1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C. 20460

OFFICE OF THE ADMINISTRATOR
SCIENCE ADVISORY BOARD

December 16, 2008

EPA-CASAC-09-003

The Honorable Stephen L. Johnson

Administrator U.S. Environmental Protection Agency 1200 Pennsylvania Avenue, N.W. Washington, D.C. 20460

Subject: Clean Air Scientific Advisory Committee’s (CASAC) Review Comments

on EPA’s Risk and Exposure Assessment to Support the Review of the NO 2 Primary National Ambient Air Quality Standard

Dear Administrator Johnson:

The CASAC Oxides of Nitrogen Pr imary National Ambient Air Quality Standards (NAAQS) Review Panel (see Encl osure A for Panel Roster) is providing

review comments on the Environmenta l Protection Agency’s (EPA) final Risk and Exposure Assessment (REA) to Support the Review of the NO 2 Primary National Ambient Air Quality Standard. We focus on Chapter 10, which summarizes the findings in the document and discusses options for revisions of the NAAQS. This is the fourth advisory letter that CASAC has provided on the NO 2 REA. 1

CASAC decided to provide review comments on this REA, even though EPA has

finalized the document to meet the cour t-ordered schedule for the NAAQS review, because this draft represents the first in stance of completing an REA under the revised approach for NAAQS review. We understa nd that CASAC’s comments will be given consideration as EPA moves forward to develop the NO 2 primary NAAQS Advance Notice of Proposed Rulemaking (ANPR) for publication in January 2009. 2 Because this review was initiated by CASAC, EPA did not provide specif ic charge questions. The CASAC panel held a public teleconference on December 5, 2008 to review the completed

REA.

1 CASAC provided a letter on June 25, 2008 (EPA-CASAC-08-014) providing peer review of the first draft REA; a letter on September 24, 2008 (EPA-CASAC-08-021) providing peer review of a second draft of the REA that did not include Chapter 8 on exposure or the summary Chapter 10; and a letter on October 28, 2008 (EPA-CASAC-09-001) providing peer review of the REA draft Chapter 8.

2 CASAC also notes that it is providing advice and revi ew on the secondary NAAQS for oxides of nitrogen and that the setting of the primary NAAQS has implications for the related secondary standard, to be published later in 2009.2 Overall, CASAC found this version of th e REA satisfactory in its approach to moving from the scientific foundation devel oped in the Integrated Science Assessment (ISA) to setting out eviden ce-based options for the NAAQS. The REA provides the needed bridge from the evidence presented in the ISA to a characterization of the exposures and the associated risks with di fferent profiles of e xposure. It draws on toxicological and epidemiological evidence and a ddresses risk to an identified susceptible population, people with asthmatic conditions. EPA has also systematically described

uncertainties associated with the risk a ssessments. We commend EPA for developing a succinct and thoughtfully developed synthesi s in Chapter 10. This summary chapter represents a long-needed a nd transparent model for lin king a substantial body of

scientific evidence to the f our elements of the NAAQS.

This letter provides the panel’s comments concerning the most critical aspect of Chapter 10, its recommendations concerning the four elements of the NAAQS for NO 2

. We also provide general comments on other ma jor issues identified by the panel in its review. CASAC also prepared a set of more specific panel comments, included as

Enclosure B with this letter. Enclosur e C provides comments of individual panel

members.

We turn first to the discussion of the NAAQS in Chapte r 10. CASAC concurs with EPA’s judgment that the current NAAQS does not protect the public’s health and that it should be revised. With regard to the options for revisions to the four elements of the NAAQS, we recommend, as follows:

• Indicator: The panel concurs w ith retention of NO 2 as the indicator.

• Averaging time: The panel concurs with having a short-term NAAQS primary standard for oxides of nitrogen and using the one-hour maximum NO 2 value. CASAC also recommends retaining the current standard based on the annual average. It bases this recommendation on the limited evidence related to potential long-term effects of NO 2 exposure and the lack of st rong evidence of no effect. Additionally, the findings of the REA do not provide assurance that a short-term

standard based on the one-hour maximum will necessarily protect the population from long-term exposures at levels potent ially leading to adverse health effects.

• Ambient air concentrations: For the short-term st andard, EPA presented two sets of recommendations: from 50 to 100 ppb and from 50 to 200 ppb NO 2 . The

evidence reviewed in the REA indicates th at adverse health effects have been documented in clinical studies of persons with asthma at 100 ppb and the REA finds “...strong support for a level at or below 100 ppb” (page 309). CASAC firmly recommends that the upper end of the range not exceed 100 ppb, given the findings of the REA. For the annual standard, the panel recommends retaining the current level, as evidence has not been cited that would lead to either an

increase or decrease.3 • Statistical form: The selection of the percentile depends on the ambient air concentration chosen for the NAAQS. CA SAC advises that EPA choose a health protective percentile appropria te for the level chosen for the one-hour standard. For example, if the lower bound of 50 ppb were recommended as the level, the 98th percentile would be appropriate. If EPA were to decide that the lower bound should be a higher number, then the Agency would need to consider a percentile higher than 98 as the form.

The REA makes some general comments a bout the role of scie ntific evidence and policy judgments in revising the NAAQS. CASAC notes that the NAAQS are based on the scientific evidence, and that policy judgments addressing gaps and uncertainties in the evidence base are within the purview of th e REA as it offers options for the NAAQS. With regard to characterization of un certainty, the REA provides a relatively comprehensive but qualitative description of the major uncertainties. We encourage

continued evolution of the characterization of uncertainty to include some quantitative analyses as well, particularly for the sources of uncertainty that are found to be major. Any biases arising from the available data or assumptions made to bridge uncertainties also need explicit c onsideration. The REA leaves open how the uncertainties should be considered in promulgating the NAAQS. CASAC offers the reminder that the intent of the Clean Air Act is to protect public health with an adequate margin of safety and consequently uncertainty should be considered as a reason to move towards the lower end of the range of levels an d not to the upper.

Second, we turn to the NAAQS review pro cess in general, which will also be the focus of a forthcoming CASAC advisory letter. CASAC is troubled by the implications of the greatly accelerated NAAQS schedule in the NO 2 review for CASAC's fulfilling its statutory advisory and review ro le. It is especially important that, in the future, sufficient time be included in the document developmen t schedule so that CASAC can receive the completed REA for review and comment before it is finalized by the EPA. CASAC also

notes that some issues criti cal to public health protecti on relating to monitoring and implementation will be addressed in the Ja nuary 2009 ANPR prior to CASAC review. One important issue concerns the siting of monitors in a manner that recognizes the spatial variability of NO 2 levels.

In closing, the panel noted that the fi nal REA has satisfied the need for a

document that can link the scientific founda tion for the NAAQS review, provided in the ISA, to future presentation of evidence-b ased options for the NAAQS, which will be provided in EPA's ANPR, now scheduled for publication in January 2009. CASAC recommends that the remaining REA technical issues identified in the panel comments in4 the enclosure to this letter be addressed in the ANPR, so that the scientific evidence in the supporting the options can be clearly and accu rately outlined in the ANPR. We look forward to reviewing the ANPR early next year.

Sincerely,

/Signed/

Dr. Jonathan M. Samet, Chair Clean Air Scientific Advisory Committee

Enclosures

cc: Marcus Peacock, Deputy Administrator5 

### NOTICE

This report has been written as part of the activities of the EPA's Clean Air Scientific Advisory Committee (CAS AC), a Federal advisory committee independently chartered to provide extramural scientific information and advice to the

Administrator and other offi cials of the EPA. CASAC provides balanced, expert

assessment of scientific matters related to issues and problems facing the Agency. This report has not been re viewed for approval by the Agency and, hence, the contents of this report do not necessarily represent the views and policies of the EPA, nor of other agencies within the Executiv e Branch of the Federal government. In addition, any mention of trade names or commercial products does not constitute a recommendation for use. CASAC reports are posted on the EPA Web site at: http://www.epa.gov/casac

.6 Enclosure A 

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

CHAIR

Dr. Jonathan M. Samet , Professor and Chair, Departme nt of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA

CASAC MEMBERS Dr. Joseph Brain , Philip Drinker Professor of Envir onmental Physiology, Department of Environmental Health, Harvard School of Public Health, Harvard University, Boston,

MA

Dr. Ellis B. Cowling , University Distinguished Profe ssor At-Large, Emeritus, Colleges of Natural Resources and Agriculture and Life Sciences, North Caroli na State University, Raleigh, NC

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

Dr. H. Christopher Frey , Professor, Department of Civil, Construction and Environmental Engineering, College of Engi neering, North Carolina State University, Raleigh, NC, USA

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

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

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. Douglas Crawford-Brown , Emeritus Professor and Director, Department of Environmental Sciences and Engineering, Univ ersity of North Caro lina at Chapel Hill, Chapel Hill, NC

Dr. Terry Gordon , Professor, Environmental Me dicine, NYU School of Medicine, Tuxedo, NY7 Dr. Dale Hattis , Research Professor, Center for Technology, Environment, and Development, George Perkins Marsh Instit ute, Clark University, Worcester, MA

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

Dr. Patrick Kinney , Associate Professor, Departme nt of Environmental Health Sciences, Mailman School of Public Hea lth , Columbia University, New York, NY

Dr. Steven Kleeberger , Professor, Lab Chief, Labor atory of Respiratory Biology,

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC

Dr. Timothy V. Larson , Professor, Department of Civ il and Environmental Engineering, University of Washi ngton, Seattle, WA, USA

Dr. Kent Pinkerton , Professor, Regents of the Univer sity of California, Center for Health and the Environment, University of California, Davis, CA

Dr. Edward Postlethwait , Professor and Chair, Departme nt of Environmental Health Sciences, School of Public Health, Univers ity of Alabama at Birmingham, Birmingham,

AL

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

Dr. Christian Seigneur , Director, Atmospheric Environm ent Center, Université ParisEst, Champs-sur-Marne, France

Dr. Elizabeth A. (Lianne) Sheppard , Research Professor, Biostatistics and Environmental & Occupational Health Sc iences, Public Health and Community Medicine, University of Washington, Seattle, WA

Dr. Frank Speizer , Edward Kass Professor of Medicine, Channing Laboratory, Harvard Medical School, Boston, MA

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

Dr. James Ultman , Professor, Chemical Engineering, Bioengineering Program, Pennsylvania State Universi ty, University Park, PA

Dr. Ronald Wyzga , Technical Executive, Air Quality Health and Risk, Electric Power Research Institute, Palo Alto, CA

SCIENCE ADVISORY BOARD STAFF Dr. Angela Nugent , Designated Federal Officer8 Enclosure B:

Additional Panel Comments

This enclosure provides more detail ed comments on aspects of the REA, particularly those chapters th at were modified since the prior peer review along with Chapter 10. In evaluating EPA’s Risk and Exposure Assessment to Support the Review of the NO 2 Primary National Ambient Air Quality Standard (REA),the CASAC panel considered the extent to which chapters cove red in previous review s had been modified. A review of Chapters 1 to 6 in the final draft indicates that th ey have not changed appreciably in any way that would affect th e conclusions in Chapte r 10. As a result, the current review does not provide comments on Chapters 1 through 6, ex cept to the extent they influence our assessment of co nclusions drawn in later chapters.

As to Chapters 7 and 8, our review focu sed initially on whether the final draft contains any significant differe nces in numerical results th at affect applications in Chapter 10. We find that the final draft does c ontain substantial revisions to the material presented originally in Chapters 7 and 8, at le ast in the quantitative magnitude of the size of the population affected by exceedances if not necessarily in the qualitative significance of the results as reflected in Chapter 10. These differences ar e due in part to methodological changes, and in part to the f act that the final dr aft report contains estimates of daily maximum exceedances while the previous draft reported total number of one-hr exceedances (so various numbers of exceedances in a day counted an equivalent number of times in calculating the average).

With regard to the analysis of exceedances in Atlanta alone (the second approach), the methodology used is close to that of the earlier draft. As a result, the estimates of key figures such as number of asthmatic-days exceeding a health benchmark

are similar in the two documents. This sim ilarity can be seen, for example, by comparing Figure 8-16 in the final draft ag ainst Figure 8-15 in an earlier draft, where the figures of

the latter are within 20% of those in the form er (the final draft values being lower than those of the earlier draft, resulting from corrections to the methodology suggested in previous CASAC reviews of the REA). These differences do not substantively affect the findings of neither the analysis nor the scientific foundation fo r any of the conclusions in Chapter 10.

We note first that the recommendations in Chapter 10 arise from three different analyses performed in Chapters 7, 8 and 9. These are specifically:

• an approach based on air monitoring resu lts and health benchmark exceedances in 18 cities throughout the U.S. (Chapter 7);

• (ii) an approach based on more de tailed exposure and health benchmark exceedance results in Atlanta (Chapter 8); and

• (iii) an epidemiologically and expos ure-response approach, based again in Atlanta (Chapter 9).

We focus our attention on the methods and resu lts of Chapters 9 and 10; the fidelity with which the results of each approach are summarized for Chapter 10; and how well the three approaches are integrated in draw ing conclusions in Chapter 10, including the impact of uncertainty on the answers produ ced through the three approaches and the9 degree to which final recommendations for the NAAQS are bounded by these three sets of analyses.

The analysis of incidence of emergenc y room visits in Chapter 9 employs a methodology identical in both reports and cons equently the incidence results are the

same. The EPA has chosen in the final draf t to summarize the results as percent of the

incidence attributable to NO 2 exposures, rather than as to tal incidence, which provides a more easily understandable summary conclusion as to the magnitude of health effects. However, it would be useful to see both tota l incidence and percent incidence in adjacent tables of the final draft, as both provide in formation of value in decision-making. This could be accomplished by bringi ng a few of the relevant tabl es, such as Table 4-1, from the Appendices back up into the body of the final draft, especi ally since the text in the

final draft mentions the incidence numbers but the reader must go to the Appendices to

find them.

In addition, the results on incidence are summarized as average daily daily number of incidents, averag ed over a year. This appro ach masks the seasonality of incidence, which can vary significantly th roughout the year. There may be policy implications of such seasonal va riations due to the capacity of the health care system to cope with periods of high incidence, a nd there may also be implications for the uncertainty in risk estimates. At the least, the REA should mention these issues and their potential implications for policy decisions.

Uncertainty analyses have improved across the sequential revisions of the REA. While it still is not possible to place rigorous and quantitative uncer tainty distributions around the key conclusions, the results of Chapters 7, 8 and 9, and therefore of Chapter 10 which relies on these chapters, now include at least substantial qual itative analyses of uncertainty. The major sources of uncertainty have been identified in all three of these chapters, and some assessments made of thei r sources and implications. In Chapter 9 (the epidemiological approach), the EPA has also developed a reasonable system of assigning measures of the degree of un certainty (low/medium/high); a nd the direction of bias (if any) introduced by a specific source of uncertainty has been noted. This characterization of each of the sources of uncertainty is usef ul and can be used for an overall and full assessment of uncertainty. However, there insufficient discussion of the basis for the specific classifications of the subjective degree of uncertainty. CASAC consequently cannot comment on whether these specific j udgments are reasonable. We support the characterization of uncertainty but recommend th at a fully transparent approach be used.

There is a difference in the approaches of the uncertainty anal yses performed in Chapters 7, 8 and 9. The useful format empl oyed in Chapter 9 is more qualitative, but summarizes the results in a way that is most relevant for subsequent decisions. By contrast, Chapters 7 and 8 c ontain more quantitative analys es of uncertainty, although the degree of quantificati on varies significantly from fact or-to-factor. The result is a somewhat unbalanced and disjointed explor ation of the “space” of uncertainty, for example with much discussion of uncertainty du e to fitting a distribut ion to data but more cursory exploration of the effects of uncer tainty in developing health benchmarks. Chapters 7 and 8 should have ended with ta bles similar to the one on uncertainty in Chapter 9.10 It is unlikely, however, that further devel opment of these procedures is needed to serve the purpose of the REA, or that a fully quantitative, Monte-Carlo-style, uncertainty analysis is feasible given the time available for the assessment process. In any event, some of the results, such as those in Chap ter 9, have had quantitative confidence intervals placed around the estimates of incidence. Th ese are admittedly conditional intervals (i.e., conditional on the choice of exposure-respon se model form and conditional on the air monitoring results used), but they are usef ul nonetheless and should be informative in decisions. In any event, we are pleased that the EPA authors have addressed the previous comments of CASAC in regards to taking uncertainty into account in developing this

most recent REA.

The choice of the Tolbert/Peel epidemiol ogical study is reasonable, given EPA's decisions to give increased weight to Nort h American studies and to use Atlanta for a model exposure analysis. In general, the REA uses and reports the results of the Tolbert at al. analyses appropriately. There is some discussion about the use of average baseline rates and some potential bias due to the potential influence of NO 2 exposures on actual incidence; this discussion c ould be extended to consider th e seasonal patterns of both ED

visits and NO 2 in Atlanta. The REA correctly discu sses the pros and cons of using single and multi-pollutant models in several places; however, on p. 273, this discussion is not as well-balanced as elsewhere. In Chapte r 10 (p. 289-90; 308), emphasis is given to

“central estimates” without mention of the uncer tainty of these “central estimates”. This description needs to be modified.

EPA has applied the concentration-re sponse function from the Tolbert study appropriately to Atlanta ambient data. The an alysis in Chapter 9 is, however, based on an implicit assumption that changes in ambient ai r concentrations associ ated with different NAAQS values will be approximately uniform in magnitude across th e 5 counties of the Atlanta metropolitan area, or at least across the areas of most significant exposure. This assumption, commonly made in virtually all time series studies, is a natural consequence of using a monitoring station result as the m easure of exposure for what is in reality a complex spatial pattern, and should be acknowle dged at some point in the chapter or perhaps in Chapter 10. We understand that th e analysis was limited by the way in which the epidemiological study characterized exposur e through this monitoring station. If the spatial field of ambient air c oncentration is simply shifted up or down at a ll spatial points equally when a different NAAQS is introduced, this assumption will be valid. But where

this uniform shift is not the case – and we are convinced it is not – the assumption will be less valid. The contribution of this problem to uncertainty in the results of Chapter 9, and to the implications for conclusions in Ch apter 10, is neither clear nor discussed. Nonetheless, the epidemiology-based appro ach provides additional information that supports EPA's evaluation that a more protective short-term standard is needed to protect public health. And again, as in uncertainty analyses, the EPA authors have been responsive to previous reviews of this RE A, using a study that is of acceptable quality.

In considering further the choice of the study by Tolbert et al. (2007) – which is an update of Peel et al. (2005) - we note that several epidemio logical studies have

examined the associations between ambient air concentrations of NO 2 and respiratory health endpoints; the results of these studies have been mi xed with a large majority of11 them finding a positive association. These results are buttressed by findings of several human clinical studies, which under controlle d exposure conditions, find an association

between NO 2 exposure and respiratory symptoms and lung function responses. The

authors chose to consider studi es conducted in the US and to consider a health endpoint that was unambiguously adverse, ED admissions . Six key studies were identified in the ISA; of the six, four consider ed multi-pollutant models, an important consideration given the relatively high correlations between ambient levels of NO 2 and other pollutants and

the concern that NO 2 could be serving as a surrogate fo r other pollutants. Two of these four studies were undertaken in Atlanta, and two in New York City. The two Atlanta studies are based in the same study with th e second updating the first with additional years of data. The REA analysis could have used any combination of these four studies;

indeed it would be useful to consider some additional analyses based upon all four studies as a sensitivity analysis. Given the variation of their results, this would likely demonstrate a range of responses, at leas t for asthma, the only endpoint that the studies have in

common.

A key issue underlying the conclusions in Ch apter 10 is whether Atlanta is to be taken as representative of exposures and eff ects in other moderately large urban areas. The EPA justification for Atlanta is found in Chapter 8, which reads “...Atlanta is roughly in the middle of the distribution with respect to estimated population and total roadway miles when compared with the other locations examined. Given that there are

factors that would lead to eith er under- or over-estimation with respect to the influence

of on-road and other mobile sources on the re presentativeness of Atlanta relative to the other 17 urban areas examined in the air qua lity analysis, EPA judges that the Atlanta exposure estimates are likely representative of other moderate to large urban areas included in this comparison. EPA does recogni ze that the Atlanta exposure results are likely lower on a population-weighted basis comp ared to the largest urban areas such as Los Angeles, New York, and Chicago given the greater proximity of the population to mobile sources in these large urban areas.”

Chapter 10 contains a direct response to a key policy question that was the basis for the existing NAAQS. The existing NAAQS was established based on the claim that “Retaining the existing standard would also provide protection agai nst short-term peak

NO 2 concentrations at the levels associated with mild changes in pulmonary function and airway responsiveness observed in cont rolled human studies” (60 FR 52874, 52880 (Oct. 11, 1995)). CASAC supports the conclusion of the REA that health effects studies conducted since implementation of the existi ng NAAQS, and the resu lts of the current REA under review, suggest that the existing standard, both in terms of level (0.053 ppm) and averaging period (annual) is not protective of human health in regards to short-term peak NO 2 concentrations. This conclusion is supported uniformly by the three approaches employed in the REA. In this regard, we do not fully agree with the statement on Page 284 that “(t)he way in wh ich exposure and risk results will inform ultimate decisions regarding the NO 2 standard will depend upon the weight placed on each of the analyses when uncertainties associ ated with those analyses are taken into

consideration.”

On Page 286, the authors note competing uncertainties, or biases. The first is that AERMOD may over-predict upper percentile exposures, and the second is that the12 Atlanta case study may under-predict near-road exposures, both in Atlanta as well as in cities where near-road populations are more common. It would be helpful if the authors were to give a summary statement as to the degree to which this introduces significant uncertainty into the final conclusions of the REA. Members of CASAC have differing opinions on the degree to which one or the other of these biases dominate and some

members believe that these two sources of bias are likely to roughly cancel each other.

Given the robustness of conclusions across the three approaches, these biases may not be the primary sources of uncertainty in drawing policy conclusions.

The authors also note that “(h)owever, to the extent that a decision regarding standard level emphasizes the general uncer tainties associated with quantifying the

contributions of NO 2 to respiratory effects in epidem iologic studies and uncertainties regarding the public h ealth significance of NO 2 -associated airway hyperresponsiveness (particularly at 0.1 ppm), a level as high as 0.2 could be supported.” We note that the treatment of uncertainty in th e causal connections between NO 2 exposures and effects is not quantified, and so it is not possible to use uncertainty as the basis for a specific magnitude of adjustment to the upper limit on leve ls to be considered (here, by a factor of 2). The lack of guidance provided in the document on how the various sources of uncertainty and the associated magnitude of uncertainty influence any specific conclusions as to exposure and risk leaves ope n as to how the uncertainty analyses should figure in their use in policy decisions. We encourage the REA authors to provide more guidance as to conclusions in Chapter 10 that are meaningfully uncertain, and the direction of this uncertainty (whether it is likel y to be for or against health protectiveness, or neutral).

A further key issue is whether the Atlant a study results (Chapters 8 and 9) can be extrapolated elsewhere, or at least be considered as repr esentative for a larger U.S. population. The ISA shows that results can vary across studies. Indeed a consideration of

the above-cited studies for asthma ED visits and NO 2 shows variable results. For this reason it would have been preferable for the risk assessment to consider additional studies as well; unfortunately the nu mber of studies that consider NO 2 in both a singlepollutant and a multi-pollutant context is limited; nevertheless some consideration of the New York studies could be helpful and consider ed as a sensitivity/uncertainty analysis. Secondly the results of a specific study are ti ed to the characteristic s of the study and the location in which the study is conducted. The REA points out several of these characteristics, but it should also show th at the use of EDs varies geographically. For some populations, EDs are a major source of healthcare, and it is unclear how Atlanta may differ from other metropolita n areas in this regard.

There is a fundamental issue, however, that is not discussed sufficiently in this chapter; namely, the issue of differe nces between exposures and monitored

concentrations of NO 2 . The REA (and the ISA) notes th at exposures are likely to be significantly higher near road ways, and monitors may not capture these high exposures. The limited discussion of this issue on p. 300 is based upon comparisons of personal exposures and ambient monitoring results fo r extended periods of time (>24 hours). For the much shorter period of one-hour, these compar isons are of uncertain relevance. The highest exposures likely occur when individuals are near ro adways, but personal-activity patterns would not lead to exte nded stays at such locations. Unfortunately there are no13 measurements of short-term personal NO 2 exposures that might better inform this issue. In the REA, adjustment is made to estimate peak NO 2 air concentrations on roadways

from monitored levels. The need for this ad justment contradicts the statement made at the bottom of p. 300. There should be an expa nded discussion of exposure issues in interpreting the results of the epidemiological analysis in the context of st andard setting. The siting of regulatory monitors is a related issue and one th at does not receive attention in Chapter 10, but needs to be considered in the ANPR.

A remaining problem with both Chapters 9 and 10 is inconsistency

inconsideration of alte rnative 1-hour concentrations. EP A shifts between reporting them in ppm and ppb. Eliminating this inconsis tency would improve the document and allow

the reader to focus on conclu sions rather than trying to understanding the basis for these differences. This inconsistency s hould addressed if possible.Comments Received -December 8, 2008

14 Enclosure C: Compilation of Indivi dual Panel Member Comments on EPA’s completed Risk and Exposure Assessment (REA) to Support the Review of the NO 2 Primary National Ambient Air Quality Standard

This enclosure contains final written comme nts of individual members of the Clean Air Scientific Advisory Committee (CASAC) Oxid es of Nitrogen Primary National Ambient Air Quality Standards (NAAQS ) Review Panel. The comm ents are included here to provide both a full perspec tive and a range of individua l views expressed by panel members during the review process. Thes e comments do not represent the views of

CASAC or the CASAC Panel.

Comments Received :

Comments from Prof. Ed Avol ...................................................................................... 15 Comments from Dr. Terry Gordon ............................................................................... 18

Comments from Dr. Dale Hattis .................................................................................... 19 Comments from Dr. Rogene Henderson ....................................................................... 24

Comments from Dr. Donna Kenski ............................................................................... 25 Comments from Dr. Stephen Kleeberger ..................................................................... 27 Comments from Dr. Timothy Larson ........................................................................... 28

Comments from Dr. Armistead Russell ........................................................................ 30 Comments from Dr. Christian Seigneur ....................................................................... 33 Comments from Dr. Richard Schlesinger .................................................................... 34 Comments from Dr. Lianne Sheppard ......................................................................... 35 Comments from Dr. Frank Speizer ............................................................................... 38 Comments from Dr. George Thurston .......................................................................... 40 Comments from Dr. Ronald Wyzga .............................................................................. 41Comments Received -December 8, 2008

Comments from Prof. Ed Avol

Comments on Draft NO2 REA Document (EPA-452/R-08-008a, November 2008)

Ed Avol

(Samet-proposed focus of CA SAC Dec 5 teleconference) Chapter 10 of the REA and the adequacy of the NOx ISA and NO2 REA for asking the question below:

What scientific evidence and/or scientific insights have been deve loped since the last

NOx review to indicate if th e current public-health based NAAQS need to be revised or if alternative levels, indicators, statistical forms, or averaging times of these standards are needed to protect public health with an adequate margin of safety ?

______________________________________

Chapter 10 should be a NO2 document “grand unif ication” of sorts, in which the salient conclusions and judgments of the severa l hundred pages of thoughtful presentation, appendices, tables, and analyses are presented in an accessibl e and succinct presentation. In general, this has been achieved, and staff should be commended for the accomplishment. The chapter is carefully organized, framing the discussion in the context of indicator, averaging time, form, and level of the standard. Clarity and logic of argument is provided across most of the four main categories of discussion.

The scientific insights and research eviden ce that have become available since the 1996

NOx review have been substantial. Severa l informative epidemiologic, and controlledhuman-exposure studies, as well as a wealth of ambient monitoring exposure information, has become available in the decad e since the previous review. The staff has carefully reviewed this data and made a rational and substantive case for the

Administrator to consider revision of the cu rrent standard to protect public health.

Chapter Section 10.4 (“Potential Alternative Standards”) is genera lly well-constructed, logically described, and clearly presented. The explanation for the choice of “Indicator” is clear, logical, and compelling. The presenta tion of “Averaging Time” considerations is informative and convincing. The discussion of “Form” of the standard helpfully provides several examples using several metr opolitan areas and seems justified.

The recommendations of the chapter section c oncerning “Level” of th e standard (Section 10.4.4), however, seemed inconsistent with the presented evidence. The staff’s conclusion that the upper end of the range of a one-hour daily maximum standard reasonably supported by the evidence is 0.2ppm seems inconsistent with the prior

conclusions that “...the scient ific evidence provides strong support for a standard at or below 0.1ppm (100ppb)...” Where is the adequa te margin of safety? Where is the acknowledgement and adjustment for sensitiv e sub-populations (such as more severe

15Comments Received -December 8, 2008

16 asthmatics) who were under-represented in th e scientific studies? It appears that uncertainty concerns, with respect to m easurement errors, health, and monitoring

outcomes have been used to move the disc ussion in only one dire ction (towards a lessprotective level). This is ar guably the wrong direction, if the stated goal is to protect the public’s health.

The final concluding section of the docume nt (Section 10.4.4.3) appr opriately lays out the range of NO2 exposure levels, which base d on the current avai lable evidence, would be protective, but this makes the conclusions of the evidence-based considerations section (10.4.4.1) seem out-of-step with the collective view of the chapter.Comments Received -December 8, 2008

Comments from Dr. James Crapo

The revised REA document, including Chapter 10, is well done and provides an excellent

review and assessment of the scientific data that underlie health risks of exposures to

NO2 at ambient or near ambient levels in the United States. The agency is to be complemented for the scope, design and implementation of this document. It is a

substantial advance over the e quivalent documents in prior reviews in which I have participated over the past 5 years.

The critical data on risk for adverse human health effects at ambient/near ambient levels of NO2 are appropriately reviewed in Chapte r 10 and I would concur with the primary recommendations for the NAAQS for NO 2

.

The indicator is appropriately recommended to remain as NO 2 . The scientific evidence now provides a sound basis for a ne w short-term standard for NO 2 . I would concur with

the staff recommendation for a 1-hour standard. There is little rigorou s data to critique

the choice of the form for the standard and I w ould concur with the selection of either the 98th or 99th percentile.

With regard to the level of a new 1-hour NO 2 standard, I find the data summarized in Chapter 10 convincing that the level should be no higher than 0.1 ppm. Controlled human exposure studies suggest that levels of NO 2 from 0.1 to 0.2 ppm w ould result in adverse symptoms in some asthmatics. I would thus strongly concur with the staff conclusion that the optimum level for the 1-hour NO2 sta ndard would be in the range of 0.1 to 0.05

ppm.

I concur with the recommendations for modi fications to Chapter 10 as summarized in

Enclosure B with the CASAC letter which can be addressed in the upcoming ANPR. With these modifications for clarity and ri gor, I compliment the staff on an excellent

REA document and on recommendations for a new NO2 standard that will reflect the

scientific data and be appropriately supportive of the public health.

17Comments Received -December 8, 2008

Comments from Dr. Terry Gordon

Chapter 10 – NOx REA

Charge question: “What scientific eviden ce and/or scientific insights have been developed since the last NOx review to indicate if the current public-health based NAAQS need to be revised or if alternativ e levels, indicators, st atistical forms, or averaging times of these standards are needed to protect public health with an adequate margin of safety?”

Overall, the chapter is an excellent concluding chapter for the NOx REA. The indicator, form, averaging time, and alternativ e levels sections are very clear and well organized. Based upon the logical pattern of th e assessment of the data, it is not clear how the range is extended up to 0.2 ppm (or even warranted). Despite the chapter’s logical flow and clarity for the suggested alte rnative standard, the Staff does not directly

address what to do with the current standa rd. This is a key issue that the NAAQS development process is required to address.

Minor comments:

Page 277, para 3 – There seems to be some issu e with plural/singular (suggests vs suggest and its vs. their support) Page 277, last bullet – ‘areas ’ is unclear (although I know it is meant for geographic region). Page 279, para 1, line 6 – Were the human e xposure and animals studies only qualitative? Page 288, para 2, line 2 – Unclear sentence: ‘effects that we cannot currently...’ implies that you did assessments on eff ects that you couldn’t quantify. Page 290, para 1 – ‘inclusion’ in th e ‘inclusion’ could be reworded. Page 290, para 2, line 7 – The sentence is unclear : ‘To the extent that these considerations are emphasized,’? Page 292, para 1, line 5 – It is unclear what the ‘air quality corre lations’ are correlating

with. Page 293, Table 10-1 –The table legend needs a little more information so that it can stand on its own (e.g., Max (99 th ): Annual – what is Annual?) Page 296, Table 10-3 – It would be more clear if ‘1-h’ we re added after 0.05, 0.1, etc. Also, ‘alternative’ was used in the title but ‘different’ was used in the table heading. Page 297, para 3, 1 st sentence – It could be me, but the second half of the sentence isn’t

clear: ‘could exceed the standard leve l and still attain the standard’? Page 299, para 1 – The font size appears to be different. Page 299, para 2, line 1 - The choice of ‘g reater protection’ is odd. Are we trying for appropiate protection or greater protection than the current standard? Page 309, para 1 – I realize that this is the conclusion paragra ph for ‘level’, but it is odd reading ‘level’ with no menti on of an averaging time (of 1 hour or anything else).

18Comments Received -December 8, 2008

Comments from Dr. Dale Hattis



### Premeeting Comments for Discussion of the Draft Final REA for NO2

Dale Hattis, Clark University

I am happy to report that there have been substa ntial efforts to addres s the issues I raised in my previous comments on the probabilistic methodology for APEX exposure modeling and the critical on road/off road concen tration adjustment factor. In particular

• EPA staff in the revised Chapter 8 has done some sensitivity analysis for their distributional assumptions related to the indoor removal rate distributions. While I am not completely happy with the anal ysis, I think it reasonably suffices to reduce concerns that there is some large hidden uncertainty that could materially

alter the results of the exposure analysis.

• EPA have now reasonably fully documen ted their database of empirical observations of Cv/Cb (or “m”) that le d to their assumption of the empirical

distributions on-road/off-road sources of emissions for modeling of the NO2 concentrations on and near roadways (Section A-8.2 beginning on A-111 of Appendix A). Based on this documentation I ha ve been able to critically evaluate EPA’s conclusion that no parametric di stribution can be found that reasonably describes the available data. Briefly, I thi nk this is incorrect. However, using the documentation provided, I have develope d a relatively simple alternative distributional suggestion that could at least be used for sensitivity analysis in the

calculations for the eventual ANPR. Th is analysis is given briefly below:

The reason why it is desirable to avoid simp le empirical distribut ions in the kind of exposure/risk analysis being done in the REA is that empirical distributions are necessarily limited to the range of values that have been directly obs erved in the available data. When there are only 41 available data points there is reason to suspect that this could effectively cut off the hi gh tail of the distribution of actual concentrations; and this is unfortunate because the high end tail of the on road and near road concentrations determines the estimates of the frequency w ith which high end concentration benchmarks are exceeded. This concern is magnified in the current case because the 41 observations used for the analysis alrea dy reflect three exclusions of extreme values (see p. A-113)— two from the “not-summer” category and one from the “summer” category.

Figure 1 shows probability plots of the logarithms of the Cv/Cb ratios in the database that EPA has assembled and classified into its “summer” vs “not-summer” categories. * It can

* In this type of plot, the st raight line represents a hypothesis that the data are lognormally distributed, and the corresponde nce of the points to the lin e is a quick qualitative indicator of the correspondence of the data to the theoretical distribut ion. The intercept and slope are estimates of the mean and st andard deviations of the log-transformed values, respectively. Lognormal distributions are expected when there are many factors

19Comments Received -December 8, 2008

be seen that the datapoints—particularly those from the “summer” distribution—are not perfectly described by the stra ight lines representing the lognormal hypothesis—but there is not a radical systematic departure either. Subdividing the “summer” points in to those

that are listed as “downwind” measurements vs those classified as “both upwind and downwind” (Figure 2) locates the departur e from lognormality mostly in the second

category.

The two distributions shown in figure 1 have relatively sim ilar slopes (standard deviations of the log-transformed values). Therefore there is reason to suspect that a simple regression analysis could capture both distributions by deriving a simple multiplicative factor to relate the distribu tions for the two seasonal categories. The regression I derived for this purpose is:

Response: log(m) Summary of Fit RSquare 0.152 RSquare Adj 0.130 Root Mean Square Error 0.227 Mean of Response -0.091 Observations (or Sum Wgts) 41

Parameter Estimates

Term Antilog(Est) Estimate Std Error t Ratio Prob>|t|
Intercept 0.643 -0.192 0.052 -3.69 0.0007

Season2--Summer 1.539 0.187 0.071 2.64 0.012

It can be seen that the “summer” parameter is statistically significant at well under P<.05. To check on whether the regres sion with its root mean square error of .227 (analogous to the standard deviation of the data points about the regression line) can be used to describe the dispersion of the observations, I di d a probability plot of the residuals ** from the regression (Figure 3). It can be seen that the regression residuals are in fact well described as lognormal--having a mean very close to zero and a standa rd deviation within rounding error of the expected 0.227. Theref ore I recommend that in place of its empirical distribution, EPA should substitute lo gnormal distributions for their “m” values with the following parameters:

Gmean GSD

Not Summer 0.643 1.685

Summer 0.989 1.685

This should be done at least for sensitivity analysis for the calculations in the final analysis for the ANPR.

that cause differences among individual obs ervations, and those factors tend to act multiplicatively on the measured parameter.

** Each “residual” is the regression model predicted-value minus the observed value for an individual data point.

20Comments Received -December 8, 2008

Figure 1

2 1 0 -1 -2 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6

Summer

Not Summer 

### Lognormal Plot of On-Road/Off-Road Ratios Sorted Into the EPA Summer/Not-Summer Categories

Z-ScoreLog(On-Road/Off-Road) Cooncentration Ratios y = - 0.005 + 0.216x R^2 = 0.924 y = - 0.192 + 0.243x R^2 = 0.971

21Comments Received -December 8, 2008

Figure 2

2 1 0 -1 -2 -0.4 -0.2 0.0 0.2 0.4 0.6

Summer Downwind Summer Upwind + Downwind Distribution of Summer Log(On-Road/Off-Road) NO2 Concentration Ratios Subdivided by Those Classified as "Downwind" vs "Both Downwind and Upwind"

Z-ScoreLog(On-Road/Off-Road) Concentration Ratios y = 0.039 + 0.219x R^2 = 0.919 y = - 0.058 + 0.230x R^2 = 0.829

22Comments Received -December 8, 2008

23 3 2 1 0 -1 -2 -3 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6

Residual (Obs-Mod pred) Probability Plot of Observed - Model Predicted Ratios of Log(On Road/Off Road) NO2 Concentrations

Z-ScoreResidual--Observed-Model Predicted "m"{Log(On Road/Off Road NO2 concentration)] y = 3e-7 + 0.226x R^2 = 0.980Comments Received -December 8, 2008

Comments from Dr. Rogene Henderson Comments on final Risk and Exposure Asse ssment to Support the Review of the NO2 Primary National Ambient Air Quality Standard

I thought the document was well prepared and provided the information needed for rulemaking. I compliment the Agency on the clarity of their presentation.

My comments will focus on Chapter 10 and will be organized according to the indicator, form, averaging time and alternative levels fo r the standard and whether these elements of the current standard need to be changed to protect the public health with a margin of safety.

Indicator: I agree with the reasoning given in Chap ter 10 that the indicator should remain as

NO 2

.

Averaging time : The current averaging time is based on ear lier studies linking long-term exposure to low levels of NO2 to adverse respiratory effects. More recent studies indicate that

there should be more concern for the short-te rm NO2 exposures. A review of the data in

Table 10-3 indicates that a standard based on annual average NO2 concentrations would not likely be adequate to protec t against the effects of short- term exposures. I agree with the analysis presented in Chapter 10 that in dicates that the standa rd should be based on either a 24-hr or a 1-hr averaging time. Base d on the data in Table 10-2, I agree that a 1- hr standard should protect against 24-hr NO2 concentrations and therefore agree with the

staff conclusion to use a 1-hr averaging time for the standard.

Form: I agree with the reasoning presented in Chapter 10 that a concentration-based form is better than a form based on expected exceedances. I agree that whether you use the 98th or the 99th percentile is dependent on the level one chooses.

Level: I agree that the health endpoint of con cern is increased airway responsiveness in asthmatics. I agree with the staff argument s given on page 303 that the lower end of the range should be 0.05 ppm. I do not agree with setting the upper end of the range at 0.2 ppm. I would prefer 0.1 ppm. My reasoning is based on the fact a meta-analysis of the controlled human exposure studies in mild asthmatics indicated a LOEL of 0.1 ppm NO2.

No severe asthmatics were studied. The Clean Air Act stipulates that we should make our recommendations to protect public health with a margin of safety. Because the endpoint of interest is in asthmatics and becau se we need a margin of safety, I would not recommend an upper level of the range higher than 0.1 ppm.

24Comments Received -December 8, 2008

Comments from Dr. Donna Kenski

Pre-meeting Comments on Risk and Exposur e Assessment to Support the Review of the NO2 Primary National Ambient Air Quality Standard

Donna Kenski Lake Michigan Air Directors Consortium December 4, 2008

The piecemeal nature of this review made it ve ry difficult to maintain a coherent picture

of the document as a whole. I understand the constraints that EPA is under to meet the court-ordered dates for publication, but I hope that future ISA and REA reviews can be scheduled so that the panel has all the parts together to review at one time. I expect it may be difficult for the panel to come to agreement on the letter in our teleconference Friday, given the particular importance of the final chapter in the REA and the fact that

this is the first chance we’ve had to discuss it. Especially since it is now several months

since we’ve had the benefit of our discussions on the rest of the document.

Despite the unfortunate logistic s of the review cycle, I though t Chapter 10 did a great job summarizing the results of the exposure a ssessment, the risk assessment, and the epidemiological assessment and outlining how each of them provides support in their various ways for a short term NO2 standard. It was thorough, logical, and nicely written as well. Only occasionally did it lose its straightforward tone. For example, on p. 290, in the middle of the first paragraph of Sec. 10.3.3., after a succinct su mmary of the ISA’s evidence for short-term effects, the REA states , “To the extent that these considerations are emphasized, the adequacy of the current st andard to protect the public health would clearly be called into question.” Surely these are exactly th e considerations that MUST be emphasized. To state it this way makes it seem like an option. I don’t think the Administrator has the option of ignoring, or even de-emphasizing, th e conclusions of the ISA and the REA. The authors are trying too hard to avoid making statements that could be construed as policy judgments, when they are really sound, logi cal conclusions based on the excellent work presented in both the ISA and REA.

Averaging time: The chapter is a little confusing about the annual vs. hourly standard. Table 10-3 gives a nice comparison of annual averages that would result from just meeting alternative 98 th percentile standards. What is somewhat startling is that, under some of the proposed alternative standard s, the current annual standard could be exceeded. It begs for more discussion. Ev en given the conclusion that evidence relating long-term exposure to adverse health effects is suggestive but not sufficient to infer causality, it’s hard to accept a new standard that potentially allows exceedances of the previous standard. This is a PR prob lem, if not a public health problem.

Form: The section on potential forms of the standard seems to have settled on the 1-h daily maximum without much discussion of the implications of multiple high concentrations in one day. I recall reading somewhere in the ISA or REA about inadequate evidence for effects of multiple exposures in a single day. That information would be appropriate to summa rize here as well. Similarl y, the reasoning behind the 3-

25Comments Received -December 8, 2008

26 year averaging period is not di scussed. Presumably this helps to stabilize the metric? The chapter notes that the 3-year averagi ng time is discussed in the PM and ozone reviews, but the rationale should at least be summarized here.

I have a modest preference for a 98 th percentile form, since it could be set to be sufficiently protective and is likel y to be more stable than a 99 th %ile standard. Thus it is more likely to avoid the awkwardness of areas that flip-flop in and out of attainment, a situation that creates confusion for the public and for the state governments that need to implement the standard and cont rols to achieve it. But as th e chapter appropr iately notes, the protectiveness depends on both the level and the form, so a 98 th percentile form must have an adequately protective level. This section could ha ve used some comparisons of, say, 98 th percentile at 0.05 ppm with 99 th percentile at 0.1 ppm. From Table 10-4, it

seems that the 99 th %ile is never more than 0.01 ppm greater than the 98 th %ile. So might

one infer that a 98 th %ile standard at 0.09 woul d be as protective as a 99 th %ile standard at 0.1 ppm? Which leads me to:

Level: After presenting an excellent summa ry on the concentration ranges at which statistically significant NO2 effects have been seen, I was surprised by the staff conclusion that the upper end of the range of levels is 0.2 ppm. I think both the ISA and REA make a very strong case that the upper e nd should be 0.1 ppm. Setting the standard no higher than 0.1 is all the more critical when one considers the requirement to include a margin of safety, and also the potential of the various analyses to underestimate exposures, which was nicely documented in Sec. 10.3.2.1.

Minor stuff: p. 300, 1 st paragraph: The discussion of av eraging time is in Sec. 10.4.2, not 10.5, and the discussion of form is in Sec. 10.4.3, not 10.6

Hyphenation is improved over previous reports , but many instances of ‘statisticallysignificant’ are hyphena ted in error.

The constant switching between ppm and ppb makes it unnecessarily difficult to compare data in one section of the chapter to a nother. Please make these consistent.Comments Received -December 8, 2008

Comments from Dr. Stephen Kleeberger

I will not reiterate comments made by other panel members regarding adequacy of chapter 10 to summarize indicator, averagi ng time, level and form except to commend staff on an exceptional effort. I thought all sections were well written and clearly outlined the questions, summarized the ex isting pertinent investigations, and

With the understanding that chapter 10 will not be revised, I would yet recommend that a

table be created to summarize the uncertainties described in the chap ter. The text does well to define the uncertainties (beginni ng on page 284), but inasmuch as chapter 10 attempts to bring together many of the key points in the entire documents, I would have

found useful a concise tabulated summary of this important consideration in standardsetting. A summary like this could also serve to better delineate precise research needs.

I would also have found useful another stat ement in section 10.3.3 (page 290) to reemphasize that other sub-groups may be as sens itive or more sensit ive than asthmatics,

and/or that other health e ndpoints may be important (e.g. bi rth outcomes)(the points were raised initially on p 279).

27Comments Received -December 8, 2008

Comments from Dr. Timothy Larson

Comments by Timothy Larson on “Risk and E xposure Assessment to Support the Review of the NO2 Primary National Ambient Air Qu ality Standard Final Draft, November,

2008”

I will limit my comments to th e air quality and exposure analyses. The discussion of the representativeness of the exposur e results and an analysis of the key uncertainties makes the final versions of Chapters 7 and 8 stronger than previous ones. These key uncertainties are summarized in Chapter 10 including the degree of independence of NO2 distributions with extrapolat ion to scenarios “just mee ting” regulatory levels, the accuracy of empirically-derived relationships between ambient and fixed-site monitors, the representativeness of the APEX activity data, the potential upward bias of the AERMOD predictions of the high end of the NO2 distribution of short-term concentrations, and the choice of Atlanta to represent urban areas within the U.S. The assessment of these specific uncertainties is well-balanced.

However, one source of uncertainty that dese rves more discussion involves the amount of exposure that occurs inside re sidences that are in close pr oximity to major roads. These exposures are, in principle, captured by APEX’s “Indoor-Residence” category. However, the perimeter of the census blocks in Atlant a do not appear in general to cross major roads, i.e., the blocks boundaries are define d in part by these roads. Therefore the assignment of an outdoor exposure level by AERMOD to the centroid of the census blocks means that a number of people reside clos er to the road than those living exactly at

the block centroid. Given th e potentially strong horizontal concentration gradients in NO2 near roads in flat terrain and the strong ve rtical gradient near roads in built-up areas, the centroid assignment approach used by EP A is probably underpredicting the exposure to those living very near the roads . This is important because 17% of the population in

Atlanta resides within 75 m of a major road. It would seem that the actual indoor exposures of this subpopulation due to NO2 pene trating from outside is greater than that predicted by APEX. As it st ands, the staff concludes that the AERMOD analyses are “overpredicting the upper percen tile exposures” (p. 286).

I agree with the proposed aver aging time. One minor point: the near road sites show annual averages that are closer to the 1-hr standards than si tes located further from major roads. These relationships may also cha nge if the near-road indoor exposures are

considered.

I agree with the proposed upper a nd lower range of the level. One additional factor to be considered in the ANPR is the possibility th at future monitoring sites may be located nearer to the roadway than they are at pres ent, i.e., the NO2 siti ng criteria may change

from “urban scale” to “microscale”. Ther e is certainly precede nt with carbon monoxide monitoring (short-term standard, major mobile source contribution).

28Comments Received -December 8, 2008

29 I do not have a strong opinion as to which of the proposed forms of the standard (98 th or 99 th percentile) are appropriate. I think that st ability of the target should be given extra weight by EPA over other arguments.Comments Received -December 8, 2008

Comments from Dr. Armistead Russell

Post-call Comments on the Revised REA, with specific focus on Chapter 10 and response to the question “What scientific evidence and/or scientific insights have been developed

since the last NOx review to indicate if the current public-health based based NAAQS

need to be revised or if alte rnative levels, indicators, statis tical forms, or averaging times

of these standards are needed to protect public health with an adequate margin of safety?”

Armistead (Ted) Russell

First, I was pleased by the progress made between our meeting and this current version of the REA. A number of issues have been addressed, but some linger. In particular, I am still concerned about the high bias in the AERMOD results, particularly for simulating higher end concentrations, and it is these concentrations that are driving the exposure analyses and the in terpretation of the results of these analyses in Chapter 10. The performance is really not that good, but I am persuaded that the results should be used, but the performance issues should be considered more objectiv ely, with particular attention to the biases in simulating upper end concentrations, and the on-road-to-monitor ratios. Uncertainty, error and bias are very different beasts when discussing and using model results. Here, bias is the major i ssue, and I am not persuaded by the staff arguments for not dealing with it more thorough ly. Also, it would be very good to give a pdf of simulated on-road concentrations. In regards to Table 8-7, it is important to note those concentrations labeled as AQ monitors are not measured, but are adjusted measured concentrations (see issues below).

A second concern is that the exposur es over specified benchmark levels dominantly occur on road unless that be nchmark level is 100 ppb AND indoor sources are included, in which case, indoor sources pl ay a major role. In that case, Fig. 8-25 suggests that a 100 ppb benchmark level has virtually no effect on the fraction of asthmatics impacted even with a 50 ppb, 99 th %ile standard. Given th at, we must be very concerned with how well we can approximate on-road exposures (which I would suggest is not very well) given the hi gh bias in the AERMOD results (Fig. 8-8 is actually rather alarming in this case, which shows the on-ro ad to monitor values ranging up to over 100, though the study of in-vehicle to monitored va lues that is cited in the ISA and REA (Riediker et al., 2003) , note that “NO2 concen trations inside the cars were always low.” , noting that the average in vehicle leve l was 31.4 ppb when the mean ambient was 30.4 and roadside was 49.9, when one high extrem e value that they could not explain was removed.). Further, the AERMOD results for on -road vs. non-road levels are virtually all greater than one (except at the 0%ile), while observed on-road-to-monitor factors are less than 1 at the 50%ile. This strongly suggests that the modeled on-road exposure is biased high, likely significantly. I also note that th e (albeit limited) comparison of observed to

modeled NO 2 exposures provided further suggest s a potentially large high bias in exposures at the higher end of the distributi ons (Fig. 8-11 vs. Fig. 8-12). Countering the concerns, above, but not quantitat ively addressed in the REA, is that there are urban areas that are not as spread out as Atlanta, and the residential or other near-road exposures could be proportionally higher. Providing a pdf of concentrations on the road, as well as,

30Comments Received -December 8, 2008

say 20m and 50 m from the road, might provide some information to how this issue might influence the interpretation of the results to other locations.

If one, instead, uses on-road-to-monitor ratio s, there is again a problem. It is not apparent that the derived ratios account for a limitation on the ability to oxidize NO to

NO 2 during the periods with the highest NOx leve ls. If the ozone leve ls are significantly reduced, as they will be in locations of high NOx emissions, NO (the primary form of NOx emitted) will not be rapidly oxidized to NO 2 . Thus, using a distribution of on-to-off road ratios (m) that does not take this in to account (e.g., using lower m’s during periods of high NOx levels, if the underlying data s uggest such) could lead to a high bias in predicted on-road NO 2 at the higher end of the distributions . Again, this leads to a bias in estimating the number of exposures of concer n (e.g., over specific benchmark levels).

Associated with this issue is that the ratio of monitor to “on-road” NO 2 levels will be very

sensitive to where the monitor is located. Us ing near-road monitors to assess attainment would require less of a buffer to protect against high on-road NO 2 exposures than one located distant from a major road (th ough studies have found lower in-vehicle NO 2 levels).

A next concern in conducting this risk assessment is that I believe that the concern over confounding is downplayed. NO 2 is a product of com bustion, so non-laboratory exposures typically will co-o ccur with other products of combustion. Of particular concern is PM, and more specifically, fi ne PM rich in carbonaceous compounds. However, combustion byproducts also include a large range of organic gases as well. Some of these gases are also of concern (e.g., formaldehyde). Thus, I consider using multi-pollutant models critical for assessing if there is an association of concern (both single and multi-pollutant models should be used, and results considered). Unlike the REA (and the ISA), given the number of studies that are no longer statistically significant when using multi-pollutant models, I would not characterize the results as robust. Further, they have not measured, and t hus do not control for, many of the other combustion byproducts of concern. Why this is of additional concern is that controls to reduce NOx emissions might actually lead to increases in those other combustion byproducts (e.g., VOCs, such as formaldehyde, and constituents of PM), and this risk is not explored in the REA. Further, incr eases in the VOC emis sions would lead to increased ozone in cities, pa rticularly those where NOx em issions appear to lead to decreases in average ozone exposure. This is also not considered in the REA.

In regards to Chapter 10, the documen t does clearly present EPA’s rationale behind their choice of an indicator, averag ing time, form, and range of levels for a modified primary NO 2 NAAQS. This chapter was very well laid out and presented, and was one of the best summary chapters of this type I have read. I agree with the rationale behind the choice of indicator (NO 2 ), and do not believe that cu rrent instrumental issues are a major problem, particularly if one us es one hour (or 24-hour) maximum levels. As for averaging time, the evidence is clear that a shorter averaging time is called for, and I agree with the rationale for a one hour average. I do not believe a 24- hour average is as strongly supported. As for form, a c oncentration-based standard, using a 98 th or 99 th% ile, averaged over three years, is appropriate, and that choice should be influenced by the

31Comments Received -December 8, 2008

32 choice of level. I tend to prefer the less extreme for stability between years. They should be clear in how this is stated, i.e., that the maximum 1 hour average is taken for each day, and that the 98 th %ile is taken from the distri bution of 1-hour averaged, daily

maximums.

EPA staff suggests a range of level for consideration between 50 to 200 ppb. The upper end could actually lead to an increase in exceedences of benchmark levels, and there is ample clinical evid ence to suggest that health effects would be found at

concentrations that would occu r if 200 ppb were the level ch osen, particularly given the meta-analysis suggesting an lowest observable effect level of 0.1 ppm (which I take as having only one significant digit) . Given the issues discusse d above, the lower end is less strongly supported, and has issues that have not been addresse d in the REA. As such, I

would be most comfortable with a 98%ile , 1-hr daily maximum, NAAQS of about 100 ppb.Comments Received -December 8, 2008

Comments from Dr. Christian Seigneur

Comments on final version of the REA

Christian Seigneur CEREA, Université Paris-Est

My comments pertain to the discussion of the uncertainties. The first paragraph of Section 8.12.1.6 provides a good introduction to th e uncertainties associ ated with the air quality modeling by clearly stating the type s of uncertainties and their causes (e.g., AERMOD is essentially a model designed to identify maximum impacts from elevated point source; it is app lied here to evaluate a distribu tion of concentrations due to emissions from mobile sources, i.e. a problem that differs significantly from AERMOD’s original purpose). However, the second paragr aph lacks objectivity and sounds more like an a posteriori justification of the use of a model with bad performance than a true discussion of uncertainties, as exemplified by the following statements (all line numbers refer to the first full paragraph of p. 236).

Lines 2-4: “the evaluatio n of modeled air quality...s hows overall good agreement

between AERMOD... and...monitored NO 2 concentrations”. AERMOD overpredicts the

mean NO 2 concentration at all three Atlanta mon itors. The REA only mentions explicitly the smallest overprediction (10%), convenien tly avoiding to mention quantitatively the larger overpredictions at the other two recepto rs. It appears clearly in Figures 8-6 and 8-7 that AERMOD overpredicts NO 2 concentrations overall and it is inappropriate to state that AERMOD shows “overall good agreement” with the measurements.

Lines 8-10: “the degree of bi as...is within the factor 2 commonly used to indicate relatively unbiased model performance”. OAQP S seems to confuse “error” and “bias”. The factor of 2 is generally expected for gr ound-level impacts of elev ated point sources; however, it does not imply that remaining within this factor of 2 means that there is no

bias. If all modeled values ar e within a factor of 2 of the measurements but overestimate the measurements, there is a bias toward overestimation.

Lines 10-12: “In considering that this upward bias occurs mainly in the early morning hours, it is possible that there may not be a large proportion of the simulated population exposed at these times of the day”. The high NO2 concentrations are due in part to the heavy traffic at those hours, which implies a large number of peopl e driving those cars. Unless this statement can be quantitativ ely substantiated, it should be deleted.

In summary, the REA document should presen t the uncertainties a ssociated with the AERMOD simulations in a more objective fa shion instead of using the uncertainty discussion as a justification for using a mode l with poor performance. It would also be appropriate to highlight the need for the fu ture development of a model that would be more appropriate than AERMOD for simulati ng the air quality impacts of roadways.

33Comments Received -December 8, 2008

Comments from Dr. Richard Schlesinger Comments on REA, specifically Chapter 10:

Overall, this final draft presents in a clear manner the scientific bases for recommending the NOx standard.

The few specific comments are as follows:

P. 283. First bullet in second paragraph. The term "control" may not be the

best word to use in this context. Perhaps the statement should read "negatively affect asthma treatment protocols."

P. 287. The last sentence in the first paragraph of section 10.3.2.2 notes that 1 hr levels above 0.2 pm are unlik ely to occur in lo cations that meet

the current annual standard. Levels at or above 0.2 pp m have been associated with adverse health outcomes. Thus, this line of thought seems to contradict

the earlier statement in the last sentence on page 282 of section 10.3.2,

which states that results of studi es support a relationship between NO2 exposures and respiratory endpoints at am bient concentrations in areas that

meet the current standard.

P. 309. Section 10.4.4.3 This section conc ludes that the standard level should be set between 50 and 100ppb. However, the prior discussion seems to

indicate that if the current leve l of 53 ppb as annual average is maintained, that shorter term excursi ons would occur that may result in adverse health outcomes in some groups of the population. Furthermore, the last sentence implies that the REA is recommending a change from the current standard. Thus, this reviewer is some what confused as to what is being

recommended here.

34Comments Received -December 8, 2008

Comments from Dr. Lianne Sheppard

Final draft NO2 REA comments

Summary : The major changes to this document are an ad ded chapter 10 and revisi ons to chapter 8 in response to CASAC comments. I am concerned that the difficulties with receptor

locations in AERMOD have not been corrected or even fully acknowledged. This is has serious implications for the results and our inference from them. Several other important changes have been introduced, such as a ta ble characterizing key uncertainties in chapter

9.

Organization and placement of policy discussions : Chapter 10 provides a bridge between the conc lusions of the ISA and REA and the policy recommendations to appear in the ANPR. Th e discussion contained in chapter 10 is an essential component of the re view process and has been well crafted. However, the outline of the current process suggests to me that the ANPR is supposed to cover policy

assessment while the REA should be confined to risk-based consid erations to inform standard setting (e.g. see figure 1-1). Therefore I suggest duplicating section 10.4 in the ANPR. Policy inferences in the REA are a helpful precursor to the ANPR because there is an opportunity for CASAC feedback with time for EPA staff to integrate this feedback into their work. The description of the pr ocess should be modifi ed to acknowledge the incorporation of this preliminary policy a ssessment into the REA and the name of the REA should be changed to refl ect its broader scope.

Important omissions :

• The assumption regarding receptor locatio ns for AERMOD predictions that are fed into APEX is not adequately just ified and is completely omitted in the Chapter 8 discussion of uncertainty. Therefore this likely major source of underprediction of exceedances is completely ignored in chapter 10.

• The data have a great deal to tell us a bout monitor siting and levels of NO2. The monitoring network design, particularly with respect to proximity to roads, will have huge implications for whether or not exceedances are measured. Chapter 10

needs to discuss the data in the contex t of insights they provide into network design. Given the move towards a short-term standard, it will be important to add regulatory monitors near roads. (Consid er the NO2 sources and the precedent set by regulation of CO.) As is evident in Table 10-3, monitors that are closer to roads have annual averages that are higher than monitors far (>100 m) from roads. The implications of network design on the annual standard also must be

discussed.

Uncertainty presentation:

• Consider using recent advances in the a ssessment and presentation of uncertainty presented by the Intergovernmental Pa nel on Climate Change (see e.g. the IPCC

4 th Assessment reports, such as the AR4 S ynthesis report and the Physical Basis report; http://www.ipcc.ch/ipccre ports/assessments-reports.htm).

35Comments Received -December 8, 2008

• Make sure to clearly delineate suspecte d biases as part of the uncertainty presentation.

• The presentation should exp licitly recognize the CAA re quirement to protect the population with an adequate margin of sa fety. Given the need for a margin of safety, uncertainty should not be used as an argument for increasing the levels under consideration for a standard (e.g. p. 304).

Specific comments chapter 8 :

• The addition of Figure 8-1 is useful. Ho wever it does not show receptor locations as inputs into AERMOD, a major oversight.

• p 150: There should be some discu ssion of the link between the receptor locations used in the AERMOD predictions and the selected census blocks used by APEX.

• p. 167: There has been no assessment of the distribution of population as defined by receptor locations related to the actual percentage of the Atlanta population living close to roads. Footnote 12 is help ful additional info, but is insufficient.

The buffers for evaluation should be sele cted based on scientific considerations, not regression model fits to predicted data (description p. 216). The locations of the centroids used in this analysis do notappear to have changed since the last

version. I am concerned that too few centr oids are within 50 or 100m of a major road relative to the population of Atla nta. Since NO2 concentration varies dramatically as a function of distance to nearby major roads, if the distribution of distances to major roads does not reflect the Atlanta populatio n, the results could be seriously biased. Give n the different buffers in the descriptions on pp 167 and 168, it is difficult to make any sense of th e limited statistics that are reported.

• P. 168-9: The description of the distri butional calculations on p 169 was clearer to me this time. Justify the selectio n of the 4 km buffer for evaluation of predicted relative to monitored concentrati ons with e.g. additional data analysis. I am concerned that the summarizing featur es of within-loca tion distributions across locations could give a misleading fo cus of attention. Since figures 8-6 and 8-7 are based on pointwise summarizati ons across locations, evaluation of the approach is important.

• p. 190: Quantify the number of non-road block centroids located near a major road and pay particular attention to shor t distances (not just the 75 m buffer). Stratify the AERMOD on-road CDF in Figure 8-9 by road proximity category. Possibly pass this through to APEX to estimate the indoor distributions also.

• Figure 8-17,18: Provide deta ils that clearly defines wh at locations, individuals, and activities that make up each categor y in the pie chart and provide this reference with the figures. It is too ea sy to make assumptions about what is contained in each category. I’m also c oncerned that near-road exposures (e.g. at residences) are underreported in AERM OD and similarly in how they pass through to APEX indoor exposures. To th at end, consider adding at least one additional micro-environment in Table 8-9: Indoors – Residence near major road.

• P. 216: Distance to roadway bins should be based on scientific considerations, not regression analyses of predicted data. Based on Zhu et al (2002), most of the

36Comments Received -December 8, 2008

37 effect is within the first 100 m. It would be entirely appropriate to have 2-3 bins completely within that first 100m.

• p 216: The description of estimation of population percentages within buffers is not transparent. It should also be made very clear that Table 8-14 is based on a model that uses unverified assumptions of uniform distributions of populations over space. How were major roadways at the boundary of the block handled?

Are boundaries “within the block”?

• p 217: Be careful about circ ular reasoning. It is possi ble that most exceedances were associated with in-vehicle expos ures because the spatio-temporal NO2 predictions relied on receptor s that were systematically farther from roads than some of the population. If the model did not properly locate residents sufficiently close to major roads, the at home predic tions of NO2 would have been biased

low.

• Section 8.12: This section does not even mention receptor locations as a source of uncertainty.

Specific comments, Chapter 10 :

• p 281, bottom 1 st paragraph: Statistical significance should not be used as a criterion for scientific importance.

• p 286: Receptor locations affect predictions and may not be aligned with the population distribution, particularly at the closest distances to major roads where the NO2 will be the highest.

• p 294: Table 10-2 presents ratios, not correlations.

• Table 10-3: Add N of monitors. Note th at the annual average is closer to the 1- hour standard for monitors close to a majo r road (<100m). This has implications for network design as well as the choice of short- and long-term standards. Add a discussion of network design and inte rpret the data in that context.

• Keep ppb or ppm throughout. I prefer ppb because more significant digits can be

retained.

• p 302: Not sure I follow the argument of why the plausible relationship between

NO2 and health events would be more unc ertain at the lower range of NO2. Is there data to suggest the mixture changes at lower concentrations?

• p 303: Recast discussions to focus on es timates and interval s, not statistical significance or posit ive associations.

• p 304: I wasn’t convinced by the 0.2 argument.

.Comments Received -December 8, 2008

38 Comments from Dr. Frank Speizer

Pre-Conference Call Review Comments on Chap ter 10 of REA- Primary NO2 document.

Dated November 2008

Submitted by: Frank Speizer

Date December 2, 2008

I have focused my comments on Chapter 10 with specific considerations of the questions posed in the email dated Nov. 21, 2008.

General Comment: Generally I found the Chapter one of the best I have read over many years. It follows a logical format, outlines the issues clearly and presents the Staff position well. (I will take issue with one conclusion , and have indicated that below).

Specific Comments:

Page275, para 2, line 6 and spilling over to the next page. There is a degree of emphasis here on “uncertainty” vs. “margin of safety ”. The issue is clarified on page 276, but starting as it does it suggests a bias that comes though late r in the Chapter, where the issue of margin of safety is all but forgotten.

Page 284, 1 st bullet, sentence beginning line 5: No t clear what is being assumed here. May require further spelling out.

Page 285, 1 st bullet, sentence beginning line 4: A lthough I agree with th e statement, it is conceivable that more severe asthmatics (be cause of treatment or chronic symptomatic state) might actually be less susceptible when actually measured.

Page 290, top discussion of two pollutant model and then effect of adding O3 or PM10: I t is not clear what makes up the two pollutant model to which O3 or PM10 is added. I would have thought that one or the other of these pollutants was added to NO2 to make up the 2 pollutant model. Please clarify.

Page 290, Section 10.3.3: Para 1, sentence beginning on line 7. I applaud the Staff’s conclusion here, but believe it could be even more direct, rather than “called into question”

Potential Alternative Standards

Indicator: Summarized br iefly and well. Agree that NO2 remain the indicator.

Averaging time: The argument summarized in Tables 10-1 and 10-2 is very convincing that moving to 1 hour is appropriate. I don’t know if another table or some example ofComments Received -December 8, 2008

39 the text on the page 293 that uses the table to convert ratios to actual estimates would be useful. Alternatively table 10-1 could be expanded to show the hourly maximums.

Form: Clearly the discussion of the 99 th and 98 th percentiles is appropriate. However,

Staff does not seem to reach a conclusion and it is at this point “uncertainty” seems to dominate the thinking rather th an “margin of safety”. I w ould agree that the form is partly related to the level, and thus move on to that discussion.

Level. Here I would disagree with the Sta ff. The argument is well presented that the

effect level is seen at or be low 0.1 ppm. Staff indicated “l ittle evidence of any effect threshold”...”key studies ...with a range of 98 th /99 th percentile 1-hr daily maximum levels from 0.05 ppm to 0.21 ppm”. The se veral bullets on page s 303 and 304 clearly

summarize that health relevant effects are not ed, including the fact that the ISA does not

draw distinctions between leve ls within the range of 0.1-0.3 ppm. The fact that there appears to be more uncertainty at the lower le vels means to me that the margin of safety issue is important. Thus I take issue with including on page 304, that there is reasonable supported by evidence to go to 0.2 ppm. In fact as the series of bu llets on pages 307 and 308 suggest at 0.2 there would be little improvement either in air quality or health effects

from the level set in 1971 and little reason to change the standard. That would clearly be wrong, as Staff points out, and I would agree (a s they conclude on page 309) that the range should be between 0.5-0.1 ppm.Comments Received -December 8, 2008

40 Comments from Dr. George Thurston

Prof. George D. Thurston comments on fina l "Risk and Exposure Assessment to Support the Review of the NO2 Primary Nati onal Ambient Air Quality Standard"

My comments will also be organized according to the indicator, form, averaging time and

alternative levels for the sta ndard, and whether these elemen ts of the current standard need to be changed to protect the pub lic health with a margin of safety.

Indicator: I agree that the indicator should remain as NO2.

Averaging time: I agree that the annual standard is not sufficiently prot ective of health, and with the

recommendation to use a 1-hr aver aging time for the NO2 standard.

Form: I agree that a concentration-based fo rm is better than a form based on expected exceedances, and that the absolute level of the standard chosen will depend on whether choose use the 98th or the 99th percentile. It will also depend on how many years are averaged to compare with the standar d, if any multi-year averaging is done.

Level: I concur with Dr. Henderson's argument that the upper level of the range should be no higher than 0.1 ppm.Comments Received -December 8, 2008

41 Comments from Dr. Ronald Wyzga

Comments of Ron Wyzga on Chapter 10

Three approaches are used in Chapter 10 to consider the implications of alternative standard formulations: one based on analyses of data from 18 monitors throughout the US; one based upon an Atlanta case study usi ng alternative benchmark levels; and one based upon the does-response taken from an ep idemiological study in Atlanta. All three approaches are reasonably well-described, a nd no one approach is emphasized to the

detriment of the others. There is a fundament al issue, however, that is not discussed as well as it should in this chapte r; namely, the issue of differences between exposures and

monitored concentrations of NO2. The docum ent (and the ISA) notes that exposures are likely to be significantly highe r near roadways, and monitors may not capture these high exposures. The first two approaches give gr eater consideration to this issue than the third. I therefore would place less weight on this approach for understanding this risks associated with NO2 exposure. There needs to be a greater discussion of the use and value of this approach th an currently exists on p. 300 given the disparity between personal exposures (especially peak expos ures) and monitored levels. The current discussion is based upon comparisons of pe rsonal exposures and ambient monitoring results for extended periods of time (>24 hours). For a much shorter period of one-hour, these comparisons are likely to be of little va lue. Highest exposures likely occur when individuals are near roadways; it is unlikely that they rema in outdoors near roadways for periods of 24 hours or more. Unfortunately there are no measurements of short-term personal NO2 exposures. In the REA adjustment is made to estimate peak levels near roadways from monitored levels. The need fo r this adjustment contradicts the statement made at the bottom of p. 300. This issue also identifies the need to expand the discussion of how to interpret the results from the ep idemiological analyses in the context of standard setting. A related issue is that of where regulatory monitors are likely to be placed; if they are placed near major sources or where ambient levels are thought to be higher (e.g., near roadways), the discussi on in Chapter 10 would be different.

There are four attributes of the standa rd discussed in Chapter 10. The REA and supporting evidence provide no support for any alternative to NO2; hence the choice of this indicator is clearly justified. The ISA gives greatest support for a short-term standard, averaging time of one to 24 hours. Epidemiological evidence supports both averages; clinical studies demonstrate respons es for shorter periods of time. The REA suggest an hourly standard based largely upon the human clinical study results. Exposure

considerations buttress this c hoice. Individuals are much mo re likely to be exposed to outdoor levels of NO2 for shorter periods of time than longer periods of time because most individuals spend less than 10% of th eir time outdoors; hence the probability of being exposed to a peak level for shorter periods of time, such as one hour, is greater than that of being exposed for longer periods of time (e.g., 24 hours). Furt her consideration of potential exposures from the behavioral and exposure pattern li terature should be incorporated into this document.Comments Received -December 8, 2008

42 The discussion of the form of the standard vis-à-vis the 98 th or 99 th percentile issue is well-discussed and well-presente d. More discussion could be given to the issue of using data over a 3 year period; no support for this time period is given in the document.

Finally the REA considers a range of standard levels. The range is large (50-200 ppb), but is appropriate for illust rating the potential impacts of alternative levels; the consideration of this range facilitates the choi ce of an appropriate level. The analyses are helpful, but could be more explicit with re spect to the uncertainties associated with estimated impacts of alternative standard levels. The presen tation of “central estimates” only, for example, on page 308 is potentiall y misleading. Although stat istical significance is not the only consideration that should be given to interpreting study results, it is an important consideration that should not be obs cured. The setting of a standard for NO2 is a difficult issue, especially given the collinear ity of NO2 levels with both measured and unmeasured pollutants. Those who set th e standards should be aware of the full

uncertainties associated with the es timated impacts of a standard.