UNITED ST ATES E N VI RON M E N T A L PR OTE C TION AGE NCY WASHING T O N D. C. 20460

OFFI CE OF THE A D M I N ISTR A T OR SCI E NCE A D VI SORY BO A RD June 12, 2008

EPA-CASAC-08-013

The Honorable Stephen L. Johnson Adm i nistra tor U.S. Environm ental Protection Agency 1200 Pennsylvania Avenue, N.W

. Washington, D.C. 20460

Subject: Consultation on EPA’s Draft Plan for Review of the Primary NAAQS for Carbon Monoxide (March 2008)

Dear Adm i nistrator Johnson:

The Clean Air Scientific Advisory Comm ittee (C ASAC) Car bon Monoxide (CO) Prim ary NAAQS Re view Panel m e t on April 8, 2008, and has com p leted its consultation on EPA’s Draft Plan for Review of the P r imary NAAQS for Carbon Monoxide (March 2008). The CASAC uses a consultation as a m echanism for individual technical experts to provide co mm ents on the Agency ’s draft plan for developing techni cal as sessm ents as the bas i s of the rev i ew o f the prim ary NAAQS for CO. W r i tten comm e n ts provided by the indivi dual Panelists are enclosed. Areas of concern

em phasized by panelists included (bu t were not li m ited to): 1) the need f o r

a m u lti-pollutant approach in considering CO sta ndards; 2) the need to consider both a secondary and a prim ary standard; 3) the inadequa cy of current m onitoring data; and 4) the requ irem ents re la ted to the new NAAQS review process.

As this is a consultation, we do not expect a formal response from the Age n cy. W e thank the Agency for the opportunity to provide advice early in the NAAQS re view process, and look forward to the review of the draft Inte grated Science Assessm e nt in April 2009.

Sincerely,

/Signed/

Dr. Rogene Henderson, Chair Clean Air S c ientif ic Advisory Comm ittee

Enclosures

### U.S. Environmental Protection Agency Clean Air Scientific Advisory Committee CO Primary NAAQS Re view Panel Roster

CASAC MEMBERS

Dr. Rogene Henderson ( Chair ) , Scientist Emeritus, Lovelace Respiratory Research Institute, Albuquerque, NM

Dr. Ellis B. Cowling , University Distinguished Professo r At-Large Emeritus, Colleges of Natural Resources and Agricultur e and Life Sciences, North Caro lina State University, Raleigh, NC

Dr. James D. Crapo , Professor, Department of Medi cine, National Jewish Medical and Research Center, Denver, CO

Dr. Douglas Crawford-Brown , Professor Emeritus and Director Emeritus, Department of Environmental Sciences and Engineering and UNC Institute for the Environment, University of North Carolina at Chapel Hill, Chapel Hill, NC

Dr. Donna Kenski, Data Analysis Director, Lake Mi chigan Air Directors Consortium, Rosemont, IL

Dr. Armistead (Ted) Russell , Professor, Department of Civ il and Environmental Engineering, Georgia Institute of Technology, Atlanta, GA

Dr. Jonathan Samet , Professor and Chairman, Department of Epidemiology, Bloomberg School of Public Health, J ohns Hopkins University, Baltimore, MD

PANEL MEMBERS

Dr. Thomas Dahms , Professor and Director, Anesthesiology Research, Department of Anesthesiology and Critical Care, Saint Louis Un iversity School of Medicine, St. Louis, MO

Dr. Russell R. Dickerson, Professor and Chair, Department of Atmospheric and Oceanic Science, University of Maryland, College Park, MD

Laurence Fechter, Ph. D., Research Scientist and Professor, Loma Linda VA Medical Center and Loma Linda University Schoo l of Medicine, Loma Linda, CA

Dr. Milan Hazucha, Professor, University of North Caro lina at Chapel Hill, Chapel Hill, NC

Dr. Michael T. Kleinman , Professor, University of Ca lifornia – Irvine, Irvine, CA

Dr. Arthur Penn, Professor, Louisiana State University, Baton Rouge, LA

Dr. Beate Ritz, Professor, University of Californi a – Los Angeles, Los Angeles, CADr. Paul T. Roberts , Executive Vice President and Ch ief Scientific Officer, Sonoma Technologies, Inc., Petaluma, CA

Dr. Stephen R. Thom , Professor and Chief of Service, In stitute for Enviro nmental Medicine, University of Pennsylvania, Philadelphia, PA

SCIENCE ADVISORY BOARD STAFF

Ms. Kyndall Barry , Designated Federal Officer, 1200 Pennsylvania Avenue, NW 1400F, Washington, DC, Phone: 202-343-9868, Fax: 202-233-0643, (barry.kyndall@epa.gov)Compilation of Individ u al Pa nel Member C o mments o n EPA’s Dr aft Plan for Review of th e Primary NAAQS for Carbon Monoxide (March 2008)

Comments receiv e d:

Dr. Ellis B. Cow ling

........................................................................................................... ........... 5 Dr. James Crapo

................................................................................................................ ......... 12 Dr. Douglas Craw ford-Brow n ................................................................................................... 13 Dr. Thomas Dahms

............................................................................................................... ...... 16 Dr. Russell R. Dickerson

....................................................................................................... ..... 19 Dr. Milan Hazucha..............................................................................................................

........ 21 Dr. Rogene Henderson...........................................................................................................

..... 24 Dr. Donna Kenski...............................................................................................................

......... 25 Dr. Michael T. Kleinman........................................................................................................

.... 26 Dr. Arthur Penn

................................................................................................................ .......... 28 Dr. Beate Ritz

................................................................................................................. ............. 30 Dr. Paul T. Roberts

............................................................................................................ ......... 31 Dr. Armistead Russell

.......................................................................................................... ....... 33 Dr. Jonathan M. Samet

.......................................................................................................... .... 35 Dr. Stephen R. Thom

............................................................................................................ ...... 36

4

### Dr. Ellis B. Co w ling

Individual Comments on the March 2008 Draft Plan for Review of the Primary National Ambient Air Qua lity Standard for Carbon Monoxide

Very General Comments on these NAAQS Re view Processes

Before dealing with the details of my sp ecific assignm ent during the April 8, 2008 C A SAC Consultation on the Prim ary (public-welfare based) NAAQS for Carbon Monoxide (CO), I would like to offer a fe w general comments a bout these periodic NAQQS Review processes and the changes that are bein g m a de in both the organization and focus of these reviews.

As described on pages 1-2 of the “Draft Plan” for review of the prim ary NAAQS for CO, the Clean Air Act of 1970 established two general goals for m a nagem e nt of air quality in the United States -- protection of hum an health and protec tion of public welfare. Section 108 of the CAA directs the Adm i nistrator of EPA to i d entify and list “air pollutants” that “in his judgm ent m a y reasonably be anticipated to endanger public health and welfare” and to iss u e air qu ality criteria f

o r those tha t are lis ted – hence th e te rm “Criteria Pollutan t s.”

Section 109 of the CAA further directs the Adm i nistrator of EPA to propose and promulgate “Prim a ry” National Am bient Air Quality S t anda rds to protect public health and “Seco ndary” National A m bient Air Quality Stan da rds to p r otect public w e lfare.

A secondary standard, as defined in S ection 109, must “specif y a leve l of air quality the
atta inm e nt and m a intena nce of which, in the ju dgm e nt of the Adm i nist rator, based on such criteria, is required to protect the public welfare from any know n or anticipated adverse effects associated w ith the presence of [the] pollutant in the am bient air ...” The welfare effects of concern include, but are not lim ited to “effect s on soils, water, crops, vegetation, m a n-m a de

m a terials, an im als, wildlif e , w eather, visibility an d clim ate, dam a ge to and deterioration of property, an d hazards to transpo r tatio n, as well as effects on econom ic values and on p e rsonal comfort and well-being.”

So far, the several Adm i nistrators of EPA since 1970 have: 1) Identified six specific “Criteria Pollu tants” – carbon m onoxide, ozone and other photochem i cal oxidants, sulfur dioxide, oxides of nitrogen, particulate m a tter, and lead – which have thus been designated officially as requiring developm ent and implem e ntation of

National Am bient Air Quality Sta ndards;

2) Em phasized protection of public health as the principal (and overwhelm ingly im portant) de facto focus of concern within the Agency, and public welf are as a (rarely openly acknowledged) but distinctly less important de facto focus of concern; 3) Established Secondary (public-welfare-bas ed) N AAQS standards for all six criteria pollutants that alm o st always were identical in f o rm (including level, indicator, statistical

5for m , and averaging tim e) to the Prim ary (public- health based) NAAQS standards for each of thes e six criteria pollutants ; 4) Developed a long-standing trad ition of deali ng with th ese s i x specific air pollutants

m a inly on a “one-at-a-tim e” basis rather than collectively – i.e., w ithout strong attention to the frequent interactions and sim u ltaneous occurrence of som e of these pollutants as

m i xtures within the air in various parts of our country; 5) Maintained a relu ctan t a ttitude abou t the c oncepts of ecologically based “Critical Loads and Critical Levels” developed in Europe as possible alternat ive or additional approaches to air-quality m a nagem e nt in the US; and 6) Maintained a long-standing general focus on the related concepts of: a) “attainm e nt counties a nd non-attainm e nt counties,” b) “attainm e nt dem onstrations” based on m a th em atical m o deling of a lim ited num b er of exceedance events under extrem e weather conditions, and c) “local anthropogenic sources” as opposed to “both local and regional biogenic and anthropogenic sources of em issions.”

In recent years, in contrast to several of th e six ideas listed above, EPA has shown increased willingn ess to think m o re holistically – and in m o re fully integ r ated ways – about both the policy-relevant science and the pr actical arts of air quality m a nagem e nt aim e d at protection of both public welfare and public health. These shifts in both emphasis and approach have included: 1) Participation with other federal agencies and international bodies in discussions about the “One Atm o sphere,” “Cr i tica l Loads– Critical Lev e ls,” and “M ultip le-Po llu tant–Mu l tiple Effects” concepts ;
2) Adoption of the “NOx SIP Call” in 1999 and both the “Clean Air Interstate Rule” (CAIR) and the “Clean Air Mercury Rule” (CAM R) in 2005 with their m o re balanced perspectives about both regi onal (interstate) and local sources of e m issions and interactions am ong NOx, SOx, VOCs, “air toxics,” and m e rcury in the form ation,

accum u latio n, and biolo g ical effects of “oz one and other pho tochem ical oxidants, ” an d fine, coarse, thoracic, and s econdary aerosol particles;

3) Recognition of both f i ne and coars e PM as com p lex and geog raphic a lly v a riab le m i xtures of sulfate-, nitrate-, a nd ammonium -dom inated aero sols; natural biogenic and anthropogenic organic substances; heavy m e ta ls including cadm i um , copper, zinc, lead, and m e rcury; and som e other m i scellaneous substances;

4) More frequent discussion about of the occurrence and both ecol ogically-important and public-health im pacts of m i xtures of air po llutants; and, m o st recen tly

5) Making the unprecedented deci sions (at least in the cas e of the NAAQS reviews for oxides of nitrogen and sulfur) to:

A) Separate the preparati on and review of documentation, the required CASAC and public reviews, and the final decision-m aking processes for the Secondary (public6welf are-bas e d) Nationa l Am bient Air Quality Sta ndards f r om the (pr e viou sly always do m i nating) Prim ary (public-health-b ased) NAAQS review processes, and

B) Prepare and publish a single dr aft plan for integrated [sim ultaneous] of two different criteria pollutants (NOx and SOx), and 6) Identify in advance a set of Key Policy-Rele vant Questions that will be the prim ary focus of attention in the design and com p letion of all four m a jor components of the new NAAQS review processes: A) An Integrated Review Plan (IRP), B) An Integrated Science Assessm ent (ISA), B) A Risk/Exposure Assessm ent (REA), and C) A Policy Assessm ent/Rulem aking docum ent de veloped in the form of an Advanced Notice of Proposed Rule Making (A NPR).

All six of th ese adjus t ments in f o cus of atte ntion, docum entation requirem ents, and sequential procedures are being undertake n with the in tentio n to:”

“... im prove the efficien cy of the pro cess wh ile e n suring th at the Ag ency’s decisions are inform ed by the best available science a nd tim ely advice from CASA and the public” ... and “... help the agency m eet the goal of re viewing each NAAQS on a 5-year cycles as required by the Clean Air Act without com p ro m i sing the scientific integrity of the process.”

Need for Policy Relevancy as the Domina nt Concern in NAAQS Re view Processes

In a May 12 2006 summary letter to Adm i nist rator Johnson, CASAC Ch air, Dr. Rogene Henderson, provided the following statem ent of purpose for these periodic NAAQS review
processes. “CASAC understands the goal of the NAAQS re view proces s is to an swer a critical scien tif ic qu estion : “What evidence has been developed sinc e the la st re view to ind i c a te if the current primary and/or secondary NAAQ S need to be revised or if an alternative level or form of these standards is need ed to protect public health and/or public welfare?”

During the past 18 m onths, CASAC has participat ed in reviews of three of the existing six criteria pollutants – particulate m a tter, ozone, and lead. CASAC has also joined with senior EPA adm i nistrato rs in a “top-to-bottom review” and th e resulting recently-co m p leted revision of the NAAQS review process e s. These two experien ces have led to a seem ingly slight but im portant need for rephrasing and refocusing of this ve ry important “c r itical s c ien t if ic question : ”

“What scien tific evidence and/or scientific ins i g h ts have been developed since the las t review that either support or call in to ques tion the current public-health based and/or the

78 current public-welfare based NAAQ S, or if alternative levels, indicators, statistical forms, or averaging times of these standards are n eeded to protect public health with an adequate margin of safety and to protect public welfare?”

With regard to the important distinction in pur pose of the primary (public health) and secondary (public welfare) NAAQS standards, it is noteworthy that in all five cases in which a secondary NAAQS standard has been established, the seconda ry standard has been set “Same as Primary.”

Thus, a second very critical scient ific question that needs to be an swered for CO as well as the other criteria ai r pollutants is:

“What scientific evidence and/or scientific insights have been d eveloped since the last review to indicate whether, and if so, what particular ecosystem components or other airquality-related public welfare values, are more or less sensitive than the populations of humans for which primary standards are establ ished and for this reason may require a different level, indicator, statistical form, or averaging time of a secondary standard in order to protect public welfare.”

I hope these two “critical scientific questions” will be borne in mind car efully as CASAC joins with the various relevant part s of the Environmental Protection Agency in completing the upcoming reviews of both the primary and seco ndary National Ambient Air Quality Standards for CO, NOx, SOx, PM, ozone, and lead.

We now have the considerable advantage that a much more complete focus can be achieved in the Integrated Science Assessment than has hist orically been achieved in the encyclopedic Criteria Documents that have been pr epared during the years since 1970.
Thus, I recommend that every chapter of the soon to be completed Integrated Science Assessment, the Risk/Exposure Assessment, and the Policy Assessment/Rule Making documents for CO contain a summary section composed al most entirely of a series of very carefully crafted statements of Conclu sions and Scientific Findings that:

1) Contain the distilled essence of the most im portant topics covered in each chapter, and

2) Are as directly relevant as possible to the two Critically Important Scientific Questions written in bo ld italic type above

. In this connection, I call attention once again to the attached “ Guideline for Formulation of Statements of Scientific Findings to be Used for Policy Purposes. ” These guidelines were developed and published in 1991 by the Oversi ght Review Board for the National Acid Precipitation Assessment Program. They are the best guides that I know of for formulation of scientific findings to be used for policy purposes.GUIDELINES FOR F O RMULATION OF SCIENTIFI C FINDI NGS

TO BE US E D FOR P O L I CY PU RPOSES The following gui delines in the form of checklist questions were developed b y t h e NAPAP Oversight Review Board to assist scientists i n form ulating presentations of r esearch r esults to be used in polic y decision processe s. 1) IS THE S T ATEM ENT SOUND? Have the cent r al issues bee n clearly identified? Does each stat e m e n t contain the distilled essence of present scientific and technical understanding of the phenomenon or pr ocess to which it applies ? Is th e statement consistent w ith all relevant evidence – eviden ce developed either thr ough NAPAP research or through anal y s i s of resear ch conducted outsid e of NAPAP? Is the statement contradicted by any i m portant evidence developed through r esear ch inside or out side of NAPAP? Have apparent contradictions or interpretations of available evidence bee n considered in form ulating the statem ent of pri n cipal findin g s? 2) IS THE S T ATEM ENT DIRECT IONAL AND, WHERE APPROPRIATE, QUANT ITAT IVE? Does the
state m ent correctly quantify both the di r ection and magnitude of tr ends and relationships in th e phenom eno n or process to which the state m ent is relevant? When pos sible, is a range of uncertainty given for each quantitative result ? Have various sources of uncertainty been identified and qua ntified, for exa m ple, does the state m ent include or acknowledge errors in actual m e asur ements, standard errors of estimate, possible biases in the availability of data, extrapolation of result s bey o nd t h e mathematical , geographica l, or tem poral relevancy of available inform ation, etc. In short, are there nu mbers in the state m ent? Are th e num bers correct? Are the num bers relevant to the general meaning of the state m ent ? 3) IS THE D E GR EE OF CERT AIN T Y OR U NCE RTAI NTY OF THE ST ATEME N T INDI CA TE D CLEA RLY? Have appropriate statistic al tests been a pplie d to the data used in drawing the conclusion set f o rth in the statement? If the statement is b ased on a m a thematical or novel conceptual m odel, has th e m odel or concept been validated? Does the state m ent des c ribe the m odel or concept on which it is based a nd the degree of validity of that m odel or concept? 4) IS THE S T ATEM ENT CORRE C T WIT H OUT QUALIFICATION? Are there li mitations of time, spac e, or other special circu m st ance s in which the state m ent is true ? If the state m ent is true only in some circu m stanc es, are these li m itati ons described adequately a nd briefly? 5) IS THE S T ATEM ENT C LEA R A ND UN AMB I GU OUS? Are the words and phrases used in the state m ent understandab l e b y the deci sion m a kers of our societ y ? Is the statement free of specialized jargon? Will too many people m i sun d erstand its meaning? 6) IS THE S T ATEM ENT AS CONCISE AS IT C AN BE MA DE WIT HOUT RIS K OF MISUNDERSTANDING? Are there a n y excess wo rds, phrases, or id eas in the state m ent w h ich are not neces sary to comm unic a te the m e aning of the state m ent? Are t h ere so m a ny caveats in the state m ent that the state m en t itself is trivial, conf using, or am b i guous ? 7) IS THE S T ATEM ENT FREE OF SCIENTIFIC OR OT HER BI ASES OR IMPL IC ATI O NS OF SOCIE T AL VALU E JU DGME NTS? Is the statement free of influence by specific schools of scientific thoug ht? Is th e statement also free of words, phrases, or concepts that have politic al, econom i c , ideological, r e ligious, m o ral, or other personal-, agency -, o r organization

- sp ecific valu es, overtones, or im plicatio ns? Does the choice of how the statement is expressed rather than its specific words suggest underly i ng biases or value judgm ents ? Is the t one i m partial and free of special pleading? If societal valu e judgm ents have been discussed, have these judgm en ts been identified as such and described both clearly and obje c tively? 8) HAVE S O CIET AL IM PLICATIONS BEEN DESCRIBED OBJECT IVELY? Consideration of al ternative courses of act ion and their consequences inherently invol ves judgments of their feasibility and the im portan ce of effects. For this reason, it is i m portant to ask if a reas onable range of alternative polic ies or courses of action have been evaluate d? Have societal i m plicati ons of altern ative courses of action been stated in the following general form ?: " If this [ p articular option] were adopted then that [ p articular outco me] would be expected." 9) HAVE T H E PR OFE SSION AL B I ASES OF A U THORS A ND RE VIE W ERS BE E N DESC RIB E D OPE N L Y ? Acknowledgment of potential sources of bias is i m portant so that r eaders can judge for them selves the cred ibilit y of reports and assess ments.

9My Assignment in this CAS AC Consul tation on the Draft Plan for Review of the NAAQS Primary St andard for Carbon Monoxide

My specific assignm ent in preparation for th e April 8, 2008 C A SAC Cons ultation on the Draft Plan f o r review of the NAAQS f o r CO, as outlin e d in Chairm an Rogene Henderson’s m e m o of 7 March 2008, is -- Key Po licy

- Rele van t Issue s . Rogene also asked Jim Crapo to deal w ith these

sam e issues. Thus, I am very m u ch looking fo rward to com p aring notes with Jim during our Consultation on April 8 – especially since he knows so m u ch more than I do about public health effects of CO and other Criteria Pollutants.

These Key Policy-Relevant Questions are summ ar ized on pages 3-1 through 3-3 in Section 3.2 and are p r es ented as a series of th irteen m a jor policy-focused “Issues to be considered in the current review”. In addition, several other deta iled questions are presented in the several Subsections of Chapter 4. In m o st cases, however, th ese m o re detailed questions are focused m a inly on scien tific issues rather than po licy issues and, I presum e, will be dealt with adequately by other m e m b ers of our CASA C Carbon Monoxides Panel.

I see the decision to develop “Key Policy-Releva nt Policy Questions” as a part of these Draft Plans for NAAQS reviews as a m a j o r step forward. I am also very satisfied with the particular set of 13 such questions listed in Chapter 3 of this Draft Plan. Of course they all relate to the effects of CO on public health – which is the principal focus of this NAAQS review.

In addition, however, I also note that Section 1.3 – History of Reviews of the NAAQS for CO -- indicates that identical prim ary and secondary NAAQS standards for CO were prom ulgated in 1971 and that the decision was m a de in 1985 to revoke the secondary standard. The rationale for this decision was not included in this “History” section,

But Section 1.4 – Scope of the Review – also indicates that

“ ... relevant scientific infor m ation on hum a n exposures and health effects associated with exposu r es to am bient concen trations of CO will be asses s ed. The possible influence of other atm o spheric pollutants on the interpretation of the ro le of CO in health effects studies will e conside r ed . This will include ot h e r pollutants with the po tentia l to co

- o ccur in the environm ent (e.g., NO 2 , SO 2 , O 3 , and PM). The review will a l so ass e ss any relev a nt sc ie ntif ic inf o rm ation a ssociated with known or antic ipated pub lic welfare ef

f

ects that m a y be identif ied.”

Thus, becau se of m y keen scien tific interes t in th e welfare effects of crite ria pollutan t s , I believe it is essen tia l tha t both c u rrent and p a st sc ientif ic literature be exam ined closely to d e term ine if:

A) The 1985 decision to revoke the secondary NA AQS standard for CO is valid in the context of current scientific know ledge --esp ecially about the effects of CO on the health of both domestic a nd w ild animals, and perhaps also on crop, forest, and ornamental plants, insects, and microorganisms as w e ll.

10B) There are significant in teractions o f ambien t concentratio ns of CO w i th other cooccurring Criteria Pollutants in te rms of their potentia l to cause either additive, competitive, or no significant interactions w i th regard to the effects of CO on both public health and public w e lfare, and
C) There are significant times and pla ces in the U S w h ere ambient concentrations o f CO are adding to the to tal oxidativ e capacity o f the atmos phere and thus increas e the rate of accumulation of o z one near the ground in urban, suburba n, rural, and

even remo t e parts of the United States. Al though CO is not a very reactive volatile organic compound, when present in high concentrations, as often occurs in the vicinity of municipal w a ste incinerators and in the plu m es of w ild fires in grasslands and forests, CO can be a very signific ant precursor of tropospheric ozone.
I suggest this last issue f o r incl usion in the First Draft Integrated Science Assessm ent for CO as a result of the discovery by W o tawa and Tr ainer during the 1994 a nd 1995 Nashville-Middle Tennessee Ozone Study by the Southern Oxidants Study -- where a cohere nt plum e containing extraordinarily high concentrations of CO were observed for severa l days about 50 m iles east of Nashville an d could be traced to wild fires in th e Northwest T e rritories of Canada that persis ted over a six-week period.

Wotawa, G. and M. Trainer. 2000. The influenc e of Canadian forest fires on pollutant concentrations in the Unite d States. Science 288:324-328.

Other im portant sources of insight about the influence of CO em i ssions from wild fires include the f o llowin g im portant ref e rence s :
Forster, C., U. W a ndingrer, G. W o tawa, P. Ja m e s, I. Mattis, D. Althausen, P. Si mm onds, S. O’Doherty, S. G. Jennings, C. Kleefeld, J. Schne ider, T. Trickly, S. Kreipl, H. Jäger and A. Srohl. 2001. Transport of boreal forest fire em issions from Canada to E u rope. J. Geophys. Res. 106(D19)12,887-22,906.

McKeen, S. A., G. Wotawa, D. D. Pa rrish, J. S. Holloway, M., G. Hübler, F. C. Fehsenfeld, and J. F. Meagher. 2002. Ozone production from Ca nadian wildf i res duri ng June and July of 1995. J. Geophys. Res. Vol. 107, NO. D14,4192, 10.1029/2001JD000697. ACH 7-1 to ACH 7-25.
Westerling, A. L., H. G. Hidalgo, D. R. Ca yan, and T. W

. Sweetm a n. 2006. W a r m ing and Earlier Spring Increase Western U. S. Fore st W i ldfire Activity. Science 313:940-943.

Wotawa, G., P. C. Novelli, M. Trainer, and C. Granier. 2001. Inter-annual variability of summertim e CO concentrations in th e Northe rn He m i sphere explai ned by boreal forest fires in North Am erican and Russi a. Geophys. Res. Lett. 28:4575-4578.

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### Dr. James Crapo

The basic p l an laid ou t b y EPA staf f f

o r review o f the prim ary National Am bient Air Quality Standard (N AAQS) for carbon m o n oxide is appropriate. The work in im plem enting this plan should focus prim arily on new data (studies carri ed out and published since the last C O review) and both on low level effects of CO that are relevant to the NAAQS and on sensitive populations who m a y be at risk.

For this review process to be ef f

ectiv e, it is im portant that the EPA staff and adm i nistration provide a clear policy as sessm ent docum ent that gives th e ran g e of opinio n s the agen c y will consider as well as the scientific basis for those decisions. Advance notice of proposed rulem a king doc um ents needs to include the m a terial th at would have been included in staff papers for prior NAAQS reviews and needs to include an assessm ent of realistic options that could be considered for the CO NAAQS as well as the rigor ous scientific justification for those options. CASAC can be of greatest assistance to the EP A adm i nistration if open dialogue on these topics is engaged in as early as po ssible in the review process.

It will also be im portant to carry out a rigorous review of the value of an independent secondary standard for CO.

A prim ary lim itation of review of single pollutants is the absence of detailed consideration of the effects of complex pollutant interactions. The proposed review process is appropriate for consideration of the NAAQS for CO; however, the EPA should consider m oving in the future to an analys is of m u ltiple pollutants a nd their in te ractions, with the cons id eration of se tting NAAQS based not only on individu a l pollu tant le vels but also on m u ltiple pollutant in terac tions.

12

### Dr. Douglas Cra w ford-Bro wn

Review of EPA’s Draft Plan for Review of the Primary N AAQS for Carbon Monoxide

The docum e n t is intended solely to provide the gene ral structure of a review , rathe r th an deta ils as to how th is will b e ca rried ou t. As a result , th e f o llowing c o mm ents are genera l in nature and

m a y change as the actual plan is form alized.

My m o st general comment is that th e draft plan contain s all of the relevant sections that m u st be

com p leted to produce a full review. The author s have therefore not left out any m a jor considerations. However, throughout the docum ent, the authors raise a series of questions that will be add r essed in each section without provi d i ng a succin c t statem ent as to the role the answers to these questio ns will play in spec if ic p o licy con s id erations. As a result, th e reade ris left unclear as to how an y specific an swer to any specific question m i ght push the discussion of a NAAQS decision in any particular direction. Perhaps this was in tentional on the part of the authors: trying not to judge how a particular an swer m i ght infor m a final decision. But it leaves the reader u n clear as to the inte nt behind specific questions, other than providing a scientific base on which any m a nner of decision m i ght be based.

The authors raise the iss u e of co-pollutants, wh ic h will be importan t in us ing epidem iologica l studies. It is not clear, however, how these co-pollutants will be analyzed. Is the p l an to treat them as confounders and then work to extr act this confounding from any slope factors developed ? Is the inten t to exam ine the effect of CO exposures on the se nsitiv ity of individuals to the co -pollutan t s, and the effect of the co-p o llu tants on th e s e nsitivit y of individuals to CO? The docum ent doesn’ t give m u ch of a hint a s to h o w this issu e will be tre a ted. Ther e is a sense a t

severa l poin t s in th e doc um ent that c linical, co ntrolled studies m i ght form the basis for any effects m eas ures, which could avoid this issue, bu t this sense is never m a de fully concrete. There also is a hint that the assessm ent m i ght stop at exposure or at blood levels, which again would avoid this issue (m uch as in the case of the early Pb standards). It would be good if som e clarity on this issue could be provided.

On Page 3-2, the authors ask whether new data mi ght ind i cate that effects occur at exp o sures lower than those previously found to induce effects. This question is too one-sided. It presum es that the only thing new data can do is push the assum e d threshold for effects to lower values. New data m i ght suggest that prev ious data suggesting a lower thre shold were incorrect, and that the threshold is in f act higher than thought.

On Page 4-1, the authors m e ntion a form al fra m e w ork for integrating health effects, found in the second draft of the NOx docum ent. The reader shoul d not need to go to that docum ent to at least find a summary of this fram e work, and in any event that docum ent provides no such summary f r am ework and so reade r s will com e away f r om it with dif f

e re nt concep tio ns of what the fra m ework m i ght be when applied to CO. More clarity is needed on precisely what this fra m ework consists of.

13On Page 4-2, the autho r s state that welfare e ffects will be no ted if any are found during the search. However, th e lite ratur e tha t is m e ntione d as form ing the basis for the search, rooted only in hum an he alth sciences, is not the appropriate set of disciplines to locate papers on w e lfare effects. So I cannot see h o w the literature review will cons titu te a “hard lo ok” at th e relevant science on welfare effects.

Around Pages 4-7 and 4-8, the authors discuss the need to perform anal yses of spatial and
tem poral variability. There is no description, how ever, of the role of these analyses in any specific decision on exposure, expos ure-response, risk, etc. I cert ainly agree that analysis of variability is needed, but without a clear statem ent as to the pu rpose of the analyses, and the questions they are intended to support, it will not be possible to determ ine whether appropriate statistical methods and da tabases are being used.

The sam e problem arises on Page 4-8 when th e authors discuss uncerta in ty analyses. They

m e ntion, for exam ple, uncertainty in extrap olating between area m onitors and personal exposures. However, no insight is provided as to why this uncer tainty would be important for specific questions to be addresse d (I agree it IS importa nt, but the docum ent doesn’t give a hint as to why).

On Page 4-9, at the bottom, the authors list a seri es of effects that will be considered. While I agree with this list, no hint is given as to how it was com p iled based on pa st stud ies. Clarity is needed here.

On Page 4-12, developmental and birth outcom e s ar e m e ntioned as chronic effects. Why are they only considered chronic effects? Surely such e ffects m i ght occur with shorter-term exposures during critical deve lopmental periods.

On Page 4-12, the authors raise the issue as to whether CO m i ght stand as a surrogate f o r exposure to the m i xture of pollutants from vehicl es. I could not find any explanation as to why they m i ght want to know this. The CO NAAQS doesn’t stand as a surrogate for control on exposures to these other pollutants.

On that sam e page, the authors m e ntion the e xposure-response curve for CO. They for m ulate the question as one of determ ining the shape of that curve. But they don’t form ulate it as an issue of uncertainty ABOUT the shape of that curve, o r how different curves would produce different NAAQS results. That bullet needs to be rethought.

At the botto m of Page 4-14, the au th ors ask for a ny m e dical conditions or m e dications that m a ke an individual susceptible. I su spect that there m i ght also be activities (e.g. running near roadways) that m a ke them susceptib le.

On Page 4-15, the authors ask about the extent to which the elderly and fetuses are m o re susceptible. This seem s to m e to beg the ques tion, which should be about the extent to which they DIFFER in susceptibility one w a y or the other. If the authors want to restrict the question to increased su sceptibility, they need to include a ju stif ica tion f o r this (perh a ps in past literatu re suggesting increased suscep tibility in th ese groups).

14On Page 5-3, the authors first introduce the idea of using 2.1 % COHb as an effects threshold. But no justification is given for th is. I realize it is analogous to the approach in Pb exposures, and that the figure of 2.1 % is based on past decisions at th e EPA, but this needs to be explained so the reader h a s som e context for th e decis i on here.

On Page 5-4, it would be good to know why th e CO NAAQS r e view in 1999 was put on hold and never completed.

Som e m a terial is m i ssing in the inco mplete bullet at the top of Page 5-6.

The final bullet on that page c onsiders the rela tionship between the 1 and 8 hour exposures. But no explanation is given as to why this is of in terest (I agree it is, but the docum e nt should state the reason).

On Page 5-8, it is not clear whether tem poral variab ility will be used to estim a te a rolling average for exposures, or whether the tim eline will be d i s c retized and averages calculated only in the discrete intervals. These genera lly give slightly different re sults with differing degrees of variability.

On the bottom of Page 5-10, the au thors ask whether a given factor contributes to uncertainty in a way that over-or-under-states th e risk/exposure. But a given factor could be neutral on average, neither system atically under-o r-over-stating the risk/exposure.

On Page 5-11, the authors state that the ideal way to assess uncertainty due to m odel form ulation is to com p are m odel results ag ains t d a ta. No f u rt h e r clarif ic ation of this comment is given. I note first that such an approach requires assum p tions as to the v a lidity of the d a ta, esp ecia l ly in geographic areas with high degrees of spatial vari ability. And I can see how this can be used to assess the quality of one m odel, but don’t see how it is to be used to com p are the degrees of belief in competing m o dels in characteri zing uncertainty due to m odel form ulation.

In that sam e paragraph, the authors speak of pa rtitioning uncertainty into model com p onents. Is

som e for m of contribution to va riance intend ed h e re? I assum e it is, but th is is no t stated.

Section 6 is too generic to justify any further state m ents here. It w ould be of interest only if the reader were provided a succinct st atem ent of the policy questions to be addressed and how these are related to the answers to specific questions asked in the previous sections.

The Morgan and Henrion 1990 reference appears to be m i ssing from the References section even though it is called out in the text.

15

### Dr. Thomas Dahms

Two of the m a in areas of evidence of health e ffects of Carbon Monoxide seem to be 1) on the cardiov ascular system in susceptible adults b a se d both on acute controlled effects (tim e to onset of angina/ischem ia) and on population studies of in farction rates, arrhythm ias etc. and 2) on the respiratory system as shown by effects in fetu ses/infants based on popula tion studies. It is not clear whether the fetus/infant is susceptible to cardiovascular eff ects of Ca rbon Monoxide. If this effect requires underlying cardiovas cular disease, then the lack of a cardiovascular effect in infants would be understandable. This issue should be raised som e how as part of page 4-11 lines 17-20.

The respiratory health effects of CO need to be raised bas e d on recen t ev idence rather than the concern identified on page 4-11 lines 7-9.

The absence of any acute effect of CO on the re spiratory system in adult hum a ns and anim als was a conclusion of the data in the 1990 AQC docum e nt whi c h was supported by the 2000 AQC docum ent. The question then becom e s: what conditions m a ke the fetal/infant lung m o re susceptible to carbon m o noxide? (This is obvious ly the case given the relationship between
atm o spheric CO and respiratory deaths). Understa nding the potential predisposing factors in fetal death due to respiratory problem s would be essential in determ ining risk.

Since m a ny of the other regulated air pollutants have m easurable effects directly on the lungs, the distinct effects of CO alone need to be carefully assessed. This is esp e cially the ca se with populations living and working nex t to highly trav eled ro adways where CO is part of the m u ltipollutant m i xture.

In addition, one of the consistent findings re lates to the anti-inflammatory effects of both exogenous and endogenous effects of CO. Howe ver, m a ny of the identified respiratory causes of infant death appear to involve infl am m a tion. It is not clear how to ensu re that this issue is part of the item identified on page 4-11, line 25-28.

Section 3

What is not clear to m e from an organizational st andpoint is how the issues identified in Section 3 relate to the m o re specific i ssues in the following sections. First, are they supposed be overarching issues, i.e., less specific? Also, it appears as though som e of these identified issues in the Draft Plan are asking questions th at would require new research and that the requested endpoints are not clearly link e d to the identified issues. I have comm ent e d on these issues. Following past reviews, summary sessions were held where such issues were identified as needs for address i ng areas of uncertainty.

It is no t c l ea r how the wr ite rs of the I S A and those of us on the panel a r e to deal with multipollutant data. Som e direction as to its relative importance shoul d be clearly spelled out in the

16Plan as some attention to this issue m a y provide insight into future use of such data even though it m a y not be possible to use this inform ation for this review.

Page 3-1, lines 22-23: T h e words short- and long-term probably refe r to 1-hr and 8-hr exposures (prim a ry standard). However given the newer p opulation exposure data in fetuses/infants, these
term s need to be m o re narrowly defined.

Page 3-2, lines 10-12: T h is issue of altern ate dose indicators othe r than carboxyhem o globin (COHb) levels probably requires future research and therefore should be elim inated from this section. As pointed ou t by Dr. Hazucha, this is n o t an easy task b ecause the current p u lse oxim e ters would provid e erroneous d a ta as they can not accou n t for COHb or m e tHb by design. That is the easily obtained non-i nvasive data would be incorrect.

Page 3-2, lines 13-14: H o w is th is issue different from the one presented on page 3-1, lines 22- 23? If the issue is different, th e qu es tion need s to be restated.

If there is felt to be any evidence that would su pport a secondary standard, should this issue be raised directly in section 3? I assum e that this w ould include effects of exposures beyond 24 hrs and have public health conse quences as is indicated in S ection 4 under long-term exposures.

Section 4

Page 4-1, lines 29-30: “E mphasis will be placed on studies conducted at or near CO concentrations found in ambient air.” Given the uncertainty in CO dosimetry and the falling
atm o spheric levels of CO, should this statem ent provide better guidance?

Page 4-2, lin e 1: Multip le studies have been ca rried out in th e m o st sensitive popu lation for CO. This language does not provide the ISA authors’ clear direction.

Liter a tur e Search : W ill only peer re viewed m a teri a l be inc l u d ed in the d a tabas e ? Th e previous AQC documents in this f i eld have unreferenced m a terial in them . It is not clear how this

m a terial should be used by the authors of the IS A.

It is not clear how this data base will be m a de availab l e to th e authors of the ISA. W i ll a r ticles not ref e rr ed to by the au thors be in th is lite ratu re data base? This is im plied by the way it is written.

Page 4-5, line 1: This statem ent im plies that if the data is unique that the paper(s) should be included even though they do m eet the other stringen t criteria? It also im plies that confirm a tory data is of less im portance which is clearly not the case.

Page 4-6, lines 4-10: The toxico logy experim e nts and the health effects experim e nts often used exposures that result in relatively rapid increases in concentrations of COHb. Hardly any of these experim e ntal exposures would m eet the guidelines as written in the draft. Alternate guidance should be provided.

17Page 4-7, line 21: W h at do current atmospheric le vels of CO have to do with setting levels of acceptable h u m a n exposure? It shou ld not m a tter if atm o sphe ric levels have decreased, there should rem a in a level(s) that should not be ex ceeded. If atm o spheric levels are decreasing, the issue becom e s one of how to alter enforcem ent not alter criteria se tting. Perhaps I have read too much into th is langu age

Page 4-8, lines 15-19: Given the concern about near roadway exposure, the following questions should be considered for inclusion. What are the uncertainties when extrapolating between stationary C O m onitoring instrum e nts and concen trations near roadways? W h at is th e spatial effect of roadway traffic on stationary CO m onitoring?

Page 4-9, line 14: The original CFK model includes endoge nously produced CO in the factors considered for predictin g increm ents in COHb.

Page 4-10, line 26-31: A ngina does not occur in h ealthy individuals even at m a xi m a l exercise. Therefore this question n eeds to be restated.

Page 4-11, lines 1-6: Delete si nce it is a repeat of previous question on page 4-10, lines 26-31.

Page 4-11, lines 7-9: This issue probably requ ires future research and therefore should be elim inated from this section. Lung diffusion capacity is routinely m e asured using CO. This is potentially an im portant issue because if it were true, it would cause a re-evaluation of basic

assum p tions regarding oxygen transf er in the lu ng. However there does not seem to be any support for this issue in the literature , prior to 2000 nor since that review.

Page 4-11, lines 23-24: Since ther e is no guidance for consideration of multi-pollutant air quality standards, how should this inform ation be dealt w ith in the ISA and how are we to consider such data? It is not clear that the population is ever exposed to CO alone in the environm ent. The only data po ssible seem s to be f r om multi-va rian t sta tis tic s.

Page 4-14, lines 5-6: I believe that this que stion is based upon the presum ed mechanism by which CO has its prim ary effect: through a relative hypoxemia. This is dem onstrated in patients who have coronary artery disease and have lost the ability to dila te the i r c o ronary arteries to m eet increased oxygen dem a nds of the heart that occu r during progressive exercise. However, the decrease in tim e to onset of angina or tim e to isch em ic changes in the EC G appears to occur when estim ates of oxygen delivery to the heart predict an adequate s upply of oxygen in the arterial blood. Therefore the m echanism of action of CO in th is susceptible population rem a ins unidentified as does a m a rker of its action. So to raise the issu e that oxygen saturation which can be estim a ted non-invasively m i ght be a surroga te for COHb is based on a false assum p tion.

Page 4-14, lines 25-29 through page 4-15, lines 1-3: An im portant part of this question should be how does the pathophysiologi c changes in this population a lter the norm al com p ensatory responses to low levels of CO observed in healthy individuals?

18

### Dr. Russell R. Dickerson

Co mm ents EPA’s Draft Plan for Review of the Primar y National Ambient Air Quality Standard for Carbon Monoxide fo r the telecon f erence on April 8, 200 8.

Three notew orthy topics: The current m onitoring program is inadequate but could easily be im proved; CO plays an m a jor role in the budge ts of other criteria pollutants and other environm ental problem s and thus a secondary standard warrants serious consideration; the process by which the scientific j udgm e nt of the CASAC and its fo cus groups is used in form ing policy needs careful considerati on - especially in light of th e recent p r oblem s with PM2.5 and ozone standards.

On page 4-7, we m a y be asking the wrong questions. It m i ght be better to ask “how can current monitoring m e thods for CO be m odi fied to pr ovide inform ation adequate to determ ine CO exposure, statistics of ambient concentrations, to evaluate models, etc? ” CO, even at concentratio ns well belo w the NAAQS, is respo n sible for a large fraction of the OH reactivity and thus production of HO 2 , H 2 O 2 , and O 3 over the US, but em issions inventories and monitoring

m e thods are inadequate. Direct investigation of HOx che m istry ha s quantified the role of CO as responsib le for 10’s of percen ts of th e total OH reactivity (e. g., Ren et al.

, 2005; Ren et al., 2008). The ratio of em is sions of CO/NOx (based on road-side research grade m easurem ents) has decreased dram atically, but MOBI LE6 CO/NOx em ission ratios ha ve not followed this trend - they are too high now. MOBILE6 indicates a ratio of 15:1 while curren t m easurem ents show 5-8 (Bishop and Stedm a n, 2008; Parrish

, 2006). In other words, current CO monitors as employed can not determ ine the concentr ation of CO much of the tim e, but with relatively m i nor modifications, these m onitors can be im proved such that the d e tec tions lim its are esse ntia lly always sufficient for am bient CO m i xing ratios [ Dickerson and Delany , 1988; Parrish et al. 2000). The Maryland D e pt. of the E nvironm ent operates one at Piney Run, MD. The

m a nufactures of CO analyzers have indicated a willingness to im prove the instrum e nts for commercial sales.

The atm o spheric chem istry and physics of CO are relatively sim p le and well understood, m a king it enorm ously useful as a tracer. Im proved m onitors would provide data useful to

• evaluate em issions inventories

• investigate the epidem iology of CO

• evaluate chem ical transport m odels (such as CMAQ) for ozone and PM2.5

• determ ine the im pact of CO e m issions on th e large scale co mposition of the atm o sphere and clim ate.

Although the EPA did not com p lete the review wh ich started in 1997, a revised CD was prepared and reviewed. That CO CD recommended change s in m onitoring technique to provide data

19useful to m o dels. Am bient concentrations are typically below 300 ppb and commercial CO analyzers can be easily modified to im prove the resolution from 200 to 20 ppb. W h ile current monitors are adequate to dem onstrate com p lia nce with the NAAQS, a m bie n t concentrations are frequently below detection lim its.

Global atm o spheric composition, th e oxidizing capacity of the troposphere, and clim a t e forcing should be considered in form ulating a secondary st andard for CO to protect public welfare. In addition to its direct health effects, the environm ental eff ects of CO include:

• A core precursor to ozone.

• As a precursor to the oxidants that form PM2.5.

• An i m pact on the large-scale com position, a nd oxidizing capacity of the atmosphere.

• A role in g l o b al rad i ative balance and clim ate.

I am not clear on the new review procedures , but the comm e n t by Dr. Henderson “The CASAC is a science advisory body and we cannot give the EPA our advice if the scie ntific analyses of the EPA staff ar e obscured f r om us,” needs substantial discussion.

References

Bishop, G. A., and D. H. Stedm a n, A Decade of On-road Em issions Measurem ents, Environ Sci. Technol ., 2008.

Dickerson, R. R., and A. C. Delany (1988), Mod i fication of a commercial gas filter co rrelation CO detector for enhanced sensitivity, J. Atmos. Ocean Technol.

, 5 , 424-431.

Parrish

, D.D ., Critical evaluation of US on-ro ad vehicle em ission inventories, A t mospheric Environment, 40, 2288-2300, 2006.

Parrish, D.D ., and F. C. Fehsenfeld, Methods for gas-phase m easure m en ts of ozone, ozone precursors, and aerosol precursors, Atmospheric E n vironment , 34, 1921-1957, 2000.

Ren, X.R., e t al., Hydroxyl and Peroxy Radical C h em istry in a Rural Area of Central Pennsylvania: Observations and Model Com p arisons, J. Atmos. Chem ., 2005.

Ren, X.R., e t al., HO x chem istry during INTEX-A 2004: Obse rvation, m o del calculation, and

com p arison with previous studies, J. Geophys. Res., 2008.

20

### Dr. Milan Ha z u cha

The Plan for Review (Plan) is structured around a series of critical activi ties/tasks clustered into four key components th at have to be accom p lishe d in develo ping the ISA and Annexes for CO. Generally, the ISA and supporting Annex docum ents a pproach has been successfully used in the developm ent of recent N AAQS docum ents. The Plan rev i ew schedule as proposed is reasonab l e.

One of the changes from the previous approach es to NAAQS reviews is the proposed elim ination of a staff paper. The staff paper served as a com p endium , identifying supporting evidence and providing rationale for decision m a king. It was an extended summ ary of t h e ISA, generally incorporating answers to questions raised in a review plan. In th e absen c e of staff paper the ISA should inclu d e a Chapter where each of the questions raised in the Plan will be briefly, in a couple of sentences or a short pa ragraph, answered. This will he lp to quickly identify the areas which m a y have not been addresse d or overlooked as well as iden tify the gaps in the current scien tif ic kn owledge and database(s).

Apart from elim inating the staff paper, I think that only m i nor adjustm e nt s , m o st likely specific in nature, will be required to th e proposed Plan. My suggestions for changes/m odifications in Chapters 3 and 4 are listed below.

Page 3-2: O n e of the issues that should be cons idered in this section is th e inte rac tion between high altitud e and CO. Both resu lt in hypoxia, ho wever, CO at altitud e m a y have additional detrim ental effects. Moreover, idle em issions are supposedly m u ch higher at altitude which m a y increase exposure load. Consequent ly, health risk m a y be greater.

Page 3-2, line 1-2: After “near-roadway” insert the words “and hot-spots such as bus stops, cityintersections , etc,”. Thes e are the places where ambient CO con centration m a y transiently reach high levels exposing substantial population incl uding individuals with comprom i sed health.

Page 3-2, line 10-12: Percent of oxygen saturati on as typically m easured would be a m i sleading indicator of CO exposure. Great m a jority of O2 saturation m easurem ents are done by pulse oxim e ters that are known to be unreliable for C OHb estim ation. Only when O2 saturation is determ ined by specialized blood gas instrum e nts the COHb level can be reasonably approxim a ted. But, in such setting, one m a y as well m easure COHb level directly by COoxim e ter.

Page 4-4, line 5: Include ISI W e b of Knowledge database in the search list. Of all m e ntioned databases, ISI is the m o st com p rehensive databa se and includes publications not found in other databases.

Page 4-4, line 19: Delete “perti nent”. W e do not know yet how pe rtinent those studies are. All potentially pertinent studies will have to be asse ssed first using study sele ction criteria listed in subsequent section.

21Page 4-4: W ill EPA consider po ten tia lly pe rtin e n t studies pu blished in a f o reign lang uage ? W ill they be translated by EP A if th ey satisf y selec tio n criter ia ?

Page 4-5 line 4: List of c onditions should be expanded to add “Sufficient statistical power”. Surprisingly high num be r of studies is statistically deficient. Partic ula r ly the la ck of statistical power is a frequent deficiency of published studies . This criterion should be specifically stated in the c r iter ia lis t.

Page 4-5, line 9: The cons a nd pros of potentially pertinent st udies, i.e. design strength or deficiencies, poor statistics, etc., should be discussed in respective Annexes. Studies that did not pass the m u ster shou ld still b e discu s sed. Inse rt a f ter the wor d “issues “ f o llowing th e text “f ully discussed in Annexes”.

Page 4-5. Change the subtitle to read “Criteria fo r Selecting F i el d and Epidem iological Studies.” The design of field studies is different and som e selection criteria m a y differ as well.

Page 4-5, line 24-27: The argum ent for m o re deta iled discussion of US and Canadian studies is a concern “the potential impact of differing health care system s” or other geographic regions m a y have on the assessm ent. W e ll, Canada has substa ntially different health care system . Suggest changing the sentence to read: ”Certain findings of the stud ies conducted in the U.S. m a y generally be discussed .......”.

Page 4-6, line 4: Change subtitle to “Crite ria for Selecting Hum a n Laboratory, Clinical and Ani m al Toxicological S t udies.” Each type of st udies should have its own criteria, particularly anim al toxicological studies.

Page 4-6, 2 nd para: There is no discussion about the se lection criteria for anim al studies. Many anim al toxicological stu d ies m a y not be relevant because of v e ry high CO concentration used, exposure duration, extrapolation difficultie s, or other experi m e ntal conditions.

Page 4-6, line 8-10: It is highly unlikely that any of the m echanism s can be elucidated under
atm o spherically relevant conditi ons, which should be defined. Studies of m echanis m s require
more severe exposure co nditions so that the m ech anism s are easier to id en tify and stud y. The sentence should be reworded.

Page 4-7, l. 24: Insert “and tem poral “ between the words spatial and variability. Both tem poral and spatial v a riab ility will influen ce averag ing tim e

. Page 4-8: O n e of the questions that should be included in this s ection is: “ W hat is the effect of averaging tim e and m e t hodology on health risk a ssessm ent?” Peak am bient CO concentrations in hot-spot areas are blunted by the current averaging m e thod. But it is the peak CO concentratio ns that will increas e the health risk to individuals. It would be desirable to weigh the peak or hourly peak concentrations w h en calculating averages.

Page 4-9, line14-15: The m odels estim ating COHb should be capable of including endogenously produced CO as a variable endpoint and not a cons tant. Several diseases , such as asthm a or

22COPD, or transient airway inflamm a tion are kno wn to increase production of endogenous CO to the lev e l th at m a y exceed am bient concentration of CO.

Page 4-10, line 28: Reword. The tim e to onset of angina is not an endpoint for healthy individuals.

Page 4-11, lines 1-6: Th is aim is iden tical to the p r eced ing on e on p.10, line26-31. Delete.

Page 4-11, line 7-9: The effects of CO on re spiratory gas exchange have been studied extensively in the past. At am bient CO concentr ations these effects are o f no clinical relev a nce even in at-risk population. A sim p le statem en t to this fact should be sufficient.

Page 4-13, line 10: Change to read “... hum a n laboratory, clinical and toxicological...” The evaluation should include hum an laboratory a nd relevant clinical studies as well.

Page 4-15, line 28-29: T h e first goal should be “t o com p rehensively and critically review the literature and subsequently iden tify.......” as stated on p.1-2, line 11-13. I also suggest adding a Chapter at the end of the ISA discussing comm on alities and differences, if any, of key factors and studies that have led to and determ ined the current W H O, EU and the NAAQS for CO.

23

### Dr. Rogene Henderson

Comm ents on Section 6. Policy Assessm ent/Rulem ak ing of the US EPA Draft Plan for Review of the Prim a r y NAAQS for Carbon Monoxide.

In a letter to the Adm i ni strator dated January 23, 2008, the CASAC expr essed their oppositio n to the use of an ANPR as a Policy As sessm ent docum ent at the end of the NAAQS review pro c ess and that oppositio n s till exists. A s pointed ou t in th at letter, the ANPR is a docum ent that belongs at the begi nning of the review process, not at the end, because the ANPR (Advance Notice of Proposed Rulem a king) is m ean t to describe every po ssible cho i ce th at m i ght be considered.

In a m e m o from Assistant Adm i nistrator Marcus Peacock of Decem ber 7, 2006, the ANPR/Policy Assessm e n t Docum e nt was described as containing essentially the analyses that had been in the form er staff paper plus m odi ficat ions related to EPA m a na gem e nt concerns. The ANPR that was presented to CASAC at the end of the lead review process was NOT such a docum ent, but was the standard ANPR with a ll options described but with no scientific justif ication f o r th e options. It is not acceptable to CASAC to rem ove from the review process the sc ientif ic analys es o f the data th at was f o rmer ly provided in the Staff Paper and substitute an ANPR that provides little or no scien tif ic ju stif ic a tions.

The CASAC is a science advisory body and we cannot give the EPA our advice if the scientific analyses of the EPA staff is obscured from us.

24

### Dr. Donna Kens k i

This draft plan puts forward a logical fra m ework for the com i ng review of the CO NAAQS. It is very sim ilar to the p l ans for NOx and SOx and, b ecause the work hasn’t b een done yet, it’s h a rd to find any serious flaws. I have two general co mm ents. First, a potentially significant problem with respe c t to am bient CO data in both the ISA and subsequent risk assessm ent. Past efforts to control CO have been rem a rkably successful and thus am bient concentrations are very low -- as with NOx and SOx, well below the NAAQS almost everywhere. Consequently many m onitors have been removed from state netw or ks, since the r e is little in centiv e for states to bear the cost of running m o nitors in areas where there is no r easonable expectation of nonattainm e nt. W h ere monitors rem a in, concentrations are frequently a t or be low th e detec tion lim it. W ith few monitors and a significant fraction of data below the detectio n lim it, the adequacy of the am bient data for assessing population exposure and risk is severely limited. It would be helpful to have EPA discuss these lim itations and their expected impact on the exposure and risk assessm e nt in particular.

Second, as we discovered in the review of the lead NAAQS, the use of the ANPR as a tool to present EPA ’ s policy ass e ssm ent was not succes sful in comm unicating EPA’s views o n NAAQS revision. I saw no indication in this docum e nt th at the process had been changed to incorporate CASAC’s concerns. Perhaps it is to o early and EPA is still c ontem plating how to use the ANPR more appropriately as a policy assessm e nt vehicle? In any case, I look forward to an ANPR that

m a kes genuine assessm ents of the science and pres ents rational policy options for consideration.

p. 5-6 is m i ssing text at the top.

25

### Dr. Mich ael T. Kl einman

Section 3

A policy relevant issue that is no t ex plicitly a ddressed is the non-uniformity of CO exposures in various environm ents. This has a profound effect on the adequacy of our ability to judge health effects as a function of high local exp o sures, i. e. n ear heav ily trafficked ro ads. Monito ring plans f

o r CO should take this into account. Perhaps this could be f o lded in to th e question : “ What do recent studies focused on the near-roadway envi ronment tell us about high-e x

posure subpopulations and the health effects of CO?”

Alternatively, it might be advisable to raise the issu e of whether the current n e twork of air sam p ling

m onitors adequately repre s ents populat ion exposure s to CO a s an explicit charge question.

Section 4

4.1 SCOPE AND ORGANIZATION Vis-à-vis the issue stated above, if ”e m phasis will be placed on studies conducted at or near CO concentrations foun d in a m bient air.” Som e guidance should be provided wit h respect to ranges of
exposure s m easured near areas of unu sually high co ncentration that are not alwa y s rep r ese n ted by the placem en t of m onitors for other criteria pollutants.

4.2 ASSESSMENT APPROACH

Liter a tur e Search The suggested search term s are rather lim ited. An im portant aspect of the current literature relates to long-term sequelae which include neur ological as well as cardiovascular endpoints. While this m a y be subs um ed in the guidance to look at specific health outcom es, it might be useful to state this explicitly. It m i ght be us ef ul to specif i ca lly include term s rela ted to the possible effects of co-pollutants both from the effects standpoint and from the m e chanistic area (i.e. pollutants that induce inflamm a t o ry eff ects could up regulate HO- 1 activity which would increase endogenous CO production).

General Cr iteria f o r Stud y Selection The criteria are well thought out. In keeping with m y previous comm ent s I suggest that we discuss the following criterion: “ To what exten t are the aero me tric data, exposure, or dose metrics of adequate quality and sufficiently repres entative to serve as indicators of exposure to ambient CO?”

This should be placed into a contex t of the exposure rang e for population s with excep tional exposures since this criteria m i ght be interpreted to exclude som e studies near CO sources that

use m easured values that are in exces s of t hose seen at central site m onitoring stations.

26Criteria for Selecting Anim al a nd Hum a n Toxicological Studies “Criteria fo r the se lec t ion of resear ch evalua tin g animal tox i colog i cal o r controlled exposure studies will focus primarily on thos e studies conducted within about an order of magnitude of ambient C O concentrations and those studies that approximate expected human exposure conditions in terms of concentration and duration.”

There are seasonal and site-spe cific factors that contribute to the non-hom ogeneity of CO exposures. The order of m a gnitude re quirem e nt m a y be too restrictive.

Many toxicological studie s are lim ited with respect to expo sure durations and am ounts of tim e subjects can be kept in the expe rim e ntal setting. Perhaps criter ia should assess whether the study was performed to assess subjects with reasonable levels of som e biom arker even when the
exposure co ncentration s are greater than am bient rather than putting too tight lim itations on the acceptable concentration ranges.

One im portant factor that should be consid ered fo r asses s ing the accep tability of hum a n toxicological studies is whether th e study was appropria tely blinded.

Section 5

Page 5-5, line29: incom p lete sentence

Page 5-6, line17: This area should be expanded to include issues rela ted to inhom ogene ity of exposures. A key question is “W hat is the relations hip between peak 1 and 8 hr levels near roads and other hotspots vs. levels m easured near central s ites ? ”

Page 5-7, lin e 19: The manner in which the hea lth , risk and ex posure ass e s s m e nts will deal with the issue of non-hom oge neous concentrations should be m o re clearly described and considered. This is a cross-cutting problem th at brings into play considerati ons of environm ental justice as well as the critical dis tin ction between “com p liance” m onitoring and m oni toring for th e purpose of providing the inform ation needed to assess th e adequacy of health protection afforded by the NAAQS.

27

### Dr. Arthur Penn

Page 1-3, lines 7-8: W h y was the staff paper omitted ? By putting the in f o rm ation in to the Federal Register notice (not the m o st “reader friendly” of docum ent fo r m ats) rath er th an providing the historical perspec tive within th e I P could esse ntia lly m a ke it m o re dif f i cult, especially fo r m e m b ers of the general public, to find im portant, clearly presented inform ation?

Page 3-1, line 29: Are there su f f i cien t data availa ble f r om f

e tal m onitorin g to allow as sessm ent of

f

e tal sensitivity ?

Page 4-2, line 14: Please define “welfare e ffects”. W h at else does this describe besides “ecosystem effects”?

Page 4-4, line 27: “sufficientl y rep r e s enta tive”

-- of CO levels?

Page 4-4, line 30: “m eaningful and reliable”. “M eaningful” is vague. Is this independent of “statis tically significan t”? W h at are the speci f i c c r iteria tha t d e term ine “re liab ility” ?

Page 4-6, lines 8-10: Should studies that elucid ate m echanism s be a m a j o r part of the data to be analyzed ? This seem s like a m a jor goal of a pos sibly related, but distin ct set of analyses.

Page 4-8, lines 12-13 (also see Page 4-13, lines 12- 14): Interactions betw een CO and these other factors will likely be very im portant. A large am ount of data from diverse sources will have to be

exam ined and analyzed. W ho will do this ?

Page 4-11, line 18: “Other system s”--genito-urin ary? digestive? endocri ne? By what criteria would any of these, or ot her system s, be selected ?

Page 4-15, lines 5-6: “Older adults and fetuses”. No neona tes? How are effects on fetuses assessed ?

Page 5-2, line 6: “Four scenar ios”-Is there a summ ary of these scenarios availab l e so that people, especially m e m b ers of the public, do not have to find a nd wade through the 1992 docum ent?

Page 5-2, line 6: W hy was the CO NAAQS revi ew put on hold? W hy, 9 y e ars later, has the exposure analysis not been com p le ted? Has there been a public i nquiry about this and a for m al response?

Page 5-6, lines 1-4: Is there a m i ssing para graph, or is this ju st a spacing error?

28Page 5-11, lines 3-17: D u ring the teleconference, a couple of the discussants noted that the distribution of CO monitors was uneven and that the m onitors m i ght be com p letely absent from certain com m unities within a la rge monitoring zone. It was also noted th at “th e em issions his t ory was a disas t er” and that in general, ambient CO m easure m ents were inadequate. Other

comm ittee m e mbers supported these comm ents. Gi ven these concerns, how reliable are the prim ary sources of the d a ta (s ee lines 4-5) th at w ill b e includ ed in the AP EX m odel inputs ?

Page 5-11, line 14: The specific reference to Morgan &Henrion, 1990, was not included in pages 7-1 or 7-2 in th e d r aft plan. Th ere are m u ltiple publications lis ted for them in 1990.

29

### Dr. Beate Rit z

Chapter 4:

page 4-4 "E mphasis in the text will be placed on discuss i on of (1) new, multi-c ity s t udies th at

em ploy standardized m e thodological analyses for evaluating CO effects a nd that provide overall estim ates for effects bas e d on com b i n ed analys es of infor m ation pooled across m u ltiple cities ; "

The em phasis on pooled results from m u lti-city s t udi es th at us e standardized m e thods m i ght be

m i splaced i. e. it is not c l ear th at such approache s will be inform ative. The problem with CO is its intr a-community he tero geneity du e to loca l s ources, heterogeneity m a y not be reflected in

am bient m o nitoring station m easurem ent data. De pending on how a m bient m onitoring is used to derive expos ure estim a tes in different commun ities, this cou l d lead to d i fferences in

m easure m ent errors depending on how dense the network is. Concerning standardized exposure modeling approaches, if different sources cont ribute to high CO in differ e nt cities, a

' s tandardized m odel' for different cities m i ght not work or be appropriate e.g. in som e cities CO

m a y depend more on vehicular traffic and in others on power plant em issions etc.

Sim ilarly questionable is the em phasis on "studi es that consider CO as a component of a

com p lex m i xture of air pollutants. " It is un cle a r whether th is m eans only multi-po llutant m odels will be take n into cons ideration and how the exp ected (and possibly s t ro ng) corr ela t ional pattern with par tic le s and NO2 will be de alt with in suc h m odels. It m i ght be impossible to a d just f o r (highly) correlated pollutants in th e model, and it is not clear how this may be addressed and/or evaluated in the report.

Furtherm ore, it is unclear what the emphasis on "new studies that provi de quantitative effect estim ates for populations of interest" m eans. For pregnancy outcom es, the issue of scaling accord ing to a (suscep tib le) tim e period is essen t ial and it is n o t clear th at 1ppm exposure on average during a trim ester is com p arable to a 1ppm average expos ure during a m onth or week of
pregnancy.

Chapter 5, page 5-4

"For this cu rrent rev i ew, EPA staff will build up on the 1999 work and subsequent improvem e nts to the exposure m odel (now called A P EX) in de veloping its plan for CO exposure assessm ent. " It is un cle a r what this wo rk will b e i.e

. what kind of data will be used to d e velop th ese m odels and whether the data already exist and/or will be retrieved from existing research (e.g. the LA RIOPA study that m onitored CO).

Given that the highest CO expos ures m i ght occur inside cars dur ing com m ute, it is unclear how this will be integra t ed in to the stated goals for CO exposure assessm ent (page 5-5), even though the Apex model uses in-vehicle m i croenvironm en ts and this is also m e ntioned on page 5-10.

30

### Dr. Paul T. Robert s

Note that this docum ent outlin es a plan f o r the se veral y ear re view proces s f o r the CO NAAQS and thus includes little or no techni cal detail. In general, this plan is we ll- written, is a d equate to

m eet its objectives, and (presum a bly) m a tches the review process currently ongoing for sulfur dioxide and nitrogen oxides, whic h are both further along than the pr ocess for CO. Overall, I am concerned about the elim ination of the EPA staff pa per from the process, si nce I am not sure how the summ ar y and integ r ative aspects of the staff pa per will be handled in the new process (within the ISA and the Scope and Methods P l an). Mayb e this should be addr essed directly in the “Plan”.

In Section 1.3, I think that there should be som e discussion of why the previous 1997-2000 CO NAAQS review process was not comp leted (see page 1-6, lines 23-24).

Table 2-1 seem s to have a duplicate listing for the first draft of the risk and/or exposure

assessm ents in January 2010 (see 3 rd and last entry under Risk/Exposure A ssessm ent in the table).

Specific comments on Sections 4 and 5:

• The introduction to Section 4 m e ntions that a form al fra m e w ork for the integration of health ef f

ects evidenc e was develop e d in th e N O x ISA (see page 4-1, lines 13-16); I think this should be summ arized here in the draft plan.

• As far as I can tell, the WH O guidelines referenced on page 5-5, lines 3-4 do not include CO; infor m ation on CO was not updated from the earlier WHO Air Qua lity Guid elin es for Europe, 2 nd edition published 2000.

• I do think that a com p arison and explanation of the different standards (and studies supporting them ) published by W H O and others for CO should be discussed in sum m a ry for m in this plan and in more detail in th e ISA and/or the Scope and Methods Plan. This specifically could help on the short-term issues discussed on pages 4-10 to 4-12 etc., since short-term standards is one m a jor area of difference.

• Text is m i ssing from the bullet that begins on page 5-5 and continues onto the top of page 5-6.

• There are several potential CO am bie n t expos ure environm ents which are not m e ntioned in this docum e nt, but should be m e ntioned he re and inform a tion for them explored during the developm ent of the ISA and the Scope a nd Methods Plan. Existing study data may be useful for determ ining levels and averaging tim es, as well as relevant to future exposure environm ents. These ambient exposure environments include other near-source environm ents such as near ship loading and unloading ports (potential exposure from trucks and other vehicles plus potential exposure from the ships them selves) and exposures near recreational boats. Both of these environm ents cover locations where people live, work, and play. Recreational boa t engines, including both 2-stroke and 4- stroke engines, do not have exhaust contro ls and several potential environm ents can result in very high CO concentrations in th e n ear-source environm ent. Even with com i ng

31em issions controls on n e w boats, fleet tu rnover is extrem ely slow and su ch exposures will likely persist for 10-20 years. Places in the d r aft pl an where these additio nal environm ents m i ght be m e ntioned include: page 3-2, lines 1-2; page 4-8, lines 3 and 28- 29; page 4-10 subsection on short-term exposure; and page 5-3, lines 23-26.

• There should be som e discussion of the types of CO m onitoring site s and how data from all types of sites will be used to characterize CO air quali ty and exposures (specifically

m e ntioned in Section 5.3, pages 5-5 to 5-7) . In particular, th ere are official CO monitoring sites, “hot-spot” si tes, and data from special purpose m onitoring sites which all m i ght inform the analysis being undertake n. This section of th e plan should discuss these additional data sets and how they m i ght be used to further the objectives of the
exposure assessm ent (note that this is also of im portance for the discussions on pages 4-7 and 4-8 regarding spatial and tem poral analys es). In addition, th e approp riateness of
current m o nitoring sites, relativ e to their purposes, should be discussed in the ISA and/or the Scope and Methods P l an. Also, existing si tes should be evaluated in som e consistent

m a nner in order to ensure that the C O data being colle cted is appropriate f o r the sta t e d purposes, both for the current review and fo r f u ture uses re la tive to the N AAQS.

• Based on discussions I heard on the April 8 th call, I was wondering how the binding tim e of COHb m i ght be related to potential averaging tim e of th e CO data? In particular,

m i ght the COHb binding tim e lead to a short- term standard that has otherwise been ignored?

• In addition to these com m e nts, I support the following comm ents by others on the Panel:

- Interest in having a short discussion of why the secondary C O standard was revoked in 1985.

- The need for the Draft Plan to specifica lly addres s the is sue whether the e x isting monitoring m e thods and network are adequate to address the questions ou tlin ed in Section 3.

- Potential upgrading of present CO monito rs to high-sensitivity m onitors, which have been tested and evaluated by O AQPS staff in the recent past.

- The notion that CO characteristics m i ght be different in different cities, especially as it relates to ‘hot spots’, thus requ iring different types of data analysis approaches and m e thods.

- The concern that co -pollutants m i ght also have an affect on the im pact of CO concentrations on health.

- How will the CO ANPR show the re sults of the a ssessm ent of the f u ll r a n g e of potential science and policy questions whic h will have been address by that tim e ?

32

### Dr. Armistead Russell

Sim ilar to past draft plans provided to CASAC, this draft plan lays out a well thought out approach to reviewing the CO N AAQS. I was pleased to see that they plan to organize the CO ISA sim ilar to that for the NOx and SOx pr im ar y NAAQS, which I found to be a very good approach. In particular, what I liked about the N O x and SOx prim ary NAAQS ISA’s was having an initia l ch apter go ing f r om s ource to dose, then the future ch apters d ealin g with health endpoints, w ith a conclusion/summ ary chapter at the end. (H owever, the bullet points do not follow this o r der.) Th is worked well, and communicated the needed inform ation in a more integrated and briefer fashion. In so doing, how ever, EPA staff should continue to provide the inform ation necessary to review th e s c ience that is m o st pertinent to reviewing the various aspects of the NAAQS.

In regards to the atm o spheric dynam i c s of CO , and the distribution of the prim ary sources (autom obile exhaust), C O is som e what unique com p ared to the othe r criteria po llu tan t s. It is chem ically reactive, both being destroyed and form ed in the atm o sphere. CO exposures of m o st concern are from prim ar y em ission, with the high est levels being near the source, and dropping off rapidly as one m oves away, though policy relevant background (PRB) levels are from secondary f o rm ation. Thus, the type of m odel used to estim a te PRB CO levels is very different from the type that would be used to estim ate expo sures. Indeed, as suggested in the Draft Plan, PRB levels will app r opriately be es tim a ted using chem ical transport m odels. On the o t her hand, the m odel(s) used to help es tim ate exposures m a y be quite di fferent, e.g., dispersion models. This is no t well spe lled out in th e Dr af t Plan. What type of dispersi on models, or chem ical transport m odels, should be m o re thoroughly discu ssed and assessed. Indeed, one of the driving questions down the road as to the exposure asse ssm e nt m a y be the m odeling approach. A further question will be how to evaluate the model, particularly if a ca se study (or studies) is used for which such an evaluation is not done. This is go ing to be particularly important as one of the possible susceptible populat ions is rather unique in regards to how air quality m odels have been

em ployed when estim a ting exposures, as discus sed below. The Draft Plan refers to consideration being m a de for confounding. The S ource-to-Dose chapter (and associated Annex) will need to address this is detail. It will be c r itic al.

The Draft Plan identifies APEX as the likel y m o del to be used for conducting the exposure modeling. This is a reasonable choice. It shou ld be noted, again, that the continued use of APEX in NAAQS assessm ents should continue to m o tivate E P A to further enhance and evaluate APEX, and t h at evaluation should consider subpopulati ons of interest. In th is case, what I think is a rather new and unique subpopulation is the target, that being pr egnant wom e n. What population specific inform ation exists for APEX to use for this target, and when insufficient inform ation is not available, how is EPA going to m odify APEX for this group? Further, how are they going to integrate result s from the air quality m odeling for use in APEX? On page 5-6, it notes that they will include various types of exposures... how, in a probabilistic fram e w ork, will you con s ider p r egnancy in the m a trix.

33I would have liked to see m o re inform ation on the planned use of case studies. This has been a critical issue in past reviews. This Draft discussed the Denver case study, and m e ntions a Los Angeles study. Both would be of interest, still, along with, possi bly, an Alaskan city (Fairbanks or Anchorage). Los Angeles would provide an interesting contrast to Denver due to the different

m a gnitude in the variation between seasons a nd tem poral distributi ons, and, possibly, the population distributions. This m i ght be of particular interest if th e exposure period of interest is long... m u lti-day / week/month (e.g., for fetal exp o sures) . Alaskan cities m i ght be extrem e in the other direction, and also m a y have the m o st extrem e short term exposures. Perhaps the analyses discussed on pages 5-5 to 5-6 (tha t is m i ssing on m i ne) covers this.

Other m i nor issues:

Pages 4-7 to 4-8 There seem s to be an over-r eliance on chemical tran sport m odels verses dispersion models or other m i cro-scale m odeling approaches. There should be a fairly m a jor section on various m odeling approaches for estim a ting CO c oncentrations and how they can be used to assess exposure and dose.

Page 4-8, line 23: Pet peeve (though I m a ke this m i stake as well): “particle” is not a phase, “condensed” can be used.

Page 4-9, line 7: This bullet asks a simple question, though the real question is how does one evaluate the models being em ployed, a nd how does one interpret those results.

Page 4-9: A sim ilar bullet point for exposure models as above.

Page 5-6: Y ou m a y want to consider what othe r procedures one m i ght us e to ro llba c k levels as part of an uncertainty assessm ent. Further, you note on page 5-6 about assessing exposures for levels just meeting the standard... that m eans you also have to rollup le vels, too. The m e thods should be consistent. Also, given that the m e t hods likely used to reduce CO e m issions m a y rely
on autom o tive standards, consideration as to how exposure reductions ar e linked between cities

m a y be appropriate.

Page 5-6: Y ou note that you will evaluate the relationsh i ps b e tween 1- an d 8-hour peaks... you should look to other averaging tim e s.

Pages 5-5 to 5-7: Som e thing is m i ssing. (Maybe this is where other case st udies are identified.)

Summ ary: The Draft Plan provides a suit able m a p for going forward, though given the introduction of a rather unique susceptible population not treated prev iously (fetus’s) and exposure route (pregnant wom e n) how expos ure and dose will be linked to am bient concentrations and forms of the st andard requires greater discussion and detail as to how this will be accom p lished.

34

### Dr. Jonathan M. Samet

General Comments:

• This Draft P l an follows the m odel that is now co m i ng into place for developing a prim ary National Am bient Air Quality Standard (NAAQS). As such, the plan draws on approaches taken already over the last severa l years. The overall plan and approach is appropriate.

• However, the new plan appears to draw little on “lessons learned” to date from dealing with nitrogen oxides and sulfur oxides. Th e plan suffers from an overall lack of specificity and vagueness of wording that will undoubtedly becom e a limitation during its im ple m entation. Additio nally, there has been li ttle advance in the EPA’s form ulation of such critical concepts as causality, confoundi ng, effect m odifi cation, and susceptibility. On reading over the qu e s tions that w ill gu id e th e review, prob lem s arising f r om this vagueness are abundant. I highl ight a num ber of exam ples in my specific comments.

Specific Comments :

Page # Line # Comment

4-4 27 “...sufficiently representative” Of what? Representative in what regard? 4-4 29 Not clear at all 4-4 30 “m eaningful ” From what perspectiv e ? Reliab l e means rep eatable. Is the concern abo u t m i sclassif i cation ? 4

- 5 5 “potential confounders...” Specify criteria for these 4-8 20 This needs greater specificity 4-8 24 Tem poral and spatial? 4-9 19 What does variability m ean here? 4-10 7-10 Lines 7-10 are sweeping. W h at is this saying? 4-11 18 All other system s? 4-11 23 “...nature of health e ffects...” Effect modification ? 4-12 4-13 20-22 1-2 What is m e ant by eviden ce again s t a causal association? Could m o re be said about EPA’s approach to causal inference? 4

- 1 3 9 “evaluate uncertainty...” Any attem p t to quantify? 4-13 17-19 What does this m ean? Is this in ref e rence to potentia l effect modification ? 4-15 6 Reference to fetuses not clear. 4

- 1 5 1 0 What results? 4-15 19-21 Not clear in the form ul ation of attr ib utable risk

35

### Dr. Stephen R. Thom

Approach & forma t fo r the integ r ated scien ce assessment section are w e ll organized and logical.

Specific co mments I s u ggest be in cl uded in the EPA document are:

A. Human exposure studies : Environm ental pollution causes a variety of disorders, although not all studies have docum ented CO per se as th e etio logic agent.

1. Neonates/infants: a) Preterm labor/de live r y - assoc i ation with e nvironm ental CO and also particulates (PM) (as sepa ra te risk facto r s & also in co mbination) b) Inf a nt m o rta lity - asso ciation with CO plus PM c) Neonate h o spita liz atio ns f o r respir at ory diseases - association with CO d) Intra-u t er ine growth r e tard ation /lo w birth weight (risks with CO, PM a nd NO 2 ) e) No relation between SIDS and CO, but a link has been established with NO 2 and SO 2

2. Children a) Childhoo d respirato r y sym p tom s ( w heezing) - association with CO and also PM.

3. Adults a) Correlatio n s between am bient CO and ischem ic heart disease ED visits (CO and also NO 2 ) b) Cardiova scular m o rta lity (esp. e l d e rly) - asso c i ations with CO and CO/PM & O 3 c) Respir ato r y-re la ted E D visits - association with CO and CO+O 3 d) Depression-related E D visits e) Pneum onia hospitalizations (CO + O 3 ) f) No link between CO and tachyarrhythm ias ( but + link with ultra- fine particulates) g) Risk of CVA elevated with CO, PM, NO x h) Cardiac irregularity (HR variability) a nd CO (+ link in som e but not all trials) i) Plasm a markers of inf l amm a tion - atm o spheri c CO contam i n ation only linked with altered album in. PM and O 3 showed additional changes in plas m a levels of vWF, Factor VIII, fibrinogen. Higher CO concentrations (& shorte r exposure tim es) linked to elevated plasm a myeloperoxidase.

B. Issues of CO dose-response, as w e ll as time-course of responses, are not clea r. The weight of the scientific findings probabl y does not warrant an alteration in EPA CO guidelines (1 hr 35
ppm ; 8 hr 9 ppm ) . Also, the vari ability am ong findings in som e tria ls indicates that combinations of CO with co-pollutants can yield disparate results, leaving the issu e of pathophysiological

m echanis m s unclear.

C. Dosimetry question s persist , an d there n eed s to be som e focus on mechanism s unrela t ed to CO-O 2 competition for hem oproteins (e.g. the C F K e quation alone is not adequate to ‘predict’ biological stresses). These include pro-inflamm a t o ry proces ses such as in travascu lar p l atelet36neutrophil interactions, and a growing body of infor m ation on oxi dative stress/free radical

m e diated mechanism s (som e linked to ‘therapeut ic’ pathways such as activation of MAPKs, NF κ B inactivation, caspase 8 inactivation). Endogenous CO production impacts m itochondrial respiration b u t whether environm ental CO will co mpound this effect is un known (current kinetic modeling suggests th is is unlike l y).

37