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 U.S. ENVIRONMENTAL PROTECTION AGENCY

 + + + + +

 CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE

 CARBON MONOXIDE NAAQS REVIEW PANEL

 + + + + +

 PUBLIC MEETING

 + + + + +

 TUESDAY, MARCH 23, 2010

 + + + + +

 The Panel met in Salon ABC of the

Marriott Research Triangle Park, 4700 Guardian

Drive, Durham, NC, at 8:30 a.m., Joseph Brain,

Chair, presiding.

CASAC MEMBERS PRESENT:

 JOSEPH BRAIN, Chair

PANEL MEMBERS PRESENT:

 PAUL BLANC

 THOMAS DAHMS

 MILAN HAZUCHA

 JOEL KAUFMAN

 MICHAEL KLEINMAN

 FRANCINE LADEN

 ARTHUR PENN

 BEATE RITZ

 PAUL ROBERTS

 STEPHEN THOM
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SCIENCE ADVISORY BOARD STAFF:

 KYNDALL BARRY, Designated Federal

 Officer

 ANTHONY MACIOROWSKI, Deputy Director

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 TABLE OF CONTENTS

 AGENDA ITEM PAGE

Response to PA Charge Question 7-8 3

Dr. Stephen Thom 

Response to PA Charge Questions 9-10 48

Dr. Paul Roberts

Response to PA Charge Question 11 56

Dr. Paul Roberts

Summary and Next Steps 167

Dr. Joe Brain

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1 P R O C E E D I N G S

2 (8:32 a.m.)

3 CHAIR BRAIN: Good morning,

4 everyone. I think we are in good shape to

5 finish by Noon, but we do have multiple tasks. 

6 We want to look at the comments that were

7 produced by all of you and assembled by

8 Kyndall, and they will be distributed in hard

9 copy sometime during the next half-hour or so.

10 The other thing we need to do is

11 to continue our initial discussion of the

12 charge questions to the PA document.

13 So in the absence of the letters,

14 why don't we continue with that. So I think

15 we are up to you, Mike. Is that right? 

16 DR. KLEINMAN: Yes.

17 CHAIR BRAIN: I think that is

18 right. So we are now talking about the Policy

19 Assessment document, Charge Questions 7 and 8,

20 and Mike will lead us through that discussion.

21 DR. KLEINMAN: I am bringing the

22 text up on my computer. Okay, sorry for the

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1 delay.

2 I put this together pretty late

3 last night. So it definitely needs some

4 editing. But I think the staff has done an

5 extensive analysis of the adequacy of the

6 current and potential alternative primary CO

7 standards.

8 So the current standard, just to

9 remind us, is a one-hour average and an eight10 hour average standard. The one-hour is 35

11 ppm. The eight-hour is nine ppm. The form of

12 the standard is that the levels are not to be

13 exceeded more than once a year.

14 In reviewing the adequacy of the

15 standards and the recent literature, the staff

16 has commented that the -- and I am going to

17 quote this, "the much expanded epidemiological

18 evidence provides support for previous

19 conclusions regarding cardiovascular disease,

20 related susceptibility, and indications of air

21 quality conditions that may be associated with

22 ambient CO related risk."
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1 They conclude that a causal

2 relationship is likely to exist between

3 relevant short-term exposures to CO and

4 cardiovascular morbidity. 

5 Having said that, there were

6 several studies, epidemiological studies, that

7 were cited in Table 2.1 which, when you look

8 at it, is really not as many studies as it

9 appears to be, because it was broken up in

10 terms of health outcomes.

11 After reviewing those studies,

12 staff concluded that -- Well, let me back up. 

13 So the table contains studies that have

14 ischemic heart disease, congestive heart

15 failure, and other cardiovascular diseases

16 broken out as separate categories.

17 Several of these studies, three of

18 them, are from the same city, Atlanta. So

19 there is a Tolbert study, a Peel study and a

20 Metzger study. Each of those studies were

21 studies that were done during periods when the

22 standards were not exceeded, and I believe it

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1 was the eight-hour standard that they were

2 focusing on.

3 There was one additional study on

4 that page which did not exceed the standard,

5 and that was a congestive heart disease --

6 congestive heart failure study, Wallenius. So

7 that one also was done during a period when

8 there was no excedence of the standard.

9 There were four other studies in

10 which, in fact, there were excedences. So I

11 think the bottom line was the staff concluded

12 that there was not enough epidemiological

13 data, since two of the Atlanta studies didn't

14 show a statistically significant outcome,

15 whereas one of them did, and they also said

16 that the congestive heart failure studies were

17 less useful, because congestive heart failure

18 has multiple causes, and it would be more

19 difficult to identify CO as a causal agent.

20 So in reviewing this, it seems

21 apparent that we need a better way to look at

22 the epidemiological studies, and what has been

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1 done in the PM sector and what has been done

2 with nitrogen oxides has been to use meta

3 analyses and other more sophisticated

4 reanalytical approaches to the epidemiology to

5 help develop concentration-response

6 relationships.

7 In this case, I think the data may

8 lend itself very well to that, because we have

9 studies, and even the studies where work was

10 done where it exceeds the standard -- those

11 can be used to help define a dose response

12 curve or a concentration response curve.

13 The beauty of it is you actually

14 don't have to extrapolate, as we often do with

15 toxicology studies, because we have lower

16 level studies that had significant effects. 

17 So I think one of the things that we need to -

18 - or that would be useful to bring out is that

19 there is a need for a more thorough analysis

20 of the epidemiological database.

21 The other thing to point out is

22 that the document calls out that there have

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1 been no new controlled human studies,

2 especially to look at some of the more recent

3 endpoints that are being brought up through

4 the epidemiology, like the field

5 susceptibility, things like that, and the

6 likelihood of being able to do controlled

7 human studies with these very susceptible

8 groups is extremely low.

9 So it may be that there will be no

10 new controlled human studies going forward in

11 the future. Therefore, epidemiology is what

12 we are going to have left to work with.

13 So again, I think we need to focus

14 on possibly suggestions for improving the way

15 that epidemiology can be used in these policy

16 assessments.

17 The staff put out -- Their keynote

18 was they said that the data provides support

19 for retaining or revising the current eight20 hour standard, which one of the members of the

21 Panel termed ambiguous. 

22 It would seem that, if we gave
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1 more weight to the epidemiological evidence,

2 one might conclude that the health effects are

3 accruing at levels below current standard, and

4 we have large numbers of individuals which

5 really haven't been tallied that are more

6 susceptible possibly than people with coronary

7 artery disease. 

8 Therefore, the evidence might lean

9 -- could be taken to lean in the direction of

10 revising the current standard. 

11 So that kind of brings us to the

12 Charge Question 8. So I think we do agree

13 that the data presented does support a range

14 of policy options or at least consideration of

15 a range of policy options, and the question is

16 how to approach that.

17 A number of proposals were raised,

18 and I personally found it sort of difficult to

19 keep track of which proposal was which, but I

20 think there are a number of approaches that

21 were brought out.

22 So, for example, the eight-hour

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1 standard: So one possibility is retain the

2 eight-hour averaging time, and give

3 consideration to levels within a range of

4 three to nine ppm, which is quite broad and

5 based on the concentration response

6 relationships derived from the coronary artery

7 disease studies, or consider revising the

8 current standard to a different form -- for

9 example, taking the 99th percentile of the

10 fourth highest maximum instead of the current

11 statistic that is being used.

12 The one-hour standard: One of the

13 options is to retain the current standard,

14 which will provide protection against more

15 infrequent acute exposures, and consider a

16 range of five to 15 ppm instead of the current

17 35 ppm. That could be combined with choosing

18 a 99th percentile or a fourth highest maximum

19 as the statistic.

20 Alternatively, they suggest it

21 might be possible if the eight-hour standard

22 is made more restrictive than perhaps the --

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1 and that would be the controlling standard,

2 and the one-hour standard could be revoked.

3 So to what extent does the

4 document provide sufficient rationale for this

5 range? We talked about this yesterday, but

6 the rationale was based on choosing ranges of

7 carboxyhemoglobin benchmarks, 1.5, 1.8 and 2.0

8 percent carboxyhemoglobin, as levels to

9 protect against, and then using the Coburn

10 force obtained relationship, going back and

11 back-calculating what the exposures would be

12 that would reach that.

13 I think, because we don't have a

14 dose response or a concentration response

15 relationship based on epidemiology, this is

16 what we have at present. I think we should

17 encourage EPA to try to find some way of

18 developing relationships for the

19 epidemiological data similar to what has been

20 done before PM, and that may give us a clearer

21 idea of what the options could be.

22 Another thing that I think would

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1 be very useful for the PA would be to

2 summarize the options, perhaps in a table, and

3 list what are the pros and what are the cons

4 of each of the options, so that the

5 Administrator can look at one place and have

6 at least a snapshot of what the consequences

7 of each decision might be.

8 The staff does mention that

9 retaining the one-hour standard might provide

10 protection independent of the type of

11 protection provided by the eight-hour

12 standard, but the discussion surrounding that

13 statement really was not very clear. So a

14 little more discussion about that would be

15 useful to include in the document.

16 Does the Panel have

17 recommendations regarding additional

18 considerations which should inform

19 characterization of these options?

20 I don't know if this is something

21 that we would normally do, but it might be

22 useful to indicate with each of the options in
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1 terms of pros and cons how many areas might

2 become out of compliance under each option. 

3 It might be something useful to at least have

4 some information on.

5 I think, as I said, a clearer

6 summary of the options' pros and cons would be

7 very helpful in evaluation of how

8 representative the risk analysis, which is

9 based on two selected cities -- how

10 representative is that of the rest of the

11 country? I think that needs to be discussed

12 a little bit in the document, and in terms of

13 setting the standard -- some mechanism or some

14 concept of how to deal with the spatial

15 heterogeneity of CO exposures, for example, in

16 near-roadway things. How is that going to be

17 incorporated into these discussions?

18 So I think those were the primary

19 views that came out of the individual

20 comments. 

21 One other individual, Ann Sweeney

22 -- I presume Ann is not on the line -- raised

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1 the issue that there is a social justice

2 parameter to carbon monoxide. I was thinking

3 about that, because it doesn't -- I don't know

4 how that fits into primary standards, but I

5 was wondering whether social justice might be

6 considered later on as part of a rationale for

7 discussing a secondary standard.

8 It would be very interesting to

9 set a secondary standard, for example, that

10 would protect against very high levels near a

11 roadside, which would have an interesting side

12 effect; because if we had a secondary standard

13 that could be applied at roadsides, should EPA

14 start to establish roadside sampling or near15 road sampling? 

16 Violations of the primary standard

17 might not necessarily accrue from the near18 road sampler being out of compliance, which it

19 may well be, even at the current standard. 

20 So those are my comments. We

21 should open it up to everybody else, I guess.

22 CHAIR BRAIN: I am impressed that

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1 you are talking really about the heart of the

2 matter, and this is a really important part of

3 our letter.

4 So you comment on the range of

5 alternatives and present some new ones. Do

6 you think we should be expressing a preference

7 in terms of -- you mentioned keeping it as it

8 is, going from three to seven. How do you

9 come down? Do you just want to comment on the

10 suite of alternatives that are presented and

11 they are adequately presented or do you think

12 the Panel should be expressing a preference

13 for overall direction of the form? How do you

14 feel about that, and then let's hear how

15 everyone else feels.

16 DR. KLEINMAN: My feeling is that

17 the data suggests that the current standard is

18 not adequately protective and that a new

19 standard should be somewhat lower than it

20 currently is. Now --

21 CHAIR BRAIN: So that is a nice,

22 concise summary. Is there general agreement

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1 with that? Any dissenters?

2 DR. KLEINMAN: Okay. I will add

3 that.

4 CHAIR BRAIN: So it sounds like

5 that should be clear. In fact, that sounds

6 like something that should be up front in the

7 covering two-page letter as well.

8 DR. KLEINMAN: Okay.

9 CHAIR BRAIN: You were in the

10 middle of continuing.

11 DR. KLEINMAN: Yes. I think that

12 we can certainly -- I think that the ranges of

13 concentrations that have been proposed by the

14 staff have relative merits. Since we don't

15 really suggest standards per se -- we just

16 advise the direction of things -- providing

17 that range of standards, but suggesting that

18 the range should not be as high as the current

19 standard. So we should trim the range to

20 something below the current level.

21 DR. HAZUCHA: Forgive my

22 ignorance, but what is social justice
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1 parameter? Apparently, everybody knows, but

2 somehow I do not know what it is.

3 DR. KLEINMAN: Well, in this

4 particular case, the properties in areas where

5 there is more pollution, and notably roadsides

6 are one among them, or areas next to

7 industrial emitters, the people who are living

8 in those areas tend to be from the lower

9 socioeconomic class. Hence, they are

10 receiving more pollution, because they have

11 lower incomes and, therefore, it is a social

12 justice issue. 

13 DR. HAZUCHA: Oh, okay.

14 CHAIR BRAIN: But it is probably a

15 component to almost every environmental

16 standard we can think of.

17 DR. KLEINMAN: Absolutely.

18 DR. HAZUCHA: So it is basically

19 socioeconomic status.

20 DR. BLANC: Yes, which you brought

21 up, although again just to come back, for

22 example, to the issue that you also brought up

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1 of endogenous CO production: If poverty is

2 concentrated in part in African American

3 communities in the United States and if that

4 is where sickle cell disease is and that is

5 where higher metabolic rates are, and that is

6 who lives near roadways, there are scenarios

7 that you can describe that make operational 

8 theoretical social justice concerns in this

9 particular example more concretely than in

10 some others.

11 CHAIR BRAIN: Other comments? We

12 also welcome our early bird on the West Coast,

13 Beate Ritz. Do you want to make any comments

14 on policy questions seven and eight?

15 DR. RITZ: I actually think my

16 colleague knows very well, and the only

17 addition I have to make here is that we really

18 have to think it through to go to spatial

19 heterogeneity being included or making a

20 recommendation for the inclusion.

21 Clearly, there will be groups that

22 are much more affected, and there is a source,

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1 a heavy source component to CO. If we really

2 believe that COHb has a lot to do with the

3 health effects, then that is very, very

4 relevant, but we probably also have to

5 consider newer sources of CO. 

6 If we think in the future there

7 may be other sources, then constructing a

8 whole measurement network based on roadways

9 right now may not do us much service, if that

10 is something we are worried about in the

11 future -- that the sources may change.

12 CHAIR BRAIN: Now how do others

13 feel about -- Do we actually want to suggest

14 a secondary standard focusing on roadways, or

15 just -- It was an interesting possibility. 

16 Should it be left out or mentioned casually? 

17 Does EPA have a comment?

18 DR. MURPHY: I just want to

19 perhaps provide clarification, and I was a

20 little confused by this point that was raised

21 by Dr. Kleinman.

22 With regard to the standards, you

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1 were speaking in terms of -- I thought you

2 were perhaps saying that an excedence of the

3 primary standard would not count, or

4 something. I want to assure you that it

5 would.

6 Where we have the data indicating

7 that the standard is not met in ambient air,

8 that would be an excedence of the standard. 

9 It would trigger a variety of control options,

10 and that is how the standards work.

11 You also made a comment with

12 regard to the secondary. I might alert you to

13 chapter three which talks about the secondary

14 and quotes from the anecdotes as to what the

15 secondary in intended to protect against. 

16 Rather than protection of public health, it is

17 protection of public welfare, and it lists a

18 variety of things which are considered in

19 that, and social justice would not

20 necessarily, I believe, fall within that

21 category. It is closer to the public health

22 protection, of course, with adequate margin of
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1 safety.

2 So just to make sure you

3 understood that an excedence of the primary

4 standard is definitely something we take

5 seriously.

6 CHAIR BRAIN: I thought he was

7 saying that, even though the primary standard

8 may be met, that along roadways there may be

9 higher levels. So I guess, is that more of a

10 monitoring issue than we are just not

11 measuring it in the right --

12 DR. KLEINMAN: What I am saying is

13 that, if the monitoring is changed to include

14 near-road samplers, those near-road samplers

15 are very likely to produce much higher levels

16 than the samplers that are out there in the

17 general public area.

18 So the question is: If, for

19 example, EPA does place roadway samplers or

20 near-road samplers out there or in areas where

21 there is really very non-homogeneous carbon

22 monoxide concentrations -- and that can occur

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1 in canyons, in cities, urban canyons; we know

2 that those things occur, and in fact,

3 placement of samplers generally avoids those

4 kinds of hot spots.

5 So the issue is, if we are going

6 to include hot spot samples or samplers, are

7 they going to be treated in exactly the same

8 way as all the other samplers or can they be

9 given sort of a secondary role for monitoring

10 these very high levels that may occur in very

11 localized areas?

12 The other point in terms of the

13 social justice, I realize that it is supposed

14 to be property issues and welfare issues. 

15 What I am thinking is that the root source of

16 the social justice argument is the property

17 values are degraded because of the presence of

18 pollution. 

19 So it is a little circuitous, but

20 it is not untenable to make that claim.

21 MR. ORLIN: My name is David

22 Orlin. I am with EPA's Office of General

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1 Counsel, and I just wanted to clarify a little

2 bit, because we do have -- You know, primary

3 and secondary have commonly understood

4 meanings, but for the Clean Air Act, you know,

5 we do have a definite understanding for the

6 NAAQS that the primary would be the health

7 based standard, and the secondary would be the

8 welfare or sort of ecological standard.

9 It is sort of theoretically

10 possible that you could define a standard in

11 terms of its monitoring siting criteria. So

12 that you would say, you know, we are not

13 going to consider monitor results that are

14 near a roadway. And if the Panel thought that

15 was important, then they could provide advice

16 on that, but as a general practice, EPA's

17 strong preference has always been to set the

18 NAAQS across an area and to look at all the

19 relevant monitoring data.

20 As Dr. Murphy said, as a general

21 matter, once we set the standard, we will look

22 at any valid data, and we don't like to look

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1 at data and then say, you know, even though

2 this is above the level of the standard, we

3 are not going to consider it a violation. But

4 if the Panel is concerned about treatment of

5 hot spots, one way or the other, then they

6 could provide some advice on that.

7 CHAIR BRAIN: I confess, I just

8 need to be educated about the way the current

9 monitoring network is working. If you have a

10 city and you have 50 monitors, and just one of

11 them is above the standard, is that a

12 violation or not? 

13 DR. MURPHY: Yes.

14 CHAIR BRAIN: It is?

15 DR. MURPHY: Yes. And if I might

16 add, my understanding of the network for CO is

17 the intention is that they be near roads. Now

18 as I mentioned yesterday, in the current

19 monitoring network there are many monitors

20 which are not near roadways, and that is one

21 thing that happens as we review the standards. 

22 We get another look at the monitoring network.
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1 So we will be looking at that

2 again, and the monitoring folks will be

3 deciding if they need to modify the monitoring

4 regulations. But my understanding of the

5 current monitoring regulations is they do

6 require that monitors be near where we expect

7 there to be CO at concentrations which might

8 exceed the standards, and clearly, those would

9 be near roadways.

10 DR. PENN: Just one question. 

11 When you had the PM meeting a couple of weeks

12 ago and you talked about -- we talked about it

13 yesterday -- did they bring up or address this

14 argument in terms of PM monitoring near

15 roadways or was that not a consideration?

16 CHAIR BRAIN: I think it was

17 mentioned. There, certainly, was discussion

18 of traffic, dust.

19 DR. PENN: Because that is a big

20 part of the papers that have been produced

21 recently.

22 DR. ROBERTS: Joe, I thought Mike

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1 brought up something interesting, and I

2 wondered if staff had looked at numbers of

3 sites that might exceed the suggested range,

4 like the three ppm eight-hour or applied 15

5 one-hour proposed possible?

6 DR. MURPHY: Right. In terms of

7 considering a decision, providing information

8 on what might support options for a standard,

9 that would normally not be something that we

10 ought to consider, and that is not something

11 that the Administrator would consider in 

12 setting the standard. However, it is not

13 unusual for that information to be available

14 and, for example, at the time of proposal

15 there are some public communication materials

16 which make clear what the impact might be, but

17 to date we have not developed that type of

18 material.

19 DR. DAHMS: It seemed to me that

20 the current monitoring network is positioned

21 based on actual exposure, projected exposure

22 and times of exposure, or for modeling

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1 purposes. In other words, you would expect

2 that, if eight percent of a person's time is

3 on a highway, that eight percent of the

4 monitors might be within 50 meters of a

5 highway, but that is not the case. There is

6 no -- In other words, there is no way of

7 making that assumption.

8 I would think that in the future

9 it would be -- You know, what is the point of

10 having a monitor in an urban canyon in L.A.

11 when less than 100 to one percent of the

12 people spent any time in that canyon. It then

13 becomes not very representative of very many

14 people's exposure.

15 There are people that -- I don't

16 know what you do. You post a sign: You are

17 entering a place of high risk; do it on your

18 own? You know, how do you -- We are talking

19 about definitely placing things where there is

20 going to be excedence of standards.

21 CHAIR BRAIN: Is there a paradigm

22 for how monitors are deployed? Again, does it

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1 represent -- Is it intended to best represent

2 the average human exposure or do you look for

3 the worst places? What is the philosophy or

4 is it just willy nilly and a matter of

5 history?

6 DR. MURPHY: Are you asking EPA?

7 CHAIR BRAIN: yes.

8 DR. MURPHY: Okay. So the answer

9 would be, in terms of required monitors, as

10 part of the standard we tend to have

11 requirements for monitors to try to identify

12 areas where the ambient air has the potential

13 to exceed the standard; because, of course, we

14 do not want the ambient air to exceed the

15 standard.

16 So we would -- and in CO -- it is

17 my understanding that the regulations, which

18 date back a bit, but their requirement was to

19 put the monitor near the places where we

20 thought the standard would be exceeded, which

21 in the case of CO, as you all well know, is

22 near roadways. So that is a requirement.
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1 Now over the years, you know,

2 evolution happens in terms of states having a

3 variety of reasons that they put monitors out. 

4 Some of them may be to meet that requirement

5 of the National Ambient Air Quality Standards. 

6 Some of their needs for the standard may be

7 that they want to have a sense of what are the

8 CO concentrations in very populated areas.

9 So when you then look across where

10 are the monitors today, they may represent a

11 variety of objectives, but the objective in

12 terms of the NAAQS is to make sure we are

13 monitoring in places where the standard has

14 the potential to be exceeded. That is the

15 purpose for the EPA regulations requiring

16 those monitors.

17 Beyond that, people may have

18 objectives. Researchers may have objectives.

19 States may have objectives. So the actual

20 network may look a little different, and you

21 might not realize an underlying objective for

22 the standard.

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1 CHAIR BRAIN: That is very

2 helpful. It is interesting, isn't it? So a

3 redeployment or more monitors in high level

4 areas, in a sense, represents a de facto

5 tightening of the standard, doesn't it, to

6 some extent?

7 DR. PENN: But one question. It

8 is the states that decide where the monitors

9 ultimately are placed, is it not?

10 DR. MURPHY: The states place the

11 monitors, but the EPA has regulations

12 requiring certain things about monitor

13 placement as a minimum requirement.

14 For example, we require that the

15 states place monitors where there is --

16 generally speaking, where the ambient air has

17 the potential to exceed the standard, and in

18 the CO -- I wish I had in front of me the CO

19 monitoring requirements, but it is my

20 understanding that they be near -- I mean, for

21 some of the pollutants, there are phrases

22 like, area of maximum concentration. That is

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1 a phrase for the lead standards -- lead

2 monitors, for example.

3 So there is an underlying federal

4 regulation that directs where we require there

5 be monitors placed, but the states are the

6 ones with the responsibility to place those

7 monitors. So they may place them additionally

8 in other locations.

9 DR. PENN: But you would suggest,

10 for instance, that there might be places on I11 5 where there should be a monitor placed or

12 you just make it more general in terms of

13 roadways, and then California can decide if

14 they want to put it down, you know, Long Beach

15 or if they want to put it up higher? 

16 There is a lot of leeway, it

17 seems. You guys make the suggestions, but it

18 is still ultimately where the states decide to

19 put it, or do you actually say we think there

20 should be something along the West Side

21 Highway in Manhattan?

22 DR. MURPHY: No. the regulations,

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1 of course, would not be that specific.

2 CHAIR BRAIN: Mike, do you have

3 enough guidance?

4 DR. ROBERTS: Can I add a couple

5 of things there? So I think what staff has

6 said is what the goals are. There are a

7 couple of things going on now.

8 The states -- All the agencies are

9 in a five-year cycle of evaluating their

10 networks. They are required to do this as

11 part of EPA requirements, and there are

12 multiple objectives for all monitoring sites,

13 including population exposure and high

14 concentrations. You know, there is a long

15 list of that. 

16 We have done some of these for

17 some areas. Traditionally, there are not very

18 many near-roadway CO monitors, as we talked

19 about earlier with the ISA. The ratings in

20 the official system aren't actually very good,

21 but there are only a couple of sites in the

22 country -- I think, three -- that are within
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1 50 meters of the edge of the roadway, which is

2 what the new NO2 requirement is, for example.

3 People want tradition. They want

4 what is the trend in CO to understand the CO

5 emissions inventory improvements, and things

6 like that. So there is a range of objectives,

7 but there have been a few monitors that have

8 been excluded from standards.

9 I know Las Vegas had a monitor on

10 the sidewalk on the Strip at the MGM Grand for

11 years that was excluded from -- it was a hot

12 spot monitor. It was excluded from the

13 standards. Now that was placed there when

14 they were actually exceeding the standard of

15 nine, but now they no longer do either.

16 So I think in the current every

17 five-year network evaluation, I think they are

18 all due July 1st this year. So this is the

19 first real time that real serious quantitative

20 analysis of monitoring networks is being done,

21 and everybody is required to do that. So I

22 think that will improve the CO monitoring

Page 35

1 network as well as others.

2 I know it is not really part of

3 our evaluation, because I think our evaluation

4 of where the standard should be -- Mike very

5 eloquently discussed what Table 2.1 is,

6 etcetera.

7 I actually suspect that near-road

8 50 meter monitors will not exceed a lowered

9 standard. I just finished a year in Las Vegas

10 with three monitors, one monitor within 50

11 meters and a couple within -- well, two within

12 50 meters and one within 120 meters of the

13 roadway. 

14 So I suspect that, if we are

15 worried that, gee, that will throw a whole

16 bunch into non-attainment, I don't think that

17 will happen, especially with the continuing

18 downward trend. There is still a strong CO

19 downward trend here. It hasn't really

20 bottomed out as much as some of the other

21 pollutants.

22 DR. THOM: Joe, aren't we dealing

Page 36

1 with the future? Shouldn't we be? We are

2 dealing with the science that we've got in

3 front of us?

4 CHAIR BRAIN: I think so. This

5 has been an interesting discussion, but let's

6 see if we can wind this up.

7 First of all, is there anybody on

8 the telephone that wants to comment on

9 Question 7 or 8? Hearing none, let's hear

10 from Paul, and then let's go back to Mike. 

11 Tell us whether you have enough guidance from

12 the Panel to write the final version of your

13 answer. Paul?

14 DR. BLANC: Although I think

15 inherent in the comments was appropriate

16 critique of the approach taken with Table 2.1,

17 I don't think it actually goes far enough. I

18 was impressed by Steve's comments regarding

19 the previous question in which you also review

20 Table 2.1.

21 I think you should share your

22 comments, because otherwise there will be a

Page 37

1 disassociation between --

2 DR. THOM: The one thing I should

3 say is, when I wrote that, it was after

4 scanning Table 2.1. In Mike's analysis,

5 actually there are only four of those

6 citations where there is no violation of the

7 current standard.

8 The point more generally is that

9 Mike and I both commented that Table 2.1, I

10 think, supports the argument rather strongly

11 that the epidemiological data drives one to a

12 conclusion that the current standards should

13 be lowered, that there is indeed a risk for a

14 variety of cardiovascular decompensations to

15 arise from ambient CO in the range of only

16 several parts per million. That was one of my

17 comments.

18 The other, I think, sort of major

19 message for our charge to Question 6 was that,

20 whereas the controlled clinical data clearly

21 justifies an emphasis on cardiac

22 decompensation, individuals with coronary
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Page 38

1 vascular disease, that they may not be the

2 most sensitive individuals.

3 In particular, there is a fair bit

4 of data to suggest that the fetus is

5 particularly at high risk from very low levels

6 of carbon monoxide. Although that data do not

7 rise to the level where you can change

8 standards -- the science isn't quite there yet

9 -- the clinical data implicates, and the basic

10 science toxicological data strongly suggests

11 that.

12 Therefore, our opinion is that

13 some of that information should be included in

14 the Policy Assessment, and it further supports

15 an argument to modify the current standard.

16 Although it doesn't give you a number, again

17 it supports the notion that something needs to

18 be done based upon the science as it stands

19 today, with the caveat that as we move

20 forward, the science presumably is going to

21 get better in terms of a clearer understanding

22 of pathophysiology. The science, however,

Page 39

1 today does support a strong recommendation to

2 modify the standard.

3 CHAIR BRAIN: That sounded to me

4 like a consensus view and not inconsistent

5 with anything that Mike said. It does add

6 that we really continue to want to highlight

7 possible effects on gestation and on the

8 fetus, and that should be mentioned. Does

9 that resonate with you? I think so.

10 DR. BLANC: Yes, it does.

11 CHAIR BRAIN: I also want to point

12 out another epidemiologic point or

13 biostatistical point about overly discounting

14 a positive relative risk association in a

15 study where a few days may exceed the

16 standard, and thus that was a study performed

17 in an area not in compliance.

18 It is very unlikely that the

19 excedence days in such a study over a long

20 period of time would explain the statistical

21 association unless there was a relative risk

22 of 1,000 on the days in which the excedence

Page 40

1 occurred. Therefore, it is likely that the

2 epidemiologic association -- It is more than

3 not that the epidemiologic association is

4 explained arterial to all the days in which,

5 in fact, the exposures as experienced were

6 within the standard.

7 So there is, on the one hand, a

8 sort of purely regulatory assessment of an

9 area as having not been completely in

10 compliance, but that shouldn't be, therefore,

11 used to misinterpret the epidemiologic

12 association as being attributable to very high

13 exposures. It is more likely than not that

14 the effect that we are seeing is explained by

15 exposure days within the standard.

16 CHAIR BRAIN: Does everyone agree

17 with that? I think so. I think we, in

18 general, want them to be somewhat more

19 positive about these epidemiological studies

20 and not discount them because there are a few

21 excedences, and I think that is common for the

22 literature for many other criteria of

Page 41

1 pollutants as well.

2 DR. DAHMS: The controlled human

3 studies are, if you look at it from the

4 standpoint of excedence -- come on.

5 CHAIR BRAIN: Big time.

6 DR. DAHMS: Yes, it is big time.

7 CHAIR BRAIN: Hundreds.

8 DR. DAHMS: Yes, right. But even

9 the effective dose is something obtained in

10 excedence of the standard. So you can't have

11 it both ways.

12 DR. BLANC: Also, I don't think it

13 goes to too much of a level of detail that one 

14 of the studies -- or a pair of studies that

15 they do endorse as being within the study

16 within compliance, and then reject because it

17 wasn't a statistically significant elevation

18 of relative risk -- the lower limit of the

19 confidence interval that excludes -- or

20 includes one is 0.9999. So in terms of the

21 possibility of beta error, I think, is -- you

22 know, it is worth noting it.
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1 CHAIR BRAIN: Can we be certain

2 that both of these, I think, succinct and

3 compelling summaries are included during --

4 DR. RITZ: Yes. There is one more

5 point, and that is that a lot of these studies

6 actually give you results for different

7 outcomes, and it almost seems like the studies

8 that give you more options of choosing your

9 outcome are being seen more critical, and the

10 ones that just lump all cardiovascular disease

11 together actually get you the significant

12 results; because, of course, they have more

13 subjects. 

14 So that is just another point

15 where you have to be careful when you review

16 these studies, trying to make a point that

17 they are not consistent when, in fact, they

18 are consistent if you don't go into the

19 subgroups.

20 DR. HAZUCHA: Well, I don't know

21 whether you will ultimately dissent or not,

22 but I agree with EPA evaluation of epi

Page 43

1 studies. We all know that there is very high

2 correlation between carbon monoxide levels and

3 PM levels. We have a lot of endpoints for PM

4 effects. Of course, it is inflammatory

5 endpoints, cardiovascular inflammatory

6 endpoints, and so on.

7 For carbon monoxide, we have

8 nothing, basically, because we don't measure

9 COHb. So we have only concentration or LH

10 concentration of carbon monoxide.

11 Because of this collinearity

12 between carbon monoxide and PM, of course, we

13 will get then a sort of high correlation

14 between the endpoints and carbon monoxide. As

15 well, we will get for PM and the endpoints.

16 So I don't know, really, how to

17 separate. Statistically, there is a lot of

18 statistical approaches were used, but still I

19 do not know how physiologically we can

20 separate carbon monoxide effects, if there are

21 any, and the PM effects, which there is plenty

22 of.

Page 44

1 CHAIR BRAIN: Anybody want to

2 respond to that? Certain, the issue of co3 pollutants -- 

4 DR. RITZ: Well, when you look at

5 the epi studies, the one agent that always

6 remains in the significant when you put

7 everything together is carbon monoxide. PM

8 actually -- PM-10 often appears much worse

9 than carbon monoxide.

10 The signal for carbon monoxide is

11 incredibly strong for these outcomes in the

12 epi studies. Otherwise, you would have to

13 really, of those, discuss PM, I think, being

14 less strong than the carbon monoxide, and we

15 are having standards for PM based on epi

16 studies.

17 DR. THOM: Is your argument that

18 you cannot fathom a mechanism? Is that your

19 argument?

20 DR. HAZUCHA: Yes, that is

21 correct. It is one of the arguments.

22 DR. THOM: So on that score,

Page 45

1 number one, I don't think the function of an

2 epidemiologic study is to link it to a

3 biochemical mechanism. I mean, it is just

4 demonstrating some sort of a causality, and

5 that leaves to the basic scientists to do the

6 mechanism. But with regard to the

7 inflammatory component, there is very clear

8 evidence that carbon monoxide is a pro9 inflammatory substance.

10 DR. HAZUCHA: At such low levels?

11 DR. THOM: Well, okay. Now so

12 there is a question, but then you come into

13 play some of the issues with regard -- Carbon

14 monoxide is pro-inflammatory, absolutely. 

15 There is clear evidence of vascular injury.

16 Now the argument that -- The

17 secondary argument would be, as you just said,

18 well, maybe it is the dose. So the animal

19 studies, our animal studies and our clinical

20 reports that have shown the pro-inflammatory

21 effects of carbon monoxide are done at higher

22 concentrations than the environmental
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Page 46

1 standards, but again the issue becomes -- That

2 doesn't discount the inflammatory component,

3 just says maybe there is more to it.

4 That is to say, a longer duration

5 at a lower level will acquire the same level

6 injury. We can't answer that question now. 

7 However, there is clear evidence that it is

8 pro-inflammatory, which -- So I don't think

9 you can discount --

10 CHAIR BRAIN: I think we need to

11 move on, and we will see how Mike does with

12 this. I think these are -- What you talk

13 about, Milan, are certainly something that the

14 Panel has worried about, the issue of co15 pollutants and interactions, and to what

16 extent is CO a surrogate for air pollution in

17 general. 

18 So I think that will certainly be

19 part of the document, and we should make sure

20 that that theme is also there, and they are a

21 little bit in tension with each other.

22 Mike, are you reasonably well

Page 47

1 informed as to what you need to put down that

2 will kind of summarize the discussion?

3 DR. KLEINMAN: I think I can do

4 it.

5 CHAIR BRAIN: Good. Okay.

6 DR. MURPHY: Could I ask a

7 question? Sorry.

8 CHAIR BRAIN: Yes.

9 DR. MURPHY: One of the comments

10 was with regard to -- There was a statement

11 made that I thought I heard. I want to make

12 sure what I heard -- that the CAD population

13 may not be the most sensitive, and while we

14 recognize that there are other -- in ISA, that

15 there may be other populations that are

16 potentially susceptible, including, of course,

17 the fetus, we don't have -- at least my

18 understanding based on the presentation of the

19 evidence in the ISA, that we don't have the

20 evidence indicating that that would be more

21 susceptible than CAD, and it sounded like

22 there was a view that perhaps that was the

Page 48

1 thought. I wanted to understand what evidence

2 was underlying that. What was the science

3 basis there? Thanks.

4 CHAIR BRAIN: So are we saying

5 that there are just other very susceptible

6 populations?

7 DR. KLEINMAN: That was what I was

8 saying. I was saying that there are large

9 numbers of other susceptible groups that

10 aren't captured in the range studies that were

11 done using the benchmarks, because I believe

12 the numbers were specifically organized

13 against -- or around the individuals with

14 coronary artery disease.

15 CHAIR BRAIN: But I don't think I

16 heard a statement about relative

17 susceptibility. We don't really have --

18 DR. KLEINMAN: I said there were

19 susceptible.

20 CHAIR BRAIN: There are other very

21 susceptible individuals.

22 DR. KLEINMAN: Right.

Page 49

1 CHAIR BRAIN: Good. Thank you. 

2 Let's press on. So now we are up to Questions

3 9 and 10. Nine seems like it is a relatively

4 simple question. Paul, take us through that.

5 DR. ROBERTS: So I guess the only

6 comments I have actually seen -- I didn't see

7 any other compiled comments.

8 CHAIR BRAIN: Was anybody else

9 assigned?

10 DR. ROBERTS: Well, Russ Dickerson

11 sent in a couple of comments. So he and I are

12 the only ones I know that put anything in on

13 this. 

14 So Chapter 3 is a fairly short

15 chapter evaluating, looking at the evidence

16 for a possible secondary standard, welfare

17 based. So this is not health based. Right? 

18 We had a little discussion about that already.

19 In general, the PA concludes that

20 there is insufficient information at this time

21 to support the consideration of a secondary

22 standard for CO. 
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1 I think, in general, there is

2 probably enough detail here, and Russ sort of

3 agreed. However, Russ was suggesting as part

4 of -- I don't know if it is really 9, 10 or 11

5 here -- that it would be helpful if the PA

6 said for the potential effects on climate,

7 which by the way, the ISA said there was

8 evidence for that, and we saw that as a panel

9 before, but there is not really enough

10 evidence to figure out how that would really

11 work and what the effect actually is. It is

12 all estimates with large uncertainty.

13 Russ was suggesting it would be

14 appropriate in the last paragraph to add some

15 summary information on what is missing that

16 would allow an evaluation of -- truly of a

17 secondary standard. 

18 The kinds of things, I think, that

19 would be in that list are more accurate U.S.

20 but especially global emissions inventories

21 for CO to evaluate the relative contribution,

22 monitoring specified for climate rather than

Page 51

1 just for standards in exposure, and maybe

2 improvements in localized chemical reactions

3 in the global models to understand CO

4 interactions with methane and ozone; because

5 the interaction with ozone especially is the

6 major potential contributor, and these global

7 models do not look at the details at a local

8 level like around a roadway. 

9 That is really where the CO would

10 have this reaction and, therefore, an effect

11 on ozone. It basically, scavenges OH

12 radicals, I guess, and doesn't allow them to

13 scavenge ozone instead. So there is more

14 ozone around, but the global models wouldn't

15 correctly recognize that.

16 So I think Russ and I sort of came

17 down on the side of, more or less, agreeing

18 with what the chapter is saying in terms of

19 what we can't really do at this point.

20 CHAIR BRAIN: So it acknowledges a

21 possible connection with CO and climate

22 change, but it doesn't go beyond that.

Page 52

1 DR. ROBERTS: Right.

2 CHAIR BRAIN: I think it was the

3 general feeling that that was appropriate.

4 DR. BLANC: But I guess what

5 confused me when I heard their presentation at

6 least was that it didn't seem consistent with

7 my memory of what the ISA section said. Maybe

8 that has -- Is what you are saying, that has

9 to do with a nuance between the ISA saying it

10 is -- there is a causative association between

11 CO and climate effects, and the policy

12 document saying, well, that may be true, but

13 there is not enough in addition to that to do

14 anything about that?

15 CHAIR BRAIN: I don't know that it

16 was causative. I think it was more a

17 recognition that CO is involved in air

18 chemistry.

19 DR. BLANC: I thought it was

20 pretty --

21 DR. ROBERTS: I think the words

22 are fairly definitive, but I think at least

Page 53

1 some of the argument then is that the

2 uncertainty, though, in those estimates are --

3 50 percent, I think, is what the ISA quotes. 

4 Okay. At least the global models don't

5 actually model this at all.

6 So you have to go do a special --

7 The EC -- I can't -- went and did some

8 estimates and got the secondary effect numbers

9 that are quoted in the ISA. So that is my

10 remembrance of what it is. Maybe staff?

11 DR. DAHMS: Paul, I think the key

12 thing is on page 3.2 where it says CO is a

13 weak direct contributing greenhouse warming. 

14 In my mind, it had a lot to do with the

15 strength of the effect. Just that one

16 sentence indicates that it is involved. It is

17 so minor as to not --

18 CHAIR BRAIN: It wasn't as though

19 CO is a greenhouse gas, but it is that it

20 affects the production or degradation of --

21 DR. BLANC: That is in the policy. 

22 You are talking about 3.2? But if we go back
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1 -- I wish somebody could find easily the

2 statement as it is written in the ISA which

3 seems less muted than that.

4 DR. DAHMS: As I recall that

5 statement in the ISA, it was talking about

6 what was possible and not really quantifying

7 it in any way.

8 DR. BLANC: Can you find it in the

9 ISA?

10 DR. LASSITER: Are you referring

11 to the causal -- the statement of causality?

12 DR. BLANC: Yes.

13 DR. LASSITER: It is in the Policy

14 Assessment as well. A causal relationship

15 exists between current atmospheric

16 concentrations of CO and effects on climate. 

17 That is in the Policy Assessment on page 3-2,

18 and that is line 12. So that is directly from

19 the ISA.

20 CHAIR BRAIN: But the magnitude of

21 the effect is unknown, not absolutely

22 described.

Page 55

1 DR. LASSITER: Right. There is

2 direct and indirect effects and, as you

3 stated, the direct effects are very weak, and

4 the indirect are greater. Yet they are mostly

5 associated with the methane and ozone, not the

6 CO directly. 

7 DR. BLANC: Where is it on 3-2?

8 I'm sorry.

9 DR. LASSITER: Line 10.

10 DR. ROBERTS: Well, line 13 and

11 14.

12 DR. LASSITER: Yes, I'm sorry,

13 line 12 and 13.

14 CHAIR BRAIN: I think we will also

15 ask Russ Dickerson and Ted Russell to look at

16 this, because I think they had the most to say

17 about it. So we will sort of put them on

18 notice.

19 DR. ROBERTS: We did have minor

20 comments from Russ, but I thought he was going

21 to call in for this, and he hasn't. 

22 DR. BLANC: And then if the

Page 56

1 interaction with ozone is likely to be in a

2 micro environment near roadways, is that

3 likely to mediate ozone damage to vegetation

4 near roadways? Has that been shown? Is that

5 just a theoretical concern?

6 DR. ROBERTS: I don't know. I

7 think -- I don't know. Do you know?

8 DR. LASSITER: State the question

9 again.

10 DR. BLANC: If there is a micro

11 environmental effect of CO near roadways, that

12 would tend to increase ozone near roadways. 

13 Would that be sufficient to have an ozone

14 related vegetation damage effect?

15 CHAIR BRAIN: I don't think ozone

16 gradients near roadways have been described.

17 DR. ROBERTS: So maybe I am

18 exaggerating when I say near roads. 

19 Certainly, in urban areas.

20 DR. HAZUCHA: In roadways it would

21 be mostly NOx, nitrogen oxide, which will

22 increase ozone, not CO.

Page 57

1 CHAIR BRAIN: I think there is

2 clarity. paul, have you dealt with 9 and 10?

3 DR. ROBERTS: Yes. I am not sure

4 where the exact comments are, but I've got a

5 draft of this.

6 CHAIR BRAIN: And then 11 sort of

7 wraps it all up. You want to -- Have you

8 dealt with that or do you want to comment on

9 charge question 11?

10 DR. ROBERTS: Well, I think, you

11 know, I guess we have discussed it already,

12 really. I think it is the same. It is the

13 same thing, and I had a hard time separating

14 out my answer for 10.b was different than 11.

15 CHAIR BRAIN: And in general, we

16 are pretty happy with what is said there?

17 DR. ROBERTS: I think so. We can

18 put these words out to the whole committee,

19 including Russ.

20 CHAIR BRAIN: Okay. Great.

21 So I think we have now finished

22 our initial discussion of the charge
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1 questions, and the remaining task for the next

2 couple of hours is to look at the draft

3 reports. 

4 So I think, let's get started on

5 the REA draft, and then maybe in half an hour

6 or so we will take a break, because we need a

7 break, and also if anyone hasn't checked out

8 of their rooms, it is probably a good time to

9 do that. So let's get started.

10 DR. LADEN: Joe, just one thing. 

11 I've got Question 1, and the answer there is

12 not the right -- I didn't send Kyndall the

13 right one. I just resent it. Did you get it?

14 MS. BARRY: And what I will do is

15 I will have that one printed in just a second.

16 DR. LADEN: So we should just -- 

17 We shouldn't talk about that one.

18 CHAIR BRAIN: So again, let's talk

19 a little bit about process. So what we have

20 or will have are sort of the initial text

21 produced by all of the lead authors last night

22 or this morning. 

Page 59

1 I am thinking that maybe a first

2 cut through this, since we do have limited

3 time, is to ask the lead authors if there are

4 areas of your statement where you are unsure. 

5 In other words, where do you need guidance? 

6 So maybe we will do that first, if everyone --

7 Presumably, you already know what is there,

8 but as you were writing it last night or this

9 morning, do you see areas of controversy, of

10 lack of clarity, where you need help from the

11 committee to be really confident that you have

12 produced a consensus summary.

13 So maybe we will do that first,

14 and simply just ask each lead author whether

15 they need help or whether they are pretty

16 satisfied that it is a consensus view.

17 Then we will -- we can also then

18 turn to the entire Panel and ask you to look

19 at each of these, and are there ones that you

20 disagree with. 

21 We are hoping that each of the

22 lead authors, by this Friday, can do

Page 60

1 additional edits that you think are needed. 

2 Then we will have about another week for

3 Kyndall and I to look at it, to refine it

4 further, and then we will get it out to you

5 and to Jon Samet for a final review before it

6 goes to the CASAC committee, and they are

7 meeting on April 19.

8 MS. BARRY: So, yes, the CASAC

9 teleconference will be April 19th. So what

10 Joe is proposing, I think, is very reasonable

11 for the leads to have your opportunity to

12 refine the language by this Friday, and then

13 we will turn it around and kick it back to you

14 guys the following week, maybe next Friday. 

15 Then we will be looking to have your final

16 comments and get everything posted somewhere

17 in the range of the 9th through the 12th of

18 April.

19 So it is an aggressive schedule

20 but, I believe, one that is very reasonable,

21 given how far we have gotten in our day and

22 half of meetings. Any questions? Okay.

Page 61

1 CHAIR BRAIN: Great, thank you. 

2 Particularly the topic leaders, if you can

3 join us for that CASAC teleconference, that

4 will be very helpful, because questions may

5 come up where you are the authority, and a

6 response from you would be very helpful.

7 So why don't we now look at the --

8 You know, these are our comments on the second

9 draft REA, and as a first cut -- We will give

10 everyone a chance later, but as a first cut,

11 why don't we simply go through the questions

12 and see whether the author has any unresolved

13 issues.

14 DR. LADEN: I can talk about my

15 unresolved issues, but you can't see what I

16 wrote.

17 CHAIR BRAIN: Okay. That is fine.

18 DR. LADEN: All right. So what I

19 tried to do -- This was -- So the first

20 question is really on Chapter 2, which is

21 really kind of -- I saw that as -- and it is

22 called the Overview Chapter. So I think that
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1 what is in that chapter is really reflective

2 of what our comments are later on.

3 So what I tried to do is present

4 that we felt that there was a good overview

5 conceptually, but that there was kind of

6 mixed concern about the presentation of the

7 epidemiology, and that -- So I just wanted to

8 make sure that I presented that correctly.

9 CHAIR BRAIN: And people should

10 not be looking at what is here.

11 DR. LADEN: Don't look at what is

12 there. That is only what I had written. I

13 sent the wrong thing last night. 

14 So what I said is that, while some

15 Panel members supported the cautious approach

16 to using the epidemiology data in the risk

17 assessment, overall there were concerns that

18 the current presentation underemphasized the

19 epidemiologic findings.

20 Even if they are not used in the

21 risk assessment, it is important to

22 incorporate them into the discussion of risk. 

Page 63

1 So I wanted to make sure that that -- because

2 I felt that there was some -- not

3 disagreement, but there was some concern -- I

4 guess disagreement about how the epidemiology

5 should be used in the risk assessment.

6 I think -- I haven't had a chance

7 to read the rest of the document, and I am

8 sure that is going to come out more in the

9 subsequent chapters. So what I then said is -

10 - At the end, I said that I felt that this

11 chapter needed to be edited as -- re-edited,

12 as the other chapters are changed. I just

13 want to make sure that is adequate.

14 The other thing that I talked

15 about is the continuing concerns about the

16 choice of the population at risk, and that the

17 choice of modeling risk for the CAD population

18 needs to be further justified and/or expanded

19 to include other susceptible populations.

20 So that is kind of how I

21 summarized the discussion, and I didn't put

22 specific comments in here. So that was my

Page 64

1 other question: Was this too much of an

2 overview summary? Did people want more of the

3 specific comments that they had put in? In

4 here, was that going to be enough that it is

5 in the addendum?

6 CHAIR BRAIN: Any responses to

7 Francine? It sounds consistent with what the

8 conversation was.

9 DR. BLANC: I just probably

10 wouldn't leave them the out of that, if they

11 want to narrow it to CAD only, they have to

12 better justify it. I just don't think there

13 is a justification.

14 CHAIR BRAIN: And I think there is

15 strong consensus that we want to include other

16 cardiovascular --

17 DR. BLANC: Not that they

18 shouldn't do their modeling with CAD, but in

19 addition, they need to broaden it.

20 CHAIR BRAIN: So we will have a

21 chance to look at that text probably after the 

22 coffee break.

Page 65

1 Number 2 is Russ Dickerson. So

2 why don't -- He is not here to comment. So

3 why don't we leave that until --

4 DR. ROBERTS: Well, I think I sent

5 it in. I don't think there is much

6 controversy in that one.

7 CHAIR BRAIN: Sounds good. Then

8 that gets us up to Charge Questions 3 and 4. 

9 So I guess the question, Milan, is not to

10 summarize what is there, but are there issues

11 that you want more input from the Panel?

12 DR. HAZUCHA: Not really. I

13 incorporated Beate's and Steve's comments, and

14 unfortunately, I don't have Joel's comments,

15 but I don't know whether he had a chance to

16 read this semi-consensus. But I do not have,

17 really, any additional questions.

18 CHAIR BRAIN: Okay. So again, we

19 will come back to all these and give everyone

20 else a chance. But now we are just sort of

21 touching base with the authors. 

22 Paul, questions 5 to 7, any
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1 unresolved or controversial issues that you

2 want advice about?

3 DR. BLANC: Well, one thing is

4 that the other contributors should look and

5 make sure that, in ways in which I

6 incorporated your comments, they are

7 appropriate.

8 In order to be coherent, I

9 incorporated other comments within the body of

10 the comments. I didn't do them sequentially. 

11 For example, I retained the comments that

12 Appendix C should have some specific

13 illustrations or examples. I want to make

14 sure that is still -- I think it was Dr.

15 Dahms' suggestion -- that you still want that

16 there, and the coupling of the nonlinear CFK

17 in CHAD would more convincing if there were

18 references to validation.

19 I think we heard that it is not

20 possible to validate. So I added some wording

21 that, basically, in the best of all possible

22 worlds, it would be great; but since there

Page 67

1 isn't, so be it, but that it is still -- we

2 accept the proposition that this is an

3 improvement over previous, which also weren't

4 validated. So we can't hold them to a higher

5 standard.

6 The wording isn't the best, but

7 that is basically what you meant. Right? 

8 Okay.

9 Then on number 6: Number 6 is --

10 I tried to incorporate various comments that

11 were made on endogenous CO production and some

12 questions that the group had about whether the

13 model -- the ranges produced by the model was

14 reflective of certain subpopulations that

15 might be out of that range, but also I think

16 one clear source of confusion to several of us

17 had been the fact that the range that came out

18 by chance with the random subset was narrower

19 than the overall simulation. 

20 That doesn't mean that there is

21 something wrong with that. It just probably

22 was randomness, but it might be helpful that

Page 68

1 the document clarify that.

2 I did also retain in there the

3 issue of providing the estimates for indoor,

4 and I tried to compromise with Joel's view. 

5 Joel Kaufman emphasized seeing what the

6 marginal increase from ambient was. So I

7 said, if it showed all three separately and

8 together, then one could interpret it either

9 way.

10 Milan, I left your series of

11 specific comments on some textual things at

12 the end of that.

13 Then number 7 --

14 DR. KAUFMAN: Paul, let me just --

15 This is Joel. Let me just hop in there. I

16 guess -- and I will suggest some additional

17 text and send it on, but I guess I would make

18 the additional -- First of all, I would

19 indicate to the staff that it was the stuff

20 that was presented in the presentation

21 yesterday that was good, where they actually

22 went the additional steps to model this

Page 69

1 contribution of ambient; because that wasn't

2 in the written document we reviewed. 

3 So it probably worth highlighting

4 that that was a good direction to go in, and

5 they should probably follow that on in order

6 to better understand the increment of the

7 ambient contribution, too, because I think

8 that is going to be a very effective part of

9 the modeling of the concentrations

10 potentially, rather than modeling the final

11 COHb, but to model the increment as a way of

12 assessing the effect of the various

13 concentrations that they are going to use in

14 the final assessment of the standard. Does

15 that make sense?

16 DR. BLANC: Yes. Send me the

17 language.

18 DR. KAUFMAN: Yes. Okay.

19 DR. BLANC: Should I go on to 7

20 then?

21 CHAIR BRAIN: Yes, please.

22 DR. BLANC: Seven comes back to
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1 the issue of cardiovascular disease versus

2 coronary artery disease and, I think, reflects

3 what I wrote originally, but I think there was

4 consensus in that regard. I don't recall that

5 -- The other authors' texts were generally

6 fairly brief or went over the same thing. 

7 That was the one I did last, and I was

8 starting to fatigue. So you should let me

9 know if you think something needs to be there

10 that isn't.

11 CHAIR BRAIN: Okay. Then we have

12 Charge Question 8 and Paul Roberts. Anything

13 you were unclear about?

14 DR. ROBERTS: Well, I mean, I put

15 in a sentence to recognize Paul's concern

16 about the indoor sources step. So he needs to

17 look at that at the very end. So I was trying

18 to recognize -- Really, the two comments were

19 mine about the modeling and his about that in

20 terms of affecting the ability.

21 CHAIR BRAIN: Great. So here is

22 what we will do. We have now had this first

Page 71

1 cut. Why don't we now give all of you time to

2 look at the answers, and again Francine

3 Laden's new version has been handed out.

4 I guess, before we give everybody

5 an opportunity to look at what is here and to

6 comment on it, does EPA staff -- Are there

7 issues that, as people review this, that you

8 want us -- I know you haven't had a chance to

9 look at it thoroughly either, but even before

10 that, are there any concerns that you have?

11 DR. MURPHY: One quick question of

12 clarification, I think Dr. Graham has.

13 DR. GRAHAM: Thank you. I don't

14 know if it is quick. Can I go through this

15 page by page, line by line, sort of?

16 CHAIR BRAIN: Probably not line by

17 line, but give us what are the microscopic

18 issues.

19 DR. GRAHAM: Just to help you or

20 save you some time.

21 CHAIR BRAIN: Yes.

22 DR. GRAHAM: On the first page at

Page 72

1 the very bottom there was discussion about the

2 .5, and we had talked about this, that that

3 was related to an analysis that was performed,

4 and it isn't related to the ambient air

5 quality data that was used as an input. That

6 was in deriving specific ratios or factors

7 that were used in adjusting concentrations. 

8 Does everybody recall that discussion?

9 Okay. Being that it was used to

10 derive that relationship, it is unclear to me

11 how that actually impacts what is stated here,

12 the threshold COHb levels, particularly since

13 the benchmark of interest or the endpoint is

14 mostly impacted by higher concentrations,

15 concentrations at the upper end of the air

16 quality distribution.

17 CHAIR BRAIN: Again, your point

18 yesterday is it was really only used to devise

19 the algorithm, but then when the actual values

20 were calculated it was not used.

21 DR. GRAHAM: Right. Absolutely.

22 CHAIR BRAIN: So that needs to be

Page 73

1 clear.

2 DR. GRAHAM: Or if you are asking

3 for more clarity.

4 DR. ROBERTS: I would just suggest

5 taking that paragraph out. It is not as high

6 level a point here at all. It is not in the

7 main model.

8 CHAIR BRAIN: Or do you want them

9 to clarify what was done? If you were

10 confused, perhaps others are.

11 DR. ROBERTS: Well, I think they

12 can clarify it. I think our individual

13 comments can have things about clarifying

14 exactly, but I don't think it is at the level

15 of the rest of the comments here.

16 CHAIR BRAIN: Okay. So when you

17 produce your next edit --

18 DR. ROBERTS: Well, I am not the

19 leader, though. Somebody else is the leader

20 in this. Right? Milan or someone.

21 DR. THOM: Yes. They clarified it

22 yesterday.
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1 DR. ROBERTS: So I think if they

2 put that in the text, and that will be in our

3 individual comments.

4 DR. GRAHAM: Then on the second

5 page, lines 6 through 9, there is a paragraph

6 asking about what was done for the overlapping

7 air quality zones. I can quickly just say we

8 used the closest monitor. So wherever the

9 resident tracked was, it used the closest

10 monitor. So if there were overlap, it was

11 whichever one was closer.

12 CHAIR BRAIN: Again, should we

13 leave in something asking you to clarify that?

14 DR. GRAHAM: Yes, because that

15 actually wasn't written in the text.

16 CHAIR BRAIN: So maybe you can

17 just modify.

18 DR. HAZUCHA: And then we can take

19 it out.

20 DR. DAHMS: Again, we could put it

21 in our individual -- Put them in this thing or

22 put them in details, too? Where do those

Page 75

1 comments go?

2 CHAIR BRAIN: If they are large

3 and important, I think they can appear here as

4 things that should be dealt with, and we are

5 reassured that they are going to be dealt

6 with. But I think, again, CASAC will be

7 looking at this whole -- the same documents we

8 have looked at, and so even if we are happy

9 with the anticipated response, it is probably 

10 not inappropriate to still point out some

11 things that require greater clarity, even if

12 we have been told that greater clarity is on

13 its way.

14 DR. GRAHAM: Lines 24 to 27, it

15 asks about the micro environments. One and 15

16 were done previously, and we did 8 here. This

17 is actually explained on page 523, lines 2 to

18 five.

19 On page 3 at the very top, we had

20 done some updating of the physiology file --

21 CHAIR BRAIN: Where are we now?

22 DR. GRAHAM: Page 3 at the very

Page 76

1 top, 1 through 3. That is about the -- Well,

2 it makes a reference to the -- We did a review

3 of the physiology file, and that is at the

4 very beginning of that text in Appendix C, but

5 we also go further in that Appendix to

6 describe the updates that were done for three

7 of the variables. 

8 We updated the data for body mass,

9 the normalized VO2 Max, as well as the

10 hemoglobin content. So those contained recent

11 algorithms and distributions.

12 CHAIR BRAIN: Again, I find that

13 paragraph a little unhelpful in that it really

14 doesn't say what data is or are obsolete, and

15 what ones are incorrect. So it seems to me,

16 it needs either greater specificity --

17 DR. GRAHAM: Yes, that would be

18 great.

19 DR. DAHMS: Joe, could I ask for a

20 point of clarification. what was the focus on

21 VO2 Max? Is that because efforts are based on

22 percentage of Max?

Page 77

1 DR. GRAHAM: It has to do with

2 controlling the activity.

3 DR. DAHMS: The activities are

4 based on percentage of VO2 Max, not of METS?

5 DR. GRAHAM: Well, the METS are

6 used to estimate the VO2, and we wouldn't want

7 to have -- like if an individual performed a

8 series of high level activities, we wouldn't

9 want them to exceed physiological expectations

10 with oxygen consumption. Does that explain

11 it?

12 CHAIR BRAIN: So, Milan, can you

13 maybe be more specific about which parameters

14 you have difficulty with?

15 DR. HAZUCHA: Sure, absolutely.

16 DR. GRAHAM: On the same page 3,

17 21 through 25, there are two examples given,

18 and on the first one it is not clear to me

19 what is being suggested. On the second one,

20 I can say -- It says an illustration of

21 variability in the peak levels, the COHb

22 throughout the year. Would variability in
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1 the daily Max be of interest? So if I can

2 have some clarity on those two examples, that

3 would be great.

4 DR. BLANC: Dr. Dahms, that was

5 your input. Can you send me clarification

6 clarifying that?

7 DR. GRAHAM: yes, that would be

8 great. 

9 CHAIR BRAIN: Anything else?

10 DR. DAHMS: Well, the concern for

11 that was to see -- We had this discussion

12 among a group of us yesterday. I don't know

13 what your on and off rates are for carbon

14 monoxide, and that is what we wanted to see.

15 DR. GRAHAM: Okay.

16 DR. DAHMS: So that is why I was

17 asking for a daily kind of -- as you walk

18 somebody through different environments, how

19 the model would track that, so we could see

20 that.

21 DR. GRAHAM: Okay.

22 CHAIR BRAIN: Again, there was

Page 79

1 specific concern that it is very asymmetric

2 and that the loading is much faster than the

3 unloading, and would your model reflect that

4 physiologic reality. Is that right? Yes.

5 DR. DAHMS: Yes, that is correct.

6 DR. GRAHAM: And you are saying

7 not just endogenous, but with the ambient

8 exposures? Okay.

9 DR. DAHMS: Particularly ambient.

10 DR. GRAHAM: Great. 

11 CHAIR BRAIN: We would find that

12 sort of reassuring, if that asymmetry were

13 reflected in the model calculations.

14 DR. BLANC: It is all for Appendix

15 C. Right? That is where this would be, up

16 here. Right?

17 DR. DAHMS: It could go anyplace,

18 as long as it is available.

19 DR. ROBERTS: Well, I would

20 suggest, if that is important, that we put a

21 sentence or two about it in the uncertainty

22 section, because that is really what we are

Page 80

1 talking about. Does the model have the

2 response that -- you know. So we could put

3 something there. Well, this section is -- No,

4 it can stay here.

5 CHAIR BRAIN: Anything else?

6 DR. GRAHAM: Just the final one

7 would be the last page. I'm sorry, page 4 at

8 the very bottom. it is a question about the

9 differences in the air quality that were used. 

10 It is lines 39 through 43 on page 4.

11 DR. BLANC: I think that either

12 came from Dr. Dahms or from Dr. Hazucha. So

13 do you remember?

14 DR. DAHMS: It is not mine.

15 DR. HAZUCHA: It is probably mine,

16 yes.

17 DR. GRAHAM: Well, if there are

18 questions about the '95 and '97, I believe it

19 is in the text, but I can improve the clarity

20 here at least. The '95 was used for Denver,

21 and that is because it was close to just

22 meeting the current standard, and that was one

Page 81

1 of the scenarios that we were trying to model,

2 and the '97 was used for Los Angeles. Again,

3 that is because it had fairly comprehensive

4 data and was used to reflect just meeting the

5 current standard.

6 The 2006 data were used the "as

7 is."

8 DR. BLANC: So I can change the

9 words, "it is not clear why." I have to say

10 "it should be made more clear why."

11 DR. GRAHAM: Yes, that would be

12 great. Well, I am hoping that it is clear

13 here that that is why it was done that way.

14 DR. HAZUCHA: Well, actually, in

15 the text, if I remember, indeed you said 1995

16 is for Denver and 1997 is for LA.

17 DR. GRAHAM: Right.

18 DR. HAZUCHA: But my concern was

19 why you haven't used data more recent for

20 Denver and LA. 

21 DR. GRAHAM: Well, we did the 2006

22 for both cities.
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1 DR. MURPHY: Maybe we could

2 clarify the purpose. Sorry.

3 So our objectives were to have

4 some air quality scenarios, one which

5 reflected, quote/unquote, "current conditions"

6 or "as is," and the 2006 is intended to do

7 that. 

8 Then we needed a set of scenarios

9 that reflected air quality just meeting the

10 current standard, which would be higher

11 concentrations than those today. Then we also

12 needed alternatives, which in this case fell

13 between just meeting the current standard and

14 the "as is" condition. 

15 I doing them, there are a variety

16 of ways we might consider to create the air

17 quality data for those simulations. One way

18 which might be done is to roll up, if you

19 will, the current conditions using a

20 proportional or some other relationship to

21 create air concentrations that just meet the

22 standard.

Page 83

1 An alternative, which we employed

2 here, which we thought was appropriate

3 reflected actual conditions that had existed

4 in the past where the concentrations were near

5 the air quality standard. 

6 So it is just the approach that we

7 used to create the air quality dataset which

8 reflected just meeting the current standard. 

9 Then we used that same dataset, rolling it

10 down to meet the alternative standards that

11 were higher than current conditions.

12 DR. HAZUCHA: So maybe a sentence

13 or two -- a clarifying sentence or two would

14 help to understand why there is differences in

15 years.

16 CHAIR BRAIN: Can you modify that? 

17 So you are simply asking them --

18 DR. BLANC: I've got it. I've got

19 it, and I will delete the very last phrase,

20 which is about the temporal trends, because 

21 once you explain it, then it is not an issue. 

22 But I will say parenthetically that is why you

Page 84

1 did it for the processes of modeling different

2 exposure scenarios, because that is what you

3 were doing.

4 DR. GRAHAM: Absolutely. Thank

5 you.

6 CHAIR BRAIN: So I think we would

7 all like the chance to look at this a little

8 more carefully. We will now go through this

9 one more time. 

10 Let's now take a break, and let's

11 give you an extra 10 minutes. So use the

12 break not only to --

13 DR. MURPHY: Excuse me. I'm

14 sorry, Dr. Brain. I didn't -- We just had a

15 question with regard to Question 1 that was

16 distributed, and I am not sure if you all

17 needed to talk about that first or not.

18 CHAIR BRAIN: Why don't we all

19 look at it, and then we can -- We will now go

20 through the document one more time, and give

21 an opportunity to EPA as well as other Panel

22 members to comment on things that are unclear

Page 85

1 or they think fail to meet the consensus

2 standard.

3 DR. MURPHY: Thank you.

4 DR. ROBERTS: Joe, I had one

5 question. We also need to suggest to you

6 which items are important enough to put in

7 your two-page letter. Is that right? So when

8 should we do that?

9 CHAIR BRAIN: Yes. I am sort of

10 making a list. Some of them, such as

11 broadening from coronary artery disease to

12 cardiovascular disease, and the importance of

13 Epi. So those will be ones. 

14 So I think I have a fairly good

15 sense of that, and again in the draft that you

16 will get in a week, it will include those

17 highlights. But again, if anybody wants -- As

18 we go around, I would very much invite people

19 saying, yes, this is something that needs to

20 be in this highlight portion for the

21 Administrator. That would be very helpful.

22 So check out of your room, if you
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1 haven't done that. Grab some coffee, and

2 especially look at the text. Then we will

3 just go through it quickly again.

4 Again, don't do wordsmithing,

5 grammatical problems. Yes, we would like to

6 hear from you, but do it by e-mail. Let's

7 deal with the big macroscopic issues. You

8 know, are there big issues that you have

9 trouble with, either because you disagree or

10 you think they are unclear, or omissions are

11 important as well.

12 (Whereupon, the foregoing matter

13 went off the record at 10:03 a.m. and went

14 back on the record at 10:24 a.m.)

15 MS. BARRY: Let's go ahead and

16 reassemble ourselves, so we can finish with

17 our review of our draft letters.

18 CHAIR BRAIN: So, yes, in the next

19 hour, hour and a half, our task is to make as

20 many improvements and clarifications as we

21 possibly can in the drafts to the

22 Administrator regarding these two documents.

Page 87

1 So let's continue, since it is

2 fresh in our mind, with the REA. Hopefully,

3 you have had time to look at parts that were

4 of particular interest to you.

5 So why don't we just sort of work

6 our way through. We have already heard from

7 the lead authors. Let's now make it available

8 to EPA staff and other members of the Panel. 

9 Do you have concerns or questions about what

10 is written?

11 Again, if there are grammatical

12 errors, lack of clarity, if you can send that

13 to the topic leader and to Kyndall by e-mail,

14 that would be best.

15 So Question 1: There is a new

16 version which was distributed, should be at

17 your plate. So not what is there, but the new

18 one in a larger font. Any questions or

19 comments about that? 

20 DR. MURPHY: Dr. Brain, are you

21 asking the Panel?

22 CHAIR BRAIN: Yes, as well as the

Page 88

1 agency. We would love to hear from you as

2 well if you have questions about that.

3 DR. MURPHY: We did have a

4 question on this one, in the middle of the

5 paragraph. I think Dr. Rajan is going to ask.

6 DR. RAJAN: Yes. I just had a

7 clarification question, and it is the sentence

8 starting on Line 9: The epidemiology provides

9 information on --

10 CHAIR BRAIN: Are you looking at

11 the new one?

12 DR. RAJAN: Yes. It is the

13 sentence: The epidemiology provides

14 information on non-hypoxy irrelevant

15 mechanisms and chronic outcomes that cannot be

16 addressed by relying on CHb levels alone.

17 We just want a clarification

18 specifically on which epidemiological studies

19 you are referring to, as well as the chronic

20 outcomes that cannot be addressed by relying

21 on COHb levels alone.

22 DR. LADEN: Beate, are you still

Page 89

1 here?

2 DR. RITZ: I am here.

3 DR. LADEN: Because I pulled that

4 sentence from your comment.

5 DR. RITZ: Yes. The non-hypoxy

6 irrelevant mechanisms -- that doesn't belong

7 to the epidemiology. That was actually from

8 the biological background. So that is not the

9 epidemiology.

10 DR. LADEN: Okay. 

11 DR. RITZ: But the chronic

12 outcomes -- I think we considered the

13 pregnancy outcomes and some of the other

14 health outcomes more chronic than acute. 

15 Right?

16 DR. LADEN: Yes.

17 DR. RITZ: So should we use some

18 examples there?

19 DR. RAJAN: Yes. 

20 DR. RITZ: I mean, you just have

21 to pull it from the ISA.

22 DR. LADEN: Yes. I mean, I can
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1 add some examples in terms of the pregnancy

2 outcomes and also there were some with the

3 hospitalizations, I think, that was more

4 chronic.

5 DR. RITZ: Right.

6 DR. BLANC: And then for the other

7 it would be biological data then?

8 DR. LADEN: Yes.

9 DR. MURPHY: With regard to

10 chronic, it is our understanding that the ISA

11 concluded, I believe -- what is the --

12 inadequate for chronic or -- I am trying to

13 find the right page -- and suggested for

14 developmental outcomes.

15 DR. LADEN: I think that it was

16 inadequate for the mortality, but not

17 necessarily for the chronic outcomes with

18 disease.

19 DR. MURPHY: Well, page 2-6 under

20 cardiovascular, inadequate to conclude causal

21 between relevant long term exposure and

22 cardiovascular morbidity.

Page 91

1 DR. BLANC: Yes. I think it will

2 help just by giving examples. I don't think

3 it is referring to cardiovascular -- I think

4 it just needs to be clarified with specific

5 outcomes.

6 DR. MURPHY: To the extent it can

7 draw directly from the ISA, since that is at

8 this point our evidence base, that would be

9 fabulous.

10 DR. LADEN: That is fine.

11 CHAIR BRAIN: So we have clarified

12 that the non-hypoxy irrelevant mechanisms does

13 not apply to the epidemiology. Since those

14 words are there, I am still a little confused

15 as to how the Panel feels about non-hypoxic

16 mechanisms in general.

17 I hear from you that you are

18 fairly enthusiastic about them and that the CO

19 may be pro-inflammatory, but I sense a lack of

20 conviction elsewhere on the Panel. Is this --

21 is it a position that it is a possibility but

22 not a certainty? 

Page 92

1 Clearly, in human studies --

2 DR. BLANC: I think the issue is

3 that it is certainly a rapidly emerging area

4 of biological investigation, and I think it is

5 unequivocal at this point that CO can act as

6 a signaling factor. I don't think anybody is

7 arguing that the data are developed to the

8 point where it is going to be the basis of

9 risk modeling. 

10 I think the point is, rather, that

11 it is a whole another direction of potentially

12 human health effects which are emerging and

13 which needs to be taken into account as both

14 an area of uncertainty and an area which may

15 explain currently confusing observational

16 associations.

17 CHAIR BRAIN: Is the evidence a

18 little stronger for CO as a signaling molecule

19 than as a pro-inflammatory molecule? They may

20 be related mechanisms.

21 DR. BLANC: Yes. That is true.

22 DR. THOM: That is correct.

Page 93

1 CHAIR BRAIN: Okay, good. That is

2 helpful.

3 DR. THOM: And just for

4 clarification, have there been epi studies

5 that would look at inflammatory related

6 outcomes? 

7 CHAIR BRAIN: Probably not.

8 DR. THOM: Probably not. 

9 Everything -- the focus seems to be on

10 cardiovascular disease.

11 DR. BLANC: Well, but of course,

12 there is an issue in terms of what is the role

13 of inflammation in cardiovascular disease. 

14 CHAIR BRAIN: Right, but that is

15 becoming more and more convincing.

16 DR. DAHMS: But in terms of

17 relationship to stroke, any of the clotting

18 disorders --

19 DR. BLANC: But there was data in

20 the ISA exploratory data that had to do with

21 coagulation and, obviously, the data on CVA

22 that have not yet sort of reached -- I guess
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1 it was classified as whatever those terms

2 were, suspicious -- you know, interesting but

3 not conclusive.

4 DR. KLEINMAN: Well, I think the

5 Delfino study where they looked at

6 inflammatory biomarkers showed systemic

7 inflammation that could be related to carbon

8 monoxide, but I don't think it is at the level

9 where you can use that biomarker data for dose

10 response.

11 CHAIR BRAIN: And in the epi

12 studies, then the co-pollutant issues become

13 even more important, since PM is known to

14 trigger some pro-inflammatory responses.

15 Okay. That is all very helpful. 

16 Anything about number 2? Any concerns,

17 questions? Hearing none, how about Charge

18 Questions 3, and we have an A and a B and a C,

19 and we have already talked about the bottom

20 paragraph of page 1. So we've clarified that. 

21 Anything else?

22 Question 4? Since at the bottom

Page 95

1 of page 2 I see DLCO, was there a consensus

2 and is this in there somewhere about that we

3 haven't thought deeply enough about pulmonary

4 disease as a significant susceptible group? 

5 You know, people who have a lower DLCO because

6 of emphysema, because of fibrosis, to what

7 extent do they represent a group that

8 theoretically at least should be more

9 susceptible to decreases in oxygen delivery? 

10 Is that something we want to say, and do we

11 say it anywhere?

12 DR. HAZUCHA: I believe we do.

13 CHAIR BRAIN: Do we?

14 DR. HAZUCHA: Yes. We have some

15 sections where the request of expansion of

16 these populations.

17 DR. DAHMS: But again, it was

18 along the lines that the pulmonary disease

19 patients did not reach the level of inclusion.

20 DR. BLANC: You know, one -- I 

21 don't know if it is even a point worth making,

22 but to the extent that there is any concern

Page 96

1 about those with chronic pulmonary diseases

2 being yet another risk group to think about,

3 even if one didn't model, one advantage of

4 expanding the at risk cardiovascular group to

5 be a cardiovascular disease more broadly

6 defined than coronary artery disease is you

7 really are going to capture many of the people

8 who you would be interested in on the basis of

9 chronic pulmonary disease, quite frankly;

10 because there will be so much overlap with

11 significant chronic obstructive pulmonary

12 disease. That is just epidemiologically the

13 case.

14 So it is just a secondary benefit

15 of looking at that more broadly defined, but

16 I don't know if that is worth saying.

17 CHAIR BRAIN: Maybe we can add a 

18 -- when we are talking about the expansion

19 from coronary artery disease to cardiovascular

20 disease more generally, we can also then add

21 a sentence or two saying that adjacent to that

22 are people with diminished --

Page 97

1 DR. BLANC: You know, I can allude

2 to that as a secondary advantage of that

3 expansion. That would be under point 7, I

4 guess. 

5 CHAIR BRAIN: And speaking of

6 susceptible populations, I think I have heard

7 the answer to this before, but why do we leave

8 out smokers? Again, when we are talking about

9 different sources of carbon monoxide and how

10 they add or interact, we don't talk about

11 smoking. Right? And why is that?

12 DR. BLANC: We don't know about

13 direct smoking, because if we do -- were

14 indoor air, nonambient sources to be included,

15 then you do capture secondhand smoke exposure.

16 CHAIR BRAIN: But what about the

17 primary smokers who start off with a higher

18 COHb? Does CO have any impact on them?

19 DR. DAHMS: The answer that I was

20 given to this 30 years ago was that they

21 choose to pollute themselves. 

22 DR. KAUFMAN: But I think this
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1 gets back to the question I was raising

2 yesterday about whether an ambient pollution

3 is just easier to model as an increment over

4 whatever they have, because they don't

5 increase your risk. If you change from having

6 a baseline of 8 percent to having a baseline -

7 - to having 10, isn't that still bad?

8 CHAIR BRAIN: But if you come in

9 with a -- because you are a smoker and you

10 have a COHb of four or five percent, then 10

11 parts per million of CO --

12 DR. DAHMS: You are going to be

13 exhaling and not -- you are not going to be

14 taking anything up. You are going to be

15 exhaling and not --

16 DR. HAZUCHA: You will be actually

17 polluting air.

18 DR. DAHMS: Yes, you will be a

19 point source.

20 CHAIR BRAIN: But isn't it

21 important to clarify that, because someone

22 less thoughtful might think that smokers with

Page 99

1 a higher COHb are -- you know, since they are

2 at still greater risk. I guess the question

3 is why don't we address that? There are all

4 kinds of -- I mean, even obesity and

5 cardiovascular, to some extent, self-induced

6 for some people.

7 DR. DAHMS: Just point them to the

8 physiology in the Appendix, and let them

9 figure it out.

10 CHAIR BRAIN: Is there some EPA

11 tradition or something in the Clean Air Act

12 that we forget about smokers? They do seem

13 conspicuous by their absence.

14 DR. MURPHY: Well, we have -- you

15 know, as was just mentioned a moment ago, in

16 terms of our focus goal of identifying what is

17 needed for an ambient air quality standard,

18 the fact that they are creating their own

19 cloud, if you will, of higher CO means that

20 they are less impacted by the low ambient

21 concentrations that exist. However, it sounds

22 to me, what you are saying, Dr. Brain, is

Page 100

1 perhaps that is a useful point of

2 clarification for a reader.

3 We did in previous air quality

4 criteria recommend -- for example, in the 2000

5 criteria document, there is a section

6 describing essentially what we just discussed,

7 that smokers will have higher COHb levels,

8 that as with anyone, depending on their

9 previous exposure, that will affect whether or

10 not they are impacted by their next exposure,

11 if you will. If their previous one was quite

12 high and their subsequent is quite low, they

13 may be off-gassing and they are not affected

14 by a lower.

15 There is some discussion of that

16 in the previous AQCD which we could bring in. 

17 I think there is little discussion in the

18 current ISA, but they had limited time and

19 focused more on the newer studies. But for

20 point of clarification as a backdrop, you

21 know, just like we make a point about there

22 being a variety of non-ambient sources,

Page 101

1 perhaps that could be brought into Chapter 2

2 of the REA.

3 CHAIR BRAIN: So is this something

4 that we would like to have in our letter as a

5 consensus view or should I just put it in my

6 own comments? What is the consensus? 

7 I think no one is saying do a risk

8 analysis. We are just talking about a

9 paragraph that would explain why we are not

10 doing much with smokers, because they don't

11 represent a susceptible population, at least.

12 DR. KLEINMAN: I think it is

13 reasonable to request that a paragraph be

14 added.

15 CHAIR BRAIN: Okay. So I will

16 write such a paragraph and put that in the

17 consensus document. Thank you.

18 Okay. So anything else on pages 1

19 or 2? Anything else about Question 4? 

20 How about Question 5 about the

21 modeling? 

22 DR. KLEINMAN: In Question 5,
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1 lines 29 to 32 asking for the -- you know,

2 they say it would be more convincing if there

3 were validation. I think that is true, but

4 can we recommend any specific studies where --

5 you know, that EPA could use to validate? I

6 can't think of any, but --

7 DR. BLANC: I think that that is

8 why I wrote that, although in an ideal world -

9 - or my implication was in the ideal world,

10 one might want validation, because that was

11 Dr. Dahms' point, that we heard previously

12 that it is not -- there isn't a scenario by

13 which there would be, but on the other hand,

14 the previous models that they have used

15 weren't validated either, and this, for other

16 reasons, is viewed as a technical improvement

17 in the modeling from a modeling point of view,

18 and so, therefore, is still advantageous. 

19 It has whatever limitations

20 previous models have. So I don't think that

21 there is anything we can recommend, because if

22 I understood the response, there is no way it

Page 103

1 could be done. So -- Is that correct?

2 DR. MURPHY: You were talking

3 about validating the population endogenous

4 COHb estimates? 

5 CHAIR BRAIN: The CFK model.

6 DR. MURPHY: I'm sorry.

7 DR. BLANC: It is the CFK with the

8 CHAD and the APEX, and you know, I guess it

9 would be a situation where you would go out

10 and actually measure carboxyhemoglobin levels

11 and see how well the model had actually

12 predicted what you saw, and it would be people

13 that you had activity diaries and location

14 diaries. 

15 I don't think it is a conceptually

16 feasible thing that one could do, and that is

17 what you said yesterday, if I understood. So

18 all I am doing is saying, okay, if this was

19 the ideal world, one would do that, but we

20 know you can't, but the model still has

21 advantages over previous models, is what you

22 said. Right?

Page 104

1 CHAIR BRAIN: Can you kind of

2 clarify that in what you have here? I mean,

3 it is a little opaque, the last line: This

4 approach is argued or relative to earlier --

5 DR. BLANC: Just argue that that

6 is advantageous relative to earlier -- it has

7 to be better written.

8 CHAIR BRAIN: So maybe you can

9 rewrite that.

10 DR. BLANC: No, I will.

11 DR. HAZUCHA: There are some

12 validation 20-25 years ago by Stewart and

13 Longa when they did measure directly blood

14 COHb level and compare it to CFK estimates,

15 but those are only a couple of studies, as I

16 said, 25 years ago. 

17 So there are no new studies, but I

18 believe that currently by simply using over

19 the decades CFK it was another validation

20 which sort of supposed that it is a good

21 model. There were other studies. They were

22 CFK and arterial blood to measure COHb level

Page 105

1 and compared it to CFK estimates.

2 CHAIR BRAIN: Okay, number 6,

3 which really deals with the carboxyhemoglobin

4 estimates, which is very important. I guess

5 at the end of 6 there is some specific items,

6 and I guess the question is should some of

7 these be swept into individual comments. 

8 I am talking about the top of page

9 5, or are some of them fundamental enough that

10 they need to be in this answer to the charge

11 question.

12 DR. BLANC: Those were -- I don't

13 think any of them were major. They are from

14 Milan, and I wanted to retain them here,

15 because I wasn't keeping parallel sets of

16 notes, but I can certainly make it an

17 addendum.

18 CHAIR BRAIN: Yes, I think so.

19 DR. BLANC: But you should look

20 and tell me if there is anything from the six

21 things that you think rises to the level that

22 it should be in the main response.
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1 DR. PENN: For lines 5 through 9,

2 in light of --

3 CHAIR BRAIN: You are back on page

4 4?

5 DR. PENN: Page 6.

6 CHAIR BRAIN: Oh, page 6. Page

7 six?

8 DR. PENN: Well, aren't we talking

9 about number 6?

10 CHAIR BRAIN: Yes, we are talking

11 about number 6, which is on pages 3 to five.

12 DR. BLANC: So you are talking

13 about the individual items on page 5 related

14 to point 6?

15 DR. PENN: Yes, I am talking about

16 question number 6 that are on page 6,

17 actually. But if I jumped ahead, go ahead

18 then.

19 DR. BLANC: No, because page 6 is

20 a response to number 7. 

21 CHAIR BRAIN: Maybe item 6 is

22 something that could be left in. Do you

Page 107

1 think, Paul -- I mean Item 6 of the list of

2 six at the top of page 5 could remain?

3 DR. BLANC: I would ask Milan.

4 DR. HAZUCHA: Oh, okay. Well, I

5 don't think, really, we need to have it here. 

6 Those are just corrections of definitions and

7 so on, and it can be under individual

8 comments, left under individual comments. I

9 am sure that they won't be ignored by EPA, and

10 they will look at it and say, okay, it is not

11 the CO2, but it is --

12 CHAIR BRAIN: Right. Exactly.

13 DR. BLANC: Does that also apply

14 to point 6?

15 CHAIR BRAIN: Point 6 seems a

16 little more --

17 DR. BLANC: Joe's question related

18 to point number 6, which is a little bit more

19 detailed. Is that something you want moved to

20 the end of -- retained in the body of the

21 response?

22 DR. HAZUCHA: Oh, I see. Well,

Page 108

1 no. It can be under individual comments. It

2 can easily be under individual comments.

3 CHAIR BRAIN: Okay. So we will

4 seep those into Milan's individual comments. 

5 Anything else about this section?

6 DR. KAUFMAN: I wrote an

7 additional paragraph that I sent to Paul. Do

8 you want me to just read it to you or how

9 would you like to address that?

10 CHAIR BRAIN: Sure. Why don't you

11 either read it or summarize it. Read it, if

12 it is not too long, please.

13 DR. KAUFMAN: It is not too long. 

14 I just wrote: In an improvement over the REA

15 draft -- rather, of the PA draft itself, the

16 staff's presentation at the meeting included

17 additional analysis of the contribution of

18 ambient CO to the COHb percent levels. 

19 While it was apparently

20 computationally intensive to develop, some

21 Panel members felt that this could be an

22 extremely useful avenue to further develop as

Page 109

1 an underpinning of the Policy Analysis. 

2 Indeed, the a priori focus of the influential

3 Allred paper was on the specified increase in

4 COHb over the subject's pre-exposure or

5 filtered air exposure, not on the magnitude of

6 the COHb percent. It may well be that the

7 ambient attributable increment in COHb is the

8 most directly analogous dose for consideration

9 in assessment of risk.

10 Some Panel members considered that

11 more attention to this ambient attributable

12 increment metric in consideration of dose

13 would simplify the assessment of risk as the

14 issue of, quote, overlap with the endogenous

15 range final COHb percent would be eliminated.

16 DR. BLANC: Joel, I think that

17 actually goes beyond the view of most of the

18 panel, and I would -- I am happy to dialogue

19 with you by e-mail so that we can come to

20 wording that would be, I think, less strong or

21 would otherwise say, although this was one

22 view, we could put in the --
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1 DR. KAUFMAN: Well, so I actually

2 think that what you said previously goes

3 beyond what most Panel members' view.

4 DR. BLANC: Well, good. That is

5 why we should have a dialogue.

6 DR. KAUFMAN: That is right. So I

7 actually think that having something that said

8 some Panel members felt this and some Panel

9 members felt that may be the appropriate way

10 to word this.

11 DR. BLANC: Well, fine.

12 CHAIR BRAIN: Okay. So we will

13 leave that to the two of you to --

14 DR. KAUFMAN Well, maybe we should

15 have a little open discussion right now to see

16 where people on the Panel are feeling about

17 this, because Paul feels pretty strongly about

18 the multi-compartment.

19 CHAIR BRAIN: Can you give us a

20 kind of a summary of the issue?

21 DR. BLANC: I think the issue --

22 the issue is, as I understand it, how

Page 111

1 important is it to have an estimate of

2 ultimate levels in the human population as

3 achieved by the combined combination of

4 endogenous exposure, ambient air exposure, and

5 indoor air exposure that is not derived from

6 ambient air exposure; and is there a way to

7 present that so that simultaneously the

8 summary value is provided as well as the

9 incremental value provided, so that the

10 implications of both the incremental and the

11 combined can be interpreted?

12 I think Joel's view is that it is

13 the incremental effect, which is the

14 biologically and epidemiologically important--

15 DR. KAUFMAN: Well, I don't think

16 biologically or epidemiologically important. 

17 I think it is the increment that is ultimately

18 the crux of what needs to be done for the risk

19 assessment. That is what is going to make

20 this process work from a policy perspective.

21 DR. BLANC: And my view is that

22 one needs to look at both the total as well as

Page 112

1 in the increment.

2 CHAIR BRAIN: The discussion of

3 smokers was interesting, isn't it, because

4 there these levels of CO are unimportant,

5 because there is not an increment.

6 DR. BLANC: So I guess what I --

7 the part of Joel's reason I take exception to

8 is not that -- I am not arguing that one

9 should not look at the increment. I would

10 just argue that one shouldn't look at the

11 increment only.

12 CHAIR BRAIN: So maybe we can

13 emphasize the value of each. Kyndall also

14 reminds --

15 DR. KAUFMAN: But I think that the

16 EPA approach that they presented in their

17 slide yesterday to looking at the increment

18 models everything into account. So they have

19 modeled the increment that actually takes into

20 account the various contributions.

21 CHAIR BRAIN: Why don't we leave

22 it to the two of you to come up with language

Page 113

1 that you like, and again Kyndall reminds us

2 that we don't need to achieve consensus on

3 every topic. So if there are somewhat

4 divergent views or two alternatives, both of

5 which should be considered, that is fine to

6 include that.

7 It sounds like it just may not be

8 either/or. It sounds like both ways of

9 looking at it, both in absolute terms and

10 incremental terms -- they both have some

11 value. Is that --

12 DR. BLANC: That would be my view,

13 but I don't think it is Joel's view.

14 CHAIR BRAIN: Do you want to

15 comment, Joel? I mean, are you arguing that

16 we should only address the incremental without

17 acknowledging the absolute?

18 DR. KAUFMAN: Well, I think the

19 absolute is of interest, but I think, from a

20 policy analysis -- I mean, I would appreciate

21 the perspective of the people who actually

22 practice risk assessment. Maybe that is EPA
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1 staff, and maybe there is somebody on this

2 committee who is a risk assessment/risk

3 analysis practitioner.

4 You know, one is going to more

5 greatly inform the risk assessment.

6 CHAIR BRAIN: Would the agency

7 like to comment on this topic?

8 DR. MURPHY: Well, we created the

9 presentation we did, and actually, in the

10 document we also present the information --

11 most of the information that was shown in

12 different form in our slides. It is in the

13 document, and we did that because we find that

14 to be a take-home message of the Allred study.

15 It has to do with the subjects

16 came in. They were given different exposures

17 to CO to achieve different increases in COHb,

18 and then in writing up the results there are

19 conclusions drawn with regard to relationships

20 between increases in COHb and various measures

21 of myocardial ischemia.

22 So in paying close attention to

Page 115

1 that study, both the papers themselves and the

2 discussion in the ISA, we did include that

3 section of the REA where we tried to see what

4 we could get the model to do for us in telling

5 us about the ambient contribution, because

6 that does seem to be informative.

7 In the end, what we are trying to

8 do is set air quality standards that protect

9 against ambient CO causing health effects in

10 the public. So I don't know if that is

11 useful, but so from a risk assessment

12 perspective that is certainly something we

13 often do, because our policy objective has to

14 do with the ambient piece of things.

15 DR. HAZUCHA: Well, currently both

16 absolute and increment values are important.

17 DR. BLANC: And I think, Dr. Penn,

18 you made some comments, having been familiar

19 with the study, about the dose response

20 element in it as opposed to the pure

21 incremental element. I don't know if you want

22 to reiterate some of those.

Page 116

1 DR. PENN: More than what I put

2 into my actual comments? 

3 DR. BLANC: Well, but your

4 comments aren't in this section. So maybe you

5 just want to -- maybe my comments should

6 direct us toward your comments, which are

7 related to the policy document -- right? --

8 not to the --

9 DR. PENN: Right, related to the

10 policy document, and that related back to the

11 ISA. 

12 DR. BLANC: Well, one thing, Joe,

13 we didn't do this morning is we actually

14 didn't go back over even once yet the late

15 afternoon presentations of the initial views -

16 - initial responses to the first six charge

17 questions on the policy document.

18 CHAIR BRAIN: We are going to do

19 that next. Right.

20 DR. BLANC: So maybe that will --

21 CHAIR BRAIN: Okay. I think we

22 have enough guidance to proceed. 

Page 117

1 Continuing down the page, what

2 about -- let's see, we are now up to Charge

3 Question 7 on page 5. Any comments about

4 that? So again, it has some of the themes we

5 have talked about several times, such as the

6 broadening of the at risk population.

7 I suppose in here we could tuck a

8 sentence or two that extends it to pulmonary

9 disease.

10 DR. BLANC: That is where I was

11 going to put the sort of --

12 CHAIR BRAIN: Right. I think that

13 would make sense.

14 DR. HAZUCHA: This seems to be a

15 good place, yes.

16 CHAIR BRAIN: So any suggestions? 

17 Again, we will all have time to quibble about

18 particular sentences or phrases, but the big

19 picture looks familiar and consistent with

20 what we have been saying?

21 DR. DAHMS: Well, is this the

22 point where we need to define for staff what
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1 we mean by -- are you asking them to put all

2 heart disease patients into their at risk

3 group? 

4 DR. BLANC: I hope that is what I

5 was asking. I thought I was explicit.

6 CHAIR BRAIN: Although I guess --

7 Tom, you were saying that perhaps we need to

8 distinguish between very likely and little

9 less likely. For example, I think there is a

10 distinction between left heart failure and

11 stroke.

12 DR. BLANC: I mean, as a practical

13 matter, I was simply suggesting that they use

14 the NHIS definition, which is basically heart

15 disease, and there is a subset, which is

16 ischemic heart disease, which is what they

17 currently use, and then there is a column

18 which is all heart disease; and it is separate

19 from hypertension. It is not that, but it is

20 sort of clear.

21 DR. DAHMS: So it is not

22 cardiovascular disease. It is disease related

Page 119

1 -- so it is the set of ICD-9 codes that relate

2 to the heart.

3 DR. BLANC: Well, it is not done

4 by the ICD-9 code, but it is a question, do

5 you have heart disease. For practical

6 matters, I think it would be the easiest and

7 most straightforward, and it would be sort of

8 an upper end estimate.

9 DR. DAHMS: And do you have any

10 idea to the extent that that increases the

11 numbers in the pool? Does it double the

12 numbers in the pool?

13 DR. BLANC It approximately

14 triples the numbers, I think. Double and a

15 half, maybe, somewhere between. I don't

16 remember. It is 28 percent instead of 11

17 percent or something like that.

18 DR. MURPHY: Right. So just to

19 clarify, if we are talking about frequency, is

20 this from the CDC publication which you are

21 referring to, the 2007 data. This is also in

22 the ISA. There is an excerpt of this table in

Page 120

1 the ISA. I don't have the page number, but

2 where it lists numbers of people with heart

3 disease all types, and it breaks it out, all

4 types and coronary.

5 So I believe Dr. Blanc is speaking

6 with regard to the all types column, and just

7 an eyeball on the numbers, it looks like that

8 column is approximately twice the coronary

9 column, plus or minus.

10 DR. DAHMS: And is there

11 justification for expanding it to that based

12 on the epidemiology data?

13 DR. BLANC: Yes, because that is

14 closer to the sort of all outcomes, all

15 cardiovascular outcomes, that are used. That

16 would be the closest parallel.

17 CHAIR BRAIN: Are you happy with

18 that or do you think we should make --

19 DR. DAHMS: No, as long as there

20 is a clear link with the epi data, if that is

21 -- because it has not always been clear to me

22 that I understood how those categories were

Page 121

1 reached in the epi studies.

2 DR. RITZ: This is Beate. The one

3 study that they are actually citing as the

4 most valid or best study under the current

5 standard is the Tolbert study, and that

6 actually has the category cardiovascular

7 disease. That includes all of the cardiac

8 diseases. So that is the epi study that

9 actually shows a relationship.

10 CHAIR BRAIN: Okay, good. That is

11 helpful. 

12 DR. BLANC: And, you know, I

13 provided to them a couple of papers that will

14 allow them to show that the National Interview

15 Survey defined prevalence that they use for

16 coronary disease is supported by other

17 national survey data, the NHANES and the

18 Behavioral Risk, even though they are slightly

19 different estimates, but they are all quite

20 similar.

21 So they have that, that they can

22 cite, but I am not going to put that in my
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1 comments with the level of detail.

2 CHAIR BRAIN: Do you want to add a

3 sentence that says that would be --

4 DR. BLANC: Maybe that is in

5 there, and I just forgot I put it in. Okay.

6 CHAIR BRAIN: Do you want to add a

7 sentence that would say that that represents

8 sort of an upper bound risk -- upper bound

9 estimate for cardiovascular risk, but that the

10 role of CO may be more important for some

11 conditions like ventricular failure and less

12 important for pulmonary embolism or stroke or

13 something?

14 DR. BLANC: Well, pulmonary

15 embolism is not in there, and stroke is not. 

16 I man, that is not subsumed in that anyway.

17 CHAIR BRAIN: Oh, good. Thank

18 you. 

19 All right, the last Charge

20 Question, Number 8. Any questions about that? 

21 Okay, good.

22 So the next step, to repeat

Page 123

1 myself, is then to ask all the lead authors to

2 taken into account what they have heard and

3 their own ideas, and by the end of this week,

4 if you can send to Kyndall your updated best

5 versions.

6 Let us now turn to the other

7 document that you got, which is the Policy

8 Assessment document, the PA, and have a look

9 at that.

10 Shall we do the same thing? I

11 suppose we could zip through it twice. We

12 could first -- maybe why don't we do it one at

13 a time, but why don't we begin -- rather than

14 going through it twice, why don't we -- for

15 example, with number 1, let us first hear from

16 the lead author as to whether there are

17 unresolved issues that they need help with,

18 and then we can open it up. 

19 So let's look at Charge Question

20 1. So this is Arthur. You are happy?

21 DR. PENN: I have no unresolved

22 issues. The only question is, on the second

Page 124

1 paragraph where we specifically talk about the

2 four NAAQS basic elements, whether that

3 belongs in here or whether it belongs

4 somewhere else. 

5 I incorporated what Stephen had

6 yesterday about indicators, and a couple of

7 other points that people made, but these are

8 really specific comments. Do they belong

9 here?

10 CHAIR BRAIN: Anybody want to

11 respond to that? They sound fairly specific,

12 perhaps too specific. Is there any kind of

13 overarching theme?

14 DR. PENN: Yes. I think that the

15 definitions that are given that are supposedly

16 key to all of this stuff are lousy. 

17 CHAIR BRAIN: So maybe you just

18 want to say that, and sweep some of the

19 specific comments into your individual. Does

20 that make sense?

21 DR. KLEINMAN: Would it be helpful

22 to just request a table of abbreviations and

Page 125

1 definitions as part of the document. That

2 way, you kind of cover it. It may be in the

3 ISA somewhere, I think.

4 CHAIR BRAIN: And it would be nice

5 if you did make a general comment to give a

6 couple of examples.

7 DR. PENN: Okay, sure.

8 CHAIR BRAIN: And then the

9 complete list of problems could be swept into

10 your own comments. Anything else about Number

11 One? 

12 Okay, then we move to Tom who will

13 tell us about Charge Questions 2 and 3. So

14 what about 2-A and B. Tom, we will start with

15 you.

16 DR. DAHMS: I think there is no --

17 I don't see any unresolved issues. I don't

18 know. Most of these other comments came from

19 Milan, other than my stuff. 

20 DR. HAZUCHA: Well, on the bottom

21 of the page 1, the document has the

22 epidemiologic studies, but my question is just
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1 a part from the previous discussion. Can they

2 -- do you think that they can present it

3 better?

4 DR. DAHMS: Well, I think that has

5 been the tenor of the whole discussion that we

6 seem to have had over the last day and a half,

7 is that -- I don't know whether we are asking

8 them to present it better, to change their

9 analysis and opinion of the epi studies based

10 on the feelings of this Panel, based on the

11 epi studies. I don't know which of those

12 things we are asking them to do.

13 We are certainly asking them to

14 put far more weight on the epi studies than

15 appears to have been put on them. Francine?

16 DR. LADEN: I just have one

17 comment. I went back and re-read parts of

18 this last night, and I really -- in reading it

19 more carefully, I felt that the epi studies

20 were actually pretty well talked about.

21 I think where I would -- in my

22 opinion, kind of where there is something

Page 127

1 lacking is more just some more clear

2 statements about the context of the risk

3 assessment and the epidemiology studies and

4 how the epi studies can inform for public

5 policy.

6 I think that there actually was

7 some good summaries of the epi data, but I

8 think it was just that next step that was

9 missing. 

10 My feeling of what is going on in

11 this committee's discussion is that, you know,

12 it is everybody here who is pretty savvy in

13 epidemiology studies isn't feeling that they

14 are given enough weight, that there is that

15 next link that needs to be made to help

16 convince people that, even though they can't -

17 - I mean, I actually feel strongly that they

18 can't really be used in the risk assessment --

19 in the quantitative risk assessment, as you

20 have done, you know, just -- I agree with the

21 decisions that were made, but I think that

22 context is what needs to be stressed more --

Page 128

1 defended more, I guess, is the word.

2 CHAIR BRAIN: I guess I heard a

3 contrary view that, in fact, this broader

4 definition of cardiovascular disease could be

5 included in the risk assessment --

6 DR. LADEN: Well, I think the one

7 way that it --

8 CHAIR BRAIN: -- and the

9 populations could be modeled --

10 DR. LADEN: -- is doing a second -

11 - like where you have the first analysis of

12 the population at risk, but you can expand

13 that population at risk and do another

14 analysis including that, and I think that is

15 one way that it can be put into the risk

16 assessment, but not in terms of the actual

17 quantitative numbers of what the exposure is.

18 CHAIR BRAIN: Not with different

19 coefficients, right.

20 DR. LADEN: Yes.

21 DR. KLEINMAN: But I think, in

22 order to use or regroup the data, it really

Page 129

1 requires a reanalysis of what is actually

2 published, since the authors of the

3 publication broke out the groups and did not

4 collectivize them.

5 So I think, yes, we can recommend

6 that EPA look at additional analyses of those

7 data.

8 DR. LADEN: I liked your idea of

9 the meta analysis. The question is, is that

10 really part of the charge? I'm not sure.

11 DR. BLANC: I think that, when we

12 dealt with the ISA, there were -- we

13 definitely -- Beate could probably reaffirm

14 this -- that we talked about the advantages of

15 meta analysis of the epidemiologic data. I

16 don't think it actually happened, but I think

17 that the part of the interpretative issues

18 with the epidemiology in the Policy Assessment

19 document is not that they don't acknowledge or

20 present epidemiologic data, but everything is

21 geared toward discounting it.

22 I am just saying what you said in
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1 a different way. The comments that I made

2 earlier about the key table which attempts to

3 undermine the epidemiologic data is not

4 convincing to me and, I think, misses the boat

5 and is used as a kind of sledge hammer,

6 inappropriately, to say let's ignore the

7 epidemiologic data, this issue about what were

8 the exposure levels in those areas.

9 For example, discounting one study

10 where the confidence interval lower limit was

11 .9999 -- that is one thing, but also

12 discounting studies which may have had some

13 excursions but where all the excursions were

14 very unlikely to be driving the observation.

15 DR. LADEN: And if you looked at

16 the ranges of the -- the interquartile ranges

17 and not the 99th percentile ranges, it is --

18 I mean, I think there could be more weight

19 given to the fact that those studies do have

20 predominantly exposures within the range that

21 we are interested in.

22 DR. DAHMS: So, essentially, what

Page 131

1 we are asking staff to do is to kind of really

2 back off of the strident approach of using the

3 dose of CO as the marker, and saying that

4 there are other unknown considerations to be

5 used; or do we say that the dose of CO at very

6 low levels with the epi -- that the epi

7 studies would result in -- this is just a

8 lower end of the continuum?

9 DR. BLANC: I think what we are

10 saying is just a bit more general, that they

11 need to recalibrate their assessment of the

12 epidemiologic literature to be more in line,

13 I think, with the ISA's weighting of the

14 epidemiologic literature.

15 I think that there is some

16 confusion in the policy document between the

17 technical requirements of risk assessment that

18 require them to use the controlled human

19 exposure data in one particular way, which I

20 don't think anybody here told them not to do

21 or to back away from, and that has somehow

22 become muddied or muddled with what the

Page 132

1 epidemiologic literature -- the very important

2 information that the epidemiologic literature

3 is providing.

4 So that there was almost a sense

5 of sidestepping the epidemiologic literature

6 in the policy document.

7 CHAIR BRAIN: It is a nuanced

8 message.

9 DR. BLANC: So I think -- in terms

10 of nuance, I think that the wording -- it is

11 not that they didn't describe the

12 epidemiologic literature. It is not a

13 question of describing it. It is a question

14 of, as you said, interpretation.

15 CHAIR BRAIN: And how prominent it

16 is, the relative balance between those two.

17 Okay, that sounds like we have

18 some guidance there. How about Charge

19 Question 3?

20 DR. MURPHY: Dr. Brain, could we

21 make a comment on this point?

22 CHAIR BRAIN: I'm sorry?

Page 133

1 DR. MURPHY: Could we make a

2 comment on this point?

3 CHAIR BRAIN: Oh, please, please. 

4 Yes.

5 DR. MURPHY: And it comes, I

6 believe, at page 5 and 6, one of the other

7 Charge Question comments that is in this

8 draft.

9 Perhaps it would be useful to talk

10 a minute about there were a couple of things

11 that were discussed here, and just for

12 clarification it might be useful to talk about

13 them.

14 So we certainly feel like we are

15 interpreting and giving full weight to the epi

16 studies, consistent with the ISA, in this

17 Policy Assessment and, as we talked about

18 yesterday, one thing they clearly provide is

19 this coherence with the clinical studies in

20 terms of the endpoints where we see these

21 statistically significant and the strong

22 associations.
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1 In terms of understanding the way

2 we have looked at things in the Policy

3 Assessment, we need to go beyond is CO causing

4 effects, and do we need a standard, to a

5 question of what should the standard be, and

6 is the current standard adequate.

7 As was mentioned previously, in

8 these epi studies -- there are two things I

9 want to speak to. In these epi studies we're

10 not measuring COHb. They are not measurements

11 of COHb. They are not measurements of total

12 personal exposure. What is done is

13 relationships between ambient concentrations

14 and outcomes. 

15 So in terms of we have struggled

16 with trying to integrate the body of evidence

17 that we have that links CO to hypoxia and COHb

18 levels to measures of ischemia in the clinical

19 studies, and in the beginning of Section

20 2.2.1, I believe, through the first question,

21 goes through pages 214 to 216, and we even

22 have a figure talking about here are the two

Page 135

1 pieces of evidence -- two types of evidence we

2 have, the clinical and the epi, and we need to

3 see how they fit together.

4 When we are lacking this internal

5 dose metric, it makes it a little more

6 difficult. So we are cognizant of the fact

7 that we don't know what the COHb levels of the

8 subjects -- or you wouldn't say subjects -- of

9 the people in the epidemiological studies, and

10 we don't know what their total exposures are. 

11 So that is a handicap for us in looking at

12 that, and your views on that would be useful.

13 The other thing, though, I want to

14 mention is that we begin to do in this part of

15 the Policy Assessment with Table 2.1 and then

16 do more of in response to a latter question

17 with regard to levels where we have Tables 2.3

18 and 2.4, is say what can the epi studies tell

19 us with regard to levels of the standard.

20 Some of the interpretations of

21 this go to the issue of the form of the

22 standard. I know the Panel has reiterated

Page 136

1 that, well, the mode, if you will -- the

2 prevalent concentrations in these epi studies

3 are quite low, but we currently do not have a

4 standard that is of the form, an annual

5 average or a multi-year average, which if you

6 were comparing to these studies, the average

7 or the median seems to be 1 to 2 ppm, 3 ppm.

8 The current form of the standard

9 is this not to be exceeded. So looking at any

10 distribution of air quality, the upper tail of

11 that distribution will be higher. When we set

12 the standard with a form of not to be

13 exceeded, we recognize that that will bring

14 the distribution of air quality down.

15 So that is why, when we are

16 thinking of the question of level of the

17 standard, it is important to think about what

18 form are we talking about for which we want to

19 identify the level of the standard.

20 So that is why, in this table, we

21 not only have, in Table 2.1 I am now talking

22 about, the bulk of the table is just

Page 137

1 reiterating descriptive information about the

2 standards, which is in the ISA, the far right

3 most columns provide what we call design

4 values, which is the statistic for the air

5 quality in those areas that would be compared

6 to the standard.

7 So that allows us to say during

8 these studies were these areas in attainment

9 or would there be controls being put in place

10 through different implementation plans, for

11 example, which is what the standard is

12 intended to achieve.

13 When we do that, we end up saying,

14 well, while all of these studies are hugely

15 useful to us in drawing connections between CO

16 and health effects, when we get to this other

17 issue of choosing a level for the standard, we

18 need to think in terms of all the elements of

19 the standard, one of them -- and think in

20 terms of form that goes with the level, and

21 the current form is second max, which is what

22 is shown in this table.
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1 So then, clearly, we are not

2 suggesting that the -- I mean, we can't take

3 apart these studies and get more out of them

4 than what is in them. So we don't know what

5 people's exposures were. We don't know what

6 people's COHb levels were. So we don't know,

7 you know, in terms of the people that went to

8 the hospital, but we can say whether or not

9 they were in areas where the standard was

10 exceeded, which is informative to us in terms

11 of our objective in identifying ambient

12 concentrations of CO, which we need to protect

13 against.

14 So maybe I am rambling a bit, but

15 I am just hopeful that you all have tried to

16 get at what we were trying to convey, and can

17 give us advice on what we were trying to

18 convey. If we did it not well, at least you

19 can tell us that.

20 DR. PENN: Could I make just a

21 comment on this? I appreciate the fact that

22 you guys do recognize -- you realize -- You

Page 139

1 are making a good balance here, and you

2 recognize our concerns, and you have told us

3 your concerns. But part of the stuff that

4 Paul pointed out yesterday is the way this

5 stuff reads, and the Policy Assessment is

6 really apparently a major document that is

7 going to come out of this.

8 So you have all of the ISA, and

9 that is the Scientific Assessment, and all of

10 these data that we talked about for the epi

11 stuff is in there; and the focus -- the way it

12 reads is that the focus now is away from that,

13 and this is the point that Paul brought up

14 yesterday, and I think it just reads -- to an

15 objective reader, it reads that there is this

16 bias that is underlying all of this.

17 So maybe my suggestion that there

18 be a meta analysis of the epi data would

19 really be worthwhile here.

20 CHAIR BRAIN: I think we need to -

21 - this has all been very helpful, and I think

22 we can take this into account. I guess the

Page 140

1 only quick comment that I would make is it

2 seems to me you are holding carbon monoxide to

3 a standard that is higher than what we have

4 used for other criteria pollutants.

5 You are saying, you know, we don't

6 have -- for the epi, we don't have COHb, we

7 don't have an internal dose metric. I mean,

8 that is true, but we don't have that for PM2.5

9 or NOx or SOx either. 

10 The existence of COHb is a really

11 pleasant, convenient biomarker, but in

12 general, for all kinds of environmental

13 threats, maybe with the exception of lead or

14 something like that, you know, we don't have

15 biomarkers for air pollution studies.

16 I think now we need -- we only

17 have about a half an hour left. So I think

18 everyone feels they have gotten good input

19 from the agency and from people around the

20 table. Tom, anything else that we need to say

21 about Questions 2 or 3?

22 DR. DAHMS: No.

Page 141

1 CHAIR BRAIN: We all set?

2 DR. HAZUCHA: Charge Question 3,

3 if I may have a comment here -- it will be

4 very, very difficult, not only for EPA but

5 certainly, even for us to link subsidiary

6 mechanisms to standards.

7 Now here oxygen in these studies -

8 - Yes, there are studies, but it is very

9 difficult yet to have enough information to

10 link it to exogenous levels of CO, and then

11 the statement that endogenous levels of CO

12 that could be altered by exogenous exposure --

13 again, I am not sure that there is any

14 evidence that you can do that, that you can

15 simply change by exogenous exposure -- change

16 endogenous levels.

17 There are studies, for example, on

18 effects of carbon monoxide on brain, and you

19 have clearly vasodilation. Yet heme 

20 oxygenase, for example, in brain wasn't

21 affected at all, although clearly, you had

22 local effects by vasodilation.
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1 So there is still, I guess -- this

2 evidence is still emerging, and I am not sure

3 whether we are in a position to say too much

4 about it.

5 CHAIR BRAIN: Is there agreement

6 with that?

7 DR. DAHMS: Well, what I wanted

8 was some acknowledgment that -- you know,

9 there is no acknowledgment that I can see --

10 and Steve may be more sensitive to this, but

11 I didn't see it and, Milan, that sentence --

12 there are some grammatical mistakes in there -

13 - that regional increases in endogenous levels

14 of CO or COHb that could be altered by

15 exogenous exposure.

16 CHAIR BRAIN: I guess I am a

17 little concerned about lumping -- you know,

18 you are mentioning two areas, the

19 epidemiologic studies and the heme oxygenase

20 studies. To me, I think those are quite

21 different. The epi has greater --

22 DR. DAHMS: Well, yes, I am still

Page 143

1 scratching to try and find some mechanism for

2 the -- you know, there is no postulated

3 mechanistic point. Maybe there doesn't need

4 to be one. If there doesn't need to be one,

5 then let's just strike it and go on.

6 CHAIR BRAIN: I don't understand,

7 because don't we have reduced oxygen delivery

8 as a common mechanism for the epi studies of

9 other cardiovascular conditions?

10 DR. DAHMS: No, we talked about

11 the internal dose metric, and how do you

12 postulate some kind of an internal dose metric

13 that is consistent between the controlled

14 human exposure data and the epi data? How do

15 you get there? Is there --

16 CHAIR BRAIN: That is a luxury we

17 don't have with any other criteria pollutants.

18 DR. DAHMS: Okay. Then let's not

19 worry about it, delete this, and go on.

20 CHAIR BRAIN: No, no. I guess I

21 just have a problem with sort of making epi

22 studies and heme oxygenase studies sort of

Page 144

1 sounding as if they were of equivalent

2 importance in the validity.

3 DR. DAHMS; No, no. That was not

4 the intent.

5 CHAIR BRAIN: So I think that is

6 one thing that I would suggest clarifying.

7 DR. DAHMS: Sure.

8 CHAIR BRAIN: I think the heme

9 oxygenase area is interesting, but very

10 contradictory, and it is unclear.

11 DR. DAHMS: I was thinking in

12 mechanistic terms and not --

13 CHAIR BRAIN: Well, then somewhere

14 we need to be clear about are there non15 hypoxia mechanisms such as signaling or heme

16 oxygenase or -- but that is sort of at a

17 different level.

18 Other comments about Question 3? 

19 Then that gets us to Question 4. Joel, are

20 there things you -- any concerns that you have

21 in terms of Question 4 where you need advice

22 or you sense lack of consensus?

Page 145

1 DR. KAUFMAN: I tried to bound

2 what I thought were some contrasting opinions

3 that were both in written comments and that I

4 heard during the discussion yesterday. I

5 guess I would appreciate people reading it

6 through and advising me if I haven't reflected

7 the Panel's opinion as well as I should have.

8 I also have the specific comments

9 at the end. I guess earlier in one of the

10 Charge Questions, we decided that maybe they

11 don't -- minor things like this don't belong,

12 but I don't know. I will defer to your

13 judgment on that.

14 DR. BLANC: Joel, those are the

15 bullets at the end?

16 DR. KAUFMAN: Yes.

17 CHAIR BRAIN: Any opinions? Are

18 these broad issues that should be part of the

19 answer to the Charge Question? Are they more

20 specific? 

21 DR. DAHMS: I think they should go

22 into the --
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1 CHAIR BRAIN: They should go what?

2 DR. DAHMS: Come out of here and

3 go into the specific comment.

4 CHAIR BRAIN: Is that a consensus,

5 that they are specific enough they can be put

6 into Joel's specific comments?

7 DR. DAHMS: Well, Joel, take

8 another look at the last bullet, because that

9 seems more general, and maybe you want that --

10 DR. KAUFMAN: Yes. I think the

11 last one is fairly substantive. Probably

12 could be a stand-alone paragraph up above.

13 CHAIR BRAIN: But not the first

14 two. DR. BLANC: I also think

15 it is excellent that you remind about the

16 discussion of the one percent threshold,

17 because I don't think that appears anywhere

18 else, and it is good not to lose track of

19 that.

20 CHAIR BRAIN: Okay, any other

21 discussion of Question 4? I think it reads

22 well. So that looks good. Thank you. Thank

Page 147

1 you, Joel.

2 DR. KAUFMAN: All right.

3 CHAIR BRAIN: Let's move on to

4 Charge Question 5, and this brings us back to

5 Tom Dahms. 

6 DR. DAHMS: Well, again, there was

7 -- you know, I started adding everything into

8 this, and some of it, obviously, needs to come

9 out and to be put into specific comments. 

10 The first -- well, the second

11 paragraph under Exposure Risk Based

12 Considerations. Again, I was still struggling

13 with trying to figure out how to deal with the

14 dose metric with the epi studies, and so this

15 is --

16 CHAIR BRAIN: Sounds like a

17 combination of some specific suggestions, but

18 then still an overarching concern that --

19 DR. DAHMS: So maybe we need to

20 edit it out of there.

21 CHAIR BRAIN: Right. Maybe we can

22 divide it.

Page 148

1 DR. DAHMS: And leave the concern.

2 DR. PENN: Well, the next three

3 paragraphs after that were mine. Do you want

4 me to just put that into my own personal

5 comments, on page 5, the first three

6 paragraphs?

7 CHAIR BRAIN: Well, there is sort

8 of the big issue of the Allred studies and how

9 they are to be interpreted and used.

10 DR. PENN: That is more general,

11 but the next two -- well, the next paragraph,

12 certainly, deals with specific stuff.

13 CHAIR BRAIN: Yes. So we will

14 leave that to the two of you to extract some

15 parts while leaving the broad macroscopic

16 judgments there. I mean, I think again the

17 last paragraph is important, the concern about

18 CO as a surrogate. So that sounds like it

19 should stay.

20 Other questions, comments, about

21 the answer to Charge Question 5? 

22 DR. PENN: Is there going to be

Page 149

1 one place where you bring together all the

2 uncertainty issues, because some of them could

3 have fit in Question 2. Some could be in 5. 

4 Some could be, I think, in 7. So when you

5 write the letter, are you going to just put it

6 altogether in one place?

7 CHAIR BRAIN: I confess, I didn't

8 have uncertainty as one of my current four or

9 five most important topics, but let's have a

10 look, and maybe -- does it rise to that level? 

11 I didn't see it quite at the importance as

12 some of the other concerns and advice that we

13 have. 

14 Charge Question 6, Dr. Thom.

15 DR. THOM: Well, Paul and I have

16 spoken, and there is a couple of things that

17 I need to change, specifically regarding Table

18 2.1, just a correction, that it is four

19 studies where the standard was exceeded in the

20 eight-hour 9 parts per million. But

21 basically, the gist remains the same in terms

22 of stronger use -- consideration of the
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1 epidemiologic data.

2 I have added a sentence from,

3 basically from what Paul had said earlier

4 today, that with regard to the studies in

5 Table 2.1, even those where the standard was

6 exceeded, it is unlikely that the positive

7 association between ambient CO and health

8 effects were related to the brief intervals

9 when the CO levels exceeded the current

10 standards. That is to say, there is still

11 valid information in the epidemiologic data.

12 So that has been changed a little

13 bit. The only other item is basically the

14 last three lines on page 6, 43 to 46, which,

15 I believe, is I don't understand what the 99th

16 percentile standard is. 

17 My understanding was that -- from

18 our discussion yesterday, was that that was

19 basically a moving target based upon actual

20 data, but Paul thinks that I've got that

21 wrong. So probably those three lines need to

22 be deleted, but I confess, I don't understand

Page 151

1 the 99th percentile component of a statistic.

2 DR. BLANC: Do you remember that

3 discussion yesterday, back and forth, and I

4 think what I heard them say, you know,

5 whatever we set the limit to, then one option

6 is to talk about the 99th percentile in that

7 range, but 99th percentile isn't a moving

8 target. So it wouldn't be a standard that

9 would shift every year, depending on what your

10 actual observed levels were.

11 DR. MURPHY: Right. The standard

12 would not shift. Which lines, though, Dr.

13 Thom? I just want to make sure I was

14 following you. Which lines on the page?

15 DR. THOM: The last three lines on

16 page 6. I wrote that based upon what our

17 discussion was yesterday. I had the sense

18 that, if the 99th percentile standard was

19 used, essentially it would drop by near 50

20 percent the acceptable eight-hour -- well,

21 whatever standard you use, it would drop.

22 DR. MURPHY: No, and I am

Page 152

1 confused. I just want to -- to be able to be

2 clear, it would help me to understand why do

3 you think 50 percent, so I understand where

4 the confusion is?

5 DR. THOM: The ambient levels are

6 now in the range of -- whatever, 5 to 6 parts

7 per million or lower.

8 DR. MURPHY: It depends on your

9 statistic. On average? As a 99th percentile?

10 DR. THOM: So I think with regard

11 to this document, I am going to just delete

12 those three lines. But fundamentally, the

13 issue comes down to I don't understand what

14 the 99th percentile standard means.

15 DR. MURPHY: All right. So it

16 goes to form, and this may -- I am struggling

17 to make sure I follow where the areas of

18 confusion are, and I am wondering if some of

19 the confusion about the tables of epi studies

20 relates to this, because one of the metrics

21 for describing air quality for the epi

22 studies, I believe, is a range of 99th

Page 153

1 percentile values in one of the columns; but

2 that is simply the 99th percentile value of

3 whatever that number is across the monitors in

4 the study.

5 Now in terms of the form of a

6 standard, we do -- as was mentioned earlier,

7 if we have five monitors in an area and one

8 exceeds the standard in the form of the

9 standard, then that area does not meet the

10 standard, and things happen.

11 So the forms of the standard could

12 be a not to be exceeded value. In the case of

13 lead, that is what it is. You cannot exceed

14 a three-month rolling average of .15 ppm lead

15 in total particles in the air at any of the

16 monitors. That is lead.

17 For CO, we say you can exceed only

18 once at any monitor the standard of 9 ppm. If

19 we were to go to a different form, we

20 mentioned you can have -- and these are -- and

21 that is in terms of an eight-hour average.

22 We have other standards which have
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1 annual average standards. Clearly, the

2 averaging time will affect the level, and also

3 the form, the statistical form, will affect

4 the level. 

5 So these things together, how we

6 measure the pollutant, what averaging time we

7 think is important for the pollutant in

8 ambient air, and what statistical form would

9 be appropriate to best protect public health

10 with an adequate margin of safety; and that

11 consideration goes a bit beyond just looking

12 at something that might be compared to a

13 simple toxicological study design. 

14 It considers -- when we implement

15 a standard, we need to make judgments about an

16 area which trigger different control actions. 

17 We don't want to make that lightly. We don't

18 want to decide someplace is out of compliance,

19 trigger some control actions, and the next

20 year have to change our mind and back off and

21 rethink the whole thing.

22 So that is a consideration we call

Page 155

1 stability, which we want to have -- we want a

2 form to be stable in that way, so that we

3 don't have area coming in and out. So that is

4 why here we have considered a more stable form

5 than a second maximum or a to be exceeded only

6 once a year might be a 99th percentile,

7 because that is not as extreme a value in your

8 dataset.

9 So that when you judge have you

10 met the standard, if your standard is a 99th

11 percentile value at 8.4 or some number -- make

12 a number -- say it is at 8.4, then you look at

13 your dataset, and you will say what is the

14 99th percentile in that dataset for that

15 monitor. Is it above that level? If it is

16 above that level, you have not met the

17 standard. If it is at or below that level,

18 you --

19 CHAIR BRAIN: I think we need to

20 get back to Charge Question 6.

21 DR. MURPHY: Oh, sorry.

22 CHAIR BRAIN: Are we clear?

Page 156

1 DR. THOM: I said that I am taking

2 it out. But the point -- I would like to make

3 the one point, though, that what allows -- the

4 99th percentile allows one percent excedences,

5 which would be three days a year instead of

6 one day a year, so at the same level.

7 So the level of the standard is

8 nine.

9 CHAIR BRAIN: Right.

10 DR. THOM; But now if you move to

11 a 99th percentile, then you could have three

12 excedences a year. That would be bad. So my

13 only point is it would drop it. 

14 DR. KLEINMAN: So if you go to the

15 more stable form, then probably we would want

16 to suggest a lower standard.

17 DR. THOM; Yes.

18 CHAIR BRAIN: So it is not

19 relevant. You are just going to delete that

20 sentence.

21 DR. THOM: Yes.

22 CHAIR BRAIN: Clearly, the form

Page 157

1 has profound implications. All right, let's

2 go on to 7, which again we talked about this

3 morning. We've got about 10-15 minutes to

4 finish up here. Mike, I guess you have

5 already talked about this today.

6 DR. KLEINMAN: Yes. 

7 CHAIR BRAIN: Is there anything

8 you want us to focus on?

9 DR. KLEINMAN: Well, based on the

10 discussion this morning, I am going to add --

11 I would like to add a paragraph that says,

12 based on the analysis of the epidemiological

13 studies presented in the PA, there is a

14 consensus in the Panel that the current

15 standards may not adequately protect public

16 health with a reasonable margin of safety and,

17 therefore, revisions that result in reducing

18 the standards should be considered.

19 CHAIR BRAIN: I think that is

20 really important.

21 DR. HAZUCHA: With one abstention.

22 CHAIR BRAIN: Let that be shown. 
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1 If you even want to add a sentence as to why

2 you abstained, we could include that.

3 DR. HAZUCHA: Because I just feel

4 there isn't enough scientific evidence for

5 changing the standard.

6 CHAIR BRAIN: Fine. Good. 

7 Anything else in regard to Charge Question 7? 

8 Then Mike also was responsible for number 8. 

9 Anything about Charge Question 8?

10 DR. KLEINMAN: Let me see. So

11 just to reiterate -- yes, I made four

12 suggestions, recommendations for additional

13 considerations. 

14 The first one I made was the

15 question about how many locations might go out

16 of compliance, and in retrospect I don't think

17 that is appropriate for this letter. So I am

18 going to delete that.

19 CHAIR BRAIN: Okay.

20 DR. KLEINMAN: Any other guidance

21 for me on what else we should do? 

22 DR. BLANC: I don't think,

Page 159

1 actually, you need it here to reiterate what

2 they said about what the range of policy

3 options are, necessarily.

4 CHAIR BRAIN: Unless you want to

5 comment on -- 

6 DR. BLANC: Well, for CASAC?

7 DR. KLEINMAN: Maybe what I will

8 do is I will just put in a sentence relating

9 the level and form, saying that if the

10 recommendation is to go to a different form,

11 then the level of the standard should be

12 appropriately modified so that we don't lose

13 protection.

14 CHAIR BRAIN: Well, I think some

15 sense of the excellent lesson that you gave us

16 on the importance of the form and how that

17 really affects how many excedences there are

18 and how stringent the standard really is

19 depends not just on the level but very much on

20 the form -- so I think -- because you said to

21 educate CASAC and give CASAC a chance to

22 comment on that, if they wish, is a good idea.

Page 160

1 DR. KLEINMAN: Okay.

2 CHAIR BRAIN: I'm sorry, what? So

3 we don't have before us 9, 10 and 11, but we

4 talked about that. Paul, is there anything

5 else you want to bring to our attention?

6 DR. ROBERTS: I don't even need

7 anything else. I have a version. I thought

8 I sent it to you last night, but I don't know

9 what happened to it. So it's fine. I can

10 make sure Kyndall gets it.

11 CHAIR BRAIN: Okay. You have his

12 version? 

13 DR. ROBERTS: I had a couple of

14 minor additions. 

15 CHAIR BRAIN: Okay. So I guess an

16 additional question is: Are there items on

17 the Policy Assessment -- in addition to the

18 answers to the Charge Questions, we have

19 already mentioned a couple of topics that we

20 want to include, but again are there any other

21 themes or comments that don't tuck into the

22 answers to the Charge Questions?

Page 161

1 DR. PENN: How does staff look at

2 our individual comments versus these summary

3 comments?

4 CHAIR BRAIN: Can you respond?

5 DR. MURPHY: Certainly, certainly. 

6 They are quite helpful to us, clearly. So we

7 certainly read them. We consider them. it is

8 useful. Often, they will note things that

9 haven't come up at the meeting, and it is

10 something for us to think about. So we

11 certainly pay attention.

12 CHAIR BRAIN: Yes, it is

13 interesting, because the individual comments

14 are really of two types. Some are

15 wordsmithing and requests for clarity that

16 everybody would endorse, and so they really

17 are consensus view. But then there are also

18 some that are perhaps more idiosyncratic or

19 forward looking that are kind of inappropriate

20 for a consensus report, but I guess we kind of

21 leave it up to you to sort out those two

22 flavors. There may be more.
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1 DR. KLEINMAN: Joe, I would like

2 to recommend that we put a sentence in the

3 letter complimenting EPA staff on this first

4 draft of the Policy document as being very

5 well put together, very cogent, and very

6 comprehensive.

7 CHAIR BRAIN: I will include that

8 in my letter. Any other sort of overall

9 comments?

10 DR. ROBERTS: Well, I think we

11 should also -- you know, they made a lot of

12 changes to the REA based on our comments from

13 last time. I think that was really great. 

14 You know, the time and everything was a

15 difficult element, I am sure, to overcome. 

16 CHAIR BRAIN: So there's general

17 enthusiasm and gratitude for really both

18 documents, the improvements in the REA and the

19 first draft of the PA.

20 DR. BLANC: And, Joe, if you are

21 going to do that, I think in the same sentence

22 you might also say that, even though we didn't

Page 163

1 discuss the final ISA, that it was also

2 responsive to our input and was quite useful

3 in the discussions. You saw we kept referring

4 back to it.

5 CHAIR BRAIN: And that could go in

6 the REA letter. 

7 DR. ROBERTS: So, Joe, I guess I

8 have a question. The PA is not going to be --

9 it is just going to be revised once, and we

10 won't see it except the final version, and

11 that is after our meeting, our phone call in

12 April?

13 MS. BARRY: Even though there is

14 not a -- there may not be a specific charge

15 from EPA to comment on the final Policy

16 Assessment, it is within CASAC's purview to

17 provide any comments that you have on the

18 final document.

19 As we have heard, you know, you

20 guys are very comfortable with the ISA. That

21 is excellent to know. When the EPA is

22 finalized in May, if you all take a look at it

Page 164

1 and have some concerns, we could -- it is

2 within the Chair's decision to say, you know,

3 we probably need to have a meeting and talk

4 about where there is still some need for

5 improvement before there is a proposal of any

6 policy.

7 CHAIR BRAIN: Or even the quote

8 final ISA, if CASAC really wanted to make some

9 comment about it -- you know, we still

10 disagree -- even though it is final, we can

11 still make a comment.

12 MS. BARRY: Yes.

13 CHAIR BRAIN: Not that anyone has

14 suggested that that is necessary. We have a

15 lot of latitude. In fact, I think that comes

16 to the top. As we have mentioned before, we

17 shouldn't be too focused, too constrained by

18 the Charge Questions. We may have other

19 issues we want to bring up.

20 DR. BLANC: But one piece of

21 feedback in terms of the Charge Questions is

22 that a couple of us around the table have

Page 165

1 responded, and I think it resonated,

2 certainly, with me, even though I didn't make

3 the comment, that there is overlap to such an

4 extent in some of the Charge Questions that it

5 makes it difficult for us as we are trying to

6 respond to them.

7 So always be sensitive to -- you

8 are so close to the document, but what is it

9 going to look like for us trying to answer

10 five versus six when they are very

11 interrelated, and also a Charge Question

12 related to a summary chapter that is first

13 puts a reviewer in a really difficult spot,

14 because they have to read the minds of

15 everybody else who is going to respond to the

16 other Charge Questions, which are going to

17 influence -- 

18 If Charge Question Number 1 is

19 what did you think about the summary chapter -

20 - right? -- but we haven't heard the input

21 from everybody else, or the introductory.

22 CHAIR BRAIN: And I guess that
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1 brings up another opportunity which we really

2 didn't have this time, as I understand it. It

3 is appropriate for CASAC to, in fact, have a

4 discussion about the Charge Questions. This

5 time, we were very constrained by time. We

6 really didn't have time to do that, but in a

7 perfect world, CASAC would have a look at

8 those Charge Questions and might say, you

9 know, we really don't understand these. 

10 Again, EPA has the final authority for the

11 Charge Questions, but we could have a

12 conversation about that to try to improve

13 their clarity.

14 DR. MURPHY: Certainly, this

15 schedule is just extremely tight, and it has

16 made things hard.

17 CHAIR BRAIN: And I think, given

18 that, let me conclude by just thanking

19 everyone. Thanks to EPA staff for your

20 presentation, and I think there is consensus

21 that the REA is really dramatically improved

22 and very responsive to our suggestions, and we

Page 167

1 appreciate the clear responses.

2 I think, you know, again we had

3 this discussion of no comment on our input and

4 too much comment and track changes, and I

5 think we have really reached some happy medium

6 where the level of detail of what has changed

7 is helpful and just right, sort of the

8 Goldilocks phenomenon, not too much, not too

9 little. Again, I think there is a lot of

10 enthusiasm for the Policy document.

11 DR. MURPHY: If I could just take

12 a minute. We certainly appreciate the time

13 and the enthusiasm that the Panel brings to

14 this project. It is difficult. It is tight

15 timelines, and we are asking you to review

16 documents in a very quick turnaround, and we

17 certainly appreciate your time on this. Thank

18 you.

19 CHAIR BRAIN: Yes, and I realize

20 this has -- you didn't have as much time

21 either to plan your travel or your comments,

22 but I think, in spite of those constraints,

Page 168

1 this was remarkably successful.

2 I look forward to hearing from you

3 all or from most of you by the end of the

4 week, and to joining the conference. You will

5 have another opportunity to look at the draft. 

6 So thanks so much.

7 MS. BARRY: Okay, and thank you,

8 everyone for all of your hard work. Thank you

9 for, really, a very productive meeting. This

10 concludes the meeting of the CASAC Carbon

11 Monoxide Panel. Thank you.

12 (Whereupon, the foregoing matter

13 went off the record at 11:51 a.m.)

14

15

16

17

18

19

20

21

22
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A

abbreviations

124:22

ABC 1:11

ability 70:20

able 9:6 152:1

absence 4:13 99:13

absolute 113:9,17

113:19 115:16

absolutely 18:17

45:14 54:21 72:21

77:15 84:4

abstained 158:2

abstention 157:21

accept 67:2

acceptable 151:20

account 92:13

112:18,20 123:2

139:22

accrue 15:17

accruing 10:3

accurate 50:19

achieve 113:2

114:17 137:12

achieved 111:3

acknowledge

129:19

acknowledges

51:20

acknowledging

113:17

acknowledgment

142:8,9

acquire 46:5

act 24:4 92:5 99:11

actions 154:16,19

activities 77:3,8

activity 77:2

103:13

actual 27:21 30:19

72:19 83:3 116:2

128:16 150:19

151:10

acute 11:15 89:14

add 17:2 25:16

33:4 39:5 50:14

90:1 96:17,20

97:10 122:2,6

157:10,11 158:1

added 66:20

101:14 150:2

addendum 64:5

105:17

adding 147:7

addition 19:17

52:13 64:19

160:17

additional 7:3

13:17 60:1 65:17

68:16,18,22 108:7

108:17 129:6

158:12 160:16

additionally 32:7

additions 160:14

address 26:13 99:3

108:9 113:16

addressed 88:16,20

adequacy 5:5,14

adequate 21:22

63:13 134:6

154:10

adequately 16:11

16:18 157:15

adjacent 96:21

adjusting 72:7

Administrator

13:5 27:11 85:21

86:22

advantage 96:3

97:2

advantageous

102:18 104:6

advantages 103:21

129:14

advice 24:15 25:6

66:2 138:17

144:21 149:12

advise 17:16

advising 145:6

ADVISORY 1:3

2:10

affect 100:9 154:2

154:3

African 19:2

afternoon 116:15

agencies 33:8

agency 1:1 88:1

114:6 140:19

AGENDA 3:5

agent 7:19 44:5

aggressive 60:19

ago 26:12 97:20

99:15 104:12,16

agree 10:12 40:16

42:22 127:20

agreed 50:3

agreeing 51:17

agreement 16:22

142:5

ahead 86:15 106:17

106:17

air 1:3 5:20 21:7

24:4 29:12,14

30:5 31:16 46:16

52:17 72:4,15

74:7 80:9 82:4,9

82:16,21 83:5,7

97:14 98:17 99:11

99:17 100:3 109:5

111:4,5,6 115:8

136:10,14 137:4

140:15 152:21

153:15 154:8

alert 21:12

algorithm 72:19

algorithms 76:11

allow 50:16 51:12

121:14

allows 137:7 156:3

156:4

Allred 109:3

114:14 148:8

allude 97:1

altered 141:12

142:14

alternative 5:6

83:1,10

Alternatively 11:20

alternatives 16:5

16:10 82:12 113:4

altogether 149:6

ambient 5:22 21:7

29:12,14 30:5

31:16 37:15 68:6

69:1,7 72:4 79:7,9

98:2 99:17,20

108:18 109:7,11

111:4,6 115:5,9

115:14 134:13

138:11 150:7

152:5 154:8

ambiguous 9:21

American 19:2

analogous 109:8

analyses 8:3 129:6

analysis 5:5 8:19

14:8 34:20 37:4

72:3 101:8 108:17

109:1 113:20

114:3 126:9

128:11,14 129:9

129:15 139:18

157:12

and/or 63:18

anecdotes 21:14

Angeles 81:2

animal 45:18,19

Ann 14:21,22

annual 136:4 154:1

answer 29:8 36:13

46:6 57:14 58:11

97:7,19 105:10

145:19 148:21

165:9

answers 71:2

160:18,22

ANTHONY 2:14

anticipated 75:9

anybody 36:7 44:1

49:8 85:17 92:6

124:10 131:20

anyplace 79:17

anyway 122:16

apart 138:3

APEX 103:8

apparent 7:21

apparently 18:1

108:19 139:6

appear 75:3

appears 6:9 44:8

126:15 146:17

Appendix 66:12

76:4,5 79:14 99:8

applied 15:13 27:4

apply 91:13 107:13

appreciate 113:20

138:21 145:5

167:1,12,17

approach 10:16

36:16 62:15 83:6

104:4 112:16

131:2

approaches 8:4

10:20 43:18

appropriate 36:15

50:14 52:3 66:7

83:2 110:9 154:9

158:17 166:3

appropriately

159:12

approximately

119:13 120:8

April 60:7,9,18

163:12

AQCD 100:16

area 22:17 24:18

31:22 39:17 40:9

92:3,14,14 144:9

153:7,9 154:16

155:3

areas 14:1 18:4,6,8

22:20 23:11 29:12

30:8 31:4 33:17

56:19 59:4,9

130:8 137:5,8

138:9 142:18

152:17

argue 104:5 112:10

argued 104:4

arguing 92:7 112:8

113:15

argument 23:16

26:14 37:10 38:15

44:17,19 45:16,17

53:1
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arguments 44:21

arterial 40:4

104:22

artery 10:7 11:6

48:14 70:2 85:11

96:6,19

Arthur 1:21 123:20

asking 29:6 73:2

74:6,13 78:17

83:17 87:21 102:1

118:1,5 126:7,12

126:13 131:1

167:15

asks 75:15

assembled 4:7

assessing 69:12

assessment 4:19

38:14 40:8 54:14

54:17 62:17,21

63:5 69:14 109:9

109:13 111:19

113:22 114:5

115:11 123:8

127:3,18,19 128:5

128:16 129:18

131:11,17 133:17

134:3 135:15

139:5,9 160:17

163:16

assessments 9:16

assessment/risk

114:2

assigned 49:9

associated 5:21

55:5

association 39:14

39:21 40:2,3,12

52:10 150:7

associations 92:16

133:22

assumption 28:7

assure 21:4

asymmetric 79:1

asymmetry 79:12

Atlanta 6:18 7:13

atmospheric 54:15

attainment 137:8

attempts 130:2

attention 109:11

114:22 160:5

161:11

attributable 40:12

109:7,11

author 59:14 61:12

123:16

authority 61:5

166:10

authors 58:21 59:3

59:22 65:21 70:5

87:7 123:1 129:2

available 27:13

79:18 87:7

avenue 108:22

average 5:9,10 29:2

136:5,5,6 152:9

153:14,21 154:1

averaging 11:2

154:2,6

avoids 23:3

a.m 1:12 4:2 86:13

86:14 168:13

B

B 94:18 125:14

back 6:12 12:10

18:21 29:18 36:10

53:22 60:13 65:19

69:22 86:14 98:1

106:3 116:10,14

126:17 131:2,21

147:4 151:3

154:20 155:20

163:4

backdrop 100:20

background 89:8

back-calculating

12:11

bad 98:7 156:12

balance 132:16

139:1

BARRY 2:12 58:14

60:8 86:15 163:13

164:12 168:7

base 65:21 91:8

based 11:5 12:6,15

14:9 20:8 24:7

27:21 38:18 44:15

47:18 49:17,17

76:21 77:4 120:11

126:9,10 147:11

150:19 151:16

157:9,12 162:12

baseline 98:6,6

basic 38:9 45:5

124:2

basically 18:18

43:8 51:11 66:21

67:7 118:14

149:21 150:3,13

150:19

basis 48:3 92:8

96:8

Beach 32:14

Beate 1:22 19:13

88:22 121:2

129:13

Beate's 65:13

beauty 8:13

becoming 93:15

beginning 76:4

134:19

Behavioral 121:18

believe 6:22 20:2

21:20 48:11 60:20

80:18 90:11 95:12

104:18 120:5

133:6 134:20

150:15 152:22

belong 89:6 124:8

145:11

belongs 124:3,3

benchmark 72:13

benchmarks 12:7

48:11

benefit 96:14

best 29:1 66:21

67:6 87:14 121:4

123:4 154:9

beta 41:21

better 7:21 38:21

64:12 69:6 104:7

126:3,8

beyond 30:17

51:22 109:17

110:3 134:3

154:11

bias 139:16

big 26:19 41:5,6

86:7,8 117:18

148:8

biochemical 45:3

biological 89:8

90:7 92:4

biologically 111:14

111:16

biomarker 94:9

140:11

biomarkers 94:6

140:15

biostatistical 39:13

bird 19:12

bit 14:12 24:2

29:18 38:3 46:21

58:19 107:18

131:10 138:14

150:13 154:11

Blanc 1:18 18:20

36:14 39:10 41:12

52:4,19 53:21

54:8,12 55:7,22

56:10 64:9,17

66:3 69:16,19,22

78:4 79:14 80:11

81:8 83:18 90:6

91:1 92:2,21

93:11,19 95:20

97:1,12 102:7

103:7 104:5,10

105:12,19 106:12

106:19 107:3,13

107:17 109:16

110:4,11,21

111:21 112:6

113:12 115:17

116:3,12,20

117:10 118:4,12

119:3,13 120:5,13

121:12 122:4,14

129:11 131:9

132:9 145:14

146:14 151:2

158:22 159:6

162:20 164:20

blood 104:13,22

BOARD 2:10

boat 130:4

body 66:9 76:8

107:20 134:16

bottom 7:11 72:1

80:8 94:19,22

125:20

bottomed 35:20

bound 122:8,8

145:1

brain 1:12,15 3:22

4:3,17 15:22

16:21 17:4,9

18:14 19:11 20:12

22:6 25:7,14

26:16 28:21 29:7

31:1 33:2 36:4

39:3,11 40:16

41:5,7 42:1 44:1

46:10 47:5,8 48:4

48:15,20 49:1,8

51:20 52:2,15

53:18 54:20 55:14

56:15 57:1,6,15

57:20 58:18 61:1

61:17 62:9 64:6

64:14,20 65:7,18

69:21 70:11,21

71:16,21 72:17,22

73:8,16 74:12,16

75:2,21 76:12

77:12 78:9,22

79:11 80:5 83:16

84:6,14,18 85:9

86:18 87:20,22

88:10 91:11 92:17

93:1,7,14 94:11

95:13 96:17 97:5

97:16 98:8,20

99:10,22 101:3,15

103:5 104:1,8
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105:2,18 106:3,6

106:10,21 107:12

107:15 108:3,10

110:12,19 112:2

112:12,21 113:14

114:6 116:18,21

117:12,16 118:6

120:17 121:10

122:2,6,17 124:10

124:17 125:4,8

128:2,8,18 132:7

132:15,20,22

133:3 139:20

141:1,18,20 142:5

142:16 143:6,16

143:20 144:5,8,13

145:17 146:1,4,13

146:20 147:3,16

147:21 148:7,13

149:7 155:19,22

156:9,18,22 157:7

157:19,22 158:6

158:19 159:4,14

160:2,11,15 161:4

161:12 162:7,16

163:5 164:7,13

165:22 166:17

167:19

break 58:6,7 64:22

84:10,12

breaks 120:3

brief 70:6 150:8

bring 8:18 26:13

100:16 136:13

149:1 160:5

164:19

bringing 4:21

brings 10:11 147:4

166:1 167:13

broad 11:4 145:18

148:15

broaden 64:19

broadening 85:11

117:6

broader 128:3

broadly 96:5,15

broke 129:3

broken 6:9,16

brought 9:3 10:21

18:20,22 27:1

101:1 139:13

bulk 136:22

bullet 146:8

bullets 145:15

bunch 35:16

C

C 4:1 66:12 76:4

79:15 94:18

CAD 47:12,21

63:17 64:11,18

calculated 72:20

calculations 79:13

California 32:13

call 55:21 137:3

154:22 163:11

called 61:22

calls 8:22

canyon 28:10,12

canyons 23:1,1

capture 96:7 97:15

captured 48:10

carbon 1:4 15:2

22:21 38:6 43:2,7

43:10,12,14,20

44:7,9,10,14 45:8

45:13,21 78:13

94:7 97:9 140:2

141:18 168:10

carboxyhemoglo...

12:7,8 103:10

105:3

cardiac 37:21

121:7

cardiovascular

5:19 6:4,15 37:14

42:10 43:5 64:16

70:1 85:12 90:20

90:22 91:3 93:10

93:13 96:4,5,19

99:5 118:22

120:15 121:6

122:9 128:4 143:9

careful 42:15

carefully 84:8

126:19

CASAC 1:14 60:6

60:8 61:3 75:6

159:6,21,21 164:8

166:3,7 168:10

CASAC's 163:16

case 8:7 18:4 28:5

29:21 82:12 96:13

153:12

casually 20:16

categories 6:16

120:22

category 21:21

121:6

causal 6:1 7:19

54:11,14 90:20

causality 45:4

54:11

causative 52:10,16

causes 7:18

causing 115:9

134:3

cautious 62:15

caveat 38:19

CDC 119:20

cell 19:4

certain 31:12 42:1

44:2 67:14

certainly 17:12

26:17 46:13,18

56:19 92:3 105:16

115:12 126:13

133:14 141:5

148:12 161:5,5,7

161:11 165:2

166:14 167:12,17

certainty 91:22

CFK 66:16 103:5,7

104:14,19,22

105:1

CHAD 66:17 103:8

Chair 1:13,15 4:3

4:17 15:22 16:21

17:4,9 18:14

19:11 20:12 22:6

25:7,14 26:16

28:21 29:7 31:1

33:2 36:4 39:3,11

40:16 41:5,7 42:1

44:1 46:10 47:5,8

48:4,15,20 49:1,8

51:20 52:2,15

53:18 54:20 55:14

56:15 57:1,6,15

57:20 58:18 61:1

61:17 62:9 64:6

64:14,20 65:7,18

69:21 70:11,21

71:16,21 72:17,22

73:8,16 74:12,16

75:2,21 76:12

77:12 78:9,22

79:11 80:5 83:16

84:6,18 85:9

86:18 87:22 88:10

91:11 92:17 93:1

93:7,14 94:11

95:13 96:17 97:5

97:16 98:8,20

99:10 101:3,15

103:5 104:1,8

105:2,18 106:3,6

106:10,21 107:12

107:15 108:3,10

110:12,19 112:2

112:12,21 113:14

114:6 116:18,21

117:12,16 118:6

120:17 121:10

122:2,6,17 124:10

124:17 125:4,8

128:2,8,18 132:7

132:15,22 133:3

139:20 141:1

142:5,16 143:6,16

143:20 144:5,8,13

145:17 146:1,4,13

146:20 147:3,16

147:21 148:7,13

149:7 155:19,22

156:9,18,22 157:7

157:19,22 158:6

158:19 159:4,14

160:2,11,15 161:4

161:12 162:7,16

163:5 164:7,13

165:22 166:17

167:19

Chair's 164:2

chance 61:10 63:6

64:21 65:15,20

67:18 71:8 84:7

159:21

change 20:11 38:7

51:22 81:8 98:5

126:8 141:15,15

149:17 154:20

changed 22:13

63:12 150:12

167:6

changes 162:12

167:4

changing 158:5

chapter 21:13

49:14,15 51:18

61:20,22 62:1

63:11 101:1

165:12,19

chapters 63:9,12

characterization

13:19

charge 3:7,12,17

4:12,19 10:12

37:19 57:9,22

65:8 70:12 94:17

105:10 116:16

117:2 122:19

123:19 125:13

129:10 132:18

133:7 141:2

145:10,19 147:4

148:21 149:14

155:20 158:7,9

160:18,22 163:14

164:18,21 165:4

165:11,16,18

166:4,8,11

CHb 88:16

check 85:22

checked 58:7
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chemical 51:2

chemistry 52:18

choice 63:16,17

choose 97:21

choosing 11:17

12:6 42:8 137:17

chronic 88:15,19

89:11,14 90:4,10

90:12,17 96:1,9

96:11

circuitous 23:19

citations 37:6

cite 121:22

cited 6:7

cities 14:9 23:1

81:22

citing 121:3

city 6:18 25:10

claim 23:20

clarification 20:19

71:12 76:20 78:5

88:7,17 93:4

100:2,20 133:12

clarifications 86:20

clarified 73:21 91:4

91:11 94:20

clarify 24:1 68:1

73:9,12 74:13

82:2 98:21 104:2

119:19

clarifying 73:13

78:6 83:13 144:6

clarity 57:2 59:10

73:3 75:11,12

78:2 80:19 87:12

161:15 166:13

class 18:9

classified 94:1

Clean 1:3 24:4

99:11

clear 13:13 17:5

27:16 45:7,15

46:7 67:16 73:1

77:18 81:9,10,12

118:20 120:20,21

127:1 144:14

152:2 155:22

167:1

clearer 12:20 14:5

38:21

clearly 19:21 26:8

37:20 92:1 133:18

138:1 141:19,21

154:1 156:22

161:6

climate 50:6,22

51:21 52:11 54:16

clinical 37:20 38:9

45:19 133:19

134:18 135:2

close 80:21 114:22

165:8

closer 21:21 74:11

120:14

closest 74:8,9

120:16

clotting 93:17

cloud 99:19

coagulation 93:21

Coast 19:12

Coburn 12:9

code 119:4

codes 119:1

coefficients 128:19

coffee 64:22 86:1

cogent 162:5

cognizant 135:6

COHb 20:2 43:9

69:11 72:12 77:21

88:21 97:18 98:10

99:1 100:7 103:4

104:14,22 108:18

109:4,6,7,15

114:17,20 134:10

134:11,17 135:7

138:6 140:6,10

142:14

coherence 133:19

coherent 66:8

colleague 19:16

collectivize 129:4

collinearity 43:11

column 118:17

120:6,8,9

columns 137:3

153:1

combination 111:3

147:17

combined 11:17

111:3,11

come 16:9 18:21

41:4 45:12 61:5

63:8 65:19 98:8

109:19 112:22

139:7 146:2 147:8

161:9

comes 69:22 133:5

152:13 164:15

comfortable

163:20

coming 155:3

comment 16:4,9

20:17 21:11 36:8

57:8 65:2 71:6

84:22 89:4 113:15

114:7 125:5

126:17 132:21

133:2 138:21

140:1 141:3 146:3

159:5,22 163:15

164:9,11 165:3

167:3,4

commented 5:16

37:9

comments 4:6

14:20 15:20 19:11

19:13 36:15,18,22

37:17 47:9 49:6,7

49:11 55:20 57:4

60:16 61:8 62:2

63:22 64:3 65:13

65:14 66:6,9,10

66:11 67:10 68:11

70:18 73:13,15

74:3 75:1 87:19

101:6 105:7 107:8

107:8 108:1,2,4

115:18 116:2,4,5

116:6 117:3 122:1

124:8,19 125:10

125:18 130:1

133:7 144:18

145:3,8 146:6

147:9 148:5,20

160:21 161:2,3,13

162:9,12 163:17

167:21

committee 1:3

57:18 59:11 60:6

114:2

committee's 127:11

common 40:21

143:8

commonly 24:3

communication

27:15

communities 19:3

compare 104:14

compared 105:1

137:5 154:12

comparing 136:6

compelling 42:3

compiled 49:7

complete 125:9

completely 40:9

compliance 14:2

15:18 39:17 40:10

41:16 154:18

158:16

complimenting

162:3

component 18:15

20:1 45:7 46:2

151:1

comprehensive

81:3 162:6

compromise 68:4

computationally

108:20

computer 4:22

concentrated 19:2

concentration 8:12

11:5 12:14 31:22

43:9,10

concentrations

17:13 22:22 26:7

30:8 33:14 45:22

54:16 69:9,13

72:7,14,15 82:11

82:21 83:4 99:21

134:13 136:2

138:12

concentration-re...

8:5

concept 14:14

conceptually 62:5

103:15

concern 56:5 62:6

63:3 70:15 78:10

79:1 81:18 95:22

147:18 148:1,17

concerned 25:4

142:17

concerns 19:8

62:17 63:15 71:10

87:9 94:16 139:2

139:3 144:20

149:12 164:1

concise 16:22

conclude 6:1 10:2

90:20 166:18

concluded 6:12

7:11 90:11

concludes 49:19

168:10

conclusion 37:12

conclusions 5:19

114:19

conclusive 94:3

concretely 19:9

condition 82:14

conditions 5:21

82:5,19 83:3,11

122:11 143:9

conference 168:4

confess 25:7 149:7

150:22

confidence 41:19

130:10

confident 59:11

confused 20:20

52:5 73:10 91:14

152:1

confusing 92:15

confusion 67:16
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congestive 6:14 7:5

7:6,16,17

connection 51:21

connections 137:15

cons 13:3 14:1,6

consensus 39:4

59:12,16 64:15

70:4 85:1 95:1

101:5,6,17 113:2

144:22 146:4

157:14 161:17,20

166:20

consequences 13:6

consider 11:7,15

20:5 24:13 25:3

27:10,11 82:16

161:7

consideration

10:14 11:3 26:15

49:21 109:8,12

149:22 154:11,22

considerations

13:18 131:4

147:12 158:13

considered 15:6

21:18 89:12

109:10 113:5

155:4 157:18

considering 27:7

considers 154:14

consistent 42:17,18

52:6 64:7 117:19

133:16 143:13

conspicuous 99:13

constrained 164:17

166:5

constraints 167:22

constructing 20:7

consumption 77:10

contained 76:10

contains 6:13

content 76:10

CONTENTS 3:3

context 127:2,22

continue 4:11,14

39:6 87:1

continuing 17:10

35:17 63:15 117:1

continuum 131:8

contradictory

144:10

contrary 128:3

contrasting 145:2

contributing 53:13

contribution 50:21

69:1,7 108:17

115:5

contributions

112:20

contributor 51:6

contributors 66:4

control 21:9 154:16

154:19

controlled 9:1,6,10

37:20 41:2 131:18

143:13

controlling 12:1

77:2

controls 137:9

controversial 66:1

controversy 59:9

65:6

convenient 140:11

conversation 64:8

166:12

convey 138:16,18

conviction 91:20

convince 127:16

convincing 66:17

93:15 102:2 130:4

copy 4:9

coronary 10:6 11:6

37:22 48:14 70:2

85:11 96:6,19

120:4,8 121:16

correct 44:21 79:5

92:22 103:1

correction 149:18

corrections 107:6

correctly 51:15

62:8

correlation 43:2,13

Counsel 24:1

count 21:3

country 14:11

33:22

couple 26:11 33:4,7

33:21 35:11 49:11

58:2 104:15

121:13 124:6

125:6 133:10

149:16 160:13,19

164:22

coupling 66:16

course 21:22 29:13

33:1 42:12 43:4

43:12 47:16 93:11

cover 125:2

covering 17:7

co-pollutant 94:12

CO2 107:11

create 82:16,21

83:7

created 114:8

creating 99:18

criteria 24:11

40:22 100:4,5

140:4 143:17

critical 42:9

critique 36:16

crux 111:18

current 5:6,8 9:19

10:3,10 11:8,10

11:13,16 15:19

16:17 17:18,20

25:8,18 26:5

27:20 34:16 37:7

37:12 38:15 54:15

62:18 80:22 81:5

82:5,10,13,19

83:8,11 100:18

121:4 134:6 136:8

137:21 149:8

150:9 157:14

currently 16:20

92:15 104:18

115:15 118:17

136:3

curve 8:12,12

cut 59:2 61:9,10

71:1

CVA 93:21

cycle 33:9

D

D 4:1

Dahms 1:18 27:19

41:2,6,8 53:11

54:4 66:15 74:20

76:19 77:3 78:4

78:10,16 79:5,9

79:17 80:12,14

93:16 95:17 97:19

98:12,18 99:7

102:11 117:21

118:21 119:9

120:10,19 125:16

126:4 130:22

140:22 142:7,22

143:10,18 144:3,7

144:11 145:21

146:2,7 147:5,6

147:19 148:1

daily 78:1,17

damage 56:3,14

data 7:13 8:7 9:18

10:13 12:19 16:17

21:6 24:19,22

25:1 37:11,20

38:4,6,9,10 62:16

72:5 76:8,14 81:4

81:6,19 82:17

90:7 92:7 93:19

93:20,21 94:9

119:21 120:12,20

121:17 127:7

128:22 129:7,15

129:20 130:3,7

131:19 139:10,18

143:14,14 150:1

150:11,20

database 8:20

dataset 83:7,9

155:8,13,14

date 27:17 29:18

David 23:21

day 60:21 126:6

156:6

days 39:15,19,22

40:4,15 156:5

de 31:4

deal 14:14 86:7

147:13

dealing 35:22 36:2

deals 105:3 148:12

dealt 57:2,8 75:4,5

129:12

decades 104:19

decide 31:8 32:13

32:18 154:18

decided 145:10

deciding 26:3

decision 13:7 27:7

164:2

decisions 127:21

decompensation

37:22

decompensations

37:14

decreases 95:9

deeply 95:3

defended 128:1

defer 145:12

define 8:11 24:10

117:22

defined 96:6,15

121:15

definite 24:5

definitely 5:3 22:4

28:19 129:13

definition 118:14

128:4

definitions 107:6

124:15 125:1

definitive 52:22

degradation 53:20

degraded 23:17

delay 5:1

delete 83:19 143:19

152:11 156:19

158:18

deleted 150:22

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delivery 95:9 143:7

demonstrating

45:4

Denver 80:20

81:16,20

depending 100:8

151:9

depends 152:8

159:19

deployed 28:22

Deputy 2:14

derive 72:10

derived 11:6 111:5

deriving 72:6

describe 19:7 76:6

132:11

described 54:22

56:16

describing 100:6

132:13 152:21

descriptive 137:1

design 137:3

154:13

Designated 2:12

detail 41:13 50:2

122:1 167:6

detailed 107:19

details 51:7 74:22

develop 8:5 108:20

108:22

developed 27:17

92:7

developing 12:18

developmental

90:14

devise 72:18

dialogue 109:18

110:5

diaries 103:13,14

Dickerson 49:10

55:15 65:1

differences 80:9

83:14

different 11:8

30:20 42:6 57:14

78:18 84:1 97:9

114:12,16,17

121:19 128:18

130:1 137:10

142:21 144:17

153:19 154:16

159:10

difficult 7:19 10:18

135:6 141:4,9

162:15 165:5,13

167:14

difficulty 77:14

diminished 96:22

direct 53:13 55:2,3

97:13 116:6

direction 10:9

16:13 17:16 69:4

92:11

directly 54:18 55:6

91:7 104:13 109:8

Director 2:14

directs 32:4

disagree 59:20 86:9

164:10

disagreement 63:3

63:4

disassociation 37:1

discount 40:20

46:2,9

discounting 39:13

129:21 130:9,12

discuss 44:13 163:1

discussed 14:11

35:5 57:11 100:6

133:11

discussing 15:7

discussion 4:11,20

13:12,14 26:17

36:5 47:2 49:18

57:22 62:22 63:21

72:1,8 78:11

100:15,17 110:15

112:2 115:2 126:1

126:5 127:11

145:4 146:16,21

150:18 151:3,17

157:10 166:4

167:3

discussions 14:17

163:3

disease 5:19 6:14

7:5 10:7 11:7

19:4 38:1 42:10

48:14 70:1,2

85:11,12 90:18

93:10,13 95:4,18

96:5,6,9,12,19,20

117:9 118:2,15,16

118:18,22,22

119:5 120:3 121:7

121:16 128:4

diseases 6:15 96:1

121:8

disorders 93:18

dissent 42:21

dissenters 17:1

distinction 118:10

distinguish 118:8

distributed 4:8

84:16 87:16

distribution 72:16

136:10,11,14

distributions 76:11

divergent 113:4

divide 147:22

DLCO 95:1,5

document 4:12,19

8:22 12:4 13:15

14:12 46:19 52:12

63:7 68:1 69:2

84:20 100:5

101:17 114:10,13

116:7,10,17 123:7

123:8 125:1,21

129:19 131:16

132:6 139:6

152:11 162:4

163:18 165:8

167:10

documents 75:7

86:22 162:18

167:16

doing 82:15 84:3

101:10 103:18

128:10

dose 8:11 12:14

41:9 45:18 94:9

109:8,12 115:19

131:3,5 135:5

140:7 143:11,12

147:14

double 119:11,14

downward 35:18

35:19

Dr 3:9,13,18,22

4:16,21 16:16

17:2,8,11,21 18:3

18:13,17,18,20

19:15 20:18,21

22:12 24:20 25:13

25:15 26:10,19,22

27:6,19 29:6,8

31:7,10 32:9,22

33:4 35:22 36:14

37:2 39:10 41:2,6

41:8,12 42:4,20

44:4,17,20,22

45:10,11 47:3,6,9

48:7,18,22 49:5

49:10 52:1,4,19

52:21 53:11,21

54:4,8,10,12,13

55:1,7,9,10,12,19

55:22 56:6,8,10

56:17,20 57:3,10

57:17 58:10,16

61:14,18 62:11

64:9,17 65:4,12

66:3,14 68:14

69:16,18,19,22

70:14 71:11,12,13

71:19,22 72:21

73:2,4,11,18,21

74:1,4,14,18,20

75:14,22 76:17,19

77:1,3,5,15,16

78:4,4,7,10,15,16

78:21 79:5,6,9,10

79:14,17,19 80:6

80:11,12,12,14,15

80:17 81:8,11,14

81:17,18,21 82:1

83:12,18 84:4,13

84:14 85:3,4

87:20,20 88:3,5,6

88:12,22 89:2,3,5

89:10,11,16,17,19

89:20,22 90:5,6,8

90:9,15,19 91:1,6

91:10 92:2,21,22

93:3,8,11,16,19

94:4 95:12,14,17

95:20 97:1,12,19

97:22 98:12,16,18

99:7,14,22 101:12

101:22 102:7,11

103:2,6,7 104:5

104:10,11 105:12

105:19 106:1,5,8

106:12,15,19

107:3,4,13,17,22

108:6,13 109:16

110:1,4,6,11,14

110:21 111:15,21

112:6,15 113:12

113:18 114:8

115:15,17,17

116:1,3,9,12,20

117:10,14,21

118:4,12,21 119:3

119:9,13,18 120:5

120:10,13,19

121:2,12 122:4,14

123:21 124:14,21

125:7,16,20 126:4

126:16 128:6,10

128:20,21 129:8

129:11 130:15,22

131:9 132:9,20,20

133:1,5 138:20

140:22 141:2

142:7,22 143:10

143:18 144:3,7,11

145:1,14,16,21

146:2,7,10,14

147:2,6,19 148:1

148:2,10,22

149:14,15 151:2

151:11,12,15,22

152:5,8,10,15
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164:20 166:14

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draft 57:5 58:2,5

61:9 85:15 86:17

108:15,15 133:8

162:4,19 168:5

drafts 86:21

dramatically

166:21

draw 91:7

drawing 137:15

drawn 114:19

Drive 1:12

drives 37:11

driving 130:14

drop 151:19,21

156:13

due 34:18

duration 46:4

Durham 1:12

dust 26:18

E

E 4:1,1

earlier 33:19 104:4

104:6 130:2 145:9

150:3 153:6

early 19:12

easier 98:3

easiest 119:6

easily 54:1 108:2

EC 53:7

ecological 24:8

edge 34:1

edit 73:17 147:20

edited 63:11

editing 5:4

edits 60:1

educate 159:21

educated 25:8

effect 15:12 40:14

50:11 51:10 53:8

53:15 54:21 56:11

56:14 69:12

111:13

effective 41:9 69:8

effects 8:16 10:2

20:3 39:7 43:4,20

43:21 45:21 50:6

52:11 54:16 55:2

55:3 92:12 115:9

134:4 137:16

141:18,22 150:8

efforts 76:21

eight 5:9 9:19

19:14 28:2,3

eight-hour 5:11 7:1

10:22 11:2,21

13:11 27:4 149:20

151:20 153:21

either 34:15 68:8

71:9 76:16 80:11

86:9 102:15

108:11 140:9

167:21

either/or 113:8

element 115:20,21

162:15

elements 124:2

137:18

elevation 41:17

eliminated 109:15

eloquently 35:5

embolism 122:12

122:15

emerging 92:3,12

142:2

emissions 34:5

50:20

emitters 18:7

emphasis 37:21

emphasize 112:13

emphasized 68:5

emphysema 95:6

employed 83:1

encourage 12:17

endogenous 19:1

67:11 79:7 103:3

109:14 111:4

141:11,16 142:13

endorse 41:15

161:16

endpoint 72:13

endpoints 9:3 43:3

43:5,6,14,15

133:20

entering 28:17

enthusiasm 162:17

167:10,13

enthusiastic 91:18

entire 59:18

environment 56:2

environmental 1:1

18:15 45:22 56:11

140:12

environments

75:15 78:18

EPA 12:17 15:13

20:17 22:19 29:6

30:15 31:11 33:11

42:22 71:6 84:21

87:8 99:10 102:5

107:9 112:16

113:22 129:6

141:4 162:3

163:15,21 166:10

166:19

EPA's 23:22 24:16

epi 42:22 44:5,12

44:15 85:13 93:4

94:11 120:20

121:1,8 126:9,11

126:14,19 127:4,7

131:6,6 133:15

134:8,9 135:2,18

136:2 139:10,18

140:6 142:21

143:8,14,21

147:14 152:19,21

epidemiologic

39:12 40:2,3,11

45:2 62:19 125:22

129:15,20 130:3,7

131:12,14 132:1,2

132:5,12 142:19

150:1,11

epidemiological

5:17 6:6 7:12,22

8:20 10:1 12:19

37:11 40:19 88:18

135:9 157:12

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