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> **UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**WASHINGTON D.C. 20460**

> **OFFICE OF THE ADMINISTRATOR**
>
> **SCIENCE ADVISORY BOARD**

November 14, 2007

EPA-CASAC-08-001

Honorable Stephen L. Johnson

Administrator

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue, NW

Washington, DC 20460

> Subject: Clean Air Scientific Advisory Committee's (CASAC)
> Consultation on EPA's *Nitrogen Dioxide Health Assessment Plan: Scope
> and Methods for Exposure and Risk Assessment* (September 2007 Draft)

Dear Administrator Johnson:

The Clean Air Scientific Advisory Committee (CASAC), augmented by
subject-matter-experts to form the CASAC Oxides of Nitrogen Primary
NAAQS Review Panel, met on October 24-25, 2007 and has completed its
consultative review of EPA's *Nitrogen Dioxide Health Assessment Plan:
Scope and Methods for Exposure and Risk Assessment (*September 2007
Draft*)*. The CASAC uses a consultation as a mechanism for individual
technical experts to provide comments to guide the Agency on technical
issues early in the development of a document, before the first draft is
ready for peer review. Panel members offered oral comments at the
meeting and their comments are reflected in the official minutes of the
meeting. Written comments provided are attached to this letter. A
consultation is conducted under the normal requirements of the Federal
Advisory Committee Act, which include advance notice of the public
meeting in the Federal Register.

There will be no formal report from the CASAC as a result of this
consultation, nor do we expect any formal response from the Agency. We
look forward to conducting a peer review of the first draft for the
Exposure and Risk Assessment document as part of the primary oxides of
nitrogen National Ambient Air Quality Standard review.

> Sincerely,
>
> /Signed/
>
> Dr. Rogene Henderson, Chair
>
> Clean Air Scientific Advisory Committee

**Attachments**

Attachment A: Roster of CASAC Oxides of Nitrogen Primary NAAQS Review
Panel

Attachment B: Compilation of Individual Panel Member Comments on EPA's
*Integrated Science Assessment (ISA) for Oxides of Nitrogen -- Health
Criteria* (First External Review Draft, August 2007, EPA/600/R-07/093)

Attachment A: Roster of CASAC Oxides of Nitrogen Primary NAAQS Review
Panel

**U.S. Environmental Protection Agency**

**Clean Air Scientific Advisory Committee**

**Oxides of Nitrogen Primary NAAQS Review Panel**

**CHAIR**

**Dr. Rogene Henderson**, Scientist Emeritus, Lovelace Respiratory
Research Institute, Albuquerque, NM

**CASAC MEMBERS**

**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. Douglas Crawford-Brown**, Professor and Director, Department of
Environmental Sciences and Engineering, Carolina Environmental Program,
University of North Carolina at Chapel Hill, Chapel Hill, NC

**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

**Dr. Jonathan M. Samet**, Professor and Chair of the Department of
Epidemiology, Bloomberg School of Public Health, Johns Hopkins
University, Baltimore, MD

**PANEL MEMBERS**

**Mr. 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. Terry Gordon**, Professor, Environmental Medicine, NYU School of
Medicine, Tuxedo, NY

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

**Dr. Patrick Kinney,\*** Associate Professor, Department of
Environmental Health Sciences, Mailman School of Public Health ,
Columbia University, New York, 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

\*Unable to participate in the October 25, 2007 Consultation

**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**, Vice President, Atmospheric & Environmental
Research, Inc., San Ramon, CA

**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, 1200 Pennsylvania
Avenue, NW

1400F, Washington, DC, Phone: 202-343-9981, Fax: 202-233-0643,
(<nugent.angela@epa.gov>)

\*Unable to participate in the October 25, 2007 Consultation

Attachment B: Compilation of Individual Panel Member Comments on EPA's
*Integrated Science Assessment (ISA) for Oxides of Nitrogen -- Health
Criteria* (First External Review Draft, August 2007, EPA/600/R-07/093)

Comments from CASAC Oxides of Nitrogen Primary NAAQS Review Panel on
EPA's

*Draft Nitrogen Dioxide Health Assessment Plan: Scope and Methods for
Exposure and Risk Assessment* (September 2007 Draft)

[Comments from Mr. Ed Avol 5](#__RefHeading___Toc182377117)

[Comments from Dr. John Balmes 9](#__RefHeading___Toc182377118)

[Comments from Dr. Ellis Cowling 10](#__RefHeading___Toc182377119)

[Comments from Dr. James Crapo 13](#__RefHeading___Toc182377120)

[Comments from Dr. Douglas Crawford Brown
14](#__RefHeading___Toc182377121)

[Comments from Dr. Terry Gordon 17](#__RefHeading___Toc182377122)

[Comments from Dr. Dale Hattis 18](#__RefHeading___Toc182377123)

[Comments from Dr. Donna Kenski 20](#__RefHeading___Toc182377124)

[Comments from Dr. Timothy Larson 21](#__RefHeading___Toc182377125)

[Comments from Dr. Kent Pinkerton 22](#__RefHeading___Toc182377126)

[Comments from Dr. Edward Postlethwait 24](#__RefHeading___Toc182377127)

[Comments from Dr. Armistead Russell 26](#__RefHeading___Toc182377128)

[Comments from Dr. Jonathan Samet 30](#__RefHeading___Toc182377129)

[Comments from Dr. Christian Seigneur 31](#__RefHeading___Toc182377130)

[Comments from Dr. 'Lianne' Elizabeth Sheppard
33](#__RefHeading___Toc182377131)

[Comments from Dr. Frank Speizer 40](#__RefHeading___Toc182377132)

[Comments from Dr. George Thurston 43](#__RefHeading___Toc182377133)

[Comments from Dr. Ronald Wyzga 45](#__RefHeading___Toc182377134)

[]{#__RefHeading___Toc182377117 .anchor}[Comments from Mr. Ed
Avol]{.underline}

Nitrogen Dioxide Health Assessment Plan: Scope and Methods for Exposure
and Risk Assessment (Draft September 2007)

General Comments:

The document provides a useful road map for how the Agency will proceed
on the Risk Assessment. If the plan is to only provide a Tier I
assessment (air quality characterization) and attempt to argue that
insufficient information exists to assess exposure, I believe the Agency
will find its own credibility and level of commitment questioned. The
annexes provide a wealth of information about the current state of
knowledge regarding NO2, and most reasonable and objective reviewers
will conclude, I believe, that sufficient information exists to perform
the Tier II assessment, and to seriously consider the Tier III
assessment. The modeling approaches can provide us with guidance if they
are applied appropriately, and we should move forward. Continuing to
vacillate and wait for complete and perfect information before deciding
that there is sufficient data to proceed (which will ultimately end with
an estimate and range, anyway) does not serve the public health or the
public's interest.

It would be helpful to have a listing of Abbreviations and Acronyms in
this document, to which the reader could refer for clarification.

Specific Comments:

P6, Sec 3.1, para2, line 1 -- "Several tools would..." should be
"Several tools will..."

P6, Sec 3.1, last paragraph discussing evaluation of uncertainties: This
discussion is well-intentioned but not well-constructed. What are the
objective criteria by which the exposure assessment will be determined
to be worthy of a qualitative or quantitative assessment? How will the
magnitude of uncertainty (minimal/moderate/maximal) be assigned? Does a
rating of "minimal" (which I would think would be the starting point for
every evaluation) lead to qualitative or quantitative determinations?
How about two "minimals" and one "moderate" in the matrix of
uncertainties, or other possible combinations? And what about over and
under-estimates -- are over-estimates going to be viewed as more
conservative and therefore less uncertain, or vice versa? It is
difficult to see how this proposed process will lead to a logical,
credible determination, based on what is provided here. Staff may well
have a clear understanding and process in mind, but that procedural
clarity has not been effectively communicated in writing in the
document.

P7, Sec 3.2, para2, last sentence -- How will "...those commuting on
roadways and persons who reside near major roadways..." be incorporated
into the modeled population?

P8, Sec3.3, para 1, first sentence -- "All available ambient monitoring
data collected since...1995...will be used as is." Presumably what is
meant is that all *[quality-assured]{.underline}* ambient air monitoring
data collected since 1995 will be used?

P8, Sec 3.3.1, para1 (regarding the selection of CMSAs for evaluation) -
Presumably some tabular summary will validate this selection of cities,
but why Atlanta, Philadelphia, and Chicago over New York, Phoenix, and
Denver? Some additional and transparent justification for CMSA selection
should be provided.

P13, Sec 3.3.1.3, para 1, last sentence -- This summary claim of
"...insignificant to limited contribution..." of biomass combustion and
ETS toNO2 personal exposure is an over-simplification and
over-interpretation of what is presented in the referenced Chapter of
the ISA. Please review the referenced chapter and re-evaluate the
accuracy of this summation.

P.15, Sec 3.3.3, para 1 (Ambient NO2 measurement), last sentence -- In
areas like Los Angeles, where significant reductions in NO2 in the past
decade have only recently resulted in achievement of NAAQS compliance,
the assumption that sources present in the past are the sources present
now is almost certainly a poor one; some sources are no longer present,
and engine/boiler/source emission reduction controls have changed
substantially to achieve emission reductions. How will this be addressed
or handled?

P15, Sec 3.3.3, para 3 (Spatial Representativeness), line 6 -- Low
spatial correlations could be the result of several circumstances other
than the presence of local sources (for example, topographical
intrusions such as canyons, hills, or slopes between sampling locations
leading to local variations in wind direction or wind speed).

P16, Sec 3.3.3, para 1 (Roadway to Ambient Monitor Relationship), lines
14-19 -- Is the implication here that NO2 is a "...reactive
pollutant..." and will tend to have a lower I/O ratio? This assertion
should be compared to more recent information about in-vehicle
measurements. It is my understanding that based on the available
information, NO is higher in the passenger compartment (due to the fresh
emissions from combustion exhaust being drawn into the vehicle
compartment), and that NO2 is somewhat elevated over ambient (reflecting
on-roadway conditions), but that NO2 is not as high as near off-roadway
(because there has been insufficient time for NO to oxidize to NO2.

P16, Sec 3.3.3, para 1 (Roadway to Ambient Monitor Relationship), last
sentence) -- Some qualifier must be missing from this statement, because
this seems to directly contradict the earlier explanation made in the
justification of Equation 3.

P17, Sec3.4 Tier II Screening-Level Exposure..., para 1, bullet 3 --
"...factors that contribute to lessened personal exposures to ambient
NO2...including time spent indoors and indoor vehicles..." -- Doesn't
the recent in-vehicle measurements suggest in-vehicle NO2 is somewhat
elevated?

P17, Sec3.4 Tier II Screening-Level Exposure..., para 2, lines 6 thru 8
-- Is there some protocol for when to apply one of these approaches or
the other? Presumably one or two hourly gaps could be filled in using
interpolation between valid values at the ends of the missing gap, but
this approach would lead to incorrect values if gaps included morning or
afternoon traffic hour peaks (since it would not capture or re-construct
the peak structure).

P17, Sec 3.4.1 Short-Term Exposure Approach, para1, "...TIGER ROAD
network..." If this refers to the road structures based from the highway
transportation files, there may be some issues with road placement
accuracy, compared to commercially available Tele-Atlas road files. In
working with the road files in Southern California to locate streets and
residents' homes for Children's Health Study-related research, the
transportation files were demonstrated to be occasionally mis-located by
100 meters or more compared to the Tele-Atlas files and the actual
location of the roadways. This variation can be critical when
considering near-road pollutant exposure (see figure below), given the
decay of pollutants with distance from roadways.

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P31, Sec 4.1 Risk Assessment Scope Overview..., para2, last sentence --
Failing to assign some risk estimate to long-term NO2 exposures runs the
risk of not protecting public health from the more potentially more
serious and persistent health effects (from long-term, low-level
exposures). This sounds akin to ignoring the quantification of the
impact because we don't yet fully understand it. At the very least, a
statement or discussion should be included discussing this.

P33, Sec 4.3 Tier II Risk... - "health responses reported to be related
to NO2 include..." lists several health outcomes, but does not include
low lung function (from the Children's Health Study).

P37, Sec 4.4 Criteria for Determining Approach, last bullet- This
undertaking is supposed to lead to the Agency's best efforts to assess
the current information regarding NO2 health effects. The suggestion
that there might not be enough time (after allowing 14 years to pass
since the previous document release) or insufficient resources to
accomplish what the Agency is charged to do is simply not credible; this
bullet should either be revised or removed.

[]{#__RefHeading___Toc182377118 .anchor}[Comments from Dr. John
Balmes]{.underline}

In general, I think the approaches described in the document are
appropriate to provide important information that will be useful in the
process of review of the NAAQS for NOx. I urge the agency to try to use
emergency department (ED) asthma visit data in the risk assessment. This
is especially important given the strength of the epidemiologic evidence
of an association between NO2 exposure and asthma outcomes. Asthma
hospitalization data only capture the tip of the iceberg of asthma
morbidity and the addition of ED data allow a greater proportion of the
burden of asthma to be assessed. I made this same point during the ozone
NAAQS review and was told that for the cities in which the exposure
assessment was done, there were inadequate asthma ED data to use in in
the risk assessment. For this review, more ED data should be available
-- for example, California now has ED as well as hospital discharge data
available state-wide.

[]{#__RefHeading___Toc182377119 .anchor}[Comments from Dr. Ellis
Cowling]{.underline}

**[Individual Comments on the *Nitrogen Dioxide Health Assessment
Plan:*]{.underline}**

***[Scope and Methods for Exposure and Risk Assessment]{.underline}***

My comments are organized below in response to each of the several
Charge Questions posed in Karen Martin's September 2007 transmittal
letter to Angela Nugent.

[Air Quality Considerations]{.underline}

**1. Do the Panel members generally agree with using historic air
quality data (e.g., pre2000) in certain analyses as a reasonable
approach to simulating air quality scenarios with higher NO2
concentrations, given that current ambient air quality concentrations
are lower than the current standard?**

Yes, I agree that historical data is a reasonable approach even though
some of the historical air concentration measurements may be higher than
current ambient air concentrations.

**2. Based on the low estimated contribution of policy-relevant
background NO2 to overall ambient NO2 levels, staff is considering a
proportional (i.e., linear) approach to adjusting air quality to
simulate just meeting potential alternative NO2 standards that are lower
than current air quality concentrations. Do the Panel members have
comments on adopting a proportional approach to simulate just meeting
more stringent alternative air quality standards?**

Although I am surprised that the contribution of policy-relevant
background is as low as it is currently estimated to be, I see no great
problem in using a proportional method of adjustment. I have no
additional comments to add.

[Exposure Analysis]{.underline}

**1. In considering the exposure analysis broadly:**

**a. Do Panel members have any comments on the general structure and
overall three-tier approach that staff plans to use for the exposure
analysis? Are the criteria that staff plans to use for deciding whether
to conduct a Tier II or Tier III analysis clear and appropriate?**

The three tier approach seems reasonable to me and the criteria
suggested by staff also seem reasonable.

**b. Have the most important factors influencing exposure to NO2 been
clearly accounted for and described?**

My only major concern is to know whether, and if so, how indoor
exposures will be considered and evaluated.

**c. The draft plan describes the basis for and selection of population
groups of interest (i.e., children, asthmatics (children and adults),
and the elderly) for which NO2 exposure estimates are to be developed.
Do Panel members generally agree with the groups of interest identified
in the draft plan?**

The suggested population groups seem very reasonable to me.

**2. In considering the Tier I exposure assessment:**

**a. Do Panel members agree that an exponential model is appropriate for
estimating expected exceedances of short-term health effect benchmarks
based on long-term annual average air quality?**

I have no experience on which to base an informed judgment in response
to this question.

**b. Do Panel members agree with the approach to enhance NO2 air quality
data by accounting for the influence of roadway emissions?**

Yes, this approach seems reasonable to me.

**3. In considering a potential Tier II exposure assessment:**

**a. Do Panel members agree with the combined emissions/dispersion
modeling approach to estimate short-term (hourly) on- and near-roadway
NO2 concentrations?**

I have no experience on which to base an informed judgment in response
to this question.

**b. Is the proposed use of time-location-activity diary data reasonable
for estimating short-term exposures for population cohorts?**

I have no experience on which to base an informed judgment in response
to this question.

**c. Do Panel members agree with the use of HAPEM6 to estimate long-term
exposures (annual average) and the approach to account for on- and
near-roadway NO2 concentrations?**

I have no experience on which to base an informed judgment in response
to this question.

**4. In considering a potential Tier III exposure assessment:**

**Do Panel members generally agree that developing individual exposure
profiles through the use of APEX is reasonable and appropriate to
estimate both short- and long-term NO2 exposures?**

I have no experience on which to base an informed judgment in response
to this question.

**5. Do Panel members have any comments or advice regarding the general
approach to addressing uncertainty and variability in each Tier of the
exposure assessment as described in the draft plan?**

I have no experience on which to base an informed judgment in response
to this question.

[Health Risk Assessment]{.underline}

I have no experience on which to base an informed judgment in response
to any of these several Health Risk Assessment questions.

[]{#__RefHeading___Toc182377120 .anchor}[Comments from Dr. James
Crapo]{.underline}

NOx Health Assessment Plan: Scope and Methods for Exposure and Risk
Assessment.

The document provides an appropriate plan for carrying out both and
Exposure and Risk assessment for NOx. The tiered approach is appropriate
and well laid out in the document. A substantial number of studies have
been published during the past decade which suggest that NOx exposures
are an important contributing factor in creating adverse health effects
from air pollutants at levels of exposure that are substantially below
the current NAAQS. The form of the standard is an important question to
include in the risk assessment. Current data suggest that short term
peak exposures may be more important than long term average exposures as
currently regulated in the NAAQS. There are also unique populations at
risk both in terms of disease (eg. Asthma patients) and proximity to
peak NOx exposures (Those living near roadways or traveling on them
frequently).

I feel strongly that both tier I and Tier II of the proposed risk
assessment should be done. As part of these assessments I concur with
the proposed focus on short term exposures at levels of NO2 in the range
of 0.2 tp 0.3 ppm. The tier II assessment to provide data on incidence
of expected adverse outcomes will be essential for the subsequent
consideration of a recommended change in the NAAQS. I also concur with
the recommendation that outcomes for both hospitalizations and ER
admissions be considered for asthmatic patients.

Finally it will be important to assess the magnitude of confounding in
the risk estimates for NOx by co-exposures to particulates and ozone.
The agency should explore ways to include this in their models of
exposure and risk assessment.

[]{#__RefHeading___Toc182377121 .anchor}[Comments from Dr. Douglas
Crawford Brown]{.underline}

**Review of the Draft Nitrogen Dioxide Health Assessment Plan: Scope and
Methods for Exposure and Risk Assessment**

**Doug Crawford-Brown**

This review follows the Charge Questions for the chapter on Exposure. A
general comment is that I approve of the overall methodology to the
extent it is specified in the document. The outline of the methodology
comports with past Agency practice and has the potential to generate the
kinds of variability and uncertainty characterizations of risk needed
for a rigorous setting of a NAAQS for NO2. However, the devil is in the
details, and this document does not lay out very clearly how the
detailed computational steps will be performed. It mentions the kinds of
models and databases that will be considered, and I generally agree with
these, but the real question is how they will be employed. This is
especially true for the uncertainty analysis, where I think there is a
lot of work still needed (not necessarily in this plan) to determine how
the more qualitative and quantitative uncertainty results will be
combined into an overall measure of uncertainty that can also serve to
guide future research. Still, as a plan, this one is reasonable so long
as the Agency can decide how to treat the on-going evolution of sources
when depicting future exposures and risks..

One other general comment is that the Agency should consider how to
balance an assessment based on individual rights, which would focus on
setting a NAAQS that protects some upper percentile of the distribution
of risk, with one based on cost-benefit analysis, which would focus on
the entire variability distribution. The former might be easier to do,
and could be a back-stop approach should the complete variability
distribution (Tier III) prove infeasible.

1a. Is the three-tier approach appropriate, and are the criteria for
deciding whether a given tier is needed clear and appropriate? Yes, I
like the three tiered approach. I would just caution that Tier I, while
providing some useful insights, is unlikely to yield a scientifically
rigorous basis for setting a NAAQS. I would instead view Tier I as
producing only a decision as to whether a new NAAQS is needed at all. If
the answer is yes, then Tiers II or III would be required to actually
generate that NAAQS. And I am confident that the methodologies and
databases exist to allow at least Tier II. I did not find the criteria
well specified, and kept wondering throughout how a decision would be
made to move to Tier II or III. After several readings, I am not certain
what the Agency would need to see in Tier I to motivate it to move to
Tier II, and from II to III. There are qualitative criteria given, but I
don't know how these would relate to any specific quantitative results.

1b. Have the most important factors influencing exposure been accounted
for? For the most part, yes. The largest problem remains in determining
how the activity patterns, and mode choice for travel, will be used to
relate ambient air levels to personal exposures. These methods have been
employed for other pollutants, however, and so I am confident the Agency
staff can obtain at least a first approximation to these issues. On this
one point, it will be important not to get too caught up in trying to
characterize intersubject variability of risk too exactly, because human
movement in an exposure field is an inexact modeling effort at best.

1c. Is the selection of population groups of interest correct? Yes, with
the caveat that there should be special focus on groups that intersect
these criteria.

2a. Is the exponential model in Tier I justified? I think any model here
is only a rough approximation, and the exponential one is as good as any
other. As I mentioned previously, it is important not to get caught up
in too much detail here, since individuals will tend to average out this
spatial curve as they move about.

2b. Is the approach to enhance roadside NO2 concentrations appropriate?
I don't know much about this topic, and so cannot comment on it. But it
is clear to me that something does need to be done to produce this
enhancement, and also to consider in-vehicle exposures.

3a. Is the combined emissions/dispersion modeling approach in Tier II
justified? As a general approach, the answer is yes. I am, however,
skeptical of the ability to perform such calculations at a refined
spatial scale. This will be especially true in road canyons. It will be
necessary, therefore, to use the modeling results only as averages over
significant geographic areas (not below a census track or block group).

3b. Is the proposed time-location-activity dairy approach correct? This
will be a state of the art approach, although it will be difficult to
get the kind of spatially accurate estimates of ambient air
concentration needed to make a refined diary approach really worth the
effort. There will, however, need to be some thought given as to the
level of effort put into the diary approach, and not put in more effort
than is justified by the spatial resolution of the ambient air field.

3c. Is HAPEM6 the correct approach? Yes, this is the model I would have
selected. It has been employed successfully by Agency staff in the past,
although the weaknesses noted during the NATA process should be
reviewed.

4\. In Tier III, is APEX reasonable? My answer here is the same as in
3c. APEX is a good approach, and one with which Agency staff have some
experience, but just be sure to match the effort to the level of spatial
resolution of the ambient air field.

5\. What is our advice on uncertainty and variability in each Tier? Here
there is a lot of work still to be done. I agree with the approach of
having both qualitative and quantitative aspects. I would not try to
force everything into a quantitative framework. The best one can do is a
series of conditional uncertainty and variability statements: that
conditional upon a certain set of scenarios, or modeling approaches, or
databases, or corrections to the data, the following quantitative
uncertainty and variability distributions are obtained. These U and V
distributions can be generated for each combination of scenario,
modeling approach, etc, and then an overall judgment of uncertainty and
variability developed from expert judgment based on these quantitative
distributions. But I recommend this for Tiers II and III, not Tier I
(where the uncertainty should be more qualitative and where variability
should be treated by examining reasonably maximally exposed individuals
rather than producing an actual variability distribution.

On a related note, the plan does not yet specify very well how model
validation will be preformed. This is an important step required by the
uncertainty analysis, and so needs to be rounded out a bit.

[]{#__RefHeading___Toc182377122 .anchor}[Comments from Dr. Terry
Gordon]{.underline}

The plan is well written and the tiered approach is appropriate for the
task. I will comment only on the health portion of the risk assessment.
The conclusion that the adverse respiratory effects are the strongest
health findings appears to be valid and substantiated by the ISA. The
exposure indices for the majority of the adverse functional and
symptomatic effects are, as documented in the ISA, associated with the
short term averaging times. The adverse children's lung growth findings,
however, although more recent, should also be included in the risk
assessment and would be associated with longer term exposure indices.

[]{#__RefHeading___Toc182377123 .anchor}[Comments from Dr. Dale
Hattis]{.underline}

**Comments on the Risk Assessment Plan**

The overall approach for the risk assessment is described as follows:

"health risk will initially be assessed through the identification of
concentration levels associated with adverse health effects, termed
potential health effect benchmarks. These.. will then be used to
determine how often air quality concentrations or estimated exposures
exceed concentrations associated with adverse health effects...."

This seems a rather indirect approach that needlessly economizes on
helpful theoretical model-building. I think EPA should essentially
discard the evident hope that only a "Tier 1" analysis will be
sufficient. What is needed are a set of estimates of the entire
population distribution of likely exposures[^1] and corresponding
distributions of population sensitivity to various health effects. These
two distributional inputs could then be used to develop estimates of the
current burden of adverse health associated with the current exposure
distribution, and the capability to estimate how the burden would change
with hypothetical changes in the exposure distribution or with possible
changes in the NAAQS or other regulatory standards or feasible non-NAAQS
technical measures (e.g. standards for auto emissions). The paragraph
goes on to say that "an additional characterization of risk may involve
use of concentration-response functions..." In my view it is not a
question of whether this level of analysis will be needed. It is
certainly needed to support the technical and policy choices that EPA
needs to make in seriously considering the effects of various options to
revise and restructure the NOx NAAQs. The EPA authors need to
immediately start their analysis by going about the business of
constructing these exposure/response functions, with due cognizance of
the need to quantitatively represent uncertainties in the functions used
to estimate health endpoints of various types from the various sources
of available scientific information.

p\. 9, equation 1.

This exponential equation is not discussed in terms of theoretical
mechanisms. I am prepared to believe that distributions of
concentrations by exposure time are likely lognormal, but it is not
clear that this is the basis of equation 1 or how equation 1 is in fact
derived from this basis. Equation 1 is simple enough to use, but there
should be some comparative testing with data to show it really works for
existing NO2 data in the sense of being free of systematic distortions
in the incidence of exceedances out to levels that are very far from the
mean.

p\. 10, Table 2. The occurrence of zero's in this table, rather than
fractional values below 1, seems unwise and potentially misleading. (As
an aside---the assertion that there are absolutely zero places in the
U.S. that exceed the current standard of 0.53 ppm annual average also
seems dubious.) The equation provided cannot yield true zero incidences.

In general I question the whole "exceedance" basis of the key
calculations that seem to be aimed at. This framework is probably
derived from an implicit threshold theory of the incidence of effects as
a function of concentration, and threshold theories seem to have little
support in the existing epidemiological data. Another presumption seem
to be that long term effects, if any, depend on short term episodes of
relatively high concentration. This assumption does not appear to be
supported by either empirical observations or theoretical analysis.
Rather, I thank what would be more useful is a distributional expression
of the total fraction of time spent at various levels of exposure for
the population as a whole and for various at groups that are at risk
because of either unusual susceptibility or residence in locations with
various levels of annual average concentrations. Many of the
exposure-response observations seem equally well analyzed

[]{#__RefHeading___Toc182377124 .anchor}[Comments from Dr. Donna
Kenski]{.underline}

Comments on Nitrogen Dioxide Health Assessment Plan: Scope and Methods
for Exposure and Risk Assessment

Donna Kenski

October 22, 2007

Air Quality Considerations: Using historic data to simulate scenarios
with higher concentrations seems reasonable, as does the proposed choice
of a linear approach to adjusting data to lower concentrations. The
proposed list of CMSAs did not include New York, which the ISA indicated
had the highest mean NO2 concentrations of selected urban areas with
multiple monitors (Table 2.5-1). Presumably it will show up in the
identification of additional locations of interest?

Exposure Analysis: The 3-tier approach is satisfactory. The important
factors influencing exposure have been accounted for. This plan
emphasized traffic exposures far more than they were discussed in the
ISA, which I thought somewhat neglected this source, so that's a
definite improvement. The groups of interest are appropriate.

The choice of exponential model is probably okay, although it would be
helpful to see what other approaches were considered and to have some
comparative assessment---the McCurdy report is not readily available.
Was survival regression considered? How does the change in variance over
time (apparent from Fig. 1) affect this model? It is not clear from the
text why the predictive equation for each location is lumping all
monitors together when, in some locations, significant siting
differences exist that will impact the number of exceedances. Why not
include a site variable in the model? As above, a comparison of various
models or additional rationale for this particular one would be helpful.

Health Risk Assessment: The approach outlined here seems fine. In
particular the proposed method of characterizing uncertainty and
variability is conceptually appealing. The actual implementation of the
Tier I/Tier II risk assessment may uncover issues not dealt with in this
document, but it seems like a reasonable approach that can be modified
as needed and especially as the data require.

[]{#__RefHeading___Toc182377125 .anchor}[Comments from Dr. Timothy
Larson]{.underline}

*Comments on NO2 Health Assessment Plan*

I have several general comments on the exposure assessment portion of
this plan. The multi-tiered approach is a reasonable one, moving from
more general to more specific in the exposure assessment. The Tier I
approach will provide a reasonable ranking of urban areas for further
consideration. However, I have concerns about the Tier II approach. In
particular, the use of near road gradient algorithms and Gaussian plume
models from line sources will not capture the actual traffic related
gradients in many urban areas. The reason for this is the presence of
buildings and associated street canyons. There are many urban areas
where this is an important factor. It would be useful to identify the
presence of canyons as part of this screening procedure prior to using
'flat world' gradients and models. The Danish AirGIS system has this
capability if information is available on building footprints and
approximate building heights. It would also be useful to develop
information on the vertical distribution of personal residences in these
same urban areas, given the importance of this parameter. Inclusion of
the above factors in a Tier III SHEDS type model seems promising, but
only if the Tier II screening is done properly.

[]{#__RefHeading___Toc182377126 .anchor}[Comments from Dr. Kent
Pinkerton]{.underline}

Review comments for the Nitrogen Dioxide Health Assessment Plan: Scope
and Methods for Exposure and Risk Assessment

Kent E. Pinkerton, Ph.D.

University of California, Davis

Center for Health and the Environment

To assess risks and exposures using a tiered assessment approach for the
level of analysis required and the anticipated utility of the results is
a highly logical process, especially in the face of possible future
limited resources and budget constraints.

Exposure estimates to compare to potential health effect benchmarks
to 1) estimate the number of individuals experiencing exposures of
concern and to 2) estimate the range of exposures above levels of
concern are appropriate and laudable. Since epidemiologic data appears
to be the major driver to establish health effects, it is also important
to better define whether uncertainties in the degree of health effects
observed are due to NO~2~ or an associated co-pollutant.

Since at the present time rare excursions of NO~2~ above the current
NAAQS occur in the nation, yet numerous health effects due to NO~2~
exposure have been reported in the literature, it is highly likely this
tiered assessment approach will need to be applied well beyond Tier I
assessment. Tier II is a critical and needed parameter, especially for
NO~2~ exposures to allow for screening-level exposure assessments to
establish the relationship between ambient concentrations, local sources
and human exposure.

It is my opinion and recommendation that exposure assessment for NO~2~
include both short and long-term measurements of ambient concentrations
through routine air quality monitoring and modeling analysis. The
identification of uncertainties in exposure estimates is also essential
to determine.

The populations to be modeled which include children (normal and
asthmatic), asthmatic adults and the elderly are the proper groups. It
may become essential in the future to further determine the influence of
gender and genetic predisposition to respiratory disease as well.

In the Tier I air quality characterization, how were the 5 cities of Los
Angeles, Houston, Atlanta, Philadelphia and Chicago chosen? Some
justification for city selection would be good. Although it is
understood motor vehicles, electric utilities and industrial combustion
processes represent the major sources of total NO~2~ emissions, why
totally exclude rural and areas of high agricultural activity? For
example, in figure 2 of the document what is the contribution of
agriculture to off-highway emissions of NO~2~?

A nice example is provided for Tier I air quality characterization in
Table 2. However, it appears Los Angeles would be the only city to
experience exceedances in NO~2~ levels, based on the current standard.
Therefore, how useful would this model be for other portions of the
country to explain potential health effects associated with NO~2~
exposure? Perhaps it is important to clarify this model can be adjusted
to deal with lower NO~2~ levels should the air quality standard be
changed to provide greater health protection.

A clear explanation of both short-term and long-term exposure approaches
to be implemented in Tier I and II exposure assessment is provided in
the document. The Decision Flow diagram for Tier II screening, as well
as the basic data required to estimate the numbers of person occurrences
of short-term exposures in Tier II exposure assessments are provided and
extremely helpful.

Again, the explanation provided for Tier III refined exposure
assessments is very helpful to better understand the approach to be
used, generated outcomes, as well as variability and uncertainty factors
that may be encountered and handled.

Figure 5 is excellent in providing an overview of the entire tiered
assessment process. Using a tiered approach as outlined seems very
reasonable and highly appropriate to insure the proper assessment of
exposure levels to NOx.

Under the overview (4.1) for risk assessment scope and methods, one of
the goals of the NO~2~ risk assessment is to estimate the number of
people exposed at or above potential health effect benchmarks associated
with NO~2~ exposures at levels just meeting the current standard. This
goal could be more specific by estimating subgroups such as children,
those with asthma, the elderly and socioeconomic classes.

It is important to clearly indicate what constitutes sufficient
scientific data to develop population-based health risks for health
effect endpoints in at-risk population groups.

Under the overview (4.1) it is not clear why the EPA would not develop
risk estimates for NO~2~-related effects associated with long-term NO~2~
exposures. Although the evidence is not strong, it has been described as
"suggestive" for long-term health effects associated with NO~2~
exposure. Mobile, stationary and indoor sources of exposure can clearly
be long-term.

Under Tier I health effect benchmarks, susceptible populations composed
of asthmatics and allergen-sensitive individuals also factor in children
and gender-based differences.

The inclusion of baseline data for emergency department visits and
respiratory-related hospital admissions for candidate US locations in
Tier II risk assessment to enhance risk assessment seems logical and
desirable.

[]{#__RefHeading___Toc182377127 .anchor}[Comments from Dr. Edward
Postlethwait]{.underline}

Comments on: Scope and Methods for Exposure and Risk Assessment

1\. The draft appears to provide a solid foundation for conducting the
planned exposure and risk assessments. It is clear that thorough and in
depth considerations were incorporated.

2\. Although it might have been dealt with elsewhere, it would seem
appropriate to have addressed the issue of the potential for confounding
in determining exposure/response relationships based on the current NOx
measurement approaches. The issue of PRB and long range transport was
addressed on page 4, with the available information suggesting that
contributions were negligible. Because NO~2~ values represent {NOx --
NO}, some effort to speciate the various NOx and how much non-NO~2~ NOx
(e.g. N~2~O~3~, N~2~O~5~, etc) might contribute to the overall NO~2~
values would be beneficial in terms of characterizing uncertainties.
This may be critical when/if clinical and/or indoor studies are compared
to environmental exposures if atmospheric NOx contains appreciable
amounts of species other than NO~2~.

3\. On page 13, indoor source influences suggest that gas cooking etc
may contribute to NO~2~ exposures but biomass combustion (word stoves,
fireplaces) appeared to be discounted under proper ventilation
conditions. Would not ventilation conditions also affect the other
indoor NO~2~ sources?

4\. An uncertainty apparently not addressed was measurement accuracy
across monitoring stations. This becomes critical when attempting to
utilize disparate population-based studies to predict health outcomes
based on predicted exposure concentrations. The current chemiluminescent
approach for measuring NO~2~ can be affected by numerous factors and
thus it would seem important to be able to estimate measurement error.

5\. On page 22 it is stated that "The ME describes the physical location
of an individual, allowing for direct contact with the immediate
surrounding air that contains a homogenous pollutant concentration." It
is assumed this statement refers to NO~2~ per se rather than the
admixture of co-occurring pollutants wherein all pollutants would be
assumed to be present in equivalent concentrations.

6\. On page 25, the document refers to ME being calculated using "a
mass-balance." This should be clarified since on a chemical reaction
and/or diffusion basis it is unclear how the use of mass balance is
intended.

7\. Only very limited attention was paid to issues regarding biological
plausibility and NO~2~ acting as a surrogate (ie., pg 34). If health
predictions are to be constructed, then it would seem critical that they
be placed into an appropriate biological context, especially since NO~2~
is generated endogenously via peroxidase activities. Furthermore, it was
not clearly evident how co-pollutants would be dealt with in
interpreting especially epidemiologic studies wherein frequently there
is limited consideration of the dose/effect relationships unique to
individual pollutants. In some studies relative toxicities are poorly
considered. Because ozone, for example, is significantly more toxic than
NO~2~, one would anticipate a need to go beyond simple considerations
wherein all pollutants are treated equally relative to exposure
concentrations.

8\. It is assumed that the impact of uncertainties will be quantified
via model output confidence intervals although it was not made
specifically clear. Clarifying this issue and discussing the potential
magnitude of uncertainty impacts would strengthen the document.

[]{#__RefHeading___Toc182377128 .anchor}[Comments from Dr. Armistead
Russell]{.underline}

Review of EPA NO2 Scope and Methods

I am generally pleased with the scope and methods as laid out. It
appears, and I hope this to be the case, that it is building upon and
building further, EPA's other exposure and risk assessments for
reviewing the NAAQS. At the end of one or two more pollutant reviews, it
should be almost a well oiled machine (though one that continually
improves and considers the unique aspects of the pollutant under
consideration).

In regards to its application to nitrogen dioxide, one of the first
question that arises is that the ISA considers more than just NO2, but
nitrogen oxides in the broad sense (not just NO and NO2). Does the Scope
and Methods also have to consider such (e.g., at least consider what the
response might be if the determination is that one should look at other
components or a sum of components)?

While I generally find that their approaches for assessing the
distributions of NO2 exposures are viable and at the level that is
appropriate. One could always do a better job, but it is not apparent
that for the task at hand it is necessary, with one exception at
present. They use an exponential decrease in NO2 going away from a road.
They should use the exponential decrease in NOx going away from the
road, and then use an appropriate method to split NOx between NO and
NO2. In an oxidant limited situation, this could be significant. Also,
this will allow them to more explicitly account for changing NO2:NO
ratios in the emissions, and assess the overall sensitivity to that
split.

Another comment is to try to identify up front the broad levels at which
the standard might be set and do some exploratory analyses to show how
EOC will very, and the primary sensitivities. While, in the end, the
panel will be interested in uncertainties and variabilities, some
assessment early on about the sensitivities will be quite useful.

Some other specifics:

In eq (3), the m should be found using linear regression, not as a
ratio.

k in eq (2) is not a rate constant. One could call it a dispersion
constant, or the like.

Carrying on my comments from the ISA: The monitor uncertainty is
overemphasized, and I do believe, mischaracterized. Further, if one is
using epidemiologic study results, that bias is built in.

Fairly early on in the process, the results from the exposures and risks
in the five cities should be put in perspective of the broader
population.

In replying to the given questions:

1.  Do the Panel members generally agree with using historic air quality
    data (e.g., pre2000) in certain analyses as a reasonable approach to
    simulating air quality scenarios with higher NO2 concentrations,
    given that current ambient air quality concentrations are lower than
    the current standard?

    a.  **Answer:** It is necessary to know exactly when and how this
        would be used, but is probably fine. A specific concern is that
        the older data may have a different NO:NO2 split due to
        different ozone levels and a different NO:NO2 split in the
        emissions. The data should be corrected for this if older data
        is used, and should also be corrected for this when considering
        future scenarios (this may be a small difference, and if they
        can show this, great, and then move on).

2.  Based on the low estimated contribution of policy-relevant
    background NO2 to overall ambient NO2 levels, staff is considering a
    proportional (i.e., linear) approach to adjusting air quality to
    simulate just meeting potential alternative NO2 standards that are
    lower than current air quality concentrations. Do the Panel members
    have comments on adopting a proportional approach to simulate just
    meeting more stringent alternative air quality standards?

    a.  **Answer:** Do you mean proportional or linear? I would prefer
        linear, though it is recognized there is little difference in
        this case.

[Exposure Analysis]{.underline}:

1\. In considering the exposure analysis broadly:

a\. Do Panel members have any comments on the general structure and
overall three-tier approach that staff plans to use for the exposure
analysis? Are the criteria that staff plans to use for deciding whether
to conduct a Tier II or Tier III analysis clear and appropriate?

**Answer:** Yes. (The approach is fine.) EPA should compare and contrast
their approach to that used for other pollutants, and document why
different methods are used. Again, use each review to make the exposure
and risk assessment a more systematic, documented and turn-key. One
could see that in about three years (a couple more pollutants) that a
system much like that used for air quality modeling is used such that
with relatively little effort exposures, risks, variabilities,
sensitivities and uncertainties can be calculated, and the system as a
whole has been intensely reviewed such that staff need not spend such
effort, and the community is more comfortable with the results.

1.  b\. Have the most important factors influencing exposure to NO2 been
    clearly accounted for and described?

**Answer:** Not totally... The large role of indoor sources on NOx, and
how that gets converted to NO2, needs a bit more work. This issue
probably should be picked up more in the ISA as well. Also, the role of
NOx in forming and destroying ozone feeds back in to converting NOx to
NO2. Further, the discussion here should also deal with the
co-occurrence of other pollutants of concern.

2.  c\. The draft plan describes the basis for and selection of
    population groups of interest (i.e., children, asthmatics (children
    and adults), and the elderly) for which NO2 exposure estimates are
    to be developed. Do Panel members generally agree with the groups of
    interest identified in the draft plan?

**Answer:** Yes.

> 2\. In considering the Tier I exposure assessment:

1.  a\. Do Panel members agree that an exponential model is appropriate
    for estimating expected exceedances of short-term health effect
    benchmarks based on long-term annual average air quality?

**Answer:** This is fine as long as the model is tested and the
appropriate measures of performance are given.

2.  b\. Do Panel members agree with the approach to enhance NO2 air
    quality data by accounting for the influence of roadway emissions?

**Answer:** See discussion above.

> 3\. In considering a potential Tier II exposure assessment:

1.  a\. Do Panel members agree with the combined emissions/dispersion
    modeling approach to estimate short-term (hourly) on- and
    near-roadway NO2 concentrations?

**Answer:** Yes, as long as the model is evaluated and performance
documented.

2.  b\. Is the proposed use of time-location-activity diary data
    reasonable for estimating short-term exposures for population
    cohorts?

**Answer:** Yes, as long as the model is evaluated and performance
documented.

3.  c\. Do Panel members agree with the use of HAPEM6 to estimate
    long-term exposures (annual average) and the approach to account for
    on- and near-roadway NO2 concentrations?

**Answer:** See discussion above (in regards to NO:NO2 splits).

> 4\. In considering a potential Tier III exposure assessment:
>
> a\. Do Panel members generally agree that developing individual
> exposure profiles through the use of APEX is reasonable and
> appropriate to estimate both short- and long-term NO2 exposures?

**Answer:** Yes, as long as the model is evaluated and performance
documented.

5.  Do Panel members have any comments or advice regarding the general
    approach to addressing uncertainty and variability in each Tier of
    the exposure assessment as described in the draft plan?

**Answer:** Provide, early on, results of some sensitivity analyses. Do
not overestimate uncertainties going in.

[]{#__RefHeading___Toc182377129 .anchor}[Comments from Dr. Jonathan
Samet]{.underline}

I write to provide brief comments on the draft version of this document
dated September 2007. As indicated in my verbal comments during the
October 24-25 CASAC meeting, I found the plan to generally be acceptable
in its present form, given the status of the ISA. The document covers
the approach that will be used in the three tiers for exposure
assessment and for health effects estimation. I have two comments:

-   With regard to exposure to NO~2~, indoor sources remain substantial
    contributors. The document is rather general in its approach to
    describing how microenvironmental concentrations will be estimated.
    There is a substantial literature on indoor NO~2~ concentrations in
    the presence of various sources that needs to be covered.

-   The plan lists the health outcomes that may be considered in the
    risk assessment, based on the first draft ISA. As indicated in my
    comments with regard to the ISA, the criteria for finding
    associations to be causal are not yet sufficiently developed. In
    general, the health outcomes considered in the risk assessment
    should be those considered as causal in the ISA. A specific
    statement to that effect is needed, on the assumption that the
    plan's authors are in agreement. The current draft plan does not
    specifically reflect this criterion.

    []{#__RefHeading___Toc182377130 .anchor}[Comments from Dr. Christian
    Seigneur]{.underline}

**Comments on the Nitrogen Dioxide Health Assessment Plan: Scope and
Methods for Exposure and Risk Assessment- Draft - September 2007.**

Christian Seigneur

Atmospheric & Environmental Research, Inc.

San Ramon, CA

The three-tier approach for exposure assessment and the two-tier
approach for risk assessment appear to be logical ways to proceed. The
various steps of each approach are described with sufficient detail for
the reader to understand the technical approach and the sources of the
data to be used.

**QA/QC:** One aspect which is not articulated in the document is the
Quality Assurance/ Quality Control (QA/QC) procedures that will be
followed by EPA. As the assessments proceed to the higher tiers, there
will be some very large amounts of data being treated and one must
ensure that the proper QA/QC procedures are in place to avoid input or
calculation errors.

**NO~2~/NO speciation -- Equations 2 and 3 on pp. 11 and 12:** The use
of particulate emission control devices on diesel vehicles typically
leads to a greater fraction of NO~2~ in the NO~x~ emissions. Such a
change in the NO~x~ speciation for mobile sources could lead to stronger
NO~2~ spatial gradients near roadways as the NO~2~/NO~x~ ratio will
increase at the roadway but the NO~2~/NO~x~ ratio at background sites,
which is driven mostly by atmospheric chemistry, may not change. The
implication is that the spatial gradient obtained from historical data
may not apply (see Equation 2 on p. 11 and associated text). How will
EPA address this possible change in the relationship as the vehicle
fleet evolves over time?

**Estimates of NO~2~ concentrations, p. 18:** EPA proposes to use the
steady-state Gaussian dispersion model AERMOD to calculate the NO~2~
concentrations near roadways. AERMOD is a dispersion model that was
designed for point sources (Cimorelli et al., "AERMOD: An dispersion
model for industrial source applications -- Part 1", *J. Appl.
Meteorol*., **44**, 682-693, 2005) and which has been evaluated with
data from point sources (Perry et al., "AERMOD: An dispersion model for
industrial source applications -- Part 2", *J. Appl. Meteorol*., **44**,
694-708, 2005). Emissions from roadways differ from those from point
sources as vehicle traffic induces some additional turbulence. The use
of a simple chemical scheme to account for the rapid titration of NO by
ozone to form NO~2~ appears appropriate here (although it is not clear
what is meant in footnote 8 on p. 18 by "simple reaction rate
constant"). However, it is unclear why EPA would want to use a point
source dispersion model that is not designed for roadway emissions when
roadway dispersion models (such as CALINE4) are available. CALINE4 has
been subjected to performance evaluation with measurements made near
roadways (Benson, "A review of the development and application of the
CALINE3 and CALINE4 models", *Atmos. Environ*., **26B**, 379-390, 1992)
and would seem more appropriate for use here, particularly if AERMOD has
not been evaluated for near-roadway estimates.

**Example calculation of Table 4:** It is not clear how the in-vehicle
concentrations are calculated. One person appears to be in a vehicle at
more than 75 m from the road but the concentration within the vehicle
does not appear to be a function of the distance from the road. Is the
NO~2~ concentration within the vehicle assumed to be constant regardless
of the location of the vehicle?

[]{#__RefHeading___Toc182377131 .anchor}[Comments from Dr. 'Lianne'
Elizabeth Sheppard]{.underline}

Comments on the Scope and Methods Plan for the Exposure and Risk
Assessment

Summary comments:

-   Overall this is a very thoughtful and structured approach that
    should help inform policy. The tiered approach to exposure and risk
    assessment seems to be generally reasonable. *However*,
    modifications to the risk assessment tier structure and additional
    process and detail are necessary.

-   To the extent feasible, *all* criteria should be specifically stated
    in advance. This should reduce the workload by defining a clear
    path. It will also make the decisions in the process more
    transparent.

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-   Clarify whether the tiers of each assessment are purely conditional
    on the results of the previous tier or whether they use different
    information to address details that overlap. If tiers are modified
    to be a pure progression (i.e. conditional on the results of the
    previous tier), this may reduce effort.

-   Throughout the document the word "would" is used when "will" is more
    correct. This is after all a plan, not a hypothetical plan.

-   In order to help assure the process is open and transparent, all
    tiers of the exposure and risk assessment need to be covered in the
    risk and exposure assessment document. In order to make the document
    as transparent as possible, this policy should be followed even if
    the final judgment is that the data are insufficient to conduct a
    specific tier of the assessment. This policy should be stated in the
    introduction.

Section 2: Shouldn't this section be folded into Section 3? It seems
premature to be discussing simulated air quality data when the purpose
of the simulation hasn't been stated.

Section 3: My suggested general improvements for this section are to
clearly state criteria and to make equations more explicit by adding
indices.

Section 3.1: Clearly define each tier in the overview section. Add the
tier numbers to Table 1. Clarify whether the information used in each
tier is conditional on the data, information, or choices made in the
previous tier.

Section 3.2: Why are no population groups defined based on exposure? I
suggest adding people living or working near roads.

Section 3.3:

-   Clearly state the intended use of the air quality characterization.
    Different simplifying assumptions will be realistic for different
    purposes (e.g. prediction of long-term averages vs.
    traffic-dependent hourly-resolved exposure). Without the intended
    use stated, it is difficult to evaluate the objectives of the
    analysis (paragraph 2). For instance, why would the analysis be
    limited to areas of potential concern, and what are the criteria for
    "potential concern". As another example, with regard to a
    statistical model (objective 3), clarifying all purposes of the
    analysis can be followed by identification of reasonable simplifying
    assumptions, thus reducing the modeling effort.

-   It is also necessary to distinguish long-term from short-term metric
    objectives. This distinction needs to be revisited *throughout* the
    section.

Section 3.3.1:

-   The first sentence is good, but now this summary statement needs to
    be made clear.

-   The second sentence appears to be missing a word at the end.

-   As an example of clarifying "aggregating data", it should be stated
    that the objective is to create a single daily (hourly?) time series
    over space of monitors that are similar. Note that criteria are
    needed for "similar".

-   The criteria for the selected cities are generally listed, but the
    reader is not informed why those cities were selected.

-   Shouldn't site characteristics be included in the list of criteria
    used to identify additional locations? This is alluded to with the
    motor vehicle traffic density criterion, although the reference to
    "by location, not monitor" is cryptic.

-   State how the aggregation will be done and what are the criteria for
    including monitors in the aggregation. Make it clear whether this is
    temporal or spatial aggregation, or both. I don't understand the
    purpose of all the statistical tests that are planned and what
    criteria will be used to determine if additional aggregation is
    appropriate. (p 8-9).

-   p 9: The first full paragraph confuses me. What are the purpose and
    the outcome of the comparisons within and between locations? What
    data are to be used?

-   p 9: Please add indices to all variables in all equations and define
    these indices!! Are these data indexed in time by year, day, or
    hour? What are the spatial indices -- site within location?

-   p 10: This document is very short on specifics. For instance, *how*
    will "regression models, parameters, and respective concentration
    exceedance estimates" be compared?

-   p 10: I don't understand how the two parts of the sentence fit
    together: "The regression model is highly dependent on the
    prevalence of concentration exceedances, justifying the aggregation
    of particular (and similar) locations."

-   Footnote 4 suggests a valid year could have an entire season
    missing.

Section 3.3.1.1:

-   Equation (2) is a general equation. None of the parameters have
    values. Will they be estimated from data? What time scale is being
    considered? Add indices.

-   Are *C~v~* and *C~b~* data or predictions? How are they obtained?

-   How will the equation (2) result be used to derive (3)? Add indices.

-   The entire plan for this section is wide open and subject to many
    interpretations.

-   Why is the goal to obtain on-road estimates of NO~2~ instead of
    characterizing NO~2~ as a function of distance from road?

-   Note that "on-road NO~2~ concentrations" are *predictions*, not
    data.

Section 3.2: Descriptive statistics should include measures of spread as
well as central tendency.

Section 3.3:

-   Paragraph 2: Restate sentence to say the tiered approach uncertainty
    assessment is done with the goal of identifying the best supported
    quantitative analysis.

-   Paragraph 2: Presumably the "identified components are, in a broad
    sense, also relevant to subsequent exposure analyses" because this
    tier I analysis is the input to the tier II analysis. Correct?
    Please state clearly.

-   Add "Choice of NO~2~ as the index compound" as one of the components
    of uncertainty.

-   Temporal representativeness: State what the "temporal profiles" are.
    Are these estimated hourly average air quality over a multi-year
    period for a given spatially aggregated location with specific
    spatial features?

-   Spatial representativeness: The purpose of the predictions really
    matters when deciding how to proceed with limited spatial data.
    State the purpose. What prediction equations are being referred to?
    What kind of correlations will be evaluated?

-   Monitor to exposure representativeness: Why is personal exposure
    even being mentioned in the Tier I estimates? Isn't it more
    important that the AQ characterization is done in locations that are
    representative of population exposure to ambient concentration?

Section 3.4:

-   p 17 line 2 -- add "ambient-source" to describe the possible lower
    bound estimate.

-   Gas stoves are an important factor in greater personal exposure and
    should be listed in the example to indicate home characteristics
    will also be considered.

-   In doing spatial interpolation of exposure, it will be important to
    only include monitors that are representative of usual population
    ambient source exposure (as opposed to those highly influenced by
    local sources that won't apply to the entire census tract or
    adjacent tracts). I am concerned that some factors could be counted
    twice if the local source monitors aren't removed first, since local
    sources will be added in with the planned adjustment.

-   Following the previous comment, I suggest discussing locations
    represented by ambient monitors as a function of monitor siting
    criteria and/or GIS covariates.

-   Insert the word "predicted" to clarify the complete set of
    concentrations won't necessarily be data.

Section 3.4.1:

-   Organizationally, why not define the on-road concentrations as the 0
    m road proximity class?

-   Why do indoor sources need to be identified as important
    contributors to ambient air concentrations to be considered?

-   Figure 4: Why can there be significant on-road concentration but
    little elevated concentration at \<75m? (see the first site)

Table 4: While it is clear that the total column is a weighted average,
it is completely unclear what the average concentration total row means
(particularly given the numbers provided).

Section 3.4.1.2:

-   There is an assumption that the spatial and temporal contributions
    to NO~2~ are relatively simply related, i.e. temporal estimates from
    one location can be linearly transformed to get estimates at a new
    spatial location. Ideally this assumption should be checked. At
    least it should be discussed.

-   I think uncertainty in model structure can be evaluated with
    sensitivity analyses.

Section 3.4.2:

-   Does the term "long-term exposure" mean "annual average exposure"?

-   Add an introductory paragraph and start a new section subheading for
    the material already at the beginning of this section.

-   Equation (4) needs indices for time, space, and microenvironment
    type. Clarify the range and units of the indices.

-   Note a different approach to roadway contribution is being used
    here.

Section 3.4.2.1:

-   Give an equation to show the relationship described in the first
    sentence.

-   On what time scale will the additional exposure metric be
    calculated? (p 24 top)

Section 3.5.1:

-   p 26 first sentence first full paragraph: The approach to predicting
    hourly NO~2~ from monitoring data and dispersion models is a major
    research topic in itself. The approach taken here is relatively
    simple, and thus it should be mentioned as a limitation and source
    of uncertainty.

-   Should in-vehicle estimates be separated by road type?

Section 3.5.3: Instead of relying solely on informed judgment, why not
compare estimates from plausible models formulated differently?

Section 3:6: Define number of peak concentrations. Discuss Figure 5 in
more detail, and possibly move it to the beginning of Section 3.

Section 4:

-   I think the risk assessment needs to be reorganized to have 3 tiers.
    The first tier should be a qualitative assessment of the health
    evidence. This will list and consider all important health effects
    based on human and animal studies. Not all of these can be used for
    benchmark calculations or quantitative risk assessment, but it will
    be important to review them all first and get a sense of the scope
    of the risk qualitatively. Then a narrower list will be used for the
    second and third tier assessments. Not only does this proposed new
    tier structure allow for better progression in the treatment of the
    health results, but it also elevates the importance of the
    qualitative risk assessment in the document and protects against it
    being treated as an afterthought.

-   Criteria for acceptable outcomes to use in the risk assessment (as
    well as other aspects of the RA such as choice of city for the
    analysis) needs to be specified in advance for each tier.

-   Criteria for even conducting a quantitative risk assessment (the
    proposed second tier) need to be specified in this document in
    advance of the risk assessment.

-   The quantitative risk assessment should move towards incorporating
    an integrated uncertainty assessment as an integral part of the
    process. This would extend uncertainties in underlying assumptions
    into the estimated risks by incorporating a probabilistically
    weighted range of assumptions into the risk estimates and
    uncertainties estimated. This will be most appropriate for the
    highest tier of quantitative assessment.

Section 4.2: State the criteria for selecting health effects to be used
for the benchmark analysis.

Section 4.2.1: State the planned health effect benchmark levels or
criteria for selecting these levels.

Section 4.2.3: Third paragraph: In addition, a distribution of
benchmarks could be applied rather than sensitivity analyses of a set of
single values. I'm confused by the end of this paragraph (starting "From
a directional perspective..."). My understanding suggests either the
wording is backwards or I am confused. Perhaps an example will help the
reader's comprehension.

Section 4.3: The criteria for what is sufficient information to develop
credible exposure-response relationships *must* be stated. I note there
is information about such criteria in later subsections. Restating the
criteria in another form, such as a list, may be helpful.

Section 4.3.1.1 (and 4.4): I believe that the last two additional
factors (2: availability if sufficient C-R data in locations relevant to
the US and 3: availability of baseline incidence data) should be given
less weight in the decision to proceed. Both can be evaluated with
sensitivity analyses.

Section 4.3.3. The analysis should move towards an integrated
representation of all the most important uncertainties. Sensitivity
analyses are typically done by altering one assumption at a time. This
approach can be useful for identifying the most influential of the
uncertainties. It is possible statistical uncertainty (e.g. estimated
variance of a parameter) will be the least influential; rather the more
influential uncertainties may be due to the form and structure of the
risk assessment such as the choice of model, rollback assumptions, etc.
The integrated analysis would extend the Monte Carlo analysis to jointly
assess a range of model assumptions by putting probabilities on
different assumptions, such as several choices of the
concentration-response model coefficient and/or its functional form. The
difficulty with the integrated approach is there is another layer of
assumptions and reasonable ranges that need to be elicited and
incorporated into the analysis. The advantage is the quantitative risk
estimates will have additional sources of uncertainty incorporated
directly into the result. Moving towards an integrated analysis of these
uncertainties will give a fresh perspective of the range of possible
effects and the probability of effects at different levels.

Section 4.5: Restating an earlier comment: Summary of the health effect
data should precede the quantitative risk assessment as the first tier
risk assessment. The qualitative risk assessment should do more than
just provide the "broad context for the quantitative risk estimates". It
should be the foundation.

Response to charge questions: Exposure assessment

1.  *Broad exposure analysis evaluation*: a. The 3-tier structure is
    fine. In the final document all tiers should be covered, even if the
    only text is justification for why the tier was not conducted. b.
    See comments regarding Charge questions 1-3 of the ISA. c. Add
    populations at higher risk due to high exposure.

2.  *Tier I assessment*: a. Without seeing an analysis of the data, I
    can't comment. I suspect sites that differ by important NOx sources
    (e.g. distance to road) may fit this model more or less well. b. The
    roadway emissions approach seems to be overly simplistic, but may be
    the most reasonable approach given this is a lower tier assessment.

3.  *Tier II assessment*: a. Again, I would like to see an analysis of
    the data before I can form an opinion. I am concerned that near road
    monitors should not be used for the spatial interpolation model.
    Regardless, there may be too few monitors over space to do a
    reasonable spatial interpolation. It is not clear why the outcome
    generated should be a measure of exceedance, or how the criteria for
    exceedances will be chosen. b. This appears reasonable, although it
    treats people-hours as exchangeable. For this purpose that appears
    to be acceptable. c. No comment without further data analysis.

4.  *Tier III assessment*: APEX is a reasonable approach. Presumably the
    ambient monitoring predictions are conditional on the Tier II
    exposure assessment. In fact, coming up with the "modified and
    interpolated hourly NO2 concentration measurements" is a major
    research topic in itself. The approach taken is relatively simple
    and thus needs to be recognized as a source of uncertainty.

5.  *Advice on general approach to addressing uncertainty and
    variability*: Our best collective scientific understanding should
    help us prioritize sources of uncertainty and variability and focus
    on the most important ones. For those, I suggest comparing estimates
    for plausible models formulated under different assumptions
    (sensitivity analyses) and working towards extending the uncertainty
    analysis to jointly assess multiple different sources of uncertainty
    simultaneously (integrated uncertainty analysis).

Response to charge questions: Risk assessment

1.  *Overall structure and two-tier risk assessment approach:* I think
    there should be 3 tiers for the risk assessment with the first tier
    being a qualitative risk assessment. The criteria for selecting the
    endpoints should flow from the ISA, particularly the Chapter 5
    summary rewritten to use open and transparent criteria. I think the
    Pilotto et al (2004) study estimates are based on a strong enough
    study design that even though they haven't been directly replicated,
    they should be considered for the risk assessment. I don't consider
    the same location or no outside US location criteria to have
    sufficient weight to limit a Tier II risk assessment.

2.  *Tier I risk assessment:* a. Criteria for identifying benchmarks
    must be clearly stated in advance. b. I think the lung growth
    effects are also important to evaluate. c. While the Pilotto et
    al (2004) study is not a controlled study, it is an intervention
    study and a much stronger design than a pure observational study.

3.  *Tier II assessment:* a&b. See section 4.3 comments.

4.  *Addressing uncertainty and variability:* An integrated uncertainty
    assessment should be considered. See section 4.3.3. comments.

Reference: Additional thoughts on how to proceed with the integrated
uncertainty analysis may be found in this report:

Committee on Estimating the Health-Risk-Reduction Benefits of Proposed
Air Pollution Regulations, National Research Council. Estimating the
Public Health Benefits of Proposed Air Pollution Regulations. NRC 2002
(see Chapter 5) <http://www.nap.edu/catalog.php?record_id=10511>

[]{#__RefHeading___Toc182377132 .anchor}[Comments from Dr. Frank
Speizer]{.underline}

**Nitrogen Dioxide Health Assessment Plan: Scope and Methods for
Exposure and Risk Assessment (September 2007 draft)**

Answers to Charge Questions (paraphrased)

Submitted by Frank E. Speizer

Date: October 17, 2007

Air Quality Considerations

1\. Use of historic air quality data pre 2000.

This is not an unreasonable use of historical data. Figure 1 on page 5
suggest a marginally significant decline in the annual average NO2, but
the variation seems to have changed substantially with a marked drop in
the 90%tile level starting around 1997. In table 2.5-1 in ISA on page
2-52 spatial variations are wide in some cities. Thus, for the last 10
years may want to inflate the variance to better take into account the
individual city variation.

2\. Use of a proportional approach to modeling alternative air quality
standards.

I think the same observation made above applies to the use of
proportional adjustments. Somehow the drop in the 90%tile values along
with the variation across regions (cities) needs to be dealt with. If
proportional models works that is fine.

Exposure Analysis

1\. Broad considerations.

General Structure. This seems reasonable but I would be disappointed if
Staff concluded that they could not get past Tier I. For factors
influencing exposure perhaps there needs to be some discussion on how
the interaction with Ozone will be handled. In some of the regions there
are likely to be competing interaction, with quenching affecting what is
being measured and difficulties attributing risk. (This may all come up
later). In addition, it might be indicated as to how, at least in a
general sense indoor exposure, will be considered. Population groups of
interest. If possible I think it would be useful to consider children
broken down somewhat differently. The text in section 3.2, page 7,
suggests birth to age 18. I think it would be better to consider birth-
preschool (near home); 4 or 5 to 9 (local community); and 10-18 (active
outdoor physical activity). I recognize that the data may not exist but
at least the breakdowns for exposure might be considered. The other
grouping seem appropriate, except might want to consider those adults
carrying a cardiovascular disease diagnosis as a separate (potentially
more susceptible) group.

2\. Tier I exposure assessment

For exponential model and accounting for emissions this seems to be
appropriate, however, what will need to be discussed later is how this
model deals with the time-varying patterns of exposure that might occur
as people "move through" their approximate exposures. This forms the
basis of the discussion of uncertainties in section 3.3.3. Although the
potential issues that might vary exposure and uncertainties are well
described, it is not made clear just how these will be handled. (Perhaps
there will not be a variable added to Equation 3 and residential time
within x number of meters of a roadway value will only be discussed
qualitatively at this level of analysis but such should be stated.
Alternatively, if there would be a way to incorporate residential time
(or other modifiers of exposure) in the equations that would be useful.

3\. Tier II. This is a exceeding well written description of what needs
to be done, and if accomplished should satisfy the numbers needed for
any risk assessment. As I read through this I am wondering if all the
comments above on Tier I are irrelevant as many of the comments above
are answered in this section. Therefore should consideration be given to
combining the two Tiers into a more expanded discussion, since much of
the uncertainty in Tier I and specified again on page 17 are dealt with
here . (Leaving it own uncertainties.) In picking the distance to
roadways (\<75 m, 75-200 m, \>200 m) some justification needs to be
added on page 18. Particularly since on page 11 the spatial drop off
exposure levels gives a range of 200-500m to get to ambient. Note also
the footnote on page 18 on age distributions is more in line with my
comments above on age groups.

What is not clear in the discussion of uncertainty is the how the nature
of the monitoring station (residential, commercial, industrial) as well
as nature of residence near roadway (single family houses, large
apartment blocks) get taken into account, for example in table 4. Will
sites that are used for regulatory control at the edge of a factory be
excluded? What if all the people in the tract live more than 200m from
the monitor? In addition I assume that "fraction of the population in
each location" somehow gets factored in when census tract is used (as
total population, and age distribution within in each census tract, are
not all the same). Again, many of these issues are discussed in the Tier
III section, and again it makes me question whether the separation into
separate Tiers in imposing more criticism than is necessary. Figure 3 on
page 29 outlines the criteria needed, it seems likely that sufficient
data are available to proceed, so no more than a descriptive discussion
of how staff gets to Tier 3 is needed and they should get on with doing
the assessment as proposed.

Risk Assessment Scope and Methods

On page 33 section 4.3 I would recommend to staff that they reverse the
order of discussion on the credible exposure response relationships for
controlled human exposure studies and the epidemiological studies,
particularly sine the section title is Risk Based on Epidemiological
Studies. Clear most if not all of the controlled studies have been
carried out in normal healthy volunteers; whereas the epidemiological
studies are in general observations on free-living population groups
that obviously contain people with vary levels of risk. Judgment on risk
assessment should be made on the latter group with the controlled human
exposures experiments mostly designed to assess and understand potential
mechanisms for the risk observed in free-living populations.

The plan as outlined a two Tier effort, like for the exposure assessment
seems somewhat arbitrary as to whether it is called a two tier effort or
a logical progression in gathering the data necessary (and I believe
from the draft ISA) available to do all that is proposed. The short term
exposure assessment is well documented to move forward, particularly for
the respiratory outcomes described. With regard to the long term
assessment particularly for hospitalizations and mortality by
sub-regions, this may have to await the assessment of the draft ISA.

With regard to the criteria for determining the approach to tier ii on
page 37, I accept that the thinking of these steps are necessary to get
to the data but as indicated above I believe there are sufficient
evidence, particularly for the short term effects, that doing the risk
assessment for respiratory outcomes should be straight forward. However,
I totally reject the placement of the last bullet on page 37, in section
4.4 as a criteria for doing what is needed. There should be sufficient
resources to complete the task in the next 15 months. It is a priority
for the task to be done in the next 15 months and if resources must be
borrowed from other activities to get it done, that should be the
decision.

[]{#__RefHeading___Toc182377133 .anchor}[Comments from Dr. George
Thurston]{.underline}

COMMENTS FROM GEORGE D. THURSTON

Comments on Nitrogen Dioxide Health Exposure and Risk Assessment
(September 2007)

General Comments

This plan successfully outlines the scope and approaches for, and
highlights key issues in, the estimation of population exposures and
health risks posed by NOx under: 1) existing air quality levels; 2) upon
just meeting the current NO2 primary NAAQS, and; 3) upon just meeting
potential alternative standards under consideration by the
Administration.

The main concern I have is in the selection of the key CMSA's for
evaluation. More justification for these choices needs to be presented.
In particular, it is surprising to me that New York City, which has a
high concentration of those whom the ISA is pointing to as most affected
(e.g., poor children with asthma living near roadways). I think
consideration of both LA and NYC would give balance to the document, as
LA has a high concentration of NO~x~ exposures, while NYC includes a
high concentration of especially affected individuals. The other three
cities selected should provide more "typical" U.S. urban
exposures/populations.

I also feel that the U.S. EPA should consider emergency department (ED)
visits to the extent possible. These data are becoming more widely
available on a routine basis throughout the U.S., and may more
accurately reflect the extent of effects, given recent cost-saving
efforts to treat problems like asthma in the ED, rather than as a
hospital admission.

Specific Comments

P8, Sec 3.3.1, par. 1 (regarding the selection of CMSAs for evaluation)
-- Why Atlanta, Philadelphia, and Chicago over New York, Phoenix, and
Denver? More justification for CMSA selection should be provided.

P8, Sec. 3.3.1, par. 2. I feel this list of criteria should include some
involving exposed populations in each CMSA in addition to the exposure
concentration profiles discussed here (perhaps %poor, ssthma prevalence,
% living within 200 yards of a highway, % minority, or the like),

P35, Sec 4.3.1.2, par. 3. I agree with the balanced discussion of the
multi-pollutant issue presented here. My only addition is that, when
possible, the models considered should consider no more than two
pollutants at a time to help clarify the role of each pollutant relative
to each of the others. When more than that are included, it becomes much
harder to sort out real effects from multi-collinearity effects.

[Comments from Dr. George Thurston]{.underline}

General Comments

This plan successfully outlines the scope and approaches for, and
highlights key issues in, the estimation of population exposures and
health risks posed by NOx under: 1) existing air quality levels; 2) upon
just meeting the current NO2 primary NAAQS, and; 3) upon just meeting
potential alternative standards under consideration by the
Administration.

The main concern I have is in the selection of the key CMSA's for
evaluation. More justification for these choices needs to be presented.
In particular, it is surprising to me that New York City, which has a
high concentration of those whom the ISA is pointing to as most affected
(e.g., poor children with asthma living near roadways). I think
consideration of both LA and NYC would give balance to the document, as
LA has a high concentration of NO~x~ exposures, while NYC includes a
high concentration of especially affected individuals. The other three
cities selected should provide more "typical" U.S. urban
exposures/populations.

I also feel that the U.S. EPA should consider emergency department (ED)
visits to the extent possible. These data are becoming more widely
available on a routine basis throughout the U.S., and may more
accurately reflect the extent of effects, given recent cost-saving
efforts to treat problems like asthma in the ED, rather than as a
hospital admission.

Specific Comments

P8, Sec 3.3.1, par. 1 (regarding the selection of CMSAs for evaluation)
-- Why Atlanta, Philadelphia, and Chicago over New York, Phoenix, and
Denver? More justification for CMSA selection should be provided.

P8, Sec. 3.3.1, par. 2. I feel this list of criteria should include some
involving exposed populations in each CMSA in addition to the exposure
concentration profiles discussed here (perhaps %poor, ssthma prevalence,
% living within 200 yards of a highway, % minority, or the like),

P35, Sec 4.3.1.2, par. 3. I agree with the balanced discussion of the
multi-pollutant issue presented here. My only addition is that, when
possible, the models considered should consider no more than two
pollutants at a time to help clarify the role of each pollutant relative
to each of the others. When more than that are included, it becomes much
harder to sort out real effects from multi-collinearity effects.

[]{#__RefHeading___Toc182377134 .anchor}[Comments from Dr. Ronald
Wyzga]{.underline}

In general the approach appears to be reasonable, but ambitious. The
challenge will be to implement this plan with available resources in a
way that is scientifically credible and in a way that illuminates the
available information to inform further discussions about the NO2
primary NAAQS.

Within this approach there are two points that I want to raise:

The input data for the assessment are subject to uncertainties (multiple
studies with different results, missing information, etc.). I would urge
the investigators to consider ways to internalize the uncertainties
within the analyses rather than to undertake base analyses accompanied
by sensitivity analyses. The outputs of such analyses are likely to
ranges or distributions of estimates rather than point estimates, but
such ranges more accurately portray reality than do point estimates.

Secondly I am disturbed by the approach taken in evaluating the risks
and exposures associated with ambient levels of NO2 associated with just
meeting the current standard. Since the entire US is currently within
compliance, the entire country has NO2 levels below the current
standard. To assume under this scenario that the entire country has NO2
levels at the standard will clearly lead to overestimates of risk and
exposure, and there is concern that the resulting estimates will be
accepted at face value and misinterpreted. I urge the staff to consider
ways to confront this issue in a way that more realistically portrays
the exposures/risks associated with current and alternative standards.

[^1]: This does not necessarily correspond to the distribution of
    concentrations/"exposures" at regulatory monitoring sites, as people
    may live in locations that are differentially represented by the
    monitoring sites, in addition to the distortion discussed in the
    document between ground level locations of people and the elevated
    locations of the air monitors.