1 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

Septem ber 24, 2008

EPA-CASAC-08-021

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: Clean Air S c ientific Advisory Comm ittee’s (C ASAC) Peer Review of EPA’s Risk and Exposure Assessment to Support the Review of the NO 2 Primary National Ambient Air Quality Standard: Second Draft

Dear Adm i nistrator Johnson:

The Clean Air Scientific Advisory Comm ittee (C ASAC), augm ented by subjectm a tter-exper t s to f o rm the CASAC Oxides of Nitrogen Prim ary National Am bient Air Quality Standards (NAAQS) Review Panel (herea fter referred to as the panel, roster provided in Enclosure A ) held a public m eeting on Septem ber 9-10, 2008 to review EPA’s Risk and Exposure Assessment to Support the Review of the NO 2 Primary National Ambient Air Quality S t an dard: Secon d Draft . EPA requested that CASAC address charge questions listed below that fell into four categories (chara cterizations of air quality, health effects ev iden ce and selection of potential alternative stand a rds for analysis, exposure, and health risks). Panel consensus comments on how the REA m i ght be further strengthened appear below in the form of responses to the Agency’s charge questions within those cate gories. Individual comments from CASAC panel m e m b e r s are enclosed in Enclosu r e B.

The CASAC Panel was generally pleased w ith the second draft of the Risk and Exposure (R EA) to support the review of the NO 2 prim ary NAAQS and found that the Agency had been responsive to the C A SAC re view of the first draft of the docum ent. However, the REA is incom p lete and the CA SAC should conduct further review prior to the docum ent becom i ng final. The next draf t should include both a completed Chapter 8 and an integration of the results of all the analyses based on clinical and epidem iological studies. CA SAC will als o review th e Advance Notice of Pro posed Rule m a king when it is published. The following describes the CASAC comm ents on the four categories of charge questions.2 Characterization of Air Qua lity (Chapters 2, 6, and 7)

1. To what extent are the air quality charac terizations and analyses technically sound, clearly communicated, appropriately characteri zed, and relevant to the review of the primary NO 2 NAAQS?

2. In order to simulate just meeting pot ential alternative 1-hour daily maximum standards, we have adjusted NO 2 air quality levels using the same approach that was used in the first draft to si mulate just meeting the curre nt annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

3. Because of the impact of m obile sources on ambient NO 2 , we have estimated on-road NO 2 concentrations. To what extent is the approach taken technically sound, clearly communicated, and appropriately characterize d? Do Panel members have comments on the relevance of this procedure for reviewing the primary NO 2 NAAQS?

4. What are the views of th e Panel regarding the ade quacy of the assessment of uncertainty and variability?

The air quality characterizations, analyses, and uncertainty and variability discussions are generally improved, but in some cases additional clarification is needed. There are inconsistencies in the air qualit y metrics used in the analyses and those considered as alternative standards and be nchmark levels. First, the concepts of alternative standards and benchmark levels, and their differences, should be clarified. Currently, the approach proposes using 98 th and/or 99 th percentile levels, but in different analyses switches betw een using the overall 98 th /99 th percentiles of the hourly values, the daily, 1-hr maximums and the annual means am ong the various monitors in a city. These multiple metrics are confusing, and make some of the analyses less informative to setting a standard.

The derivation and use of the on-road modification factor ( m ), needs to be strengthened, with improved documentation as to its basis and more explicit comparison with observations. Staff should consider us ing different weightings over the range of m values employed, based on a strengthened un certainty characteriza tion. The discussion of the measurements upon which m are based needs to address how those measurements represent on- and near-roadway exposures. This expansion should be part of additional discussion about how well the monitoring netw ork represents actual population exposures and provides meaningful information for expos ure analysis and model evaluation. This should include a better characterization of vertical concentration gradients and how monitoring height might affect the relations hip between observed levels and exposure. There is some concern that the importance of the biases associ ated with monitoring height and monitor in terferences might be misinterpreted.3 Characterization of Health Effects Eviden ce and Selection of Potential Alternative Standards for Analysis (Chapters 3, 4, 5)

1. The presentation of the NO 2 health effects evidence is based on the information contained in the NO 2 Integrated Science Assessment. What are the views of the Panel on the overall characterization of the health evidence for NO 2 ? To what extent is the presentation clear and appropriately balanced?

Chapter 3 covers susceptibility, descri bing the range of populations found to be susceptible, both to air po llution generally and to NO 2 specifically. The document would be improved by sharpening its conclusions. Cl early, one important overall finding is that a large number of people could be susceptible, when considering the full range of groups identified. On the other hand, the experi mental and epidemiological evidence would appear to converge in finding that asthma tics are highly susceptible. The concept of vulnerability, as distinct from susceptibili ty, is introduced, and appropriately followed through.

This draft REA appropriately reflects the NO x Integrated Science Assessment (ISA) in summarizing conclusions regarding the currently available health evidence related to NO 2 exposures. The choice to express th e overall evaluation of the data on the major findings in terms of five levels of “confidence” is applauded, since a consistent application of this approach can bring a new level of rigor and consistency to this type of evaluation. On page 32, lines 1-3, the sta ff makes the judgment that it will focus on endpoints for which the ISA “concludes that th e available evidence is sufficient to infer either a causal or a likely casual relationship” . This represents a decision that sets a precedent with regard to the level of ev idence in support of out comes that will be considered in the REA. Given the preceden t-setting nature of the decision, clearer justification is needed.

The REA concludes that a “likely causal rela tionship” can be inferred from the data for short-term NO 2 exposure and adverse effects on the respiratory system at near ambient levels of exposure – and that the susceptible populations include people with asthma or airways hyperresponsiveness (AHR) and the young and elderly. The ISA and the REA conclude that there is suggestive, but not sufficient, data to infer a causal relationship between short term concentrati ons near those associated with ambient NO 2 exposure and cardiopulmonary mort ality and between long-term NO 2 exposure and respiratory morbidity.

The bases for the above conclusions should be more clearly defined in the REA with clear linkages to the ISA. Both the ISA and the REA build on primary conclusions related to weight of evidence for causalit y. Ideally, an ISA needs to have a full discussion of the application of the Hill criteria, as adapted by the Agency for its review process: strength of association, experi mental evidence, consistency, biological plausibility, coherence, temporal relationshi p and the presence of an exposure-response relationship. The ISA should refer to each of these criteria and assess the data with respect to each for each of the major health ou tcomes considered. If done in the ISA, the causal conclusions could then be summarized in the REA with explicit reference to the ISA. It is not clear in the ISA that the se ven criteria were consistently considered in coming to the final conclusions for the various health outcomes for NO 2 . Absent such in-4 depth analyses in the ISA, the conclusions of the ISA and consequently the basis for the REA are weakened.

A remaining task for this document is to compare and synthesize the results of the assessments based on the epidemiologic studie s and the human clinical studies. For example, one challenge in accomplishing this is addressing differences in doses received in these two different contexts . Human clinical studies invo lve controlled exposures to NO 2 concentrations at the breathing zone of the subject while the epidemiology studies rely on a small number of fixed monitors whic h may not necessarily represent the actual human exposure concentrations. The next dr aft REA should describe the different doseresponses from clinical and epidemiological st udies and discuss how to interpret them.

A stronger justification is needed to set aside the studies of indoor NO 2 . The stated rationale acknowledges that these studies focused on NO 2 alone to the extent possible and that the exposure situation indoors differs from that outdoors. On the other hand, the experimental literature is based on exposure to NO 2 alone as well. Given the emphasis placed on the human clinical studies, there does not appear to be a solid rationale for setting aside the studies di rected at exposure to NO 2 from indoor sources.

2. The specific potential alternative standards that have been selected for analysis are based on both controlled human exposure studies and on epidem iological studies conducted in the United States. What are the Panel’s views on the appropriateness of these potential alternative standards (in te rms of indicator, av eraging time, form, and level) for the purpose of conducting air qual ity, exposure, and risk assessments and on the rationale used to sele ct them for that purpose?

In general, the bases for selecting the i ndicator, averaging time, form, and level for the NO 2 NAAQS are clearly stated. The CASAC agrees that NO 2 is the best indicator for gaseous forms of oxides of nitrogen because the majority of our information on health effects and exposure involves this oxide form. The Integrated Science Assessment for NO x provides a detailed description of the relationship between NO 2 and other oxides of nitrogen and can be used as a reference fo r other forms of gaseous nitrogen oxides that may be present.

The averaging time of 1-hour is reflective of the durat ion of the experimental studies and the finding that th ere are adverse health effect s. CASAC would recommend that consideration be given to the need to explore scenarios for the 24-hour averaging time as well.

The proposed alternative form of the sta ndard is considered appropriate. The REA should better define the strengths and weaknesses of using the 98 th or 99 th percentile form for the standard – including defining how well the exposure distribution influences the magnitude and extent of high level exposur es. The epidemiological studies that form the basis for the proposed alternative standards are well described in the REA. However, the REA should more clearly describe how controlled human exposures were used to establish or validate th e proposed range for NO 2 analyses.5 With regard to level, the document provide s a clear rationale for assessing a lower range extending to 0.05 ppm, with which CASA C agrees. The upper end of the range is quite reasonable, based on th e experimental findings.

The REA should develop a scientific foundation for any decision regarding retaining or revising th e long term NAAQS for NO 2 . The REA does not establish that a short-term standard alone would be suffici ent to meet the public health protection mandate of the Clean Air Act. Are there ar eas of the United States that would be in compliance with a short-term standard but not with a long-term standard? The REA needs a discussion of the utility of the current long-term standard for NO 2

.
Characterization of Exposure (Chapters 6 and 8):

1. To what extent is the assessment, interpre tation, and presentation of the results of the exposure analysis technically sound, clearly communicated, and appropriately characterized?

2. The second draft assessment document evaluat es exposures in Atlanta. What are the views of the Panel on the approach taken and on the interpretation of the results of this analysis?

3. What are the views of th e Panel regarding the ade quacy of the assessment of uncertainty and variability?

Staff provided an update on progress, becau se Chapter 8 is still under revision. The Atlanta case study location is a reas onable one. The panel commends the responsiveness of staff and th eir ongoing consideration of adequate prediction of air quality. The strategies Staff have outlined to improve the modeling are likely to bring the model results closer to observed concentratio ns. There is some concern that the modeling approach may underestimate high exposures to residents who live near roads. We encourage Staff to include a clear characteriza tion of biases and additional assessment of the predicted versus observed concentrations . Though not discussed at this meeting, the rest of the exposure modeling is expected to be similar to the first draft REA, which we previously commented on. The personal expos ure data from Atlanta should also be compared with the model results. The CASA C looks forward to reviewing the completed exposure chapter in the future.

Characterization of Health Risks (Chapters 7, 8, 9):

1. Based on conclusions in the final ISA re garding airway responsiveness, we have expanded the range of potential health eff ect benchmark values to include 0.1 ppm. Do Panel members have comments on the range of potential health effects benchmark values chosen to characterize risks associated with 1-hour NO 2 exposures?

2. To what extent are the assessment, interp retation, and presentation of health risk results technically sound, clearly comm unicated, and appropriately characterized?

3. A focused risk assessment has been conduc ted for emergency de partment visits in Atlanta, GA. To what extent are the asse ssment, interpretation, and presentation of6 health risk results technically s ound, clearly communicated, and appropriately characterized? What are the views of the Panel on the approach taken and on the interpretation of the results of this analysis?

4. What are the views of the Panel regarding the clarity and adequacy of the discussion of uncertainty and variability with respect to the characte rization of health risks?

The health risk assessment methodology de scribed in Chapters 7 and 9 is welldeveloped and generally of high quality. Th e basis for expanding the range of exposure levels considered in the REA to include 0.1 ppm NO 2 is well-developed in the document. It is less clear, however, why a value as low as 0.05 ppm is not proposed, given results in the ISA. This decision should be more clearl y justified, or the ra nge expanded downward accordingly. At a minimum, 0.05 ppm and 0 .1 ppm should be included in the Chapter 7 exceedances tables (e.g., 7-5 thru 7-16) to a llow comparisons across cities at relevant ambient conditions. On a related note, it woul d be more informative for the tables and discussion to include the rate of exceedances as well as the absolute number.

An improved description of the rationale l eading to the selection of Atlanta as the representative site for detailed exposu re and risk calculations would improve understanding of the selection’ s implications. Ju stification for Atlanta’s results being generalizable is needed, given the ultimate objective of assessing national health risks and the potential for possible recommendation of an alternate national air quality standard.

The topics of uncertainty and variability are central to interpretation of the analyses in the REA. The presentation of these concepts throu ghout the document is uneven, repetitive, lacks suffi cient specificity, and should be more quantitative. The discussion should highlight the most important and relevant sources of uncertainty and variability for the main analyses. One uncer tainty that needs to be mentioned is the possible effect of lowering the level of one pollutant on the level of co-pollutants. The document should address that multi-pollutant modeling in the risk assessment assumes co-pollutants are unchanged across altern ative standards and should discuss the implications for such an assumption. Key poi nts and issues should be addressed in the document, with supporting additional details located in appropriate appendices.

In closing, the CASAC was pleased to review the second draft of the REA for the primary NO x review. We look forward to review ing the completed draft in the near future and to continue to advise you as the Agency completes the ANPR.

Sincerely,

/Signed/

Dr. Rogene Henderson, Chair Clean Air Scientific Advisory Committee

Enclosures

### NOTICE

This report has been written as part of the activ ities of the EP A' s Clean Air Scientif ic Advisory Co mmittee (C AS AC), a Federal advis o ry comm ittee independently chartered to provide extram ural scientific inform ation and advice to the Adm i nistrator and other offici als of the EPA. The CASA C provides balanced, expert

assessm ent of scientif ic m a tters related to issues and problem s facing the Agency. This report has not been re viewed for approval by the Agency and, hence, the contents of this repo rt do not necess a rily represen t the v i ews and policies o f the EPA, nor of other agencies within the Executiv e Branch of the Federal governm ent. In addition, an y m e ntion of trade n a m e s or comm erc i al p r oducts does not con s titu te a

recomm endation for use. CASAC reports are posted on the E P A W e b site at: http://www.epa.gov/casac

.

78 Enclosure A 

### U.S. Environmental Protection Agency Clean Air Scientific Advisory Committee Oxides of Nitrogen Prim ary NAAQS Review Panel

CHAIR Dr. Rogene Henderson , Scientist Emeritus, Lovelace Re spiratory Research Institute, Albuquerque, NM

CASAC MEMBERS 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 Crapo , Professor of Medicine, Department of Medicine, National Jewish Medical and Research Center, Denver, CO

Dr. Douglas Crawford-Brown , Professor and Director, Departme nt of Environmental Sciences and Engineering, Carolina Environmental Program, Un iversity of North Carolina at Chapel Hill, Chapel Hill, NC

Dr. Donna Kenski , Data Analyst, Lake Michigan Air Di rectors Consortium, Des Plaines, IL

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

Dr. Jonathan M. Samet , Professor and Chair of the Depa rtment of Epidemiology, Bloomberg School of Public Health, Johns H opkins University, Baltimore, MD

CONSULTANTS

Professor Ed Avol , Professor, Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA

Dr. John R. Balmes , Professor, Department of Medi cine, Division of Occupational and Environmental Medicine, University of California, San Francisco, CA

Dr. Terry Gordon , Professor, Environmental Medici ne, NYU School of Medicine, Tuxedo, NY

Dr. Dale Hattis , Research Professor, Center for Tec hnology, Environment, and Development, George Perkins Marsh Institute, Clark University, Worcester, MA

Dr. Patrick Kinney , Associate Professor, Department of Environmental Health Sciences, Mailman School of Public Health , Columbia University, New York, NYDr. Steven Kleeberger , Professor, Lab Chief, Labor atory of Respiratory Biology, National Ins titu te of Environm ental Health Scie nces, Nation a l Ins t itutes of Health, Research Triangle Park, NC

Dr. Timothy V. Larson , Professor, Departm e nt of Civ il and Environm ental Engineering, University of W a shi ngton, Seattle, WA, USA

Dr. Kent Pinkerton , Professor, Regents of the Univer sity of California, Center for Health and the Environm ent, Unive r sity of California, Davis, CA

Dr

. E d wa r d P o s t l e t h wa i t , Professor and Chair, Departm e nt of Environmental Health Sciences, School of Public Health, Univers ity of Alabam a at Birm ingha m, Birm ingham, AL

Dr. Richard Schlesinger , Associate Dean, Departm e nt of Biology, Dyson College, Pace University, New York, NY

Dr. Christian Seigneur , Vice President, Atm o spheric & Environm ental Research, Inc., San Ra m on, CA

Dr. Eliz a b eth A. (Lianne) Sheppard , Research Professor, Biostatistics and Environm ental & Occup a tiona l Health Sc iences, Public Health and Community Medicine, University of Washington, Seattle, WA

Dr. Frank Spei z er , Edward Kass Professor of Medici ne, Channing Laboratory, Harvard Medical School, Boston, MA

Dr. George Thurston , Professor, Environm ental Me dicine, NYU School of Medicine, New York University, Tuxedo, NY

Dr. James Ultman , Professor, Chem ical Engin eering, Bioengineering P r ogram , Pennsylvania State Universi ty, University Park, PA

Dr. Ronald Wyz g a , Technical Executive, Air Quality Health and Risk, Electric Po wer Research In stitu te, Pa lo Alto, CA

SCIENCE ADVISORY BOARD STAFF Dr. Angela Nugent , Designated Federal Officer, 1200 Pennsylvania Avenue, NW 1400F, W a s h ington, DC, Phone: 202-343-9981, Fax: 202-233-0643, ( nugent.angela@epa.gov )

9Enclosure B: Compilation of Ind i vidual Panel Member Comments on EPA’s Risk and Exposure Assessment to Support the Review o f the NO 2 Primary National Ambient Air Quality S t a ndard: Firs t Draft

This enclo s u r e contains the prelim inary and/or final written comments of individual mem b ers of the Clean Air Scien tif ic Advisory Comm ittee (C ASAC) Oxides of Nitro g en Prim ary National Am bient Air Quality Standards (NAAQS) Review Pa nel. The comm ents are included here to provide both a full pers pective and a range of individual views expressed by panel m e mbers during the review process. Th ese co mments do not represen t the v i ews o f the CASAC or the CASAC Pan e l.

Comments Received :

Comm ents from Prof. Ed Avol

..................................................................................................... 11 Comm ents from Dr. John Balm es

................................................................................................. 16 Co mments from Dr. James Crapo

................................................................................................. 19 Co mm ents from Dr. Do uglas Crawford-Brown

........................................................................... 21 Comm ents from Dr. Terry Gordon

............................................................................................... 27 Comm ents from Dr. Dale Hattis

................................................................................................... 31 Comm ents from Dr. Donna Kenski

.............................................................................................. 33 Comm ents from Dr. Patrick Kinney

............................................................................................. 37 Comm ents from Dr. Steven Kleeberger

........................................................................................ 39 Comm ents from Dr. Timothy Larson

........................................................................................... 41 Comm ents from Dr. Kent Pinkerton

............................................................................................. 44 Comm ents from Dr. Edward Postle thwait

.................................................................................... 48 Comm ents from Dr. Arm i stead Russell

........................................................................................ 50 Comm ents from Dr. Jonathan Sam e t

............................................................................................ 54 Comm ents from Dr. Richard Schlesinger

..................................................................................... 57 Comm ents from Dr. Christian Seigneur

....................................................................................... 59 Comm ents from Dr. Elizabeth “Lian n e” Sheppard

...................................................................... 60 Comm ents from Dr. Frank Speizer

............................................................................................... 64 Comm ents from Dr. George Thurston

.......................................................................................... 69 Comm ents from Dr. James Ultm an

.............................................................................................. 72 Comm ents from Dr. Ronald W y zga

............................................................................................. 73

10Comm ents from Prof. Ed Avol

Comments on the Second Draft NO2 Ri sk Exposure Assessment Document Ed Avol, CASAC NO2 Primary R e view Pa n e l

Characteriz a tion of Air Quality (Chaps 2, 6, and 7): This second draft is a marked improvement over the previous version. There is additional detail, explanation, characterization, and continuity of presentation in the revised doc ument. Several alternative approac hes to the air characterization analyses have been developed and pres ented, and provide a useful perspective on consideration of the current standard and the basis for re-consideration.

The discus s ion of on-road and roadway-related exposures is timely, important, useful, and insightful. To be complete, however, it is important to note that not ALL expos ure is determined by roadside vehicle exhaust at a height of a few meters. Even on-road, the hot exhaus t from on-road heavy- duty trucks (most o f w h ich have elevated pipe exhaust systems) w ill tend to rise. Similarly, exhaus t from rail locomotive s, from cruise and cargo vessels in port communities , and from stationary boilers and power pla n ts will contribute to higher exposure concentrations at elevations of several meters. Accordingly, blanket assumptions about se veral-fold increases in ambient air concentrations at ground level compared to several meters above the ground may be mistaken in several important exposure scenarios.

The discus s ion of uncertainty and variability is an important one and should be in the document, but in my opinion, is somew hat out of place and better located in an appendix, with a shortened summary in the main text. Moreover, essentially the same discussion is presented in more than one secti on of the document ( again in Chapter 9), so some editing is suggested.

Characteriz a tion of Health Effects Evidenc e and Selection of Po tential Alternative Standards (Chaps 3,4,5): The health evidenc e has been presented in a useful and detailed manner, although in some sections (see detailed com m ents below ), it seemed a presentation of the data was being made rather than a summary of findings from the ISA document. The challenging topics of susceptibilit y and vulne r ability wer e again pre s ented and described, and in this presentation, a cl earer differentiation between the two has partially em erged. The challenge and objecti ve for staff should now be to maintain consistent and discrete separation bet ween these working definitions.

Characteriz a tion of Exposure (Chaps 6, 8): It was somewhat surprising that the occasi onally presented lower benchmark value of 50ppb NO2 was not consistently carried through the various presentations of health, alternative standards, and expos ure characterizations. If this was an intentional decision, then a justification for thi s omi ssion and path of action should be pres ented for evaluation.

11The issues of on-road and in-vehicle exposur es are important ones thankfully discussed in the revised document. While there are st i ll some portions of the discussion that would benefit from additiona l comment and data (including consideration of increased on-road speeds leading to higher air exch ange rates, and pot entially important differences in decay of pollutants with distan ce from roadside as a function of time of day and meteorologic a l conditions (interwov en with temporal and s patial activities and opportunities for exposure), the presentation was generally focused, well-done, and appropriate.

(Review of Chapter 8 is delayed until the revi sed draft chapter is provided by s t aff)

Characteriz a tion of Health Risks (Chaps 7,8,9): The range of potential health effects benchm arks does seem appropriately dis c ussed, but the appearance/disappearance of 50ppb as a presented level for consideration in the presentation seems odd. The ED visits discussion related to Atlanta appeared to be well-done (but out of my immedi ate are of expertise). Given that Atlanta is the single location ev aluated, some discussion would be appropriate as to why Atlanta is representative of the country (aside from the fact that da ta was available for it).

(I await receipt of Chapter 8 to provi de additional comments for consideration)

Specific Editing Comments and Questions Page ii: Section 5. font changes in listing; make consistent

Page vi: several abbreviations missing from l i sting: BAL, CAMP study, ECP, EDAA, EDRA, MS, P M N

P4, Figure 1-1: (top right box, “qualitative ch aracterization of US epidemiology studies” – Throughout the docum ent, there are references to relevant European/ Australian/ Mexican/Norwegian res earch results, so thi s comment is inaccurate. (Note – if the notation “NO 2 ” were changed to “pollutant ”, this figure would be generically applicable to virtually all subsequent REA doc uments)

P9, lines 25-26 (“...model-base estimates indi cate that NO2 levels in many non-urban areas of the United States are less than 1ppb...”): What level of confidence is there for assigning modeled c oncentrations to areas with little or no actual measurements? Have spot assessments confirmed that levels in non-urban areas are in fact less than 1ppb, or is this a modeling artifice imposed by boundary conditions of the application ?

P11, line 21 (...”because most sources of NO2 are near ground level...”) – I assume you’re actually talking about on-road traffic tailpipe emis sions, so why not be explic itly clear? Also, this is not always true (see discussion abov e regarding emissions from HDD trucks, locomotives, ships, boilers, etc.

12P11. line 24 (...”levels are likely even higher at elevations below 4 meters...”) – I would certainly agree that this is broadly true, but there are not able except ions with elevated exhaust, such as from trucks, trai ns, ships, boilers, power plants, e t c, so this is not a universal truth...

P14, line4: “evaluates” should be “evaluated”

P14, lines 24-25 (...there is only limited supporting evidence fr om clinical or toxicologic a l studies on potential susceptibil ity to NO2 in persons with cardio vascular disease...”) : but aren’t there also just limited studies of these people, period?

P15, lines 11-17 (paragraph on cr iteria that must be met for establishing usef ul links between polymorphis m s and adverse respirator y effects): I agree wit h these points, but don’t these three criteria (involvement in the pathogenesis pathway, observable functional c hange, and careful consideratio n of possible confounding) equally apply to every potential adverse health effect?...so it seems to me, this pa ragraph is either broadly generic and applic able or unnecessa ry in this specific section.

P17, lines 1-4 (discussion of violence and elevated risk of exposure): what about confounder s, such as being more likely to be “out on the streets”, or in closer proximity to traffic, or other environm ental justice angles (more li kely to be closer to higher exposure areas such as train yards, truc k depots, shipping docks – less affluent areas)? In other words, there a num ber of potentially confounding variables, so making any sweeping general conclusions is simplistic and probably incorrect.

P19, line 12 (and in multiple locat i ons th roughout the document)” re peated reference is made to the “last revi ew of the NO2 NAAQS” , but it would be more useful to readers and more accurate to refer to the date of the last review (1995?) rather than “the last review”, to underscore the time period unt il now and the opportunity for new and more refined research to have been performed but not yet have been considered...

P19, lines 14 and 15 (“...children and older adults....”): referenc e in a consistent manner to ages would be helpful to anchor the discu ssion, e.g. “...children (<18yrs) and older adults (>65yrs)...”

P22, line 2 – spell out what CAMP stands for (and place it in the abbreviation table)

P22, line 5 (“...each subject having an approxim ate average of tw o months of data...”): This is poorly worded and inaccurate (an “ approximate” average wa s not presented, the mathematical average was; I assume the “appr oximate” part refers to the tw o months’ time period?), and should be re-worded.

13P22, line 1 6 (“...intervention study in Australia ...”): this is scientifically fine (as far as I am concerned) , but it is inconsistent with your earlier declaration about emphasizing only US studies.

P24, line6 – “sites” should be “cites”

P25, lines 20-31: This section seems pretty detailed and more suited to the IS A; the findings should be summarized here, not pres ented in detail. Additionally, BAL, ECP, and PMN should also be placed on the Abbrevia tions listing and defined in the text when they first appear.

P26, line 11 – replace “and” with “or”

P29, line12 – “thrombos is”, not thombosis

P32, line 4 – the presentation would be ma rkedly improv ed with a two-column summary table for short-term N O 2 exposure effects, listing the endpoi nt (respiratory, mortality,...) and the ISA determination (causal, insufficient,...)

P41, line 3- 7 – In a previous discussion (P19, section 4.2.2, lines 23+), the Linn study was down- weighted (if not dismissed) for usi ng having em ployed one-pollutant modeling; here it is identified as appropriate for use and included; isn’t this inconsistent?

P42, Figur e 5.1: include EDRA and EDAA to Abbreviat i ons listing

P43, Figur e 5.2: include MS in Abbreviations listing

P45, line 9 – change “thee” to “three”

P51, lines 8-10: Delete the sentence begi nning with “while an individual ambient monitor...” since it adds nothing to the discussi on and is a duplicat ion of part of the next
sentence.

P58, lines 14 and 20 seem to be contr adictory; it see m s to say near-road measurements were used to calculate on-road NO2 in Line 14, then say near-road measurements were not used in Line 20...???

P72, lines 16-18: if NO2 le vels are generally declining and vehic l e exhaust is the primary source, how to explain the increas e in exceedances between 2004-2006 and 2001-2003 data sets?

P72, line18: replace “that” with “than”

P91, line 1 (“...if the monito rs are not evenly distributed (causing a bias)...”): one doesn’t nec essarily always follow the other. If the monitoring su rface is both smooth

14and rough terrain, evenly distributed samplers can miss the variability in the rough terrain (in valleys, up hills, etc) and over-report the smoo th terrain.

P92, line 15: change “being” to “of this bias would be”

P95, line 16: change “froma” to “from”

P95, line 18: change “selecting monitors thes e monitors” to “selecting these monitors”

15Comm ents from Dr. John Balm es

John Balm e s

GENE RAL COMMENT S

Characterization of Health Effects Eviden ce and S e lec tion of Potential Alte rnative Standards for Analysis (Chapters 3, 4, and 5)

1. The presentation of the NO2 health effe cts evidence is based on the information contained in the NO2 Integr ated Science Assessm ent. Wh a t ar e the views of the Panel on the overall characterization of th e hea l th evid e nce for NO2? To what exten t is the presentation clea r and appropriately balanced?

Overall, I feel that the p r esentation o f the NO2 health effects evid ence in Chapters 3 and 4 is clear and appropriately balanced.

2. The specific potential alterna tive standards that have been selected for analysis are based on both controlled human exposure studies and on epidem iological studies conducted in the United States. What are th e Panel’s views on the appropriateness of these potential alternative standards (in te rms of indicator, av eraging time, form, and level) for the purpose of conducting air qual ity, exposure, and risk assessments and on the rationale used to sele ct them for that purpose?

I feel quite strongly that the epidem i o logi cal evidence supports a short-term averaging tim e, i.e., an annual standard is not the av eraging tim e appropriate to protecting persons with asthm a from developing exacerbations that result in health care utilization. I think the epidem i o logical data best support a 24- hour averaging tim e , but controlled hum a n exposure study data better support a 1-hour av eraging tim e. The alternative standard f

o rm s and levels th at Ch apter 5 s t a t e s will be con s idered in th e subsequen t risk analy s is are appropriate and reasonably well justified.

Characterization of Health Risks (Chapters 7, 8, 9)

1. Based on conclusions in the final ISA re garding airway responsiveness, we have expanded the range of potential health eff ect benchmark values to include 0.1 ppm. Do Panel members have comments on the range of potential health effects benchmark values chosen to characterize risks associated with 1-hour N O 2 exposures?

The range of potential health effects benchm ar k values chosen as described in Chapter 5 is appropriate, but there is inconsistency in how these valu es are app lied in Chapters 7 and 9. In Chapter 5 (p. 44, lines 16 -17), it is s t ated that 0.05 ppm will be considered in the risk assessm ent. I support doing so, but in Chapter 7, exceed ance data for 0.05 ppm are not presented in the tables. In fact, data for 0.1 ppm are not cons is ten t ly presen ted. To im prove clarity and avoid confusion, I sugge st being consistent in the application of potential health effect benchm ark values.

162. To what extent are the assessment, interp retation, and presentation of health risk results technically sound, clearly com m unicated, and appropriately characterized?

The presentation of health ri sk results is technically sound, clearly communicated, and appropriately characterized.

In addition to the prom ulgation of a short-term standard, I also thi nk that consideration should be given to retaining an annual standard to protect children from potential adverse effects of NO2 on growth of lung function.

3. A focused risk assessment has been conduc ted for emergency departm ent visits in Atlanta, GA. To what extent are the assessm ent, interpretation, and presentation of health risk results technically s ound, clearly com m unicated, and appropriately characterized? What are the views of th e Panel on the approach taken and on the interpr e ta tio n of the r e su lts of this an alysis?

The Atlanta-based risk assessm en t of the im pact of varying NO2 air quality standards is an appropriate approach to pr ovide useful information to policy m a kers about the public health im pa ct of a lte rnative standard s.

4. What are the views of the Panel regarding the clarity and adequacy of the discussion of uncertainty and variability with respect to the charac terization of health risks?

The discussion of uncertainty and variability is reasonably clear, but there is som e needless repetition. Chapter 7 contains an in-depth discussion of uncertainty and variability. It seem s unnecessary for Chapter 9 (S ection 9.6) to repeat this discussion in

so m u ch detail (to th e po int of using som e identical text. Th is section of Chapter 9 would be im proved if it placed the key issues regard ing uncertainty and vari ability in th e risk

assessm ent in context. S p ecifically, how i m por tant are the various so urces of uncertainty and variability in a relative sense, and how should they im p act the interpretation of the results ? As curren tly wr itten, thes e q u estions are lost in the sy stem atic listing of all sources of uncertain ty and variability.

SPECIFIC COMMENT S

p. 13, lines 18-21 Diet is anothe r factor that m a y affect vul nerability to NO2. A diet low in antio x idant m i cro nutrients likely increases vulnerability to NO2.

p. 18, lines 5-11 The REA us es the sam e five -level hierarchy to assess the level of evidence for a causal relationsh i p th at was discussed by CASAC during the SOx m eeting on 7/30-31/08. The panel wrote about the use of this hierarchy as follows: “W e concur with using the five levels but recom m e nd that th e descriptions be chan ged to better reflect the lev e l of certainty o r confidence in the cl assification of the level of evidence. The phrasing of the second level is particularly problem atic in its addition of the wording

17‘lik ely cau sa l re lationshi p.’ The app r oach to evidence in terpretation should avoid using statistical significance as a criterion for ev idence interpretation. CASAC recomm ends that EPA reconsider the language used to descri be the weight of evid ence, particularly for the firs t three catego r ies which cover a ra nge of certainty or confidence in causal inference that extends from full certainty to lesser degrees. T h e language used should be consistent w ith other such schem e s used by EPA.” The panel’s previous comm ents about this hierarchy are relevant here.

p. 23, lines 21-24 The statem e n t, “In the laboratory, airway responses can be

m easured by assessing changes in pulm onary function (e.g., decline in FE V1) or changes in the inflamm a tory response (e.g., using m a rk ers in bronchoalveolar lavage (BAL) fluid or induced sputum ) (ISA, section 3.1.3),” is som e what m i sleading in a sub-section entitled “Airway Responsiveness.” Bronchoalv eolar lavage and induced sputum cannot be used to d i rectly ass e ss airway resp onsiveness.

p. 25, line 21-p.26, line 11 Unlike enhanced lung function responses to inhaled allergen after NO2 exposure, the discussion of airway inflamm a tory responses to inhaled allergen do not properly fit under the sub-sec tion title of “Airway Responsiveness.” I would m ove this discussion to the next sub-section (4.2.6) on “A irway Inflamm a tion.”

p. 95, line 3 Ozone would be a better exam ple of a reactive po llutant with a low indoor/outdoor ratio than PM2.5.

p. 95, line 13 Should be “from a m a jor road...”

p. 116, lines 1-4 Should be “For exam ple, changing from a 98th percentile 1-hour daily m a ximum standard based on 0.1 ppm to one based on 0.05 ppm reduces the estim ated incidence of respir atory-related ED visits in Atlanta by about 49 percent in 2007 (from 4700 to 2400);...

18Co mments from Dr. James Crapo

Review Comments Prepared by : James D. C r apo MD Risk and Ex posure Asse ssment to Support the Review o f t h e NO2 Pri m ary Natio n al Amb i ent Air Quality Standard: Second Draft

Charact e rizati on of H e alth Effect s Evide n ce and Selec t ion of P o ten t ial Alternative Standard s for Analysi s (Chapters 3, 4 an d 5).

Charge que s tion 1: Wh at are the vi ews o f the Panel on the overall characterization of the health evidence for NO2 ?

This REA d o c u ment appropriately reflec t s the NO x IS A in summari zing conclusi ons regarding the currently av ailable health evidence related to NO2 ex posure s. Thi s se cond draf t of the REA i s substanti a lly improved, and I would conc ur with the pr imary conclu sions th erein. The ch oice to o express th e overall evalu a ti on of the d a ta on th e maj o r findings in terms of five levels of “confidence” i s applauded

, since a c o n s istent applic ati o n of thi s app r oach c a n bring a new lev e l of rigor and c o nsi s tency to this type of e v aluati on. Th e REA c o nclu des th at a “lik ely causal relation ship” can be inferred from the data for short-term NO2 exp o sure and ad verse effects on the respir ator y system at n e ar ambien t levels of exp o sure – and th at the su scep tible populati ons include subje c ts with asth ma or AH R and the yo ung and elderly. The ISA and the REA concl u de that th ere is suggestive, bu t not sufficien t data to infer a cau s al rel a tionship between sh ort ter m near ambien t NO2 expos u re and cardiop u lm onary m o rtality and between l o ng-term NO2 exposure and respiratory morbidity. The exi s ting data i s con s idered inadequate to infer th e presence or absence of a r e lation ship be tween l o ng-te r m near ambi ent NO2 expo sure and over all mortality

.

The ba sis f o r the abov e co nclusion s sh o u ld be more c l early defined in the REA

. Both the ISA and the REA alleg e that the primary conclu si ons on Health Evidence ar e based on an application of 7 of the Hill criteria: str e ngth of associati o n, experimental evidence, consi s tency

, biological plausibility, c o herenc e, temporal relationship and the presence of an exp o sur e -r espon s e relation ship. The REA should refer to each of th ese criteria and assess the d a t a with re spec t to them for eac h of the maj o r conclusi ons. This w o uld greatly streng then the pre s entati on of th e REA and mak e the basis f o r the final con c lusion s clear. As curren t l y written on e gets the impressi on th at the 7 criter ia were inc o n s istently considered in com i ng to the fin al conclu sion s. In the judgment of thi s reviewer, the pr imary co nclu sion regarding adverse r e sp iratory health effects on sensitive popul a tions exposed to near ambi ent NO2 woul d meet all 7 of the Hill criteria that were put forward as stan dards f o r d a ta as se ss me nt.

There i s difficulty in comparing the resul t s of epidemi o logic studies and those of human clinic al studies in ter m s of exposu re levels f o r shor t-term dose. Hum a n cli n ical studies i n volve
measurement s

of NO2 exp o sure at th e breathing zon e of the subje c t while the e p idemiology studies rely on distan t, fixed monitor s

th at are c o mm only 4-5 meter s

high. There needs to be a discussion of the projec ted relation ship between the effective dose in these two very different circumstances. If breathin g zone NO2 levels are com m only sub s tantially higher than th at

meas ured at a fixed moni t o r at 4

- 5 met e rs height , th en the REA should make adjustmen t s in its discussion of how epidemi o logy and clin ical studie s ar e used t o

pro j ect and as se ss lev e ls th at are used in risk assessment.

19Charge question 2: What are the Panel’ s vie w s on the ap propriateness of the potential alternative standards for t h e pu rpose of conducting air quality, exposure, and risk assessments and the rational used to select them?

R e v i e w C o m m e n t s

- C r a p o P a g e 2

The prop osed alternative standards f o r analysi s ar e ap propriate. I would concur with the choice of NO2 as the indicator

, 1 hour as the av eraging time, the 98 th or 99 th percentile as th e form and levels from 0

. 05 to 0.20 pp m as th e levels to be c o n s idered when modeling the effect of a revised stand a rd. Having agreed with the ulti mate recommend ati o ns, I would l ike to see a strong er and more det a iled defense of t h ese deci sion s in the te xt of the REA. The choice f o r averaging tim e als o

include d a con s idera t ion of a 24 h o ur st andard

. The s t rengt h s and limitation s of focusing on 1 hr instead of 24 hrs need to be mor e fully defended. The ration ale for choosing the 98 th or 99 th percentile as the f o rm needs a substan t ially greater discussion r a ther than ju st noting that thi s f

o rm was chosen for an alysi s of P M

. The strength s an d weakne ss es

of using this type of form dep e nd on the sh ape of th e exposure curv e and the degr ee to w h ich t h e 98 th or 99 th p e rcentile reflects both the magnitude an d ex tent of hi gh level exposures than c a n be expect ed for these p o pulat i ons. Th e ch oice of e x posure levels to be cons ider e d was said t o

be based on both epidemiology studies and contro lled h u man exp o su res – however the sub s equ e nt discussion and tables 5

- 1 and 5-2 discuss only th e epi d emiology. This section sh ould more clearly descri be how the c o ntrolled hu man exp o sur e s wer e used to establi s h or validat e th e proposed ran g e for NO2 analysi s . Sinc e the sub s eq uent exp o sur e analy s is will be based on ambient air measurements of NO2 it is essenti a l to di scuss th e comparability of levels measu r ed in the breathi n g zone for c o ntrolled hu man exp o su r e s with those obtained fr om ambient m o nitor s located at hei g hts of 4

- 5 m e ters.

The REA also needs a discu ssi on of th e u t ility of the cu rrent long-ter m stand a rd f o r NO2. A revised stand a rd focu sed on short-term NO2 levels is being considered. Would this replace th e long-term standard?—or would it be an additional standard. If it is contemplated to retain th e current long-term standard , then thi s needs a detailed analysi s

.

20Co mm ents from Dr. Do uglas Crawford-Brown

Comments on Risk and Exposure Assessmen t (REA) to Support the Review of the
NO2 Primary National Ambient Ai r Quality Standard: Second Draft

Douglas Craw ford-Brown (3-9-08)

This review is built around the charge quest ions provided. I f o cus on Chapters 3, 4 and 5,
and then on chapters 7, 8 and 9.

First, a m o re general comment is appr opriate. T h e overall R E A is both a good step

f

o rward f r om the f i rst d r af t, and con t ains a wealth of usef ul m a terial. I w ill n eed to

withhold co mplete judg m e nt until Chapter 8 is com p lete, but the existing chapters are
generally in good shape and m a ke for a com p e lling argum ent. There is strong consistency

between this docum ent and the IS A, with cavea ts noted la ter.

There is, however, a need for a global edit of the docum ent. The chapters differ in writing
style and even, to som e extent , in the way they have used t h e I S A mat e r i al . Ther e al so

seem s to m e m o re detail in the Appendices than are reflected in the docu m ent. It is
appropriate for their to be m o re technical detail, but I felt that the Appendices suggested

that m o re detailed studies had been done yet not reflected in the m a in docum ent. I m a y be
wrong about this, but I did get th is sense, and it again sugge sts the need for a global edit
to be sure all of the chap ters, and the m a in document and Appendices, are consistent.
Finally, the levels of exposure considered don’t seem to m e c ons istent throughout. Each
chapter and section should us e identical ranges of values.

For Chapters 3, 4 and 5:

1. The prese n tation of the NO2 health effe cts evidence is bas ed on the in formation
contained in the NO2 Integrated S c ience Assessment. Wh at ar e the views of the

Panel on the overall ch aracterization of the he alth evidence for NO2? To what extent is
the presentation clear an d appropriately balanced?

21The authors have done a good job of track ing th rough the IS A and cullin g the m o re

im portant results. These results have then been su mmarized quite well in the REA an

from the basis for the assessm ent.I found it quite easy to follow th e discussion although,
as noted in my general comments, I had a sense that there w a s m o re detail in the
Appendix than is evident in the body of these chapters.

I notice that only the hum a n data seem to play any sort of role in the assessm ent. I had
thought that the anim al data were at least go ing to play som e modifying role, although I

adm it we had decided on the CASAC that th e hum a n data would form the prim ary basis
for setting the health benchm arks. At the le ast, the docum ent should explain the lack of

use of the anim al data.

I also feel the ISA provided a better understand ing of the issue of sensitive, susceptible,
vulnerable populations. Why is there no m e ntion of infants throughout? T h ere is
significantly m o re nuance and s ubdivision of populations in th e ISA, and it was just odd

to find so little included in the REA. I suppose the decision may have been m a de to
abstract the ISA discussion and use only the m o st im portant results for the REA, but if
this is the case, it should be explained. I also suppose the results m i ght be the sam e if
they were culled out as a special subpopulation, but can’t tell from the analysis.

I agree with the decision to us e th e studies for which the c onclusion is “... the available

evidence is s u fficient to infer either a causa l or a likely casual relationship”. However,
this judgm ent is in trodu ced with little suppor ting justification

. As it m a y s e t a precedent

for further REAs, it deserves a bit of disc ussion both in the docum e nt and in CASAC
deliberations. Fortunately, the issue is not so pr essing since, even if one uses this set of
criteria, the evidence is sufficient to suppor t the EPA assessment and to m a ke a good case
for regulatory consideration.

Finally, am I correct that the indoor NO2 exposure studies are playing no role? This is a
bit odd, given that they seem to m e t o be studies focused largely on NO2 exposures by

22them selves, which is pre c ise l y what we are tr ying to get at here. Or is the assum p tion

m a de that they, too, are confounded by other expo sures? At the least, there needs to be a
better explanation as to why these st udies are being rejected f o r use.

2. The specific po tentia l altern ative standards th at have been selected for analysis are
based on both controlled human exposure studies and on epidemiological studies

conducted in the United States. Wh at are th e P a nel’s views on the appropriateness of
these potential alternative standards (in term s of indicator, averaging time, form, and
level) for th e purpose of cond ucting air quality, exposure, and risk assessments and on
the rationale used to select them for that purpose?

I first note that I was pleased to see an assessm ent based on both the clinical and
epidem iological studies. This was a good step forward in letting the latter results play a

role.

I support the use of NO2 as the Indicator , if for no other reason than that I don’t know
how any other indicator would be implem ented.

I support the Averaging Time suggested, although would like to see som e discussion of

the im plications of a daily aver aging tim e, as it links m o re di rectly to the epidem iological

studies. But I doubt this would ch ange the level of exposure selected. And in nay event, I
don’t think the epidem iological studies can fully support the choice of a daily average

value, s i nce there is a lot of intra-d a ily va riab ility at a lo cation

, and this m eans the
appearance of health effects m a y not be related to the daily average (but rather to shorterterm periods of elevation throughout the day).

On the Form , I wasn’t clear how this 98 th or 99 th percen tile issue is to be dealt with

m e thodologically. The docum e nt would prof it from having an exam ple stream of

m easure m ents, then showing how they are to be abstracted down to som e sort of

cum u lative distribution function and the 98 th or 99 th percentile estim a ted and then
averaged. I support the use of the 98 th or 99 th percentile as at l east a good policy choice (I

23am not sure it has any real sc ientif ic basis – whic h is not to say it goes against the

scienc e, only that it is n o t rea lly a sc ientif ic issue), but just am not clear what it m e ans

m e thodologically.

As to the Level, I am aga i n supportive, both of the lower and upper bounds selected.
However, there is a reasonable argum e nt to be m a de that the incidence of hospital

adm i ssion for asthm a tics m a y be high even at th ese levels. And the levels don’t reflect, in
my kind, any sort of m a rgin of safety. So ther e is m e rit in at least considering shifting the
range down by factor of 2 or so. Still, I susp ect th e current ran g e c ontains a value likely

to em erge as the Level for the final NAAQS.

For chapters 7, 8 and 9:

1. Based on conclusions in the final ISA re garding airway responsiveness, we have
expanded the range of potential health ef fect benchmark values to in clu d e 0.1 ppm.

Do Panel members hav e comments on the ra nge of poten tial health effects benchmark

values chosen to characterize risks associated with 1-hour NO2 exposures?

I support this decision, especially since the fraction of asthmatics showing response at
between 0.1 and 0.2 ppm (or 0.15) is so high. As I noted in the answer to Q u estion 2
above, there is at least an argum ent to be m a de for a further reduction below 0.1 ppm

based on a m a rgin of sa fety, but I am com f orta ble that the expansion of the range down to
0.1 ppm now encom p asses the range of values likely to be considered seriously in
regulation.

2. To what extent are th e assessmen t , interp retation, and presentation of health risk

results tech nically sound, clearly communi cated, and appropriately characterized?

I found this a section that was easy to fo llow, and support the unde rlying m e thodology. I

will withho ld full judgment until Ch apter 8 is pr esented and integ r ated, as that is where

the wheels m a y fall off. But the m e thodology fo r estim a ting health im pa cts contingent on

24exposure is well developed and sophisticated. Th e one point that will need clarity is how

the health ef fects can be rela ted properly to the spatial gr adient of exposures in the
epidem iological studies and in actual populat ion exposures. T h is is an area that will
require m o re substantive discussi on of uncertainties, as I suspect it is an important driver
of the results. It is also importa nt to note that exposures close to roadways are likely to be
controlled not just by the concentration field (w hich is considered in the assessm ent) but
by m ode choice in trav el, which in turn is know n to be affected by the q u ality of the built

environm ent (i.e. how attractive and safe it is to walk or bike near roads). T h is again is an
issue of uncertainty and not assessment m e thodology, since there is no good way to
account for this at present.

3. A focused risk assessment has been cond ucted for emergency department visits in
Atlanta, GA. To what extent are the assessm ent, interpre tatio n , and presentation of

health risk results techn i cally sound, clearly communicated, and appropriately
characterized? What are the views of the Panel on the approach taken and on the
interpre tatio n of the res u lts of this a n alysis?

I am generally supportive of this analysis. It was well written and sim p le to follow, and

m a kes a good addition to the other analyses in supporting the case being m a de overall in

the REA. Atlanta seem s to have been a good choice, leading to (som ewha t) clear
conclusions). My sole concern is whether the baseline can really be established well. O n e year is used, but I worry about such a short baseline given the clim ate in Atlanta, which
can swing substantially from year to year. This can change both exposures and the
background incidence of related respiratory diseases. I would have preferred to see an
average taken over at least several y e ars as a b a seline, and sus p ect th e resu lts a r e driven
significantly by the choice of this baseline year.

4. What are the views of the Panel regarding the clarity and adequa cy of the discussion
of uncertain ty and varia b ility with r e spect to the character i z

a tion of hea lth risk s.

25As with the other REAs, I rem a in concerned that the ana l ysis of uncertain ty is so
qualitative. There has been so m u ch work done within the EPA on developm ent of tools
for uncertainty analysis, I don’t understa nd why there is the continued reliance on
qualitative studies. The reader is lef t with the im pression tha t all we can s a y is th at th e

results are uncertain to som e unspecified degr ee. An uncertainty analy s is need not be a
full Monte Carlo appro ach, with P D Fs fo r each param e ter and nesting of m odel
uncertainty, but there should at least be m o re quantitativ e statem ents about the key

param e ters and m odel form s that affe ct uncer ta inty, the sens itivity of the e s tim ates to

these com ponents, and som e idea as to how larg e of an error m i ght be introduced (and in
what direction). This would also greatly im pr ove the utility of the unce r ta inty resu lts in
the Appendix (around page 86) concerning exce edences. These seem to m e particularly

im portant re sults that d e serve a b it more reflection and analysis for uncertainty.

Variability is treated a bit better in ex isting REA, although there is still not a good
discussion of how variability and uncertainty are being separated; the purpose behind

each kind of analys is; o r how variability can at tim es affect uncertainty in the analyses
preform e d.

To be helpful, the uncertainty analysis s hould also provide better understanding as to why
the uncertainty exists. A summary code c ould be given for each source indicating

whether th e issue is one of represen tativen ess (as in m onitor location s ), measurem ent

m e thodology, num b er of sa m p les, incom p lete scie nce to back a m odel, etc. It would then
be possible to target future resources on re duction of uncertainty. At som e point m a ny years ago, the EPA had a significant program aim e d at reducing residual uncertainty, and
that work or kind of approach doesn’t seem to be showing up in these REAs.

26Comm ents from Dr. Terry Gordon

Terry Gordo n

Charge Question Responses

Characte r iz a tion of Air Qua lity (Chapters 2, 6, a nd 7)

1. To what extent are the air quality charac terizations and analyses technically sound, clearly com m unicated, appropriately characteri zed, and relevant to th e review of the primary NO2 NAAQS?

The characterizations and analyses appear to be sound and clearly comm unicated.

2. In order to simulate just meeting poten tial alternative 1-hour daily maximum standards, w e have adjusted NO2 air quality le vels using the same approach that was used in the first draft to si mulate just meeting the current annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

To the extent of m y somewhat low level of expertise in this ar ea, I understood a great deal m o re of the approach in this draf t of the REA. Therefore, I’d say the approach appears to b e clearly co mm unicated and characterized.

3. Because of the impact of mobile sources on ambient NO2, we have estimated on-road NO2 concentrations. To what extent is th e approach taken technically sound, clearly communicated, and appropriately characterize d? Do Panel members have comments on the relevance of this procedure fo r review ing the primary NO2 NAAQS?

This is qu ite relev a nt to the exposure of individuals to am bient NOx. Because the tim e spent ‘on-road’ m a y differ significantly am ongst MSA’s (i .e., traffic-dom inated Los Angeles vs. other U.S. cities), it m a y be appropr ia te to ex tend this an alys is with dif f

e re nt factors for low or high traffic/commuting.

4. What ar e the views of th e Panel regarding the adequacy of the assessment of uncertainty and variability?

The uncertainty and variability assessm e nt were thoroughly covered.

Characterization of Health Effects Eviden ce and S e lec tion of Potential Alte rnative Standards for Analysis (Chapters 3, 4, 5)

1. The presentation of the NO2 health effect s evidence is based on the information contained in the NO2 Integrat ed Science Assessm ent. Wh a t a r e the views of the Panel on the overall characterization of the health evidence for NO2? To what extent is the presentation clear and appropriately balanced?

27The characterization of the health evidence was q u ite clea r an d the decisio n pathway to choosing the appropriate benc hm arks was excellent. The one exception might be the explanation of the different choices of NOx exposure concentrations in the risk analyses. It took careful a nd repeated reading to understand w hy som e ana l yses would range from 50 ppb and up and why others starte d at higher values. Perhaps, a summ a r y paragraph at the beginning or end of the sec tion (5.5) would provide a clearer explanation of the pathway forward for the choices.

2. The specific potential alternative standards that have b een selected for analysis are based on both controlled human exposure st udies and on epidemio logical studies conducted in the United States. What are th e Panel’s views on the appropriateness of these potential alternative standards (in term s of indicator, averaging time, form, and level) for the purpose of conducting air qualit y, exposure, and risk assessments and on the rationale used to select them for that purpose?

The potential alternativ e standa rds are appropriately chosen. It is unclear, however, what

to m a ke of t h e current annual standard give n the language in the REA that states the “evidence is suggestive but not sufficient to infer a causal relationship between long-term NO2 exposure and respiratory m o rbidity”.

Characterization of Exposure (Chapters 6 and 8):

1. To what extent is the assessm ent, interpretation, and presenta tion of the results of the exposure analysis technically sound, cl early com m unicated, and appropriately characterized? W a iting f o r Chapter 8. 2. The second draft assessment document evaluat es exposures in Atlanta. What are the views of the Panel on the approach taken and on the interpretation of the results of this analysis?

W a iting f o r Chapter 8. 3. What ar e the views of th e Panel regarding the adequacy of the assessment of uncertainty and variability?

The assessm ent of uncertainty was very t horough although presenting it twice in the text and once in a table m a y be overkill.

Characterization of Health Risks (Chapters 7, 8, 9):

1. Based on conclusions in the final ISA regar ding airway responsiveness, we have expanded the range of potential health effect benchmark values to include 0.1 ppm. Do Panel members have comments on the range of potential health effects benchmark values chosen to characterize risks a ssociated with 1-hour N O 2 exposures?

I concur with the selected benchm ark and value.

282. To what extent are the assessment, interp retation, and presentation of health risk results technically sound, clearly com m unicated, and appropriately characterized?

Waiting for Chapter 8.

3. A focused risk assessment has been conduc ted for emergency departm ent visits in Atlanta, GA. To what extent are the asse ssment, interpretation, and presentation of health risk results technically sound, clearly com m unicated, and appropriately characterized? What are the views of th e Panel on the approach taken and on the interpr e ta tio n of the r e su lts of this an alysis?

The approach is excellen t and clearly communi cated. If this focus on one city will be used to project risk across the nation, it m i ght be appropriate to include other cities for valida tion / cr oss com p arison (Phila delphia was done previously?).

4. What are the views of the P anel regarding the clarity and ad equacy of the discussion of uncertainty and variability with respect to the characte rization of health risks. The assessm ent of uncertainty was very t horough although presenting it twice in the text and once in a table/conclusion m a y be overkill.

Minor Comm ents:

Page 13, line 27 – conduction disorders – heart or nerve? Page 13, line 28 – hypertension – vascular or pulmonary? Page 17, line 1 – Is the 4.3 ppb increase 24 hr or annual or 1 hr? Page 20, lin e 14 – Delete space after ‘12’ Page 24, line 6 – Change ‘sites’ to ‘cites’ Page 24, Table 4-1 and line 17 – The 76% listed on line 17 does not m a tch the 0.75 fraction in the Table. A l so, th ere appears to be a typo on the 2 nd row of data – the fraction for All Exposures (0.68) is higher th an both of its com ponents (Exercise is 0.59 and Rest is 0.67) Page 30, line 12 – chronic is m i sspelled Page 31, line 15 – fetal ‘growth retardation’? Page 42, Figure 5-1 – The legend says 95% CI but such data are not presented in the Figure. Page 46, line 11 – delete the 2 nd ‘to ’ Page 52, line 27 – a space is need ed between scenario and 4. Page 53, lin e 16 – It is u n clear what is m eant by “A screen in g...” because the previo us sentence already said th e am bient ai r quality data would be screened. Page 73, line 15 – ‘other tim e not’ is unclear Page 73, line 26 – insert ‘are’ before ‘provided’ Page 91, lines 7-17 – It is unclear why the ve rtical height discu ssion is included here rather than in the Spatial Representation sec tion 7 .4.4. I consider spatial/space to hav e 3 dim e nsions.

2930 Page 109, lines 1-4 – The wording is su ch that someone could grab this reasoning/sentence, even after the earlier careful elucidation of the potential for confounding by co-pollutants, to dismiss the c onclusions of the entire risk assessment.31 Comments from Dr. Dale Hattis

Dale Hattis—Premeeting Comment on Charge Qu estion 4 for the Analysis of Air Quality

3. Estimation of On-Road NO2 Concentr ations—Technically Sound? Adequately Characterized

In view of the prominence of on-road exposur es in the exceedance an alysis, I also think that it is important for the authors to document the underl ying data they use and do quantitative uncertainty analysis for key pa rameters that determine the results. In particular they should document their conclusi ons about the distribution of values for “m“ in equation 4 on p. A-107. The authors should do cument the m values they derived from each study and evaluate the uncer tainty in this value they infer for this key parameter from each study. Documenting the individual m values for each study would allow an independent assessment of the authors’ conclu sion that the data ca nnot be well described by a parametric distriibution (e.g., lognormal, normal, etc.) whose values are not limited to those directly inferred from the existing st udies. The current empirical distribution treatment implies that each observed “m” should be treated as having equal uncertainty/weight and that the differences in “m” values observed by the various authors under various circumstances should be consid ered to adequately represent the real variability that would be seen in a repres entative sample of roads in the locations modeled. In fact it is likely that the different measurements carry different uncertainties that could be assessed in a comparative an alysis of the likely errors in different measurements. Such an analysis could poten tially lead to different weighting of (1) measurements that were done with greater vs lesser accuracy (taking account relative confidence/measurement uncer tainties) and (2) measurem ents that were done under conditions of traffic volume and meteorology that are rela tively common vs relatively rare (taking into account the representativeness of the measur ed conditions relative to the real variability among sites, et c., that is being modeled).

4. What are the views of the panel regarding the adequacy of the assessment of uncertainty and variability?

The assessment at present is entirely qualitati ve. In my opinion there should be at least some quantitative assessment of some of the important sources of uncertainty. For example in previous comments on an earlier dr aft of the REA I reported that model-based analyses of the likely effect of distribution of elevations of monitoring heights indicated that NO2 concentrations observed at those hei ghts were likely to understate NO2 levels at breathing elevations of about 2 meters by 17-35% depending on the mathematical form of the function used for the decline of concentr ations with height. Instead of creating its own more sophisticated analysis of this issue, the current document simply repeats a dismissal of the issue as not lik ely to be substantial in the light of the fact that most monitors are not as elevated as the monito r studied in the paper that documented the likely bias with monitoring height. Where an approximate quantitative analysis of this bias is possible, I think it should be done.

It is also important to quantitatively analyze and discuss the model biases and uncertainties indicated in Figures A- 97 through A-99 on pages A-86 and A-87 of32 Appendix A. To my eye, these figures s uggest quite a bit of low bias in model predictions of observed exceedances, although th e figures are not especially clear on this point. It would be better to put obser ved exceedances on the y axis and predicted exceedances on the x axis, and also to include an identity line (y = x) to better show the reader the magnitude and direction of the biases.

Also please see my comment in response to que stion 3 on the uncertainties in the present estimation of on-road concentrations.33 Comments from Dr. Donna Kenski

Pre-meeting comments on 2 nd Draft REA for NOx Primary NAAQS Donna Kenski

Characterization of Air Quality

1. To what extent are the air quality char acterizations and analyses technically sound, clearly communicated, appropriately characterized, and relevant to the review of the primary NO2 NAAQS?

Chapter 2 was very brief but accurately summarized the air quality data from the ISA. The summary of sources of NO2 in Sec. 2.1 was succinct but adequately quantitative.

2. In order to simulate just meeting pot ential alternative 1-hour daily maximum standards, we have adjusted NO2 air quality levels using the same approach that was used in the first draft to simulate just meeting the current annual standard. To what extent is this approach cl early communicated and appropriately characterized?

This discussion was fine.

3. Because of the impact of mobile sources on ambient NO2 we have estimated onroad NO2 concentrations. To what ext ent is the approach taken technically sound, clearly communicated, and appropria tely characterized. Do Panel members have comments on the relevance of this procedure for reviewing the primary NO2 NAAQS?

I think the approach is probably fine, a nd Appendix 8 did a nice job describing the derivation of the on-road factors. Neverthe less, the REA is still lacking information validating this particular model. I was e xpecting a plot or two showing how well the model fit the data it was derived from at th e very least, and hopefully also an assessment of how it fit an independent dataset or a subset of the original data. Both demonstrations are necessary to support this an alysis. It is difficult to ha ve confidence in the estimated on-road concentrations if we don’t have a sens e of how well the model fits the data it was derived from. I do appreciate that Appe ndix B included additional comparisons of estimated on-road concentrations from the ambient data and AERMOD, but that’s still not demonstrating the original model validity (and the Appendix B comparison wasn’t all that encouraging in matching estimated numbers of benchmark exceedances).

4. What are the views of th e Panel regarding the ade quacy of the assessment of uncertainty and variability?

Again, the discussion in Secs. 2.3.2 and 2.3.3 were very brief, but captu red the essence of the discussion in the ISA so I think they were adequate for this document.

Characterization of Health Effects Eviden ce and Selection of Potential Alternative Standards for Analysis (Chapters 3,4,5)34 1. What are the views of the Panel on the overall characterization of the health evidence for NO2? To what extent is the presentation clear and appropriately balanced?

Chapters 3 and 4 were essentially distillations of the ISA. I found them faithful to the more comprehensive presentation in that doc ument and as such, a clear, balanced, and adequate summary for this analysis.

I’m not quite sure what to make of Sec tion 4.4.1 and its conclusion that evidence is suggestive but not sufficient to infer a causal relationship between long-term NO2 exposure and respiratory morbidity. Does th is mean the current a nnual standard should be dropped entirely, to be replaced with a sh ort-term standard? The evidence for a shortterm standard is convincing and the REA a ppropriately focuses on that, but it would be helpful to have some discussion, before th e ANPR arrives, about the ramifications of replacing the annual standard, perhaps in S ection 5. Even without such discussion, however, Section 5 was a very helpful additi on in weighing the vari ous combinations of averaging time, form, and level.

2. What are the panel’s views on the appropria teness of the pote ntial alternative standards (in terms of indicator, aver aging time, form, and le vel) for the purpose of conducting air quality, exposure, and risk assessments and on the rationale used to select them for that purpose?

As noted above, Chapter 5 was a great addition.

Characterization of Exposure

1. To what extent is the assessment, interp retation, and presentation of results of the exposure analysis technically sound, clearly communicated, and appropriately characterized? 2. The second draft assessment deva luates exposures in Atlanta. What are the views of the panel on the approach taken and on the interpretation of th e results of this analysis? 3. What are the views of th e panel regarding the adequa cy of the assessment of uncertainty and variability?

(1,2,3 to be answered after Chapter 8 is delivered)

Characterization of Health Risks

1. Based on conclusions in the final ISA re garding airway responsiveness, we have expanded the range of potential benchmar k values to include 0.1 ppm. Do panel members have comments on the range of potential health effect benchmark values chosen to characterize risks asso ciated with 1-hour NO2 exposures?

The expanded range of benchmarks is an improvement. However, the document was quite confusing in the presenta tion of results with respect to those benchmarks. Some35 additional clarification should be made somewhere up front, e xplaining why some analyses used lower benchmarks of 100 ppb a nd some used 150. The use of a potential standard of 50 ppb added to the confusion as well. Although it’s possi ble that a standard of 50 ppb might be proposed in order to li mit exposures to 100 ppb, it’s not necessarily intuitive, so warrants further discussion.

2. To what extent are the assessment, interp retation, and presentation of health risk results technically sound, clea rly communicated, and appropriately characterized? (to be answered after Chapter 8 is delivered)

3. A focused risk assessment has been conduc ted for emergency de partment visits in Atlanta. To what extent are the assessm ent, interpretation, and presentation of health risk results technically s ound, clearly communicated, and appropriately characterized? What are the views of the panel on the approach taken and on the interpretation of the results of this analysis?

This analysis was a nice addition to the REA. It would be helpful to have added an explanation of why Atlanta was selected (this was documented in Appendix A but not explained so concisely in Chapte r 9) and also to make some a ttempt to put these results in the context of other cities. Ho w similar is Atlanta to other US cities with respect to NO2 concentrations and populati on characteristics?

4. What are the views of the panel regarding the clarity and adequacy of the discussion of uncertainty and variability with respect to the characte rization of health risks.

I’m not sure we can really answer this without Chapter 8. Section 9.6 seems quite thorough, but again in a qualitative way. Can the bulleted items be ranked or prioritized?

Minor editorial comments: p.9, several lines: anthropogenic is misspelled. p.10, line 9: though -> through p.30, line 23: chonic -> chronic p.45, line 9: thee -> three p. 51, line 26: The discussion of the empiri cal model is in App. A Sec. 7, not Sec.6. p. 72, line 18: that -> than p. 73, lines 23-26; fix grammar p. 82, line 28: percentile is misspelled p. 83, line 21: range of estimates provided p. 108, line 15: though -> through p. 108, line 18: thee -> three p. 108, line 26: Refers to Sec 3.8 in App. C, but App. C doesn’t have Section numbers. p. 111, lines 2 and 6: thee -> three Appendix C: Table numbers are incorrect.

A-107, line 42 and p. A-108, line 16: References to equation 1 should be to equation 3 as numbered in this draft.36 Please review rules for hyphenation. Especially in section 4, hyphens are used erratically and incorrectly, frequently in the phr ase “statistically significant.” The phrase “as is” is sometimes italicize d, sometimes not. Should be consistent.37 Comments from Dr. Patrick Kinney

Kinney Comments on NO2 REA September 8, 2008

I commend EPA staff on a much-improved document for review. My comments are largely either editorial or focus on improving the precision of the writing.

p. 11, lines 4-7: Edit sentence for clarity. Th is should be understandable to an educated lay person.

p. 11, line 15: at end of sentence, insert ex amples of oxidation products of concern in parentheses.

p. 12, lines 11-12: change “change the principa l conclusions” to “bias conclusions in a positive direction”

p. 17, line 4: It would be helpful to mention here though that there is some evidence that low SES people tend to live nearer to busy road ways than more wealthy people. I think Margo Schwab’s research demonstr ated this in Washington, DC.

p. 29, line 13: mention residences too in this context.

p. 18, line 28: the noted range of increas ed risks (2-20%) means little without information on the exposure range and time s cale. Better would be something like, “Effect estimates from epidem iologic studies conducted in th e US and Canada indicate that ED visits may increase by 2-20% on days when NO2 concentrations are X ppb higher than on other days.” This same problem recurs on lines 29-30 of p. 19, and elsewhere when presenting epi findi ngs. See also page 27, line 14.

p. 20, line 1: I don’t think the word “detected” is appropriate here . Better would be “inferred” or “estimated.” Any calculation th at is based on an arbitrary concentration range (say 30 ppb) is an inferred value, not a finding or observati on from a specific study, especially where observed concentrations in the study were typically much lower than 30 ppb, and day to day changes as large as 30 ppb may never have been, or only rarely, observed. This problem occurs again at line s 14-15 of page 20, where it is stated that “The authors found a 12% increase in risk per 20 ppb increase in 24-hr ambient NO2.” They may have calculated that, but I doubt they found that.

p. 20, line 26: this statement that “NO2 associ ations in multicity studies are generally robust” is contradicted by one of the thr ee studies noted. Seems like a more nuanced summary is needed, e.g., in the few multi city studies that have been conducted, more often than not, NO2 was robust.

p. 28, line 5: should the word “generally” be changed to “more often than not”?

p. 42, figure e5-1: I believe the NYC DOH resu lts are for all ages, not just children. Also, caption should include 24 hour.38 p. 43, figure 5-2: caption should also mention 4 and 24 hour results.

p. 45, line 9: “three” is misspelled.

p. 59, line 19: change “two year-groups” to “two six-year groups” This occurs elsewhere also.

p. 70, Table 7-10 and tables which follow: In spite of the footnote, I have a hard time understanding what these numbers mean in te rms of spatial and temporal averaging. Need a better explanatio n to aid interpretation.

p. 72, line 18: change “that” to “than”

p. 93, lines 4-6: please expand further on why you think this is likely to a be a problem and why it would go in a partic ular direction. Same goes fo r line 16. Not obvious to this reader why this would be the case.

p. 94, lines 19-23: this sentence needs editing for clarity.

p. 107, line 7: Since some of the observed baseline incidence is due to as-is NO2 concentrations, do these ED visits need to be subtracted out to ge t the true “baseline”?

p. 111, line 6: “three” is misspelled.

p. 115, line 5: however, as noted above, NO2 was only moderately correlated with PM10 and O3 in this study. The text as-wri tten is misleading in this context.

p. 116, line 2: I think the concentrations should be swapped in this sentence.39 Comments from Dr. Steven Kleeberger

I thought the second draft of the REA for NO2 was very well written, and overall have very few substantive comments. The sections were largely very clearly presented and approaches adequately explaine d. Minor issues are raised be low in response to specific questions.

Characterization of Air Quality (Chapters 2, 6, and 7)

1. To what extent are the air quality charac terizations and analyses technically sound, clearly communicated, appropriately characteri zed, and relevant to the review of the primary NO 2 NAAQS?

I thought the air quality charac terizations and analyses we re appropriately presented.

2. In order to simulate just meeting pot ential alternative 1-hour daily maximum standards, we have adjusted NO 2 air quality levels using the same approach that was used in the first draft to simulate just meeting the cu rrent annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

This approach was well communicated and characterized.

3. Because of the impact of mobile sources on ambient NO 2 , we have estimated on-road NO 2 concentrations. To what extent is the approach taken technically sound, clearly communicated, and appropriately characterized? Do Panel members have comments on the relevance of this procedur e for reviewing the primary NO 2 NAAQS?

No comments. As above, I the approach wa s technically sound a nd well communicated.

4. What are the views of the Panel regar ding the adequacy of the assessment of uncertainty and variability?

This is not my particular area of expertise.

Characterization of Health Effects Eviden ce and Selection of Potential Alternative Standards for Analysis (Chapters 3, 4, 5)

1. The presentation of the NO 2 health effects evidence is based on the information contained in the NO 2 Integrated Science Assessment. What are the views of the Panel on the overall characterization of the health evidence for NO 2 ? To what extent is the presentation clea r and appropriately balanced?

This area was largely well-written, and the presentation was appropr iately balanced. However, the general lack of inclusion of animal modeling data was somewhat surprising. Most of the discussion focuse d on epidemiology and chamber studies.

I also thought that a table was going to be created to illustra te/list susceptibility factors known to be, or potentially could be, important in responsivity to NO2. In the "Age" section, perhaps a statement that indicates, in addition to children and the elderly, infants40 could also be a particularly susceptible s ubgroup. Some evidence, though not sufficient to indicate absolute causality, would suggest that this is th e case (e.g. increased incidence of SIDS associated with NO2).

In general, I believe it is important to empha size that strong biological plausibility exists for other subgroups to be susceptible to NO2-induced effects. The evidence that children, elderly, and individuals with asthma are susceptible is clear, and correctly indicated in the REA. However, other factor s could also be important but simply haven't been investigated sufficiently. A strong statement to this effect is warranted.

An important point to be emphasized in Sect ion 3.2 (Susceptibility: Pre-existing Disease) is that controlled NO2 exposures of asthmatics have been restricted to mild asthmatics for ethical and safety concerns. It is likely th at severe asthmatics are even more susceptible to the effects of NO2 exposures than mild as thmatics, and further illustrates the health concerns for this large subpopulation.

A minor point: it is not clear what is mean t by "physiological susceptibility" (page 17, line 12).

2. The specific potential altern ative standards that have been selected for analysis are based on both controlled human exposure studies and on epidem iological studies conducted in the United States. What are th e Panel’s views on the appropriateness of these potential alternative standards (in te rms of indicator, av eraging time, form, and level) for the purpose of conducting air qual ity, exposure, and risk assessments and on the rationale used to sele ct them for that purpose?

I thought the introduction and e xplanation of form was appropriate and nicely tied to other criteria pollutants.

Characterization of Exposure (Chapters 6 and 8):

1. To what extent is the assessm ent, interpretation, and presen tation of the results of the exposure analysis technically sound, clearly communicated, and appropriately characterized?

The assessment, interpretation and presentation were clearly presented in Chapter 6.

2. The second draft assessment document evalu ates exposures in Atlanta. What are the views of the Panel on the approach taken and on th e interpretation of the results of this analysis?

N/A

3. What are the views of the Panel regar ding the adequacy of the assessment of uncertainty and variability?

N/A41 Comments from Dr. Timothy Larson



### Review of the Risk and Exposure Asse ssment to Support the Review of the NO 2 

### Primary National Ambient Air Quality Standard: Second Draft

Comments by Dr. Timothy Larson

This is a much improved draft, including the useful appendices. The staff has been very responsive to the major comments from CASAC. I look forward to hearing more about the exposure assessment approaches to be pr esented in Chapter 8. In the meantime, I have a few preliminary comments regardi ng exposure assessment in addition to addressing several of the charge questions.

Air Quality Analyses

1. To what extent are the air quality charac terizations and analyses technically sound, clearly communicated, appropriately characteri zed, and relevant to the review of the primary NO 2 NAAQS?

These characterizations, including th e accompanying appendices, are clearly communicated. The different approaches to estimating the spatial distribution of NO 2 are a good mix of direct measurements and statistical methods.

The choice of a 98 th or 99 th percentile 1-hour value is pres umably done to provide a stable target over time. It would be good to show how stable these targets are over time. Specifically, it would be good to show the relativ e rankings of this metric between cities over time. If these relative rankings are reasona ble stable (non-paramet ric statistical tests are available), then it would appear justified.

The downwind conversion of NO to NO 2 is mentioned briefly in the REA long after introduction of equation 7-1. This conve rsion can produce a maximum value of C x that is not necessarily at x = 0. In the section intr oducing equation 7-2, it might be instructive to emphasize that the distribution of m values reflects both decay (by dispersion) and formation (via ozone reaction) of NO 2

.

2. In order to simulate just meeting poten tial alternative 1-hour daily maximum standards, we have adjusted NO 2 air quality levels using the same approach that was used in the first draft to si mulate just meeting the curre nt annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

In general, this approach is clearly co mmunicated and the appropriate caveats are provided. The distinctions between the benchm ark levels versus the alternative standards needs further clarification, po ssibly showing a graph of fre quency distributions of air concentrations under “as is” and “CS” levels and a representation of the accompanying number of exceedances of a given benchmark le vel under different alternative standards. The fact that considering an alternative 1-hr standard of 100 ppb at the 98 th percentile will allow some 1-hr 150 ppb concentration exceedances in a given year will be clarified in such a figure and this might help to make the distinction between the benchmark values42 and the alternative standards and help to inte rpret the numbers in the relevant tables (e.g. Table 7-15).

3. Because of the impact of m obile sources on ambient NO 2 , we have estimated on-road NO 2 concentrations. To what extent is th e approach taken technically sound, clearly communicated, and appropriately characterize d? Do Panel members have comments on the relevance of this procedur e for reviewing the primary NO 2 NAAQS?

The on-road and near-road exposures are an important aspect of the overall exposure assessment. It would be interesting to know whether the monitors showing the extreme values of the distribution in figure A-101 are different from the others, specifically are these very near the road or confined in street canyons.

While I agree that the range of average m va lues discussed in the REA is reasonable for both flat on-road conditions and street canyons, there can be larger values observed on an hourly basis in street canyons under certain wind direction and traffic level combinations. In a given hour, m can exceed 4 assuming r ooftop levels are equivalent to urban background levels [c.f. Xie et al, Atmos. Environ. V37 (2003) 3214-3224 and Ghenu et al, Environmental Modeling and Software v23 (2008) 314-321].

4. What are the views of th e Panel regarding the adequacy of the assessment of uncertainty and variability?

It would be good to clearly desc ribe which monitors were bei ng used to compare with the Aermod predictions. If these monitors are furt her than 100 meters from major roads, this limitation should be included.

Exposure Assessment

3. A focused risk assessment has been conduc ted for emergency department visits in Atlanta, GA. To what extent are the asse ssment, interpretation, and presentation of health risk results technically s ound, clearly communicated, and appropriately characterized? What are the views of the Panel on the approach taken and on the interpretation of the results of this analysis?

This is a very useful Appendix that clarifie s some of the issues described in the main report. I think it should be referred to earlier in the main report to help put the major ideas in context.

The other city that was seriously being consid ered for this analysis was New York. In this major urban area, people live next to street canyons and spend more time there than those that commute on roads. Zhou and Levy ( Atmos. Environ. v42 (2008), 3087-3098) looked at the issues of popul ation exposures to NOx in street canyons in dense urban areas from the perspective of NOx intake fr action. Due to the hi gh population density in the New York City urban canyons and to the fa ct that the canyons can trap the pollutants relative to unobstructed ro ads, Zhou and Levy predicted intake fractions for NO 2 in New York that approach those for s econd hand smoke (on the order of 10 -3 ). These exposures43 may not occur in Atlanta and that should be clearly communicated. Can the intake fractions be estimated in the upcoming exposure analyses in chapter 8? This would help put such analyses in a broader context.

Health Assessment

1. Based on conclusions in the final ISA re garding airway responsiveness, we have expanded the range of potential health effect benchmark values to include 0.1 ppm. Do Panel members have comments on the range of pot ential health effects benchmark values chosen to characterize risks associated with 1-hour NO 2 exposures?

I think the new range of benchmark values that include 0.1 ppm is reasonable.44 Comments from Dr. Kent Pinkerton

Comments on Risk and Exposure Assessment to Support the Review of the NO 2 Primary Ambient Air Quality Standard: Second Draft

Kent E. Pinkerton, University of California, Davis

Characterization of Air Quality (Chapters 2, 6, and 7)

1. To what extent are the air quality charac terizations and analyses technically sound, clearly communicated, appropriately characteri zed, and relevant to the review of the primary NO 2 NAAQS?

REPLY: The characterizati on of the sources of NO 2 , ambient levels of NO 2 and uncertainties associated with ambient NO 2 monitoring are clearly pr esented in a brief, but adequate fashion in Chapter 2. Approach es to assess exposures and risks to NO 2 are clearly outlined in Chapter 6 with reasonabl e explanations of formulas and equations implemented to simulate current and alternative standards for NO 2 . Air quality characterization and analyses appear to be scientifically sound, appropriately characterized and communicated in Chapter 7. Each are highly relevant to the review of the primary NO 2 NAAQS, but need to clearly identify how these approaches may lead to a completely different basis for a standard th at is currently not the approach used for assessment - i.e., a 1-hour standard.

2. In order to simulate just meeting pot ential alternative 1-hour daily maximum standards, we have adjusted NO 2 air quality levels using the same approach that was used in the first draft to simulate just meeting the cu rrent annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

REPLY: The approach to simulate just mee ting the current annual standard is clearly communicated and well characterized.

3. Because of the impact of mobile sources on ambient NO 2 , we have estimated on-road NO 2 concentrations. To what extent is the approach taken technically sound, clearly communicated, and appropriately characterized? Do Panel members have comments on the relevance of this procedur e for reviewing the primary NO 2 NAAQS?

REPLY: Since mobile sources represent a primary origin for the genesis of NO 2 and personal exposure to NO 2 , to evaluate the impact of roadway levels of NO 2 is extremely logical. The formulas applied to estimate on-road NO 2 concentrations are clearly stated and explained with a highly reasonable degree of characterization. However, it was not clear why some locations (Denver, Los Angele s, Phoenix and St. Loui s - line 2, page 60) found higher NO 2 concentrations at greater distances from roadways that those within 100 m of roadways. The authors should clarify this point and/ or provide further rationale for estimating on-road NO 2 concentrations.

4. What are the views of the Panel regar ding the adequacy of the assessment of45 uncertainty and variability?

REPLY: Although the assessment of uncertainty and variability is not an area I have much experience, this section is logically or ganized into specific sources of uncertainty (air quality data, ambient measurement techni ques [height of monitor, etc], temporal and spatial representation, air quality adjustment s, on-road estimations and the choice of potential health benchmarks) that are all reasonably explained and presented. The definitions for uncertainty and variability are also highly beneficial. The presentation of all these factors provides great value to this portion of the document.

Characterization of Health Effects Eviden ce and Selection of Potential Alternative Standards for Analysis (Chapters 3, 4, 5)

1. The presentation of the NO 2 health effects evidence is based on the information contained in the NO 2 Integrated Science Assessment. What are the views of the Panel on the overall characterization of the health evidence for NO 2 ? To what extent is the presentation clea r and appropriately balanced?

REPLY: This section is logical and well presented. The authors of these chapters have been careful to provide balance in the studies reported. Although it is unfortunate that the discussion of the biological plausibility a nd potential mechanisms for adverse health effects due to NO 2 is limited due to a lack of the pr esentation of animal toxicology, the chapters are excellent in the presentation of health effect s evidence. The discussion is in large measure based on human clinical studies and epidemiology. At risk populations are well described to include those with pre- existing disease, children and the elderly, as well as those that those with genetic conditions that might involve the glutathione Stranferase (GST) gene. The evidence is clear that health implications occur well below the current NAAQS standard for NO 2

.
2. The specific potential altern ative standards that have been selected for analysis are based on both controlled human exposure studies and on epidem iological studies conducted in the United States. What are th e Panel’s views on the appropriateness of these potential alternative standards (in te rms of indicator, av eraging time, form, and level) for the purpose of conducting air qual ity, exposure, and risk assessments and on the rationale used to sele ct them for that purpose?

REPLY: This section is hi ghly appropriate in the appr oach taken to define NO 2 risk and exposure assessment based on current levels of ambient NO 2 and NO 2 levels associated with just meeting the current standard. Th e section is well written and appropriate to identify potential alternative standards in te rms of indicator, averaging time, form and level and well as providing the rationale used to select these alternative standards. The selection of a one-hour averaging time to ev aluate standards is highly appropriate. A concentration-based form for the NO 2 standard would also mu ch better reflect health risks posed by elevated NO 2 concentrations. The level to include both the 98th and 99th percentile NO 2 concentrations averaged over 3 year s as recommended by the staff also seems to be highly logical and appropriate.46 Characterization of Exposure (Chapters 6 and 8):

1. To what extent is the assessm ent, interpretation, and presen tation of the results of the exposure analysis technically sound, clearly communicated, and appropriately characterized?

REPLY: The assessment, interpretation and pr esentation of the results of the exposure analysis are technically s ound, clearly communicated and ap propriately characterized. The approach to 1) compare NO 2 air quality levels to poten tial health effect benchmark values derived from the literature for contro lled human exposures, 2) the evaluation of an inhalation exposure model to generate more re alistic estimates of pe rsonal exposures and 3) the estimation of emergency department (E D) visits are all highly appropriate and well communicated in Chapter 6 of the document.

2. The second draft assessment document evalu ates exposures in Atlanta. What are the views of the Panel on the approach taken and on th e interpretation of the results of this analysis?

REPLY: The selection of Atlanta to evalua te exposures would appear to be highly appropriate, based on the information availabl e to perform this an alysis. Appendix C provides an excellent summary for the NO 2 health risk assessment for Atlanta for the consideration of the relationship between NO 2 and adverse health effects. The methods used for the selection of hea lth endpoints based on epidemio logic studies as well as the selection of concentration-re sponse functions and air quality considerations are welldescribed and appropriate. This type of analysis for Atlanta NO 2 exposures is extremely well done.

3. What are the views of the Panel regar ding the adequacy of the assessment of uncertainty and variability?

REPLY: Again the presentation of uncertain ty and variability a ppear to be very reasonable, however, this presentation also a ppears again in Chapters 7 and 9 as well as to a limited (and appropriate degree) in Appendix C.

Characterization of Health Risks (Chapters 7, 8, 9):

1. Based on conclusions in the final ISA re garding airway responsiveness, we have expanded the range of potential health effect benchmark values to include 0.1 ppm. Do Panel members have comments on the range of potential health effects benchmark values chosen to characterize risks a ssociated with 1-hour NO2 exposures?

REPLY: The range of potential health effect s benchmark values chosen to characterize risks associated with 1-hour NO 2 exposures is highly appropriate. Based on the health effects information available through human clinical and epidemiol ogical studies using a 1-hour exposure air quality charac terization, the most relevant NO 2 concentration range appears to be 100 to 300 ppb. However, in the body of the text 50, 100, 150 and 200 ppb47 are stated, but in the tables (7-5 to 7-8) the four potential health effect benchmark levels used are 150, 200, 250 and 300 ppb to estimate the number of exceedances for NO 2 . The authors should clarify this poi nt. Never-the-less, the select ed potential health effect benchmark levels are highly appropriate.

2. To what extent are the assessment, inte rpretation, and presentation of health risk results technically sound, clearly comm unicated, and appropriately characterized?

REPLY: From the data provided to date, th e assessment, interpretation, and presentation of health risk results in the document have been technically s ound, clearly communicated, and appropriately characterized.

3. A focused risk assessment has been conduc ted for emergency department visits in Atlanta, GA. To what extent are the asse ssment, interpretation, and presentation of health risk results technically s ound, clearly communicated, and appropriately characterized? What are the views of the Panel on the approach taken and on the interpretation of the results of this analysis?

REPLY: The approach for conducting a risk assessment for emergency department visits in Atlanta, GA is thorough with excellent pr esentation of the findings that have been clearly communicated. The focus on Atlanta seems highly appropria te; however, further comparisons using other cities may also be appropriate in making a decision for national risk and possible consideration in th e current air quality standard for NO 2

.

4. What are the views of the Panel regarding the clarity and adequacy of the discussion of uncertainty and variability with respect to the characte rization of health risks?

REPLY: The uncertainty analys is throughout the document has b een clearly stated with a reasonable degree of discussion to provide a logical explanation of factors impacting on uncertainty. The use of data such as the temporal re presentation of NO 2 levels into distinct time periods (page 92) may also prove useful in better dealing with issues of uncertainty and variability. Table 7-19 is us eful as a summary of those factors that impact on uncertainty and how it may affect (positive or negative) the analysis for the characterization of air qu ality and health risk.48 Comments from Dr. Edward Postlethwait

Edward M. Postlethwait, Ph.D.

Comments on the NO x second draft REA for the Sept 2008 CASAC meeting (in no particular order)

1. The document is clearly improved and the extensive efforts by EPA staff in crafting the REA are evident.

2. Section 3.4 (Susceptibility: Genetics) needs some minor editing to correct inaccuracies (e.g., “absent peroxide activity” which I assume is “peroxidase”; not all ROS are electrophilic).

2. The statements in sectio n 6 regarding the utility of airway hyperresponsiveness versus ED visits are not always clear a nd thus some editing would strengthen the document. “For example, the public health si gnificance of the effect in question (i.e., ED visits) is less ambiguous in term s of its impact on an individual than in the case of airway hyperresponsiveness.” While the ra tionale for this is likely evid ent to those in the field, it does raise questions as to how ED visits are characterized with regard to NO 2 -specific related pathophysiological even ts. Thus, in the absence of more characterizations, counting all ED visits rather than at tempting to relate AHR to ambient NO 2 levels does not necessarily appear to strengthen risk estimates.

3. The benchmark NO 2 concentrations are not consis tent throughout the document. For example, on pg 49, 50 ppb 1 hr levels are included but to not appear elsewhere.

4. A graphic and/or pictorial representati on of the best estimates of the spatial distribution of NO 2 levels around roadways would be useful. Although there appears to be uncertainties in the precise spatial distribution, a consen sus best estimate that would give the reader an improved feel for exposur es relative to highway proximity and that would help identify where the 100 m boundaries exist (middle of the median outward, edge of road, etc) would seem germane.

5. The estimated risks/exposures appear to be based on Atlanta due to a single publication. However, Atlanta represents neither a worst or best case scenario and has missing data in many of the presented tables. Thus, staff should consid er either including additional cities or at leas t providing a more compelling rationale for the focus on Atlanta. Furthermore, to this reader all th e figures/tables in chap ter 7 do not lend clarity but rather make this section more difficult to readily decipher. Perhaps final compilations should be presented with the numerous iterations moved to the appendix.

6. Tables 9-1,2,3 suggest th at the inclusion of PM 10 and O 3 reduce the NO x related ED visit incidence by factors of > 4 fold br inging into question the strong statements regarding causality and the “robust” NO x related outcomes in multi-pollutant models. These discrepancies should be resolv ed to improve internal consistency.49 7. While the numerous potential limitati ons and confounding factors are noted and discussed, it is unclear how they factor into the risk analyses. Based on the presented information, there appears to be a large number of uncertainties that could have substantial impacts on estimating health impacts. Thus, it seems critical that sensitivity analyses are incorporated to evaluate the extent of confounding and how any and all of the uncertainties affect the h ealth/exposure outcomes boundaries.50 Comments from Dr. Armistead Russell

Pre-meeting Review of EPA’s “Risk and Expos ure Assessment to Support the Review of the NO2 Primary National Ambient Air Quality Standard” Armistead (Ted) Russell

General Review:

My overall view of the REA (sans Chapter 8) is positive. I think it begins to lay out the information needed to inform setting of a NAAQ S. One aspect I felt missing was that as it focuses on the need, and the respective level, etc., of a short term standard, I was a bit disappointed at the lack of discussion and anal ysis of “what about the old one”? Will it still be needed and why? What happens if it is removed? The latter question has to go beyond just the health issues, but welfare as well. Certainly, a one hour standard for NO2 has little relevance to addr essing environmental acidifica tion or nutrient enrichment. Given the recent decision by the administrato r to not promulgate a separate welfare NAAQS (i.e., for ozone), not having a long term NO 2 standard has major implications. What might be needed in this case is to look specifically at the sources likely to be affected by a short term standard and assess how controls targeted at a one hour standard might impact longer term concentra tions and emissions overall.

I might also suggest against the wording on page 5, line 4 “... and of any potential alternative standards.” This is not limiting in any way shape or form, and in particular, suggests that standards could be introduced he re that have not been subject to any prior relevant analysis. Given the current appr oach to the NAAQS revi ews, it would be appropriate to have this altered to suggest standards for which informative analyses have been conducted and reviewed.

One part that needs to be much more precise is section 5.4 as to the Form of the standard. In particular, you note that it is the 98 th percentile averaged over 3 years. By that, I assume one means taking the 98%ile from the daily maximum one hour average for each of three calendar years, and ta king that average. An alternative is to take all 24-hr measurements, and taking the 98 th %ile, and then averaging. (This was less ambiguous for PM since only 24-hr measurements are used.) This should be spel led out specifically and precisely, along with the mathematical formula.

It seems as though the levels of concern exam ined vary between chapters, sometimes not including the 0.05 ppb mark (e.g., figures in Chapter 7).

1. To what extent are the air quality charac terizations and analyses technically sound, clearly communicated, appropriately characteri zed, and relevant to the review of the primary NO 2 NAAQS?

There is a current weakness here, that raises its ugly little head later in the document. It would help, at this point, to have a more comprehensive description of the range of measured NO 2 levels across the US. As noted below, we are led to believe that there are areas where the monitored mean is 3 ppb (page 3 2, line 8). Is this true? What type of51 area might this be? Given the proposed form of the short term standa rd, it would be best if, instead of showing just the annual mean, the 98 th %ile (or other characterization of the peak 1-hr levels) also be provided (as available).

It would be good if the air quality characterizations done in Ch apter 7 were related to the epidemiologic studies considered.

The order of cities in Table 7-1 is not appa rent at this point, becoming apparent when looking at Table 7-2. I pr efer alphabetizing.

Tables 7-3 and 7-4 need to be more precisely described in the foot notes. In particular, what annual means are being described? Are those the %iles of the annual means? (Apparently, yes). Are these the annual means of the 98 th %iles of the daily one hour maximums? (Apparently not, but this is more pertinent.) Are they the %iles of the whole distributions? The document should be ma de clear, and the analyses consistent, throughout the document. Please make the st atement of the standard in a precise mathematical form.

The relationship between annual average and specific target standards should be provided, i.e. in a table in the REA for the cities analyzed, what is the current annual average, the 98 th and 99 th %iles (using the proposed averag ing) should be given. I think this might be provided in 7-4... but the footnotes have to be clearer that this is given.

Much of the more pertinent information is given in Appendix A, and it seems that some of the less pertinent info is in the tables and discussion in the body of the report. There should be a continuous link between the air qua lity characterization and the metrics given there and the following exposure an d risk assessments later on.

2. In order to simulate just meeting pot ential alternative 1-hour daily maximum standards, we have adjusted NO 2 air quality levels using the same approach that was used in the first draft to simulate just meeting the cu rrent annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

The approach used is reasonable, though the assumptions (and justifications) should be stated, preferably with some foundation as to why the assumptions are appropriate. This may involve considering specific sources and control approaches and saying “There is no more appropriate approach given what is currently known.” However, this should be done after consideration of specific sources.

As a detail, the mathematical formula descri ption should be tightened up some, i.e., :

F ij = Adjustment factor for locat ion i and year j (unitless)

This tightening should be done for both Eq. 6- 1 and 6-2 (though j stands for two different things in the two equations). Further, they should specifically state, here, that the PRB is taken as insignificant.52 In Table 7-12, I would add a characterization of the F’s for each area. This info is in the Appendix, but some info here would be good (not as much detail needed).

3. Because of the impact of mobile sources on ambient NO 2 , we have estimated on-road NO 2 concentrations. To what extent is the approach taken technically sound, clearly communicated, and appropriately characterized? Do Panel members have comments on the relevance of this procedure for reviewing the primary NO 2 NAAQS?

My major concern about this analysis is how well founded is the calculation of “m”. While I guess this would come later, this is an area where some quantitative uncertainty analysis should be done.

In equation 7-1, k is the “decay” constant, not the “rate” constant.

4. What are the views of the Panel regar ding the adequacy of the assessment of uncertainty and variability?

At present, the discussion is largely qualitative, with little information as to even the ordering of major versus minor uncertainties . Section 7.4.2 has much of the discussion on monitor location not technique. This s hould be moved to 7.4.4. The authors should be specific on the extent of biases and uncertain ties. In regards to a standard based on the 1-hr maximum of NO2, I woul d argue that the 50% value for the technique bias is irrelevant. Further, it would be good if you can be much more quantitative as to the likely bias introduced from having a 4-to-5 m sampling height at a monitor 100 m away from a major road. Bring in the AERMOD results here.

It is here that we get some discussion on the adjustment factor that should also be present when the process is introduced. Introduce the issues earlier on, givi ng the more detailed discussion later on. This uncertainty analysis could also be a bit more quantitative (or semi-quantitative).

I appreciate Table 7-19., but would like to see a column characterizing level of uncertainty.

P 93, l 26: Not sure what you mean by “concentration profile”.

Specific Points:

P 20, l 26: Make sure that everyone would concur that th e results are “robust”. This word is subjective, and can mean different th ings to different peopl e. I would be more specific, specifying how many studies still find statistically significant results when multi-pollutant models are used. My take of 3.1-7 does not suggest the word “robust” is quite correct. Furthe r, they only control for PM10, not PM2.5 or, say, EC. Looking at 3.1-10 and 3.3-2 leads me to further suggest the word “robust” shoul d not be used here.

P24, l 6: “cites”

P27, l 14: 2-20% increase per “what”53 P32, l 8: This sentence, as wr itten, indicates that adverse hea lth effects can be identified for a mean 24-hr concentration of 3 ppb. This seems a bit far fetched. Indeed, looking at the Table 5.4-1 of the ISA, I think the 3 ppb comes from the Linn study, and if that is the case, it was 3.4 pphm, not 3.4 ppb. I might re -check the units on the various studies summarized in this table. Looking at Figure 2.4-13, it appears as though the minimum mean NO2 is 5 ppb, and I would have to imagin e that is at a pret ty sparsely populated location. I am curious, at what locations wh ere epi studies have been conducted is the mean NO2 under 10 ppb? I will also add, the fact that an adverse outcome associated with NO2 exposure is found in areas where the mean is, say, 10 ppb, does not mean that the adverse outcome results from an exposure of 10 ppb.

P36, l 11: This line should be “NOx, for the purpose of this document, includes...”

P41, l 16: “Figures 1 and 2” (Capitalize) . Check capitalization of “Figure”, “Chapter” and “Table”, etc. throughout.

P 45, l 9: three (not thee)

P 67: footnote: Table 7- 10. P72 l18: “than” not “that” P72, l28: remove “that” P 73, l26: “) as provided...”

P107, l 17-18. One should note that in the Peel et al., and Tolbert et al., studies, that having only 36 out of 42 hospitals providing us able data does not mean that a similar fraction of potential ED visits are captured (or, c onversely that 6/42 are missed). Often, it is the smaller hospitals that are not captured, so a very high fraction of ED’s are included. Also, are you sure o the 36 nu mber, particularly for 2004?

Section 9.6 seems out of place. Shouldn’t it go later on?

Still check on the Philadelphia NOx emissions from aircraft.54 Comments from Dr. Jonathan Samet

Review Comments Prepared by: Jonathan M. Samet, MD, MS Risk and Exposure Assessment to Support the Review of the NO 2 Primary National Ambient Air Quality Standard: Second Draft

Characterization of Health Effects Eviden ce and Selection of Potential Alternative Standards for Analysis (Chapters 3,4,5)

.

1. Charge Question 1:

In general, the document adequately repr esents the key evidence in the ISA with regard to the overall findings. Chapte r 3 covers susceptibility, describing the range of populations found to be susceptible , both to air pollution generally and to NO 2 specifically. The document might be improved by a sharpening of its conclusions. Clearly, one important overall finding is that a large number of people could be susceptible, when consid ering the full range of groups identified. On the other hand, the experimental and epidemiological evidence would appear to converge in finding that asthmatics are the most sus ceptible. This conclusion may be stated obliquely on page 14, lines 17-19 in Chapter 3.

The concept of vulnerability, as distinct from susceptibilit y, is introduced, and appropriately followed through. It will be im portant to continue to maintain this same distinction between vulnerabilit y and susceptibility in subsequent documents related to the NAAQS for other pollutants.

Chapter 4 provides the relevant findings of the ISA from the literature on the health effects of NO 2 . As with Chapter 3, the ISA is satisfactorily distilled for the main points relevant to the REA. Ther e are several important issues to be discussed. This set of evaluations for NO 2 uses the five-level classification of strength of evidence for causation. On page 32, lines 1-3, the staff makes the judgment that it will focus on endpoints for which the ISA “concludes that the available evidence is sufficient to infe r either a causal or a likely casual relationship”. This represents a decision that sets a precedent with regard to the level of evidence in support of outcomes that will be considered in the REA. I do not dispute the choice, but I would suggest that it be better justified, given the future significance of this decision.

I also suggest that a stronger justificati on is needed to set aside the studies of indoor NO 2 . The stated rationale acknowledge s that these studies focused on NO 2 alone to the extent possibl e and that the exposure situ ation indoors differs from that outdoors. On the other hand, the e xperimental literature is based on exposure to NO 2 alone. Given the emphasis placed on th e experimental studies, there does not appear to be a solid rationale for sett ing aside the studies directed at exposure to NO 2 from indoor sources.55 The results of selected epidemiological st udies will be considered in the REA. A rather weak argument is made for the a ppropriateness for this purpose in lines 12- 13 on page 33. This sentence, giving staff judgment, follows a reasonably comprehensive discussion of the strengths and limitations of the epidemiological data.

Charge Question 2:

In general, the basis for selecting the indi cator, averaging time, form, and level for the NO 2 NAAQS are clearly stated. The aver aging time of 1-hour is reflective of the duration of the experimental studies and the finding that there are adverse health effects. Should consideration be given to exploring scenarios for the 24- hour averaging time as well? It might be useful to learn of maintenance of this averaging time would accord the same pr otection for deeper exposures as would be reached by having the one-hour standard.

With regard to level, the document provide s a clear rationale for assessing a lower range extending to 0.05 ppm. The upper end of the range is quite reasonable, due to the experimental findings.

The REA states that alternative long-ter m standards to the current annual value will not be considered. On the other hand, the evidence does not provide certain evidence that there are long-term conse quences. Would a short-term standard alone be sufficient? Are there areas that would be in compliance with a shirt-term standard but not with a long-term standard?56 Specific Comments:

Page # Line # Comment
9 5 Correct spelling anthropogenic
9 11 “ “ “ 10 19 Can’t the concentrations va ry over the time of exposure? 10 28 “On average.(add in the United States) people spend...”
11 21 Delete “this produces” insert there is.
11 23 “2.5-fold (delete incr ease in) substitute higher
12 11 “However, (insert the possible cons equences of this exposure error do not) delete “is not expected to” 13 3 Delete subpopulations (insert gr oups within the general population) are at increased risk for su ffering (adverse effects from NO 2 exposure.) 13 25 Delete are believed (insert have been found)
14 19 What is meant by “most sensitive”? 15 1 Delete agreed (insert had comparable findings) 15 13 “First the product “ Necessa rily? What about regulations? 16 9 “the vicinity” (Insert of roadways) 18 21 “recent studies” (or the entire body of evidence?)
23 12 Delete lead to the type of outco mes assessed (Insert be the basis for the effects observed) (insert incr eased before respiratory illness
24 6 “In addition the ISA” de lete sites (insert cities)
24 Table row 3 column 2 Should be 66%?
27 15 In association with? What exposure?
27 22 Redundant phrasing
27 27 Adverse (insert respiratory) health 28 10 Add (and the potential for confounding)
33 12 This sentence seems overly strong in view of the prior discussion of limitations of the epidemiological findings. 33 19 But don’t these studies address NO 2 alone as in the exposure studies? 34 20 “levels is (increased) airway hyperresponsiveness” 39 7 Would it be reasonable to consider the 24-hr averaging time as well? 45 9 “...we have employed thee approaches” Change to three.57 Comments from Dr. Richard Schlesinger

RICHARD SCHLESINGER

Overall, this draft is an improvement over the first. Certain concepts that were not clear in the first draft have been clarified in th is one. Some comments on the specific questions follow:

To what extent are the air quality charac terizations and analyses technically sound, clearly communicated, appropriately characteri zed, and relevant to th e review of the primary NO2 NAAQS?

From my perspective, these are clearly communicated.

In order to simulate just meeting pot ential alternative 1-hour daily maximum standards, we have adjusted NO2 air quality le vels using the same approach that was used in the first draft to si mulate just meeting the current annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

This is explained much better in this th an in the first version of the document.

Because of the impact of mobile sources on ambient NO2, we have estimated on-road NO2 concentrations. To what extent is th e approach taken technically sound, clearly communicated, and appropriately characterize d? Do Panel members have comments on the relevance of this procedure fo r reviewing the primary NO2 NAAQS?

No specific comment.

.What are the views of the Panel regarding the adequa cy of the assessment of uncertainty and variability?

These are clearly addressed in th is version of the document.

Chapters 3, 4, 5

The presentation of the NO2 health effect s evidence is based on the information contained in the NO2 Integrat ed Science Assessment. Wh at are the views of the Panel on the overall characterization of the health evidence for NO2? To what extent is the presentation clear and appropriately balanced?

The health outcomes evidence was clearly presented. However more animal toxicology studies should have been included as ba sis to support findings in epi studies.

The specific potential alternative standards t hat have been selected for analysis are based on both controlled human exposure st udies and on epidemio logical studies conducted in the United States. What are th e Panel’s views on the appropriateness of these potential alternative standards (in term s of indicator, averaging time, form, and58 level) for the purpose of conducting air qualit y, exposure, and risk assessments and on the rationale used to select them for that purpose?

I agree with the chos en alternatives

Chapters 7, 8, 9

Based on conclusions in the final ISA regar ding airway responsiveness, we have expanded the range of potential health effect benchmark values to include 0.1 ppm. Do Panel members have comments on the range of potential health effects benchmark values chosen to characterize risks a ssociated with 1-hour NO2 exposures?

I agree with this approach. However, there do es seem to be some inconsistency in the specific benchmark concentrations in different sections of the document.

A focused risk assessment has been conducte d for emergency depar tment visits in Atlanta, GA. To what extent are the asse ssment, interpretation, and presentation of health risk results technically sound, clearly communicated, and appropriately characterized? What are the views of th e Panel on the approach taken and on the interpretation of the results of this analysis?

I agree with this approach

What are the views of the P anel regarding the clarity and adequacy of the discussion of uncertainty and variability with respect to the characte rization of health risks.

The discussion is quite sound.59 Comments from Dr. Christian Seigneur

Comments on the NO 2 Risk and Exposure Assessmen t- Second Draft – September 2008.

Christian Seigneur CEREA – Joint Laboratory ENPC/EDF R&D Université Paris-Est Champs sur Marne, France

The second Draft shows some clear improvement over the first draft. For example, the uncertainty in the measurement of NO 2 ambient concentrations is now qualified as being small near emission sources (p. 11, lines 17-19). Furthermore, EPA has added benchmark concentrations as low as 0.05 ppm and has added a new analysis based on the epidemiological studies where the effect of NO 2 concentrations on emergency department visits are compared for different NO 2 concentration benchmark values. These latter revisions required a significant amount of new work by EPA staff and they clearly demonstrate that EPA listened and responde d in an effective manner to the CASAC Panel’s comments.

Most of my comments on the previous draf t focused on the air quality modeling. It appears that the modeling of NO 2 with AERMOD is more ch allenging than expected, possibly because NO 2 is both a primary pollutant (emitted directly from vehicle exhaust and power plants, for example) and a sec ondary pollutant (formed by oxidation of NO by HO 2 and O 3 for example). The simplest appr oach to calculate secondary NO 2 concentrations near an emission source is to use an “oxidant-limited” approach, which assumes that the reaction of NO with O 3 is fast and stops when all O 3 has been depleted. The reaction of NO with HO 2 radicals and other peroxyl radicals can generally be neglected near a NO x source because the conc entrations of those radicals are typically negligible when NO concentrations are hi gh. Nevertheless, such a simple chemical scheme must be implemented carefully to co rrectly represent the atmospheric chemistry (for example, it is implemented incorrectly in the current regulatory version of CALPUFF).

Other air quality modeling rela ted comments made on the prev ious draft pertained to the model performance of AERMOD, taking in to account the uncertainty in model formulation in the uncertainty analys is, and the assumption made for the NO 2 /NO x emission ratio. I will wait to see Chapter 8 and related material before providing additional comments on the revised air quali ty modeling of this second REA draft.

Minor editorial comments:

p. 45, line 9 and p. 109, line 41: three instead of thee

p. 57, line 17; 0 meter instead of 0 me ters (since it is less than 1)60 Comments from Dr. Elizabeth “Lianne” Sheppard

General comments : This second draft REA is signi ficant improvement over the first draft. I commend EPA staff for their success. The document is appropriate in its length and depth of coverage of the material, and it gives a concise yet clear discussion with improved flow. Chapter 5 is a good addition. It uses the ISA re sults to justify the standards to be considered in the risk and exposure assessment. Chapter 6 discusses the risk and exposure assessment approaches used in the remainder of the document. It is easier to follow this revised discussion. [Notably, there is no mention of the tiers described in the Health Assessment Plan. Th is language should be revisited in future rounds of the review process so there is more cross-document integration.] Chapter 9 has been added in response to CASAC comments and appropriately presents an example scenario to put the epidemiological results in context. There is no concluding chapter. The document may further benefit from this addi tion in order to integrate the conclusions from the three risk and exposure assessment approaches.

Now that it is becoming apparent that the REA is to more directly take on some of the role of the previous Staff Paper, modificat ions are needed to bring forward all policyrelevant aspects. As only one of many possi ble examples, it is important to explicitly recognize in the REA that NO2 is the indicator for NOx.

There was good support and referencing to rele vant ISA sections. The same should be done with the appendices.

Air quality characterization : Chapter 7 is much improved. I have several major comments as well as a host of specific comments noted below.

• I appreciate the additional stratification of monitors by distance from major roads and the ability to see the differences in the analyses as a function of this stratification. More refinement is need ed prior to presenting this analysis to describe the stratification and also the f eatures of the two strata. Specifically, Table 7-1 should be expanded to show the number of complete monitors in each time period that fall into each stratum. In addition, it would be valuable to know how much heterogeneity there is acro ss monitors in each of the strata on important characteristics such as th e population density in a buffer surrounding the monitor, the dominant land use with in the surrounding buffer, the types of major roads nearby, and the distribution of distances to major roads. An entire subsection should be added to Section 7.2 to further describe these features. Much of this information is described in Appendix A (as tabu lar lists); now all that is needed is an analysis and concise description.

• This chapter still suffers from the assumption that the monitoring network actually represents a sample of monitors that provides meaningful information about population exposure. This assump tion should be stated up front and evaluated in the beginning of the chapter. I sugg est adding a section that discusses the monitoring obj ectives of the NOx regulatory monitoring network, presents an analysis of the proportion of monitors sited to meet each objective, and provides a qualitative di scussion of how these obj ectives align with the intended inference from data analysis presented in chapter.61 • The discussion of monitoring height suggest s that in general further analysis of monitoring data with respect to monitor features should be conducted for eventual incorporation into the REAs. The most important features will vary by pollutant; for NOx this will include vertical placement, proximity to nearby roads, and other pertinent geographic features

Health effects evidence characterization and selection of potentia l alterna tive standards : This appears appropriate.

Characterization of exposure : The plans for Chapter 8 suggest the content of the chapter will be similar to the previous version with an improved air quality analysis and a new location (Atlanta). EPA staff have been ve ry responsive to CASAC’s comments and are still struggling with providing predictions that are acceptable.

• For the air quality modeling, expand the prediction assessment with additional figures and tables. In addition to the diurnal and cumulative distribution figures we saw, ideas include observed vs. predic ted scatterplots, time series plots over 3 years of predicted and observed series on the same plot (probably aggregated to the daily average), scatterplots stratified by season, etc.

• Develop criteria for predictions that are “good enough”. For instance, overpredicting the tails of the distribution for NO2 particul arly when these are still below NOx may not be so bad from the benchmark assessment perspective. Alternatively, and particularly since the effort is time-limited, clearly quantify how good the predictions are.

Characterization of health risks : The addition of the health risk assessment for ED visits in Atlanta is generally appr opriate and appears to be s ound. I appreciate this added perspective.

Specific comments :

• p. 7 1.3: Expand this section to disc uss the full scope of the document, particularly given the September 8, 2008 memo from Marcus Peacock that suggests an expanded role for the REA.

• p. 11 l 4-7: I think this statement is too general. The consequences of exposure misclassification will depend upon the use of the data.

• p. 11: The distinction between exposure a nd concentration are blurred. The focus is on exposure but the discu ssion is about concentration.

• p 12 l 11-13: Again I think this statement is too general here. In the context of personal exposure-response vs. conc entration-response estimates from epidemiological studies, I think an important distinction is that the two types of studies are estimating different parameters. This is more important than a focus on measurement error bias (which I would agree shouldn’t be neglected).

• P 22 l 7-8: This mistake came forward from the ISA and must be fixed. The outcome for the CAMP study is asthma symptoms, not cough. Also the “multipollutant” models reported are joint models, i.e. the effect of changing bothpollutants at the same time. The sentence implies the more common use of multipollutant which is the effect of a single pollutant when the other pollutant is held62 constant in the model. I suggest re placing “Multi-pollutant” with “joint” and “included” with “added”.

• P. 24 Table 4-1: There is an error in the 0.1-0.15 row since the all exposure average is outside the range of the separate strata.

• P 39 4-7: For completeness, inclusion (or citation) of an analysis of the comparability of the 1-hr and 24-hr da ta would (hopefully) help support this

statement.

• P 45 l 24-25 and rest of page: The resu lts being reasonably “considered a broad characterization” is only appropriate if the monitors actually characterize air quality and human exposure. The existi ng monitors don’t capture all types of locations where people spend their time a nd to the degree that they are a biased representation of these locations, th ey may be far from a good “broad characterization”.

• P 46 l 8: Justify why Atlanta here?

• P 46 footnote: Say why Philadelphia is inadequate/only reserved for the appendix?

• P 51 l 10: insert “quality of the” after “The”.

• P 51 l 23-25: Unclear at this early place in the document.

• P 52 l 28-29: Even though all monitors ar e included, it is quite possible that the existing network doesn’t broadly characte rize national air qual ity. There is no discussion in the document of what the monitoring network represents. The stated assumption is too strong and no t justified. It should be evaluated thoroughly.

• P 53: Add a discussion of the regulat ory monitoring objectives and how they align with population exposure.

• P 54 l 2-5: This validity cr iterion could be met but sti ll allow most or all of an entire season to be missing.

• P 54 l 16: insert “long-term” before “temporal”.

• P 54 Table 7-1: Expand the description to include number of near vs. far from road monitors in the “complete” columns, e.g. as “58 (40, 18)” for the early years in Chicago.

• P 55 section 7.2.2.: This assumes these cr iteria really capture areas with high NO2 levels and that geographic location is the most important determinant.

• P 58 l 17: What percent of locatio ns are such monitors available?

• P 58 l 20-1: How many such monitors?

• P 58 l 23: What does the empirical di stribution represent? Is the random assignment appropriate?

• P 58 l 29: Is there a new m each time the data are simulated?

• P 57: The notation on this page appears to be unnecessarily complex. Equation 7-2 is essentially Cb+Cv.

• P 59 7.3: This discussion following the on-road simulation needs some kind of transition so the reader is clear that we ’ve moved from a simulation approach to a data analysis. This section has much better focus than the previous version.

• Tables 7-5 – 7-8: These tables need to better reflect the variable number of siteyears that go into each ro w of data. Otherwise cross-row comparisons within the table have no meaning. Ditto for 7-10 – 7-11.

• P 67 l 6-8: Is this assumption reasonable?63 • P 68 l 16: This is a strong and unsupported assumption.

• P 72 1 14: I had trouble digesting “sub tle” particularly gi ven the dramatic differences illustrated in e.g Figure 7-2.

• P 72 Figure 7-2 and others: These are nice summaries. Consider adding the 25 th

to 75 th percentiles (or the 5 th to 95 th ) as vertical bands to suggest variation.

• P 90 7.4.1: Discuss here and/or earlier how regulatory siting rules affect this application and the qua lity of inference.

• P 91 l 1: “not evenly distributed” is too superficial. Cover more carefully.

• P 91 l 20-22: This potential bias can be assessed. Ho w often is there unequal representation?

• P 92 7.4: The assumption that the monitori ng data are spatially representative is strong and unevaluated. In addition, ther e must be a discussion of network monitoring design in this document and its implications for the inference in this chapter. Finally, it is un clear why it obviously follows that there would be more bias in locations with fewer monitors . While on average one expects more coverage to better represent the populati on, specifically the degree of bias will depend more on where the monitors are sited in the various locations. If monitors aren’t placed to represent population expos ure, more monitors won’t fix the bias problem.

• P 93 top paragraph. I had diffi culty with this discussion.

• P 95 l 21: Insert “and higher mean” after “variable”

• P 97 table 7-19: Not sure I agree with the bias assessment of both air quality adjustment types.

• P 110 baseline incidence: Previous years can be used to estimate missing baseline data.

• Table 9-1 and others: Reflect that thes e numbers are for one year in the title.

• P 119 l 11-13: I suggest replacing tables 9-1 – 9-3 with tables 4-7 – 4-9 from the appendix.64 Comments from Dr. Frank Speizer

Comments on the NO2 Risk and Exposure Assessment Document dated August 2008

Submitted by: Frank E. Speizer, MD

Date: Sept. 1, 2008

Chapter 3:
Discussion of Susceptibility by depende nt variables: The REA document
appropriately presents the conclusions of the ISA as to the adequacy of the evidence (and
were appropriate) lack of adequacy of the ev idence for a wide variety of risk groups. For
preexisting disease it appear s that only asthma app ears to be supported by both
epidemiological and clinical or toxicologica l studies. For cardiovascular disease and
diabetes only epidemiological studies are cited. Further comment needs to be presented

that the reason there is not more supporting evidence is beca use the studies really have
not (and maybe cannot) been done, rather th an there being nega tive clinical or
toxicological studies to report. For age the onl y data appear to be epidemiologic and this
point although indicated by the studies cited could be more specifically stated. The
discussion on the genetics of susceptibility is appropriately qu alified. One genetic

marker is identified and t hough plausible the studies do not provide specific support.
Finally, a little more could have been said to rule out gender as a specific susceptibility
factor as it seems illogical not to indicate that it really must relate to degree of exposure
rather than anything inherent in being male or female.
Issues of vulnerability: The Staff has made the definition of vulnerability to
essentially mean increased risk of higher e xposure. This is an acceptable definition but
not clear that all would agree. It is also not clear that it will defi ne groups separate from

those that are at incr eased susceptibility. There own ex ample of selected ethnic groups at
higher risk of asthma indicates that susceptibi lity cannot be separated from vulnerability.
It is not clear why in section 3.7 Staff ha s focused on the study of Clougherty et al

where violence is mentioned as a modifier. Surely figure 5.3.1 of the ISA gives the
strong impression that most of the studies of asthma ED admissions are positive, without
suggestion that these are all associated with chronic violence exposure.
Chapter 4.65 The table presented on page 24 (table 4.1), and text on page 25 provides an
important summary statistic that needs to be ca rried forward in analysis (I hope I find it).
Two-thirds of asthmatics appear to be res ponsive as defined as airway responsiveness
with exposure between 0.1 ppm- 0.15 ppm.
Top of page 32: Staff appears to have made a decision that only outcomes that

result in a consensus that the overall effect is either cau sal or likely causal would be
considered for formal quantitative risk asse ssment. This is reasonably well supported but

could be considered too cons ervative. Since the differences between likely causal and
suggestive but not sufficient to be considered causal are for the most part related to the

numbers of studies rather than the potential plausibility of results, it seems to me to
include this category at least in itially would be warranted.

Choice of studies: Preferred US based studies. OK but would add or at least
consider some of the European studies, in which NO2 exposure in particular may very

well be better documented.
Ambient over indoor. Again, OK but the bla nket rejection of st udies that include
an indoor component seems inappropriate.
ED visits and hospital admissi on, OK there are more data but this works for me.
Single and multiple pollutant models—good.
Range of 0.1-0.3 ppm chosen for constructi ng health risk estimates appropriate.
However, some of the latter tables go down to 0.050 ppm.
Chapter 5

Indicator of NO2 still reasonable.
Averaging time: Issue here is wh ether suggestive is enough to make
consideration of a standard appr opriate. This is one of the concerns brought about by the

formalization of causation status . It must be remembered th at whatever criteria are use
they are a “suggested plan” for formalizing re asoning and should not be considered as

“written in stone”.
The fact that previous work lead to the conclusion that a long term standard was
needed and new work in the ISA only indicate s there is a suggestiv e relationship cannot
be the sole criteria for dropping the standard. Th is issue will need to be discussed further.
A better argument for dropping th e standard will have to do with the degree to which the66 public is protected by an alte rnative short term standard and whether the levels of
exposure for a long term standard simply do not exist.

Form of standard: consideration of the concentration level rather than frequency

of exceedences seems reasonable. The issue will be how this concentration is determined
in the 1 hour averages and if a longer time period is required. Although the Staff appears

to want to be consistent with what was done with PM, my recollec tion is that the final
choice of 98%ile over 3 years was an admini strative decision and not a scientific one.
The fact that both 98 and 99%ile is being looked at is good.
Level: Upper bound of 0.2 ppm is appropria te, however data presented in Figure
5.1 suggest a lower upper bound should be consid ered. Given that 5% excess risk for
asthmatics for admission is occurring with a 98 or 99%ile level of 0.09-0.1, respectively,
to allow the upper bound to go higher will most likely double the risk if one speculates
from Figure 5.2 that 30-40% excess symptoms of asthma occurs with a 98 or 99%ile at
0.05. This becomes too high. With regard to the lower bound Staff seems to be
accepting this relatively high risk of asthma tic symptoms as the norm. This is not
reasonable and some margin of safety or meas ure of uncertainty must be factored in. I
would suggest at least cutting th e lower bound by a factor of 2.
Chapter 6
A brief description of apparently what is being done in Chapter 8. If I understand
it what is being done with the “role down’ is to bring the calculated estimates of
benchmark levels to below currently found levels. Given the change from Annual
averages to 1-24 hour averages, I would like to be assured, a nd it will be interesting to

see, if we have sufficient short term measure at Background levels to do this.
(Unfortunately, Chapter 8 did not a ppear in time for the meeting).
Chapter 7
Approach: The selection cr iteria of sites seems reas onable Unfortunately, ~20 of

sites selected did not meet criteria and in looking over Tabl e 7-1 as a summary of the
sites it is apparent that the sites at altitude (Denver, Colorado Springs) as well as the hot
dry climate of Phoenix in the 2001-06 period di d much worse than the sea level sites in
terms of completeness of data. This will need to be discussed and considered in terms
both of exposure representativeness as well as po tential for health risk at altitude. This is67 particularly troublesome since two of these three sites had the most exceedences in the
study period summarized in table 7-2.
Although I may have missed it, it needs to be made clear in discussion of tables 7-

5 to 7-8, and 7-10- 7-11, that the number of excee dences at 150 contains the total of those

at levels over 150 (if that is the case). Othe rwise looking at the tabl es can be confusing
and misinterpreted.
Not clear why in tables 7-12, 7-13, 7-16 p98 is not included in the tables. Up to
this point this value is included and is likely to be part of the discussion on the form for
setting the standard.
Uncertainty analysis: Exposure discu ssion is good with consideration of a

number of issues. More could be said of the “missingness” and potential biased
representativeness of the avai lable data (for example, th e concern about the selective
nature of the missingness at al titude). With regard to th e statement on page 95 of the

overestimated effects of in-vehicle levels, it seems a little too st rong for the available

limited data. It is conceivable that under particular traffic c onditions (heavy traffic
resulting in idealing) the in vehicle values could be considerably higher than roadside

measures. Table 7-19 is particularly troubling. Ta ken out of context it suggests that there
are very defined bias directions that can be accounted for in each of the source questions.
The text provides much of the discussion of just how complex these issues are and seems
to stand alone. Even though the Table is ti tled “Summary of qualitative uncertainty...” it
doesn’t add very much and might be poorly us ed to simply confuse the administrator in
assuming that the results for each category of s ource can be defined better than is really

the case.
Chapter 9
It would appear that the c hoice of Atlanta to model the risk assessment is quite
appropriate. (It might also be useful to consid er another city with more sustained excesses
or more traffic like Los Angeles if time permitted). However, it seems to me that the
selection of one year (2004) as the baseline incidence may not be appropriate. Although
it is probably true that the gene ral incidence of respiratory ED visits does not change over
a period of a few years, the potential for a unique year to be influenced by events such as68 a high or low flue season is great and theref ore averaging an incidence figure over even 2
consecutive years would have been better.

In tables 9-2 and 9-3 it is not clear what is used in the calculation of the figures
for the “current annual standard”. (I may ha ve missed the explanat ion of how the daily
max hourly is derived). Is a footnote n ecessary to clarify th is for the reader?
Although it is useful to summarize the uncertain ties at the end of the chapter, there is

considerable confusion and variab ility of the nature of the ki nds of uncertainty expressed.
For example uncertainty about the level of certa inty of causality is quite different for the
uncertainty of the representativeness of A tlanta to other urban areas. Similarly the
statistical uncertainty due to sampling error is quite different from the estimate of
baseline incidence. The more thoughtful discussion of each of the topics as presented in
Section 9.6 is there is not helped by this e ffort to put it all in one paragraph.69 Comments from Dr. George Thurston

Prof. George Thurston’s Initial Pre-Meeti ng Comments on CASAC Oxides of Nitrogen Primary NAAQS Review Panel on EPA’s Second Draft of: Risk and Exposure Assessment to Support th e Review of the NO2 Primary National Ambient Air Quality Standard

Overall, I find the document much improved, and feel that the EPA staffers are to be congratulated on an excellent job respondi ng to CASAC’s concerns regarding the first draft. I am especially pleas ed to see the epidemiology-base d risk assessment provided in Chapter 9, and am hoping to see something sim ilar provided in the next draft of the SOx REA. My specific responses to the assigned questions for this 2 nd draft 

### NO
x REA are provided below.

Characterization of Air Quality (Chapters 2, 6, and 7) 1. To what extent are the air quality charac terizations and analyses technically sound, clearly communicated, appropriately characteri zed, and relevant to the review of the primary NO 2 NAAQS?

RESPONSE: This is done well, in genera l. However, the reference benchmarks considered seem to vary in different part s of the document: Page 46 (line 18) says 100, 150, 200, 250, and 300 will be considered, but Ta ble 7-8 considers only exceedances of 150, 200, 250, and 300 (no 100?). In addition, Chap ter 5 says that a standard of 50 ppb will be considered (on line 16), so shouldn’t EPA also present the number of exceedances of that level in Table 7-8 etc., too? Si milarly, Table 7-5 and 7-6 only consider 150, 200, 250, and 300 ppb. Shouldn’t these all consider the same benchmarks to allow maximum comparability? Also, with regard to term usage in the te xt, the word “historic” is used sometimes applied to describe data collected in the past (e.g., footnote on pg. 52, line 15 of page 54, line 14 on pg. 62, etc.), while sometimes it is call “historical” data : I believe the latter is the more correct usage. Similarly, “less th an” is occasionally used (e..g, line 25, pg. 67), but I think “fewer than” is the more accepted usage when referring to counts.

2. In order to simulate just meeting pot ential alternative 1-hour daily maximum standards, we have adjusted NO 2 air quality levels using the same approach that was used in the first draft to simulate just meeting the cu rrent annual standard. To what extent is this approach clearly communi cated and appropriately characterized?

I think that the explanation of, and justif ication for, the roll ing upward and rolling downward could be worded a bit more clearly on page 47, lines 21-30. I think it has to be made clearer that each roll-up/back mode l is seeking to allow us to see how much

more acute 

### NO
x effects protection a potential new s hort-term standard might provide, vs. the existing annual standard, and vs. other potential short-term standard options.

3. Because of the impact of mobile sources on ambient NO 2 , we have estimated on-road NO 2 concentrations. To what extent is the approach taken technically sound, clearly communicated, and appropriately characterized? Do Panel members have comments70 on the relevance of this procedure for reviewing the primary NO 2 NAAQS?

I think this is a very important analysis, as it is said that people spend something like 6% of their time commuting, but get some thing like 60% of their daily outdoor air pollution exposures during that time (Source: CARB). I think the approach taken is a reasonable one.

4. What are the views of the Panel regar ding the adequacy of the assessment of uncertainty and variability?

This is a very good qualitative assessment of the factors affecting uncertainty and variability, but I would have liked a more quantitative a ssessment by which to intercompare the importance of each factor: are th ey of differing orders of magnitude? A figure with a range of possible uncertainty effect (e.g., max-min range of % change) would be more helpful, if it could be developed.

Characterization of Health Effects Eviden ce and Selection of Potential Alternative Standards for Analysis (Chapters 3, 4, 5)

1. The presentation of the NO 2 health effects evidence is based on the information contained in the NO 2 Integrated Science Assessment. What are the views of the Panel on the overall characterization of the health evidence for NO 2 ? To what extent is the presentation clea r and appropriately balanced?

This section is concise and well done: sufficiently clear and balanced.

2. The specific potential altern ative standards that have been selected for analysis are based on both controlled human exposure studies and on epidem iological studies conducted in the United States. What are th e Panel’s views on the appropriateness of these potential alternative standards (in te rms of indicator, av eraging time, form, and level) for the purpose of conducting air qual ity, exposure, and risk assessments and on the rationale used to sele ct them for that purpose?

The choice of 50, 100, 200, 250, and 300 is appropria te, but not all levels are consistently considered in all sections of the document. For example, Table 7-5 considers only 15, 200, 25, and 300, ignoring 50 and 100 ppb. Similarly, on page 55, line 7, the minimum benchmark is stated to be 200, not 50. The lower benchmarks should also be addressed throughout to allow comparison with other Tables and Figures in the document. Characterization of Exposure (Chapters 6 and 8): 1. To what extent is the assessm ent, interpretation, and presen tation of the results of the exposure analysis technically sound, clearly communicated, and appropriately characterized?

Chapter 6 does a good job of this. Chapter 8 remains to be seen.

2. The second draft assessment document evalu ates exposures in Atlanta. What are the views of the Panel on the approach taken and on the interpretation of the results of this analysis?71 This remains to be seen, as Chapter 8 not provided yet.

3. What are the views of the Panel regar ding the adequacy of the assessment of uncertainty and variability?

I assume that this will be provided in Chapter 8.

Characterization of Health Risks (Chapters 7, 8, 9): 1. Based on conclusions in the final ISA re garding airway responsiveness, we have expanded the range of potential health eff ect benchmark values to include 0.1 ppm. Do Panel members have comments on the range of potential health effects benchmark values chosen to characterize risks associated with 1-hour NO 2 exposures?

I feel that the benchmarks should also include 50 ppb across all analyses, as it is already used in the epidemiological rise assessment.

2. To what extent are the assessment, inte rpretation, and presentation of health risk results technically sound, clearly comm unicated, and appropriately characterized?

The application of the ep i-based risks are sound and clearly and appropriately characterized.

3. A focused risk assessment has been c onducted for emergency department visits in Atlanta, GA. To what extent are the asse ssment, interpretation, and presentation of health risk results technically s ound, clearly communicated, and appropriately characterized? What are the views of th e Panel on the approach taken and on the interpretation of the results of this analysis?

I highly commend Staff for this effort: this work is excellent, and highly useful in the standard-setting process. I strongly recommend that this approach be emulated in future REA’s (e.g., SOx).

4. What are the views of the Panel regarding the clarity and adequacy of the discussion of uncertainty and variability with respect to the characte rization of health risks.

This seems adequate, though the addition of quantitative estimates (e.g., order of magnitude) would help in inter-comparing the potential importance of each source of uncertainty.Comm ents from Dr. James Ultm an Comm ents on the Risk and Assessment Docum e nt – Jam e s Ultm an (Sept. 8, 2008)

Much thoughtful work went into developm ent of the analyses that are included in this docum ent. There is, however, an organizati onal shortcom ing in the present docum ent. In particular, the various analyses of air qua lity, exposure m o deling and health effects are not evalu a ted and prioritized as a whole. An effective way of accom p lishing this would be to add a f i nal integ r ative chapter in wh ich the fra m ing questions posed on pages 1 and 2 of the REA are revisited. I understand that it is not the role of this docum ent to argue for or against a particular NAAQS, but the result s of the analy s es need to put in a con t ext that exp e dites the po licy

- setting phase of the standard setting.

Specific co mments on chapter 6 : T h ere is a lack of clarity in the e xplanation of the basis of the equations on pages 38 and 40 (both labeled as eq. 2). This leads to confusion as to the m eaning of all the va riab les—pa r ticu l ar ly the dif f

e rence b e tween C a and C b . Given the high frequency of on-road exceedances, it is important th a t thes e equations be better explained and justified.

Answers to Specific Questions on A i r Characterization

1

. To wh at ex ten t are th e ai r q u a lity ch aracteri zatio n s and an alyses techn i cally so un d, cl early

comm unicated, appropriately characte r i zed, and rel e vant t o t h e revi e w of t h e pri m ary NO 2 NA A Q S ? This was su mmarized very well in the m a in body and well-characterized in Appendix A.

2. I n or der t o si m u l a t e just m eet i ng pot e n t i a l al t e rnat i v e 1- h o u r dai l y m a xim u m st andards

, we ha ve a d ju st ed NO2 ai r q u a lity lev e ls u s i n g th e sam e ap proach th at was u s ed in th e first draft to sim u late ju st m eetin g th e
current a n nual standa rd. T o what exte nt is thi s ap pr oac h cl e a rl y com m uni cated and a p propriately characte r ized ? Proportional roll-up and roll-down have a ppeared to becom e a common process for adjusting ambient air quality data. The pr operties of the data that allow such an extrapolation should be more explicitly st ated. D o es the NO2 data set m e et these criterion. Is there any way to validate the process?

3. B eca use o f t

h e i m pact of m obi l e s o urces o n am bi ent N O 2

, we ha ve est i m a t e d on -r oa d N O 2 con cen t r atio n s . To wh at ex ten t is t h e app r o a ch tak e n tech n i cally sound , clear l y

comm unicated, and a p propriately character i z ed ? Do Pa nel m e m b ers ha ve com m e nt s

o n th e r e lev a n c e of th is pr o c ed ur e f o r r e v i ew ing th e pr im a r y NO 2 NAAQ S ? Better explanation of the equations in chap ter 6 is needed (s ee my specific comments on chapter 6.

4

. What are th e v i ews o f t

h e Pan e l reg a rd i n g th e ad eq u acy of th e assessm en t of un certain t y an d v a riab ility ? The use of ambient data monitored above ground level m a y underpredict the actual concentration at ground level where the subjec ts reside. It is possible to conduct a quantitative uncertainty analys is to s ee how this will af f

ect o n -road ex ce edances ?

72Comm ents from Dr. Ronald W y zga

Comm ents on CASAC Oxides of Nitrogen Pr im ary NAAQS Review Panel on EPA’s Second Draf t of : Risk and Exposure Assessment to Support the Review of the NO2 Primar y National A m bient Air Quality S t an dard

Comm ents on Second Draft of: Risk and Exposure Assessm ent to Support the Revi ew of the NO2 Pri m ary National Am bient Air Quality Stan dard

Overall comm ent:

There is a very im pressive am ount of work th at has gone into this docum ent; I am c l early im pressed by the volum e of m a terials and the tho ught behind much of the written m a terial. My

m a jor problem is that it appears as if the various chapte rs wer e written by different individuals and it is unclear how m u ch of the m a terial fits to g e ther. Indeed at tim e s the m a terial in the various chapters/appe ndices appears to contradict m a terial in other sections. I personally believ e tha t the autho r s of this docu m ent would have benefited substantia lly if additional tim e had been av ailab l e to th em before the release of this draft.

Characterization of Air Qua lity (Chapters 2, 6, and 7) 1. To what extent are the air quality characte rizations and analyses technically sound, clearly communicated, appropriately char acterized, and relevant to the review of the prim ary NO 2 NAAQS?

The air quality characterizatio ns are well presented and summ arized. I have two m a jor questions, however. The docum ent uses a dich otom y of >/<100 m of a r o adway in order to characterize monitors an d their re su lting data. Ye t it also s t ate s that und er most circum stances there is a 90% reduction of the NOx roadway em i ssions within 10m of a r o adway. Given these inform ation, is the 100m breakpoi nt appropriate? Should an alte rnative breakpoint have been considered ? Are there an y m onito rs within 10 m of a roadway? W h at do they show ? Also I would like to see data on the diurnal patterns of NOx levels, especially around roadways. APEX says it inclu d es such inf o rm ation, but it is not ex plicitly covered els e where; hence I am confused. Intuitively it seem s to me that the highest e xposures could occur around roadways during rush hour, but I don’t see anything in this docum ent that addr esses this issue.

It would also help m e to understand the data if Tables 7-3 and 4 explicitly indicated the num ber of m onitors considered for each city ; this would give som e indication of the exten t there was coverage in a given city.

Tables 7-5 through 7-8, Tables 7-10-7-18 also indicated the total num ber of opportunities for there to be exceedances; in pother words, what is the denom inator fo r th e rate of exceedance. It is not clear from the text.

732. In order to sim u late just m eeting potential alternative 1-hour daily m a xim u m standards, we have adjusted NO 2 air quality leve ls u s ing the s a me approach that was used in the f i r s t d r af t to sim u late just m eeting the curren t ann u al standa rd. To what extent is this ap proach clearly communicated and appropriately ch aracterized ?

The m a terial is clearly presente d; I rem a in uncomfortable with a concept that shows far greater risks and exposures resulting from confor m a nce to the cu rren t stand a rd th an with an “as is”

scenar io. I a m also unco m f o rtable with th e grea t variab ility in m u ltiplier constan t s ac ross different geographic areas; I have no solution for this proble m, but it is disturbing and suggests

to m e that th ere are cons iderable uncer ta inties in tr oduced by this approach.

3. Because o f the im pact of m obile sources on am bient NO 2 , we have estim ated on-road NO 2 concentrations. To what extent is the approach taken techni cally sound, clearly communicated, and appropriately characterized? Do Panel m e m b ers have comments on the relevance of this procedure for reviewing the prim ary NO 2 NAAQS?

See m y response to question 1. I would like to see m o re data on diur na l v a riab ility ne ar roadways and from m oni tors closer than 100m roadways.

I am also unclear about how va lues of the on-road factors ( m ) were ran d om ly assig n ed? W h at distributions were assumed for m ? p. 58, ll. 23-24.

4. W h at are the views of the Pane l regarding the adequacy of th e assessment of uncertainty and variab ility ?

See responses to the above questi ons. Som e of my questions m a y need to be addressed in the uncertainty section.

Characterization of Health Effects Eviden ce and Selectio n of Potential Alternative Standards for Analysis (Chapters 3, 4, 5)

1. The presentation of the NO 2 health effects evidence is based on the inform ation contained in the NO 2 Integrated Science Asses s m ent. What ar e the view s of the Panel on the overall characterization of the health ev idence for NO 2 ? To what extent is the presentation clear and appropriately balanced?

I believe it is accurate and fair.

2. The specific potential alternativ e standards that have been sele cted for analysis are based on both controlled hum an exposure studies and on ep idem iological studies conducted in the United States. W h at are th e Pan e l’s v i ews o n the approp ri ateness of these poten tial altern ativ e standards (in term s of indicator, averagi ng tim e, for m , and level) for th e purpose of conducting air quality,

74exposure, and risk assessm e nts and on the rationa le used to select th em for that purpose?

There is inconsistency within the docum e nt about the level chosen for analysis. Personally I believe that a shorter-term exposure (e.g., 1 hour) is m o re appropriate than a longer-term one (24-hour); this also allows gr eater congruence between the hum a n clinical and epidem iological studies. If I recall co rrectly, didn’t the Clean Air Act Am endm ents of 1977 suggest that a standard of 3hours or less be cons idered; is this still relevant?

Characterization of Exposure (Chapters 6 an d 8):

1. To what extent is the assessm ent, interpre tation, and presentation of the results of the exposure analysis technically sound, cl early com m unicated, and appropriately characterized?

I have m i xed feelings here. I read the Chapter 6 and feel that I have a good understanding of the analytical approach taken. Then I read the A ppendix, which is also well -written, but seem s to take a m o re detailed approach than is conveyed in the Chapter. For example, I am unclear how and the extent to which APEX is app lied from reading the docum e nt per se

.

2. The second draft assessm ent document evaluate s exposures in Atlanta. What are the views of the Panel on the approach taken and on the interpretation of the results of this analys is ?

I am basing my comm ents on Appendi x C, which I basically like.

In the discussion of the T o lbert et al. and Peel et al. studies, it s hould be noted that the authors considered an a priori lag structure for hypothesis testi ng purposes. Peel et al does present lag-specific results for asthm a and upper respiratory illness, which show that most response is for lags 0-2 although there is also som e response for NO2 for lag 3 as well.

I would ask whether th e risk as sessm ent should consider tim e of day. Ne ar-ro ad expo sures could be considerably higher during certain pe riods, and I wonder given the capabilities of APEX can this be addressed?

It should be noted the Peel et al . and Tolbert et al. papers were part of a larger study (ARIES) that considered other health endpoints as well. In particular, daily re spiratory m o rtality and unscheduled physician visits were considered in papers by Klemm et al and Sinclair and Tolsm a . Ca rdiovascular responses w e re also addressed in other pape rs. It should be noted that NO2 was highly co rrelated with s o m e com p onen ts on PM , especially EC, in this d a tase t.

Extrapolation of the underlying incidence data fo r em ergency departm e nt visits to other areas could be im pacted by socio-econom i c considerati ons. For those without health insurance or the ability to pay for healthcare, ED visits are m o r e frequent as those with other options seek them out before visiting an ED.

753. What are the views of the Panel regarding th e ad equacy of th e assessm ent of uncertainty and variability?

See responses to the above. It should be noted that the statistical si gnificance of results is im pacted by the presence of other pollutants in the m odel. The P eel et al. results particularly found ozone to be of concern for respiratory endpoints.

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Characterization of Health Risks (Chapters 7, 8, 9):

1. Based on conclusions in the final ISA regardin g airway responsiveness, we have expanded the range of potential health effect benchm ark values to include 0.1 ppm

. Do Panel mem b ers have comments on the range of potential health effects benchm ark values chosen to ch aracterize risks associated with 1-ho ur NO 2 exposures?

There appears to be inconsistencies in the document about benchm arks or exposure levels utilized.

2. To what extent are the assessm ent, interpreta tion, and presentation of health risk resu lts technically sound, clearly communicate d, and appropriately characterized?

See above comm ents. I also await the results of risk analysis for hum a n clinical study data.

3. A focused risk assessm e nt has been conducted for e m ergency department visits in Atlanta, GA. To wha t extent are the assessm ent, interpre tation, and presentation of health risk results technically sound, clearly communicat ed, and appropriately characte rized? W h at are the views of the Panel on the approach taken and on the inte rpretation of the result s of this analysis?

See above comm ents.

Minor com m e nt: P. 45, l. 9: “three”

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