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 NO2 

Primary National Ambient Air Quality Standard

Dear Administrator Johnson: 

 The CASAC Oxides of Nitrogen Primary National Ambient Air Quality 

Standards (NAAQS) Review Panel (see Enclosure A for Panel Roster) is providing 

review comments on the Environmental Protection Agency’s (EPA) final Risk and 

Exposure Assessment (REA) to Support the Review of the NO2 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 NO2 REA.1

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

finalized the document to meet the court-ordered schedule for the NAAQS review, 

because this draft represents the first instance of completing an REA under the revised 

approach for NAAQS review. We understand that CASAC’s comments will be given 

consideration as EPA moves forward to develop the NO2 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 specific 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 review 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 the REA satisfactory in its approach to 

moving from the scientific foundation developed in the Integrated Science Assessment 

(ISA) to setting out evidence-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 different profiles of exposure. It draws on 

toxicological and epidemiological evidence and addresses risk to an identified susceptible 

population, people with asthmatic conditions. EPA has also systematically described 

uncertainties associated with the risk assessments. We commend EPA for developing a 

succinct and thoughtfully developed synthesis in Chapter 10. This summary chapter 

represents a long-needed and transparent model for linking a substantial body of 

scientific evidence to the four 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 NO2. 

We also provide general comments on other major 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. Enclosure C provides comments of individual panel 

members. 

 We turn first to the discussion of the NAAQS in Chapter 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 with retention of NO2 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 NO2 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 NO2 exposure and the lack of strong 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 potentially leading to adverse health effects.

• Ambient air concentrations: For the short-term standard, EPA presented two 

sets of recommendations: from 50 to 100 ppb and from 50 to 200 ppb NO2. The 

evidence reviewed in the REA indicates that 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. CASAC advises that EPA choose a health 

protective percentile appropriate 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 about the role of scientific 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 the REA as it offers options for the NAAQS. 

With regard to characterization of uncertainty, 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 consideration. 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 and not to the upper. 

 Second, we turn to the NAAQS review process 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 NO2 review for CASAC's fulfilling its 

statutory advisory and review role. It is especially important that, in the future, sufficient 

time be included in the document development 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 critical to public health protection relating to monitoring and 

implementation will be addressed in the January 2009 ANPR prior to CASAC review. 

One important issue concerns the siting of monitors in a manner that recognizes the 

spatial variability of NO2 levels. 

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

document that can link the scientific foundation for the NAAQS review, provided in the 

ISA, to future presentation of evidence-based 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 in 
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the enclosure to this letter be addressed in the ANPR, so that the scientific evidence in the 

supporting the options can be clearly and accurately 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 Administrator 
5

NOTICE 

This report has been written as part of the activities of the EPA's Clean Air 

Scientific Advisory Committee (CASAC), a Federal advisory committee 

independently chartered to provide extramural scientific information and advice to the 

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

assessment of scientific matters related to issues and problems facing the Agency. 

This report has not been reviewed 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 Executive 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 Primary NAAQS Review Panel 

CHAIR 

Dr. Jonathan M. Samet, Professor and Chair, Department of Preventive Medicine, 

Keck School of Medicine, University of Southern California, Los Angeles, CA 

CASAC MEMBERS 

Dr. Joseph Brain, Philip Drinker Professor of Environmental Physiology, Department of 

Environmental Health, Harvard School of Public Health, Harvard University, Boston, 

MA 

Dr. Ellis B. Cowling, University Distinguished Professor At-Large, Emeritus, Colleges 

of Natural Resources and Agriculture and Life Sciences, North Carolina 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 Engineering, 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 Medicine, 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, University of North Carolina at Chapel Hill, 

Chapel Hill, NC 

Dr. Terry Gordon, Professor, Environmental Medicine, NYU School of Medicine, 

Tuxedo, NY 
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Dr. Dale Hattis, Research Professor, Center for Technology, Environment, and 

Development, George Perkins Marsh Institute, Clark University, Worcester, MA 

Dr. Rogene Henderson, Scientist Emeritus, Lovelace Respiratory Research Institute, 

Albuquerque, NM 

Dr. Patrick Kinney, Associate Professor, Department of Environmental Health 

Sciences, Mailman School of Public Health , Columbia University, New York, NY 

Dr. Steven Kleeberger, Professor, Lab Chief, Laboratory of Respiratory Biology, 

National Institute of Environmental Health Sciences, National Institutes of Health, 

Research Triangle Park, NC 

Dr. Timothy V. Larson, Professor, Department of Civil and Environmental Engineering, 

University of Washington, Seattle, WA, USA 

Dr. Kent Pinkerton, Professor, Regents of the University of California, Center for 

Health and the Environment, University of California, Davis, CA 

Dr. Edward Postlethwait, Professor and Chair, Department of Environmental Health 

Sciences, School of Public Health, University 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 Environment Center, Université ParisEst, Champs-sur-Marne, France 

Dr. Elizabeth A. (Lianne) Sheppard, Research Professor, Biostatistics and 

Environmental & Occupational Health Sciences, 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 Medicine, NYU School of Medicine, 

New York University, Tuxedo, NY 

Dr. James Ultman, Professor, Chemical Engineering, Bioengineering Program, 

Pennsylvania State University, 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 Officer 
8

Enclosure B: 

Additional Panel Comments 

 

This enclosure provides more detailed comments on aspects of the REA, 

particularly those chapters that 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 NO2 Primary National Ambient Air Quality Standard (REA),the CASAC panel 

considered the extent to which chapters covered in previous reviews had been modified. 

A review of Chapters 1 to 6 in the final draft indicates that they have not changed 

appreciably in any way that would affect the conclusions in Chapter 10. As a result, the 

current review does not provide comments on Chapters 1 through 6, except to the extent 

they influence our assessment of conclusions drawn in later chapters. 

As to Chapters 7 and 8, our review focused initially on whether the final draft 

contains any significant differences in numerical results that affect applications in 

Chapter 10. We find that the final draft does contain substantial revisions to the material 

presented originally in Chapters 7 and 8, at least 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 are due in part to 

methodological changes, and in part to the fact that the final draft 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 similarity can be seen, for example, by comparing 

Figure 8-16 in the final draft against Figure 8-15 in an earlier draft, where the figures of 

the latter are within 20% of those in the former (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 for 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 results and health benchmark exceedances in 

18 cities throughout the U.S. (Chapter 7); 

• (ii) an approach based on more detailed exposure and health benchmark 

exceedance results in Atlanta (Chapter 8); and 

• (iii) an epidemiologically and exposure-response approach, based again in 

Atlanta (Chapter 9). 

We focus our attention on the methods and results 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 drawing conclusions in Chapter 10, including the 

impact of uncertainty on the answers produced through the three approaches and the 
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degree to which final recommendations for the NAAQS are bounded by these three sets 

of analyses. 

The analysis of incidence of emergency room visits in Chapter 9 employs a 

methodology identical in both reports and consequently the incidence results are the 

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

incidence attributable to NO2 exposures, rather than as total incidence, which provides a 

more easily understandable summary conclusion as to the magnitude of health effects. 

However, it would be useful to see both total incidence and percent incidence in adjacent 

tables of the final draft, as both provide information of value in decision-making. This 

could be accomplished by bringing a few of the relevant tables, such as Table 4-1, from 

the Appendices back up into the body of the final draft, especially 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, averaged over a year. This approach masks the seasonality of 

incidence, which can vary significantly throughout the year. There may be policy 

implications of such seasonal variations due to the capacity of the health care system to 

cope with periods of high incidence, and 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 uncertainty 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 qualitative analyses of 

uncertainty. The major sources of uncertainty have been identified in all three of these 

chapters, and some assessments made of their sources and implications. In Chapter 9 (the 

epidemiological approach), the EPA has also developed a reasonable system of assigning 

measures of the degree of uncertainty (low/medium/high); and 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 useful 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 judgments are reasonable. We support the 

characterization of uncertainty but recommend that a fully transparent approach be used. 

There is a difference in the approaches of the uncertainty analyses performed in 

Chapters 7, 8 and 9. The useful format employed 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 contain more quantitative analyses of uncertainty, although the 

degree of quantification varies significantly from factor-to-factor. The result is a 

somewhat unbalanced and disjointed exploration of the “space” of uncertainty, for 

example with much discussion of uncertainty due to fitting a distribution to data but more 

cursory exploration of the effects of uncertainty in developing health benchmarks. 

Chapters 7 and 8 should have ended with tables similar to the one on uncertainty in 

Chapter 9. 
10

 

It is unlikely, however, that further development 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 Chapter 9, have had quantitative confidence intervals 

placed around the estimates of incidence. These are admittedly conditional intervals (i.e., 

conditional on the choice of exposure-response model form and conditional on the air 

monitoring results used), but they are useful 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 epidemiological study is reasonable, given EPA's 

decisions to give increased weight to North 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 NO2 exposures on actual 

incidence; this discussion could be extended to consider the seasonal patterns of both ED 

visits and NO2 in Atlanta. The REA correctly discusses 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 Chapter 10 (p. 289-90; 308), emphasis is given to 

“central estimates” without mention of the uncertainty of these “central estimates”. This 

description needs to be modified. 

EPA has applied the concentration-response function from the Tolbert study 

appropriately to Atlanta ambient data. The analysis in Chapter 9 is, however, based on an 

implicit assumption that changes in ambient air concentrations associated with different 

NAAQS values will be approximately uniform in magnitude across the 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 measure of exposure for what is in reality a 

complex spatial pattern, and should be acknowledged at some point in the chapter or 

perhaps in Chapter 10. We understand that the analysis was limited by the way in which 

the epidemiological study characterized exposure through this monitoring station. If the 

spatial field of ambient air concentration is simply shifted up or down at all 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 Chapter 10, is neither clear nor discussed. 

Nonetheless, the epidemiology-based approach 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 REA, 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 epidemiological studies have 

examined the associations between ambient air concentrations of NO2 and respiratory 

health endpoints; the results of these studies have been mixed with a large majority of 
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them finding a positive association. These results are buttressed by findings of several 

human clinical studies, which under controlled exposure conditions, find an association 

between NO2 exposure and respiratory symptoms and lung function responses. The 

authors chose to consider studies 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 considered multi-pollutant models, an important consideration given 

the relatively high correlations between ambient levels of NO2 and other pollutants and 

the concern that NO2 could be serving as a surrogate for 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 the 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 least for asthma, the only endpoint that the studies have in 

common. 

A key issue underlying the conclusions in Chapter 10 is whether Atlanta is to be 

taken as representative of exposures and effects 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 either under- or over-estimation with respect to the influence 

of on-road and other mobile sources on the representativeness of Atlanta relative to the 

other 17 urban areas examined in the air quality analysis, EPA judges that the Atlanta 

exposure estimates are likely representative of other moderate to large urban areas 

included in this comparison. EPA does recognize that the Atlanta exposure results are 

likely lower on a population-weighted basis compared 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 against short-term peak 

NO2 concentrations at the levels associated with mild changes in pulmonary function and 

airway responsiveness observed in controlled 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 existing NAAQS, and the results 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 NO2 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 which exposure and risk results will inform 

ultimate decisions regarding the NO2 standard will depend upon the weight placed on 

each of the analyses when uncertainties associated 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 the 
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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 uncertainties associated with quantifying the 

contributions of NO2 to respiratory effects in epidemiologic studies and uncertainties 

regarding the public health significance of NO2-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 the causal connections between NO2 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 levels 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 open 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 likely to be for or against health protectiveness, 

or neutral). 

A further key issue is whether the Atlanta study results (Chapters 8 and 9) can be 

extrapolated elsewhere, or at least be considered as representative 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 NO2 shows variable results. For this 

reason it would have been preferable for the risk assessment to consider additional 

studies as well; unfortunately the number of studies that consider NO2 in both a singlepollutant and a multi-pollutant context is limited; nevertheless some consideration of the 

New York studies could be helpful and considered as a sensitivity/uncertainty analysis. 

Secondly the results of a specific study are tied to the characteristics 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 that 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 metropolitan areas in this regard. 

There is a fundamental issue, however, that is not discussed sufficiently in this 

chapter; namely, the issue of differences between exposures and monitored 

concentrations of NO2. The REA (and the ISA) notes that exposures are likely to be 

significantly higher near roadways, 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 for extended periods of time (>24 hours). For 

the much shorter period of one-hour, these comparisons are of uncertain relevance. The 

highest exposures likely occur when individuals are near roadways, but personal-activity 

patterns would not lead to extended stays at such locations. Unfortunately there are no 
13

measurements of short-term personal NO2 exposures that might better inform this issue. 

In the REA, adjustment is made to estimate peak NO2 air concentrations on roadways 

from monitored levels. The need for this adjustment contradicts the statement made at 

the bottom of p. 300. There should be an expanded discussion of exposure issues in 

interpreting the results of the epidemiological analysis in the context of standard setting. 

The siting of regulatory monitors is a related issue and one that 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 alternative 1-hour concentrations. EPA shifts between reporting them 

in ppm and ppb. Eliminating this inconsistency would improve the document and allow 

the reader to focus on conclusions rather than trying to understanding the basis for these 

differences. This inconsistency should addressed if possible. 
Comments Received -December 8, 2008 

14

Enclosure C: Compilation of Individual Panel Member Comments on EPA’s 

completed Risk and Exposure Assessment (REA) to Support the Review of the NO2

Primary National Ambient Air Quality Standard 

This enclosure contains final written comments of individual members of the Clean Air 

Scientific Advisory Committee (CASAC) Oxides of Nitrogen Primary National Ambient 

Air Quality Standards (NAAQS) Review Panel. The comments are included here to 

provide both a full perspective and a range of individual views expressed by panel 

members during the review process. These 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.............................................................................. 41 
Comments 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 CASAC 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 developed since the last 

NOx review to indicate if the 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 unification” of sorts, in which the salient 

conclusions and judgments of the several hundred pages of thoughtful presentation, 

appendices, tables, and analyses are presented in an accessible 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 evidence that have become available since the 1996 

NOx review have been substantial. Several informative epidemiologic, and controlledhuman-exposure studies, as well as a wealth of ambient monitoring exposure 

information, has become available in the decade 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 current standard to protect public health. 

Chapter Section 10.4 (“Potential Alternative Standards”) is generally well-constructed, 

logically described, and clearly presented. The explanation for the choice of “Indicator” 

is clear, logical, and compelling. The presentation of “Averaging Time” considerations is 

informative and convincing. The discussion of “Form” of the standard helpfully provides 

several examples using several metropolitan areas and seems justified. 

The recommendations of the chapter section concerning “Level” of the 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 scientific evidence provides strong support for a standard at or 

below 0.1ppm (100ppb)...” Where is the adequate margin of safety? Where is the 

acknowledgement and adjustment for sensitive sub-populations (such as more severe 

15
Comments Received -December 8, 2008 

16

asthmatics) who were under-represented in the scientific studies? It appears that 

uncertainty concerns, with respect to measurement errors, health, and monitoring 

outcomes have been used to move the discussion in only one direction (towards a lessprotective level). This is arguably the wrong direction, if the stated goal is to protect the 

public’s health. 

The final concluding section of the document (Section 10.4.4.3) appropriately lays out 

the range of NO2 exposure levels, which based on the current available 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 equivalent 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 Chapter 10 and I would concur with the primary 

recommendations for the NAAQS for NO2. 

The indicator is appropriately recommended to remain as NO2. The scientific evidence 

now provides a sound basis for a new short-term standard for NO2. I would concur with 

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

the choice of the form for the standard and I would concur with the selection of either the 

98th or 99th percentile. 

With regard to the level of a new 1-hour NO2 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 NO2 from 0.1 to 0.2 ppm would 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 standard would be in the range of 0.1 to 0.05 

ppm. 

I concur with the recommendations for modifications 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 rigor, 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.

17
Comments Received -December 8, 2008 

Comments from Dr. Terry Gordon

Chapter 10 – NOx REA 

Charge question: “What scientific evidence 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 alternative levels, indicators, statistical 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 alternative levels sections are very clear and well 

organized. Based upon the logical pattern of the 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 alternative standard, the Staff does not directly 

address what to do with the current standard. 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 issue 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 exposure and animals studies only qualitative? 

Page 288, para 2, line 2 – Unclear sentence: ‘effects that we cannot currently...’ implies 

that you did assessments on effects that you couldn’t quantify. 

Page 290, para 1 – ‘inclusion’ in the ‘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 correlations’ 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 (99th): Annual – what is Annual?) 

Page 296, Table 10-3 – It would be more clear if ‘1-h’ were 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, 1st sentence – It could be me, but the second half of the sentence isn’t 

clear: ‘could exceed the standard level 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 ‘greater 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 paragraph for ‘level’, but it is odd 

reading ‘level’ with no mention of an averaging time (of 1 hour or anything else). 

18
Comments 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 substantial efforts to address the issues I raised 

in my previous comments on the probabilistic methodology for APEX exposure 

modeling and the critical on road/off road concentration 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 analysis, 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 documented their database of empirical 

observations of Cv/Cb (or “m”) that led 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 have been able to critically evaluate 

EPA’s conclusion that no parametric distribution can be found that reasonably 

describes the available data. Briefly, I think this is incorrect. However, using the 

documentation provided, I have developed a relatively simple alternative 

distributional suggestion that could at least be used for sensitivity analysis in the 

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

The reason why it is desirable to avoid simple empirical distributions 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 observed in the available 

data. When there are only 41 available data points there is reason to suspect that this 

could effectively cut off the high 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 with which high end concentration benchmarks 

are exceeded. This concern is magnified in the current case because the 41 observations 

used for the analysis already 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 straight line represents a hypothesis that the data are lognormally 

distributed, and the correspondence of the points to the line is a quick qualitative 

indicator of the correspondence of the data to the theoretical distribution. The intercept 

and slope are estimates of the mean and standard deviations of the log-transformed 

values, respectively. Lognormal distributions are expected when there are many factors 

19
Comments Received -December 8, 2008 

be seen that the datapoints—particularly those from the “summer” distribution—are not 

perfectly described by the straight 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 departure from lognormality mostly in the second 

category. 

The two distributions shown in figure 1 have relatively similar 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 distributions 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 regression 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 did 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 standard deviation within 

rounding error of the expected 0.227. Therefore I recommend that in place of its 

empirical distribution, EPA should substitute lognormal 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 observations, 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. 

20
Comments 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-Score

Log(On-Road/Off-Road) Cooncentration Ratios

y = - 0.005 + 0.216x R^2 = 0.924

y = - 0.192 + 0.243x R^2 = 0.971

21
Comments 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-Score

Log(On-Road/Off-Road) Concentration Ratios

y = 0.039 + 0.219x R^2 = 0.919

y = - 0.058 + 0.230x R^2 = 0.829

22
Comments 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-Score

Residual--Observed-Model Predicted "m" {Log(On Road/Off Road NO2 concentration)]

y = 3e-7 + 0.226x R^2 = 0.980
Comments Received -December 8, 2008 

Comments from Dr. Rogene Henderson

Comments on final Risk and Exposure Assessment 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 for 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 Chapter 10 that the indicator should remain as 

NO2. 

Averaging time: 

 The current averaging time is based on earlier 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-term 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 protect against the effects of short-term exposures. I agree with 

the analysis presented in Chapter 10 that indicates that the standard should be based on 

either a 24-hr or a 1-hr averaging time. Based 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 concern is increased airway responsiveness in 

asthmatics. I agree with the staff arguments 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 because we need a margin of safety, I would not 

recommend an upper level of the range higher than 0.1 ppm. 

24
Comments Received -December 8, 2008 

Comments from Dr. Donna Kenski

 Pre-meeting Comments on Risk and Exposure 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 very 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 logistics of the review cycle, I thought Chapter 10 did a great job 

summarizing the results of the exposure assessment, 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 summary 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 standard to protect the public health would 

clearly be called into question.” Surely these are exactly the 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, the 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, logical 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 98th percentile standards. What is somewhat startling is that, under 

some of the proposed alternative standards, the current annual standard could be 

exceeded. It begs for more discussion. Even 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 problem, 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 summarize here as well. Similarly, the reasoning behind the 3-

25
Comments Received -December 8, 2008 

26

year averaging period is not discussed. Presumably this helps to stabilize the metric? 

The chapter notes that the 3-year averaging 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 98th percentile form, since it could be set to be 

sufficiently protective and is likely to be more stable than a 99th %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 controls to achieve it. But as the chapter appropriately notes, 

the protectiveness depends on both the level and the form, so a 98th percentile form must 

have an adequately protective level. This section could have used some comparisons of, 

say, 98th percentile at 0.05 ppm with 99th percentile at 0.1 ppm. From Table 10-4, it 

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

one infer that a 98th %ile standard at 0.09 would be as protective as a 99th %ile standard at 

0.1 ppm? Which leads me to: 

Level: After presenting an excellent summary 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 end 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, 1st paragraph: The discussion of averaging 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 hyphenated in error. 

The constant switching between ppm and ppb makes it unnecessarily difficult to compare 

data in one section of the chapter to another. 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, averaging 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 existing 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 chapter. The text does 

well to define the uncertainties (beginning 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 statement in section 10.3.3 (page 290) to reemphasize that other sub-groups may be as sensitive or more sensitive than asthmatics, 

and/or that other health endpoints may be important (e.g. birth outcomes)(the points were 

raised initially on p 279). 

27
Comments Received -December 8, 2008 

Comments from Dr. Timothy Larson

Comments by Timothy Larson on “Risk and Exposure Assessment to Support the Review 

of the NO2 Primary National Ambient Air Quality Standard Final Draft, November, 

2008” 

I will limit my comments to the air quality and exposure analyses. The discussion of the 

representativeness of the exposure 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 extrapolation to scenarios “just meeting” 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 deserves more discussion involves the amount of 

exposure that occurs inside residences that are in close proximity to major roads. These 

exposures are, in principle, captured by APEX’s “Indoor-Residence” category. However, 

the perimeter of the census blocks in Atlanta do not appear in general to cross major 

roads, i.e., the blocks boundaries are defined 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 closer to the road than those living exactly at 

the block centroid. Given the potentially strong horizontal concentration gradients in 

NO2 near roads in flat terrain and the strong vertical gradient near roads in built-up areas, 

the centroid assignment approach used by EPA 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 penetrating from outside is greater than that 

predicted by APEX. As it stands, the staff concludes that the AERMOD analyses are 

“overpredicting the upper percentile exposures” (p. 286). 

I agree with the proposed averaging time. One minor point: the near road sites show 

annual averages that are closer to the 1-hr standards than sites located further from major 

roads. These relationships may also change if the near-road indoor exposures are 

considered. 

I agree with the proposed upper and lower range of the level. One additional factor to be 

considered in the ANPR is the possibility that future monitoring sites may be located 

nearer to the roadway than they are at present, i.e., the NO2 siting criteria may change 

from “urban scale” to “microscale”. There is certainly precedent with carbon monoxide 

monitoring (short-term standard, major mobile source contribution). 

28
Comments Received -December 8, 2008 

29

I do not have a strong opinion as to which of the proposed forms of the standard (98th or 

99th percentile) are appropriate. I think that stability 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 alternative levels, indicators, statistical 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 interpretation 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 objectively, 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 issue, and I am not persuaded by the staff 

arguments for not dealing with it more thoroughly. 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 exposures over specified benchmark levels 

dominantly occur on road unless that benchmark level is 100 ppb AND indoor sources 

are included, in which case, indoor sources play 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, 99th%ile standard. Given that, we must be very 

concerned with how well we can approximate on-road exposures (which I would suggest 

is not very well) given the high bias in the AERMOD results (Fig. 8-8 is actually rather 

alarming in this case, which shows the on-road to monitor values ranging up to over 100, 

though the study of in-vehicle to monitored values that is cited in the ISA and REA 

(Riediker et al., 2003) , note that “NO2 concentrations inside the cars were always low.” 

, noting that the average in vehicle level was 31.4 ppb when the mean ambient was 30.4 

and roadside was 49.9, when one high extreme 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 the (albeit limited) comparison of observed to 

modeled NO2 exposures provided further suggests a potentially large high bias in 

exposures at the higher end of the distributions (Fig. 8-11 vs. Fig. 8-12). Countering the 

concerns, above, but not quantitatively 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, 

30
Comments 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 ratios, there is again a problem. It is not 

apparent that the derived ratios account for a limitation on the ability to oxidize NO to 

NO2 during the periods with the highest NOx levels. If the ozone levels 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 NO2. 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 suggest such) could lead to a high bias in 

predicted on-road NO2 at the higher end of the distributions. Again, this leads to a bias in 

estimating the number of exposures of concern (e.g., over specific benchmark levels). 

Associated with this issue is that the ratio of monitor to “on-road” NO2 levels will be very 

sensitive to where the monitor is located. Using near-road monitors to assess attainment 

would require less of a buffer to protect against high on-road NO2 exposures than one 

located distant from a major road (though studies have found lower in-vehicle NO2

levels). 

A next concern in conducting this risk assessment is that I believe that the concern 

over confounding is downplayed. NO2 is a product of combustion, so non-laboratory 

exposures typically will co-occur with other products of combustion. Of particular 

concern is PM, and more specifically, fine 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 thus 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, increases in the VOC emissions would lead to 

increased ozone in cities, particularly those where NOx emissions appear to lead to 

decreases in average ozone exposure. This is also not considered in the REA. 

In regards to Chapter 10, the document does clearly present EPA’s rationale 

behind their choice of an indicator, averaging time, form, and range of levels for a 

modified primary NO2 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 (NO2), and do not believe that current instrumental issues 

are a major problem, particularly if one uses 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 concentration-based standard, using a 98th or 99th%ile, 

averaged over three years, is appropriate, and that choice should be influenced by the 

31
Comments 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 98th%ile is taken from the distribution 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 evidence to suggest that health effects would be found at 

concentrations that would occur if 200 ppb were the level chosen, 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 discussed above, the lower end is less 

strongly supported, and has issues that have not been addressed 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 the uncertainties associated with the air 

quality modeling by clearly stating the types of uncertainties and their causes (e.g., 

AERMOD is essentially a model designed to identify maximum impacts from elevated 

point source; it is applied here to evaluate a distribution of concentrations due to 

emissions from mobile sources, i.e. a problem that differs significantly from AERMOD’s 

original purpose). However, the second paragraph 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 evaluation of modeled air quality...shows overall good agreement 

between AERMOD... and...monitored NO2 concentrations”. AERMOD overpredicts the 

mean NO2 concentration at all three Atlanta monitors. The REA only mentions explicitly 

the smallest overprediction (10%), conveniently avoiding to mention quantitatively the 

larger overpredictions at the other two receptors. It appears clearly in Figures 8-6 and 8-7 

that AERMOD overpredicts NO2 concentrations overall and it is inappropriate to state 

that AERMOD shows “overall good agreement” with the measurements. 

Lines 8-10: “the degree of bias...is within the factor 2 commonly used to indicate 

relatively unbiased model performance”. OAQPS seems to confuse “error” and “bias”. 

The factor of 2 is generally expected for ground-level impacts of elevated point sources; 

however, it does not imply that remaining within this factor of 2 means that there is no 

bias. If all modeled values are 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 people driving those cars. 

Unless this statement can be quantitatively substantiated, it should be deleted. 

In summary, the REA document should present the uncertainties associated with the 

AERMOD simulations in a more objective fashion instead of using the uncertainty 

discussion as a justification for using a model with poor performance. It would also be 

appropriate to highlight the need for the future development of a model that would be 

more appropriate than AERMOD for simulating the air quality impacts of roadways. 

33
Comments 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 unlikely to occur in locations that meet 

the current annual standard. Levels at or above 0.2 ppm 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 studies support a relationship between NO2 

exposures and respiratory endpoints at ambient concentrations in areas that 

meet the current standard. 

P. 309. Section 10.4.4.3 This section concludes that the standard level 

should be set between 50 and 100ppb. However, the prior discussion seems to 

indicate that if the current level of 53 ppb as annual average is 

maintained, that shorter term excursions 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 somewhat confused as to what is being 

recommended here. 

34
Comments Received -December 8, 2008 

Comments from Dr. Lianne Sheppard

Final draft NO2 REA comments 

Summary: 

The major changes to this document are an added chapter 10 and revisions 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 table characterizing key uncertainties in chapter 

9. 

Organization and placement of policy discussions: 

Chapter 10 provides a bridge between the conclusions of the ISA and REA and the policy 

recommendations to appear in the ANPR. The discussion contained in chapter 10 is an 

essential component of the review 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 considerations 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 process should be modified to acknowledge the 

incorporation of this preliminary policy assessment into the REA and the name of the 

REA should be changed to reflect its broader scope. 

Important omissions: 

• The assumption regarding receptor locations for AERMOD predictions that are 

fed into APEX is not adequately justified 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 about 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 context 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. (Consider 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 assessment and presentation of uncertainty 

presented by the Intergovernmental Panel on Climate Change (see e.g. the IPCC 

4th Assessment reports, such as the AR4 Synthesis report and the Physical Basis 

report; http://www.ipcc.ch/ipccreports/assessments-reports.htm). 

35
Comments Received -December 8, 2008 

• Make sure to clearly delineate suspected biases as part of the uncertainty 

presentation. 

• The presentation should explicitly recognize the CAA requirement to protect the 

population with an adequate margin of safety. 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. However it does not show receptor locations 

as inputs into AERMOD, a major oversight. 

• p 150: There should be some discussion 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 helpful additional info, but is insufficient. 

The buffers for evaluation should be selected based on scientific considerations, 

not regression model fits to predicted data (description p. 216). The locations of 

the centroids used in this analysis do not appear to have changed since the last 

version. I am concerned that too few centroids are within 50 or 100m of a major 

road relative to the population of Atlanta. 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 population, the results could 

be seriously biased. Given the different buffers in the descriptions on pp 167 and 

168, it is difficult to make any sense of the limited statistics that are reported. 

• P. 168-9: The description of the distributional calculations on p 169 was clearer 

to me this time. Justify the selection of the 4 km buffer for evaluation of 

predicted relative to monitored concentrations with e.g. additional data analysis. I 

am concerned that the summarizing features of within-location distributions 

across locations could give a misleading focus of attention. Since figures 8-6 and 

8-7 are based on pointwise summarizations 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 short 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 details that clearly defines what locations, individuals, 

and activities that make up each category in the pie chart and provide this 

reference with the figures. It is too easy to make assumptions about what is 

contained in each category. I’m also concerned that near-road exposures (e.g. at 

residences) are underreported in AERMOD and similarly in how they pass 

through to APEX indoor exposures. To that 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 

36
Comments 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 circular reasoning. It is possible that most exceedances 

were associated with in-vehicle exposures because the spatio-temporal NO2 

predictions relied on receptors 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 predictions 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 1st 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 that the annual average is closer to the 1-

hour standard for monitors close to a major 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 interpret 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 uncertain at the lower range of NO2. Is 

there data to suggest the mixture changes at lower concentrations? 

• p 303: Recast discussions to focus on estimates and intervals, not statistical 

significance or positive 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 Chapter 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 later in the Chapter, where the 

issue of margin of safety is all but forgotten. 

Page 284, 1st bullet, sentence beginning line 5: Not clear what is being assumed here. 

May require further spelling out. 

Page 285, 1st bullet, sentence beginning line 4: Although I agree with the statement, it is 

conceivable that more severe asthmatics (because 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 briefly 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 of 
Comments 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 99th and 98th 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 than “margin of safety”. I would agree that the form is 

partly related to the level, and thus move on to that discussion. 

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

effect level is seen at or below 0.1 ppm. Staff indicated “little evidence of any effect 

threshold”...”key studies ...with a range of 98th/99th percentile 1-hr daily maximum 

levels from 0.05 ppm to 0.21 ppm”. The several bullets on pages 303 and 304 clearly 

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

draw distinctions between levels within the range of 0.1-0.3 ppm. The fact that there 

appears to be more uncertainty at the lower levels 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 bullets 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 (as 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 final "Risk and Exposure Assessment to Support 

the Review of the NO2 Primary National Ambient Air Quality Standard" 

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

alternative levels for 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 that the indicator should remain as NO2. 

Averaging time: 

 I agree that the annual standard is not sufficiently protective of health, and with the 

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

Form: 

 I agree that a concentration-based form 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 standard, 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 using alternative benchmark levels; and one 

based upon the does-response taken from an epidemiological study in Atlanta. All three 

approaches are reasonably well-described, and no one approach is emphasized to the 

detriment of the others. There is a fundamental issue, however, that is not discussed as 

well as it should in this chapter; namely, the issue of differences between exposures and 

monitored concentrations of NO2. The document (and the ISA) notes that exposures are 

likely to be significantly higher near roadways, and monitors may not capture these high 

exposures. The first two approaches give greater 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 than currently exists on p. 300 given the disparity between 

personal exposures (especially peak exposures) and monitored levels. The current 

discussion is based upon comparisons of personal 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 value. Highest exposures likely occur when 

individuals are near roadways; it is unlikely that they remain 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 for 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 epidemiological 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 discussion in Chapter 10 would be different. 

There are four attributes of the standard 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 responses for shorter periods of time. The REA 

suggest an hourly standard based largely upon the human clinical study results. Exposure 

considerations buttress this choice. Individuals are much more 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 their 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). Further consideration of 

potential exposures from the behavioral and exposure pattern literature should be 

incorporated into this document. 
Comments Received -December 8, 2008 

42

The discussion of the form of the standard vis-à-vis the 98th or 99th percentile issue is 

well-discussed and well-presented. 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 illustrating the potential impacts of alternative levels; the 

consideration of this range facilitates the choice of an appropriate level. The analyses are 

helpful, but could be more explicit with respect to the uncertainties associated with 

estimated impacts of alternative standard levels. The presentation of “central estimates” 

only, for example, on page 308 is potentially misleading. Although statistical significance 

is not the only consideration that should be given to interpreting study results, it is an 

important consideration that should not be obscured. The setting of a standard for NO2 is 

a difficult issue, especially given the collinearity of NO2 levels with both measured and 

unmeasured pollutants. Those who set the standards should be aware of the full 

uncertainties associated with the estimated impacts of a standard.