slide. 10 We have used both trajectories and 11 local wind information to determine conditions 12 representative of air coming off the Pacific 13 Ocean. During the daytime hours, the ozone 14 measured at Trinidad Head is overwhelmingly 15 representative of the marine background. This 16 is the conclusion of a number of studies in 17 addition to our own. 18 Next slide. 19 Vertical measurements of both 20 ozone and carbon monoxide provide additional 21 information on the representativeness of the 22 Trinidad Head observations for determining

### 202-234-4433 Neal R. Gross & Co., Inc. Page 98 1 background levels of ozone. 2 Regular aircraft measurements 3 above Trinidad Head, which measure a number of 4 trace species, including carbon monoxide and 5 ozone, show that air coming onshore at the 6 observation location has levels of carbon 7 monoxide that are representative of global 8 background at that latitude, at the latitude 9 of the station, implying that we are measuring 10 background ozone signal as well. 11 An intensive six-week campaign of 12 daily Ozonesonde measurements at six sites in 13 California in May and June of 2010, as part of 14 CalNex, showed that ozone measured at sites 15 running along the coast of California have 16 similar average concentrations to Trinidad 17 Head in the lower troposphere. Thus, ozone 18 measured at Trinidad Head is generally 19 representative of air entering the coast of 20 California. 21 Next slide. 22 From the CalNex data, when we

### 202-234-4433 Neal R. Gross & Co., Inc. Page 99 1 screened the data below 3 kilometers for 2 possible North American influence, there is 3 essentially no difference in ozone amounts 4 from the complete set of measurements and, in 5 fact, there is slightly less ozone when North 6 American influence is included. 7 Interior continental locations can 8 also provide information on background ozone 9 levels. An example at Denali National Park in 10 Alaska shows that the highest ozone amounts at 11 this remote site are not associated with North 12 American influence, but, rather, long-range 13 transport from Eurasia. 14 Slide 9. 15 Careful analysis of data from 16 several relatively-remote locations shows 17 that, when local effects such as land/sea wind 18 circulation at Trinidad Head or 19 downslope/upslope circulation -- 20 DR. SAMET: Thirty seconds. 21 DR. OLTMANS: -- at mountain 22 locations at Niwot Ridge, that such locations

### 202-234-4433 Neal R. Gross & Co., Inc. Page 100 1 can provide information on background ozone. 2 The conclusions are that Trinidad 3 Head is a well-located site for monitoring air 4 entering the West Coast of the U.S. 5 Understanding of measurement conditions at a 6 continental site can yield important 7 information on background ozone. Intensive 8 ozone observations confirm that ozone measured 9 at Trinidad Head -- 10 DR. SAMET: Okay, five minutes are 11 up. Thank you for your presentation. 12 DR. OLTMANS: Okay. 13 DR. SAMET: Sorry, I don't think

14 we have -- 15 DR. STALLWORTH: No, I don't think 16 I have the slides posted. I am just checking 17 my email. I got a text file from you, but I 18 don't think I got PowerPoint slides. 19 DR. OLTMANS: No, I have an email 20 message that -- 21 DR. STALLWORTH: Okay. 22 DR. OLTMANS: -- says you loaded

### 202-234-4433 Neal R. Gross & Co., Inc. Page 101 1 those onto the site. 2 DR. STALLWORTH: George found 3 them. You said they are posted? Okay. I was 4 looking for one that just had Oltmans. So, it 5 is the Oltmans and Lefohn slides. Okay. 6 DR. SAMET: There is a text file. 7 I did not see, actually, a PowerPoint 8 presentation. 9 Yes, you might, I think to 10 supplement the presentation, it would be 11 useful to get them. We will get them posted,

12 so that we can see them. 13 Maybe it was hard to follow since 14 we do not have the slides, but I wonder if 15 anyone has any clarifying questions. 16 (No response.) 17 Any of the CASAC members on the 18 phone, I have not forgotten that you are there 19 completely. 20 (No response.) 21 No? Okay. 22 Then, let me thank the public for

### 202-234-4433 Neal R. Gross & Co., Inc. Page 102 1 your comments and input. 2 Now, actually, this happens 3 sometimes, we are ahead of schedule. And what 4 I think we should do is proceed to take a 5 break, and let's get back together at 10:15 6 and, then, go on with a discussion of the 7 charge questions. 8 Deborah Shprentz is not 9 commenting. 10 (Whereupon, the foregoing matter

11 went off the record at 9:58 a.m. and resumed 12 at 10:22 a.m.) 13 DR. SAMET: Okay. We are back in 14 session. 15 And we are going to move on to the 16 discussion of the charge questions. Again, 17 the way we have usually done this is with our 18 lead discussant providing their input first. 19 We, of course, have the compilation of

20 comments. 21 Let me check, Sverre, are you on 22 the phone? Sverre Vedal, are you on the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 103 1 phone? 2 (No response.) 3 So, we will check if Sverre is

4 here. 5 But why don't we lead off, then, 6 John with your comments? 7 DR. BAILAR: I am not going to 8 read my comments, but, rather, hit a couple of 9 high points and expand on them some. 10 The first is that I think EPA 11 needs to revisit its definition of cause. It 12 is given here on page 1-14 as "Cause is a 13 significant effectual relationship between an 14 agent and an effect on health or public

15 welfare." 16 First, it is not clear to me what 17 you mean by significant. Does this refer to 18 the size of the effect? Does it refer to 19 statistical significance? I don't know. 20 The second is that effectual is 21 not very well-defined. The point is that I 22 would not know how to apply this definition in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 104 1 an unambiguous fashion. So, I ask EPA to 2 revisit that. 3 The second point I want to talk 4 about is the Hill criteria. I am concerned 5 about two things here. 6 First, I would like to say that I 7 think the discussion on a micro-level is right 8 on target with one exception I will get to in 9 a minute. It is the macro-use of these that

10 concerns me. 11 The first aspect of that is that I 12 think these should be taken in a very broad 13 way as providing a point of view or a context 14 and not a checklist. 15 The second thing is that I think 16 it is inappropriate to assign weights to 17 these, to say, for example, that consistency 18 is more important than specificity. You have 19 to look at the whole body of evidence. 20 The one thing I would like to add 21 to that is that failure to satisfy one or more 22 of the criteria can be as telling as meeting

### 202-234-4433 Neal R. Gross & Co., Inc. Page 105 1 them. And I would like to see that brought 2 out as well. Again, it is important to look 3 at the whole body of evidence. 4 I might add that I heard Bradford 5 Hill himself talk about these just a very few 6 years after he published his paper in 1964, 7 and I think he would agree with both points of 8 view, that this is not a checklist and that 9 you should not assign weights or relative 10 importance to the specific items. 11 Thank you. 12 DR. SAMET: Okay. Is that it?

13 DR. BAILAR: Yes. 14 DR. SAMET: Okay. All right.

15 Good. 16 I will say that, and maybe a 17 little history, John, for you and for the 18 others, and EPA may want to elaborate. I 19 think a lot of this text was originally 20 developed with the particulate matter ISA. 21 And undoubtedly, it continued to be refined. 22 I think the definition of cause is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 106 1 a paraphrase of what is in the `64 Surgeon 2 General's Report, which sort of lapsed to 3 that. I understand your picking on it. I 4 think, actually, that is what is in the very 5 brief chapter on causation in the `64 report, 6 or something very similar, I think. And 7 perhaps, again, obviously, this issue can be 8 as tough and as deep as anybody wants to take 9 it. 10 DR. BAILAR: Well, regardless of 11 the history of this, I don't know how to use 12 that definition. 13 DR. SAMET: Okay. I think we can, 14 after we hear from the other discussants, I 15 think we can come back because I agree it 16 should be clear how it is going to be used in

17 the document. 18 Sverre is on the line. 19 Sverre, you are with us? 20 DR. VEDAL: Yes. Yes. Hi, John. 21 DR. SAMET: Hi. 22 DR. VEDAL: Can you hear me?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 107 1 DR. SAMET: Yes, we can hear you. 2 Why don't you go ahead? 3 DR. VEDAL: Yes. So, I don't 4 have, I think, a lot of overlap with what John 5 has said, but I do have, I guess, a little bit 6 of a different tact with the issue of 7 causation. And I don't think we need to 8 belabor this an awful lot. 9 I took exception, first, with 10 causes needing to be significant. They don't. 11 And it is also an ambiguous term. 12 But, you know, the term just 13 effectual, as in an effectual relationship, it 14 just not very informative, and it is in some 15 sense just a little circular. So, it is 16 probably right, but it is not really useful. 17 So, I was making a pitch, 18 basically, for -- and to their credit, there 19 is some allusion to counterfactuals, but I am 20 a fan of that perspective. In this context, 21 it actually has a lot of merit just because 22 the incorporation of the notion of sort of all

### 202-234-4433 Neal R. Gross & Co., Inc. Page 108 1 else being equal, which manifests itself in 2 controlled exposures, both in the toxicologic 3 experiments and the human clinical studies, 4 and then in observational studies in the 5 notion of control for confounding. 6 So, I think you can do a lot more 7 than just putting up sort of a knee-jerk 8 definition of causation. But, again, this 9 whole exercise isn't going to sink or swim on 10 the definition of causation. So, that is 11 enough on that. 12 The confounding and effect 13 modification sections, having seen previous 14 ISAs, this is a clear improvement over 15 previous discussions. There are a couple of 16 things I will elaborate on. 17 One is bringing up the notion of 18 multiple pollutants. But it is sort of 19 couched in a sort of weird sort of a 20 framework. It is has to be upfront expressed 21 in the context of confounding, that we are 22 talking about confounding by co-pollutants.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 109 1 And it is not clear that that's the sort of 2 crux of the discussion there, even though it 3 is in a confounding section. 4 Again, effect modification, I 5 think there is a much better job this time as 6 opposed to other ISAs in distinguishing it 7 from confounding. I think in the discussion 8 of it, rather than sort of launching into how 9 it differs from confounding, it is probably 10 best to define effect modification first. 11 It is interesting how temperature, 12 as an example, is sort of brought forward as 13 an example of an effect modifier, which it 14 certainly can be. But I think it would be 15 valuable to sort of compare and contrast it 16 to, just by expressing or discussing the 17 notion of temperature as a confounder, which 18 it clearly is, front and center, in the issue

19 of ozone effect. 20 The discussion of measurement 21 error, and it kind of sticks out there in the 22 middle, it should refer to the discussion, a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 110 1 much more detailed discussion of measurement 2 error that is in Chapter 4. I think here the 3 discussion is a little bit confusing. 4 I think the main point that should 5 be made there, and I think maybe it is 6 attempted to be made, is this notion of 7 pollutants being measured with different 8 degrees of measurement error. And when you 9 have two pollutants in a model, this notion 10 that the pollutant that is measured with less 11 error tends to dominate the effects of a 12 pollutant that is measured with more error, 13 regardless of which of the two of them 14 actually has a greater effect on health. So, 15 that is the point that needs to be made here 16 with respect to measurement error. 17 Causality determination, weighted 18 evidence, so just a small point. John touched 19 on the sort of Hill points. Just a little 20 elaboration on the coherence issue. 21 It doesn't just refer to coherence 22 across, for example, epidemiology, toxicology,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 111 1 clinical studies, et cetera. It also refers 2 to coherence within epidemiology, not in the 3 sense of consistency by repeated studies, but 4 across different study designs. 5 I don't really find, with all due 6 respect to Bradford Hill, and he probably 7 didn't mean it in that way, I don't find his 8 criteria all that useful, except I think the 9 notions of consistency and coherence. And I 10 think the ISA kind of brings that up, that 11 they are not sort of wedded to this framework 12 in assessing the causality, but those issues 13 are clearly part of the discussion. 14 We have been through this grade of 15 causality before. I think it is a good idea. 16 It has worked well, certainly in the PM 17 setting reasonably well, although it has some

18 warts. 19 I like the fact, although it 20 probably has no utility, I like the fact that21 there is now a not-likely-to-be-a-causal22 relationship category, which I don't think was

### 202-234-4433 Neal R. Gross & Co., Inc. Page 112 1 present in earlier versions. It may have been 2 in one version subsequent to the PM ISA. I 3 don't know. But I kind of like that for 4 symmetry, if nothing else. 5 Under that section, there is some 6 reference to studies from the perspective of 7 the concentrations of ozone that are used. 8 That is, studies with what concentrations are 9 going to be deemed to be relevant for this 10 causality assessment? And they throw in that 11 concentrations of an order of magnitude or two 12 orders of magnitude higher would be 13 appropriate for this. I think that is just 14 silly. And I gave an example about what path 15 that would lead us down. And I don't think 16 that is going to be meaningful in terms of 17 causality determination. 18 The section on the effects on 19 human population -- a couple of points. First 20 is the shape of the exposure response 21 relationship. I think they do actually 22 categorize sort of the issues that would tend

### 202-234-4433 Neal R. Gross & Co., Inc. Page 113 1 to influence that. 2 I think one that perhaps deserves 3 a little bit more emphasis in the context of 4 ozone particularly is the measurement error 5 issue. Here we have a pollutant where, 6 arguably, you have the potential for more 7 measurement error than most of the pollutants 8 that we deal with. So, this issue of blurring 9 of a potential threshold is upfront and 10 probably a more meaningful or a more 11 concerning issue than it would be for other 12 pollutants that might exhibit less measurement

13 error. 14 It was great to see the discussion 15 of publication bias here. I thought that an 16 attempt was being made to sort of minimize the 17 impact of publication bias, but I think that 18 has been put to rest. It is not a small 19 issue, both by the work from Ross Anderson and 20 Michelle Bell, both showing, I think, clearly, 21 Michelle in the context of ozone, that 22 publication bias is at work, comparing multi-

### 202-234-4433 Neal R. Gross & Co., Inc. Page 114 1 city study effects estimates from other effect 2 estimates. 3 Finally, the issue of adversity, 4 and I know this has been beat to death in some 5 settings, and it is clearly an issue in the 6 context of ozone, where we have got lung 7 function decrements, where some points can be 8 raised about adversity. Lots of markers being 9 used, and no discussion really of where these 10 markers, markers of inflammation and oxidated 11 stress, for example, where these markers fit 12 in in this discussion of adversity. So, I 13 thought it was kind of a perfunctory little 14 section in there, but it didn't really get at 15 the crux of the issues regarding adversity in

16 the context of ozone. 17 So, those are my largest 18 observations. The rest I have some small 19 points. 20 DR. SAMET: Okay. Thank you.

21 Howard?

22 DR. NEUFELD: There's not a lot

### 202-234-4433 Neal R. Gross & Co., Inc. Page 115 1 left for me to say after these two. But I 2 think that the framework set up here is pretty 3 reasonable, and I don't want to belabor some 4 of the points that were made earlier. 5 I think that the scenarios laid 6 out here for evaluating causation and the 7 associations, and so on, are well-thought-out. 8 I don't really have too many criticisms of

9 that. 10 And I think that most of the 11 points that need to be addressed in terms of 12 determining the relationships and conclusions13 that are going to be drawn are all well14 thought-out. And the idea of dealing with 15 confounding and uncertainty and variance and 16 other sort of things are all laid out in here 17 pretty well. 18 And I think that I would emphasize 19 -- I am going to be real short here because I 20 don't want to say the same thing over -- but 21 I think that the section on the publication 22 bias is really important. It is also

### 202-234-4433 Neal R. Gross & Co., Inc. Page 116 1 important in the vegetation and ecosystem 2 literature, too. If you don't get any 3 significant results, you tend not to publish 4 that. So, we tend to get a somewhat biased 5 point of view. So, there is some emphasis in 6 those fields to actually start to publish 7 those kinds of papers. 8 But I do think this sets up the 9 rest of the document here fairly well. So, I 10 will just leave at that, at that point. 11 DR. SAMET: Okay. Thank you. 12 I would just add my own comment 13 that I think, to the extent this chapter 14 really should be setting out the template for 15 the evidence evaluation process that will 16 follow it, I think as we move forward I think 17 what we should really be doing is saying, 18 well, is there evidence, in fact, that this 19 has been used and followed in summarizing the 20 evidence, in reaching conclusions. 21 I think we are saying that most of 22 this is reasonable and that there are ways

### 202-234-4433 Neal R. Gross & Co., Inc. Page 117 1 that it might be improved. I think, then, the 2 real question is, has it been used throughout 3 the document in roughly the same way, given 4 the multiple authors, and so on, that are 5 contributing here. 6 I just want to flag for our 7 discussion, because it enters here the first 8 time, this sort of, I think, redefinition of 9 susceptibility that incorporates both the 10 notion of something that would change the 11 risk, given exposure, as well as the 12 likelihood of exposure. 13 I think in the past with PM we 14 were dealing with these issues of response to 15 exposure versus determinants of exposure as 16 separate phenomenon. They are now grouped 17 here in subsequent chapters. I think this 18 will need some discussion, but I am going to 19 suggest that we defer that at this point, but 20 just simply flag it because it is here. 21 And again, I think Sverre's 22 comments about the interpretation of the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 118 1 biomarker information are relevant. The ATS 2 document did address these issues in a fairly 3 general way. I think that document is now 4 over a decade old and may not be fully 5 reflective of all the possibilities now in 6 terms of where modern biology has taken us. 7 Other comments on this charge 8 question? Judy? 9 DR. GRAHAM: I very much like the 10 idea of having causality as a concept. I 11 think that is a major improvement from past

12 documents I have read. 13 I am concerned about two things. 14 One is on page 110. Animal studies, animal 15 tox studies are basically dismissed. "Oh, 16 they are high; they are different." And, I 17 mean, I could dismiss them for a lot of 18 chemicals, but not for ozone. With ozone, 19 there is a congruence of animal tox, human 20 clinical, and epi. And the animal tox, the

21 effects are at low levels. 22 So, I think that, basically, this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 119 1 paragraph is wrong. It is factually 2 incorrect, but, then, it just sets a tone of,

3 who cares? 4 And the reason I feel strongly 5 about this is not only a personal bias because 6 I am an animal toxicologist, but the animal 7 tox provides a lot of causative information, 8 and it tells us things that humans can never 9 tell us because of the invasive procedures. 10 So, I think this kind of sets a negative stage

11 for that. 12 The other comment I have is on 13 page 124. There is a whole subsection on 14 concepts in evaluating adversity. I know 15 that, ultimately, adversity is a determination 16 of the Administrator, but the science will 17 inform her on this. And so, when I saw this 18 title, I was really excited. 19 And, then, I read it, and it 20 didn't really say much. Like it waved a hand 21 at ATS, but, then, it didn't tell us what ATS 22 said. Now, frankly, I haven't read the ATS

### 202-234-4433 Neal R. Gross & Co., Inc. Page 120 1 stuff. I read like two versions ago. 2 I mean this is the most important 3 section here, in my opinion, And so, expand 4 it some and tell us what did ATS say. 5 DR. SAMET: As it is relevant to

6 ozone. 7 DR. GRAHAM: Ozone, yes. Yes. 8 DR. SAMET: Yes, Ed? 9 MR. AVOL: Yes, I wanted to pick 10 up on, I guess, a recurring theme. This is 11 that Section 1.6.6 on adversity. 12 It is clear that, as we move 13 forward technologically speaking, we can 14 measure much more exquisite and subtle 15 changes. But what is not clear is whether it 16 is important or not biologically. 17 And so, I think, given that this

18 sort of sets the tone for the rest of the 19 document, I think we really do need to say 20 something in here about where the bar is being 21 set. And so, whether you refer to ATS and 22 explain that, or sort of define what you are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 121 1 going to set the threshold at, something needs 2 to be said because we can make these 3 measurements. We can measure things at very 4 low levels. We can measure biological 5 response. But we don't integrate yet -- just 6 because we measure it doesn't mean it is or 7 isn't important.

8 DR. SAMET: Fred? 9 DR. MILLER: I have two questions. 10 One is for Sverre and one is for Dr. Bailar. 11 Sverre, given that we can measure 12 ozone to the part per billion, where are you 13 coming from when you say that there's more 14 measurement error for this pollutant? Are you 15 referring to personal exposures or what? 16 Because I was under the impression that we had 17 a very good ability to measure ozone. 18 DR. VEDAL: Yes, we have a great 19 ability to measure ozone, yes, I mean in the 20 first context, the link between ambient 21 concentrations that are used in many of the 22 studies and personal exposure.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 122 1 So, in ozone, I mean that is 2 probably the -- it's really the pollutant 3 where this issue is most prominent because of 4 the clear difference between indoor and 5 outdoor concentrations, the link with activity 6 levels and dose, all those things that make 7 measurement error, I think, more of an issue 8 for ozone than, arguably, any other pollutant. 9 DR. MILLER: Okay. Thank you. 10 And, then, Dr. Bailar, I wondered 11 if you could expand on your comment about 12 specificity, in particular, when you mentioned 13 about multiple causes being possibly involved. 14 Because, to me, I think this goes to 15 addressing the point collectively of the 16 cascade of events that may be occurring. They 17 clearly, in my mind, do not involve a single 18 mechanism. So, I thought you were right on 19 there, but I am wanting to make sure I 20 understand what you are getting at. 21 DR. BAILAR: This refers, I think, 22 to my written note rather than what I said.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 123 1 Because this was more addressed to EPA at a 2 very specific level, and I thought they could 3 check on this and be sure. 4 It is my understanding that 5 specificity in Hill's original criteria 6 referred to a single cause having multiple 7 effects. He thought it was unlikely 8 biologically that a single cause could have a 9 lot of unrelated effects on birth outcome and 10 pulmonary function in adult life and cancer 11 incidence, and so forth. He said his feeling 12 was that, if you had one effect that had all 13 -- I'm sorry -- one cause that seemed to have 14 all those effects, it was more likely to be 15 due to bias. 16 The way I interpret this document, 17 they are looking at it the other way around. 18 Are there a lot of causes for a single effect? 19 And if you limit yourself to where there is 20 only a single cause or a single major cause, 21 I think that is really very restrictive, and 22 I wouldn't want to go along with that.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 124 1 DR. VEDAL: So, John, this is

2 Sverre. 3 I thought they had it right, but I 4 need to go back there again. Let's see. Yes, 5 let's see. Yes, I mean, what they say, "As 6 originally intended, this refers to increased 7 inference of causality if one cause is 8 associated with a single effect or disease." 9 I see where you are. "So, this is 10 now considered one of the weaker guidelines 11 for causality. For example, many agents cause 12 respiratory disease." 13 Yes, I think -- so your point is a 14 good one. 15 DR. SAMET: Okay. Other 16 questions? Joe? 17 DR. BRAIN: Yes, I have one other 18 comment about the causality assessment 19 template, as you call it, Jon. 20 I guess the big question is, does 21 ozone cause health and environmental outcomes? 22 But I guess my question is, in terms of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 125 1 causality, which ozone? Is it ozone per se or 2 is it the increment of ozone produced by what 3 humans do? Is it the difference between 4 ambient ozone and baseline ozone? 5 And it seems to me that is really 6 an important question as we think about 7 causality. As we look for to what extent 8 ozone causes diseases, environmental 9 consequences, are we concentrating on the 10 increment we are responsible for or are we 11 just looking at ozone per se? I think that is 12 an issue that we will have to struggle with 13 throughout the document. 14 DR. SAMET: I think that is almost 15 a risk-of-exposure analysis issue as you 16 phrased it. I am sure we will be discussing 17 that. Is that fair? 18 Let me check, those on the phone, 19 other comments on this? Who else is on the 20 phone right now besides Sverre? 21 DR. FREY: This is Chris Frey. 22 DR. WEATHERS: Kathy.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 126 1 DR. SAMET: Chris and Kathy, do 2 you guys have any comments? I just don't want 3 to forget you. 4 DR. WEATHERS: No additional ones

5 for me. 6 DR. SAMET: Okay. Anything else 7 on charge question 2? 8 (No response.) 9 So, what we are going to do is ask

10 one of our members of the commenters to sort 11 of draft up a summary response, John, and I am 12 going to offer you that as a part of being a 13 victim of the alphabet. 14 (Laughter.) 15 But, Sverre, you are not 16 forgotten. 17 (Laughter.) 18 So, if you could, I think, look at 19 compiling a draft response to this from the 20 comments of your colleagues, anything you 21 heard here that you feel needs to be 22 incorporated? And these don't need to be

### 202-234-4433 Neal R. Gross & Co., Inc. Page 127 1 particularly lengthy. 2 (Off the record comments.) 3 DR. SAMET: Okay. Then, we will 4 leave question 2 and go to question 4. Ted? 5 DR. RUSSELL: Okay. On Chapter 3, 6 this has to do with the atmospheric chemistry, 7 physics, and characterization of the 8 spatial/temporal ozone levels. 9 My first read of the chapter, 10 actually, you know, it basically was 11 appropriate. I thought it did its job pretty 12 well. And when I went through the question, 13 for the most part, at first brush, I would say 14 yes. 15 And, then, I started thinking down 16 the road. There may be one general area that 17 I think requires more work. And that has to 18 do with, if you start thinking about where we 19 might end up in this process, we may be 20 talking about an ozone standard of 60 to 70 21 parts per billion again. 22 And, then, we are also talking

### 202-234-4433 Neal R. Gross & Co., Inc. Page 128 1 about PRB levels that are not that much lower 2 than the 60 and are expected to increase with 3 time. And that is something that I think is 4 important here, is that, with time, background 5 ozone levels are going to be increasing. So, 6 it is going to become an increasing issue. 7 So, my major concern after reading 8 this was I think the chapter needs to do a 9 more thorough job of looking at the lower 10 ozone levels. Let's say the 20 to 60 part per 11 billion levels. Again, if we are looking at 12 a no-threshold response to ozone in linear 13 whatever, what is happening at those low 14 levels becomes just as important as what is 15 happening at the high levels because, in fact, 16 we are spending more time at the lower levels. 17 So, I just think we need to characterize those 18 more than we currently are. 19 So, in response to some of the 20 questions, if we go to sub-question -- you 21 know, for the most part, my answers are yes, 22 but with a caveat: needing to look more at

### 202-234-4433 Neal R. Gross & Co., Inc. Page 129 1 the lower levels. 2 So, in response to 4A, again, I 3 think the discussion on the measurement of 4 ozone and its components is fine. That is 5 something that we have been doing for a long 6 time, and we do it well, for the locations 7 where we have monitors. 8 And, then, for the spatial and 9 temporal patterns, in terms of what is 10 happening at the higher end in looking at the 11 temporal and spatial trends, it was fine, but 12 I think we need to know more about what is 13 happening at the lower ends to see how they 14 are going to respond to controls. 15 Luckily, Table 3-6 provides some 16 evidence there that our current controls 17 aren't doing that much at the lower end, but 18 it would still be nice to have more analysis 19 of that, just because if there is going to be 20 some response to controls at the lower end, 21 those should be considered. 22 When looking at the PRB, I am one

### 202-234-4433 Neal R. Gross & Co., Inc. Page 130 1 of those who thinks that the modeling approach 2 is the appropriate way to address the PRB 3 because I think you cannot directly measure 4 it, given all the issues that have been 5 discussed and are adequately discussed in the

6 document. 7 Though, I think my real concern 8 here is how you are going to mix and match 9 modeled quantities and measured quantities. 10 And if you look at the modeling, there are 11 areas where you can find high biases and low 12 biases, which isn't surprising. And, overall, 13 I would say that they have adequately shown 14 that the model is generally working well, but 15 you have got these biases that ultimately you 16 have to do something with. And I think that 17 is something that you need to address within 18 part of the ISA, is to provide the scientific 19 background about how you are going to do it. 20 I personally think that the model 21 is probably doing better on the anthropogenic 22 ozone impact. So, I would probably look to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 131 1 see how you can use that information within 2 the model, but, then, there is a problem of 3 scale. Even when they go down to the finer 4 scales, still you are not going to be able 5 capture the really highest levels associated 6 with urban plumes. 7 So, it is going to be a tough one. 8 And I think you just have to lay out how you 9 are going to do it, provide the evidence, and 10 address what sort of uncertainties and biases 11 will also still be there. 12 Sub-question C, for the most part, 13 it does address what is happening with the 14 seasonal and urban and diurnal patterns. But, 15 again, maybe not so much the low end, and, 16 actually, not so much in the non-urban 17 locations. Much more is specific to the urban 18 locations. 19 If we start looking at what the 20 use of the information here for the W-126 or 21 the welfare standard, I think more has to come 22 out and show what has been happening

### 202-234-4433 Neal R. Gross & Co., Inc. Page 132 1 temporally with the W-126 standard and what 2 would likely happen at the low ends with more

3 controls. 4 And in sub-question D, I think the 5 emphasis on ozone is appropriate and the 6 discussion on other pollutants is adequate. 7 DR. SAMET: Okay. Thank you. 8 George?

9 MR. ALLEN: Thanks. 10 First of all, I would like to 11 acknowledge the staff. They did a pretty good 12 job in writing this section. It is a pretty 13 big section and there is a lot of work, there 14 is a lot of components to it. 15 I think in Section A, certainly, 16 measuring ozone is not hard. That is the good 17 news. We have a lot of sites nationwide 18 ongoing, long-term. That is the other good

19 news. 20 But when you get down to the urban 21 scale and trying to look at gradients within 22 an urban area, we often don't have much

### 202-234-4433 Neal R. Gross & Co., Inc. Page 133 1 information. In my own backyard, Boston, for 2 example, if you look at the core urban area, 3 there is only one ozone monitor, and it is an 4 ozone hole. But if you go five miles away, 5 the levels are very different. We have a 6 station in Lynn, which is about 12 miles 7 downwind. It is very different. 8 In the REA part, I show some 9 associations. In fact, I am getting ahead of 10 myself. But the correlation can be often 11 pretty good, but there's actually an offset 12 which is due to the local titration effect. 13 So, in terms of, you know, if it 14 is a large urban area where you are really 15 looking at your own stuff, the patterns might 16 be different. So, LA is not Atlanta is not 17 New York is not Boston. Each urban area does 18 behave differently. 19 And, in general, most of these

20 urban areas don't have a lot of ozone 21 monitors. So, the spatial issue is 22 complicated.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 134 1 We have a decent amount of rural 2 ozone monitors, and I think we are going to 3 get more soon. And there, of course, the 4 spatial patterns, at least horizontally, 5 aren't that large. Of course, if you go 6 vertically, it is a different story. 7 PRB really is, I think, the 8 gorilla on the block here for a lot of what we 9 are going to be talking about. And I think 10 here the ISA on Chapter 3 probably could do a 11 better job of explaining the process, not only 12 how/why, but making a distinction between 13 direct stratospheric and intrusion events, 14 which I give a couple of examples from at Mt. 15 Washington, versus the overall contribution as 16 described in the Thompson paper from 2007, 17 which is what probably really matters. 18 In essence, what happens is you 19 can have the actual events themselves, it is 20 a wave propagation, and they are only two to 21 three hours in duration. But you are 22 injecting stratospheric ozone into the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 135 1 troposphere, which then gets mixed around and 2 can become a multi-day timescale process, at 3 much lower levels. I think there could 4 probably be a better discussion of that. 5 Let me see. I am getting out of 6 order here. I will come back to that in a 7 bit. 8 One issue that does get into 9 measurement effects is the concern about wood 10 smoke and the ozone. Certainly, that is a 11 national-scale problem. In the Eastern U.S. 12 it is more wildfires transport from either 13 Ted's part of the country or up north in 14 Canada. And ozone is often associated with 15 these events, and it is usually considered to 16 be the fact that you are injecting a lot of 17 VOCs into the atmosphere. 18 But there is the possibility 19 -- this does need to be sorted out -- that 20 there may be some interference from mercury. 21 There certainly is mercury associated with 22 forest fires, at least in the Eastern U.S.,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 136 1 where you have substantial deposition of 2 mercury. And, actually, I think Hopke just 3 put out a paper assessing some of those 4 emissions. 5 And mercury is a very, very potent 6 interference, as noted in Chapter 3, on the UV 7 ozone analyzers that are used. So, it would 8 be useful to sort out when it comes to forest 9 fire contribution, which presumably is natural 10 background, how much of that is real and how 11 much of that is actually driven by mercury 12 interference. 13 On page 3-31, they did not 14 consider using carbon monoxide as a 15 reasonably-conserved tracer, at least at this 16 timescale, for urban air masses. It would 17 seem, in the context of that discussion, lines 18 20 to 24, that that would make some sense

19 there. 20 Also, on page 3-31, there is a 21 very large dataset that seems to have been 22 overlooked, possibly because it is not in AQS.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 137 1 It was a 10-year research-grade ozone hourly 2 dataset at the summit of Mt. Washington, 3 northern New Hampshire, just about 2 4 kilometers elevation, 6300 feet, and pretty 5 much a probe into the troposphere. 6 And I think there is an awful lot 7 of information to be mined there. It was part 8 of the Air Map Program out of UNH. I show a 9 couple of examples of some smoothed and events 10 in my comments. But I would hope that would 11 be included as an eastern site in this process

12 of the PRB. 13 And I talked with Daniel about 14 this, and he said he might -- and you can nod 15 or shake your head -- might be able to do some 16 additional GEOS-Chem modeling up at that 17 elevation, because you don't go that high in 18 your runs normally.19 But we had an event, direct20 intrusion event in `03, in the spring of `03 21 -- they are all in the spring -- in the spring 22 of `03 and the spring of `08. And those are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 138 1 the only two clear events, you know, real 2 hits, over a 10-year period. And they lasted

3 two to three hours. 4 So, I think there is a really 5 useful dataset there, in part because of the 6 duration, in part because there aren't many 7 high elevations in the sites in the East. In 8 fact, in all of the high-elevation sites in 9 the document, none of them are in the East. 10 And there are some sites. There's 11 Mt. Mitchell. There's the Shenandoah National 12 Park and the Mt. Washington and Whiteface. 13 But, of all those, Mt. Washington is probably 14 the least -- there is no influence of local 15 sources at that site. You might occasionally 16 have titration from the local generator that 17 they generate their power with, the diesel 18 generator there, but that is a downward spike, 19 not an upward spike. 20 So, it ought to be easy to model 21 the GEOS-Chem because the spatial scale is 22 huge. And it might be helpful not only to see

### 202-234-4433 Neal R. Gross & Co., Inc. Page 139 1 it -- well, basically, to see how well 2 GEOS-Chem can do that, because it ought to 3 work fairly well. I don't expect you to be 4 able to those three-hour spikes of intrusion. 5 That is asking too much. But, certainly, the 6 patterns, and there are clear spring peaks, 7 which is consistent with what others have seen 8 in that dataset. So, Shenandoah, Mt. 9 Washington, maybe Mt. Mitchell, these are all 10 eastern sites that might be worth including. 11 Let's see, what else? Section 12 3.5.2, there are a number of plots there, but 13 they are a little hard to look at. It would 14 be more useful perhaps to plot the 95th 15 percentiles along with the other information. 16 I certainly agree on monitoring 17 methods both the specifications in The Federal 18 Register for ozone FRMs and the FRM itself are 19 seriously outdated, and ORD needs to do the 20 right thing in this round and, as they did 21 with SO2, revise the ozone FRM. NO 22 chemiluminescence would be a good choice. It

### 202-234-4433 Neal R. Gross & Co., Inc. Page 140 1 is robust. It doesn't use the ethylene, and

2 so on and so forth. 3 The FEM is pretty good. Again, 4 the specifications are outdated. They can do 5 a lot better than what is required in The 6 Federal Register, and those should be 7 tightened up. 8 There certainly are questions 9 about interferences with the FEM. I think 10 they are rare. I don't think they really 11 contribute to what we are talking about here. 12 They are moisture-related. There are fixes, 13 and maybe that could also be done in the next 14 round of the regulations, to deal with some of 15 the transient events that are due to rapid 16 moisture changes on the UV FEM. 17 A correction to Section 3.5.6.1, 18 page 3-52, line 23: the NCore sites, the 19 parameters got a little skewed there. Ammonia 20 and nitrate acid are not measured at the NCore 21 sites, but SO2 is. So, for whatever that is 22 worth, just a correction there, a technical

### 202-234-4433 Neal R. Gross & Co., Inc. Page 141 1 one. 2 Also, on the same page, the FEM 3 sites measure NOy, at least they are supposed 4 to, although, generally, it is a fuzzy 5 measurement because it has not been using 6 research-grade NOy techniques. So, it is 7 really more "NOwhat" But, hopefully, that 8 will change over the near future. 9 Urban spatial scale, as I said, 10 just, again, knowing my own backyard, and that 11 Boston was one of the focused studies last 12 time around and may or may not be this time 13 around, it is worth knowing that one of the 14 sites, Blue Hill, 10 miles south of Boston, is 15 actually an elevated site, high relative to 16 the rest of Boston. It is only about 630 17 feet, but it does behave very differently much 18 of the time. 19 So, if you are trying to integrate 20 over the urban area for Boston, you need to be 21 aware that some of these sites are not at 22 ground -- what we would consider ground level.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 142 1 And although 630 feet doesn't sound like much, 2 certainly in the West, in Metro Boston it is 3 a lot. And it is often above the mixing 4 height in the early mid-part of the day. 5 It is not run year-round, however, 6 and that might be worth something, a site like 7 that might be worth running year-round. There8 are two sites in Boston that do run year9 round, the downtown and the one in Lynn 12 10 miles to the northeast. 11 As I said earlier, the Boston CSA 12 is very large. It includes part of Rhode 13 Island and New Hampshire. And if you are 14 trying to do health effects at that scale, 15 that might be problematic. 16 As has been noted earlier, 17 exposure misclassification has a huge effect 18 when you try to assess the actual effects, the 19 beta of the effect, as seen in the comparison20 between the ACS studies for PM and the six21 city study for PM, where the difference was 22 six cities took a neighborhood, you know, a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 143 1 radius of a few miles, where ACS took the 2 entire Metro CSA, or whatever you want to call 3 it, and got different effects because the 4 exposure misclassification was much larger. 5 Some minor points on page 385, 6 line 11, which sites are A and D for Boston? 7 It is just not clear. 8 Some of the plots on page 396, 9 Figure 343, it would be useful to have similar 10 plots with weekend and weekdays separated out. 11 And for that matter, even Mondays versus 12 Fridays because there tends to be a pattern 13 where things build up during the week. 14 One final general comment on the 15 concept of other data that may be useful to 16 incorporate. It is below most people's radar, 17 but the Canadian Government -- it is finally 18 out now -- although it is not readily 19 available, the Canadian Smog Science 20 Assessment from Environment Canada and Health 21 Canada. I am familiar with it because I did 22 some of the review on it. It is available if

### 202-234-4433 Neal R. Gross & Co., Inc. Page 144 1 you request it. 2 And there are two chapters that 3 are probably very relevant to this discussion, 4 especially in terms of PRB, Chapter 3 on 5 "Ambient Measurements and Observations" and, 6 then, Chapter 7, "Air Quality at 7 Regional/Local Scales". 8 So, I would encourage EPA to 9 obtain that document. And if there are any 10 questions on getting it, you can talk to me. 11 And to the extent that it is relevant to this 12 process, incorporate it. But I think there is 13 a lot of information there that may be quite

14 useful.

15 Thanks. 16 DR. SAMET: Okay. Daniel? 17 DR. JACOB: Okay. So, following 18 up on Ted and George, overall, I thought this 19 was a very good chapter, very informative, and 20 I have a bunch of specific comments sprinkled 21 through the chapter. I won't go through them

22 here.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 145 1 What I would like to make here is 2 four general comments about what George 3 appropriately described as a gorilla in this 4 chapter, which is a specification of the PRB. 5 And here, in the interest of disclosure, the 6 PRB ozone values that are shown in this 7 chapter and the ones that are expected to be 8 used in this ISA come from my group. So, I am 9 not going to talk about how good they are. 10 (Laughter.) 11 But I will say that they are 12 represented in the chapter, from what I 13 consider -- I had nothing to do with writing 14 the chapter -- that they are presented very 15 fairly. And, in particular, talking about the 16 issue that Allen raised, that they make a good 17 point about showing the variability in the PRB 18 in the model, and how it captures the 19 variability in the observations, at least on 20 a daily timescale. 21 Okay. So, I have four general 22 comments to make. The first one is about the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 146 1 integration of modeling observations. The 2 second one is about chemical uncertainties. 3 The third one is about the difficulty of 4 dealing with extremes, and the fourth one is 5 about current and projected trends. This is 6 what I am going to touch on. 7 The first thing about integrating 8 modeling observations, I think that there is 9 a false debate going on here because Ted 10 pointed out the PRB has to be a model 11 quantity. There is no way around it. You 12 know, Trinidad Head doesn't measure the PRB, 13 if only because of the North American 14 contribution to background hemispheric 15 pollution. 16 So, it has to be a model 17 construct, but, at the same time, it is very 18 important to look at the data from Trinidad 19 Head and some of the other background sites 20 that Allen and Sam talked about, and test the 21 models with those baseline sites because they 22 have concentrations and variability that are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 147 1 highly relevant to the ability of the model to 2 simulate the PRB. 3 So, in other words, I don't think 4 there should be any kind of debate about

5 whether we should use the model versus 6 observational approach to PRB. The two have 7 to work together. The PRB has to come from a 8 model. The models have to be extensively 9 evaluated, tested, and, if necessary, 10 falsified with observations. 11 The second point I want to make is 12 about chemical uncertainties. There I think 13 that the chapter could do perhaps a little 14 better job. There are, in my view, three 15 major areas of uncertainty that could affect 16 the PRB calculations. 17 The first one is the effect of 18 halogen chemistry, which is a debate, an 19 intense debate right now, going on in the 20 literature. The chapter talks about it in 21 terms of affecting urban ozone, but it would 22 also affect background ozone, due to sources,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 148 1 in particular, roaming radicals that are 2 widely distributed in the free troposphere. 3 And this could actually bring down the PRB 4 values by maybe, I don't know, 3 to 5 ppb, 5 depending on who you believe right now. The 6 science is in flux. 7 A second large area of uncertainty 8 where the science is very much in flux is the 9 whole business of isoprene chemistry. It is 10 very clear that representation of isoprene 11 chemistry in models under low NOx conditions 12 is wrong. It is just plain wrong. 13 And we really don't know what the 14 impacts are for ozone. Again, this is 15 something where there is some literature out 16 there that could be referenced in the chapter 17 and more work will be coming out over the next 18 couple of years. 19 The last point with regard to 20 chemical uncertainties I would like to raise 21 has to do with ozone production in fire 22 plumes. And here, there is a lot of confusion

### 202-234-4433 Neal R. Gross & Co., Inc. Page 149 1 right now in the scientific community. In 2 general, we think, based on our models and 3 based on aircraft campaigns, of which I have 4 been part, that fire plumes don't make ozone, 5 at least at mid-latitudes in the boreal zone. 6 And that is because all the NOx gets converted 7 to PM and that is the end of it. 8 But, of course, PM eventually 9 decomposes to produce NOx, and, then, that 10 will eventually make ozone with a very high 11 production efficiency. And we have 12 observations in the Western United States that 13 show elevated ozone clearly associated with 14 fires. So, here this is something really that 15 we need to understand because wildfires and 16 even prescribed fires are presently considered 17 to be part of a PRB. 18 My third point has to do with the 19 difficulty of simulating extremes. And here 20 I would consider both extremes in the 21 frequency distribution at a given site and, 22 also, extreme sites.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 150 1 So, the first point with regard to 2 extreme and frequency at a given site, models 3 cannot simulate 100 ppb of ozone at 4 Yellowstone. No, they can't.

5 And there's a number of reasons 6 why they can't that have to do with numerical 7 diffusion in the models, even when you use 8 high-order advection algorithms, that have to 9 do with your ability to specify the temporal 10 variability of these sources.

11 There's a number of factors. 12 Okay, so what that means, now these are 13 really, really the very high extremes. What 14 we find is that we can reproduce ozone quite 15 well up to a very high percentile, 95th 16 percentile, 98th percentile, up to about 75 17 parts per billion at very remote sites. 18 And, then, you have these spikes. 19 And those spikes, well, you know, the model 20 can't do it. So, does that mean that you 21 throw away the model? Well, of course not; 22 that's silly.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 151 1 What that means is that you have 2 got to deal with those extremes in a different 3 way. And we have the tools to deal with 4 extreme events. We can use satellite data to 5 observe the structure of exchange events. We 6 can look at occurrences of fires, and so on. 7 We have tools for this. So, I don't think 8 that the debate should be distracted by this. 9 The other point about extreme is 10 extreme sites. We spend a lot of time, when 11 we discuss PRB, talking about mountain sites. 12 Oh, stratospheric exchange influencing a 13 mountain side, and so on. Those are 14 interesting to look at in models. I think we 15 should consider the fact that nobody lives

16 there. 17 And so, if we are going to use a 18 PRB concentration with reference to public 19 health effects, well, you know, is Gothic, 20 Colorado really relevant? Clearly, there 21 there's going to be elevated PRB. The models 22 can capture that. They can't capture the high

### 202-234-4433 Neal R. Gross & Co., Inc. Page 152 1 extremes. Should we hang the whole debate on 2 a PRB condition that is really irrelevant to 3 most of the country and certainly everywhere 4 where people live? 5 Okay. Finally, I would like to 6 make a point about long-term trends, both 7 observed trends and projected trends. And 8 here, you know, the chapter talks about 9 trends, about present trends. It could do a 10 little better job because, interestingly, 11 while we have an overall downward ozone trend 12 in this country, the background, the trend, 13 the background as might be relevant to the PRB 14 -- notice I don't use PRB; I use background -- 15 the trend is on the rise. And we see this 16 from sites on the West Coast. We see this in 17 air over the Pacific. We see this at many of 18 our national parks. 19 And it is interesting to wonder 20 whether that is relevant to the PRB. 21 Presumably, it is. But the models cannot 22 capture properly these trends. And this is,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 153 1 again, something that we need to address. 2 You might say, well, you know, of 3 course, background should increase because of 4 Asian pollution. Well, you know, yes, but, 5 according to our models, Asian pollution 6 doesn't contribute that much to the 7 background. And the trend in Asian sources 8 has not contributed that much to an increase 9 in the background. 10 My own bet is increasing frequency 11 of wildfires, but this is something that is 12 debated in the literature. The point is that 13 there are trends, in particular, shown in the 14 work by Dan Jaffe and Dave Parrish, and that 15 should be recognized. 16 With regard to projections for the 17 future, here the chapter doesn't really say 18 anything at all. It might try to say 19 something. 20 There is a general perception 21 that, of course, the background is going to 22 increase in the future because everywhere

### 202-234-4433 Neal R. Gross & Co., Inc. Page 154 1 except North America people are increasing 2 their emissions. Well, that is not 3 necessarily true. And China is starting to 4 implement some pretty aggressive controls. 5 Interestingly, if you look at the6 projected global trends in emissions of air7 quality-relevant gases from the latest IPCC -- 8 that is the one that will be out in 2014, the 9 AR5 -- what they show is all these emissions 10 going down in the future. Okay? The NOx 11 going down, VOCs going down, way down, SO2, 12 like a rock. Methane, flat. 13 Well, the point is that now there 14 is a lot of debate as to whether those are 15 good projections for the future. They assume 16 a pretty aggressive policy, in particular, in 17 developing countries in controlling pollutant 18 emissions. But there is a lot of debate going 19 on about whether we can expect the background 20 to go up or to go down. 21 Then, there is also the effect of 22 climate change. On one hand, one would expect

### 202-234-4433 Neal R. Gross & Co., Inc. Page 155 1 climate change to bring down PRB values, just 2 because of having higher water vapor in the 3 atmosphere and, therefore, more chemical loss. 4 But, at the same time, if climate change means 5 more frequent and larger wildfires, as there 6 is pretty good evidence for that, then that 7 could bring PRB up. 8 So, all this could be 9 described/discussed a little bit more in the 10 chapter. 11 That's it. Thank you. 12 DR. SAMET: Okay. Thank you. 13 So, you all three liked the 14 chapter, but had an awful lot of comments. 15 (Laughter.) 16 Let me see if others want to 17 comment. And, clearly, the PRB issue is going 18 to be a critical one in further steps in this 19 process. 20 Michelle? 21 DR. BELL: I thought this chapter 22 had a lot of really useful information. I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 1561 enjoyed it, but I think it is quite poorly2 integrated with the rest of the document. But 3 this is something that can be fixed. I will 4 just give you an example. 5 So, if you read the document 6 towards the back, you run into this primer on 7 air quality modeling, which incorporates a lot 8 of scientific evidence, you know, chemical and 9 physical transformation of pollutants. It is 10 an incredibly-useful tool to gain more 11 scientific evidence, but the air quality model 12 is not scientific evidence itself. 13 And so, when reading through this, 14 I found it quite odd that we have pages and 15 pages about this, but it is out of balance 16 with the rest of the document. Like we don't 17 have pages about to deal with to design a 18 chamber study or how do you pick a reference 19 period for a case crossover model, and so on. 20 I mean I think there is a good 21 rationale for why this is in here. 22 Particularly, I am looking at the background

### 202-234-4433 Neal R. Gross & Co., Inc. Page 157 1 levels. But if you look at like how Section 2 2.3 opens up, it is just very general. So, I 3 think talking about why is air quality 4 modeling so heavily emphasized in the document 5 is going to be really useful for helping 6 people read it, so that it doesn't just become 7 a primer about air quality modeling, just for8 the sake of understanding this state-of-the9 science tool, but we may want to talk about 10 this later because you are going to use it 11 later. So, this is kind of out of sequence

12 and unbalanced. 13 And my other point I would like to 14 make is that I think that this section would 15 benefit tremendously from more information on 16 the evaluation of air quality modeling, which 17 is really missing from most of the document. 18 I mean you have figure after figure, you have 19 over a dozen figures comparing the GEOS-Chem

20 model ozone to the absorbed values.

21 But what would be better would be 22 like a synthesis of the overall quality of the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 158 1 models in terms of what does it measure well 2 and what does it not. And this really gets to 3 some of the other points that were made, like 4 we really care about how well it estimates low 5 levels. So, that may be more important in 6 some context than getting like the one-hour 7 peak on a given day, and things of that

8 nature. 9 So, I think that tables or a 10 section that kind of synthesized the overall 11 model evaluation of CMAC, where does it do 12 well, where does it not, what are some of the 13 limitations, the isoprene chemistry, the 14 biogenic emissions, and so on, would be really

15 useful. 16 DR. SAMET: Okay. Other comments? 17 Anybody on the phone? 18 DR. WEATHERS: Yes, Jon, this is 19 Kathy Weathers. 20 DR. SAMET: Yes, Kathy? 21 DR. WEATHERS: I would to support 22 that as well, and what Daniel and Ted said.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 159 1 I think it is incredibly important that the 2 evidence and rationale for evaluation of the 3 model be presented and I'll underscore as well 4 what Michelle said. Based on the CASAC 5 NOx/SOx process, it will just be critically 6 important to lay all of that out upfront. 7 DR. SAMET: Okay. Fred? 8 DR. MILLER: I was disappointed in 9 the Section 3.4 because there is no bottom 10 line. Everywhere else in the document, this 11 is suggestive of causality. This is 12 causative. This is so and so. 13 This gorilla, as it's been 14 described, is just left hanging there. And I 15 don't have a sense, if you are punting to 16 OAQPS, and having read OAQPS's plan, they are 17 punting to the future. I think this is such 18 an important topic that it has got to be laid 19 out here more as definitive options. 20 As for example, the 12 cities that 21 are talked about in the health plan, it would 22 be great to take at least a couple of those

### 202-234-4433 Neal R. Gross & Co., Inc. Page 160 1 and see the different methods that are 2 discussed here relative to the PRB. What are 3 the values that end up in these cities? 4 Because those are the ones that are going to 5 be in the risk assessment. 6 And by the way, I am from Wyoming, 7 and we don't like to let a lot of people in. 8 (Laughter.) 9 But several million a year go to 10 Yellowstone. Okay? So, you may not live 11 there, but you visit a lot. 12 So, this whole concept of the PRB 13 I think has got to be treated more and come to 14 some bottom line as far as the direction 15 because, for me, it just was lacking. 16 DR. SAMET: John, do you want to 17 comment on this point that Fred raises? I 18 mean, where does the bottom line on PRB come 19 in in the process? 20 DR. DUTTON: I will just add in 21 the second draft ISA -- Steve Dutton, EPA -- 22 in the second draft ISA, as Jim alluded to, we

### 202-234-4433 Neal R. Gross & Co., Inc. Page 161 1 are doing some additional modeling work. And 2 that will address a lot of the questions that 3 Michelle brought up and as well as yourself, 4 with the model evaluation at different urban 5 and rural locations and, also, addressing some 6 of the uncertainties in the model and 7 characterizing more fully some of the PRB 8 estimates that come out of that. 9 So, we are working on that right 10 now, getting preliminary results in. You will 11 have a chance to look at that in the second

12 draft. 13 DR. SAMET: I wonder, as a general 14 point, if it would be useful when we get, 15 let's say, a first draft, if we had perhaps 16 some placeholders and something as to what is 17 not there. I think that would probably be 18 helpful to us. I think, then, it would save 19 some questions and pondering and maybe you 20 might be a little less flagellated. So, think

21 about that.

22 Joe?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 162 1 DR. BRAIN: I have an adjacent 2 comment. Again, I kept looking, you know, 3 well, what is the PRB value? And that relates 4 to integrating into other chapters, as we look 5 at the epidemiology, as we look, you know, for 6 a particular study, what is an appropriate PRB

7 value. 8 And then I guess maybe this goes 9 beyond our Committee, but, as I understand it, 10 the PRB excludes human contributions as long 11 as it is outside of North America. And is 12 that really appropriate, given the fact that 13 we have exported metal mining, smelting, 14 manufacturing to China? It is not as though 15 we are not, to some extent, responsible for 16 the PRB that enters the country, but maybe 17 that goes beyond our purview. 18 But I agree, I think it really is 19 the elephant in the room, given the magnitude 20 of the PRB and how close it sometimes is to 21 the .6, .7, .8 that we are worried about. 22 DR. SAMET: Okay. Anybody else?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 163 1 Chris? Let me just check on the phone. 2 DR. FREY: I don't have anything

3 to add. 4 DR. SAMET: Okay. Ed? 5 MR. AVOL: Two comments. One, 6 just to pick up more generically with what 7 Fred alluded to, and that is sort of what I 8 found missing from this was just a general 9 integrated summary of what the point of all 10 the presentations were in this chapter. It 11 just sort of ends. And so, it would be 12 helpful to sort of say, you know, bring to the 13 end what you think are the key elements of 14 this. 15 And, then, secondly, Section 3.6.4 16 and the association with the co-pollutants, I 17 especially appreciate that. As we move more 18 to thinking about multi-pollutant exposures, 19 I think it is important to think about how 20 they interact and what the importance of them 21 is in the ambient atmosphere. 22 In the case of ozone, of course,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 164 1 it sort of behaves as a different sort of 2 creature compared to, say, the traffic-related 3 emissions. But it still is good -- I think 4 the plots and so forth were great to see. I 5 think they are very useful, and I think you 6 ought to say something about that, expand on 7 that piece. 8 DR. SAMET: David? 9 DR. CHOCK: Yes, I find Table 3-1 10 and Table 3-2 to be very helpful. These 11 tables refer to seasonal means, daily max, 12 eight-hour ozone concentration. And the sites 13 listed are definitely not PRB sites. 14 But the important thing is that 15 one is on the seasonal means, and Table 3-2 is 16 on the seasonal maximums. And if we are 17 talking about the fourth highest in three 18 years, then we ought to emphasize the extreme 19 maximum. 20 So, maybe I would recommend that 21 EPA would do a table perhaps that shows what 22 the fourth highest value in three years would

### 202-234-4433 Neal R. Gross & Co., Inc. Page 165 1 look like for these sites, even though they 2 are not PRB sites. But they may be a preview 3 in case we one day actually would be able to 4 meet those concentrations. 5 DR. SAMET: Okay. Anyone else? 6 Okay, Ted? 7 DR. RUSSELL: I want to point out 8 that George Allen comes earlier in the 9 alphabet on this one. 10 (Laughter.) 11 DR. SAMET: Thank you for pointing 12 that out. Thank you for pointing that out, 13 Ted, but that was not the question. 14 (Laughter.) 15 Would you?

16 DR. RUSSELL: Yes.

17 DR. SAMET: Thanks. 18 MR. ALLEN: Ted, we'll help, okay? 19 DR. SAMET: You, of course, are 20 going to enlist help from your colleagues, and 21 nobody escapes. 22 Let's move on to environmental

### 202-234-4433 Neal R. Gross & Co., Inc. Page 166 1 effects. Kathy? 2 DR. WEATHERS: Sure. I think the 3 advantage of this chapter is that it builds 4 upon a lot of past work. The disadvantage is

5 that there hasn't been a tremendous amount of 6 new work since 2006, the space studies 7 notwithstanding and the meta-analyses 8 notwithstanding. 9 I have some general comments that 10 I will offer. And looking at my colleagues' 11 reviews, it looks like there are some very 12 specific ones as well. 13 In answer to the question, have 14 the major effects been characterized, I think 15 that the answer to that is yes, especially for 16 plants and looking at mechanisms, but it 17 appears that there are some errors as well in 18 some of the literature review and the analyses 19 that, again, my colleagues have pointed out. 20 And there is some confusion in parts about 21 indirect and direct effects. 22 The integration question, I think

### 202-234-4433 Neal R. Gross & Co., Inc. Page 167 1 that that could be done a little bit better 2 than it has been done from, quote, "scales", 3 going from issues to ecosystems. I have made 4 a couple of specific suggestions about how 5 that might be done. And I think that there 6 are some conceptual pieces and syntheses that 7 might be done to indicate where some of these

8 scales are connected and where some of the 9 effects of the ozone are connected from plant 10 to ecosystem. So, there is some better 11 synthesis that I think can be done. 12 The chapter is quite extensive, 13 and it has been pointed out that it is 14 redundant with earlier chapters. It certainly 15 could be condensed and better integrated. I 16 wasn't particularly bothered by its length, 17 but it certainly could be. 18 Let's see. I think those are the 19 major comments I had. 20 What seems to be missing is the 21 literature on lichens and bryophytes, which 22 one of my colleagues has pointed out is quite

### 202-234-4433 Neal R. Gross & Co., Inc. Page 168 1 extensive, and it doesn't appear in this 2 chapter. 3 So, I will pass it on to my 4 colleague. 5 DR. SAMET: Okay. Thanks.

6 Dave? 7 DR. GRANTZ: Well, first of all, I 8 want to say that I think this was a tremendous 9 amount of work and a very nice job. There is 10 a lot of vertical integration. I thought all 11 the questions got a short answer of, yes, they 12 did a very good job. 13 I also want to say that I agree 14 with the conclusions of causality in Table 15 9-1. I think that was pretty nicely done. 16 And, then, I want to make a few 17 points that sort of highlight things that are 18 in my written comments. I think it is very 19 important that we come back to this question 20 of open-top chamber versus non-chambered 21 exposures for vegetation. The ISA does a very 22 god job of repeating the conclusion that all,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 169 1 or virtually all, of the recent work confirms 2 what we knew from open-top chambers. 3 That is important because it has 4 been a point of contention. It has been a 5 point of criticism of what we know about ozone 6 effects, welfare effects, and I think we can 7 lay that to rest. I think the ISA does a very 8 nice job of doing that. 9 Now, having said that, there is a 10 question whether it is appropriate to use the 11 exposure response relationships from the NCLAN 12 studies. I think one thing that needs to be 13 put in the ISA is that current crop cultivars 14 in places with high ozone exposure tend to be 15 less sensitive than the crops that were in 16 existence at the time of the NCLAN studies. 17 So, to some extent, those exposure 18 response relationships may overstate 19 sensitivity. This is certainly true, for 20 example, with cotton cultivars in California. 21 The current cultivars are just less sensitive

22 for sure.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 170 1 My written comments talk about gas 2 exchange, water use, water cycling, 3 extensively. This is just incredibly 4 important. The discussion is somewhat 5 diffuse, scattered throughout that chapter, 6 and it is somewhat contradictory. 7 I would have to say that I am not 8 exactly sure what the bottom line is. We have 9 the studies of Sandy McLaughlin and the 10 indirect bringing in of watershed -- water 11 production from an ecosystem, but we also have 12 lots of experimental evidence that stomata 13 close in response to ozone. I don't think 14 there is a clear one answer, I suspect it 15 depends on type of vegetation and on other 16 factors. But I think a much clearer 17 discussion of those problems needs to be put 18 into the ISA. 19 That is not just a picky point 20 because the whole question of stomatal 21 conductance leads into the whole problem of 22 modeling based on uptake or fluxes. It

### 202-234-4433 Neal R. Gross & Co., Inc. Page 171 1 relates to other things, very important

2 confounders such as water use and water 3 stress, stomatal closure, excluding ozone, et

4 cetera. 5 So, there are a whole bunch of 6 reasons that the stomatal argument needs to be 7 gotten right. I think there are a number of 8 studies in there that need to be better 9 explained and better integrated. The Sandy 10 McLaughlin studies are one. They kind of 11 stand out by themselves. And I think the 12 Jillian Gregg studies from Cornell, the Todd 13 Dawson/Jillian Gregg studies, have to be put 14 in there. When a paper hits Nature, it 15 becomes a very important study. But that is 16 a quirky study in many ways, and it comes up 17 on every third page in that chapter. 18 I really think somebody ought to 19 really go back and look at that and see really 20 what is that study telling us and what is it 21 not telling us? But they had an 85 percent 22 growth reduction with ambient ozone. I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 172 1 haven't seen that in chambers. I mean, that 2 is big. So, I would just go back and look at 3 how much weight we want to put on that single 4 study. 5 Another element is that it is 6 appropriately pointed out that ozone enters 7 the response mechanism of plants through the 8 ROS signaling networks, pre-existing networks 9 that are there for pathogen defense, 10 essentially. I think that is very important. 11 I also think that is at an 12 incredibly early stage of development. There 13 are sections where the authors start to go off 14 in explanations of jasminate and ethylene and 15 interactions here and there. First of all, 16 the explanations are a little bit simplistic, 17 particularly with jasminate, which I happen to 18 know a little bit about. Jasminate does a 19 great many things, and I don't think it is 20 well laid out. 21 But I also don't think it is 22 important that it be well laid out in this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 173 1 chapter. I don't think the science is at a 2 stage where that really adds plausibility, and 3 I don't think we need to get into that very 4 much. I elaborate on that in my written

5 comments as well. 6 There is another issue that comes 7 up in several places in this chapter. For 8 example, in talking about genomic effects or 9 transcriptional effects: just because 10 something responds does not mean that is a 11 mechanism of resistance, because you are 12 really looking at the potential for a response 13 that indicates something about upstream 14 defenses. And I think that logical mistake is 15 made in a number of places and probably ought

16 to be corrected. 17 Just because genes are transcribed 18 or not doesn't mean that is why the plant is 19 sensitive. It simply may mean that is the 20 plant that ozone got past the first level of 21 defense. We just don't really know the answer

22 to that.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 174 1 A number of times the extreme 2 sensitivity of reproductive tissues is brought 3 up. I don't think there is evidence for that. 4 Even the very early papers that are by Black 5 that are cited numerous times don't really 6 show that. They show compensatory responses, 7 certainly; they may show effects directly on 8 reproductive structures, but they may not, 9 because those are photosynthetic stocks as 10 well. So, I think I would tone that argument 11 down a little bit. 12 And it doesn't detract from the 13 argument that the yield, which are 14 reproductive structures in most crops, are 15 heavily impacted by ozone; that is true. But 16 to make a big deal out of the extreme 17 sensitivity of reproductive structures, it is 18 not shown by the data that are presented. 19 There are other types of data, pollen growth, 20 et cetera, that may be more direct to that 21 question. 22 And, then, there is another sort

### 202-234-4433 Neal R. Gross & Co., Inc. Page 175 1 of general comment I wanted to make that in 2 several places it is measured that there was 3 a change without any indication whether it is 4 an adverse change or not an adverse change. 5 And in some cases, it doesn't even indicate 6 the direction of change. 7 And, then, there is one wonderful 8 spot, which I don't remember where it is, but 9 it is in my written notes, where it only says 10 that something was measured, without even 11 worrying about whether or not it was changed. 12 I think you need to really think about whether 13 these changes have some biological 14 significance. 15 That's it. Thanks. 16 DR. SAMET: Is the latter issue -- 17 I mean, right now I think the focus in Chapter 18 1 on what is an adverse effect is all human, 19 isn't it? Is there one paragraph? I guess 20 maybe that concept needs to be broadened there 21 as well, as we move through the broader 22 ecological effects.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 176 1 DR. GRANTZ: Whether or not you 2 determine if it is or isn't adverse, one would 3 at least want to describe the direction -- 4 DR. SAMET: Right. 5 DR. GRANTZ: -- and the logic by 6 which you might decide if it is adverse. 7 DR. SAMET: And certainly, the 8 American Thoracic Society statement is not the 9 right reference to cite.

10 Howard? 11 DR. NEUFELD: Okay. Thank you. 12 It is always good to go third. 13 I think, if you look at this, the 14 beginning of Chapter 9 is almost identical 15 word for word with that in Chapter 2. So, 16 again, I would say that perhaps we can shorten 17 this chapter, get out some of the redundancy 18 and things like that. 19 And the section on the stomata, 20 echoing Dave, is that those discussions are 21 kind of scattered throughout in different 22 sections and somewhat redundant there. I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 177 1 think if it was reorganized a little better, 2 brought together, it would make the material 3 flow better and the conclusions come out

4 better also. 5 And, then, there are some specific 6 comments I had about some of the way things 7 were described, some of the biochemical 8 responses. 9 There was a discussion on page 9.6 10 about sensing ozone with proteins in the cell 11 wall or membrane and then gene activation. 12 But there can be just pure physical reactions 13 prior to any gene activation. I think that 14 kind of argument should be brought in. I made 15 the analogy with auxin, where there is an 16 initial quick response, and then genes are 17 upregulated on a longer-term basis after that. 18 We have had a lot of hypotheses 19 about antioxidants and their role in defense, 20 and particularly their temporal status and 21 whether there is a minimum of defenses at 22 nighttime and things like this. There is a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 178 1 lot of speculation in the literature, but 2 there isn't a lot of hard-core evidence for 3 one way or the other. I think that is just an 4 area that we should at least leave open that

5 needs more work. 6 Then, I had trouble at the time 7 when I wrote these comments of getting into 8 the HERO database. So, if it has been cited, 9 I apologize. 10 But there was a paper by Heinrich 11 Sandeman published, that I didn't see in 12 there, I think, talking about some additional 13 biochemical reactions with antioxidants, 14 especially ascorbate, that when reactive with 15 those, it actually produces some other toxic 16 compounds. Perhaps that reaction ought to get 17 a little more weight in the document. 18 Let's see, and there's a couple of 19 other specific comments here about, again, 20 antioxidants, but I won't go into details on 21 those. They are in the written comments. 22 I echoed Dave's thing about the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 179 1 stomatal patterns with ozone, this stomatal 2 sluggishness, where they become less 3 responsive to environmental stimuli. There is 4 a lot of evidence that that is happening. 5 Sandy McLaughlin's data indirectly seems to 6 indicate that. Nancy Grulke and Elena 7 Paoletti's data seem to indicate that across 8 a wide spectrum of life forms. 9 But there is not evidence 10 sometimes in looking at differences between 11 sensitive and tolerant individuals that that 12 is the mechanism causing that. Because when 13 there are no foliar symptoms seen, sometimes 14 you can't see any differences in stomatal 15 reaction among sensitive and tolerant plants. 16 It is something that comes up as a result of 17 the injury. So, it would be inaccurate to say 18 that they are predisposing factors. Now they 19 could be in some species, but not all. 20 There hasn't been a lot of work in 21 recent years, but nitrogen deposition is 22 extremely important. I think nitrogen

### 202-234-4433 Neal R. Gross & Co., Inc. Page 180 1 deposition can have a huge impact possibly on 2 responses of plants and ecosystems to ozone. 3 And I think that that discussion needs to be 4 built up in the ISA.5 I echo Kathy's comment that non6 vascular plants are almost totally ignored in 7 here. Mosses, for example, they may not be 8 particularly ozone-sensitive, but they cover 9 huge swaths of the earth's surface. And if 10 they do turn out to be affected by ozone, even 11 though they may have low rates of exchange, 12 the vast area they cover could end up having 13 ecosystem and landscape consequences. 14 Let's see. The section on 15 plant/insect interactions, it seems not to 16 have any real sharp general conclusion. I had 17 suggested that maybe the consensus is that 18 there is no consensus on how insects respond 19 to feeding on ozone-exposed plants. And that 20 is an area that, again, needs more work. 21 And, then, I don't know if it was 22 in, I can't remember if it was in the criteria

### 202-234-4433 Neal R. Gross & Co., Inc. Page 181 1 document from before, but there was a paper a 2 number of years ago by Peter Tobiason on dark 3 opening of stomata. And if you have species 4 growing at high elevation where you have 5 essentially a flat ozone profile, so that the 6 ozone is high in the morning if the stomata 7 are open, then other conditions being 8 conducive to uptake, then you could have an 9 appreciable amount of ozone going into the 10 plants at a time when, at low elevations, that 11 same species would not be getting ozone.

12 And other work on that has also 13 been done by Lisa Donovan and others, looking 14 at fluxes at nighttime. So, that may be 15 something to back up, to look at. 16 And, again, I echo Dave's concern 17 about Gregg's data. That is a huge reduction. 18 But there has been some other work by Paul 19 Brang and Dave Karnosky. It was in the 20 earlier document where they speculated that 21 some genotypes actually were eliminated from 22 the landscape, growing in high-ozone areas.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 182 1 So, perhaps that discussion should be brought 2 back to put the Gregg paper into better

3 context. 4 And the rest of the chapter I 5 thought was a good summary of how natural 6 agricultural ecosystems responded to ozone. 7 And, then, I will leave it at

8 that. 9 DR. SAMET: Okay. Other comments? 10 Yes, Peter? 11 DR. WOODBURY: Just a couple of 12 comments. I will be brief because I agree 13 with almost everything that has been said by 14 my colleagues on this topic. 15 I think this was brought up, but I 16 want to emphasize that a more critical 17 discussion and interpretation of model results 18 is needed. We've had some discussion today 19 already about atmospheric models. In the 20 plant world, we have a range of models that 21 have been used to try to understand and scale 22 up effects from specific organs or individual

### 202-234-4433 Neal R. Gross & Co., Inc. Page 183 1 plants to the ecosystem scale. 2 These models have very different 3 assumptions. They operate in different ways. 4 For example, some models assume that all 5 vegetation is one giant leaf and that it all 6 responds to ozone in one way. I will point to 7 a paper that is cited by Scott Ollinger using 8 a peanut model. 9 Other models represent many 10 physiological responses within plants, 11 individual plants. Other studies have linked 12 these more complex physiological models, such 13 as tree growth with stand-level models, to try14 to assess the interaction of both ozone15 sensitive and less sensitive species in a 16 mixed vegetation community. 17 So, those are very kind of 18 different animals. And I think there needs to 19 be a little more critical discussion of the 20 strengths and weaknesses of various models and 21 what information can really be gained from

22 them.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 184 1 Similarly, I think bringing some 2 of that modeling discussion together and 3 linking it with the suggestion of bringing 4 together the discussion on stomatal 5 conductance, those two topics are related. 6 So, if models make an assumption that stomatal 7 conductance decreases, you are going to have 8 a very different implication in the results of 9 that model than another study that may be 10 using data that suggests that things are 11 changing in the opposite direction. 12 So, again, I am adding to this 13 point of a need for a more integrated 14 discussion of effects on stomatal conductance 15 and then, a separate but related topic of an 16 integrated discussion of what we can learn 17 from different kinds of models. 18 There is a brief discussion of 19 effects of ozone on sacred fir forests in 20 Mexico and forests in the Carpathian 21 Mountains. I would suggest that this 22 discussion either needs to be expanded with a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 185 1 clearer kind of bottom line, what can we 2 actually tell from the studies that have been 3 done in these regions? 4 If it is the case that there is 5 fairly strong evidence of ecosystem effects, 6 then the inclusion of them is warranted. If 7 the evidence is not strong enough to really 8 point to ozone effects, that needs to be 9 clarified and, again, maybe related to some of 10 the other material in the chapter. 11 My last point, I have some written 12 comments that I have submitted. I won't go 13 over some of those detailed ones. But the 14 last point is that -- it has been brought up 15 by Kathy Weathers that there isn't that much 16 new literature. Some of the new literature 17 includes meta-analyses. 18 And as is well discussed in the 19 chapter, these meta-analyses of the new 20 studies tend to be a very limited type of 21 ozone exposure, usually an ambient and a twice 22 ambient. So, this is a limitation, especially

### 202-234-4433 Neal R. Gross & Co., Inc. Page 186 1 in developing exposure response functions. 2 But I wonder whether it is 3 possible to try to compare these more recent 4 data with earlier data on a common metric of 5 exposure, even if it is a seven-hour mean. I 6 am not suggesting that a seven-hour mean is a 7 more appropriate metric. It is not, and I 8 don't think we need to discuss that too much 9 today. But it might provide a way to say, are 10 the new studies really showing something 11 different from the older studies or not? 12 That's it. 13 DR. SAMET: Okay. Other comments? 14 DR. GRANTZ: If I could make just 15 another couple of comments that Howard 16 reminded me of? 17 DR. SAMET: Yes, Dave? 18 DR. GRANTZ: First of all, this 19 nighttime stomatal opening appeared in the 20 early eighties in the context of the blue 21 light response. And there are a couple of 22 papers by Eduardo Zeiger and Chris Fields, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 187 1 others, that you should probably think about, 2 because nighttime opening is a real 3 phenomenon, and maybe not just in high 4 elevations. 5 The other thing that I actually 6 meant to say and forgot is that there is a lot 7 of text in this chapter on target proteins in 8 the apoplast. I don't think we know anything 9 about target proteins in the apoplast. And, 10 then, when it said that the initial site of 11 impact of ozone is likely to be in the 12 apoplast, that is hedged multiple ways. 13 Well, I would reverse that. I 14 think we know that ozone hits the apoplast 15 first, just because physically it more or less 16 has to. And I think we know absolutely 17 nothing about target proteins. I think that 18 is a completely mistaken way to say that. 19 There may be proteins that are targets, but 20 there is no ozone target. There is no ozone 21 receptor, at least at current levels of 22 understanding. I think that is a mistake to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 188 1 have it in there that way. 2 DR. SAMET: Okay. Ed? 3 MR. AVOL: Just to follow up on 4 something Dave Grantz suggested earlier, this 5 is out of my field, so I didn't actually 6 appreciate this. But, on page 9-18, there is 7 a section on experimental exposure 8 methodology. If, in fact, it is the case that 9 you sought to dispel this sort of simmering 10 controversy between the open chambers versus 11 the indoor chambers, but that doesn't come 12 out. I was trying to figure out why we 13 diverged into this discussion of how you go 14 about doing these studies. 15 And so, if, in fact, that is the 16 case, and in that context that makes a lot of 17 sense why he would say something, I think you 18 should say something in that introductory 19 paragraph, that there has been this concern 20 about it. 21 DR. SAMET: Okay. 22 DR. HERRICK: I just want to say,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 189 1 later on in the chapter, we talk more about 2 the comparisons toward the end of the chapter. 3 So that part, we are just sort of setting up 4 what are the methodologies that we are going 5 to refer to later in the chapter. 6 So, that 9.3 was sort of just to 7 get our terms down, like what is an open-top 8 chamber and what is a field study, so we 9 wouldn't have to rephrase it every time during 10 the rest of the chapter. 11 MR. AVOL: Right, but without the 12 guidance -- 13 DR. STALLWORTH: Can you introduce 14 yourself? 15 DR. HERRICK: Oh, I'm sorry. I am 16 Jeff Herrick from NCEA, an ecologist. 17 MR. AVOL: Okay, but as a naive 18 reader without the guidance about why this is 19 all being set up in parallel, I would say, in 20 the acute effects study why don't we talk 21 about all the different kinds of chambers and 22 how people go about doing the exposures, which

### 202-234-4433 Neal R. Gross & Co., Inc. Page 190 1 I think would be out of place in this

2 document? 3 DR. SAMET: Okay. Other comments? 4 Anyone on the phone? Yes, Dave? 5 DR. CHOCK: This is not a comment. 6 DR. SAMET: Okay. 7 DR. CHOCK: Being not an expert in 8 this area, I can ask some wild questions. 9 First, vegetation also emits biogenic 10 emissions, so I wonder if ozone has any impact 11 on the biogenic emissions. So, this is sort 12 of a feedback issue. 13 And the second question is, I look 14 at the slide that EPA showed on the cottonwood 15 thing. The plant becomes very tiny after 16 exposure to ozone. So, my question is whether 17 there are any studies on the carbon storage 18 issue when the plants are exposed to ozone. 19 DR. HERRICK: Yes, we cover some 20 of the studies on carbon storage. It is very 21 difficult to study because you have to expose 22 a whole ecosystem, and there's a few field

### 202-234-4433 Neal R. Gross & Co., Inc. Page 191 1 studies that try that. But a lot of it, we 2 used modeling examples to look at carbon 3 sequestration. 4 DR. SAMET: Okay. One other issue 5 that came up, and I can't remember who 6 commented on this sort of overlap between 7 Chapters 2 and 9, and there is sort of 8 verbatim text from others that have gone in. 9 Chapter 2, I think, is intended to 10 be integrative, and there is some comment 11 about, I think, across the different panel 12 members as to whether it is an executive 13 summary or what exactly is it. It is clearly 14 not yet what it should be. And I think that 15 is why these comments have surfaced, and this 16 is only one example where people are saying, 17 well, why say in Chapter 9 what you have 18 already essentially said in Chapter 2? The 19 meat of what is in Chapter 9 is there. 20 I mean, what really should be 21 carried forward are the main points and, then, 22 there should be some integrative discussion.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 192 1 I know we are going to discuss Chapter 2 2 later, but this is one of the places where 3 that comment has surfaced. And I think I just 4 wanted to again flag that, recognizing that 5 Chapter 2 is still, I'm sure, a work in 6 progress. 7 Let's see. Perhaps, David, if you 8 could take on the summary for this, since 9 Kathy is not here? So, it is, apparently, a 10 good way to avoid the job of drafting the 11 answers, to stay on the phone. 12 (Laughter.) 13 DR. WEATHERS: Right. If your 14 last name doesn't start with "W", then -- 15 DR. SAMET: That's right. I can 16 see at our next panel meeting everybody will 17 be on the phone. 18 (Laughter.) 19 DR. WEATHERS: Yes, exactly.

20 DR. SAMET: Peter? 21 DR. WEATHERS: Dave, would you 22 mind emailing to me the draft, and I will

### 202-234-4433 Neal R. Gross & Co., Inc. Page 193 1 respond via email? 2 DR. GRANTZ: Yes, of course. 3 DR. WOODBURY: I did just want to 4 repeat a point that was already made because 5 it is really extremely important. And that 6 is, first of all, I want to say good job on 7 this chapter. I think it does cover the 8 material in general that needs to be covered. 9 But the new information coming 10 from the FACE studies, the free-air exposure, 11 and the linkage that is made in this document 12 with the former NCLAN studies. It is 13 emphasized in the document how critical that 14 is, but that is really extremely important. 15 As Dave Grantz said, it is basically a whole 16 other technology that has laid to rest 17 concerns that have been brought up for 20 18 years about the NCLAN data, and demonstrates 19 conclusively that the exposure response 20 functions are valid and are applicable from an 21 entirely separate line of evidence. 22 So, I think you did a good job of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 194 1 emphasizing that. I just want to say it again 2 because it can't be overemphasized, as we move 3 into the next phase of trying to do a more 4 quantitative assessment of response to ozone 5 exposures.

6 DR. NEUFELD: And I wanted to add 7 two other points. One is sort of 8 methodological. If you don't have open-top 9 chambers or any way of doing controlled 10 exposures, then you are faced with a situation 11 of trying to assess an ozone impact in the 12 natural world without a control. So, how do 13 you do it? 14 And so, my group has adopted a 15 strategy, whether it is flawed or not, of 16 looking at individual variability within 17 individuals of a species, looking at sensitive 18 and tolerant genotypes and at least saying, 19 okay, we see this range of response due to 20 ambient ozone. Maybe there should be some 21 discussion of that tactic or methodology, and 22 the limitations that are associated with it,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 195 1 but also the information that you do get. 2 The other thing would be, related 3 to that is the elimination of sensitive 4 genotypes. You can't see it. So, you can get 5 changes in ecosystem function like nutrient 6 cycling that you might be able to see. But if 7 you lose the sensitive genotypes, you have got 8 a change in composition. The species is still 9 there, but not the full complement of 10 genotypes. So, that is something that maybe 11 should be brought up. 12 And the last thing is, as one of 13 the people who lives at high elevation, the 14 profiles at high elevation tend to be fairly 15 flat. There isn't much discussion in Chapter 16 3 or the ISA about the mountain profiles of 17 ozone, you know, diurnal profiles. Perhaps I 18 would like to see that a little beefed-up, and 19 whether it has changed, say, over the last

20 decade or so. 21 Because there was a mention in 22 there of the lower-elevation profiles being

### 202-234-4433 Neal R. Gross & Co., Inc. Page 196 1 fairly similar, even though maybe the absolute 2 levels are going down, but there was no 3 discussion of high-elevation profiles. I 4 think that is an important thing to add.

5 DR. SAMET: Fred? 6 DR. MILLER: Yes, Jon, I wanted to 7 return to your comment and the questions about 8 Chapter 2. I think before we leave here, and 9 maybe it is at the end-of-the-day discussion, 10 whether or not, personally, I feel that this 11 chapter is out of place, that it ought to be 12 the last chapter, if it is really integrative. 13 And it might serve, a shortened version of it, 14 as an executive summary. 15 But I think we ought to give some 16 clear guidance because, to me, you shoot half 17 your wad to start with, but you don't really 18 make the case as strongly because, if the 19 reader had read all the other chapters and 20 they got to this, they would have a tight hold 21 on how this has been integrated. 22 And so, I think your point is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 197 1 well-taken is this is something that we really 2 ought to provide very specific advice before

3 we leave. 4 DR. SAMET: George? 5 MR. ALLEN: A quick follow-up to 6 the flat diurnal profiles. There actually are 7 cases where you get that not at high 8 elevation. In rural areas, in this case my 9 experience was in central Wisconsin, I did an 10 audit of a site, and I thought the ozone 11 analyzer was broken because it was flat at 60 12 ppb hour after hour after hour after hour 13 after hour. Now it turns out it is just the 14 middle of nowhere, and even though it is 15 surface and flat, very little profile. So, 16 I'd throw that out there as something to 17 consider. 18 I was stunned, and I suspect you 19 can go out there and get the data now. This 20 was 15 years ago. It is probably still the 21 same, maybe a little higher. 22 DR. SAMET: Okay. I am going to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 198 1 suggest that we move on to one more charge 2 question before lunch and deal with question 3 11. Then, we would be ready to shift after 4 lunch back to human health. So, this is 5 climate change and UV-B effects. 6 Howard, you are the lead here. 7 DR. NEUFELD: This is Chapter 10, 8 right? 9 DR. SAMET: Chapter 10, correct. 10 DR. NEUFELD: Okay. I thought 11 this was a well-written summary of the direct 12 and indirect -- I am essentially reading what 13 I have here because I only had very short 14 comments here. But it was a well-written 15 summary of the direct and indirect effects of 16 tropospheric ozone on UV-B radiation impacts. 17 I thought the chapter discussed 18 climate forcing due to ozone and relative to 19 CO2 and methane in a really nice way and20 distinguished it between long-term and short21 term greenhouses gases. 22 In discussing recent ozone trends,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 199 1 Henry Lee and others had a paper out recently, 2 2003, going back trying to reconstruct the 3 trends in California. I am not sure if that 4 was, again, because of the HERO database, I am 5 not sure if that was cited, but maybe they 6 could consider that. 7 But, in conclusion, it was fairly 8 evaluated, the research to date, and showed 9 that there is a paucity of studies of how 10 tropospheric ozone is going to affect UV-B. 11 The last sentence I agree with. It says, "The 12 effects of changes in surface-level ozone 13 concentrations on UV-induced health outcomes 14 cannot yet be critically assessed within 15 reasonable uncertainty." And I agree with

16 that. 17 DR. SAMET: Okay. Let's see,

18 Peter? 19 DR. WOODBURY: Yes. In response to 20 this question, I think this chapter is useful. 21 It is a complex topic. I am not an 22 atmospheric modeler. So, I have a couple of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 200 1 questions and a couple of comments. 2 I guess a question I have for both 3 the staff and perhaps some of the atmospheric 4 chemists and modelers in the room here is: 5 might there be effects of ozone at the 6 regional and continental scale, in addition to 7 the global scale? So, I am thinking of 8 radiative impacts. I don't have an answer to 9 that question. I will put that out there in 10 case anyone else does. 11 And I guess, to elaborate on that, 12 could such regional impacts be additional to 13 the range of impacts on radiative forcing that 14 are cited from IPCC? If so, then maybe a 15 regional or a continental impact discussion

16 would be warranted. 17 Another point, on interaction with 18 vegetation, so there may be complex and 19 important interactions with vegetation. So, 20 I think this is a challenge, due to the 21 limitations of the modeling and the 22 heterogeneous response of different types of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 201 1 vegetation. So, in other words, the 2 publication that is cited by Sitch et al., 3 from 2007, I am not sure whether that 4 publication really could represent a variation 5 in response to ozone among genotypes within a 6 species or among species, the discussion we 7 have just been having. 8 So, there is evidence from both 9 experimental -- direct evidence from 10 experimental work with open-top chambers, as 11 well as a number of modeling studies that show 12 that in a mixed-species community, where you 13 have sensitive and insensitive species, the 14 overall effects may not be so much a change in 15 total growth, that may not be the most 16 sensitive response of a vegetation community. 17 Instead, you may see a replacement of 18 sensitive species with insensitive ones or 19 sensitive populations being eliminated, as we 20 have already discussed. 21 So, I think -- the reason I am 22 bringing this up in the context of climate

### 202-234-4433 Neal R. Gross & Co., Inc. Page 202 1 change is, I think we shouldn't overemphasize 2 impacts of ozone only on growth of an entire 3 ecosystem or net carbon exchange. There may 4 be such effects, but that may not be the most 5 sensitive response, either to ozone or to 6 direct effects of ozone or effects of climate 7 change on vegetation. 8 Again, I guess I will raise this 9 as a question. My understanding of current 10 atmospheric models are that they seem to 11 overestimate pre-industrial ozone 12 concentrations; I think Daniel Jacob brought 13 up this point earlier today. 14 And my understanding of that, and 15 I would be glad to be corrected or have other 16 folks speak on this who know more than I do, 17 but my impression is that that my be 18 inadequate parameterization. Obviously, we 19 don't have the historical data we would like 20 from 100 years ago to parameterize models, but 21 there also may be missing chemistry. 22 So, this implies to me that there

### 202-234-4433 Neal R. Gross & Co., Inc. Page 2031 may be substantial uncertainty about non2 anthropogenic ozone concentrations. And I 3 guess I am raising this again in the context 4 of the policy-relevant background 5 concentrations. In other words, if the models 6 are overestimating pre-industrial 7 concentrations, does that imply they are also 8 overestimating policy-relevant background 9 concentrations? Again, that is a question. 10 And then the conclusion, that 11 there is a causal relationship between 12 tropospheric ozone and radiative forcing 13 certainly seems warranted, as is the 14 conclusion that there is likely to be a causal 15 relationship between tropospheric ozone and 16 climate change. 17 That's it. 18 DR. SAMET: Okay. Thank you. 19 Daniel? 20 DR. JACOB: Yes. Overall, I 21 thought it was a very good chapter. 22 Just to follow up on Peter's point

### 202-234-4433 Neal R. Gross & Co., Inc. Page 204 1 and respond to a couple of his comments, he is 2 right that the regional structure of climate 3 response to ozone radiative forcing could 4 receive a little bit more play. 5 It is still pretty large-scale, 6 because the ozone forcing is only happening in 7 the middle and the upper troposphere. So, it 8 is not like you are going to have a regional 9 climate response, like you have for aerosols. 10 But, still, you have more response in the 11 Northern Hemisphere than the Southern 12 Hemisphere to emissions or precursors in the 13 Northern Hemisphere. And that could be played 14 up a little bit more. 15 Yes, with regard to the fact that 16 models overestimate ozone concentrations 17 observed at the turn of the 20th century, this 18 is a very sore point because, if we use the 19 observations at the turn of the 20th century 20 to anchor a radiative forcing calculation, we 21 get a radiative forcing that is double what 22 you have in the IPCC estimate. So, radiative

### 202-234-4433 Neal R. Gross & Co., Inc. Page 205 1 forcing then becomes comparable to, say, that

2 of methane. 3 And it is interesting because, 4 whereas for the other gases you have ISCOR 5 data to anchor the pre-industrial values that 6 are used for radiative forcing calculation, 7 for ozone all you have are models. And as8 Peter points out, the models for pre9 industrial atmosphere may not be very good. 10 And so, therefore, yields in radiative forcing 11 may be underestimated. This maybe could 12 receive also a little bit more play. 13 I have a sprinkling of other 14 comments on that chapter. I just want to 15 bring up two points that I think are 16 important. 17 The first one is, when you express 18 radiative forcing with respect to ozone, it is 19 actually not very helpful for policy because 20 you can't directly control ozone. So, you 21 control NOx. But when you control NOx, you 22 have effects on methane, you have effects of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 206 1 aerosol nitrate, which actually counter the 2 benefit that you would have in decreasing 3 ozone, and controlling NOx is actually 4 considered not to be very good for climate 5 change. 6 So, the only way to effectively 7 control ozone, in a way that provides a 8 winning scenario for climate change, is to 9 control methane. And that point was made in 10 the last IPCC report for the first time, and 11 I think it definitely should receive more play 12 in that chapter. I have this in my written

13 comments.14 In fact, if you look at the short15 term horizon, that is, if you look at the 16 effect of present-day emissions on climate 17 change over the next 20 years, what you find 18 is that methane emissions are more important 19 than CO2 emissions. And that is in the IPCC 20 report. I am not making that up. 21 They are more important than CO2 22 emissions. And that is, in part, about one

### 202-234-4433 Neal R. Gross & Co., Inc. Page 207 1 third, because of the effect on ozone. So, 2 this is, again, a really big deal. 3 Okay. The second thing that I 4 thought should be played up a lot more is the 5 so-called RCP scenarios that are going to come 6 out in the fifth IPCC Assessment Report, the 7 one that is going to come out in 2014. 8 Right now, all the calculations 9 that are being done for 21st century climate 10 change are done based on the so-called SRES 11 scenarios that were put out in the third IPCC 12 report back in 2000. Those are going to be 13 retired as of this year. As of next year, 14 nobody is going to be using them anymore. 15 People are going to be using those so-called 16 RCP scenarios, Representative Concentration 17 Pathways, which kind of map the previous 18 scenarios in terms of CO2 and overall 19 radiative forcing.20 But in terms of the air-quality21 relevant gases -- and it is a point I made 22 before -- they are totally, totally different

### 202-234-4433 Neal R. Gross & Co., Inc. Page 208 1 than the previous SRES scenarios. And, in 2 particular, methane doesn't increase any more 3 in the 21st century. NOx is dropping. VOCs 4 are dropping. 5 These drops are global, right? 6 So, maybe they have to be taken with a grain 7 of salt. Maybe work has to be done on those 8 emission scenarios. But they are really going 9 to totally change the outlook in terms of the 10 effect of air-quality-relevant gases for 11 climate forcing. 12 And before we lament and say, oh, 13 maybe that makes the air-quality-relevant 14 gases not so important for radiative forcing, 15 I would say, on the contrary, because if NOx 16 emissions really drop a lot, then we have a 17 chance to witness the effect of NOx emissions 18 on climate forcing over the next few decades. 19 So, those are my comments. 20 DR. SAMET: Okay. Other comments 21 on charge question 11, Chapter 10? 22 (No response.)

### 202-234-4433 Neal R. Gross & Co., Inc. Page 209 1 Anybody on the phone? 2 DR. WEATHERS: No, nothing to add. 3 DR. SAMET: Nothing to add? Okay. 4 Let me just -- last chance for 5 takers. Then, let's see, sticking with the 6 first, doing the summary, Howard, would you 7 feel comfortable taking that on? 8 DR. NEUFELD: For this one? 9 DR. SAMET: Yes, for this one. 10 DR. NEUFELD: Sure. As long as I 11 get lots of help from Daniel. 12 DR. SAMET: Okay. All right. 13 Help is promised. 14 Well, we are running ahead of 15 schedule, which is okay. So, we are at lunch. 16 What I am going to suggest that we 17 do stick with the one hour for lunch. So, try 18 to get back by 1:15 to get going again. 19 (Whereupon, the foregoing matter 20 went off the record at 12:13 p.m. and resumed 21 at 1:23 p.m.)

22

### 202-234-4433 Neal R. Gross & Co., Inc. Page 210 1 A-F-T-E-R-N-O-O-N S-E-S-S-I-O-N 2 1:23 p.m. 3 DR. SAMET: So, we are moving on. 4 We are back to people, human health. And we 5 are going to start with exposure.

6 Ed? 7 And why don't you just make the 8 assumption that you are going to be writing 9 this up, Avol. 10 DR. FREY: You should have phoned 11 in. 12 (Laughter.) 13 MR. AVOL: All right. So, this is 14 charge question 5 on Chapter 4, the exposure 15 discussion, as Jon mentioned, to open the 16 discussion on human effects.

17 There are several useful and well18 done pieces of the chapter, but, in general, 19 one comment I had was that I think it needs a 20 better summary. The summary that it has in 21 there is four-pages-plus long. And it is not 22 a summary as much as another section.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 211 1 And so, I think it would be 2 helpful to sort of be concise about what 3 actually is going on there. In my written 4 comments, I made some suggestions for you 5 which you can take or not, but I think the 6 point is to try to improve it. 7 Another comment, just on sort of 8 the structure, is I think it would be useful

9 to have some sort of needs assessment about 10 what you think is missing that would really 11 help make a meaningful contribution for the 12 next cycle, if not the current cycle, in terms 13 of where the data gaps are that are missing 14 from the studies, missing from the 15 information, missing in terms of exposure or 16 monitoring, et cetera, to sort of help guide 17 what the agency thinks is needed to make 18 progress. And I don't see any of that there. 19 On the scientific side, I do have 20 a couple of questions. There's a couple of 21 sections, one on population proximity to ozone 22 monitors and another on spatial temporal

### 202-234-4433 Neal R. Gross & Co., Inc. Page 212 1 variability. 2 And so, the focus of the document 3 pretty quickly gets to talking about 4 population urban exposures and picks 12 urban 5 communities and talks about them. Obviously, 6 that is important, because you study effects 7 where the people are. 8 But, I mean, I think there are 9 some important differentiation between urban 10 and rural exposures that I think are lost 11 here. And that is that, in the urban case, 12 because of the combustion emissions and the 13 NOx titration, you generally have a sharper, 14 more defined peak, in terms of ozone exposure 15 during the course of the day. And so, that 16 has implications both in terms of exposure and 17 dose and temporal spatial activity patterns, 18 et cetera, and how that all interplays into, 19 ultimately, the effects. 20 In rural areas, that peak is a 21 much broader, more sort of mountain-type 22 representation. And so, while you don't get

### 202-234-4433 Neal R. Gross & Co., Inc. Page 213 1 the high peak exposures, you get a longer 2 duration of exposure. And for people that 3 live not in the city, but sort of downwind of 4 it or something, and in southern California, 5 for example, the examples might be downtown 6 Los Angeles or Riverside compared to Lake 7 Arrowhead or Lake Gregory up in the mountains. 8 And for those that are cognizant 9 of the monitoring data, Lake Arrowhead reports 10 the highest exposures, probably, in the 11 country because, you know, the exposures sort 12 of look like a broad mountain for hours and 13 hours at a time. They don't go down. They 14 are not titrated by NOx. There are no local 15 core emissions. And so, I think in terms of 16 thinking about exposure, somehow that has to, 17 I think, be captured in there. 18 And, then, that sort of gets into 19 the issue of intercommunity variability of 20 ozone concentrations. I mean, we have always 21 sort of thought about that, partially because 22 of this neighborhood scale approach of placing

### 202-234-4433 Neal R. Gross & Co., Inc. Page 214 1 monitors, sort of hoping to, you know, 2 specifically being away from roadsides, et 3 cetera. Now we have this broad sort of 4 regional view of what ozone is, that it is a 5 regional pollutant, that we don't see this 6 sort of fine resolution. 7 But when, in fact, we look within 8 communities, we see very strong variation. 9 And understanding exposure, understanding 10 dose, has to somehow take into account 11 understanding that variation, that finer 12 structure variation, which we don't see by 13 looking at the neighborhood scale monitors. 14 But, in fact, many studies, our 15 studies, the Children's Health Study and 16 others, around the world, in fact, are showing 17 this roadside effect, which is sort of a 18 reverse ozone effect. But, again, looking 19 across the community, you see this much more 20 variegated pattern of exposure than this broad 21 sort of regional look at ozone. Somehow, I 22 think we have to sort of capture that.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 215 1 Then, I had some other minor 2 comments that will be in my written 3 participation, but I think that is it. And 4 with that, I will turn it over to Chris, I 5 think maybe on the phone. 6 DR. STALLWORTH: Chris, are you on 7 the line? 8 DR. FREY: I am on the line. 9 Yes, I liked Ed's comments and I 10 support those. I have some written comments. 11 I just emailed them a few minutes ago to Holly 12 and Ed and David. And, also, on Chapter 2, I 13 emailed my comments to Helen. So, just so you

14 know those are there. 15 I think maybe what I would add to 16 what Ed said, and I think it follows on to 17 what he just said, was I guess in this 18 chapter, and also Chapter 2, there are

19 statements to the effect that there's low 20 spatial variability in ozone, and that the 21 temporal correlation in ozone is moderate and 22 implied to be strong enough that it wouldn't

### 202-234-4433 Neal R. Gross & Co., Inc. Page 216 1 introduce bias in epidemiological studies. 2 And I am not an epidemiologist, so I would 3 defer to some others on the panel. 4 But I guess I would at least 5 suggest that what is given in Chapter 4 6 doesn't convince me as a reader that that is 7 a particularly strong conclusion or finding. 8 And it seems more like an assumption or what 9 we hope would be -- our wish, if we could have 10 our wish, that that be true. 11 So, the claim of low spatial 12 variability seems contradicted, as Ed 13 indicated, by things like NOx titration just 14 downwind of roadways. And we know those are 15 significant locations for either residential 16 populations or work or school activity. And 17 so, those are non-negligible parts of looking 18 at human exposure. 19 And, then, in terms of the 20 temporal correlations, the evidence that is 21 given in the chapter is a little bit unclear 22 maybe or could be organized more clearly as

### 202-234-4433 Neal R. Gross & Co., Inc. Page 217 1 far as averaging time. But what I interpreted 2 was, as you go to longer averaging times the 3 correlation gets stronger, which we would 4 expect. But the correlation gets strong when 5 you get to averaging times of a day or four 6 days, and that is well beyond at least the 7 current eight-hour average that is used in the

8 current standard. 9 So, maybe there needs to be some 10 consideration of a little more association 11 between averaging time and temporal 12 correlation, and then whether or not the 13 assumption that a central site monitor is 14 relevant would depend on the averaging time, 15 as well as the spatial variability. 16 I think George Allen also alluded 17 to, in Boston, that there are some issues 18 there with spatial variation that are a little 19 complex than just assuming a central site 20 monitor or the nearest monitor would be

21 useful. 22 So, I think, just to summarize,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 218 1 the chapter, either this chapter or later, 2 should more critically address the adequacy of 3 central site monitors for use in 4 epidemiological studies, because I really 5 wasn't convinced by what was written there and 6 it seems a little weak. 7 I think my other comments on 8 Chapter 4 are really more editorial. And so, 9 they are in my written comments, but I won't 10 take time now. 11 So, that's it. 12 DR. SAMET: Okay. Thanks. 13 I think Dave. 14 DR. CHOCK: Okay. I want to echo 15 the comments of Ed and Chris. I think the 16 chapter is very well-written. 17 And I would say that my answers to 18 some of those questions are really in the 19 affirmative and just questions maybe, 20 especially when we are talking about long-term 21 exposure and short-term group-level and, also, 22 community-level exposure based on temporal

### 202-234-4433 Neal R. Gross & Co., Inc. Page 219 1 variability rather than spatial variability. 2 I do have a few comments. One, in 3 particular, is that even though both ambient 4 PM 2.5 and ozone are secondary pollutants, 5 special concentration patterns need not be 6 similar, especially in a populated urban 7 environment with spatially uneven NO sources, 8 as has already been pointed out. 9 But I want to point out a specific 10 paper that was quoted in the chapter, a 2010 11 paper by Sona, et al. It concluded that the 12 PM 2.5 and ozone are spatially more 13 homogeneous and, thus, the effects are less 14 sensitive to the choice of ambient monitors as 15 compared to primary pollutants monitors like 16 CO and NO2 monitors. 17 And if you look at the paper, 18 however, you will see that the authors used 19 different averaging times to characterize the 20 pollutant concentrations: 24 hours for PM 21 2.5, 8 hours for ozone, 1 hour for CO and NO2. 22 This would actually inadvertently and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 220 1 preferentially increase the smoothing of the 2 spatial distribution and, also, of PM 2.5 and 3 ozone. And this spatial smoothing is applied 4 only to ozone and PM 2.5 and not to CO and 5 NO2. So, the message is misleading there. 6 But I would still say that the 7 value of the paper is not diminished because 8 the paper, in effect, smooths out the interday 9 spatial variability in order to study the 10 health effects of ozone concentrations based 11 on their interday variability. 12 The chapter describes the 13 correlation between indoor ozone and, also, 14 the outdoor ozone, but they only have one 15 correlation coefficient number provided by Ed, 16 the .58 in the Los Angeles study. I wish that 17 the authors would look more into this kind of 18 correlation coefficients for other cities as 19 well. I don't know whether they are 20 available.

21 And there are also some 22 mischaracterization of the work by Soo and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 221 1 Zanobetti. And I describe this in my writeup. 2 And so, I don't want to make any further

3 comment on that. 4 And that is about all I have. 5 DR. SAMET: So, I think two 6 comments. One, I just want to go back to Ed's 7 comment about research needs. I suspect that, 8 at least in my mind, probably the ISA may not 9 be the right place to put the research needs. 10 Maybe it is in the policy assessment document.

11 I am not sure. 12 What is your view? I mean, if the 13 ISA is the integrated synthesis, it does allow 14 one opportunity to say, having done the 15 synthesis, here is what is needed. But it 16 seems to me that, when you get to the point 17 of the policy assessments, at that point that 18 you can highlight the key uncertainties from 19 the point of view of future decisionmaking 20 that might best be addressed for research. 21 So, John, your thoughts about 22 that? And I would like other panel members to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 222 1 weigh-in. 2 DR. VANDENBERG: Well, I very much 3 would appreciate other views as well. But in 4 the past we had created a separate document 5 which is a research needs document. I think 6 that we stopped doing that in the nineties, 7 sometime mid-nineties, as I recall. 8 And it was really a reflection of 9 time and resource limitations. We were not 10 meeting any of the timelines we were needing

11 to meet. 12 So, it was a focusing on just the 13 air quality criteria documents. I think that 14 certainly the research community would benefit 15 a lot, and I think we have heard that from a 16 number of different committees and people here

17 as well. 18 You raise a very good point, 19 though. What is the right time to do that? 20 Is it the end of the cycle when you see really 21 how the risk and exposure assessment benefit 22 from the ISA? The policy assessment benefits

### 202-234-4433 Neal R. Gross & Co., Inc. Page 223 1 from both the ISA and the risk and exposure

2 assessment. 3 So, I think we can take back your 4 encouragement to perhaps developing a research 5 needs item, because I think there is a lot of 6 interest within the agency as well. 7 Similarly, we would benefit from the 8 perspective of perhaps the entire process, not 9 just this part of the process, but I certainly

10 would welcome -- 11 DR. SAMET: Yes. I mean I propose 12 a policy assessment because it is at that 13 point that there will have been a judgment 14 made in the face uncertainty. And, 15 presumably, those key uncertainties that might 16 have, had they not been points of uncertainty, 17 the standard might have gone one way or 18 another, would seem to be most critical for 19 highlighting for future research. But, I 20 mean, again -- yes, Steve? 21 DR. KLEEBERGER: So, Jon, this 22 came up in the NOx and SOx discussions as

### 202-234-4433 Neal R. Gross & Co., Inc. Page 224 1 well. How did we handle it then? Do you

2 recall? 3 DR. SAMET: I am looking at John. 4 I am not sure I actually remember anything 5 very specific about this.

6 DR. VANDENBERG: I don't know. Do 7 you remember? 8 MR. LONG: I will just add one 9 thing, and that is that -- oh, I'm sorry, my 10 name is Tom Long. I am on the staff here, and 11 I worked on this Chapter 4, the exposure 12 chapter. 13 In certain areas where there has 14 clearly been an emerging area of research that 15 we think is going to be beneficial going 16 forward or that will provide some really 17 critical information for us, we have gone 18 ahead and put that in the document. But we 19 have not tried to be comprehensive in saying 20 here's everything that would need to be done 21 in order to get a perfect world. 22 And so, I think we can kind of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 225 1 follow a similar kind of path to identify some 2 areas that would be beneficial, but not maybe 3 go through this entire process of research 4 planning, research needs, because they are 5 somewhat of a separate function of that, too, 6 of course, in EPA to identify research 7 planning. 8 DR. SAMET: Judy? 9 DR. GRAHAM: I would support 10 John's statement of doing it later, after the 11 policy evaluation is done. I say that for 12 several reasons, many of which are historical. 13 And in the good old, bad old days 14 there was actually a separate section in all 15 the old criteria documents that talked about 16 research needs. They ended up being laundry 17 lists, for which there never was any funding. 18 And, then, it evolved to CASAC 19 would actually write the research needs. Now, 20 of course, staff wrote it and CASAC tweaked it 21 and put CASAC's name on it. Again, it was a 22 long list of laundry needs. Because, I mean,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 226 1 any researcher worth his salt can give you 10 2 more years and $100 million worth of research, 3 independent of its importance. 4 But I like the idea of waiting for 5 the result, so that it can be focused. But, 6 if you go that way, I would suggest that CASAC 7 be involved. 8 I do agree with what John said, to 9 be cautious about resources. I mean you see 10 in the OAQPS document: if resources permit, if 11 resources permit. 12 Well, I mean, I think there needs 13 to be a broader priority. EPA has a planning 14 process for its research program. And I guess

15 I am concerned about some of the research 16 needs that are in here, not they aren't good, 17 but that they are not consistent. 18 You could put a research need on 19 every other page. And so, why have it on this 20 section and not on that section?

21 DR. SAMET: Helen? 22 DR. SUH: I have a couple of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 227 1 comments, some of which has been touched on 2 before. But part of it has to do, I think, 3 with the writeup here. 4 I think when you talk about some 5 of the issues about day-to-day variability, 6 population monitors, describing the day-to-day 7 variability, well, that is really for a very 8 limited set of studies, I would say. That is 9 really looking at the time series kind of 10 studies. 11 But that I think doesn't really 12 speak to the long-term ozone studies. It 13 doesn't really speak maybe to the cohort type 14 of studies that people do. 15 And, also, I think the conclusion 16 that, given the spatial variability and the 17 activity patterns, and all these other 18 caveats, that it is still the population 19 monitors still explain the day-to-day 20 variability really might ignore, might be 21 appropriate maybe for children who spend a lot 22 of time outside, but for the elderly, for the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 228 1 mortality studies, maybe it is not 2 appropriate. So, I think an overall blanket 3 statement like that is dangerous. 4 And I think this goes to the 5 research needs, in that I think within there, 6 because there is not a lot of studies looking 7 at indoor/outdoor relationships or personal 8 ambient relationships, or even spatial9 relationships within a city over the long10 term. But it could be pointed out that there 11 isn't that much data on this, but there should 12 be some caveat to know that this statement 13 might only apply to maybe the children only or 14 maybe workers outdoors. But their relevance 15 to people spending a lot of time inside, or 16 even people in low SES groups, might not be 17 there because those people often tend to live 18 near major roadways, where there might be less 19 ozone. There might be more error. So, I 20 think we just have to be very careful about 21 how those big, overarching conclusions are

22 framed.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 229 1 And I would suggest for these 2 research priorities that in some ways I think 3 the foundation should be laid throughout the 4 process. So, in the ISA I think it should 5 really say, well, this is the data that we 6 have, but we can't answer these questions

7 because we don't have that data. 8 And, then, as you get to the 9 policy assessment, I think, with the 10 uncertainty analysis, I think in the PM when 11 you had high priority, this really would 12 affect your risk assessment, can that somehow 13 lay out what kind of research might be needed

14 more. 15 And, then, I have some other 16 comments that I think relate to Chapter 2 as 17 well as Chapter 4. So, we will just hold that 18 maybe for later. 19 DR. SAMET: Okay. Fred? 20 DR. MILLER: Well, I never like 21 to, and never do, totally agree with my 22 colleague Dr. Graham.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 230 1 (Laughter.) 2 So, I think I ought to chime in 3 here and say I don't agree with waiting until 4 all of the policy is done because you will now 5 be at the next revision cycle, and you are now 6 another five years down the road. If you are 7 going to do it, it ought to be after the first 8 draft, where you have some aspects of policy, 9 and not wait until the finished product. 10 And the bottom line is that it 11 doesn't really matter anyway because research 12 at EPA is a zero-sum game. And when the PM 13 stories come about, if you had ozone 14 separately, you didn't get funded. So, this 15 is much ado about nothing, and we are kidding 16 ourselves to think that we can spend all this 17 time, identify all these research needs, and, 18 then, the agency is going to come up with 19 money and solve the problem. It does not 20 happen. 21 And quite frankly, we are at a 22 time cycle on this revision process where,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 231 1 after this, you don't have a hell of a lot 2 more space to go. And so, I really have to 3 say prioritize your money more carefully, and 4 coming up in the risk assessment stuff, it is 5 just not going to impact these other research

6 needs. 7 That is just 40 years of 8 experience, and 20 of them at EPA. 9 DR. SAMET: Fred, are you going to

10 tell me there's no Santa Claus? 11 (Laughter.) 12 DR. MILLER: Oh, Virginia, come on 13 now. I have grandchildren. Come on. 14 (Laughter.) 15 DR. SAMET: Actually, I think 16 Lydia wants to weigh-in, too. 17 I think one thing that I don't 18 think you should do is haphazardly sprinkle 19 research recommendations through the document. 20 So, whatever you do, don't do that. 21 I mean I think Fred's point about, 22 well, timeliness of the recommendations is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 232 1 probably important, but the reality is a 2 different matter. But I think maybe you 3 should think about this and come back and tell 4 us what you want to do. 5 But Lydia I think was going to -- 6 MS. WEGMAN: Just a small point, 7 which is we certainly do plan to include 8 research needs in the policy assessment. And 9 we will think about, Fred, your suggestion 10 that we include something in the first draft 11 of the policy assessment, if I understood you 12 correctly. 13 DR. SAMET: And perhaps if there 14 is a place in the document, as it is 15 constructed now, it would be in this 16 integrative Chapter 2. And there is sort of 17 where you are pointing to how the information 18 is coming together. And if you see key gaps 19 that need immediate attention, that at least 20 would be the place to do it. 21 There was one other point that Ed 22 made that I just wanted to come back to. And

### 202-234-4433 Neal R. Gross & Co., Inc. Page 233 1 that was his comment about the summary and its 2 length. I was just sort of scanning across 3 some of the chapters and looking at what comes 4 at the end. And it ranges from summary and 5 conclusions to summary and causal 6 determinations, to overall summary, to 7 nothing. 8 And I think you ought to have some 9 standardization of what you put at the end of 10 these documents, whether it is a brief rehash, 11 i.e., a summary, but, then, it shouldn't be 12 four pages, which I think was Ed's point. And 13 if it is a place where you are bringing 14 everything together, then maybe give it the 15 right name and decide if something called 16 "summary" comes after that. But I think it 17 probably ought to be a somewhat -- I mean, 18 admitting to the fact that the chapters have 19 somewhat different purposes, there still ought 20 to be some sort of commonality, I think, in 21 how you bring them to a close. 22 Let me say, anybody on the phone

### 202-234-4433 Neal R. Gross & Co., Inc. Page 234 1 want to weigh-in here? I'm sorry, George. 2 Okay. Let's see, who is on the 3 phone, actually? Chris, you're there?

4 DR. FREY: I am here. 5 DR. SAMET: Okay. And, Sverre, 6 are you? 7 DR. WEATHERS: Kathy Weathers. 8 DR. SAMET: Kathy is there, okay. 9 And, Sverre, are you there? 10 (No response.) 11 Oh, good. Okay. 12 (Laughter.) 13 George?

14 MR. ALLEN: Thanks. 15 I want to do a sidebar here. And 16 that is exposure to products of ozone 17 decomposition, once the ozone from outdoors 18 gets inside. Now if we use the process of the 19 NAAQS lead exposure models, they worry about 20 lead inside that came from outside. So, I am 21 assuming we have a similar situation here. 22 There's literature out there.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 235 1 Charlie Weschler, for one example, did a nice 2 piece on atmospheric environment in 2004, 3 saying, you know what? The ozone may go away, 4 but it doesn't go away nicely. Basically, you 5 have hydroxyls, radicals forming when the 6 ozone reacts with whatever is inside. And 7 that can, then, react with all sorts of indoor 8 stuff to make a lot of very nasty byproducts 9 which, presumably, have health effects. 10 Now there is a fair amount of that 11 in the literature, but I am wondering if that 12 is something that we need to be including in 13 this discussion of exposure, just a broad, 14 very broad question. 15 MR. LONG: There is a brief 16 section in the chapter on that citing some of 17 Charlie Weschler's work. But I would 18 appreciate some input on how much weight to 19 place on that. 20 DR. MILLER: You bring up a very 21 good point. Phil Hopke has an in-press 22 article measuring all the reaction products,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 236 1 secondary organic aerosols, and the mass rate 2 production in information that I think is 3 going to be a sentinel publication for how to 4 look at how much is produced for a whole 5 variety of these reaction products. And it is 6 hot off the press. It goes exactly to the 7 point you are making. It does actually give 8 you quantitative data to be able to 9 characterize this. 10 DR. SAMET: Judy? 11 DR. GRAHAM: Looking at the 12 exposure modeling section on page 4-12, 13 Section 4.4, it describes a bunch of models. 14 And, fine, but I said, so what? It doesn't 15 give me any results. 16 Now it could be this was 17 purposeful because you have to have a delicate 18 balance with the exposure assessment that 19 OAQPS is going to be doing. But what I am 20 thinking is that there might be a couple of 21 instances here where you could describe the 22 results of a model. Even instead of giving

### 202-234-4433 Neal R. Gross & Co., Inc. Page 237 1 like the activity pattern data from the NHAP 2 survey, to maybe just give a couple of results 3 of what the exposures might be based upon 4 that. Make it a little bit more meaningful. 5 DR. SAMET: Okay. Anything else 6 on this question? 7 (No response.) 8 Okay. Ed, you are -- if you don't 9 mind? 10 And, then, Fred will move on to 11 dosimetry. 12 DR. MILLER: Given that I have the 13 floor, I think it would be appropriate to 14 request a motion of the floor that the last 15 discussant listed now be the person in charge 16 of writing things up. 17 (Laughter.) 18 Do I hear a second on it? 19 (Laughter.) 20 Well, enough said.21 In terms of dosimetry and mode-of22 action chapter, the first question was about

### 202-234-4433 Neal R. Gross & Co., Inc. Page 238 1 whether or not basic dosimetric principles of 2 ozone uptake were accurately presented in 3 sufficient detail. I maintain they are not, 4 except the things that are discussed are 5 factors that influence dosimetry. 6 If Jim Ultman would get involved, 7 he would tell you these are not principles of 8 dosimetry. The principles involve bulk 9 convection, axial dispersion, effective radial 10 diffusion, solubility, Henry's Law, all of 11 these kinds of things. And this just isn't

12 touched on at all. 13 What is really covered is more of 14 the reaction to ozone with various molecules 15 in the ELF and in the tissue. And that is 16 just one part. 17 So, this may have been just a 18 running-together of words, but these are not 19 principles that are discussed in here. They 20 are factors like exercise, age, et cetera, 21 ventilation, that affect dose. But the 22 principles of dosimetry are grounded on the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 239 1 physics of gas transport and removal. And 2 there is nothing in here on that. 3 So, if you want to rephrase the 4 question, I would say they have done a good 5 job at looking at most of the factors that 6 influence dosimetry, but not really a writeup 7 on dosimetric principles, per se. 8 In terms of the mode-of-action 9 question, the overview was, the approach taken 10 to characterize it and related effects, what 11 are our views? I will say that, as an aside, 12 it is not clear why the two are lumped,13 dosimetry and mode of action. In the mode-of14 action material, it is a mixture of effects 15 studies described as well as mechanistic. And 16 so, it really is debatable about, wherever it 17 is placed, it may be here just as well as 18 another, but it does lead to some duplications 19 of material that maybe could be avoided, if 20 you were trying to cut down more. 21 The summary figure on page 5-62 of 22 possible modes of action, to me, is an

### 202-234-4433 Neal R. Gross & Co., Inc. Page 240 1 excellent one. But I would have put it at the 2 beginning of the discussion of mode of action 3 and I would have included the section numbers 4 that now discuss subsequently, and, then, I 5 would keep it at the end as far as the summary 6 because, when I got through all of this to the 7 end, I thought, boy, I wish I had seen that 8 earlier because it now started to make sense 9 in terms of the end relationships and the 10 different pathways. So, that was a 11 possibility. 12 As far as some of my general 13 comments that I have written up, I want to 14 address a few of them. There is a number of 15 places in here where, when you are looking at 16 these factors, and they are all from human 17 exposure studies and chamber studies, and it 18 basically says this study shows that ozone 19 does that. Almost every single one of them 20 are merely a reaffirmation of what was 21 predicated by mathematical dosimetry models a 22 minimum of 10 to 20 years earlier. And, yet,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 241 1 those models aren't mentioned at all. 2 Now the fact that I am a senior 3 author of one, you know, you can say okay, but 4 there are other people in the room that have 5 developed also. And it would strengthen the 6 conclusions that you draw by referring to 7 these models along the way, that, in fact, 8 these things are in agreement and what has 9 been predicted. 10 And as an example of this, in the 11 homology section, there is a statement about 12 that it is difficult to cross species and 13 that. And, yet, if you presented a figure 14 from Gary Hatch, who has worked with monkeys, 15 and you presented my 1985 figure for the 16 tissue dose of ozone, they are absolutely 17 reflective images of one another in terms of 18 the amount at 1803 that he measured 15 years 19 after I predicted it in monkeys in the tissue 20 pattern identical to what the model shows for 21 ozone. Now the Y-scale is different, but the 22 pattern is there. And if that doesn't talk

### 202-234-4433 Neal R. Gross & Co., Inc. Page 242 1 about species homology, I don't know what in

2 the hell does. 3 And so, some of these things just 4 really get to the point of not maybe going far 5 enough in terms of the interrelationship of 6 tying together not only the mathematical 7 models and the human studies, but also the 8 animal tox results. There's situations in 9 here where some of the studies are described 10 in terms of the primate studies that are more 11 recent. And, yet, there is no mention at all 12 of the Crapo-Chang studies in rats at .12 13 parts per million, showing structural changes. 14 There's no reference to the EPA chronic study 15 of a diurnal ambient pattern that showed 16 structural and functional changes in pulmonary 17 function. 18 So, when you talk about the 19 potential causal aspects, these are things 20 that are left out that really drive the nail 21 home about the commonality between ozone 22 exposures in animals and humans. And it is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 243 1 just missing right now. 2 Another major thing that I just 3 have to -- and I won't give the microphone up 4 until I get done with this for sure -- has to 5 do with there's multiple places in this 6 chapter where it is stated, based upon prior, 7 that ozone can't penetrate more than .1 8 microns in the ELF. And you talk about that 9 everything in the alveolar region, it has to 10 be a cascade of products. 11 The alveolar region is 95 percent 12 surface area of type 1 cells. The surfactant 13 film is at most .02 microns in thickness over 14 those cells. And because when you breath the 15 surfactant cools into areas, it gets down to 16 a monolayer of surfactant. Now don't tell me 17 that ozone can't get through that and directly 18 react to the tissue. This is a greatly 19 misconceived statement here about what can go 20 on in these layers. 21 The other thing is, when it comes 22 to the mucous layer, there is no discussion in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 244 1 here because of the fact that the cilia beat 2 at 1200 beats per minute, you have 3 instantaneously mixing of the periciliary 4 layer. And so, there is the capability of 5 ozone to penetrate to the tissue, not as much, 6 clearly, and that is reflected in the net dose 7 patterns versus the tissue does patterns. 8 So, this has got to be changed in 9 here because it just doesn't flat meet with 10 the physiology, and it doesn't meet with the 11 statements in terms of where the regions of 12 effects occur and how the tissue could be 13 getting exposed to ozone. 14 I have to take, also, exception on 15 page 15, where it says that the models are 16 limited because they don't take care of the 17 URT. When we published, and Jim has done the 18 same thing, the doses normalized to the 19 micrograms per microgram of ozone entering the 20 trachea. So, all you have to do, if 50 21 percent is taken out on the head, and you are 22 exposed to 200 parts per billion, that says it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 245 1 is 200 divided by 2 is 100 parts per billion 2 got to the trachea. And you now go to our 3 dose curves and you multiple those results on 4 the Y-axis by 100, and you have the dose. 5 That is not a limitation at all. And what's 6 more, you have now the uptake information for 7 rats, for guinea pigs, for rabbits. 8 So, I have to take issue with this 9 because Gerrity also showed the human uptakes 10 in that. So, this goes again at the issues 11 about statements in here how you can't do 12 interspecies dosimetric comparisons. You want 13 to give me a contract? I will do them for 14 you. It is just not true. 15 There is another one in here, and 16 I will get down to the last couple. It 17 relates to the statements about why uptake 18 can't be related to functional changes, and 19 that the FEV1 breaks down. I brought this up 20 in previous reviews, and I guess, until I 21 dictate it into the record, it won't get 22 through.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 246 1 John Overton and I published in 2 1996 in terms of the influence of the 3 expansion of the conducting airways on 4 delivered dose. And we showed in that paper, 5 if you selected subjects in clinical studies 6 using the anatomical dead space, you would 7 normalize for dose. And, in fact, Jim Ultman 8 has done work like that and showed that you 9 get a much more reproducible response. 10 And so, some of these aspects of 11 statement about correlation of what you can do 12 and what you can't do are just not really 13 looking at the literature and the information 14 that is available. 15 There is another one last point. 16 That has to do with the Kim publication. In 17 the homology part there, it is discussed about 18 the GSTM one, and you go on for a couple of 19 pages. But that article isn't cited, and that 20 article showed that the GSTM one has no role 21 in modifying the effects of neutrophilic 22 inflammation at environmental exposure levels.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 247 1 And so, you go on describing what 2 is going on in terms of other studies, and, 3 then, you get down and don't even include the 4 chem work showing this is not an issue. And 5 it was one of the specific hypotheses that 6 they tested, along with the specific 7 hypothesis that they state a priori in their 8 study was: we are interested in the effects 9 after 6.6 hours of exposure to ozone compared 10 to control. They didn't say they want to 11 study every possible linear combinations along 12 the hours as they went, which was alluded to 13 earlier today. 14 So, these are some of the things, 15 and I have a lot more written up in specifics. 16 But some of the aspects that really on this 17 next revision need to be taken into account, 18 and in that regard, some of the things -- the 19 greatest influence of exposure dose is 20 exercise, and exercise is not really brought

21 out here as a factor. You talk about 22 children. You talk about age. And, yet, that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 248 1 is why the studies and the clinical went to 2 the longer hours and the higher levels of 3 exposure, okay, because it is a function of 4 dose and it is nonlinear. 5 And we can show proportionately 6 that you get a tenfold increase in dose when 7 you double the tidal volume. It doesn't go 8 up. And there is a statement in here that 9 current thinking is that it is directly 10 proportional. It is not. 11 And what's more, because the lungs 12 are set up to fast deliver oxygen to the lower 13 respiratory tract, there is less taken out in 14 the trachea bronchial region and more taken 15 out in the lower region. And as you increase 16 the dose, you get a twentyfold increase to

17 those areas. 18 So, these are the kinds of things 19 that are available from published studies, 20 some of them modeling, some of them 21 experimental, also showing in terms of the 22 human uptake studies that, to me, have escaped

### 202-234-4433 Neal R. Gross & Co., Inc. Page 249 1 inclusion at this point. 2 And I'll stop there. 3 DR. SAMET: And your final grade? 4 (Laughter.) 5 DR. MILLER: My final grade? It 6 is a good start. 7 (Laughter.) 8 You did an excellent job of 9 describing how these other factors affect the 10 ozone uptake. That discussion and review of 11 the literature was very good. But you go weak 12 on saying that you can go between species, and 13 the species homology is a very weak section. 14 It can be strengthened more. 15 Good God, I mean you can look at 16 the Tepper studies. What you can do in 17 animals you could do in humans. And they come 18 up, and guess what? You have attenuation of 19 pulmonary function, but when you open up the 20 animals, you have more serious lesions. They 21 progress. 22 And this whole time together of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 250 1 the causality and the information needs to be 2 woven together, and it is not done to the 3 extent that it can be done in this particular 4 version. 5 DR. SAMET: I think just to

6 elaborate on Fred's comments about the 7 dosimetry and the historical development of 8 models, I think you face a dilemma which comes 9 up here and elsewhere as to whether you start 10 from the beginning of the story or you start 11 at a temporally-arbitrary point in time 12 defined by when the review cycle happens to 13 come up. 14 And I think maybe what you are not 15 doing, and I think it is something that Fred 16 alludes to here, and comes up elsewhere, it is 17 not clear exactly sort of what part of the 18 rest of the movie you are not telling us about 19 and why. I think if these links were there, 20 then it would be clear that there was this 21 major foundation of work in ozone and other 22 gas dosimetry that is well-known. You know

### 202-234-4433 Neal R. Gross & Co., Inc. Page 251 1 it. I think the question is, in terms of 2 staging the document, how you put this in. 3 And I think this same theme is 4 going to come up elsewhere. And I think what 5 Fred is making clear is, if you are not going 6 to show something, say we are looking at some 7 of the more recent attempts to validate 8 earlier dosimetry models, say so and say what 9 those earlier models were. 10 Joe? I was just going to go 11 around. I will get to you, Mike. 12 DR. BRAIN: I will only add a 13 little to all the things that Fred has had to 14 say. 15 The entire document, it is very 16 encyclopedic. There's lots of references 17 there. And again, I think what is really 18 needed is more critical commentary of really 19 singling out the publications that are most 20 important and are most likely to influence our 21 view of what is an acceptable level. 22 One of the novel things, at least

### 202-234-4433 Neal R. Gross & Co., Inc. Page 252 1 for me, in this was a section that appeared, 2 a rubric that appeared repeatedly in different 3 sections called recent publications. And so, 4 in a sense, that was nice, to really say what 5 is really new since we have looked at this 6 last time. On the other hand, it is important 7 that that be integrated into the past, as you 8 have just heard. 9 Also, it was very uneven as to 10 whether or not there was sort of a summary in 11 this section called recent publications. 12 5.1.3.2 said: The studies reviewed are in 13 agreement with previous studies and do not 14 change the dosimetry conclusions of the last

15 document. 16 So, that was very helpful in sort 17 of a bottom line of all the new material. 18 Other times when there was a 19 recent publication statement, there was not 20 any sort of summary or conclusion. I think 21 that would be helpful. 22 The dosimetry and the mode-of-

### 202-234-4433 Neal R. Gross & Co., Inc. Page 253 1 action sections are really very, very 2 different. I found myself looking at the mode 3 of actions and seeing, then, how incomplete 4 the epi and the clinical studies were. We 5 really do love pulmonary function. It really 6 is easy to measure the FEV1. 7 But when you look at the modes of 8 action, and particularly when you look at the 9 comparative studies, you realize how many 10 other things ozone does. The airway11 remodeling, the stuff that was done in non12 human primates, in rats, that Fred has talked 13 about. And I really don't see the clinical 14 studies or the epi studies really following up 15 on some of these key observations. 16 Again, as you know, the FEV1 is 17 really dominated by what happens in large 18 airways. You can have significant changes in 19 small airways or changes in the alveoli, and 20 that may influence the FEV1 very, very little. 21 And again, this brings up the 22 topic of really doing a better job on

### 202-234-4433 Neal R. Gross & Co., Inc. Page 254 1 comparative dosimetry. It seems to me, in the 2 absence of being able to look at airways, and 3 maybe we will now, HCRT is becoming more 4 sophisticated. I don't know whether there 5 will ever be enough money to apply that to 6 some human populations in relation to air 7 pollution. 8 But it seems to me we really do 9 need, as Judy at the outset said, I think in 10 the ozone area the animal toxicology is really 11 very critical because it tells us about some 12 long-term, progressive, irreversible anatomic 13 changes that aren't always easily detected by 14 the kind of pulmonary function studies that we

15 can do. 16 Another area that I think is 17 really important and is mentioned, but should 18 be given more attention, is the whole 19 phenomenon of adaptation. This is really a 20 very important phenomena in relation to ozone. 21 And as you know, animals that are 22 pre-exposed or animals or humans that see high

### 202-234-4433 Neal R. Gross & Co., Inc. Page 255 1 levels of oxygen can then be given higher 2 levels of ozone or hyperoxia and have a much

3 reduced level. 4 And I was going to mention this 5 earlier in relation to exposure assessment. 6 It seems to me, as we characterize exposure, 7 we really need to pay attention to how uniform 8 and steady the ozone exposures are. I can 9 imagine huge differences, you know, if a 10 community lives at a fairly high level of 11 ozone all the time and, then, there are a few 12 little blips compared to a community that sees 13 very little ozone, and, then, suddenly, in the 14 summertime has higher levels. I could imagine 15 the responses being very different. 16 So, it seems to me the whole 17 phenomenon of adaptation, its documentation, 18 and animal studies, really needs to be 19 reflected in our exposure assessment 20 adaptation analysis as well. 21 I agree with what Fred said about 22 the alveoli, and I think it brings up another

### 202-234-4433 Neal R. Gross & Co., Inc. Page 256 1 area. The whole dosimetry is very complicated 2 because the uptake of ozone varies as we march 3 down through the lung from the nose to the 4 pharynx, large/small airways, and finally, the 5 alveolar region, and the other things such as 6 the mucous thickness or the thickness of the 7 alveolar layer, again, varies considerably. 8 So, it is very complicated. 9 So, I think that is all I want to 10 add at this point. 11 DR. SAMET: Okay. Jack?

12 DR. HARKEMA: I can't add to much 13 more to what has been said. But I want to 14 just echo a couple of things, but, also, ask 15 the first question. 16 The title, I don't think the title 17 actually reflects what is in the chapter 18 because there is dosimetry and, then, there is 19 mode of action, but in between you have to 20 have response. And it is really a dose 21 response chapter that I see that you have

22 here.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 257 1 So, I had problems with what you 2 were trying to do with this chapter with the 3 next chapters which have to do with short- and 4 long-term effects because there is a lot of 5 redundancy in here. So, I had a hard time 6 grasping what is this chapter supposed to be 7 doing. Is it concentrating just on dosimetry? 8 Is it starting to give a prelude to effects? 9 And, then, you throw in the mode 10 of action, which I agree with Fred that that 11 is a nice figure to start with, but I had a 12 hard time, after I got done with that, the 13 whole chapter, I thought it would be a lot 14 more question marks in a lot of other things 15 in that mode of action that would have been in 16 there that weren't in there. And there was no 17 really justification of why you included some 18 things in the mode of action and not other 19 things. 20 So, I would just add to, upfront, 21 say what the purpose of this chapter is and 22 give a little hint to the reader about the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 258 1 mode of action and the link between the 2 dosimetry. I do think you have a lot of 3 responses in here and effects, and dosimetry, 4 if you want to include that in your 5 definition, the dose response relation, then 6 just say that upfront. 7 The other thing is you talked 8 about summary. Summary, this is the shortest 9 summary that I have ever seen for all the 10 information that you gave us there. And I 11 think, of all the chapters, this one, if you 12 are going to have mode of action, that summary 13 has to be an explanation of why you came up 14 with that mode of action. 15 You could spend a lot of time 16 talking about, well, based on all of this, the 17 dose and the response, this is, we think, the 18 mode of action. But it is really cursory and 19 it really needs to be expanded. 20 And, then, you throw in at the end 21 the gaps of knowledge. I think the other 22 chapters later on do that, or maybe if they

### 202-234-4433 Neal R. Gross & Co., Inc. Page 259 1 don't, then explain how it is going to be 2 integrated into your mode of action, or 3 whatever. It is very cursory there, too. 4 And I want to echo what Fred said, 5 but qualify it first. First, I like all the 6 historical things, and especially in this 7 chapter, of all the other chapters, most of 8 the best -- and I am even giving you a 9 compliment here -- but some of the best work 10 in this dosimetry was done a long time ago, 11 and, also, the effects. 12 And there is so much homology 13 between animal and human. What the animal 14 studies are doing is providing a clue of the 15 pathology that is assumed in the human. And 16 actually, there are studies that have tried to 17 get to that. 18 But that is ignored. I mean there 19 is not a lot of emphasis on the epithelial 20 remodeling that goes on there. And if you get 21 epithelial remodeling, you are going to change 22 your thickness.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 260 1 And the dosimetry is really, I 2 mean the chapter is biased with short-term 3 exposure. Okay? And that is probably because 4 of some of the data, but it should be brought 5 up that this dosimetry could change quite 6 radically if you have repeated exposure. You 7 get a glimpse of that through the pathology 8 that happens. And so, I think that somehow 9 that should be woven in there, if you are 10 going to have this dose response chapter. 11 There were just a few other minor 12 things that I had in here. I would just end 13 with something to think about that maybe you 14 could weave into this that would make the 15 point about where lesions are and where the 16 dose is, and so on. 17 They show that nice figure, and I 18 think it is an appropriate figure, of the 19 terminal bronchial and alveolar duct area 20 where the epithelium gets smaller and you get 21 thinner airway fluid on there. And you get 22 the primary lesion of ozone right in that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 261 1 center region. That has been verified with 2 dosimetry. 3 On the other hand, if you 4 emphasize the fact that you have a thin -- you 5 know, that the effect is based just on that 6 thin layer there in an exposure, why don't you 7 get deep ozone lesions in the outer 8 parenchyma, where, supposedly, they are more 9 exposed? Well, the simple fact is it is much 10 more complicated than that. 11 And one way to think about maybe 12 organizing this a little bit different is to 13 think about talking about dosimetry in very14 cursory, the historical, starting with whole15 animal physiology, all the elegant, but doing 16 it a very concise way, and then talk about to

17 the cellular level. 18 And that way, I don't know, the 19 reader, I think it would flow a lot better, 20 instead of starting with the extra -- there is 21 a lot of emphasis just on the fluid and the 22 cell part. So, anyway, that is just the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 262 1 writer's prerogative. 2 Then, finally, there is not much - 3 - if you are going to do looking about 4 response, there is no mention about 5 differences in response of airway types, which 6 is huge, I think. I think it is really, 7 really important to talk about why some cells 8 respond and others don't. I personally don't 9 think it is just the airway lining fluid that 10 is running the whole show here. 11 So, anyway, that's my comment. 12 DR. SAMET: Okay. Thanks. 13 And before we go to you, Jim, just 14 two comments. I mean I think, one, the 15 comments about the summary again point to the 16 need for getting the summaries right, which I 17 think the point is made. 18 The other thing I think this 19 chapter should be doing, and I think this 20 really comes out in part of what Jack was 21 saying, is it should be laying, in a sense, 22 the biological story out for the human health

### 202-234-4433 Neal R. Gross & Co., Inc. Page 263 1 effects that are going to be addressed in the 2 next chapters. It seems to me that does 3 involve integrating dose with mode of action. 4 And if you are going to talk later about 5 incident asthma, for example, or exacerbation 6 of asthma or reduction of lung function, that 7 squarely gets you at this question of what 8 target size within the respiratory tract might 9 be relevant, and what could be the underlying 10 mechanisms of injury that would lead, say, to 11 reduction of lung function? Is that upper 12 airway deposition and triggering of air 13 receptors or effects on small airways with 14 inflammation? 15 I mean I think that is maybe the 16 way. I would appreciate thoughts from others, 17 but it seems to me that is the way the story 18 ought to be coming here and setting up for the 19 next two chapters. 20 Right now, it is sort of here's a 21 chuck on dosimetry and here's a chunk on mode 22 of action. It is not integrated in fact to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 264 1 set up for the effects, for the discussion of

2 health outcomes at all. You have the mode-of3 action figure that Fred highlights, but it is 4 not brought together. 5 DR. HARKEMA: I think it would 6 help the other chapters later on, too. 7 DR. SAMET: Exactly. 8 DR. HARKEMA: Because you could 9 eliminate a lot of redundancy. 10 DR. SAMET: Yes, that's true. 11 Yes. But this is where it maybe should be 12 brought together. 13 Jim? 14 DR. ULTMAN: I agree with 15 everybody's comments that there needs to be 16 better justification between the dosimetry 17 part and the mode-of-action parts of the 18 chapter. 19 I think part of the problem is 20 that the dosimetry work that has been taken on 21 in the past kind of ended at the epithelial 22 wall, or even before that, at the gas/liquid

### 202-234-4433 Neal R. Gross & Co., Inc. Page 265 1 interface. That is reflected by much of the 2 material that you have. 3 You talk about how much dose, how 4 much ozone uptake occurs through the upper 5 airways versus the acinar regions versus the 6 deeper lung. And the uptake of ozone is only 7 the beginning of the story. Then, you talk 8 about how it gets converted into other, could 9 get converted into other byproducts that are 10 toxic to the epithelium. And that is kind of 11 where we are now. And things have kind of 12 stopped at that point. 13 So, dosimetry really hasn't 14 progressed so that it can be connected up with 15 the mode of action because we don't have 16 models and we don't have experimental data

17 that does that. 18 So, I think part of the chapter 19 reflects kind of a dead-end in where we are in 20 dosimetry relative to the biological effects. 21 But I think you could put an introduction in 22 the beginning, and you could bridge the two

### 202-234-4433 Neal R. Gross & Co., Inc. Page 266 1 sections and make them clearer. 2 I think that -- there are two 3 sections in the chapter on reactions of ozone 4 in the substrate -- I'm sorry -- in the ELF 5 with various substrates. There are two 6 sections. 7 The division between what material 8 goes in one section versus what material goes 9 in the other section is not clear. One of 10 these reaction sections is in the dosimetry 11 part. One is in the mode-of-action part. It 12 is not clear what is different between them. 13 They seem to be somewhat redundant. 14 And I had some suggestions in my 15 comments that maybe you can somehow take the 16 first section and focus it more on the kinds 17 of modeling and measurements that have been 18 done to reflect on the penetration of ozone 19 into the liquid lining layer, how much of it 20 can really reach the epithelial surface. 21 You have already got material on 22 the reaction rates that occur in ELF. Maybe

### 202-234-4433 Neal R. Gross & Co., Inc. Page 267 1 talk a little bit more of the state-of-the-art 2 and what we know about these reactions. But 3 kind of move it away from the mechanisms of 4 the reactions because I think that should go 5 in the mode of the action. You know, the 6 mechanisms by which ozone combines with 7 antioxidants versus other compounds maybe 8 should go in that second section. 9 So, I think you need a clearer 10 division between those two, and that may help 11 bridge things a little bit more because it may 12 show how dosimetry ends at one point and, 13 then, it gets picked up by mode of action at 14 another point. 15 Maybe a figure would help in that 16 regard where you show a continuum. You know, 17 you inhale ozone. It gets distributed into 18 the lungs. It gets absorbed into the ELF, 19 reacts in the ELF, goes on to the tissue, et 20 cetera, et cetera. 21 And, then, the first part of the 22 chapter focuses on this part of the process.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 268 1 The second part is on this part, and we are 2 missing a middle part that we just don't know 3 at this point, so we can't say anything about 4 it. But that may be a way of putting the 5 whole thing, I think, in context. 6 Again, I think what Fred mentioned 7 about the factors, you know, convection, 8 diffusion. I agree with what Jon said that to 9 go into that in a lot of detail in a document, 10 in an area where we are creating these 11 criterion documents, is very advanced now, is 12 very sophisticated. To go back to square one 13 and talk in length about some of the 14 principles maybe seems like you are taking a 15 step backward. But, again, maybe a figure 16 would help. 17 And I think Fred, in an earlier 18 publication you had, it showed up like a 19 profile, remember, of the different mechanisms 20 and different parts of the lung. Do you know 21 which figure I am talking about? I think that 22 would be well-placed.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 269 1 You wouldn't have to talk much 2 about the principles. At least show how the 3 principles impact on the various factors. 4 Okay. 5 I think there is a weakness in the 6 chapter in your ability to connect the various 7 factors in breathing that are affecting 8 dosimetry. Because you talk about, well, when 9 you increase frequency, this happens to 10 uptake. You say there is not much known about 11 the effect of minute volume in uptake.

12 But these factors are connected. 13 Within the particular situation you are in the 14 factors are connected. For example, you show 15 a figure that happens to be from one of my 16 papers, Figure 5.3. I have got it in my 17 writeup. 18 Oxygen uptake efficiency among 19 different subjects decreased with increasing 20 breathing frequency. That is what that shows. 21 What you don't say is that the minute volume 22 is being held constant, essentially. The

### 202-234-4433 Neal R. Gross & Co., Inc. Page 270 1 subjects have been coached to look at a 2 constant minute volume. 3 Do you understand what I am 4 getting at? So, it means nothing to say the 5 frequency is increasing unless you know what 6 happens to the minute volume. 7 So, that happens at several 8 different places. And I think it is really 9 important to be able to discipline yourself 10 to, when you say this changes, but this is 11 held constant, or this has changed and the 12 subjects were at liberty to do whatever they 13 wanted with the other two, so I think that is 14 important to do. Otherwise, you get the wrong 15 idea. 16 In fact, I think the idea of 17 frequency, increases in frequency with 18 exercise, giving you more penetration of the 19 ozone into the lung, and therefore, more 20 damage to the lower airways, bias in damage, 21 do you remember that statement that is in 22 there or not? You have that statement in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 271 1 there. 2 Higher frequencies, I think you 3 actually have it in Chapter 2 also. 4 Increasing frequency because of exercise will 5 drive ozone deeper in the lung. Well, it is 6 not the frequency that really does it. It is 7 the tidal volume that is doing it. You know, 8 when you have a greater minute volume demand, 9 then you need to increase your tidal volume

10 somewhat. 11 So, I am not trying to give you a 12 lecture on dosimetry, but these are various 13 things that are kind of mixed up in the 14 chapter. 15 (Laughter.) 16 Again, I have notes on this. 17 The other thing that I wanted to 18 go onto, I think this is the last thing I 19 really had to say. I think exercise, physical 20 activity, you have a section called physical 21 activity. It is very important, obviously, to 22 the whole process of risk assessment because

### 202-234-4433 Neal R. Gross & Co., Inc. Page 272 1 it is built into the exposure modeling, and it 2 is going to be a factor in determining what 3 the risk is because many of the measurements, 4 at least the controlled human measurements, 5 are made under specific exercise conditions. 6 And we know that when you change the exercise 7 condition, that will change the response. 8 But in this chapter you say 9 nothing about how exercise affects breathing 10 pattern. So, on the one hand, you say how 11 certain factors change the dosimetry picture, 12 but you don't say how those factors change 13 during exercise. And it is not uniform. When 14 you increase exercise, frequency and tidal 15 volume don't change simultaneously. 16 If I have got it right -- and the 17 respiratory physiologists in the room will 18 straighten me out -- I think when you go from 19 low levels of exercise to moderate level, you 20 may know this, too, I am not sure. When you 21 go from low to moderate, I think the frequency 22 goes up fast.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 273 1 DR. MILLER: Only two or three 2 breaths' increase.

3 DR. ULTMAN: Pardon me? 4 DR. MILLER: Only two to three 5 breaths' increase. 6 DR. ULTMAN: The frequency 7 increases -- 8 DR. MILLER: The frequency only 9 goes up two or three. 10 DR. ULTMAN: The frequency goes up 11 first, I think.

12 DR. MILLER: Yes. 13 DR. ULTMAN: And, then, when you 14 get up to higher levels of exercise, the tidal 15 volume starts going up. 16 So, it is more complicated than 17 just saying, well, the minute volume increases 18 with exercise; therefore, you get a bigger 19 dose. Because depending on how these 20 different factors change, it will affect the 21 nature of how the dose changed. 22 So, what I am suggesting is to put

### 202-234-4433 Neal R. Gross & Co., Inc. Page 274 1 in some very short paragraph discussing the 2 relationship between breathing pattern and 3 exercise. You don't have to go through a lot 4 of detail, I mean, but just how does the 5 breathing pattern change during exercise. 6 Based on your examination of the 7 various factors, how various factors in the 8 breathing pattern affect dose, now when people 9 change exercise, how do we expect these 10 various breathing pattern changes now to 11 affect the dose? You have done a little bit 12 of that, but I think you can go beyond that. 13 And it will be helpful, I think, in the risk 14 assessment to know some of these things. 15 DR. SAMET: Okay. Mike? 16 DR. FOSTER: I just want to give 17 Jim Brown a little bit of a break here. 18 (Laughter.) 19 You know, Fred, Gary Hatch, Tim 20 Gerrity, Jim Ultman -- Jim Ultman and Tim 21 Gerrity have done all the human dosimetry data 22 with ozone. There isn't anybody else. And

### 202-234-4433 Neal R. Gross & Co., Inc. Page 275 1 that work has stopped. Okay? 2 And that work did not consider 3 gender differences in a large way or with a 4 designed experimental way, or ethnicity 5 differences. And we know now that they seem 6 to be factors playing into it. 7 In terms of the animal model 8 stuff, in terms of some of the programs you 9 were involved with, Margaret Menache, Gary 10 Hatch, it was all done, basically, with guinea 11 pigs and rats. 12 The biggest model -- and Steve, I 13 think, and Jack will confirm -- the biggest 14 model studies that have come over -- and, Jim, 15 in deference to Jim Crapo and Mercer and you, 16 Fred, those mechanistic models are 25 years 17 old. And over the last three decades, the 18 mouse model has taken over, a tremendous

19 amount of work. 20 There is not a single study done 21 on dosimetry of ozone in the mouse that I am 22 aware of. The best aerosol work was done by

### 202-234-4433 Neal R. Gross & Co., Inc. Page 276 1 Loveless 40 years ago. And you know this. 2 So, the rat models are good, yes, 3 to a certain --

4 DR. MILLER: And there's no reason 5 that Gary Hatch can't do the mouse now.

6 DR. FOSTER: Pardon? 7 DR. MILLER: I say there is no 8 reason Gary Hatch can't do the mouse now. 9 DR. FOSTER: Well, we are not 10 talking about -- 11 DR. MILLER: It goes back again to 12 my point.

13 DR. FOSTER: -- research 14 initiatives here. We are talking about 15 critiquing. 16 And I just think that it is a 17 little difficult to start saying things about 18 dosimetry when the biggest mechanistic models 19 are the mouse, and there is no data. 20 So, I think you have to take a lot 21 of things into consideration here. 22 DR. SAMET: Okay. Good. I have

### 202-234-4433 Neal R. Gross & Co., Inc. Page 277 1 enjoyed the catchup on the story here. 2 I just want to make sure -- we 3 have spent a lot of time on this chapter. I 4 think we have probably covered most of the 5 major points, unless Judy has one more. 6 DR. GRAHAM: I will be very quick. 7 Most of my comments have been voiced. 8 I will begin with the easy one. 9 On page 5-62 there is this figure of potential 10 mechanisms. I mean, in detail, I could say, 11 well, define acute versus chronic, but I guess 12 I am pretty much troubled by parts of it. 13 Even if I say that it doesn't matter that the 14 immune system is not in color, but, for 15 example, there is a dotted line between immune 16 system modulation and decreased pathogen 17 clearance and impaired host defenses. Well, 18 to me, if you have decreased pathogen 19 clearance, you are going to have impaired host 20 defense. It is a straight line. 21 So, I mean I could talk for five 22 minutes about this figure, I won't. But that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 278 1 is an indication of, I think, whenever you try 2 to do a schematic that is oversimplified, 3 somebody is going to come along and say it is 4 too oversimplified. Who would that person be? 5 The other item I have, and this is 6 where I might disagree a little bit with some 7 of my colleagues, I was quite concerned about 8 the incorporation of MOA here. And I was

9 concerned at two levels. 10 One, it was confusing. There was 11 a lot of effects there, and there has to be. 12 An MOA of what? So, you have to state an

13 effect. 14 But there were some papers there, 15 effects, that were not in the effect chapters. 16 And there were some things in the effects 17 chapters that I thought could have been over 18 here in the MOA. 19 So, this is more than just an "Oh, 20 gee, you missed a reference" thing. It was 21 interrupting the story. So, to me, the MOA 22 that should stay here is the MOA related to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 279 1 dosimetry. So, what might happen with the 2 fluid lining layers, that kind of thing would 3 be here. But when you get to MOA of pulmonary 4 function, MOA of inflammation, I think that 5 should be incorporated with the discussion of 6 that effect. And, then, that way, you would 7 have the story all in one place. 8 DR. SAMET: And I will say I think 9 this is what I was trying to touch on in my 10 comments. I think this could be a chapter 11 where you do that, but you would have to make 12 a different chapter than it is now. 13 And I think maybe Judy's point is 14 that, without some form of integration around 15 the health effects, either here or somewhere, 16 you are not serving the needs of what will 17 follow when you discuss the observational and 18 other experimental data. 19 And I think we have highlighted 20 this for you, and I think you really need to 21 think through a solution, because it will be 22 critical in laying the foundation for

### 202-234-4433 Neal R. Gross & Co., Inc. Page 280 1 interpretation of what follows. 2 Let's see, any other comments? 3 (No response.) 4 We have actually lavished an 5 extraordinary amount of time on dosimetry. I 6 think this is what happens when you put one, 7 two, three, four, five people, or something 8 like that, in the room who care about 9 dosimetry. 10 (Laughter.) 11 And I think they all have a 12 somewhat different view of the past. 13 (Laughter.) 14 But I think we certainly 15 highlighted the major issues for the chapter 16 for you, I think. 17 Is that a finger? Yes? 18 MS. WALSH: Yes, I just want to 19 point out that in the ISA, since we have been 20 evolving, we have used a mode-of-action 21 chapter somewhere towards the beginning 22 separate than the effects chapter. So, this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 281 1 is the third time I have kind of used this 2 model, and it was well-received in the last

3 two documents. 4 (Laughter.) 5 And, yes, we can reduce redundancy 6 between the effects mentioned here and the 7 effects mentioned elsewhere. Sure, that is 8 very doable. 9 But this is the model that has 10 evolved over the past couple of ISAs. 11 DR. SAMET: But the point really 12 is that you want to be able to, as you 13 interpret the evidence, be able to go very 14 clearly to where you have laid sort of the 15 biological foundation of plausibility. I 16 think right now what you have is just not 17 going to serve that purpose very conveniently. 18 I think what we are saying is think about how

19 to do that. 20 DR. GRAHAM: With plausibility in 21 one chapter and the outcome in another 22 chapter, you have to remember an awful lot.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 282 1 DR. SAMET: So, I think we 2 appreciate your dilemma. Solve it. 3 (Laughter.) 4 Anybody on the phone want to 5 weigh-in? Chris? Kathy? 6 DR. WEATHERS: No, nothing for 7 anything. 8 DR. SAMET: Okay. Okay, thanks. 9 So, what I am going to do, this 10 may not work out, but I am going to suggest 11 that we move on to the question 7, which is 12 the short-term exposure. I know that perhaps 13 this discussion could be lengthy. If it 14 becomes real lengthy, we will take a break in 15 the midst of it. 16 But why don't we get started on 17 question 7, Mike? 18 Oh, wait. Wait, wait. The lead 19 discussant, Fred, you were so eloquent that I 20 think you should be the writer here. 21 DR. MILLER: Only if everyone 22 sends me, particularly Jim his comments, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 283 1 Joe and Jack. And I will integrate them, and 2 we will get a draft out to you. 3 I think Jim, as usual, provided 4 you a way forward with his recommendation on 5 how you could restructure this, I think. 6 DR. SAMET: Okay. Thanks. 7 Mike? 8 DR. FOSTER: So, I am going to 9 just make some brief comments because I am10 sure there's a lot of people that will weigh11 in. 12 This is an immense chapter that 13 was prepared similar to Chapter 3 in terms of 14 breadth. It is 170-some pages of text, and 15 not counting 20-some pages of references. So, 16 it is just immense. 17 It covers acute chamber exposures 18 in humans, some toxicity in animal models, 19 and, then, it drifts into some epidemiology 20 studies. So, I really do not have the 21 expertise to comment, but there's plenty of 22 other people that can comment on the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 284 1 epidemiology aspect. 2 I think I would just like to 3 keynote one or two items. And that is the 4 fact that, for the plant biologists here, 5 FEV1, you have heard what that stands for is 6 the forced expired volume in one second. So, 7 that means if you inhaled as much as you 8 could, and you exhaled as hard as you could in 9 the first second, how much volume comes out, 10 with the reflection of how much you actually 11 had taken in entirely and exhaled. 12 So, that is what that FEV1 means. 13 It is a reproducible measurement. As Joe 14 alluded to, it doesn't tell you a lot about 15 where the problems are. 16 But with ozone exposure, actually, 17 the counterpart, the amount of air that you 18 can actually take in is driving the changes in 19 FEV1. That has been shown several times over. 20 So, it is not all airflow 21 obstruction for using this metric. But what 22 that metric has shown, if you look at the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 285 1 FEV1, is a dose response. Now, as Joe said 2 earlier, the elephant in the room is, where is 3 the threshold and what is the background level 4 of ozone, and that what gets added to that by 5 anthropomorphic activities? So, we are not 6 sure where exactly that threshold is. But as 7 you increase levels of ozone, FEV1 in chamber 8 studies shows decrements. 9 The other important point that 10 goes on with chamber studies is the fact that 11 you could call it a dichotomous or a binary 12 kind of response. No matter what group levels 13 you look at, there are high responders and 14 there are low responders.

15 And that could be due to a lot of 16 different factors. It could have to do with 17 diet, closeness to the highway, what your 18 grandmother may have done, what your mother 19 may have done, and where they lived. So, 20 there's lots of new activity going on trying 21 to explain why there is a binary response to

22 ozone.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 286 1 There are questions that are now 2 arising about ethnicity in terms of 3 sensitivity for that binary response. 4 So, I think I will just stop 5 there. I will just add one thing. The one 6 comment, Jim, that I had on the chapter was7 the fact about there is a well-known, well8 characterized obesity component. And that has 9 all been demonstrated in the mouse models, 10 primarily by Stephanie Shore's laboratory at

11 Harvard. 12 But all the studies in humans have 13 been retrospective analyses done either by 14 Bill Bennett or Bill McDonald on archived data 15 acquired at UNC. And I don't think the data 16 is at all strong. It is all retrospective. 17 I think there are current studies going on 18 presently. 19 So, I think, Jon, that is where I 20 would like to pull it off there. 21 DR. SAMET: Okay. Thanks, Mike. 22 Jim?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 287 1 DR. ULTMAN: Yes, I just had a 2 couple of comments. 3 First, I want to commend the 4 authors. This was a bear of a chapter to put 5 together. I can see that. There is a lot of 6 information in there. 7 And I thought the writing was 8 really good. I don't know who wrote it. Was 9 it written by more than one person? Yes, 10 well, they were good writers. I really 11 appreciated it. 12 First of all, I think a key figure 13 in this chapter is Figure 6.1, the one that 14 compares the low ozone concentration data to 15 the McDonald model. I think it is important 16 to go into more detail about the McDonald 17 model, exactly what data were used to validate 18 the model. It might even pay to put an 19 equation in there and explain. I know it is 20 a complicated equation, and it appears in the 21 exposures and the risk assessment planning

22 document.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 288 1 But I think it would pay to put 2 the equation and explain the elements in the 3 equation, so that it is clear what factors 4 affect that dose response and what data was 5 used to validate it because it is going to 6 become a key point, I think. 7 And I may be naive, but it also 8 begs the question, I think, of where there is 9 a threshold, if there is a threshold or not 10 when you look at that data. I don't know. 11 You don't discuss it all in the chapter. You 12 don't say anything about whether that plot and 13 that data somehow indicates that there is a

14 threshold. You don't conclude about that 15 anywhere in the chapter. 16 DR. BROWN: I was just going to 17 say that all I said was that there was a 18 smooth dose response curve --

19 DR. ULTMAN: Yes.

20 DR. BROWN: -- down to about 40. 21 DR. ULTMAN: Yes, right. Right. 22 Okay. I don't know if it is possible in this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 289 1 chapter to make some kind of a speculation 2 based on that data in the model. I guess the 3 model is smooth, but I don't know if you can 4 say anything about it. 5 But I do know, when we did the 6 reconsideration, there was a couple of places 7 in the documents that it said there was no 8 threshold. So, this document maybe should 9 take a look at that, and take a second one. 10 And, then, there is another issue 11 that I think is going to come out in the risk 12 assessment that I am sure we will talk about 13 later. And that has to do with the use of, 14 you know, what we use as a reference point to 15 be able to estimate risk. Because, clearly, 16 in the real world you have to use some kind of 17 a background, a real background, as a 18 reference point. You know, whatever the PRB 19 is, somehow in your risk assessment that has 20 to be used, and I think it will be used, to do 21 the risk assessment. 22 But in this laboratory data that I

### 202-234-4433 Neal R. Gross & Co., Inc. Page 290 1 am talking about, the controlled human data, 2 there is at least one place in the chapter,3 maybe more, where you talk about the ozone4 induced response, is it? Which means the 5 response of ozone pre- to post- in a chamber 6 exposure relative to the change in response 7 when breathing clean air in the chamber. So, 8 it is a double-delta. It is a delta pre- to9 post- with ozone minus the delta pre- to post10 with clean air. 11 Now the problem is with clean air 12 in many experiments, maybe most of these 13 chamber experiments, when a person is 14 exercising with clean air, with filtered air, 15 their pre- to post- values of pulmonary 16 function measurements like FEV1, they are 17 actually improved. So, instead of a decrement 18 because of exposure to clean air and exercise, 19 actually, you get an increase. So, a person's 20 function is better because of the exercise. 21 So, now when you do this 22 delta/delta, what that does is it exaggerates

### 202-234-4433 Neal R. Gross & Co., Inc. Page 291 1 the effect of ozone because you are taking a 2 decrement, and from that, you are subtracting 3 a minus decrement, essentially. So, it 4 exaggerates that effect. 5 Now in the risk assessment, that 6 will be taken care of; I realize that, because 7 the referencing will be done relative to the 8 effect of the policy-relevant background. 9 But this chapter doesn't talk 10 anything about that. You know, it points out 11 that there is this ozone-induced dose, and 12 then it goes on to quote results from13 experiments on the basis of a pre- to post14 ozone exposure dose, which is different. That 15 is clear that those are different things. 16 But you don't compare them at all. 17 I think one sentence in the chapter says 18 something about it, but I think it is such an 19 important issue. If you can spend a little 20 bit more time on it, and even stretch it to 21 putting in some information on what the effect 22 is of just breathing clean air and exercising,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 292 1 in other words, what happens in studies, 2 because the data is available. 3 And I think it is important to 4 know what the magnitude, to kind of get an 5 idea what is the magnitude of that beneficial 6 effect of exercise, if you will, and breathing 7 clean air, what is the magnitude of that 8 relative to being exposed to a small level of 9 ozone which creates a decrement that kind of 10 offsets that. How big are the relative sizes

11 of those two effects? 12 So, again, this is not to direct 13 you to draw any conclusions, because I think 14 that is going to be done in a risk assessment 15 in terms of how important these effects are 16 and how they impinge, you know, correcting

17 them to be able to calculate. 18 But I think in the chapter you 19 need to lay the groundwork by having some of 20 the information there, so people understand 21 when you read the risk assessment document why 22 they did what they did.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 293 1 That's it. 2 DR. SAMET: Okay. Thank you.

3 John? 4 DR. BAILAR: I have three points

5 to add. 6 First, and most important, it 7 appears to me that the evidence for mortality 8 as a result of short-term exposure to ozone is 9 stronger than likely. It is compelling. 10 I am not trying to separate the11 effects of mortality displacement from longer12 term effects. I am not trying to separate PRB 13 from anthropogenic sources. But, overall, I 14 find it hard to escape the conclusion that 15 short-term ozone exposure is sometimes lethal. 16 This view of mortality is guided 17 by two broad principles. First, there can be 18 no heterogeneity in effects, whether it is 19 interreaction, synergy, effect modification, 20 what have you. There can't be heterogeneity 21 unless there is something to be heterogenous. 22 There has to be some kind of an effect to be

### 202-234-4433 Neal R. Gross & Co., Inc. Page 294 1 altered in at least some subset of the study 2 population. 3 And the second pillar of this 4 conclusion is that any mortality effect cannot 5 be zero overall if there is an effect for some 6 cause, however minor, or for some set of the 7 population, however small, unless there is a 8 compensating effect in the other direction for

9 some other cause of death. And I have not 10 seen any evidence here suggesting that ozone 11 exposure is protective against any lethal 12 disease. 13 These principles hold even if 14 overall mortality cannot be shown to be 15 elevated, cannot be shown directly to be 16 elevated. An effect can be real, but too 17 small or too complicated to be evident in 18 overall mortality or even in broad categories

19 of causes of death. 20 It may be that EPA is really 21 asking whether the all-cause mortality data 22 alone show an effect, rather than whether a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 295 1 broader view shows an effect. I agree that a 2 narrow view of all-cause data supports that 3 phrase "likely to be", but the broader view

4 seems to me to leave no room for doubt. 5 My second point, briefly, is that 6 the epidemiologic findings of increased 7 overall mortality are quite remarkably 8 consistent in direction, though not in size, 9 consistent over space, time, and a wide range 10 of circumstances and study types, despite a 11 few exceptions for single cities or other 12 subgroups. And I think that this might be 13 made a stronger point in this chapter. 14 Third, I would like to see a table 15 showing, for each of the short-term mortality 16 studies considered, the crude effect and the 17 effect after adjustment for PM and any other 18 factors in the reported study. 19 In my experience, when adjustment 20 for confounders reduces a crude estimate of an 21 effect by a substantial amount, more and 22 better information about confounders, et

### 202-234-4433 Neal R. Gross & Co., Inc. Page 296 1 cetera, including additional items, is likely 2 to lead to a further reduction, possibly down 3 to zero. If the initial adjustment has little 4 effect, using more items and better data is 5 not likely to have much effect. 6 The limited information on this in 7 the present report suggests that co-pollutants 8 and other confounders do account for some, but 9 not all, of the relation to ozone measures in 10 the crude measures of mortality, but I would 11 like to see this laid out in a table.

12 That's all. 13 DR. GRAHAM: Okay, I have a couple 14 of major comments with regard to this chapter. 15 First of all, I only skimmed the 16 epi part. So, I kind of took it on faith the 17 epi was correct, and I figured that you guys 18 would take care of it, so we could all stand 19 in a circle and point. 20 (Laughter.) 21 So, I think that, with that 22 caveat, I think the causation statements are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 297 1 very well supported scientifically. I think 2 that many of them have been well-established 3 for many years. 4 But this answer leads to key 5 questions, and especially for susceptibles 6 that require more attention in the text; 7 namely, what exposures are sufficient to cause 8 the effects of interest and what is the 9 severity of the effects at these effective 10 exposures? 11 Now I am sure, like I say, 12 somebody could point, well, this line and that 13 line, but you have to hunt and you get so 14 buried; it is very hard to figure it out. 15 I think the epi studies are easier 16 to interpret because a hospital admission is 17 a lot clearer in terms of severity than is a 18 morphological change in a rat or a small 19 change in FEV1 in humans. 20 I would say another point here, 21 with rare exception of some of the epi tables, 22 the tables are wholly inadequate. And there

### 202-234-4433 Neal R. Gross & Co., Inc. Page 298 1 is a reason for this. They don't exist. 2 If you go and look at this, the 3 data presented very unevenly. Like some of 4 the summaries of the old human data, it says 5 this and that happened. It doesn't tell you 6 what concentration, what duration, and whether 7 there was exercise. Even with some of the 8 more recent studies that are described, you 9 don't know what the exercise level was. 10 For some of the animal studies -- 11 this is an acute session -- some of them are 12 90 days. And, then, you go over to the 13 chronic chapter, some of those are 90 days. 14 I mean you could make a decision one way or 15 the other, but in some cases you don't know 16 how long the animals were exposed, whether it 17 was one day or one week. For some studies you

18 do know. 19 So, there is no consistency of 20 presenting this information that is definitive 21 in terms of how should you even interpret it. 22 With a lot of human clinical studies, it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 299 1 doesn't even indicate whether they had 2 exercised, much less to say whether it was 3 light, moderate, or heavy. 4 There is an answer to this, and 5 the answer is tables. And in my 6 recommendation, probably one of my strongest 7 recommendations would be to go back to your 8 old tables in the 1996 document and in the 9 2006 document. And the reason I say that is 10 because for some of these things I went 11 hunting and there were actually references 12 missing, important references in my view, from 13 the 2006 document that were in the 1996

14 document. 15 So, I think if you kind of like 16 had word processing people pull those tables 17 together, and then add the new studies, you 18 would have everything in one place. You 19 wouldn't need to put all these details in the 20 text. You could use words like one-day 21 exposure, acute. You could use little 22 subterfuges like that because a person could

### 202-234-4433 Neal R. Gross & Co., Inc. Page 300 1 go look at the study. 2 Sample sizes used in the human 3 clinical studies, these things become 4 important. And actually, the only way you can 5 find them is to look in the old documents. 6 Another point here, there is an 7 artificial separation between the old and the 8 new studies and the MOA and effects. These 9 two major artificial separations lead to a 10 choppy presentation and weak integration. 11 I think it really concerns me 12 because we are basing the standard on health 13 risks, not on health risks that were 14 discovered since 2006. And to simply have two 15 paragraphs from 1970 to 2006, and then have 10 16 pages on something later, you don't get a gist 17 of it. 18 So, I think that each document 19 needs to be standalone. But it doesn't get 20 standalone simply by getting taller and 21 taller. That is why I think the tables can be 22 a good way to manage all the data.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 301 1 So, you could put, let's say, five 2 animal studies looking at lung remodeling. 3 Fine. Talk about one of them in general, but 4 say, "Go look at the table for the five 5 studies." So, there's ways to do this without 6 artificially separating it. 7 And now my personal favorite about 8 the artificiality of this is Bob Devlin's 9 study, humans exposed to ozone, and he looked 10 at alveolar macrophage function. You've got 11 like one line, two lines. You didn't know 12 what the concentration was, didn't know the 13 exercise, but, boy, there's three or four 14 lines there about effects of ozone on alveolar 15 macrophages in marine toads. Okay? That is 16 my favorite. 17 I'm sorry. I couldn't help it. 18 (Laughter.) 19 Then, as another main point, the 20 animal toxicological studies on respiratory 21 and morphological morphometric changes are not 22 adequately discussed. And I mean that is the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 302 1 polite way in writing. It is like it is 2 pitiful how little discussion there is on

3 them. 4 When they are mentioned, the 5 discussion is buried, too brief, does not 6 allude to supporting evidence, and does not 7 discuss implications to severity effects in

8 humans.

9 There's dozens of references to 10 effects below .5 ppm down to .15 and .2 ppm in 11 non-human primates that are not included. I 12 mean this is all pretty relevant stuff, and it 13 contributes to the story of what might be 14 happening. 15 I mean inflammation has a whole 16 story to it, not just what is discoverable in 17 humans. I mean here in the animal studies 18 inflammation has been more linked to parallel 19 sorts or even consequential sorts of 20 morphological changes. 21 And I think this whole story of 22 lung structural changes is important in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 303 1 understanding severity in humans. So, it 2 contributes a lot. 3 And, then, I think I will just 4 pick one or more. Okay, on page 67, there is 5 a discussion of the Slagle studies, the 2009 6 study. That is the human clinical study that 7 goes down to 60 ppb. So, it is really 8 important. 9 And it says that there are no 10 statistically-significant group effects. But 11 I have a question here. Did EPA evaluate the 12 quality of the statistics in this paper? Did 13 the study have adequate power to detect 14 effects? What exercise levels were involved? 15 And so, this is an indication 16 that, to me, it is a pretty doggone big deal 17 about a study at 60 ppb. Like I think another 18 three or four sentences would have helped the 19 reader say, "Wow, this is important" or "Who

20 cares?" 21 I have a question about the 22 Slagley 2009 paper and the Adams 1998 data.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 304 1 It says that the data are unavailable to EPA, 2 and they provide the reason for the Adams 1998 3 data being unavailable. And apparently, Adams 4 published some of that 1998 data in a 5 subsequent paper which was available. But it 6 doesn't talk about the reason for the Slagley 7 studies not being available to EPA. 8 And this is just something -- food 9 for thought. How does this jive with the 10 Information Quality Act if the data are not 11 available? 12 Oh, yes. Okay, I do have to say 13 one thing about missing references. The text 14 says in one line about the animal studies,

15 "Levels as low as .08 have caused effects on 16 infectivity." There's not even a reference

17 there. 18 Some of this is close to heart 19 because the man that hired me into EPA, his 20 name was Dave Coffin, and he did those studies 21 way back when. And those mouse infectivity 22 studies were they found effects at .8 ppm. A

### 202-234-4433 Neal R. Gross & Co., Inc. Page 305 1 fellow by the name of Fred Miller replicated 2 that work several years later. So, this is 3 pretty low stuff. 4 That paper, that original paper, 5 is what was the basis for the very first ozone 6 standard at .08 ppm oxidants. So, here's this 7 whole rich literature that even drove a 8 standard, and the reference isn't even here. 9 That is just an example of how the older data 10 is getting dismissed, even though it has

11 values. 12 I have here, too, on page 6-134, 13 this is the CNS effects. It says there is a 14 paragraph summarized in the 2006 air quality 15 criteria document; it is totally insufficient. 16 And it talks about epi effects with no 17 significant details, calling it adverse. The 18 rodent studies are described in two sentences 19 with no indication of species, concentration, 20 duration, specific endpoints. And so, you 21 can't get a feel of it. 22 In some cases, here is new work.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 306 1 There is a section, potential relationships 2 between relevant ozone exposure of rats and 3 Alzheimer's. That is a pretty big stretch. 4 So, when that kind of an association is going 5 to be made, particularly for rats, I think it 6 is deserving of more rationale, more intense

7 effort. 8 So, with that, I do have to say 9 that, having written the animal tox chapters 10 in a lot of the early documents, I do feel 11 your pain. It may not sound like it, but I

12 do. 13 DR. SAMET: So, one comment I 14 think, there is a patchiness that I think has 15 been described already in the comments in the 16 way you provide at least figures for the 17 epidemiological studies and text descriptions 18 that are sometimes lengthy, but still 19 inadequate for the toxicology studies. 20 And I think what you heard, in 21 part, is that those people who understand that 22 literature can't find what they need in the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 307 1 text descriptions to interpret it. There 2 probably should be supporting tables. I mean 3 a lot of the stuff around page 130-131 is 4 illustrative of the kinds of things that I 5 think you should avoid doing, you know, the 6 paragraphs that start with so-and-so, and the 7 next one is so-and-so. It is just really not 8 helpful. 9 And what you need is a template 10 for capturing what the experimental design was 11 and what the concentrations were at which the 12 experiment was done, and what the outcomes 13 were that were looked at. I think that would 14 solve a lot of this and shorten the document, 15 which becomes, I think, very difficult to

16 follow. 17 Mike? 18 DR. FOSTER: I just don't want to 19 belabor the point, but the people that are 20 doing the chamber studies fully read this 21 document and can understand this document. 22 Okay? So, there is not a great deal of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 308 1 emphasis that has been placed on the exposure 2 or concentration during the exposures. That 3 is another question that has come up, whether4 you should use a gradually5 increasing/decreasing, like a triangular, or 6 a wave form, a straight wave form. So, there 7 are questions that have some relevance to what 8 is going on ambiently. 9 In addition to that, many of the 10 studies have, if you don't do exercise, Fred, 11 you have to go up above 500 ppb to get a 12 response. Okay? So, then, the idea is to 13 assimilate someone in the ambient conditions 14 with light activity or, then, to err on the 15 side of safety, they really ramp up, and some 16 of the California studies that Ed Slagle has

17 done and the Adams lab. 18 But the other point that comes 19 into play that maybe John will comment on is 20 that many of the studies will scale that mV 21 level to a body surface area. But there's 22 ethnicity differences on body surface area,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 309 1 and you would be better off scaling to just 2 height or just the lung volumes because you 3 are going to overdose, say, for example, 4 African-Americans compared to a Caucasian 5 because of body surface area. 6 They are all things that are being 7 tweaked out now. So, I think that the 8 document and Figure 6.1 and 6.2, they are 9 making an effort to translate the information 10 that, one, there is some threshold slightly 11 above whatever it is, ozone above, slightly 12 above whatever ambient is. 13 And, then, two is the fact of this 14 dichotomy of response, which I wish Steve 15 would jump in because maybe it is going to 16 come in later, and it is in later chapters, 17 but there's definitely host factors that come 18 into play. 19 So, that's all. 20 DR. KLEEBERGER: Actually, could I 21 just make a quick point? 22 I didn't read this chapter real

### 202-234-4433 Neal R. Gross & Co., Inc. Page 310 1 carefully, but -- 2 DR. FOSTER: I can't blame you. 3 (Laughter.) 4 DR. KLEEBERGER: But I did notice 5 that there is appropriate sort of emphasis on 6 interindividual variation in responses. But 7 most of these, as you point out, are FEV1 8 sorts of measurements or metric measures, 9 because they are reproducible, they are easy.

10 And I seem to recall that there 11 were other studies that had looked at lavaged 12 PMNs and also found that there are individual 13 variations and responses -- 14 DR. FOSTER: John Balmes did -- 15 DR. KLEEBERGER: Balmes did it. 16 Slagle did it. I think Al Koren had done some 17 studies. 18 DR. FOSTER: The problem is they 19 are terrifically underpowered. 20 DR. KLEEBERGER: Well, they are, 21 but, still, if you look at the points, and if 22 you plot them -- you can sometimes take these

### 202-234-4433 Neal R. Gross & Co., Inc. Page 311 1 data out of the tables and plot them yourself 2 -- I mean there is a very wide dichotomy 3 between those responders and non-responders. 4 And at least some mention ought to 5 be made that it is not just FEV1, but there 6 are also other factors that are important.

7 DR. SAMET: Fred? 8 DR. MILLER: First of all, you're 9 right, but, also, the Kim study is not 10 underpowered and they did show effects on the 11 PMNs. They had an "N" of 59, more than 12 adequate for the statistical power. 13 But, Mike, I hear what you are 14 saying, but this document is supposed to be 15 able to be read by individuals that aren't 16 total experts in their own field. And that is 17 what I think ends up being missing by not 18 being able to tell the whole story. 19 You know the literature. You can 20 fill in, and you automatically fill it in. 21 But that is not the case for everyone who 22 would read this, and there is a certain level,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 312 1 I think, of expectation as to a reasonable 2 intellect, that you can then follow 3 everything. And right now, I think the 4 commenters are saying some of that is just 5 missing. 6 DR. SAMET: Let's see, who else 7 would like to comment here? Yes? Ed? And, 8 then, George. 9 MR. AVOL: Okay, not on this 10 point? 11 DR. SAMET: Not on this point. 12 Any other point. 13 (Laughter.) 14 MR. AVOL: It is a new point.

15 DR. SAMET: What? 16 MR. AVOL: It is a new point. 17 DR. SAMET: A new point. 18 MR. AVOL: A new point. So, I 19 have a comment on a section here that sort of 20 re-stirs a decades-old discussion, sort of 21 like the Hatfields and McCoys.

22 And I am not sure whether I am a

### 202-234-4433 Neal R. Gross & Co., Inc. Page 313 1 Hatfield or a McCoy, but I know I don't like 2 the word "adaptation". This issue of 3 discussing repeated exposures and the blunting 4 of the response, the development of 5 toleration, describe it any way you will, but 6 I don't believe it is adaptation. 7 And when this was first reported 8 in chamber work, now 25-30 years ago, there 9 was a discussion about this. I think while it 10 may not have been agreed upon, there was 11 certainly strong discussion about it not being 12 adaptation. 13 DR. SAMET: So, what would you 14 suggest, that there should be a more broader 15 discussion of the phenomenon and its potential 16 implications, and adaptation is too strong a 17 term, I think, from your point of view?

18 MR. AVOL: Yes. 19 DR. MILLER: Yes, and it is also 20 used interchangeably. To me, the functional 21 changes and their decline in decrement, it is 22 attenuation. Attenuation, adaptation, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 314 1 tolerance, they are all kind of used 2 interchangeably at different times by 3 different people. And so, it ends up being 4 very sloppy and misleading. 5 DR. SAMET: Point taken.

6 Howard 7 DR. NEUFELD: I was just going to 8 say, in the ecological literature, I mean we 9 reserve adaptation for an evolutionary change. 10 (Laughter.) 11 And for a physiological change, we 12 use adjustment. 13 MR. AVOL: This is a side issue, 14 but this is a temporary physiological change. 15 Because if you come back to these same people 16 next spring, and you get a similar response, 17 they start from zero again. 18 DR. SAMET: And certainly, 19 whatever you do, it should be done the same 20 throughout the document, which I think was the 21 point. 22 George?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 315 1 MR. ALLEN: I guess it is a 2 question for EPA. On page 6-8, where it 3 summarizes the 60 ppb chamber studies, it says 4 on line six, so it is line six, page 6-8,5 "Although not found to be statistically6 significant in the original studies, they 7 group mean changes in FEV1 at 60 ppb are 8 consistent." But the Kim study, 2011, did 9 find FEV1 to be significant. 10 So, does that need correction or

11 am I confused? 12 In fact, just reading from it, 13 FEV1 change was 1.71 plus or minus .5 percent, 14 mean plus or minus SEM. 15 So, does that need to be --

16 DR. BROWN: It needs to be 17 corrected after adding the Kim study to it. 18 This was written before the Kim study came

19 out. 20 MR. ALLEN: Well, no, the 21 reference is the Kim study. 22 DR. BROWN: No, but Kim was added

### 202-234-4433 Neal R. Gross & Co., Inc. Page 316 1 to the prior --

2 MR. ALLEN: And the text wasn't

3 corrected? 4 DR. BROWN: Yes. So, some of the 5 text is still -- 6 MR. ALLEN: Oh, okay. Okay. It

7 needs another rev.?

8 DR. BROWN: Yes. 9 MR. ALLEN: Okay. Thanks. 10 DR. SAMET: Let me check. Chris, 11 Kathy, Sverre, if you are there, any 12 questions, comments?

13 DR. WEATHERS: It's me. 14 DR. SAMET: Anything? No? 15 (No response.) 16 Let's see, any other comments on 17 the short-term chapter? 18 (No response.) 19 It's interesting, we spent half 20 the time on this one as on the dosimetry. 21 Maybe that's it. 22 DR. MILLER: I didn't read this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 317 1 chapter carefully. 2 (Laughter.) 3 I don't think I read it at all. 4 (Laughter.) 5 DR. SAMET: George? 6 MR. ALLEN: Actually, Jim and I 7 talked about this over lunch. And my take, 8 and he seemed to like it, was that all these 9 chamber studies, whatever effect estimate you 10 come up with, are probably low-end bounds for 11 the real-world effects because, first of all, 12 they are using fairly healthy subjects. 13 Second of all, you are using just 14 ozone as opposed to the overall photo-oxidant 15 mix that is out there with ozone as an 16 indicator. So, your actual exposure metric is 17 different, and a few other things. And they 18 all kind of push these to be a lower bound of 19 effect estimates, and that, I think, is worth 20 keeping in mind when you integrate the chamber 21 work with the epi. 22 DR. SAMET: Okay. Yes?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 318 1 DR. FOSTER: So, chamber studies 2 have involved chronic obstructive pulmonary 3 disease patients, asthma patients, the 4 elderly, children, and normals. 5 So, you know, the dichotomy is 6 covered. It is just a matter that a lot of 7 them are underpowered, but certainly the 8 trends are there to be able to guide in terms 9 of how this correlates to ambient exposures in 10 the kid studies and the camp studies, and so

11 forth. 12 DR. SAMET: Okay. Let's take the 13 break and come back at 3:20, and, then, we 14 will go to the long-term. 15 (Whereupon, the foregoing matter 16 went off the record at 3:09 p.m. and resumed 17 at 3:25 p.m.) 18 DR. SAMET: Okay. So, we are 19 going to move on to the health effects of 20 long-term exposure. And let's see, Michelle, 21 you are leading off. 22 And, actually, Mike, I don't think

### 202-234-4433 Neal R. Gross & Co., Inc. Page 319 1 we designated you. You thought you were going 2 to get away. Yes, well, you've got this one. 3 So, you can take on the synthesis. 4 Michelle? 5 DR. BELL: Okay. For this 6 chapter, I will just start by saying, overall, 7 not even overall, I agree with EPA's 8 assessments on the degree of the evidence in 9 terms of causality -- 10 DR. SAMET: Can you get closer to 11 the microphone? We can't hear you.

12 DR. BELL: Is that better?

13 DR. SAMET: Yes. 14 DR. BELL: Thank you. 15 So, I was saying that I agree with 16 EPA's assessment on the degree of evidence for 17 causality for the different causes. I do have 18 a lot of comments, and I am just going to go 19 over the big-picture comments here, and the 20 more detailed ones you will see in my notes. 21 I do think there is a lot of 22 things that can be done to this chapter to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 320 1 improve it in terms of presentation and to 2 help people read it and interpret it 3 correctly. But I don't think these are things 4 that would change the conclusion for the 5 causality. So, I think EPA did a very good 6 job for that. 7 One thing I think that could help 8 the interpretation of causality for this 9 chapter, or actually for the whole document, 10 is to talk about what type of evidence would 11 be needed for you to have a more conclusive 12 picture for causality. And I am not talking 13 about writing out what research needs are. 14 But, for example, reading through 15 this, for the topics I am very familiar with, 16 I can know in my head like, well, you know, 17 for more causality evidence, we really would 18 like to see a different study design or a 19 study with more sample size or something else 20 of that nature. But if I didn't already know 21 that, I wouldn't know from this document. 22 So, if there is a way to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 321 1 incorporate that, just so people know exactly 2 where your causality evidence is coming from 3 for why you choose suggestive versus likely, 4 and so on, I think that could be stated 5 explicitly without making it the research 6 needs documents. And I agree with Jon's 7 earlier comment that this document is not the 8 best place to put that. 9 I actually think that the 10 causality in the long-term exposure chapter 11 could borrow more heavily on the short-term 12 exposure. I think you almost sold yourself

13 short on that. 14 So, just to give an example, for 15 the short-term health effects for respiratory 16 endpoints, you have a lot of information in 17 the previous chapter, looking at a wide range 18 of respiratory endpoints. And even though now 19 we are talking about a different timeframe of 20 exposure, I think it is very compelling 21 towards some evidence of causality, that you 22 have effects for short-term respiratory

### 202-234-4433 Neal R. Gross & Co., Inc. Page 322 1 outcomes, for example, and then you have 2 effects for long-term respiratory outcomes. 3 So, I know that in itself would not be 4 causality, but I think that is a piece of 5 evidence that is left out of this document 6 that could be included in terms of looking at 7 the long-term exposure, borrowing from where8 you found similar health endpoints for short9 term exposure. 10 I think the biggest problem in 11 this chapter that can be fixed is, what 12 exactly do we mean by long-term exposure? And 13 so, this is partly just a language issue. So, 14 there were times where, if I didn't already 15 know the study, I would have no idea what the 16 exposure metric was. Like, was it a few 17 months? Was it a few years? Was it two 18 weeks? And I think it would actually be 19 useful maybe even to lay out at the beginning 20 of the chapter what do you mean by long-term 21 exposure. 22 I think that, whenever a study is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 323 1 mentioned, in all of the tables that it should 2 say what the exposure timeframe is. Like is 3 three months, this was a trimester, and so on. 4 And some of the tables do that very nicely, 5 and some of the tables and figures don't list 6 the exposure timeframe at all. So, I think it 7 needs to be listed. 8 This chapter has a huge range of 9 what is meant by long-term exposure. It is 10 probably too big a range because there are 11 actually studies in the long-term exposure 12 chapter that range from exposure metrics of 13 like a 10-year average to a single-day 14 exposure. And I don't know what framework a 15 single-day exposure counts as long-term 16 exposure. So, that is a huge problem. 17 And what I suspect happened is 18 that a decision was made to keep the birth 19 outcomes work together. Is that what 20 happened? I see some nods. 21 I could kind of figure that out, 22 that that was what was happening. For me, it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 324 1 didn't work because you have like the same 2 health endpoint. Like take respiratory 3 mortality, and you will put the short-term 4 studies in the short-term chapter and the 5 long-term studies in the long-term chapter. 6 So, there you have chosen to cluster the 7 studies based on the timeframe of the exposure 8 metric, but for birth outcomes you have chosen 9 to cluster it based on the health endpoint. 10 So, I think you have options of 11 either making birth outcomes its own section, 12 if you think it is really critical to keep 13 those together, or splitting them out to be 14 consistent with what you have done previously. 15 I mean, really, I think it was extra-confusing 16 given that there is so much lack of 17 specification of what you mean by long-term 18 exposure. 19 The evidence is probably weakest 20 for long-term exposure to ozone in mortality, 21 although I do agree with EPA's conclusion that 22 there is suggestive evidence. But given that

### 202-234-4433 Neal R. Gross & Co., Inc. Page 325 1 this evidence is not quite as strong as some 2 of the others, and you are really relying 3 incredibly heavily on one single study, on the 4 Jarrett study, so I would have liked to have 5 seen more information on those studies, on 6 what they did, what was good about them, and 7 what some of the limitations were.8 So, for example, you have a long9 term exposure study where we only know where 10 the person was in enrollment. You don't 11 actually know where they were throughout these 12 many years. So, it is a little potentially 13 misleading to say we had ozone followup for 14 several years of these people. You really 15 didn't. They are just assuming a low level of 16 residential mobility. 17 And the authors do explicitly 18 state this in their Journal article. So, you 19 could even borrow that example and make sure 20 it comes in here. But I think, in general, I 21 would like to see more information on that, 22 just because it is so heavily based on one

### 202-234-4433 Neal R. Gross & Co., Inc. Page 326 1 study, even though I do agree with the overall 2 conclusion. 3 And just one last point, there are 4 a lot of examples in here, and I will have 5 some specifics in my written notes and I can 6 add some more, but a lot of examples of 7 wording that is going to be quite misleading 8 to people. My read of this is that it was not 9 a misunderstanding of the study, but it was 10 just poor wording choices by the EPA staff 11 that wrote it. So, I will just give two 12 examples that I think make this point. 13 One is when you talk about the 14 seasonal studies. And here, the seasonal 15 studies in this chapter are referring to 16 exposure over a few months. So like, what is 17 my exposure over the summer and how does that 18 affect my health risk? Whereas, when I see 19 seasonal study, I immediately think of the 20 short-term studies that like only looked at 21 what is your present-day ozone exposures 22 association with mortality risk just in the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 327 1 summer, for example. 2 So, language like seasonal studies 3 is going to be a problem. And you can fix 4 this by going through the whole document and 5 putting in those specific exposure metrics 6 everywhere. 7 And there is just one more example 8 that I will bring up that, again, I think is 9 a not a misunderstanding of the study, but, 10 rather, it is just a poor wording choice. So, 11 I will just read this sentence. 12 "A 10-ppb increment and exposure 13 to ozone elevated the risk of death from 14 respiratory causes," and so on. That 15 sentence, it's not wrong, but it is not what 16 happened. There is nothing magical about 10 17 ppb. And this type of language, in fact, a 18 version of this sentence shows up over and 19 over. So, there is nothing magical about 10 20 ppb. That is just the increment the authors 21 used to express their results. 22 What they found is that higher

### 202-234-4433 Neal R. Gross & Co., Inc. Page 328 1 levels of ozone are associated with higher 2 risk. So, you can keep 10 ppb and put in the 3 central estimate, so that it makes sense, or 4 you can take out 10 ppb, but, I mean, it could 5 have been 9, it could have been 5, it could

6 have been 17. 7 And so, that is the type of 8 language that I think, if you already 9 understand the literature, you know what is 10 meant. But if you don't, it is going to be 11 incredibly confusing. 12 So, I would suggest to take a step 13 back from this chapter, and in terms of the 14 wording, just to go through it and make sure 15 all of it is going to be clear and accurate, 16 because there is really no reason we can't fix 17 those types of things in this document. 18 Those are my main big-picture

19 comments. 20 DR. SAMET: Okay. Thanks.

21 John? 22 DR. BAILAR: I think, overall,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 329 1 this is quite a strong start. And I don't

2 have much to add to the draft and to what 3 Michelle has already said. 4 I would like to underline the fact 5 that short-term data and long-term data can 6 really reinforce each other. And I would be 7 glad to have a very short section, maybe just 8 a couple of paragraphs, that bring them 9 together. 10 I understand the reasons, and 11 agree with the reasons, for keeping them 12 separate in the initial analysis, but I think 13 at some point they should be integrated in a 14 way I have seen here. 15 Just a few other things. I would 16 like to see a short discussion of why current 17 findings differ from those in the previous 18 review. Are the prior results fully 19 consistent with current results, given the 20 differences in study methods, precision, and 21 so forth? Again, I think that could be dealt 22 with very briefly.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 330 1 Asthma is a lethal disease. Death 2 from asthma is sufficiently uncommon that it 3 might not show up in studies of total 4 respiratory mortality. If the relative risk 5 is high, a relation to ozone might be evident 6 in a mortality analysis focused on asthma, and 7 I don't know whether this has been done. If 8 not, that might be worth a comment.

9 I understand the effect on 10 mortality of adding PM to the ozone model, but 11 what about the reverse? I would like to see 12 side by side the effects of PM alone, of ozone 13 alone, and their separate effects when both 14 are in the model. That is the only way that 15 I could understand whether the apparent effect 16 of either one is in part or totally a result 17 of their co-occurrence. 18 Overall, I concur with the ISA 19 that there is likely to be a causal 20 relationship between long-term exposure to 21 ozone and respiratory morbidity. I might even 22 make a statement a bit stronger. The evidence

### 202-234-4433 Neal R. Gross & Co., Inc. Page 331 1 is really pretty persuasive, though not as 2 strong as for short-term effects. This 3 conclusion, my conclusion here, is based 4 primarily on the epidemiologic evidence, but 5 seems to be fully supported by toxicological 6 and human experimental findings.

7 That's all. 8 DR. SAMET: Okay. Thank you. 9 Judy? 10 DR. GRAHAM: With the caveat 11 offered before, I really just scanned the epi 12 studies. So, having said that, a fair amount 13 of this work here is supported by the animal 14 studies. And so, based upon that, I support 15 the causality conclusions. The problem is I 16 support the causality conclusions based upon 17 what I know, not what I read. 18 I would say that, more so than the 19 acute chapter, there are distractions in here 20 and missing references. For example, on page 21 7-14, the evidence from toxicological studies, 22 the first paragraph, for all practical

### 202-234-4433 Neal R. Gross & Co., Inc. Page 332 1 purposes, dismisses animal studies, in 2 particular, basically, the rats, who cares? 3 Really it is, I mean I will use the word 4 egregious in terms of how these animal studies 5 are totally dismissed. And even the Plopper 6 studies in monkeys are just all truncated. 7 So, here's like six or seven lines of 8 references to the Plopper studies, and some of 9 them that are teased out without quite knowing 10 what -- you can't get shape to it. 11 One of the important things, and I 12 think Michelle or maybe you, John, talked 13 about getting a sense of the acute and chronic 14 timeline. There are actually some excellent 15 figures in the last document that show like 16 the time course of events, how the 17 inflammation comes and wanes and then 18 interstitial changes increase. You get more 19 fibroblasts. You get fibrotic-like changes. 20 When I was done reading this, I 21 did my little search thing. And the only 22 place in this whole chapter that I found the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 333 1 word fibrosis, and I looked for F-I-B-R-O in 2 case it was fibroblast or something, fibrotic 3 changes were mentioned only in the summary, 4 one line where it was cross-referencing the

5 2006 document. 6 Now these interstitial changes, 7 fibrotic-like changes, I think that a 8 pathologist would probably call them mild, but 9 it is not even mentioned. I mean these are 10 significant effects that have implications to 11 severity of effects, and they are just not 12 brought out. 13 I think, in particular, like 14 there's three major studies of seasonal 15 effects, but only once referenced. There are 16 several studies on age, but only a couple of 17 them are mentioned. And in my writeup here I 18 mentioned some specifically. 19 For example, .12 ppm in rats for 20 six weeks; .12 ppm, that is not that high, 21 give the dosimetric comparisons. And guess 22 what? You can actually do dosimetric

### 202-234-4433 Neal R. Gross & Co., Inc. Page 334 1 comparisons from this study. It wasn't done.2 They compared morphometry of one3 day-old rats and six-week-old rats at the 4 beginning of the study. There were some age 5 effects. You wouldn't know it from reading

6 here. 7 The effects on children, we call 8 children a major susceptibility group that we 9 are concerned about, but here are these age 10 studies that aren't even here. 11 Chang, et al., they had a couple 12 of chronic studies. They had a baseline of 13 .06 ppm on which was superimposed a spike to 14 .25 ppm. At the time it was done to model an 15 urban pattern, and they were looking for 16 chronic effects. And the lungs were examined. 17 It was James Crapo's lab that did it. So, 18 they had all this very sophisticated 19 morphometry even after exposure ceased. And 20 guess what? Some of the changes were 21 irreversible. 22 So, there's some of these

### 202-234-4433 Neal R. Gross & Co., Inc. Page 335 1 important sorts of concepts that have a great 2 bearing on severity of effects and 3 understanding some of the things that may be 4 happening in the epidemiology, some 5 feasibility sorts of things. The papers

6 aren't even here. 7 I won't repeat in any detail what 8 I have said, but show me the tables. I mean 9 there is just so much overwealth of stuff that 10 could be handled in the tables, and you can 11 pick one or two studies for like a full 12 paragraph and say, hey, there's five of these 13 studies; go look at the table. 14 The separation between the old and 15 the new literature is the same problems that 16 I have in the other chapters I have in this 17 chapter, too. I won't repeat that. 18 The only additional thing I might 19 have to mention here is the whole section on 20 repro developmental effects. I have some 21 detailed sorts of comments. 22 But in the big picture, and you

### 202-234-4433 Neal R. Gross & Co., Inc. Page 336 1 don't need to answer this here, I hope that 2 either you have had or will have an 3 epidemiologist who does reproductive 4 developmental stuff. I mean like some of the 5 NICHD epidemiologists. I am not expert in 6 that area, but some of these writeups just 7 kind of worried me. So, that is my only

8 comment. 9 DR. SAMET: Okay. Thank you.

10 Others? Fred? 11 DR. MILLER: I want to follow up 12 on the last sentence on page 7-62 about that, 13 collectively, the evidence is suggestive of a 14 causal relationship between long-term ozone 15 exposure and all-cause mortality. And I will 16 follow it up with what was an earlier comment

17 here. 18 I have a problem with that 19 conclusion when you really have only the 20 Jarrett study, and you look in that table, and 21 any cause, it is statistically not significant 22 because the relative risk, where the ozone 96

### 202-234-4433 Neal R. Gross & Co., Inc. Page 337 1 MSA contains one, when you add in PM, it is 2 statistically-significantly protective. Give

3 me a break. 4 These data in this chapter, 5 collectively, relative to the mortality, in 6 the birth weights, for example, this study 7 showed 1.4 ounces change. This study did not 8 show that. And, then, for them to come down 9 to this kind of a statement of causality with 10 mortality is, to me, it is before primetime. 11 It is not ready. I don't see it when I look 12 at the statistics. 13 And you are talking here about 14 confidence limit, 1.003 to 1.026. And when 15 they flip, and as Dr. Bailar pointed out, when 16 you add in other pollutants and you get a 17 shifting, you know, that is a question of a 18 concern about, if you could look at other 19 things, would the effect go away? Well, here 20 you had it statistically shift for all causes 21 to be protective. And, then, your conclusion 22 is that it is suggestive of a causal

### 202-234-4433 Neal R. Gross & Co., Inc. Page 338 1 relationship between long-term ozone exposure 2 and all-cause mortality. It is a non sequitur 3 in logic. 4 DR. BAILAR: I think this whole 5 relationship of ozone to other pollutants 6 needs more consideration than I have seen in 7 this document, though I have to admit that I 8 haven't read the whole 1,000-plus pages. 9 It is not uncommon to find that A 10 has an effect, B has an effect. When they are 11 in the same model together, neither one of 12 them has a significant effect. 13 What that tells you is that A or B 14 does have an effect, and the data are not 15 sufficiently strong to tell which one. This

16 sort of effect could even account for an 17 apparently protective effect. 18 That is why the whole thing needs 19 more exploration. 20 DR. BELL: Yes, I just want to 21 comment on that sentence, versus all-cause 22 mortality. I mean even the authors of the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 3391 study only drew conclusions for respiratory2 related mortality, which is the one that is 3 statistically-significant all the way across 4 the three different columns in Table 7.7.5 So, I think that I agree that all6 cause mortality is a stretch. I think if that 7 sentence said respiratory mortality combined 8 with the word suggestive versus causal, that 9 I think would be more in line with my 10 interpretation of what the authors are 11 writing. Even in the Journal article, they 12 refer to a relationship of respiratory 13 mortality, not all-cause mortality. 14 DR. SAMET: It is probably a more 15 general issue here, and that is related to the 16 extent of evidence that moves one from 17 inadequate to suggestive in general, as 18 opposed to in particular. And it would appear 19 that here, in particular, might be only one 20 study bolstered with some of the other 21 evidence that we have been discussing. 22 So, I guess a question would be,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 340 1 and this is you setting precedent, in the 2 minds of the agency, as you apply your rules 3 for weight of evidence, is one study with some 4 of the limitations of the evidence pointed 5 out, particularly around all-case, I think, 6 you know, it is not a whoppingly-strong 7 effect. Of course, we would not expect a8 whoppingly-strong effect on such a non9 specific outcome. But is this enough your 10 minds? 11 Well, apparently, it is, but it 12 may not be in the minds of everyone else 13 around this table, and probably even within 14 the agency, I suspect. If you were to put 15 this in front of people, you would get a range 16 of opinions. 17 So, I think maybe you should be 18 thinking about that general question as well 19 as the particular one that has been raised. 20 Let's see, other comments? Yes,

21 Helen? 22 DR. SUH: I want to actually

### 202-234-4433 Neal R. Gross & Co., Inc. Page 341 1 reinforce that notion also with regard to 2 cardiovascular effects. I think for 3 cardiovascular effects the potential for 4 confounding by PM might be particularly of

5 concern. 6 And from the writeups certainly in 7 Chapter 2, but also in Chapter 6 and 7, I 8 don't think it was justified enough in my mind 9 to say that -- the difference between 10 suggestive and inadequate, it was very murky 11 to me. And from the definitions of causality, 12 it still wasn't that clear. 13 And so, whether it was right or 14 wrong, I am not sure. But I think there 15 needed to be some additional either better 16 definition of what suggestive means and what 17 inadequate means and/or, also, better 18 justification for whichever one was decided. 19 DR. SAMET: Okay. Anyone on the 20 phone want to comment? 21 DR. WEATHERS: No additional words

22 from me.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 342 1 DR. SAMET: Okay. All right. 2 Anyone else? Again, so we are dealing with 3 Chapter 7. Anything else? Yes? 4 I don't know. Sverre, are you on? 5 (No response.) 6 If he were, I am sure he would

7 have had comments. 8 DR. MILLER: Yes, I can't believe 9 that Sverre's written comments would endorse 10 a lot in this chapter. They would not. I

11 mean there has been an awful lot of hand12 waving here. 13 DR. SAMET: Okay. Well, we will 14 see this again. 15 Let's move, then, to question 9, 16 Chapter 8, susceptible populations. Steve? 17 DR. KLEEBERGER: Okay. 18 DR. SAMET: Oh, actually, 19 Michelle, sorry, could you summarize, please, 20 be the summarizer?

21 DR. BELL: You want me to be the 22 summarizer?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 343 1 DR. SAMET: For the charge 2 question response. Thanks. 3 DR. KLEEBERGER: So, there are two 4 questions. 5 DR. SAMET: Steve, you might just 6 pull it closer.

7 DR. KLEEBERGER: Are the 8 characteristics included within the broad 9 susceptibility categories appropriate and 10 consistent with the definitions used? I have 11 got a couple of comments about this. 12 Actually, given the amount of 13 discussion we had with the previous two 14 criteria discussions that I have been involved 15 with, NOx and SOx, when we had a lot of 16 concern about what vulnerable means, what 17 susceptible means, the fact that they came 18 upfront and said susceptible, they are going 19 to be lumpers here; everything is included 20 under the sort of heading of susceptible. I 21 thought that was appropriate and made it 22 easier for me to sort of read through this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 344 1 chapter. So, that was very helpful in moving

2 forward. 3 I think that the authors also did 4 a really good job of capturing what I think 5 are considered to be the most important sort 6 of susceptibility categories. Clearly, the 7 authors are splitters here, and that is fine. 8 I could have actually been more of a lumper 9 and put some of these together into more broad 10 categories. 11 But, given the question, are all 12 the categories included, I would say yes. The 13 way that they are captured might be changed a 14 little bit. You might think about tweaking 15 that a little. 16 So, again, in general, I think 17 that they got most, if not all, the categories 18 that I would consider to be important, sort of 19 pre-disposing or susceptibility factors for 20 response to ozone. 21 Are there any key susceptibility 22 factors that were not included and need to be

### 202-234-4433 Neal R. Gross & Co., Inc. Page 345 1 added? So, given my response to the previous 2 question, my answer is probably no. But I 3 think that there are some sections that could 4 have been expanded just a little bit, and 5 these are in my comments, my written comments. 6 And I won't go into all of those, 7 but I will sort of spend some time with the8 genetics section, which I thought was well9 written. I think it really does sort of 10 consider most of the association studies, the 11 epidemiologic studies, some of the chamber 12 studies that have been done recently that have 13 looked at polymorphisms that associate with

14 adverse outcomes. 15 One of the things I think I 16 probably might recommend that you add is that 17 especially the chamber studies are limited to 18 only those genes that have a very high minor 19 allele frequency. That doesn't mean that 20 there aren't other genes that couldn't be 21 important, but because of the small sort of 22 scale of the exposure studies, you really

### 202-234-4433 Neal R. Gross & Co., Inc. Page 346 1 can't do some of these other genes that have 2 a smaller minor allele frequency. So, I think 3 I would put that sort of bit of information in

4 the document. 5 I was a little bit surprised that 6 there was limited discussion of tox studies 7 done in animal models. So, my recollection is 8 that there were discussions about NQ01 and one 9 or two other genes, but in terms of 10 susceptibility genes in animal models, there 11 are many, many studies with knockout models, 12 transgenics, knockouts. Positional cloning 13 studies have identified QTLs that associate 14 with differential responsitivity to ozone. 15 I think that we have kind of 16 short-shrifted all the animal studies in terms 17 of the genetic susceptibility. And I would 18 recommend putting in a table of some sort that 19 would list categories of genes that might be 20 involved in, or have been shown to be involved 21 in, these animal studies. I think that would 22 be really helpful. Because, again, we have

### 202-234-4433 Neal R. Gross & Co., Inc. Page 347 1 the limitations in the human studies, the 2 animal studies can help inform going forward. 3 Inclusion of diet as a 4 susceptibility factor, I think this is the 5 first time it was included in this sort of a 6 document. I think it was a great idea. 7 It was a little bit short. So, 8 vitamin C and E were considered. There are 9 studies with vitamin A that have been done in 10 the past. There has been work on caloric 11 restriction that could and should be included 12 in terms of susceptibility to ozone-induced

13 effects. 14 I have got a number of minor 15 comments that, again, are written. I won't go 16 through all of those. 17 I think obesity could be included 18 in the table of potentially-important factors. 19 It wasn't clear to me why Nrf2 was 20 stated as a possible susceptibility gene. I 21 don't think any studies have been done on Nrf2 22 and ozone. I think I would have known about

### 202-234-4433 Neal R. Gross & Co., Inc. Page 348 1 those. It just said that it is a possible 2 susceptibility factor, but there is no 3 evidence to suggest that it is. 4 And, then, my last comment, INF1 5 and INF2 should be identified as quantitative 6 trait loci, not genes. They are regions on a 7 chromosome that were associated with 8 susceptibility. 9 But, otherwise, I was actually 10 pretty pleased with this chapter. 11 DR. SAMET: Okay. Fred? 12 DR. MILLER: Well, this will be 13 shorter than the dosimetry. 14 (Laughter.) 15 The first charge question about if 16 the characteristics included are consistent 17 with the definition and that, and the answer 18 certainly is, yes, but I don't like the 19 definition. 20 As a statistician, I am used to 21 seeing tolerance distributions. And you are 22 lumping in tolerance distributions which

### 202-234-4433 Neal R. Gross & Co., Inc. Page 349 1 should be really the definition for 2 susceptibility because in a dose response 3 situation, at the lower dose you have a broad 4 tolerance distribution due to the sensitivity 5 of various individuals to be able to respond. 6 And as you dose higher and higher, that 7 narrows. And that tolerance distribution is 8 really what is talking about capturing the 9 innate biological sensitivity. 10 You have written a definition that 11 you capture everything under the sun. And it 12 is a good thing that you did because, without 13 it, I couldn't have really read the chapter 14 and agreed with a lot of your statements. So, 15 while I don't personally like it, you stuck 16 with your definition and you adhered and put 17 the material that basically supports what you 18 have chosen to write as that. 19 On this other major charge 20 question, are there key susceptibility factors 21 that were not included, I tend to say, yes, 22 there was one. It is exercise, and it was

### 202-234-4433 Neal R. Gross & Co., Inc. Page 350 1 only indirectly treated as part of the 2 sections on children and on the outdoor 3 activities. But, yet, at ambient exposure 4 levels, exercise or the level of minute 5 ventilation is by far the single most 6 important driver for the amount of ozone 7 inhaled and the probability of causing effects 8 in any subject of any age of any disease 9 condition. And it is just not here. 10 To me, the chapter would be 11 stronger if there was more brought in on 12 evidence from animal tox studies at various 13 points. 14 I will point out Section 8.1.1 on 15 influenza infections. It is a short paragraph 16 about the epi studies, but there are a number 17 of animal studies showing disability for 18 increased respiratory infections even to 19 exposures as low as .08 parts per million. 20 So, more cross-correlation in 21 building between the two I think is a 22 situation where the animal studies in some

### 202-234-4433 Neal R. Gross & Co., Inc. Page 351 1 areas can add strength to what you are 2 describing. 3 I thought the Section 8.2.2 on 4 older adults, you know, you have indicated in 5 the summary that older adults are one of the 6 more susceptible subpopulations. But when I 7 read that section, I got pluses and minuses, 8 and I didn't see a clear pattern that said 9 that older adults are one of the susceptible 10 subgroups. So, I don't know if it was just a 11 matter of the way I focused on particular 12 studies, but that story didn't come through to

13 me. 14 And, then, one thing, when you 15 talk about not having enough power, why on 16 8.4, line 9, would you even discuss an 17 epidemiology result based on an N of four? It 18 is absolutely ludicrous. Nobody in their 19 right mind would put any faith from an epi 20 study on such a sample size. And it is not 21 even worthy of discussion, in my view. 22 The same way about why ozone

### 202-234-4433 Neal R. Gross & Co., Inc. Page 352 1 studies back in the animal tox at 3 parts per 2 million for three hours that absolutely 3 obliterated the lungs of the animals and 4 caused the ability of ozone to interact 5 directly with the blood, why such studies 6 would even get one line in here? It just 7 shouldn't happen. 8 So, overall, those are the things. 9 But I think, as a chapter, I enjoyed reading 10 it because I thought you were comprehensive. 11 I don't know what other kinds of categories, 12 except maybe a little more, like I say, on the 13 exercise, that you could have needed to bring 14 in to say these are possible susceptibility 15 aspects. 16 So, those are my comments. 17 DR. SAMET: So, just a comment. I 18 was refreshing my memory here on the PM 19 document. And I think I already voiced my 20 opinion. I don't like what you have called 21 susceptible because you have really grouped 22 susceptible in a biological sense with more

### 202-234-4433 Neal R. Gross & Co., Inc. Page 353 1 heavily exposed. 2 And, in fact, I went back and 3 looked at the equivalent chapter in the PM 4 ISA, and some of the same language is there. 5 I don't think I liked it then. I probably 6 said that. I hope I did. 7 But, then, what you actually say 8 here is entirely inconsistent with the use of 9 the word susceptible in the policy assessment. 10 It does not line up at all. Where there is 11 extensive discussion of protection of 12 susceptible populations, susceptible 13 individuals, limiting exposure to protect 14 susceptible individuals, okay? 15 And so, I mean, you have actually, 16 I think, muddled the concept as it will be 17 used when you sort of get to the critical 18 point of decisionmaking, at least in my 19 thinking. 20 So, again -- and I think Fred 21 alluded to this -- we are talking about a 22 distribution of likelihood of response, given

### 202-234-4433 Neal R. Gross & Co., Inc. Page 354 1 exposure, and that there is such a 2 distribution, and some people, for one reason 3 or another, are out at the higher or the lower 4 end. And some people, for one reason or 5 another, will have exposures at the higher or 6 lower end, and those relate to diverse 7 characteristics. I don't see that you do 8 anything but muddle by putting this together. 9 And, then, later, when you have to 10 come to the policy assessment and deal with 11 the issues of exposure of the susceptible 12 population, I don't think susceptible, in 13 thinking about that issue and thinking about 14 the adequate margin of safety has ever been 15 used in the context of the way you are 16 defining susceptible in this chapter. 17 So, I am actually sort of 18 concerned about the path you have set, and I 19 am not sure why you need to stick to it.

20 DR. BRAIN: I have the same 21 recollection and remember a long discussion. 22 Didn't we finally end up with susceptibility

### 202-234-4433 Neal R. Gross & Co., Inc. Page 355 1 and then vulnerability? 2 DR. SAMET: And vulnerability. I 3 thought vulnerable was the other -- 4 DR. SUH: I think, though, we 5 decided we didn't like that, either. 6 DR. BRAIN: We didn't like that? 7 DR. SAMET: Well, we talked about 8 it. Some of us did. 9 DR. SUH: I think we were muddled

10 ourselves. 11 DR. BRAIN: We certainly liked the 12 distinction between inherent biologic 13 responsiveness -- 14 DR. SUH: Right. 15 DR. BRAIN: -- versus increased 16 likelihood of exposure. 17 DR. SUH: Right.

18 DR. SAMET: Yes. 19 DR. SUH: It was a highly 20 exposed -- 21 DR. SAMET: If I ever said I liked 22 what was in the PM ISA, I don't like it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 356 1 anymore. 2 (Laughter.)

3 DR. BRAIN: But we should have a 4 uniform -- 5 DR. SAMET: It should be uniform. 6 But I actually do think there is this 7 disconnect between the way the word will be 8 eventually used that is of concern. 9 DR. VANDENBERG: So, can I just 10 rehash old history? We did go back and forth 11 between PM draft one and CO first draft, and, 12 then, PM draft two and CO draft two. We kind 13 of came to this with a lot of discussion with 14 the other panels, actually. 15 So, this is very consistent with 16 what we ended up with in CO. And part of it 17 was Jason did an analysis and a 18 presentation -- 19 DR. SAMET: Right.

20 DR. VANDENBERG: -- about the use 21 of susceptible versus vulnerable. 22 DR. SAMET: Right.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 357 1 DR. VANDENBERG: Well, it was this 2 confusion about susceptible and vulnerable. 3 And there is a lot of different language that 4 has been used in a lot of different settings 5 within EPA, outside of EPA. It is muddled. 6 Muddled? I guess that's a word. Muddy. 7 And so, this is where we ended up. 8 We certainly welcome comments, but, again, 9 this is sort of trying to be consistent across 10 the different ISAs. 11 And Helen is shaking her head 12 because I think she was one of the ones that 13 commented at the time. 14 But it certainly is something that 15 has been muddied in the literature as well as 16 in the discussions. 17 DR. SAMET: Well, would it be 18 reasonable to go back to first principles? I 19 think we are talking about two phenomena. 20 One, increased risk, given exposure, and, two, 21 increased likelihood of higher exposure. I 22 think that is actually the --

### 202-234-4433 Neal R. Gross & Co., Inc. Page 358 1 DR. VANDENBERG: Higher exposure 2 or higher response? 3 DR. SAMET: What? No, they are

4 both. 5 DR. SUH: I think one of the 6 things we had talked about, but I don't think 7 it made it through, was I think originally we 8 didn't understand what vulnerable meant and 9 susceptible meant, really with the 10 definitions. 11 But one idea was one was 12 susceptibility in that you have some innate 13 characteristics that make you more at risk.14 But, then, the other idea was of highly15 exposed groups, which is not really 16 susceptible. 17 But maybe that is one way of just 18 taking that whole other, you know, things like 19 people who exercise outside or like if you 20 have air conditioning. That would be an21 exposure-related parameter rather than a risk22 related parameter, I would say. And so, maybe

### 202-234-4433 Neal R. Gross & Co., Inc. Page 359 1 that is a way to try to separate them a little 2 bit. 3 Or at least in the writeup you 4 could put them separately. You could have5 them a whole other character, like exposure6 related -- 7 DR. VANDENBERG: So, just as a 8 clarification, we have talked about exercise 9 as an important consideration here. How would 10 you consider that? 11 DR. SUH: Well, and I thought 12 about that, too. That is why I didn't say

13 that. 14 I mean I guess you could argue 15 that exercise gives you a higher exposure 16 level, a higher dose. So, I would put that in 17 the more highly-exposed because the same 18 person, for example, could exercise or not 19 exercise and, then, have different risks, you 20 know, based on a different exposure level. 21 But it is not based on their intrinsic self. 22 And I think that is really the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 360 1 idea of susceptibility, is there is something 2 intrinsically about you, your gender or your 3 race or your body shape, or whatever it might 4 be, that makes you more at risk; whereas, 5 those factors really control how much ozone 6 you will be exposed. 7 So, I mean I don't know if it is 8 clearer, but it might help separate a little9 bit without putting a tagline on the highly10 exposed or the exposed category. 11 DR. KLEEBERGER: I was just going 12 to say, in papers that I have written where I 13 have tried to actually make this distinction, 14 what I have done is essentially what they have 15 done. I said there is a susceptibility, sort 16 of, factor. There are intrinsic factors and 17 there are extrinsic factors. 18 The intrinsic factors are 19 genetics, gender, age, health status, perhaps 20 nutrition. I mean these are all sort of 21 intrinsic factors. 22 The extrinsic factors are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 361 1 everything else: exercise, pre-exposure. You 2 name it, it sort falls in that category. But 3 I still consider them as being susceptible

4 factors. 5 DR. GRAHAM: Yes, I would say the 6 important thing is to define it, and, then, to 7 use that definition throughout. I personally 8 like this definition because, personally, the 9 language I use is sensitivity to represent the 10 intrinsic factors. Oh, you have got asthma;11 you are young. And, then, you can be in high12 end exposure. You are an outdoor worker; you 13 are a kid and you are outside playing in the 14 school yard at three o'clock in the afternoon. 15 So, I like this definition. 16 If you stick to this definition, 17 you have to follow through on it. My concern 18 is that you have a separate section on 19 preexisting disease, a separate section on 20 age. You don't have a separate section on 21 exposure and dose, to actually call that out, 22 because it is kind of like the exercise is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 362 1 one. So, since exercise and dose, I think it 2 should be its own little subsection. 3 The other thing I would say is 4 that, I mean, I think we can all agree that 5 this is one of the most important sections of 6 the document because this is where you 7 highlight what groups of people need to be 8 protected and why. So, I would suggest that, 9 for each of these susceptibility groups, that 10 you be very clear about providing certain 11 types of information, four types of 12 information. 13 One, what is the prevalence of 14 this group in the general population? Now for 15 most cases you have it, like here's the 16 prevalence of asthmatics; here's the 17 prevalence of kids. But I think on some of 18 the genetic polymorphisms that information 19 isn't there. For different exercise levels, 20 so get the prevalence for that group in the 21 general population. 22 The other thing is, what is the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 363 1 nature and severity of the risk? I didn't see 2 a discussion in here about the impact on COPD 3 patients. It was clear in here that COPD 4 patients and smokers had about the same FEV1 5 changes as a healthy person, but I didn't see 6 the discussion of, well, what then? 7 And I know the issue often 8 discussed is that, even though you might have 9 the same degree of change in FEV1s, if you 10 have COPD, that degree of change may have more 11 impact because you have less pulmonary 12 reserves. So, that story. 13 What is the number of hospital 14 admissions for asthmatic kids? What does a 5, 15 10, 20 percent change in FEV1s in healthy,16 exercising young people mean to their well17 being? So, to get at this issue, what is the 18 nature and severity of the risk for this 19 population? 20 And, then, a third item, what is 21 the concordance of human clinical epi and 22 animal tox data for this particular group?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 364 1 And as a fourth, does this group 2 have characteristics that result in greater 3 exposure or dose? And that is where you get 4 like the double-whammy going on. 5 I mean the classic is lead. I 6 always use that as an example here. A young 7 child is actually more sensitive, more 8 intrinsically responsive to lead because of 9 the developing nervous system. And, then, 10 they have the double-whammy that they are 11 eating lead paint. 12 So, for this particular 13 susceptible group, do they have any 14 characteristics that make it even worse 15 because they have a higher exposure or dose? 16 DR. SAMET: So, I want to return 17 to this issue. I am going to do a couple of 18 things first. 19 I am going to remind you of what 20 we said about PM. We did not say stick with 21 one term. We actually had some very 22 thoughtful language there, as you would

### 202-234-4433 Neal R. Gross & Co., Inc. Page 365 1 expect. 2 (Laughter.) 3 And, second, I am going to read to 4 you the definition straight off page 8-1 and 5 make you listen to it. 6 Here is the definition of 7 susceptible populations: Individual- and 8 population-level characteristics that increase 9 the risk of 03-related health effects in the 10 population, including, but not limited to, 11 genetic background, birth outcomes (e.g., 12 blah), race, sex, life stage, lifestyle, 13 (e.g., blah), preexisting diseases, SES (e.g., 14 blah) and, finally, characteristics that may 15 modify exposure to 03, e.g., time spent

16 outdoors. 17 I am just going to propose this is 18 not useful, and that when you come to have to 19 talk about protection of susceptible 20 individuals in the context of what the Act 21 requires, this generality and vagueness here 22 really doesn't suffice. And it is not even

### 202-234-4433 Neal R. Gross & Co., Inc. Page 366 1 limited in any way. It opens itself up to 2 essentially any definition. 3 And since I am now finding myself, 4 I think, in several of these categories, I 5 will have to stop exercising because I am now 6 at risk. 7 In our comments in the first draft 8 ISA, there is actually, I think, a pretty 9 thoughtful dissection of the issues and a need 10 for clarity is what we really called for. And 11 I don't think you have achieved clarity. If 12 you think this is clarity, you have redefined 13 clarity. 14 Not yet. Not yet. 15 So, I just want to finish the 16 point that you are doing all this for a 17 reason. And I think that the way you are 18 developing it is not going to serve the next 19 user of this document as well as it should. 20 So, you know, I think you can call 21 it what it is, and Helen said one thing. You 22 can talk about factors that increase risk,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 367 1 given exposure, or you can talk about factors 2 that increase exposure or dose. And that 3 comes from a variety of reasons. 4 So, I don't think you've got it. 5 And I don't know whether others agree, but I 6 think you just don't have it right now. 7 DR. VANDENBERG: If I might, just 8 to clarify, I think that our feedback we were 9 focusing on was not the comments on the first 10 draft ISA, it was the comments in response to 11 the final. 12 DR. SAMET: Well, I liked the 13 first draft ISA. 14 (Laughter.) 15 We'll pull out the second draft. 16 I am sure they are equally wonderful. 17 But, Fred? 18 DR. MILLER: I would like to ask 19 that you discuss with your OAQPS colleagues if 20 your definition puts them into a hole that 21 they can't climb out of. Because, basically, 22 this says that exercise, you can avoid issues

### 202-234-4433 Neal R. Gross & Co., Inc. Page 368 1 relative to the ozone standard if you simply 2 don't exercise. And you get no significant 3 changes in FEV1. And I don't think that is 4 the intended story. 5 And so, the question is -- I like 6 Steve's intrinsic/extrinsic, and you would be 7 able to discuss. I like Judy's statements 8 about sensitivity and, then, increased 9 exposure aspects. 10 But the way it is now, to call 11 them all equally important aspects of the 12 definition of sensitivity, to me, clouds the 13 issue. It comes back, again, to my basic 14 understanding from Finney Bioassay 101 about 15 tolerance distributions. And this is doing a 16 disservice to what has been the basic 17 understanding in biomedical research relative 18 to sensitivity -- or susceptibility now at 19 this point. 20 So, OAQPS is very important 21 because you guys have to work together, and 22 you can't put the excuse now that they are in

### 202-234-4433 Neal R. Gross & Co., Inc. Page 369 1 Durham, because you guys are all in the same 2 building. 3 (Laughter.) 4 I know you don't excuse yourself 5 anyway. Don't get me wrong. 6 DR. SAMET: Ed, are you poised to

7 comment here? 8 MR. AVOL: No. I mean I think you 9 have covered most of it. I mean I think, 10 internally, they were consistent; I just think 11 that they don't have the right definition. 12 And I think that if you follow the logical 13 extension of what you describe as some 14 susceptibility factors, there are a whole host 15 of other ones that get you into all kinds of 16 trouble, like things that might affect your 17 personal cloud. So, now you get into consumer 18 products and what kind of perfume you wear, 19 because that might change the ozone in your 20 community there, and make you more or less 21 susceptible. 22 And, you know, if you are going to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 370 1 talk about outdoor activities as opposed to 2 exercise, then you have to start to worry 3 about indoor time because indoor time invokes 4 some sort of different kind of indoor/outdoor 5 ratio. So, now I mean there are whole kinds 6 of other things. So, I just think it gets 7 very problematic. 8 DR. SAMET: Okay. Other thoughts 9 about this? 10 Somebody on the phone? 11 DR. WEATHERS: Yes, someone is on 12 the phone. 13 (Laughter.) 14 DR. SAMET: Oh, good. 15 Do you want to comment? 16 DR. WEATHERS: I think I am alone

17 here. 18 DR. SAMET: Maybe. Do you have 19 any comments? 20 DR. WEATHERS: No. Well, yes. In 21 hearing the discussion, am I correct in 22 assuming that there are not clear definitions

### 202-234-4433 Neal R. Gross & Co., Inc. Page 371 1 in the literature? 2 DR. SAMET: Well, I think, 3 actually, the table that was put together 4 before shows the terms are used widely and 5 differently. And I think some of that 6 discussion was captured when we were dealing 7 with other pollutants. 8 I mean, again, I think what you do 9 here could be very helpful to everyone, but I 10 don't think you have got it right yet, in case 11 you didn't figure that out. 12 (Laughter.)

13 DR. VANDENBERG: We welcome 14 suggestions. 15 DR. SAMET: Okay. Any others?

16 Howard? 17 DR. NEUFELD: The socioeconomic 18 status section in this chapter, is there -- 19 DR. SAMET: Oh, microphone. 20 DR. NEUFELD: Is there any 21 evidence that people of lower socioeconomic 22 status would actually live in areas with

### 202-234-4433 Neal R. Gross & Co., Inc. Page 372 1 higher ozone? 2 DR. SAMET: Well, yes and no. I 3 mean, because if they are in the inner cities 4 with high NOx, then there is something 5 different going on. But, yes, potentially, 6 yes. 7 DR. SUH: I think it would be 8 lower. Well, it depends. But if lower 9 socioeconomic groups live near roadways, then 10 that would suggest that there will be less 11 ozone. But I don't know if anybody has really 12 ever looked at that explicitly. But it seems 13 that that would be my guess. 14 DR. SAMET: Yes, Michelle? 15 DR. BELL: We did look at this in 16 terms of the overall -- and other people have, 17 too. It basically depends on where you are. 18 So, there are specific locations where higher 19 levels of exposure to ozone are in groups with 20 higher socioeconomic status, and there's 21 locations where higher exposure to ozone is in 22 communities with lower socioeconomic status.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 373 1 So, there will be some overall trends, but 2 certainly any possibility is true. 3 DR. MILLER: And it is also more 4 reflective of your availability and ability to 5 pay for health-related visits. If you have 6 money, I don't care what the ozone level is, 7 your kid, you are going to get him to the 8 hospital. There is a greater chance that they 9 are going to say, "Well, we had better watch 10 him overnight to be sure." Whereas, the 11 person that doesn't have that kind of health 12 insurance, they just don't go. So, there is 13 a selection bias that SES helps to adjust for. 14 DR. SAMET: Okay. Then, Steve, 15 you're it on this one. 16 DR. KLEEBERGER: Okay. 17 DR. SAMET: Okay? 18 And one other thing we are going 19 to do is -- Holly will do this -- we will 20 compile our prior comments on this issue 21 around the PM, and I guess we have CO, and we 22 will take a look at what we have said.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 374 1 Okay. Integrative summary. 2 Helen, I think this is you. 3 DR. SUH: Okay. So, this charge 4 question is about Chapter 2. I think it is a 5 good start. I think it does a good job of 6 taking the results from 2006 or the findings 7 and talking about what is new and different, 8 which I think is important for this chapter. 9 As reflected in many of the 10 comments from earlier today, I think the 11 chapter has a bit of an identity crisis. I 12 think in many ways it is a good summary, but 13 I think, really, given that there is a lot of 14 summaries already in the rest of the document, 15 and there seems to be a lot of repetition and 16 borrowing of phrases, perhaps the way I would 17 think of this chapter as being really 18 effective is if it was really more of an 19 integration of the findings across -- across 20 exposure, mode of action, health impacts. 21 And as an example of it, I would 22 say that, for example, with the exposure

### 202-234-4433 Neal R. Gross & Co., Inc. Page 375 1 chapters there has been discussions about the 2 relationship between or how well ambient 3 concentrations reflect exposures. And you 4 could argue that it doesn't do very well, 5 especially perhaps at the low ozone 6 concentrations that are relevant maybe to this 7 consideration of the evidence. 8 And so, given that the 9 relationship between ambient concentrations 10 and personal exposures might not be so strong, 11 what does that mean in terms of the epi 12 results, for example? What does that mean in 13 terms of susceptibility of different groups? 14 What is that? 15 And it would be nice to be able to 16 take all that information and put it together 17 in one chapter, including with the modes of 18 action. And I think that would be a very, 19 very useful addition beyond what is in the

20 rest of the document. 21 And I think that the summaries are 22 spread throughout the different chapters, and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 376 1 maybe that could be fixed by putting an 2 overall summary at the end of each chapter. 3 That maybe is a little bit more integrated. 4 But I think this part really would 5 benefit from taking all the information and 6 trying to put it together in a story, like 7 what Judy talks about. What is really needed 8 is a story. 9 So, given the results that we know 10 about exposure, what does that mean in terms 11 of the toxicity of ozone that is observed in 12 the controlled laboratory studies? Are all 13 these pieces consistent to tell the same 14 story? 15 And I think that goes together 16 with issues about exposure, error, 17 confounding. What does this mean in terms of 18 epi evidence? How do the controlled 19 laboratory studies -- there are some studies 20 that look at ozone and PM together. How does 21 that inform our conclusions about potential 22 confounding and epi studies?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 377 1 So, I think there is a lot of 2 evidence that can come together in one 3 cohesive chapter that I think could make a 4 really compelling story for where you got to, 5 I mean where you are going to get to in the 6 future, like in the REA and the policy

7 assessment. 8 So, I think this is a great 9 opportunity. And I would argue that it would 10 come upfront in Chapter 2 rather than all the 11 way in the back because I think this will be 12 a chapter that people will read and really 13 could tie everything together. 14 So, instead of really separating 15 the sections to mirror the chapters that are 16 in the ISA, I would try more for an integrated 17 assessment, maybe by effects. Maybe there is 18 a respiratory or maybe -- I am not exactly 19 sure how you might want to do it. But I think 20 that this is your opportunity to really put 21 all that together. 22 So, I would get rid of like the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 378 1 exposure, the mode of -- I would just try to 2 put it together. And I think Section 2.6, I 3 thought that was a good job of starting to 4 integrate at least the dosimetry mode of 5 action and the health effects pieces. And I 6 thought that was actually better than the 7 separate sections together. 8 I really liked the use of 9 diagrams, the tables. I thought that was 10 extremely effective. I think something like 11 that as the model would be a great, a better 12 identity for this chapter, I think. I think 13 it would be less repetition. So, I think 14 there would be less complaints about that. I 15 think it would help to reorganize the thought 16 process. 17 And so, that is sort of my main 18 piece. And I guess one little thing. I mean 19 I was very puzzled about this throughout, and 20 I didn't talk about it. But the PRB whole 21 section creates a lot of talk today. Then, 22 also, there was a discussion, a pretty big

### 202-234-4433 Neal R. Gross & Co., Inc. Page 379 1 discussion in the document. 2 It is clear very spatially and 3 temporally, right? But, then, I wasn't really 4 clear how it was going to fit in with all the 5 rest of the conversation later on. Like in 6 the REA it is clear it is going to play a 7 part, but from this, it just sort of stood

8 alone to me somehow. 9 And I was wondering if it could be 10 better integrated with the rest. I am not 11 sure how exactly, but I think it has to go in 12 with the whole idea of what happens at this 13 low ambient concentration range. 14 And so, anyway, those are just 15 like my overall comments. 16 DR. SAMET: Okay. Let me see. 17 Chris, are you on? 18 DR. FREY: I am on the phone, yes. 19 DR. SAMET: Okay. Good. Why 20 don't you go ahead? 21 DR. FREY: Okay. Well, I liked 22 Helen's comments. I thought she did a nice

### 202-234-4433 Neal R. Gross & Co., Inc. Page 380 1 job of organizing lots of thoughts in her 2 written comments, and I support what she said. 3 I don't have a lot to add, but I will anyway. 4 (Laughter.) 5 I guess, as a reader, I was kind 6 of frustrated with Chapter 2 because I think 7 maybe we don't have a clear idea of who the 8 audience is. We need to have that in order to 9 revise it. 10 The thing that frustrated me is 11 that I think each section was written for the 12 domain expert of each section. And so, it 13 wasn't integrative in the sense of helping 14 people of different disciplines digest this 15 material. You know, if you are not a health 16 effects expert, you are not going to 17 understand those parts of the summary, and so 18 on. And so, it is a hard thing to do, but I 19 think that needs to be the goal. So, I think 20 most of the sections are probably unreadable 21 to someone who is not a domain expert. 22 I agree with Helen about that it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 381 1 actually needs to be more integrated. It is 2 kind of like a summary of here's the details 3 of specific things in each chapter, but it 4 doesn't necessarily tie things together well. 5 And another frustrating thing for 6 me is it references figures in other parts of 7 the document. I am feeling like I have to 8 flip through hundreds of pages to read this 9 chapter, which is counterproductive. So, it 10 should be a standalone, self-contained

11 document. 12 And I agree with Helen that having 13 figures and tables and graphics is helpful, 14 and I think there should be more of that. And 15 so, for example, where there is a tendency to 16 go off and summarize several studies, why not 17 try to make a table and, then, use the text to 18 synthesize what the key findings are, rather 19 than present sort of a data dump? 20 So, I think that is probably all I 21 am going to say. You know, I submitted some 22 written comments, but, frankly, my comments

### 202-234-4433 Neal R. Gross & Co., Inc. Page 382 1 are really kind of more editorial rather than 2 technical since we have covered the technical 3 issues in the chapter reviews. And, 4 obviously, whatever revisions happen in those 5 chapters will need to be reflected in the 6 revised integrative overview.

7 Thanks. 8 DR. SAMET: Okay. Howard? 9 DR. NEUFELD: Well, I want to say 10 I thought it was generally a well-written 11 chapter. I may differ a little bit. I 12 actually was able to read the human physiology 13 and tox studies and figure out what was going

14 on. 15 I think that it is a little long, 16 and there are sections, for example -- and we 17 have already talked about this -- that are 18 verbatim the same in later chapters. I think 19 if we eliminate that, then we can shorten the 20 document up some. 21 But there are certain things that 22 could be improved. But, in general, I thought

### 202-234-4433 Neal R. Gross & Co., Inc. Page 383 1 in reading this -- you know, I am new to this 2 process here -- that I got a fairly good idea. 3 I mean this is like the condensation of the 4 entire document here. And if someone will 5 take the time to read the 40 or so, 50, 60 6 pages here, as opposed to the 1,000, you are 7 going to get a pretty good idea of the rest of 8 the document, which I think is the purpose of 9 this chapter. 10 And it may be improved. It may be 11 better integrated perhaps with a little more 12 effort, but, in general, I was actually 13 pleased with it. 14 I wasn't pleased with some things, 15 though. I wasn't a fan of some of the 16 figures. I think they were confusing to me, 17 particularly 2-1. It is just too much stuff. 18 Or maybe it could be -- 19 DR. SUH: Well, I loved that one. 20 DR. NEUFELD: Oh, you liked it? 21 Okay. Well, okay. 22 (Laughter.)

### 202-234-4433 Neal R. Gross & Co., Inc. Page 384 1 And, then, the one in my field is 2 a little too simplified, Figure 2-3. It is 3 just overly simplified. 4 Let me go on for a few other 5 things here. When I wrote this, it was more 6 specific for some of the larger chapters. So, 7 I won't go through the technical details. 8 There is one sentence that I 9 thought was important, and here's where 10 English matters. It is in Section 2.5.2, and 11 the authors are talking about single-day 12 exposure underestimate the public health 13 impact. So, the first phrase states that. 14 And, then, the second phrase starts off with 15 a disclaimer "but," and, then, it states that 16 multi-day effects are limited to the first few 17 days. 18 So, to me, the way that is 19 constructed, it seems as if the latter part of 20 the sentence is not as important as the first 21 part. And I would think they are both equally 22 important. So, you might want to change

### 202-234-4433 Neal R. Gross & Co., Inc. Page 385 1 "but", take "but" out, and substitute the word 2 "while", which, then, to me, gives equal 3 weight to both the clauses. 4 And let me see. There is some new 5 literature coming in that I reference, but the 6 EPA people can pick that up. 7 Let me get to the last part. 8 There is one section here, the atmospheric 9 chemistry people can tear into me on this 10 since I am not. But in the section, this 11 actually ought to go probably in Chapter 10, 12 but at least it is summarized here. So, I was 13 just going to bring the subject up.14 And this is on the idea of UV-B15 induced catalyst of elemental mercury. And, 16 then, it is revolatilized into the atmosphere. 17 So, Dave Schindler has written on this. So, 18 again, it is not a health effect unless you 19 are looking at it like a secondary or tertiary 20 effect, where you have acid rain, you have 21 UV-B, you have ozone, and, then, you have 22 mercury all mixed together. So, it is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 386 1 something to consider maybe putting into the

2 document. 3 And the other thing is I think 4 this whole document needs a very, very short 5 Executive Summary. Okay? I think we all 6 maybe agree on that. And the last part of 7 this chapter is almost that, those long tables 8 on the last two pages. I think that right in 9 the beginning of this whole document maybe 10 there ought to be an Executive Summary, and it 11 could come right out of these last two pages

12 here. 13 So, okay, I think those are my 14 main comments. 15 DR. SAMET: Okay. Thank you. 16 John, I think we can assume this 17 chapter is a work-in-progress and that it will 18 become more integrative as you integrate? 19 DR. VANDENBERG: Yes, the whole 20 document is a work-in-progress. 21 (Laughter.) 22 DR. SAMET: Oh, really? Oh, okay.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 387 1 DR. VANDENBERG: That's right. 2 DR. SAMET: But, I mean, I think 3 this fact that some people see it as a useful 4 summary suggests that it is obviously not 5 integrative enough yet. I think if you could, 6 as you rewrite it, resist the cut-and-paste 7 temptation, it would probably help the 8 development of integration. 9 I think the other comment, which I 10 think probably many would support, and 11 obviously you will decide, is whether the 12 document does need a short, upfront Executive 13 Summary, so that someone can go there. 14 I think in answer to who is the 15 readership of this chapter, presumably, it is 16 everyone and that is a wide range of 17 individuals who are going to look to this 18 chapter in a sense as sort of the 19 justification of the bottom lines that are 20 going to be important for advancing. So, it 21 should be broadly readable and not one that 22 you can't move fluidly from section to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 388 1 section, depending on what your own personal 2 area is. 3 Yes, Ed? 4 MR. AVOL: So, I have two issues. 5 One was I thought that, as an integrative 6 overview, in some sections it sort of 7 meandered and never quite got to the point. 8 And one example is in the policy-relevant 9 background discussion. It sort of talked 10 about it. It talked about what effects. It 11 never came right out and said what it was or 12 whether it was going up or down. So, I think 13 you just sort of need to sharpen the 14 presentation a bit. 15 Then, the second issue is this 16 notion that has been discussed somewhat in 17 terms of what the purpose, who the audience, 18 and the placement of this ultimately in the 19 document. And so, I think in terms of 20 placement, if this is going to serve as an 21 Executive Summary, maybe it ought to be at the 22 front. If it is going to serve as an

### 202-234-4433 Neal R. Gross & Co., Inc. Page 389 1 integrative overview, maybe it ought to be at 2 the back. I don't know what it serves as in 3 the middle. And so, I think you sort of have 4 to think about what its character is and what 5 you want to do with it.

6 DR. SAMET: Fred? 7 DR. MILLER: Along those lines, if 8 you leave it where it is now, to me, you 9 relabel it and call it "document roadmap". 10 There is no real integration here. The way I 11 would think of integration is what was the 12 kind of chapters in the previous criteria 13 documents. But I would actually favor, 14 because I am not sure what that really adds, 15 that you make it a true integration and you 16 have it as the last chapter, and, then, the 17 boiling down of that becomes your Executive 18 Summary. So, I don't get any value out of 19 this chapter as it stands now. 20 And so, I think you have to decide 21 what you are really after. Because if it is 22 truly integrative and is a summary, then, why

### 202-234-4433 Neal R. Gross & Co., Inc. Page 390 1 read the rest? So, who is it really intended 2 for, and what function do you want? And, 3 then, that will dictate what you decide to do 4 with it to me.

5 DR. SAMET: Dave? 6 DR. GRANTZ: Yes, I think that 7 this group is where we should resolve this 8 identity crisis, as somebody called it. 9 Clearly, this is a combination of several 10 different things. 11 I would argue that it should be an 12 expanded Executive Summary, but not the 13 typical three-page Executive Summary. I like 14 having it upfront. 15 But just a little personal 16 history. When I first started reviewing that 17 chapter, I started inserting references. 18 There is so much detail there, I kept making 19 the comment this is missing a reference. And, 20 then, I realized there weren't any references

21 at all. 22 I think it should be integrative

### 202-234-4433 Neal R. Gross & Co., Inc. Page 391 1 and shorter, but should be upfront and should 2 be essentially a good, clean roadmap that can 3 be read quickly by anybody. 4 DR. SAMET: Well, let me comment. 5 If my memory serves me well, which it may not, 6 the purpose of this chapter was to force a 7 kind of integration across the entire body of 8 evidence that was not happening in the 9 individual chapters that we felt was 10 important. And some of this has been alluded

11 to. 12 Short-term/long-term effects, for 13 example, or short-term/long-term effects and 14 susceptibility brought together. There are 15 many overarching issues that in the structure 16 of the document, as it is written, those kinds 17 of connections aren't made. 18 And I think we thought that those 19 connections should be made here, and that this 20 kind of integration across everything -- and 21 maybe this argues for Fred's point about 22 placement -- was not being done and achieved,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 392 1 but, yet, it was important. 2 To do that, of course, you are 3 bringing forward some of the most critical 4 points and findings of the chapters that 5 follow, but this, I think, again, as we 6 originally discussed the concept, it was not 7 to be sort of an Executive Summary. That 8 would be a different purpose. 9 It was, I think, put in the 10 Chapter 2 position in the ISA because we 11 thought it was so important that, if it came 12 later, just simply people would not get to it. 13 Now that is a decision that could be 14 revisited. 15 So, it is not supposed to be a 16 roadmap, although Chapter 1 should provide 17 that roadmap. And maybe the right spot, if we 18 think that this truly sort of integrative 19 across the chapters is what is needed, at that 20 point it brings in the welfare effects and 21 climate change, and so on. I think the 22 chapter would be important. It doesn't have

### 202-234-4433 Neal R. Gross & Co., Inc. Page 393 1 to be long necessarily. 2 And right now, I think it reads 3 too much like an Executive Summary. So, if 4 you want an Executive Summary, you have got a 5 good start on one. But if you want an 6 integrative chapter, you have got a lot of 7 work to do. And probably maybe we want both. 8 I would suggest that the document could have

9 both. 10 So, why don't others weigh-in on 11 this? John? 12 DR. VANDENBERG: Just one aspect 13 that you might help me clarify here is that 14 part of the goal -- and you can see that it 15 says "a work-in-progress" -- is both to strive 16 towards integration, and of course integration 17 is the last thing you do when you understand 18 everything else that is happening. So, it is 19 the kind of last thing that we create. But it 20 is also to highlight the difference between 21 what the knowledge is now and what the 22 knowledge was in the last review.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 394 1 And so, some of the tables that 2 people pointed to that they liked specifically 3 said this was 2006, this is 2011. And some of 4 that is because we have changed our framework. 5 So, you know, there is a change in the whole 6 way we are doing things. 7 But we are also trying, through 8 some of those figures, as Jim presented, 9 highlighted in circles and red some of the 10 newer knowledge areas that had come to light 11 since the last review, because that is an 12 important consideration as we move towards the 13 latter steps of the policy assessment 14 especially, is: what's new for the15 Administrator to consider in the standard16 setting process compared to what was known, 17 say, five years hence? 18 So, it is an attempt to try to 19 integrate it. It is an attempt to try to 20 highlight the newer knowledge areas and not to 21 just rehash everything that follows. 22 And again, as we have stated, the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 395 1 reason it was put upfront is people didn't 2 want to read through 1,000 pages before they 3 got to it. But it also tends to be where we 4 point some of those -- you know, within the 5 agency, outside of the agency, there's a lot 6 of different audiences -- to say, well, if you 7 want to read something that is kind of to the 8 point, read Chapter 1 and 2, 1 for the 9 framework; 2 is how we applied it. 10 DR. SAMET: Could we also agree 11 that a well-done Executive Summary, which is 12 probably needed for a 1,000-page document, 13 could serve much of that purpose, and perhaps 14 have this additional chapter doing what we 15 have been discussing here? 16 DR. VANDENBERG: It could very 17 well be. And when we tried, I think it was on 18 a NOx document, to do like an Executive 19 Summary, it didn't work very well. It was too 20 short. And so, there was a sense of 21 dissatisfaction that it just didn't do it. 22 And so, your recommendations,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 396 1 suggestions are certainly welcome here on how 2 to get this right. 3 DR. SUH: I would really argue, I 4 like it -- if it is an integrative summary, I 5 think it belongs in Chapter 2. I would say 6 that it is how you frame it. So, you could 7 say, well, what follows is really the 8 justification for what comes in Chapter 2 with 9 your integration. 10 But I think if you put at the very 11 end, I think this is the meat. I really do 12 think that in some ways this is really the

13 heart of the document. 14 Chapter 1 explains what happens. 15 Chapter 2 is sort of the overall. And it is 16 a little odd in the placement, but I think 17 because it is the heart of it, that you go 18 early, and, then, what follows is really the 19 justification and the evidence for what is in 20 Chapter 2. 21 And I think that Chapter 2 really 22 in some ways could be very, very long. So, it

### 202-234-4433 Neal R. Gross & Co., Inc. Page 397 1 is not really an Executive Summary. It is 2 really a long, I don't know, I guess it just 3 integration. 4 But I guess I think of it, this is 5 really the thing that people are going to take 6 home with them. It is going to say what is 7 different. So, if there is a standard change 8 or there is different causality terms, it is 9 going to lay it out right here. I think that 10 is what you want. And I think it should go 11 early. 12 DR. SAMET: There are lots of ways

13 to -- 14 DR. WEATHERS: This is Kathy. 15 DR. SAMET: Yes, Kathy? Go ahead. 16 DR. WEATHERS: Oh, yes, I agree 17 with what I think you said, Jon, which is, 18 whatever step it is, that there be an 19 integrative chapter, whether it is integrative 20 of what is new since the last review or not, 21 I am not sure of, but that there also be an 22 Executive Summary. And maybe that will follow

### 202-234-4433 Neal R. Gross & Co., Inc. Page 398 1 in this evolving document. So, maybe that is 2 not the goal for the next round, but an 3 integrative chapter upfront should be. 4 DR. SAMET: I mean another way to 5 do this, I am reminded of BR6, biological 6 effects of ionizing radiation, Report No. 6, 7 which, hopefully, none of you have read. 8 (Laughter.) 9 The main point was that we really 10 only had one chapter that was the presentation 11 of the risk model and the risk assessment. 12 Everything else was an appendix. 13 So, for example, for the point of 14 view of having a linear no-threshold model, 15 what was critical was our understanding of 16 mechanisms and biological facts of alpha 17 particles. 18 I mean, in a way, what you are 19 saying is that Chapter 2 is likely to contain 20 what is going to be most important, the 21 advances in knowledge, how those advances fit 22 together, how our understanding has evolved.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 399 1 The substrate for that is all 2 these separate chapters. So, another way, if 3 you are worried about the structure, would be 4 to say, well, we have two chapters or an 5 Executive Summary and an introduction, and a 6 50-page integrative summary, and, then, a 7 series of supporting appendices or something 8 that are literature reviews and compilations 9 of evidence. 10 So, I mean I am thinking of 11 different ways to cast this. And perhaps what 12 is best at this point is to -- I don't think 13 we are going to resolve this around the table. 14 There are a number of ways that you might do 15 this. I think you are going to have to think 16 about what would work best, and probably what 17 will work best for your colleagues who are 18 going to be moving from this onto the policy 19 issues. 20 Yes, John? 21 DR. BAILAR: Different readers 22 will have different kinds of tolerance for

### 202-234-4433 Neal R. Gross & Co., Inc. Page 400 1 length. I think there is a very strong 2 argument to be made for having a two-page 3 summary because that is all that some of the 4 most important readers are going to get 5 through. 6 I think, also, there is a place 7 for something like a 20-page Executive 8 Summary, if it is written with particular care 9 for understandability by people who are not 10 expert in any of this. 11 I think there is a place for 12 something like the present Chapter 2. And 13 there is a place for the summaries at the ends 14 of each chapter. 15 Each of these things serves a 16 different function for a different set of 17 readers. And I would keep them all. 18 DR. SAMET: Yes, I will just make

19 a comment back to BR6 for a moment. We 20 actually had a two-page public summary, the 21 idea being that anyone could pick it up and 22 read it. And as a Committee, we actually

### 202-234-4433 Neal R. Gross & Co., Inc. Page 401 1 spent probably more time per word in writing 2 that than anything else in the document. I 3 mean we really sort of battled over every word 4 for probably a day in putting that together.

5 Jack? 6 DR. HARKEMA: And so, if you go 7 that route with this, and I think that is 8 probably good, I just want to emphasize that, 9 even though Helen liked Figure 2-1, the 10 figures are probably going to be what stick in 11 the people's minds the most. And I would be 12 very careful about that figure that you have, 13 especially that one, that Tower of Babel that 14 you have of effects here. I think that is 15 dangerous. 16 So, if you do that, you know, a 17 lot of those reports, like IARC, and whatever, 18 people remember the figures. 19 DR. SAMET: Judy?

20 DR. GRAHAM: Two comments about 21 length. One is a short story. Three or four 22 ozone standards ago, we sweated bullets and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 402 1 produced a criteria document, maybe 20-30 2 pounds at the time. We sweated bullets. 3 And, then, the Administrator goes 4 to promulgate the standard. I saw it on TV. 5 She stood up and she said, "We are doing this 6 because it hurts your lungs." 7 I wanted to cry. I thought we did 8 all this work. "It hurts your lungs." We 9 could have gone right to the chase. 10 (Laughter.) 11 I was trying to think about what 12 John said about the new versus the old, and 13 trying to marry that with my profound 14 frustration with the separation of the new and

15 the old. 16 This is something for you guys to 17 think about. Perhaps in a policy sense what 18 is important about new versus old is, did 19 anything change? Are there any game-changers? 20 It is not a function of, gee, my favorite 21 marine toad is new; therefore, it gets more 22 space. That is not it. The marine toad is

### 202-234-4433 Neal R. Gross & Co., Inc. Page 403 1 not a game-changer. 2 Perhaps the Kim study is not 3 necessarily a game-changer, but it really 4 pounds in what may be happening at 60 ppb. 5 So, to look for the game-changers, I mean if 6 you are switching from a possible causative to 7 a definitively causative, the game-changers 8 may only be a page or two pages and, then, the 9 rest of it could be here's the story; here's 10 what has happened.11 So, even though there is no game12 changer on lung pathology changes, it doesn't 13 mean that it is still not important. 14 DR. SAMET: So, I think, let's 15 see, Helen, you are the writer of this. You 16 know, what I would suggest for now is that you 17 say that we had a wide-ranging discussion of 18 options, and that you list some of the 19 options. 20 (Laughter.) 21 You know, that we have discussed 22 sort of stay where we are. We have discussed

### 202-234-4433 Neal R. Gross & Co., Inc. Page 404 1 putting this integrative chapter at the end. 2 We have discussed sort of the two-chapter 3 model. I think there is probably some 4 agreement that some summary is needed, and I 5 think ranging, as John proposes, from very 6 brief to a little bit longer. And I think 7 what we should do is lay that out. 8 I mean, clearly, there is a lot of 9 ways, and I think you are going to have to 10 think about what works and what best gets the 11 messages on to the users of the document. So, 12 you probably need to have some dialogue with 13 them, I suspect. 14 So, I think, unless somebody has 15 another possibility here -- Fred?

16 DR. MILLER: I have one. I 17 actually want to add a chapter. This new, you 18 know, in what's changing, could be in here as 19 a subsection at the beginning. I really favor 20 your integrative summary being the last thing. 21 I get really tired of reading 15- 22 20 pages of the Executive Summary and, then,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 405 1 15 pages later I am reading the same stuff 2 over, just in a different way. But if you 3 actually included upfront some highlights of 4 the things that are really new, and then go 5 back and taking what you now have as Chapter 6 2 and placing it at the end, and really making 7 it integrated, I think you really have a story 8 to tell for different audiences that they each 9 can get something out of. 10 And I wouldn't call this short 11 thing about what is really new a separate 12 chapter, but it could be part of Chapter 1, 13 you know, of here's where we stand. But I 14 like that from the viewpoint of telling the 15 spectrum from the two-page summary to the 16 short Executive, to, hey, really what are the 17 hot things that are added, but, then, at the 18 very end here's how it is all integrated. So, 19 it is another -- what? -- option 7? I don't 20 know how many we have discussed. 21 DR. SAMET: Let me ask, I think it 22 was Helen in her comments that, in discussing

### 202-234-4433 Neal R. Gross & Co., Inc. Page 406 1 Chapter 1, said you have to put so much 2 legislative history in it. Was that you? 3 DR. SUH: That was definitely not

4 me. 5 (Laughter.) 6 DR. SAMET: That was not you? 7 Well, it was Michelle, maybe it was Michelle. 8 Somebody made that comment. 9 And I wonder again, in sort of 10 cutting to the chase, I mean, do you have to 11 put all this in? I mean, is it sort of 12 requisite or -- 13 DR. VANDENBERG: No, I think the 14 requirement, of course, was that we develop 15 air quality criteria to support the decision. 16 DR. SAMET: Right. 17 DR. VANDENBERG: And what exactly 18 that is, we have interpreted it as a 19 reflection of the state of the science. The 20 legislative history is just for the reader to 21 have some history. 22 DR. SAMET: Again, you know,

### 202-234-4433 Neal R. Gross & Co., Inc. Page 407 1 perhaps this could be an appendix. I mean I 2 am just reading, in 1982, in 1977, you know, 3 et cetera. Again, it just sort of diverts 4 you. It sort of sets a tone for the document 5 to go, "Oh, no." 6 (Laughter.) 7 DR. VANDENBERG: Point taken. 8 DR. SAMET: So, our last item here 9 is the length of the document. 10 And, oh, yes, Helen, you are 11 summarizing. 12 So, Judy, you are the leader on 13 this critical topic. 14 (Laughter.) 15 DR. GRAHAM: I guess my general 16 comment is that any collection of 17 knowledgeable people is going to have a 18 different view of this. So, there is no right 19 answer. There is no number of pages that is 20 perfect. 21 I mean the important thing that we 22 need to focus on is clarity of presentation

### 202-234-4433 Neal R. Gross & Co., Inc. Page 408 1 for the various audiences who will use it, and 2 particularly for regulatory users. And so, in 3 some cases, you could find places to shorten, 4 but in other cases you might find places to 5 lengthen. I mean to keep your eye on the 6 ball, you know, communicating about the 7 underlying science, about health risk and eco 8 risk. 9 I won't belabor the point, but I 10 think you could go a long distance by putting 11 tables in. That would take care of the 12 problem of insufficient detail in some areas. 13 It would enable you to say, hey, there's five 14 studies on this; the general picture is da, 15 da, da; go look at the table. 16 I know tables would get pretty 17 long, but I think the text itself would be 18 shorter. So, the story may come through. You 19 don't have to wade, swim through all the 20 details. 21 I do think that there is another 22 case in that the old studies in most cases are

### 202-234-4433 Neal R. Gross & Co., Inc. Page 409 1 summarily summarized, and with excessive 2 attention put on the new studies. So, I think 3 that that could be dealt with. In some cases, 4 a new study, I mean even really good new 5 studies, I mean I joke about the frog, but 6 there are some reasonable new studies that are 7 there, but they don't really say anything that 8 the old studies didn't say. 9 So, again, I think in some cases, 10 when you are talking about new studies, you 11 say, well, they are similar to the old study. 12 When you talk about the old studies, then 13 there's the new study. The new studies refer 14 back to the old studies. So, there is a lot 15 of this overlapping, this duplication, when 16 you have a separate section. 17 There is also a lot of duplication 18 with the summaries. And we have had extensive 19 discussion about Chapter 2 and about its 20 being, at present, it is almost a total 21 duplication. 22 In fact, here in my preliminary

### 202-234-4433 Neal R. Gross & Co., Inc. Page 410 1 comments, until I heard this, I was saying, 2 well, just take it away; throw it out. But 3 now, with this discussion we have had, I think 4 that it has hope and it could have value.

5 There are other areas where there 6 is a lot of overlap between MOA sections, 7 effects sections, and susceptible subpops. In 8 some cases, a given paper might apply to all 9 three, but it is only quoted in one place. 10 So, I think the full story doesn't come 11 through. 12 In other cases, you have the 13 effect, and the effect chapter actually talks 14 about MOA. And, then, the MOA chapter talks 15 about effects. And, then, susceptibles 16 chooses some of those to talk about it even

17 more. 18 So, I think there is a lot of 19 duplication of the same study. And this is 20 really, really difficult to deal with because 21 you almost have to have a susceptible chapter 22 -- as I said before, I think your MOA could be

### 202-234-4433 Neal R. Gross & Co., Inc. Page 411 1 integrated with the effects, so you didn't 2 have to duplicate it. But, I mean, it is 3 difficult. 4 Maybe if you have kind of got in 5 your mind that you needed to duplicate on the 6 big-deal studies, that might shorten it some. 7 So, I mean this is very difficult because, 8 too, at the end of the day you want to walk 9 away with a clear understanding of the 10 exposure dose response. And when I say 11 "exposure", I mean concentration and duration 12 and dose-rate-type sorts of things. And so, 13 I mean I defy you to get a good sense of that 14 outside of the ever-popular FEV1 studies. 15 DR. SAMET: Michelle? 16 DR. BELL: Yes. So, I am going 17 to, hopefully, not be lengthy because Judy has 18 already said a lot of my points. 19 I actually think it is appropriate 20 for this document to be painfully long. 21 (Laughter.) 22 I mean there is a huge amount of

### 202-234-4433 Neal R. Gross & Co., Inc. Page 412 1 scientific literature. And I think that if we 2 try to err on the side of making it too brief, 3 I think that we have done a disservice to the 4 science. I think that when you go through 5 this document, you really need to see the 6 incredible amount of work that has been done, 7 the incredible amount of evidence that is very 8 compelling. 9 And I like that the document is 10 kind of long. So, I don't think its overall 11 length is a problem. I mean we have already 12 talked about Chapter 2 and summaries. So, I 13 won't go into that. But once that gets taken 14 care of, I think it is fine that this is long. 15 However, it is kind of uneven. 16 So, there are some places where you have 17 incredible amount of detail and some places 18 where things are really kind of glossed over. 19 And I think part of that is just, due to the 20 length of the document, you had different 21 chapters being written by different people. 22 And so, in my written comments and

### 202-234-4433 Neal R. Gross & Co., Inc. Page 413 1 others, you are going to get some specific 2 examples of things that could be lengthened or 3 shortened up. And I will just give a couple 4 of quick examples of what I mean now. 5 So, like there was a sentence in 6 the first chapter that said, "Typically, only 7 information that had undergone scientific peer 8 review and had been published or accepted for 9 publication was considered." I went up and 10 down this document trying to figure out what 11 does that mean, that you're typically only 12 including peer review documents, but what kind 13 of non-peer-review literature is in here? I 14 have actually like tried to find out. I still

15 don't know. 16 But that is an example of 17 something. You can't just make that statement 18 and, then, leave me hanging. I want to know 19 why is non-peer-review literature in here and 20 what is it. So, that is an example of 21 something. There are a lot of places where I 22 think you want to make sure you don't leave

### 202-234-4433 Neal R. Gross & Co., Inc. Page 414 1 people hanging. 2 And an example of something that 3 is incredibly detailed is Chapter 3. I mean, 4 if you look at the detail in Chapter 3, all of 5 which is really wonderful, it is so far out of 6 balance with the rest of the document. I mean 7 it really stood out to me. 8 I mean there are 20 maps of cities 9 that show where their ozone monitors are. You 10 don't have that level of detail for anything 11 else in this chapter. There are 15 figures 12 comparing time series of GEOS-Chem ozone 13 estimates to measurements. You know, I think 14 one is probably fine. And nor is there any 15 text describing what I am supposed to do with 16 those 15 figures? It just goes on and on and

17 on. 18 So, it is not that that 19 information isn't useful, but I think those 20 are two examples of a place where you really 21 want to think about, are you making your key 22 points and a place where you really want to

### 202-234-4433 Neal R. Gross & Co., Inc. Page 415 1 reel it in maybe about those key points. 2 So, finally, on the issue of the 3 duplication, it has already been mentioned. 4 I know that is going to be taken care of when 5 someone goes through to kind of make these 6 chapters match. 7 And on the issue of tables, I know 8 a lot of people didn't like the criteria 9 document kind of mammoth tables at the end. 10 I always like the tables. I thought they were 11 incredibly useful. I thought they were a 12 phenomenal reference. I mean I would go to 13 them over and over. I don't think there is a 14 better way to do it. 15 So, I agree that the tables are 16 useful. Even if you end up with like these 17 30-page tables, which you will, I think that 18 is going to be more useful, more clear, more 19 systematic than having the text go on and on. 20 So, I think that when you add the tables, if 21 you decide to add them, they are going to be 22 very, very lengthy, but, then, you can cut out

### 202-234-4433 Neal R. Gross & Co., Inc. Page 416 1 a lot of this text. 2 So, some of the concerns I had 3 about Chapter 7 with long-term exposure, you 4 won't have to go through every sentence and 5 add in three months, two weeks, and so on. It 6 will be in the table, and some of the tables 7 already have that kind of information. 8 So, I, again, just highly support 9 Judy's comment to add in the tables, even 10 though I suspect this was in response to the 11 table backlash that some people had. Is that 12 true? But I think that the tables work, work 13 really well, and that it doesn't work without

14 them. 15 So, those are my comments.

16 DR. SAMET: John? 17 DR. BAILAR: I agree with Judy 18 about the value of adding tables. I would add 19 adding some figures where they are 20 appropriate. 21 Another way that you might deal 22 with length is to put parts of this, maybe

### 202-234-4433 Neal R. Gross & Co., Inc. Page 417 1 quite a few parts, in appendices. Legislative 2 history is an obvious candidate. That whole 3 bunch of maps in Chapter 3 is a candidate. 4 There may be some others that EPA could 5 identify, so that the interested reader will 6 have them when they are necessary, but they 7 won't get in the way of the readers who want 8 less in the way of detail. 9 I do not entirely agree with Fred 10 about the location of a summary. There may be 11 a few readers who will look for it in the 12 beginning, as I would, and there may be some 13 who would like an overall view of what is in 14 this document as a whole before they go to 15 individual chapters that may be of special 16 interest. And again, I am one of those. 17 So, I would support keeping maybe 18 the 20-page summary at the beginning. Maybe 19 the equivalent of Chapter 2 could go at the 20 end. So, I am not sure how much we agree or 21 disagree.

22 DR. SAMET: Fred?

### 202-234-4433 Neal R. Gross & Co., Inc. Page 418 1 DR. MILLER: You are saying 2 exactly what I was getting at. Really, that 3 is what I meant to come across. 4 But I like what Michelle brought 5 up and reinforced about the tables. In 6 particular, it would allow you to interpret 7 and describe what the collection of studies is 8 showing in the text, instead of having to say, 9 "Jones, et al., exposed 26 people to" blah, 10 blah, blah, blah, blah. Okay? 11 The bottom line, "This collection 12 of studies shows that ozone affects PM in 13 flux, and this is important relative to 14 inflammatory responses that have been shown in 15 animals, humans," blah, blah, blah. And that 16 tells the story, and the tables allow you to

17 do that. 18 Whereas, right now, a lot of the 19 text is having to describe that. Now it would 20 be able to become more interpretative and 21 discuss really the highlights of what is the 22 take-home message. And so, I think it is the

### 202-234-4433 Neal R. Gross & Co., Inc. Page 419 1 way to go.

2 DR. SAMET: Go ahead. Go ahead. 3 DR. NEUFELD: I would just say the 4 other thing, too, to help the clarity of the 5 entire document is I think a standardized 6 format for the chapters. Decide what you want 7 in the beginning, in the middle, and the end, 8 and, then, we talked about having your chapter 9 having a summary. Decide whether you want to 10 have interior portions coming to some 11 conclusion and, then, final ones at the end. 12 But if you adopt a consistent 13 format, it will make the readability improve. 14 DR. SAMET: Okay. Peter? 15 DR. WOODBURY: Well, I have heard 16 enough comments here that I am sure I will be 17 repeating what someone said already. 18 But I think it is important to 19 have a summary chapter of approximately the 20 length of Chapter 2 that includes the main 21 conclusions. So, Chapter 2 does that now. 22 I think there is a structure here

### 202-234-4433 Neal R. Gross & Co., Inc. Page 420 1 with the causal relationships. So, these are 2 essentially, I guess the jargon I would use 3 would be these are knowledge claims. That is 4 the level of integration that I think is 5 appropriate for this document. 6 I think it is unrealistic to 7 expect that a summary of the state of the 8 science, I don't think that is going to lend 9 itself to an extremely high degree of 10 integration. We have disparate pieces of 11 knowledge. 12 We have a whole bunch of disparate 13 experts in this room. And I would mention 14 that few of us have really dug deeply into 15 every chapter in here. If we aren't doing all 16 that, then I think the audience for reading 17 this entire document is rather small. 18 The audience for reading something 19 that is 50 pages or so is much larger. I 20 think when you go to the two-page Executive 21 Summary, you have no room for definitions. It 22 becomes very, very difficult, as you have

### 202-234-4433 Neal R. Gross & Co., Inc. Page 421 1 discussed. That may be important. 2 And I think that the two-page kind 3 of summary can really just be the knowledge 4 claims without definitions of terminology, 5 without explanation of how they were arrived 6 at. So, it is essentially a list of the 7 conclusions of the main knowledge claims. 8 So, I guess I would say I am in 9 favor of something like Chapter 2. I think it 10 does need to be linked very well with the 11 remaining chapters. And whether the remaining 12 chapters are called annexes or something else, 13 I think there needs to be a very clear way to 14 get there. 15 One way may be by organizing it by 16 these knowledge claims. So, for each of the 17 knowledge claims in Chapter 2, then it tells 18 you the page number to go in the rest of the 19 document to understand how that conclusion was 20 arrived at. 21 I think it is inevitable there is 22 going to be some duplication throughout this

### 202-234-4433 Neal R. Gross & Co., Inc. Page 422 1 document. So, I am less concerned about that 2 than that there be, again, a readable summary 3 of the knowledge claims with clear linkages to 4 the supporting evidence for those. 5 DR. SAMET: Okay. Thank you. 6 Anybody on the phone, comments?

7 DR. WEATHERS: Not here. 8 DR. STALLWORTH: Chris just mailed 9 you some comments. 10 DR. SAMET: Okay. Chris, do you

11 have comments? No? 12 DR. FREY: I don't think I have 13 anything substantially more to say, except I 14 am in the camp of kind of trying to keep 15 Chapter 2 early in the document. 16 I was wondering about, I kind of 17 like the idea of a two-page overview and maybe 18 something that is more like a story of what 19 this document is about. I don't see why that 20 couldn't actually be the first couple of pages 21 of Chapter 2. Then, the current meat of 22 Chapter 2 probably could be a little bit

### 202-234-4433 Neal R. Gross & Co., Inc. Page 423 1 shorter. 2 I am thinking that each of the 3 subsequent chapters ought to close with some 4 clear findings. If that were done, then 5 Chapter 2 wouldn't have to repeat a lot of the 6 technical support for the findings. It could 7 just echo the findings and be more concise. 8 Then, that would allow maybe some more thought 9 to be given to the synthesis and the 10 integration. 11 DR. SAMET: Okay. Thanks. I am 12 going to summarize as follows: 13 We have given you many ways to 14 organize the document, but we don't have a 15 preference. And the document should be 16 neither too long nor too short. 17 (Laughter.) 18 I think we are done, but we have a 19 little bit more work to do. 20 I am actually not going to be here 21 tomorrow except by phone. I am flying back 22 tonight because I am leaving for France

### 202-234-4433 Neal R. Gross & Co., Inc. Page 424 1 tomorrow night from LA. 2 I think Chris or -- 3 DR. STALLWORTH: Chris will chair

4 tomorrow. 5 DR. SAMET: Chris will chair, 6 unless his illness keeps him away. And 7 otherwise, we have reserved backup plans here. 8 One thing we want to do is just 9 look at setting a date. So, we will need to 10 discuss our draft letter by teleconference, 11 and we need some time to announce that. There 12 will likely be some exchanges amongst the 13 three or four people who are writing these 14 different sections together, and that will 15 take several weeks. So, we are probably 16 looking at potentially the week of July 4th 17 perhaps to hold that conference call. And 18 setting aside the day of July 4th, although 19 that may be available -- 20 (Laughter.) 21 Is it a federal holiday?

22 DR. STALLWORTH: Yes.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 425 1 DR. SAMET: Setting aside that 2 day, if everyone will do something a little 3 more refined, but with that week, likely most 4 people have one day of availability. I think 5 that is really the question, and we will have

6 to hone down. 7 DR. STALLWORTH: Jon, just pick a 8 date and we will see if people are -- 9 DR. SAMET: All right. I am now 10 going to pick a date, a favorite date. How 11 about July 6th? That is the Wednesday. July 12 4th is Monday.

13 DR. STALLWORTH: 10:00 a.m. 14 Eastern Time. Wednesday, July 6th, 10:00 a.m. 15 Eastern Time. 16 DR. SAMET: Can't do it? Well, we 17 will send out a couple of days that week. I 18 know Holly wants to get this done. It is a 19 challenge. We will send out a couple of days

20 that week. 21 DR. MILLER: Anytime you have a 22 holiday with the week, people take vacation

### 202-234-4433 Neal R. Gross & Co., Inc. Page 426 1 and you really need to go to the next week in 2 July, July 11th and 12th, or something like

3 that. 4 DR. SAMET: Okay. I told you, 5 Holly, this wouldn't work. 6 DR. STALLWORTH: Yes. All right. 7 DR. SAMET: So, we gave it a try. 8 So, anyway, just again, let me go through the 9 schedule of events with you, which is that I 10 asked that the groups, the leaders, summarize 11 and synthesize the comments.

12 Remember that all the comments 13 don't have to be brought forward from the 14 individuals because your individual comments 15 will be included. So, it is the draft 16 response to the charge question that needs to 17 be prepared. If somebody could take the lead 18 in assembling that, based on what was written, 19 plus the discussion here, and then circulate 20 that to your colleagues, I think with a few 21 iterations smooth that out. Then, when you 22 are ready, send it on to Holly.

### 202-234-4433 Neal R. Gross & Co., Inc. Page 427 1 DR. STALLWORTH: Right, and you 2 need to be ready. One week from tomorrow, is 3 that too soon? You need more time? Okay, the 4 following Friday. 5 DR. SAMET: So, let's say two

6 weeks.

7 DR. STALLWORTH: In two weeks.

8 DR. SAMET: Two weeks -- and 9 again, Holly will send out a note -- to get 10 these to Holly. Then, she and I will work on 11 the letter, and there will be some chance

12 to -- 13 DR. STALLWORTH: So, that will be

14 due June 3rd. 15 DR. SAMET: June 3rd. We will 16 work on the letter, and you will have a chance 17 to look at that, of course, before -- 18 DR. MILLER: Jon, can you give us 19 some guidance? Like when a specific question 20 was asked, two or three paragraphs seem to me 21 the amount that you would be -- 22 DR. SAMET: Right, right. Yes, we

### 202-234-4433 Neal R. Gross & Co., Inc. Page 428 1 have tried to keep these relatively brief, and 2 more detailed comments really would stay with 3 the individual's responses. 4 So, I think we have gotten our job 5 done for the first day. I want to thank 6 everybody for their hard work. I mean there 7 is so much to talk about, and I think our job 8 here really is to hone in on what is most 9 critical and to give guidance to the agency in 10 making the revisions.

11 You are back at 8:30 tomorrow 12 morning to discuss these two documents that 13 will be presented. 14 DR. STALLWORTH: The scope and

15 methods. 16 DR. SAMET: The scope and methods. 17 There will be public comments. 18 DR. STALLWORTH: Just a couple, 19 yes. 20 DR. SAMET: A couple tomorrow as

21 well. 22 For those of you not familiar with

### 202-234-4433 Neal R. Gross & Co., Inc. Page 429 1 Chapel Hill, there's lot of restaurants out 2 the door, and that is one advantage of being

3 here. 4 We have not lately been doing 5 group dinners, but please feel free to form 6 up, you know, dosimetrists with dosimetrists. 7 (Laughter.) 8 I suspect from the locals we can 9 get some restaurant recommendations. 10 So, thanks to everybody for the 11 hard work, to the public for comments, and to 12 EPA for your presentations. Thanks. 13 (Whereupon, at 5:08 p.m., the 14 foregoing matter went off the record.)

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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 486

Ozone Review Panel

US EPA Clean Air Advisory Committee

05-19-11

Chapel Hill, NC