respiratory morbidity at ambient concentrations below the current
NAAQS. The robustness of epidemiologic findings to adjustment for co-
pollutants, coupled with data from animal and human experimental
studies, support a determination that the relationship between
NO2 and respiratory morbidity is likely causal, while still
recognizing the relationship between NO2 and other traffic-
related pollutants.''
    A related uncertainty is that associated with the estimated
NO2 coefficient in the concentration-response function. This
coefficient has been characterized by confidence intervals reflecting
sample size. However, these confidence intervals do not reflect all of
the uncertainties related to the concentration-response functions, such
as whether or not the model used in the epidemiologic study is the
correct model form. Concerning the possible role of co-pollutants in
the Tolbert et al. (2007) study, single-pollutant models may produce
overestimates of the NO2 effects if some of those effects
are really due in whole or part to one or more of the other pollutants.
On the other hand, effect estimates based on multi-pollutant models can
be uncertain, and can result in statistically non-significant estimates
where a true relationship exists, if the co-pollutants included in the
model are highly correlated with NO2. As a result of these
considerations, we report risk estimates based on both the single- and
multi-pollutant models from Tolbert et al. (2007).

D. Considerations in Review of the Standard

    This section presents the integrative synthesis of the evidence and
information contained in the ISA and the REA with regard to the current
and potential alternative standards. EPA notes that the final decision
on retaining or revising the current primary NO2 standard is
a public health policy judgment to be made by the Administrator. This
judgment will be informed by a recognition that the available health
effects evidence reflects a continuum consisting of ambient levels of
NO2 at which scientists generally agree that health effects
are likely to occur, through lower levels at which the likelihood and
magnitude of the response become increasingly uncertain. The
Administrator's final decision will draw upon scientific information
and analyses related to health effects, population exposures, and
risks; judgments about the appropriate response to the range of
uncertainties that are inherent in the scientific evidence and
analyses; and comments received in response to this proposal.
1. Background on the Current Standard
    The current standard, which is an annual average of 0.053 ppm (53
ppb), was retained by the Administrator in the most recent review in
1996 (61 FR 52854 (October 8, 1996)). The decision in that review to
retain the annual standard was based on consideration of available
scientific evidence for health effects associated with NO2
and on air quality information. With regard to these considerations,
the Administrator noted that ``a 0.053 ppm annual standard would keep
annual NO2 concentrations considerably below the long-term
levels for which serious chronic effects have been observed in
animals'' and that ``[r]etaining the existing standard would also
provide protection against short-term peak NO2
concentrations at the levels associated with mild changes in pulmonary
function and airway responsiveness observed in controlled human
studies'' (60 FR 52874, 52880 (Oct. 11, 1995)). As a result, the
Administrator concluded that ``the existing annual primary standard
appears to be both adequate and necessary to protect human health
against both long- and short-term NO2 exposures'' and that
``retaining the existing annual standard is consistent

with the scientific data assessed in the Criteria Document (EPA, 1993)
and the Staff Paper (EPA, 1995) and with the advice and recommendations
of CASAC'' (61 FR 52852 at 52854).
    As noted previously, the 1993 AQCD concluded that there were two
key health effects of greatest concern at ambient or near-ambient
levels of NO2: increased airway responsiveness in asthmatic
individuals after short-term exposures and increased occurrence of
respiratory illness in children with longer-term exposures. Evidence
also was found for increased risk of emphysema, but this was of major
concern only with exposures to levels of NO2 much higher
than then-current ambient concentrations. The evidence regarding airway
responsiveness was drawn largely from controlled human exposure
studies. The evidence for respiratory illness was drawn from
epidemiologic studies that reported associations between respiratory
symptoms and indoor exposures to NO2 in people living in
homes with gas stoves. The biological plausibility of the epidemiologic
results was supported by toxicological studies that detected changes in
lung host defenses following NO2 exposure. Subpopulations
considered potentially more susceptible to the effects of
NO2 included individuals with preexisting respiratory
disease, children, and the elderly.
    In that review, health risks were characterized by comparing
ambient monitoring data, which were used as a surrogate for exposure,
with potential health benchmark levels identified from controlled human
exposure studies. At the time of the review, a meta-analysis of
controlled human exposure studies indicated the possibility for adverse
health effects due to short-term (e.g., 1-hour) exposures between 200
ppb and 300 ppb NO2. Therefore, the focus of the assessment
was on the potential for short-term (i.e., 1-hour) exposures to
NO2 levels above potential health benchmarks in this range.
The assessment used monitoring data from the years 1988-1992 and
screened for sites with one or more hourly exceedances of potential
short-term health effect benchmarks. Predictive models were then
constructed to relate the frequency of hourly concentrations above
short-term health effect benchmarks to a range of annual average
concentrations, including the current standard. Based on the results of
this analysis, both CASAC (Wolff, 1995) and the Administrator (60 FR
52874) concluded that the minimal occurrence of short-term peak
concentrations at or above a potential health effect benchmark of 200
ppb (1-hour average) indicated that the existing annual standard would
provide adequate health protection against short-term exposures. This
conclusion, combined with the conclusion that the current annual
standard would maintain annual average levels well-below those
associated with serious effects in animal toxicological studies, formed
a large part of the basis for the decision in the 1996 review to retain
the existing annual standard.
2. Approach for Reviewing the Need To Retain or Revise the Current
Standard
    The decision in the present review on whether the current annual
standard is requisite to protect public health with an adequate margin
of safety will be informed by a number of scientific studies and
analyses that were not available in the 1996 review. Specifically, as
discussed above (section II), a large number of epidemiologic studies
have been published since the 1996 review. Many of these studies
evaluate associations between NO2 and adverse respiratory
endpoints (e.g., respiratory symptoms, emergency department visits,
hospital admissions) in locations where annual average NO2
concentrations are well-below the level allowed by the current standard
(53 ppb). In addition, the meta-analysis of controlled human exposure
studies has been updated for this review to include information on
additional exposure concentrations. Finally, the REA described
estimates of NO2-associated health risks that could be
present in locations that just meet the current annual standard. These
types of risk estimates were not available in the last review. The
approach for considering this scientific evidence and exposure/risk
information is discussed below.
    To evaluate whether the current primary NO2 standard is
adequate or whether consideration of revisions is appropriate, EPA is
using an approach in this review that has been described in chapter 10
of the REA. The approach outlined in the REA builds upon the approaches
used in reviews of other criteria pollutants, including the most recent
reviews of the Pb, O3, and PM NAAQS (EPA, 2007d; EPA, 2007e;
EPA, 2005), and reflects the body of evidence and information that is
currently available. As in other recent reviews, EPA's considerations
will include the implications of placing more or less weight or
emphasis on different aspects of the scientific evidence and the
exposure/risk-based information, recognizing that the weight to be
given to various elements of the evidence and exposure/risk information
is part of the public health policy judgments that the Administrator
will make in reaching decisions on the standard.
    A series of general questions frames this approach to considering
the scientific evidence and exposure-/risk-based information. First,
EPA's consideration of the scientific evidence and exposure/risk
information with regard to the adequacy of the current standard is
framed by the following questions:

     To what extent does evidence that has become available
since the last review reinforce or call into question evidence for
NO2-associated effects that were identified in the last
review?
     To what extent has evidence for different health
effects and/or sensitive populations become available since the last
review?
     To what extent have uncertainties identified in the
last review been reduced and/or have new uncertainties emerged?
     To what extent does evidence and exposure-/risk-based
information that has become available since the last review
reinforce or call into question any of the basic elements of the
current standard?

    To the extent that the available evidence and exposure-/risk-based
information suggests it may be appropriate to consider revision of the
current standard, EPA considers that evidence and information with
regard to its support for consideration of a standard that is either
more or less protective than the current standard. This evaluation is
framed by the following questions:

     Is there evidence that associations, especially causal
or likely causal associations, extend to ambient NO2
concentrations as low as, or lower than, the concentrations that
have previously been associated with health effects? If so, what are
the important uncertainties associated with that evidence?
     Are exposures above benchmark levels and/or health
risks estimated to occur in areas that meet the current standard? If
so, are the estimated exposures and health risks important from a
public health perspective? What are the important uncertainties
associated with the estimated risks?

    To the extent that there is support for consideration of a revised
standard, EPA then considers the specific elements of the standard
(indicator, averaging time, form, and level) within the context of the
currently available information. In so doing, the Agency addresses the
following questions:

     Does the evidence provide support for considering a
different indicator for gaseous NOX?
     Does the evidence provide support for considering
different averaging times?
     What ranges of levels and forms of alternative
standards are supported by the evidence, and what are the associated
uncertainties and limitations?

     To what extent do specific averaging times, levels, and
forms of alternative standards reduce the estimated exposures above
benchmark levels and risks attributable to NO2, and what
are the uncertainties associated with the estimated exposure and
risk reductions?

    The questions outlined above have been addressed in the REA. The
following sections present considerations regarding the adequacy of the
current standard and potential alternative standards, as discussed in
chapter 10 of the REA, in terms of indicator, averaging time, form, and
level.

E. Adequacy of the Current Standard

    In considering the adequacy of the current standard, the policy
assessment chapter of the REA considered the scientific evidence
assessed in the ISA and the quantitative exposure- and risk-based
information presented in the REA. A summary of this evidence and
information as well as CASAC recommendations and the Administrator's
conclusions regarding the adequacy of the current standard are
presented below.
1. Evidence-Based Considerations
    As discussed in chapter 10 of the REA, evidence published since the
last review generally has confirmed and extended the conclusions
articulated in the 1993 AQCD (ISA, section 5.3.2). The epidemiologic
evidence has grown substantially with the addition of field and panel
studies, intervention studies, time-series studies of effects such as
emergency department visits and hospital admissions, and a substantial
number of studies evaluating mortality risk associated with short-term
NO2 exposures. As noted above, no epidemiologic studies were
available in 1993 that assessed relationships between NO2
and outcomes such as hospital admissions, emergency department visits,
or mortality. In contrast, dozens of epidemiologic studies on such
outcomes, conducted at recent and current ambient NO2
concentrations, are now included in this evaluation (ISA, chapter 3).
While not as marked as the growth in the epidemiologic literature, a
number of recent toxicological and human clinical studies also provide
insights into relationships between NO2 exposure and health
effects.
    As an initial consideration with regard to the adequacy of the
current standard, the REA noted that the evidence relating long-term
(weeks to years) NO2 exposures at current ambient
concentrations to adverse health effects was judged in the ISA to be
either ``suggestive but not sufficient to infer a causal relationship''
(respiratory morbidity) or ``inadequate to infer the presence or
absence of a causal relationship'' (mortality, cancer, cardiovascular
effects, reproductive/developmental effects) (ISA, sections <IP_ADDRESS>-
<IP_ADDRESS>). In contrast, the evidence relating short-term (minutes to
hours) NO2 exposures to respiratory morbidity was judged to
be ``sufficient to infer a likely causal relationship'' (ISA, section
<IP_ADDRESS>). This judgment was supported primarily by a large body of
recent epidemiologic evidence that evaluated associations of short-term
NO2 concentrations with respiratory symptoms, emergency
department visits, and hospital admissions. These conclusions from the
ISA suggest that, at a minimum, consideration of the adequacy of the
current annual standard should take into account the extent to which
that standard provides protection against respiratory effects
associated with short-term NO2 exposures. As noted in the
REA, such an emphasis on health endpoints for which evidence has been
judged to be sufficient to infer a likely causal relationship would be
consistent with other recent NAAQS reviews (e.g., EPA, 2005; EPA,
2007d; EPA, 2007e).
    In considering the NO2 epidemiologic studies as they
relate to the adequacy of the current standard, the REA noted that
annual average NO2 concentrations were below the level of
the current annual NO2 NAAQS in many of the locations where
positive, and often statistically significant, associations with
respiratory morbidity endpoints have been reported (ISA, section 5.4).
As discussed previously, the ISA characterized that evidence for
respiratory effects as consistent and coherent. The evidence is
consistent in that associations are reported in studies conducted in
numerous locations and with a variety of methodological approaches
(ISA, section <IP_ADDRESS>). It is coherent in the sense that the studies
report associations with respiratory health outcomes that are logically
linked together (ISA, section <IP_ADDRESS>). The ISA noted that when the
epidemiologic literature is considered as a whole, there are generally
positive associations between NO2 and respiratory symptoms,
hospital admissions, and emergency department visits. A number of these
associations are statistically significant, particularly the more
precise effect estimates (ISA, section <IP_ADDRESS>).
    As discussed previously, the interpretation of these NO2
epidemiologic studies is complicated by the fact that on-road vehicle
exhaust emissions are a nearly ubiquitous source of combustion
pollutant mixtures that include NO2. In order to provide
some perspective on the uncertainty related to the presence of co-
pollutants, the ISA evaluated epidemiologic studies that employed
multi-pollutant models, epidemiologic studies of indoor and personal
NO2 exposure, and experimental studies. Specifically, the
ISA noted that a number of NO2 epidemiologic studies have
attempted to disentangle the effects of NO2 from those of
co-occurring pollutants by employing multi-pollutant models. When
evaluated as a whole, NO2 effect estimates in these models
generally remained robust when co-pollutants were included. Therefore,
despite uncertainties associated with separating the effects of
NO2 from those of co-occurring pollutants, the ISA (section
5.4, p. 5-16) concluded that ``the evidence summarized in this
assessment indicates that NO2 associations generally remain
robust in multi-pollutant models and supports a direct effect of short-
term NO2 exposure on respiratory morbidity at ambient
concentrations below the current NAAQS.'' With regard to indoor
studies, the ISA noted that these studies can test hypotheses related
to NO2 specifically (ISA, section <IP_ADDRESS>). Although
confounding by indoor combustion sources is a concern, indoor studies
are not confounded by the same mix of co-pollutants present in the
ambient air or by the contribution of NO2 to the formation
of secondary particles or O3 (ISA, section <IP_ADDRESS>). The ISA
noted that the findings of indoor NO2 studies are consistent
with those of studies using ambient concentrations from central site
monitors and concluded that indoor studies provide evidence of
coherence for respiratory effects (ISA, section <IP_ADDRESS>). With regard
to experimental studies, the REA noted that they have the advantage of
providing information on health effects that are specifically
associated with exposure to NO2 in the absence of co-
pollutants. The ISA concluded that the NO2 epidemiologic
literature is supported by (1) evidence from controlled human exposure
studies of airway hyperresponsiveness in asthmatics, (2) controlled
human exposure and animal toxicological studies of impaired host-
defense systems and increased risk of susceptibility to viral and
bacterial infection, and (3) controlled human exposure and animal
toxicological studies of airway inflammation (ISA, section <IP_ADDRESS> and
5.4).
    In drawing broad conclusions regarding the evidence, the ISA

considered the epidemiologic and experimental evidence as well as the
uncertainties associated with that evidence. When this evidence and its
associated uncertainties are taken together, the ISA concluded that the
results of epidemiologic and experimental studies form a plausible and
coherent data set that supports a relationship between NO2
exposures and respiratory endpoints, including respiratory symptoms and
emergency department visits, at ambient concentrations that are present
in areas that meet the current NO2 NAAQS. Thus, taking into
consideration the evidence discussed above, particularly the
epidemiologic studies reporting NO2-associated health
effects in locations that meet the current standard, the REA concluded
that the scientific evidence calls into question the adequacy of the
current standard to protect public health.
2. Exposure- and Risk-Based Considerations
    In addition to the evidence-based considerations described above,
the REA considered the extent to which exposure- and risk-based
information can inform decisions regarding the adequacy of the current
annual NO2 standard, taking into account key uncertainties
associated with the estimated exposures and risks. As noted above,
NO2-associated health risks were characterized with three
approaches. In the first, NO2 air quality from locations
across the country was used as a surrogate for exposure. In the second,
exposures were estimated for all asthmatics and for asthmatic children
considering time spent in different microenvironments in one urban
area, Atlanta, GA. For both of these analyses, health risks were
characterized by comparing estimates of air quality or exposure to
potential health benchmark levels. Benchmark levels spanned the range
of NO2 concentrations that have been reported to increase
airway responsiveness in asthmatics (i.e., 100-300 ppb). In the third
approach to characterizing NO2-related health risks,
occurrences of NO2-related respiratory emergency department
visits were estimated for Atlanta. This quantitative risk assessment
was based on NO2 concentration-response relationships
identified in an epidemiologic study of air pollution-related emergency
department visits in Atlanta. The results of each of these analyses are
discussed in this section, specifically as they relate to the current
standard.
    When considering the Atlanta risk assessment results as they relate
to the adequacy of the current standard, the REA noted that central
estimates of incidence of NO2-related respiratory emergency
department visits in Atlanta ranged from approximately 8 to 9% of total
respiratory-related emergency department visits per year (or 9,800-
10,900 NO2-related incidences) based on single pollutant
models when air quality is adjusted upward to simulate a situation
where Atlanta just meets the current standard. Central estimates of
incidence of NO2-related respiratory emergency department
visits ranged from 2.9-7.7% of total respiratory-related emergency
department visits per year (or 3,600-9,400 NO2-related
incidences) based on two-pollutant models. Inclusion of O3 and/or PM10
in multi-pollutant models resulted in the inclusion of an estimate of
zero NO2-related respiratory emergency department visits
within the 95% confidence intervals.
    When considering the Atlanta exposure results as they relate to the
adequacy of the current standard, the REA noted the number of days per
year asthmatics could experience exposure to NO2
concentrations greater than or equal to potential health benchmark
levels, given air quality that is adjusted upward to simulate just
meeting the current standard. If NO2 concentrations were
such that the Atlanta area just meets the current standard, nearly all
asthmatics in Atlanta (>97%) would be estimated to experience six or
more days per year with 1-hour NO2 exposure concentrations
greater than or equal to our highest benchmark level (300 ppb) (REA,
Figure 8-22). Six days per year was the largest number of days
specifically considered in the REA, but these results suggest that some
asthmatics could experience 1-hour NO2 exposure
concentrations greater than or equal to 300 ppb on more than six days
per year. In addition, more frequent exceedances would be expected for
the lower benchmark levels.
    When considering the air quality-based results as they relate to
the adequacy of the current standard, the REA noted the number of
benchmark exceedances estimated to occur in different locations given
air quality that just meets that standard. In situations where annual
NO2 concentrations were adjusted upward to simulate just
meeting the current standard, 1-hour NO2 concentrations
measured at fixed-site monitors in locations across the U.S. could
exceed benchmark levels. Most locations were estimated to experience at
least 50 days per year with 1-hour ambient NO2
concentrations at fixed-site monitors in the current network greater
than or equal to 100 ppb (Figures 7-2 and 7-3 in the REA) under this
hypothetical scenario. Far fewer ambient exceedances were predicted for
the higher benchmark levels. For example, only 5 areas were estimated
to experience any days with 1-hour ambient NO2
concentrations at fixed-site monitors greater than or equal to 300 ppb,
and none of those locations were estimated to experience more than 2
such days per year, on average (REA, Appendix A).
    However, on-road NO2 concentrations were estimated in
this analysis to be an average of 80% higher than concentrations at
fixed-site monitors (though this relationship will vary across
locations and with time). In the majority of locations evaluated,
roadway exceedances of the 100 ppb benchmark level could occur on most
days of the year when air quality is adjusted upward to simulate just
meeting the current standard (Figure 7-6 in the REA). Even for higher
benchmark levels, most locations were estimated to have exceedances on
roadways. All locations evaluated except one (Boston) were estimated to
experience on-road NO2 concentrations greater than or equal
to 300 ppb (REA, Appendix A). Four of these locations were estimated to
experience an average of greater than 20 days per year with on-road
NO2 concentrations greater than or equal to 300 ppb (REA,
Appendix A).
3. Summary of Considerations From the REA
    As noted above, the policy assessment chapter of the REA considered
the scientific evidence with regard to the current standard. This
included consideration of causality judgments made in the ISA regarding
the level of support for effects associated with short-term and long-
term exposures, the epidemiologic evidence described in the ISA
including associated uncertainties, the conclusions in the ISA
regarding the robustness of this evidence, and the support provided for
epidemiologic findings by experimental studies. The REA concluded that,
given these considerations, particularly the evidence for
NO2-associated effects in locations that meet the current
standard, the adequacy of the current standard to protect the public
health is clearly called into question. This evidence provides support
for consideration of an NO2 standard that would provide
increased health protection for at-risk groups, including asthmatics
and individuals who spend time on or near major roadways, against
health effects associated with short-term exposures ranging from
increased asthma symptoms to respiratory-related emergency department
visits and

hospital admissions, in addition to potential effects associated with
long-term exposures.
    In examining the exposure- and risk-based information with regard
to the adequacy of the current annual NO2 standard to
protect the public health, the REA noted that estimated risks
associated with air quality adjusted upward to simulate just meeting
the current standard can reasonably be concluded to be important from a
public health perspective. In particular, a large percentage (8-9%) of
respiratory-related ED visits in Atlanta could be associated with
short-term NO2 exposures, most asthmatics in Atlanta could
be exposed on multiple days per year to NO2 concentrations
at or above the highest benchmark evaluated, and most locations
evaluated could experience on-/near-road NO2 concentrations
above benchmark levels on more than half of the days in a given year.
Therefore, the REA noted that exposure- and risk-based results
reinforce the scientific evidence in supporting the conclusion that
consideration should be given to revising the current standard so as to
provide increased public health protection, especially for at-risk
groups, from NO2-related adverse health effects associated
with short-term, and potential long-term, exposures.
4. CASAC Views
    With regard to the adequacy of the current standard, CASAC
conclusions were consistent with the views expressed in the policy
assessment chapter of the REA. CASAC agreed that the primary concern in
this review is to protect against health effects that have been
associated with short-term NO2 exposures. CASAC also agreed
that the current annual standard is not sufficient to protect public
health against the types of exposures that could lead to these health
effects. Given these considerations, and as noted in their letter to
the EPA Administrator, ``CASAC concurs with EPA's judgment that the
current NAAQS does not protect the public's health and that it should
be revised'' (Samet, 2008b). CASAC's views on how the standard should
be revised are provided below within the context of discussions on the
elements (i.e., indicator, averaging time, form, level) of a new short-
term standard.

5. Administrator's Conclusions Regarding Adequacy of the Current
Standard

    In considering the adequacy of the current NO2 NAAQS,
the Administrator has considered the conclusions of the ISA, the
conclusions of the policy assessment chapter of the REA, and the views
expressed by CASAC. In particular, the ISA concluded that the results
of epidemiologic and experimental studies form a plausible and coherent
data set that supports a likely causal relationship between short-term
NO2 exposures and adverse respiratory effects at ambient
NO2 concentrations that are present in locations meeting the
current NO2 NAAQS. With regard to the exposure and risk
results, the REA concludes that central risk estimates suggest that the
current standard could allow important adverse public health impacts.
    Based on her consideration of these conclusions, as well as
consideration of CASAC's conclusion that the current NO2
NAAQS does not protect the public's health, the Administrator concludes
that the current NO2 standard does not provide the requisite
degree of protection for public health against adverse effects
associated with short-term exposures. In considering approaches to
revising the current standard, the Administrator concludes that it is
appropriate to consider setting a new short-term standard to supplement
the current annual standard. The Administrator notes that such a short-
term standard could provide increased public health protection,
especially for members of at-risk groups, from effects described in
both epidemiologic and controlled human exposure studies to be
associated with short-term exposures to NO2.

F. Conclusions on the Elements of a New Short-Term Standard and an
Annual Standard

    In considering alternative NO2 primary NAAQS, the
Administrator notes the need to protect at-risk individuals from short-
term exposures to NO2 air quality that could cause the types
of respiratory morbidity effects reported in epidemiologic studies and
the need to protect at-risk individuals from short-term exposure to
NO2 concentrations reported in controlled human exposure
studies to increase airway responsiveness in asthmatics. Considerations
with regard to potential alternative standards and the specific options
being proposed are discussed in the following sections in terms of
indicator, averaging time, form, and level (sections II.F.1-II.F.4).
1. Indicator
    In past reviews, EPA has focused on NO2 as the most
appropriate indicator for ambient NOX. In making a decision
in the current review on the most appropriate indicator, the
Administrator has considered the conclusions of the ISA and REA as well
as the view expressed by CASAC. The REA noted that, while the presence
of NOX species other than NO2 has been
recognized, no alternative to NO2 has been advanced as being
a more appropriate surrogate. Controlled human exposure studies and
animal toxicology studies provide specific evidence for health effects
following exposure to NO2. Epidemiologic studies also
typically report levels of NO2 though the degree to which
monitored NO2 reflects actual NO2 levels, as
opposed to NO2 plus other gaseous NOX, can vary
(REA, section 2.2.3). In addition, because emissions that lead to the
formation of NO2 generally also lead to the formation of
other NOX oxidation products, measures leading to reductions
in population exposures to NO2 can generally be expected to
lead to reductions in population exposures to other gaseous
NOX. Therefore, an NO2 standard can also be
expected to provide some degree of protection against potential health
effects that may be independently associated with other gaseous
NOX even though such effects are not discernable from
currently available studies indexed by NO2 alone. Given
these key points, the REA concluded that the evidence supports
retaining NO2 as the indicator. Consistent with this
conclusion, the CASAC Panel recommended in its letter to the EPA
Administrator that it ``concurs with retention of NO2 as the
indicator'' (Samet, 2008b). In light of the above considerations, the
Administrator proposes to retain NO2 as the indicator in the
current review.
2. Averaging Time
    The current annual averaging time for the NO2 NAAQS was
originally set in 1971, based on epidemiologic studies that supported a
link between adverse respiratory effects and long-term exposure to low
levels of NO2. As noted above, that annual standard was
retained in subsequent reviews in part because an air quality
assessment conducted by EPA concluded that areas that meet the annual
standard would be unlikely to experience short-term ambient peaks above
concentrations that had been reported in a meta-analysis of controlled
human exposure studies to increase airway responsiveness in asthmatics.
In the current review, additional scientific evidence is available to
inform a decision on averaging time. This includes the availability of
a number of epidemiologic studies that have evaluated endpoints
including respiratory symptoms, emergency

department visits, and hospital admissions as well as an updated meta-
analysis of controlled human exposure studies of airway responsiveness
in asthmatics.
    In order to inform conclusions with regard to averaging time in
this review, the REA considered judgments on the evidence from the ISA,
results from experimental and epidemiologic studies, and an analysis of
correlations between short- and long-term ambient NO2
concentrations. These considerations are described in more detail
below.
a. Short-Term Averaging Time
    As described previously, the evidence relating short-term (minutes
to hours) NO2 exposures to respiratory morbidity was judged
in the ISA to be ``sufficient to infer a likely causal relationship''
(ISA, section <IP_ADDRESS>) while the evidence relating long-term (weeks to
years) NO2 exposures to adverse health effects was judged to
be either ``suggestive but not sufficient to infer a causal
relationship'' (respiratory morbidity) or ``inadequate to infer the
presence or absence of a causal relationship'' (mortality, cancer,
cardiovascular effects, reproductive/developmental effects) (ISA,
sections <IP_ADDRESS>-<IP_ADDRESS>). Thus, the REA concluded that these judgments
most directly support an averaging time that focuses protection on
short-term exposures to NO2.
    As in past reviews of the NO2 NAAQS, it is instructive
to evaluate the potential for a standard based on annual average
NO2 concentrations, as is the current standard, to provide
protection against short-term NO2 exposures. To this end,
Table 10-1 in the REA reported the ratios of short-term to annual
average NO2 concentrations. Ratios of 1-hour daily maximum
concentrations (98th and 99th percentile) \10\ to annual average
concentrations across 14 locations ranged from 2.5 to 8.7 while ratios
of 24-hour average concentrations to annual average concentrations
ranged from 1.6 to 3.8 (see Thompson, 2008 for more details). The REA
concluded that the variability in these ratios across locations,
particularly those for 1-hour concentrations, suggested that a standard
based on annual average NO2 concentrations would not likely
be an effective or efficient approach to focus protection on short-term
NO2 exposures. For example, in an area with a relatively
high ratio (e.g., 8), the current annual standard (53 ppb) would be
expected to allow 1-hour daily maximum NO2 concentrations of
about 400 ppb. In contrast, in an area with a relatively low ratio
(e.g., 3), the current standard would be expected to allow 1-hour daily
maximum NO2 concentrations of about 150 ppb. Thus, for
purposes of protecting against the range of 1-hour NO2
exposures, the REA noted that a standard based on annual average
concentrations would likely require more control than necessary in some
areas and less control than necessary in others, depending on the
standard level selected.
---------------------------------------------------------------------------

    \10\ As discussed below, 98th and 99th percentile forms were
evaluated in the REA. A 99th percentile form corresponds
approximately to the 4th highest 1-hour concentration in a year
while a 98th percentile form corresponds approximately to the 7th or
8th highest 1-hour concentration in a year. A 4th highest
concentration form has been used previously in the O3
NAAQS while a 98th percentile form has been used previously in the
PM2.5 NAAQS.
---------------------------------------------------------------------------

    In considering the level of support available for specific short-
term averaging times, the policy assessment chapter of the REA noted
evidence from both experimental and epidemiologic studies. Controlled
human exposure studies and animal toxicological studies provide
evidence that NO2 exposures from less than 1-hour up to 3-
hours can result in respiratory effects such as increased airway
responsiveness and inflammation (ISA, section <IP_ADDRESS>). Specifically,
the ISA concluded that NO2 exposures of 100 ppb for 1-hour
(or 200 ppb to 300 ppb for 30-min) can result in small but significant
increases in nonspecific airway responsiveness (ISA, section <IP_ADDRESS>).
In contrast, the epidemiologic literature provides support for short-
term averaging times ranging from approximately 1-hour up to 24-hours
(ISA, section <IP_ADDRESS>). A number of epidemiologic studies have detected
positive associations between respiratory morbidity and 1-hour (daily
maximum) and/or 24-hour NO2 concentrations. A few
epidemiologic studies have considered both 1-hour and 24-hour averaging
times, allowing comparisons to be made. The ISA reported that such
comparisons in studies that evaluate asthma emergency department visits
failed to reveal differences between effect estimates based on a 1-hour
averaging time and those based on a 24-hour averaging time (ISA,
section <IP_ADDRESS>). Therefore, the ISA concluded that it is not possible,
from the available epidemiologic evidence, to discern whether effects
observed are attributable to average daily (or multi-day)
concentrations (24-hour average) or high, peak exposures (1-hour
maximum) (ISA, section <IP_ADDRESS>).
    As noted in the policy assessment chapter of the REA, given the
above conclusions, the experimental evidence provides support for an
averaging time of shorter duration than 24 hours (e.g., 1-h) while the
epidemiologic evidence provides support for both 1-hour and 24-hour
averaging times. At a minimum, this suggests that a primary concern
with regard to averaging time is the level of protection provided
against 1-hour daily maximum NO2 concentrations. However, it
is also important to consider the ability of a 1-hour (daily maximum)
averaging time to protect against 24-hour average NO2
concentrations. To this end, Table 10-2 in the REA presented
correlations between 1-hour daily maximum NO2 concentrations
and 24-hour average NO2 concentrations (98th and 99th
percentile) across 14 locations (see Thompson, 2008 for more detail).
Typical ratios ranged from 1.5 to 2.0, though one ratio (Las Vegas) was
3.1. These ratios were far less variable than those discussed above for
annual average concentrations, suggesting that a standard based on 1-
hour daily maximum NO2 concentrations could also be
effective at protecting against 24-hour NO2 concentrations.
The REA concluded that the scientific evidence, combined with the air
quality correlations described above, support the appropriateness of a
standard based on 1-hour daily maximum NO2 concentrations to
protect against health effects associated with short-term exposures.
b. Long-Term Averaging Time
    While the REA concluded that the combination of the scientific
evidence from the ISA and air quality analyses most directly support an
averaging time that focuses protection on short-term exposures to
NO2, some evidence does support the need to also consider
health effects potentially associated with long-term exposures. As
noted above, the ISA judged the evidence relating long-term (weeks to
years) NO2 exposures to respiratory morbidity to be
``suggestive but not sufficient to infer a causal relationship.'' The
available database supporting the relationship between respiratory
illness in children and long-term exposures to NO2 has
increased since the 1996 review of the NO2 NAAQS. Results
from several studies, including the California-based Children's Health
Study, have reported deficits in lung function growth (Gauderman et
al., 2004) in association with long-term exposure to NO2. In
addition, some studies have reported associations between asthma
incidence and long-term NO2. The plausibility of these
associations is supported by some animal toxicological studies.
Specifically, morphological effects following chronic NO2
exposures have been identified in animal studies that

link to these increases in collagen synthesis and may provide
plausibility for the deficits in lung function growth described in
epidemiologic studies of long-term exposure to NO2 (ISA,
section 3.4.5).
    Therefore, though the evidence provides strong support for the need
to protect against health effects associated with short-term
NO2 exposures, it may also be appropriate to consider the
extent to which the NO2 standard could protect against
potential effects associated with long-term exposures. To address this
issue, the REA estimated annual average NO2 concentrations
assuming different 1-hour standards were just met. For the locations
evaluated, a 1-hour area-wide standard with a level at or below 100 ppb
was estimated to be associated with annual average NO2
concentrations below the level of the current annual standard (53 ppb)
(REA, section 10.4.2). Therefore, it is possible that a 1-hour standard
could also provide protection against potential effect associated with
long-term exposures, depending on the level of the standard.
c. CASAC Views
    CASAC agreed with the conclusions of the policy assessment chapter
of the REA that a primary consideration of the NO2 NAAQS
should be the protection provided against health effects associated
with short-term exposures. In their letter to the EPA Administrator,
CASAC stated that they concur ``with having a short-term NAAQS primary
standard for oxides of nitrogen and using the one-hour maximum
NO2 value.'' In addition, the letter noted that ``CASAC also
recommends retaining the current standard based on the annual
average.'' CASAC based this recommendation on the ``limited evidence
related to potential long-term effects of NO2 exposure and
the lack of strong evidence of no effect.'' In addition, CASAC
concluded that ``the findings of the REA do not provide assurance that
a short-term standard based on the one-hour maximum will necessarily
protect the population from long-term exposures at levels potentially
leading to adverse health effects'' (Samet, 2008b).
d. Administrator's Conclusions on Averaging Time
    In considering the most appropriate averaging time(s) for the
NO2 primary NAAQS, the Administrator notes the conclusions
and judgments made in the ISA about available scientific evidence,
conclusions from the REA, and CASAC recommendations discussed above.
Based on these considerations, the Administrator proposes to set a new
standard based on 1-hour daily maximum NO2 concentrations.
In addition, the Administrator notes that CASAC recommended retaining
the current annual standard to account for the fact that some evidence
suggests that long-term NO2 exposures could cause adverse
effects on respiratory health. Taking into account these
considerations, in addition to proposing a new 1-hour NO2
primary NAAQS to provide increased protection against effects
associated with short-term exposures, the Administrator also proposes
to retain an annual standard.
3. Form
    When evaluating alternative forms in conjunction with specific
levels, the REA considered the adequacy of the public health protection
provided by the combination of level and form to be the foremost
consideration. In addition, the REA recognized that it is desirable to
have a form that is reasonably stable and insulated from the impacts of
extreme meteorological events. As noted in the review of the
O3 NAAQS (EPA, 2007e), forms that call for averaging of
concentrations over three years better reflect pollutant-associated
health risks than forms based on expected exceedances. This is because
such ``concentration-based'' forms give proportionally greater weight
to periods of time when pollutant concentrations are well above the
level of the standard than to times when the concentrations are just
above the standard, while an expected exceedance form would give the
same weight to periods of time with concentrations that just exceed the
standard as to times when concentrations greatly exceed the standard.
Averaging concentrations over three years also provides greater
regulatory stability than a form based on allowing only a single
expected exceedance in a year. Therefore, consistent with recent
reviews of the O3 and PM NAAQS, the REA focused on
concentration-based forms averaged over 3 years.
    In considering specific concentration-based forms, the REA focused
on 98th and 99th percentile concentrations averaged over 3 years. With
regard to these alternative forms, the REA noted that a 99th percentile
form for a 1-hour daily maximum standard would correspond approximately
to the 4th highest daily maximum concentration in a year (which is the
form of the current O3 NAAQS) while a 98th percentile form
(which is the form of the current short-term PM2.5 NAAQS)
would correspond approximately to the 7th or 8th highest daily maximum
concentration in a year (Table 10-4 in the REA; see Thompson, 2008 for
methods). The REA concluded that either of these forms could provide an
appropriate balance between limiting peak NO2 concentrations
and providing sufficient regulatory stability. This is consistent with
judgments made in the 2006 review of the PM NAAQS (EPA, 2005).
    When considering the extent to which exposure and risk analyses
inform judgments on the form of the standard, the REA noted that a 99th
percentile form could be appreciably more protective than a 98th
percentile form (for the same standard level) in some locations, as
shown by the results of air quality analyses. For example, a 99th
percentile standard of 200 ppb was estimated to decrease the number of
benchmark exceedances, relative to a 98th percentile form, by
approximately 50-70% in Boston, Philadelphia, and Washington, DC (Table
10-5 in the REA). However, a 99th percentile form was estimated to
decrease the number of benchmark exceedances by only approximately 10%
in St. Louis, Detroit, and Las Vegas (Table 10-5 in the REA). For most
locations analyzed, the difference was estimated to be between
approximately 10 and 50% (Table 10-5 in the REA). With regard to the
Atlanta exposure assessment, a 99th percentile form was estimated to
decrease the number of days with 6 or more benchmark exceedances (for
300 ppb), relative to a 98th percentile form, by 5-35% depending on the
standard level selected (REA Appendix B, table B-48). With regard to
the Atlanta risk assessment, a 99th percentile form was estimated to be
associated with approximately 6% to 8% fewer NO2-related
emergency department visits than a 98th percentile form, across the
levels of the potential 1-hour standards examined.
    When considering these results as they relate to the form of the
standard, the REA noted that a decision on form must be made in
conjunction with selection of a particular standard level. The primary
emphasis in such a decision will be on the degree of public health
protection provided by the combination of form and level.
    CASAC agreed with the importance of considering the public health
protection provided by the combination of form and level. In its letter
to the EPA Administrator with regard to the final REA, the CASAC panel
stated that it ``advises that EPA choose a health protective percentile
appropriate for the level chosen for the one-hour standard.'' CASAC
went on to recommend that a 98th percentile form would be

appropriate for a standard level at the lower boundary of the range
evaluated (50 ppb, see below) but that a higher percentile should be
considered for higher levels (Samet, 2008b).
    When considering alternative forms, the Administrator notes the
views expressed in the REA and the recommendations from CASAC, as
described above. In particular, she notes that a 99th percentile (or
4th highest) form could be appreciably more protective in some
locations than a 98th (or 7th or 8th highest) form. Given these
considerations, and in light of the specific range proposed for level
below, the Administrator proposes to adopt either a 99th percentile or
a 4th highest form, averaged over 3 years. In addition, the
Administrator notes that a 98th percentile form could be appropriate,
particularly for standard levels at the low end of the range considered
in the REA. Therefore, she also solicits comment on both 98th
percentile and 7th or 8th highest forms.
4. Level
    In assessing the level of the standard to propose, the
Administrator has considered the broad range of scientific evidence
assessed in the ISA, including the epidemiologic studies and controlled
human exposure studies, as well as the results of exposure/risk
analyses presented in the REA. In light of this body of evidence and
analyses, she has determined that it is necessary to provide increased
public health protection for at-risk individuals against an array of
adverse respiratory health effects related to short-term (i.e., 30
minutes to 24 hours) exposures to ambient NO2. Such health
effects have been associated with exposure to the distribution of
short-term ambient NO2 concentrations across an area. This
distribution includes both the higher short-term (i.e., peak) exposure
concentrations that can occur on or near major roadways and the lower
short-term exposure concentrations that can occur in areas not near
major roadways. In considering the most appropriate approach to
providing this protection, the Administrator is mindful of the extent
to which the available evidence and analyses can inform a decision on
standard level. Specifically, the range of proposed standard levels
discussed below (section II.F.4.e) is informed by controlled human
exposure and epidemiologic studies.
    As discussed above (section II.B.1.d), controlled human exposure
studies have reported associations between various levels of
NO2 exposures and increased airway responsiveness in
asthmatics. These studies can inform an evaluation of the risks
associated with exposure to specific NO2 concentrations,
regardless of where those exposures occur in an area. Controlled human
exposure studies most directly inform consideration of the risks
associated with peak short-term NO2 exposure concentrations,
such as those that can occur on or near major roadways. This is the
case because NO2 concentrations around major roadways could
include concentrations within the range evaluated in the studies.
Controlled human exposure studies have not been conducted at the lower
concentrations of NO2 typically expected in areas not near
major roadways.
    In addition, epidemiologic studies (section II.B.1.a and b) have
reported associations between ambient NO2 concentrations,
measured at area-wide monitors in the current network, and increased
respiratory symptoms, emergency department visits, and hospital
admissions. Area-wide monitors in the urban areas in which these
epidemiologic studies were conducted do not measure the full range of
ambient NO2 concentrations that can occur anywhere in the
area, because they are not sited in locations with more localized peak
concentrations. Thus, they do not measure the full range of ambient
NO2 concentrations that are likely responsible for the
exposures linked to the NO2-associated health effects
reported in the studies. Rather, the area-wide NO2
concentrations measured by these monitors are used as surrogates for
the entire distribution of ambient NO2 concentrations across
the area, a distribution that includes NO2 concentrations
that are both higher and lower than the area-wide concentrations
reported for the study locations. Specifically, this distribution of
concentrations includes the higher short-term peak NO2
concentrations that occur on or near major roadways and the lower
short-term concentrations that occur away from roadways. Thus, the
epidemiologic studies can inform an evaluation of the risks associated
with the full range of exposures likely to occur across an area.
    The available evidence and analyses support the importance of
roadway-associated NO2 exposures for public health.
Specifically, the exposure assessment presented in the REA estimated
that roadway-associated exposures account for the great majority of
exposures to peak NO2 concentrations (REA, Figures 8-17 and
8-18). In addition, the ISA (section 2.5.4) noted that in-vehicle
NO2 exposures could be 2-3 times higher than indicated by
ambient monitors in the current area wide-oriented network. Millions of
people in the U.S. live, work, and/or attend school near important
sources of NO2 such as major roadways (ISA, section 4.4) and
ambient NO2 concentrations in these locations are strongly
associated with distance from major roads (i.e., the closer to a major
road, the higher the NO2 concentration) (ISA, section
2.5.4). Therefore, these populations, which likely include a
disproportionate number of individuals in groups with higher prevalence
of asthma and higher hospitalization rates for asthma (e.g. ethnic or
racial minorities and individuals of low socioeconomic status ) (ISA,
section 4.4), are likely exposed to NO2 concentrations
higher than those that occur away from major roadways.
    Given the above considerations, the Administrator proposes to set a
level for the 1-hour NO2 primary NAAQS that reflects the
maximum allowable NO2 concentration anywhere in an area.
This concentration is likely to occur on or near a major roadway. As
discussed above (section II.A.2), monitoring studies suggest that
NO2 concentrations near roadways can be approximately 30 to
100% higher than concentrations in the same area but not near the road.
This NO2 concentration gradient around roadways is one
factor considered by the Administrator in determining the appropriate
standard level to propose. EPA proposes to set the level of the
standard such that, when available information regarding the
concentration gradient around roadways is considered, appropriate
public health protection would be provided by limiting the higher
short-term peak exposure concentrations expected to occur on and near
major roadways, as well as the lower short-term exposure concentrations
expected to occur away from those roadways.
    The Administrator notes that this approach to setting the standard
would provide a relatively high degree of confidence regarding the
level of protection provided by the standard against peak exposures,
such as those that can occur on or near major roadways. This is a
particularly important consideration given the available information
and the air quality and exposure analyses, discussed above in section
II.F.4.b, which indicated that roadway-associated exposures account for
the majority of exposures to peak NO2 concentrations. The
Administrator concludes that the proposed approach would directly
address the great majority of peak exposures and associated health
effects. In addition, the range of standard levels proposed below
(section II.F.4.e) would provide a reasonable degree of confidence that
the

accompanying area-wide NO2 concentrations would be
maintained well below concentrations that have occurred in locations
where epidemiologic studies have reported associations between ambient
NO2 concentrations and health endpoints such as increased
respiratory symptoms, emergency department visits, and hospital
admissions. Therefore, the Administrator proposes to set a standard
level reflecting the maximum allowable NO2 concentration
anywhere in an area that, in combination with the proposed decisions on
indicator, averaging time, and form, will protect public health with an
adequate margin of safety against the array of NO2-
associated health effects.
    The remainder of this section describes the considerations relevant
to the Administrator's proposed decisions on standard levels for a new
1-hour standard and the annual standard. Specifically, with regard to a
1-hour standard evidence-based considerations drawn from the ISA and
discussed in the policy-assessment chapter of the REA are discussed in
section II.F.4.a. Exposure- and risk-based considerations for a 1-hour
standard drawn from the analyses in the REA and discussed in the policy
assessment chapter are discussed in section II.F.4.b. A summary of the
considerations relating to a 1-hour standard from the policy assessment
chapter of the REA is presented in section II.F.4.c and CASAC views
expressed in the context of their comments on the final REA are
presented in section II.F.4.d. The Administrator's proposed approach to
setting a 1-hour standard and her conclusions regarding the level of
such a standard are presented in section II.F.4.e. An alternative
approach to setting a 1-hour standard is discussed in section II.E.4.f.
Comment is solicited on both approaches. Finally, the Administrator's
proposed conclusions on the level of the annual standard are presented
in section II.E.4.g.
a. Evidence-Based Considerations
    Evidence-based considerations take into account the full body of
scientific evidence assessed in the ISA. When considering the extent to
which this scientific evidence can inform a decision on the level of a
1-hour standard, the policy assessment chapter of the REA notes that
NO2 concentrations represent different measures of exposure
when drawn from experimental versus epidemiologic studies.
Concentrations of NO2 tested in experimental studies, such
as controlled human exposure studies, represent exposure concentrations
in the breathing zone of the individual test subjects. In cases where
controlled human exposure studies report effects, those effects are
caused directly by exposure to a specified concentration of
NO2. In contrast, concentrations of NO2 drawn
from epidemiologic studies are often based on ambient monitoring data.
In the case of key U.S. studies that have been specifically considered
within the context of assessing the appropriate level for the standard,
these monitors measure area-wide NO2 concentrations that
occur away from major roadways. NO2 concentrations recorded
at these ambient monitors are used as surrogates for the distribution
of NO2 exposures across the study area and over the time
period of the study. As noted above, these monitors do not measure the
full range of ambient NO2 concentrations that can occur in
an area and, thus, they do not measure the full range of ambient
NO2 concentrations that are likely responsible for the
NO2-associated health effects reported in the studies.
Instead they capture one part of the distribution (the area-wide
concentration) and this is used as a surrogate for the entire
distribution, which includes peak roadway-associated concentrations. As
noted in the REA, the interpretation of NO2 concentrations
from different types of studies is an important consideration for
decisions on standard level. These implications are discussed in more
detail below in section II.F.4.e.
    In considering the epidemiologic evidence, the REA noted the ISA
conclusion that epidemiologic studies provide the strongest support for
the link between short-term NO2 exposure and respiratory
morbidity. In addition, epidemiologic studies provide evidence for the
most serious NO2-associated respiratory effects, including
respiratory-related hospital admissions and emergency department
visits. As noted above, these effects have been reported to be
associated with area-wide NO2 concentrations in key U.S.
epidemiologic studies. Because area-wide NO2 concentrations
are used as surrogates for the distribution of NO2 exposures
across the study area and over the time period of the study (see
above), the health effects reported in these epidemiologic studies are
reasonably inferred to be associated with exposure to ambient
NO2 concentrations that are both higher and lower than the
area-wide concentrations reported for the study locations. As noted
above, this distribution of exposure concentrations includes both the
higher short-term peak NO2 concentrations that occur on or
near major roadways and the lower short-term concentrations that occur
away from roadways.
    When evaluating the epidemiologic literature for its potential to
inform the selection of an appropriate range of standard levels, the
REA noted the ISA conclusion that NO2 epidemiologic studies
provide ``little evidence of any effect threshold'' (ISA, section
<IP_ADDRESS>, p. 5-15). In studies that have evaluated concentration-
response relationships, those relationships appear linear within the
observed range of data (ISA, section <IP_ADDRESS>). Given this lack of an
apparent threshold below which effects do not occur, an important
consideration with regard to providing an adequate margin of safety is
the extent to which it is appropriate for the range of proposed
standard levels to extend below NO2 concentrations that have
been associated with health effects in these studies. For purposes of
using the epidemiologic evidence to identify a range of standard levels
for evaluation in the absence of an apparent threshold, the REA
considered the range of NO2 concentrations that have been
monitored in locations, and during time periods, of key U.S.
epidemiologic studies (ISA, Table 5.4-1).
    Figures 4 and 5 below (REA, Figures 5-1 and 5-2) show standardized
effect estimates from single pollutant models and the 99th and 98th
percentiles of the 1-hour daily maximum NO2 concentrations
recorded at area-wide monitors in the locations, and during the time
periods, of key U.S. studies. The peak NO2 concentrations to
which individuals were exposed on and/or near major roadways in these
locations during the study periods would be expected to be
substantially higher than the concentrations recorded at these area-
wide monitors. The lowest area-wide 1-hour daily maximum
concentrations, 53 (99th percentile) and 50 (98th percentile) ppb, were
monitored in the location of the study by Delfino et al. (2002). This
single study reported mixed results for respiratory symptoms with most
reported NO2 effect estimates being positive, and with some
but not all positive effect estimates being statistically significant.
A cluster of 5 studies (Ito et al., 2007; Jaffe et al., 2003; NYDOH,
2006; Peel et al., 2005; Tolbert et al., 2007) were conducted in
locations with area-wide 1-hour daily maximum NO2
concentrations ranging from 93 to 112 ppb (99th percentile) and from 85
to 94 ppb (98th percentile). In these studies, single pollutant models
yielded generally positive and often statistically significant
NO2 effect estimates for respiratory-related emergency

department visits and hospital admissions in a variety of locations
across the U.S. Of these 5 studies, 4 studies (Ito, 2007; NYDOH, 2006;
Peel et al., 2005; Tolbert et al., 2007) also reported NO2
effect estimates using multi-pollutant models, as discussed above
(section II.B.1.a). In the study by Ito (2007), risk estimates were
robust and remained statistically significant in multi-pollutant models
that included PM2.5, O3, CO, and
SO2.\11\ In the study by Peel et al. (2005), the authors
reported that ``The estimates for NO2 were generally not
attenuated in multipollutant models, while the estimates for the other
pollutants [PM10, ozone, NO2, and CO] suggested
weaker or no associations in the multipollutant models.'' The
quantitative results for these multi-pollutant models were not
presented in this study. In the remaining 2 studies (NYDOH, 2006;
Tolbert et al., 2007), NO2 effect estimates that were
positive in single pollutant models remained positive but not
statistically significant in multi-pollutant models.\12\ Two additional
studies which evaluated only single pollutant models (Linn et al.,
2000; Ostro et al., 2001) reported positive and statistically
significant NO2 effect estimates in locations with
appreciably higher area-wide 1-hour daily maximum NO2
concentrations (i.e., around 200 ppb).
---------------------------------------------------------------------------

    \11\ In this study, multi-pollutant models were evaluated only
for the warm months. Single pollutant effect estimates for
NO2 were statistically significant for the warm months,
but not for the cold months.
    \12\ As discussed above in section II.B.1, the conclusion from
the ISA that NO2 effect estimates generally remain robust
in multi-pollutant models is based on evaluation of the broader body
of epidemiologic evidence which includes, but is not limited to,
these U.S. studies (e.g., see Figures 1-3 above and ISA, Figures
3.1-7, 3.1-10, and 3.1-11). Effect estimates from these U.S. studies
were not included in the multi-pollutant figures in the ISA because
the studies generally reported multi-pollutant model results only
qualitatively. They generally did not report the quantitative
information that would have been necessary to include the results in
the ISA figures.
---------------------------------------------------------------------------

---------------------------------------------------------------------------

    \13\ Effect estimates presented in Figures 4 and 5 are from
single pollutant models.
---------------------------------------------------------------------------

---------------------------------------------------------------------------

    \14\ Authors of relevant U.S. and Canadian studies were
contacted and, for each study, air quality statistics were requested
from the monitor that recorded the highest NO2
concentrations. In cases where authors provided 1-hour daily maximum
air quality statistics, this information is presented in Figures 4
and 5 (studies by Tolbert, Peel, NYDOH, Delfino). In four cases
(studies by Ito, Jaffe, Linn, Ostro), we were not able to identify
1-hour NO2 statistics from the information provided by
the authors. In these cases, we evaluated monitored NO2
concentrations reported to EPA's Air Quality System (AQS) for the
location and time of the study. Figures 4 and 5 present the highest
98th/99th percentile 1-hour daily maximum NO2
concentrations that correspond to each study location and time
period. Prior to identifying potential alternative standards, we did
not receive air quality information from any of the Canadian authors
contacted and we were unable to reconstruct the air quality data
sets for the Canadian studies. Therefore, for purposes of
identifying levels of potential alternative standards, our analysis
was based on these key U.S. studies. Note that the NO2
concentrations reported in the study by Jaffe are labeled as 24-hour
concentrations, but the author indicated in a personal communication
(Jaffe, 2008) that they actually represent 1-hour daily maximum
concentrations.
[GRAPHIC] [TIFF OMITTED] TP15JY09.003

[GRAPHIC] [TIFF OMITTED] TP15JY09.004

    When evaluating the controlled human exposure literature for its
potential to inform the selection of a range of appropriate standard
levels for evaluation, the REA noted that available studies have
addressed the consequences of short-term (e.g., 30-minutes to several
hours) NO2 exposures for a number of health endpoints
including increased airway responsiveness, reduced host defense and
immunity, inflammation, and decreased lung function (ISA, section 3.1).
In identifying health endpoints on which to focus for purposes of
informing decisions about potential alternative standard levels, the
REA concluded that it was appropriate to focus on those endpoints that
occur at or near ambient levels of NO2 and endpoints that
are of potential public health significance. As described above in more
detail (section II.C.1), the only endpoint to meet both of these
criteria is increased airway responsiveness in asthmatics. The ISA
concluded that NO2 exposures between 200 and 300 ppb for 30
minutes and 100 ppb for 60-minutes can result in small but significant
increases in nonspecific airway responsiveness (ISA, section <IP_ADDRESS>)
and that ``transient increases in airway responsiveness following
NO2 exposure have the potential to increase symptoms and
worsen asthma control'' (ISA, sections 3.1.3 and 5.4). This effect
could have important public health implications due to the large size
of the asthmatic population in the United States (ISA, Table 4.4-1). In
addition, NO2 effects on airway responsiveness in asthmatics
are part of the body of experimental evidence that provides
plausibility and coherence for the observed NO2-related
increase in hospital admissions and emergency department visits in
epidemiologic studies (ISA, section <IP_ADDRESS>). For all of these reasons,
the REA considered the extent to which results reported for the
NO2-associated increase in airway responsiveness in
asthmatics could inform decisions on alternative standard levels.
    With regard to controlled human exposure studies of airway
responsiveness, the ISA and the REA discussed an update to a meta-
analysis that was originally published by Folinsbee in 1992 and
considered in the 1993 NOX AQCD. The original analysis by
Folinsbee (1992) included individual level data from 19 studies
involving asthmatic volunteers. Folinsbee reported that 65% of resting
asthmatics (57 of 88) exposed to NO2 concentrations between
100 and 140 ppb experienced an increase in airway responsiveness. In
addition, 76% (25 of 33) of resting asthmatics experienced increased
airway responsiveness following exposure to NO2
concentrations between 200 and 300 ppb. These results in resting
asthmatics were statistically significant. Smaller, and statistically
non-significant, percentages of exercising asthmatics experienced
increased airway responsiveness following exposure to NO2
concentrations (ISA, section <IP_ADDRESS>). The reason for this difference
is not known as the factors that predispose some asthmatics to
NO2 responsiveness are not understood (ISA, section
<IP_ADDRESS>).\15\
---------------------------------------------------------------------------

    \15\ When the asthmatic results were grouped together for all
exposures, both at rest and during exercise, the percent of
asthmatics with increased airway responsiveness decreased at the
higher exposure concentrations. This result could be attributed to
the lack of an effect in the asthmatics exposed during exercise.

---------------------------------------------------------------------------

    The update of this meta-analysis presented in the ISA (Table 3.1-3)
included one additional study of non-specific responsiveness and
removed an allergen responsiveness study that was included in the
original \16\ (see ISA, section <IP_ADDRESS> for more discussion). While the
updated analysis does not include new results at lower concentrations
(100-250 ppb), we interpreted the results with a greater focus on 100
ppb due, in part, to the greater body of evidence available, including
new epidemiologic evidence. Therefore, the updated analysis also
reported results specifically for an NO2 exposure
concentration of 100 ppb. As with the original analysis by Folinsbee
(1992), the updated meta-analysis reported that a larger percentage of
resting asthmatics, as opposed to exercising asthmatics, experienced an
NO2-related increase in airway responsiveness. The updated
analysis reported that, when exposed at rest, 66% (33 of 50) of
asthmatics experienced an increase in airway responsiveness following
exposure to 100 ppb NO2, 67% (47 of 70) of asthmatics
experienced an increase in airway responsiveness following exposure to
NO2 concentrations from 100 to 150 ppb, 75% (38 of 51) of
asthmatics experienced an increase in airway responsiveness following
exposure to NO2 concentrations from 200 to 300 ppb, and 73%
(24 of 33) of asthmatics experienced an increase in airway
responsiveness following exposure to NO2 concentrations
above 300 ppb. The fraction of resting asthmatics experiencing an
increase in airway responsiveness was statistically significant at each
of these NO2 concentrations.
---------------------------------------------------------------------------

    \16\ The updated meta-analysis added a study that evaluated non-
specific airway responsiveness following exposure to 260 ppb
NO2 and removed a study that evaluated allergen-induced
airway responsiveness following exposure to 100 ppb NO2.
---------------------------------------------------------------------------

    Based on this evidence, we have identified exposure to
NO2 at a level of 100 ppb to be the lowest level at which
effects have been observed in controlled human exposure studies, noting
that it is also the lowest level tested in the studies used in the
meta-analysis. There is no evidence from this meta-analysis, however,
of a threshold below which NO2-related effects do not occur.
b. Exposure- and Risk-Based Considerations
    Chapters 7-9 of the REA estimated exposures and health risks
associated with recent air quality and with air quality, as measured at
monitors in the current area-wide network, which had been adjusted to
simulate just meeting the current and potential alternative standards.
The specific standard levels evaluated, for an area-wide standard based
on the 3-year average of the 98th and 99th percentile 1-hour daily
maximum NO2 concentrations, were 50, 100, 150, and 200 ppb.
    The results of the air quality, exposure, and risk analyses are
presented below in Table 1. With regard to the air quality results,
Table 1 presents the number of days per year that NO2
concentrations on/near roads were estimated to equal or exceed the
lowest and the highest health benchmarks evaluated (100 and 300 ppb).
Compared to just meeting the current annual standard, exceedances
estimated to be associated with just meeting 99th percentile 1-hour
daily maximum area-wide standard levels of either 50 or 100 ppb were
substantially lower. In contrast, exceedances estimated to be
associated with 1-hour area-wide standards of 150 or 200 ppb were
either similar to, or slightly higher than, those estimated for just
meeting the current standard. Table 1 also presents the results of the
Atlanta exposure and risk assessments. As is the case for the air
quality analyses, NO2 exposures and risks estimated to be
associated with just meeting 1-hour area-wide standard levels of either
50 or 100 ppb were substantially lower than those associated with just
meeting the current annual standard. Exposures and risks estimated to
be associated with 1-hour area-wide standard levels of 150 or 200 ppb
were somewhat lower than, or similar to, those estimated for just
meeting the current annual standard.

                                   Table 1--Summary of Results of the Exposure and Risk Analyses Presented in the REA
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                      Mean estimated number of days        Mean percent of Atlanta            Mean percent of total
                                                        per year with 1-hour NO2           asthmatics estimated to      respiratory ED visits in Atlanta
                                                      concentrations on/near roads      experience 6 or more days per    estimated to be related to NO2
                                                        greater than or equal to        year with 1-hour NO2 exposure       (based on the year 2007)
                                                      benchmark levels (in location    concentrations greater than or  ---------------------------------
                    Air quality                      with largest number of estimate  equal to benchmark levels (based
                                                              exceedances)                    on the year 2002)
                                                   --------------------------------------------------------------------      Single           Multi-
                                                                                100 ppb          300 ppb         pollutant        pollutant
                                                        100 ppb          300 ppb         benchmark        benchmark         estimate        estimates*
                                                       benchmark        benchmark        (percent)        (percent)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Current annual standard...........................              338               38              100               97              8.1          1.7-6.9
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                  Potential Alternative Standards Evaluated in the REA
--------------------------------------------------------------------------------------------------------------------------------------------------------
99th 1-hour: 200 ppb..............................              350               56              100               89              7.1          1.5-6.1
99th 1-hour: 150 ppb..............................              337               13              100               57              5.4          1.1-4.6
99th 1-hour: 100 ppb..............................              229                4              100               11              3.6          0.7-3.1
99th 1-hour: 50 ppb...............................               13                1               57                0              1.8          0.4-1.6
--------------------------------------------------------------------------------------------------------------------------------------------------------
* Ranges represent the range of risk estimates that result from including different co-pollutants in the model.

c. Summary of Considerations From the REA
    The policy assessment chapter of the REA considered the scientific
evidence and the exposure/risk information as they relate to
considering alternative 1-hour NO2 standards that could be
judged to be requisite to protect public health with an adequate margin
of safety. The conclusions of the REA were based, in large part, on
scientific evidence (i.e., key U.S. epidemiologic studies) and
exposure/risk analyses that were based on the use of the available
NO2 air quality data from area-wide monitors, as discussed
above in sections II.B and II.C. The implications of these conclusions
for a standard level that reflects the maximum allowable concentration
anywhere in an area (a

concentration likely to occur near major roads) are discussed below in
section II.F.4.e.
    When considering an appropriate upper end of the range of 1-hour
daily maximum standard levels supported by the scientific evidence, the
REA noted the following:
     Positive and statistically significant associations were
observed in several key U.S. epidemiologic studies in locations with
area-wide 98th and 99th percentile 1-hour daily maximum NO2
concentrations ranging from 85 to 112 ppb \17\ (Peel et al., 2005;
NYDOH, 2006; Ito et al., 2007; Tolbert et al., 2007) (see Figure 4
above).
---------------------------------------------------------------------------

    \17\ As noted above, the health effects reported in
epidemiologic studies are reasonably inferred to be associated with
exposure to ambient NO2 concentrations that are both
higher than and lower than the area-wide concentrations reported for
the study location.
---------------------------------------------------------------------------

     The meta-analysis of airway responsiveness presented in
the ISA reported increased airway responsiveness in most asthmatics
(66% or 33 out of 50) following short-term exposures to 100 ppb
NO2, which was the lowest concentration for which such data
were available. Although some uncertainties associated with this
evidence, as described above, provide support for considering standard
levels below 100 ppb (i.e., studies have typically involved volunteers
with mild asthma and data are lacking from more severely affected
asthmatics, who may be more susceptible (ISA, p. 3-16)), other
uncertainties (i.e., the undetermined magnitude and clinical
significance of the NO2-associated increase in airway
responsiveness) provide support for considering higher standard levels.
    Given these considerations, the REA concluded that the scientific
evidence provides support for a standard level up to 100 ppb. The REA
also noted that, to the extent more emphasis is placed on the
uncertainties associated with ascribing effects to NO2 in
the cluster of epidemiologic studies and on the magnitude and clinical
significance of the NO2-associated increase in airway
responsiveness following exposure to NO2, standard levels
higher than 100 ppb could be considered. However, the strongest support
was concluded to be for standard levels at or below 100 ppb.
    When considering an appropriate lower end of a range of levels
supported by the scientific evidence, the REA noted the following:
     The epidemiologic study by Delfino et al., (2002)
evaluated associations between short-term ambient NO2
concentrations and respiratory symptoms in a location (Alpine, CA)
where area-wide NO2 concentrations were well below levels in
other key U.S. epidemiologic studies. As noted above, this single study
provides mixed evidence for NO2-associated effects in a
location with 99th and 98th percentile 1-hour daily maximum area-wide
NO2 concentrations of 53 and 50 ppb, respectively.
     The meta-analysis of controlled human exposure studies
reported increased airway responsiveness in asthmatics at the lowest
NO2 concentration for which data were available (i.e., 100
ppb). In identifying the specific lower level for the standard that
could be reasonably supported by this controlled human exposure
evidence, there are several reasons why it is appropriate to consider
levels below 100 ppb. First, the meta-analysis did not provide
information on the potential for an NO2-induced increase in
airway responsiveness at concentrations below 100 ppb, leaving open the
possibility for effects following exposures to lower concentrations.
Second, the studies included in the meta-analysis did not evaluate
severe asthmatics and most of the subjects included in these studies
were mild asthmatics. Asthmatics characterized as having more severe
asthma may be more susceptible than mild asthmatics to the effects of
NO2 exposure (ISA, section <IP_ADDRESS>).
    Thus, the REA concluded that it was appropriate to base the lower
end of the range of standard levels on NO2 concentrations in
the location of the epidemiologic study by Delfino and on providing
increased protection relative to the lowest level at which increased
airway responsiveness in asthmatics was reported in controlled human
exposure studies. Given the mixed results reported in the Delfino
study, the REA concluded that it was appropriate to consider standard
levels approximately equal to, rather than below, those measured in the
location of the study. Given these considerations, the REA concluded
that the lower end of the range of levels that is reasonably supported
by the scientific evidence is 50 ppb for a 1-hour standard that would
protect public health with an adequate margin of safety.
    In addition to these evidence-based considerations, the REA
compared the health risks estimated to be associated with just meeting
the current standard to those estimated to be associated with different
1-hour standards. As noted above (section II.C), the REA characterized
NO2-associated health risks by estimating the potential
occurrence of ambient NO2 concentrations greater than or
equal to concentrations reported to increase airway responsiveness,
exposures of asthmatics to NO2 concentrations reported to
increase airway responsiveness, and the incidence of NO2-
associated emergency department visits. Given the REA conclusion that
the available evidence and information clearly call into question the
adequacy of the current standard, the adequacy of alternative 1-hour
standards would also be called into question if those standards were
estimated to be associated with similar or higher risks. In considering
the three analyses that characterized NO2-associated health
risks, the REA noted that just meeting 1-hour area-wide standard levels
of 150 and 200 ppb was estimated to be associated with risks ranging
from somewhat lower to slightly higher than those estimated for the
just meeting the current standard. In contrast, just meeting 1-hour
standard levels of 50 or 100 ppb, in conjunction with the current area-
wide monitoring network, was estimated to result in appreciably lower
health risks than the current standard. Given this, the REA concluded
that the exposure/risk information reinforces the scientific evidence
in supporting a standard level from 50 to 100 ppb.
d. CASAC Views
    CASAC expressed their views in a letter to the EPA Administrator
(Samet, 2008b) within the context of their review of the final REA, a
review which focused primarily on the policy assessment chapter.\18\ In
drawing conclusions regarding the level of a short-term standard, CASAC
considered the scientific evidence evaluated in the ISA, the exposure
and risk results presented in the REA, and the evidence- and risk-based
considerations presented in the policy assessment chapter of the REA.
CASAC concurred with the conclusion from the policy assessment chapter
that the strongest support is for standard levels between 50 and 100
ppb. Their letter noted that, ``CASAC firmly recommends that the upper
end of the range not exceed 100 ppb.'' In considering the impact of
margin of safety on standard level, CASAC noted that ``the intent of
the Clean Air Act is to protect public health with an adequate margin
of safety and consequently uncertainty should be considered as a reason
to move towards the lower end of the range of levels and not to the
upper.'' In addition, with regard to the NO2 concentration
gradient

around roadways, CASAC noted that ``the highest exposures likely occur
when individuals are near roadways.'' As a result they recommended that
the Agency consider the implications of this exposure issue when
interpreting the evidence and when considering the siting of regulatory
monitors.
---------------------------------------------------------------------------

    \18\ Earlier CASAC letters focused on their review of the air
quality, exposure, and risk analyses as presented in other chapters
of the draft REA.
---------------------------------------------------------------------------

    CASAC comments were offered within the context of their review of
the final REA. As noted above, the conclusions from the policy
assessment chapter of the final REA were based, in large part, on
scientific evidence and exposure/risk information based on
NO2 air quality data from the current area-wide
NO2 monitoring network. Therefore, it is not clear the
degree to which CASAC recommendations might differ for a standard level
that reflects the maximum allowable NO2 concentration
anywhere in an area, including near major roads. As noted in section
I.C above, we are specifically soliciting CASAC comment on the use of
this approach and on the proposed range of levels for a standard set
using this approach.
    In drawing conclusions regarding the level of an annual standard,
CASAC noted the scientific evidence assessed in the ISA. Specifically,
CASAC concluded that while there is evidence supporting the link
between long-term NO2 exposure and adverse health effects,
this evidence does not provide a strong quantitative basis for changing
the level of the current annual standard. Therefore, with regard to the
annual standard, CASAC recommended ``retaining the current level, as
evidence has not been cited that would lead to either an increase or
decrease'' (Samet, 2008b).
e. Administrator's Conclusions on Level for a 1-Hour Standard
    In considering the appropriate level for an NO2 standard
based on the 3-year average of the 99th percentile (or 4th highest) 1-
hour daily maximum NO2 concentration, the Administrator has
considered the broad body of scientific evidence and exposure/risk
information. She draws from that evidence and information the need to
protect at-risk individuals against the distribution of short-term
ambient NO2 exposure concentrations across an area and the
array of health effects that have been linked to such NO2
exposures.
    Specifically, the Administrator has considered the extent to which
a variety of levels, which would reflect the maximum allowable 1-hour
NO2 concentration anywhere in an area, would be expected to
protect at-risk individuals against increased airway responsiveness,
respiratory symptoms, and respiratory-related emergency department
visits and hospital admissions. The Administrator notes that these
health endpoints are logically linked together in that the evidence for
increased airway responsiveness in asthmatics is part of the body of
experimental evidence that the ISA recognized as supporting the
plausibility of associations between ambient NO2 and the
respiratory morbidity endpoints (i.e., respiratory symptoms, emergency
department visits, and hospital admissions) reported in epidemiologic
studies.
    As noted above, NO2 exposure patterns associated with
respiratory morbidity in epidemiologic studies are reasonably expected
to include short-term peak exposures on and/or near major roadways of a
magnitude that has been reported to increase airway responsiveness in
asthmatics. Therefore, to inform the identification of an appropriate
range of standard levels to propose, the Administrator has considered
the scientific evidence, the exposure/risk results, and information on
the NO2 concentration gradient around roadways.
    In making judgments regarding the weight to place on the scientific
evidence and exposure/risk information, the Administrator has
considered the results of epidemiologic studies, controlled human
exposure studies, and exposure/risk analyses as well as the
uncertainties associated with this evidence and these analyses.
Specifically, she notes the following:
     The ISA concluded that epidemiologic studies provide the
strongest support for the relationship between short-term exposure to
NO2 and respiratory morbidity. Despite the possibility that
associations between health effects and NO2 in epidemiologic
studies may be confounded by the presence of co-occurring pollutants,
particularly other traffic-related pollutants, the ISA concluded that
NO2 effect estimates remain robust in multi-pollutant models
and that the evidence supports a direct effect of NO2
exposures on respiratory morbidity, independent of associations with
other traffic-related pollutants. Given this conclusion, along with
conclusions from the ISA regarding the consistency and the coherence of
results across the relatively large number of NO2
epidemiologic studies (both indoor and outdoor) and the supporting
evidence from experimental studies, the Administrator has judged it
appropriate to place substantial weight on epidemiologic studies in
identifying an appropriate range of levels to propose.
     Controlled human exposure studies report that short-term
exposures to NO2 can increase airway responsiveness in
asthmatics. With regard to this evidence, the Administrator also has
considered the uncertainties associated with the magnitude and the
clinical relevance of the NO2-associated increase in airway
responsiveness, noting that this effect may or may not be clinically
significant for any given asthmatic. However, given the potential
public health importance of this effect, due to the large size of the
asthmatic population in the U.S. and the possibility that the
NO2-associated increase in airway responsiveness could
worsen asthma symptoms and decrease control of asthma, the
Administrator judges that it is also appropriate to place weight on
this evidence when identifying an appropriate range of levels to
propose.
     The results of the risk and exposure analyses presented in
the REA provide information on the potential public health implications
of setting the standard at different levels. The Administrator
acknowledges the uncertainties associated with these analyses which, as
discussed in the REA, could result in either over- or underestimates of
NO2-associated health risks. However, she also notes that
those uncertainties should be similar across different air quality
simulations within the air quality, exposure, and risk analyses.
Therefore, the Administrator judges that these analyses are potentially
useful for considering the relative levels of public health protection
that could be provided by specific standard levels.
    After considering the scientific evidence and the exposure/risk
information (see sections II.B, II.C, and II.F.4.a through II.F.4.c),
as well as the available information on the NO2
concentration gradient around roadways (section II.A.2), as they relate
to a standard level reflecting the maximum allowable NO2
concentration in an area, the Administrator concludes that the
strongest support is for a standard level at or somewhat below 100 ppb.
The Administrator's rationale in reaching this conclusion is provided
below.
    First, the Administrator notes that a standard level of 100 ppb or
lower under the proposed approach would be expected to limit short-term
peak NO2 exposures to concentrations that have been reported
to increase airway responsiveness in asthmatics. With regard to this,
the Administrator specifically notes the following:
     The meta-analysis of controlled human exposure data in the
ISA reported increased airway

responsiveness in asthmatics at rest following exposure at and above
100 ppb NO2, the lowest NO2 concentration for
which airway responsiveness data are available in humans.
     This meta-analysis does not provide any evidence of a
threshold below which effects do not occur. The studies included in the
meta-analysis evaluated primarily mild asthmatics while more severely
affected individuals could respond to lower concentrations. Given this,
it is possible that exposure to NO2 concentrations below 100
ppb could increase airway responsiveness in some asthmatics.
     However, the magnitude of the NO2-induced
increase in airway responsiveness, and its clinical implications,
cannot be quantified from the meta-analysis. As noted previously, the
NO2-induced increase in airway responsiveness may or may not
be clinically significant. Further, there was a lack of an effect in
asthmatics exposed during exercise.
    Given the above considerations, the Administrator concludes that
the controlled human exposure studies of airway responsiveness provide
support for limiting exposure to NO2 concentrations at or
somewhat below 100 ppb. While she acknowledges that exposure to lower
concentrations could increase airway responsiveness in some asthmatics,
the Administrator concludes that, given the uncertainties regarding the
magnitude and the clinical significance of the NO2-induced
increase in airway responsiveness, the greatest support is for limiting
exposures to 100 ppb.
    Second, the Administrator notes that a standard level at or
somewhat below 100 ppb under the proposed approach would be expected to
maintain peak area-wide NO2 concentrations considerably
below peak area-wide concentrations measured in locations where
multiple key U.S. epidemiologic studies have reported associations with
emergency department visits and hospital admissions. With regard to
this, the Administrator specifically notes that 5 key U.S. studies
provide evidence for effects in locations where 99th percentile 1-hour
daily maximum NO2 concentrations measured at area-wide
monitors ranged from 93 to 112 ppb. The Administrator notes that the
study by Delfino provides mixed evidence for effects in a location with
a 99th percentile 1-hour daily maximum NO2 concentration, as
measured by an area-wide monitor, of 53 ppb. In that study, most of the
reported NO2 effect estimates were positive, but not
statistically significant. Focusing on these studies, the Administrator
concludes that they provide support for limiting area-wide
NO2 concentrations to below 90 ppb (99th percentile) in
order to provide protection against the reported effects. She also
concludes that limiting area-wide concentrations to considerably below
90 ppb would be appropriate in order to provide an adequate margin of
safety. Given the mixed results of the Delfino study, the Administrator
concludes that it may not be necessary to maintain area-wide
NO2 concentrations at or below 50 ppb to provide protection
against the effects reported in epidemiologic studies.
    Given that NO2 concentrations near roads may be 30 to
100% higher than concentrations away from roads (see section II.A.2),
the Administrator notes that a standard level at or somewhat below 100
ppb under the proposed approach could limit area-wide NO2
concentrations to well below 90 ppb (99th percentile). With regard to
this, she specifically notes the following:
     If NO2 concentrations near roads are 30% higher
than concentrations away from roads, a standard level of 100 ppb could
limit area-wide concentrations to approximately 75 ppb.
     If NO2 concentrations near roads are 65% higher
than concentrations away from roads (the mid-range of the 30% to 100%
gradients), a standard level of 100 ppb could limit area-wide
NO2 concentrations to approximately 60 ppb.
     If NO2 concentrations near roads are 100%
higher than concentrations away from roads, a standard level of 100 ppb
could limit area-wide concentrations to approximately 50 ppb.
    Therefore, a standard level at or somewhat below 100 ppb under the
proposed approach would be expected to maintain area-wide
NO2 concentrations well below 90 ppb across locations
despite the expected variation in the NO2 concentration
gradient that can exist around roadways in different locations and over
time. Such a standard level recognizes the substantial weight that the
Administrator judges is appropriate to place on the cluster of key U.S.
epidemiologic studies that reported positive, and often statistically
significant, associations between NO2 and emergency
department visits and hospital admissions. This judgment takes into
account the determinations in the ISA, based on a much broader body of
evidence, that there is a likely causal association between exposure to
NO2 and these kinds of morbidity effects, and that there is
no evidence of a threshold below which such effects would not occur.
    As noted above, based on the Administrator's consideration of the
controlled human exposure and epidemiologic evidence, she concludes
that the strongest support is for a standard level reflecting the
maximum allowable NO2 concentration in an area at or
somewhat below 100 ppb. In addition to these evidence-based
considerations, the Administrator notes that a standard level of 100
ppb under the proposed approach would be consistent with the results of
the exposure and risk analyses presented in the REA. As described in
sections II.F.4.b and II.F.4.c above, the results of these analyses
supported limiting area-wide NO2 concentrations to between
50 and 100 ppb, which would be expected with a standard level at or
below 100 ppb under the proposed approach. Given all of these
considerations, the Administrator concludes that a standard level at or
somewhat below 100 ppb under the proposed approach would be requisite
to protect public health with an adequate margin of safety against the
array of NO2-associated health effects.
    To the extent it is determined appropriate to emphasize the
possibility that NO2-induced airway responsiveness in
asthmatics could occur following exposures below 100 ppb and/or the
clinical significance of such increase in airway responsiveness, the
Administrator notes that the evidence would support setting the
standard level below 100 ppb. The Administrator also notes that a
standard level below 100 ppb would be consistent with placing greater
emphasis on the mixed results reported in the epidemiologic study by
Delfino et al. (2002). Specifically, she notes that a standard level of
80 ppb would be expected to limit area-wide NO2
concentrations to approximately 50 ppb (80 is 65% higher than 50) and
that a standard level of 80 ppb would be expected to provide protection
against exposure concentrations below those that have been reported to
increase airway responsiveness in asthmatics.
    For the reasons stated above, the Administrator proposes to set the
level of a new 1-hour standard between 80 ppb and 100 ppb. In so doing,
the Administrator proposes to place emphasis on reported findings from
both epidemiologic studies and from controlled human exposure studies.
In order to protect against NO2-associated emergency
department visits and hospital admissions reported in multiple key U.S.
epidemiologic studies, and against reported NO2-induced
increases in airway responsiveness, the Administrator proposes to set
the standard level no higher than 100 ppb. In addition, in light of the
fact that the Administrator is considering, and soliciting comment

on, the appropriate weight to place on the potential risk of
NO2-associated effects in locations with relatively low
area-wide NO2 concentrations and on the significance of
potential NO2-induced increases in airway responsiveness in
some asthmatics following exposures to concentrations below 100 ppb,
the Administrator is proposing to set a standard level within a range
that includes 100 ppb but is no lower than 80 ppb.
    The Administrator solicits comment on the appropriateness of this
proposed range of standard levels as well as on the approach she has
used to identify the range. Specifically, the Administrator solicits
comment on the following:
     The weight she has placed on the epidemiologic evidence,
the controlled human exposure evidence, the exposure/risk information,
and the uncertainties associated with each of these.
     Her use of available information on the NO2
concentration gradient around roadways (i.e., that concentrations near
roadways can be 30 to 100% higher than concentrations in the same area
but not near the road) to inform an appropriate range of standard
levels.
     The most appropriate part of the proposed range in which
to set the standard level given the available scientific evidence,
exposure/risk information, NO2 air quality information, and
the uncertainties associated with each.
    With regard to the proposed range of standard levels, the
Administrator notes that the proposed range is consistent with the
recommendation by CASAC to set a standard level no higher than 100 ppb.
However, much of the evidence and exposure/risk information that
informed CASAC's advice was based on NO2 concentrations
measured at area-wide monitors in the current monitoring network. CASAC
did not explicitly address whether or how the standard level should
differ if it reflects the maximum allowable NO2
concentration in a location (including near major roads) rather than
the maximum allowable area-wide concentration.
    The Administrator also solicits comment on setting a standard level
above 100 ppb and up to 150 ppb. In so doing, the Administrator
recognizes that there are uncertainties with the scientific evidence,
such as that associated with the magnitude and clinical significance of
the NO2-induced increase in airway responsiveness in
asthmatics and with attributing effects reported in epidemiologic
studies specifically to NO2 given the presence of co-
occurring pollutants. The Administrator invites comment on the extent
to which it is appropriate to emphasize these uncertainties in
considering the standard level and on whether it would be appropriate
to set a standard level as high as 150 ppb.
    The Administrator notes that, in order to consider the potential
implications of a standard level as high as 150 ppb, it is important to
put such a standard in the context of potential ambient concentrations.
A standard level of 150 ppb under the proposed approach could be
associated with 1-hour area-wide NO2 concentrations of
approximately 90 ppb (150 is approximately 65% higher than 90), and
potentially with concentrations ranging from 75 to 115 ppb (150 is
approximately 100% higher than 75 and 30% higher than 115) depending on
location.
    The Administrator notes that a standard level as high as 150 ppb
would place more emphasis on uncertainties associated with the
scientific evidence. Specifically, a standard level of 150 ppb would
emphasize the uncertainty associated with the magnitude and the
clinical significance of the NO2-induced increase in airway
responsiveness in asthmatics and would be based on an assumption that
NO2-associated health effects reported in epidemiologic
studies are due in large part to exposure to co-occurring pollutants,
rather than exposure to NO2. As noted above, the
Administrator seeks comment on the extent to which it would be
appropriate to emphasize these uncertainties in considering the
standard level and the extent to which the scientific evidence would
support levels up to 150 ppb.
    In addition, the Administrator notes that a standard level lower
than 80 ppb could be appropriate to the extent that near-road
concentrations are determined to be closer to 30% higher than area-wide
concentrations or to the extent that additional emphasis is placed on
the possibility that exposure to NO2 concentrations below
100 ppb could increase airway responsiveness in some asthmatics.
Accordingly, the Administrator also solicits comment on standard levels
as low as 65 ppb (30% higher than an area-wide concentration of 50
ppb).
f. Alternative Approach to Setting the 1-Hour Standard Level
    As discussed above, the Administrator is proposing a standard level
reflecting the maximum allowable NO2 concentration anywhere
in an area. However, for the reasons discussed below, EPA also solicits
comment on an alternative approach to setting a 1-hour NO2
standard. Under this alternative approach, the standard level would
reflect the maximum allowable NO2 concentration measured at
an area-wide monitoring site. Such a site would not be located in close
proximity to major roads and, for a given area, would not be the
location of the maximum NO2 concentration anywhere in that
area. In conjunction with soliciting comment on this alternative
approach, EPA solicits comment on setting the level of such a standard
within the range of 50 to 75 ppb. In addition, as with the proposed
standard, EPA solicits comment on NO2 as the indicator, a 1-
hour (daily maximum) averaging time, and the 3-year average of the 99th
percentile (or 4th highest) or 98th percentile (or the 7th or 8th
highest) as the form.
    With regard to the range of levels from 50 to 75 ppb, which would
reflect maximum allowable area-wide NO2 concentrations under
this approach, the Administrator notes the following. First, a standard
level within in this range would be expected to maintain area-wide
NO2 concentrations below peak 1-hour area-wide
concentrations measured in locations where key U.S. epidemiologic
studies have reported associations with respiratory-related emergency
department visits and hospital admissions. Second, she notes that
standard levels from the lower end of this range would be expected to
limit roadway-associated exposures to NO2 concentrations
that have been reported in controlled human exposure studies to
increase airway responsiveness in asthmatics. A standard level of 50
ppb under this approach could limit near-road concentrations to between
65 and 100 ppb, given that near-road NO2 concentrations can
range from 30% to 100% higher than area-wide concentrations. Assuming
the mid-point of the range of gradients (i.e., that near-road
concentrations are 65% higher than area-wide concentrations), a
standard level of 50 ppb under this approach could limit near-road
concentrations to approximately 80 ppb and a standard level of 60 ppb
could limit near-road concentrations to approximately 100 ppb. Third,
to the extent that relatively more emphasis is placed on the
uncertainties regarding the magnitude and clinical significance of the
NO2-induced increase in airway responsiveness, the
Administrator notes that a standard level from the upper end of the
range could be determined to be appropriate. Finally, this approach
would provide more confidence than the proposed approach regarding the
degree to which a specific standard level would limit area-wide
NO2 concentrations but less confidence regarding the degree
to which a specific

standard level would limit the peak NO2 concentrations
likely to occur near major roadways.
    The Administrator recognizes that her proposed approach results
from a comprehensive evaluation of alternative approaches to
determining the level of the NO2 primary NAAQS, but that
these approaches have not previously been presented to CASAC, or other
stakeholders, for their evaluation and public discussion. More
specifically, the Administrator notes that much of the information
included in the policy assessment chapter of the REA, which formed the
foundation for CASAC's recommendations regarding standard level, was
based on evaluation of data drawn from the current area wide-oriented
monitoring network. Further, the Administrator notes that CASAC did not
explicitly discuss in their recommendations whether and how the
standard level should differ if that level reflects the maximum
allowable NO2 concentration anywhere in an area rather than
the maximum allowable NO2 concentration measured at an area-
wide monitoring site. Given this, the Administrator recognizes the
possibility that comments received on this proposal, particularly those
received from CASAC, could provide important new information for
consideration.
g. Level of the Annual Standard
    With regard to the annual standard, the Administrator notes that
the ISA concluded that the scientific evidence is suggestive but not
sufficient to infer a causal relationship between long-term
NO2 exposure and respiratory morbidity. While some studies
have reported associations between long-term NO2 exposure
and respiratory endpoints such as decrements in lung function growth
(Gauderman et al., 2004; Rojas-Martinez et al., 2007a and b; Oftedal et
al., 2008), the ISA notes that the high correlation among traffic-
related pollutants makes it difficult to accurately estimate
independent effects in these long-term studies. CASAC recommended
retaining an annual standard in order to provide protection against
potential health effects associated with long-term exposures. They
based this recommendation on ``the limited evidence related to
potential long-term effects of NO2 exposure and the lack of
strong evidence of no effect'' (Samet, 2008b). With regard to the level
of an annual standard, CASAC recommended retaining the current level as
the evidence considered did not provide a basis for either increasing
or decreasing it. Given these considerations, and recognizing that a
new 1-hour standard level as proposed would also provide some degree of
protection from long-term exposures, the Administrator proposes to take
a cautious approach and retain the current annual standard. The
Administrator solicits comment on this approach.

G. Summary of Proposed Decisions on the Primary Standard

    For the reasons discussed above, and taking into account
information and assessments presented in the ISA and REA as well as the
advice and recommendations of CASAC, the Administrator proposes that
the current annual standard is not requisite to protect public health
with an adequate margin of safety. The Administrator proposes to
establish a new short-term standard that will afford increased
protection for asthmatics and other at-risk populations against an
array of adverse respiratory health effects related to short-term
NO2 exposure. These effects include increased asthma
symptoms, worsened control of asthma, an increase in respiratory
illnesses and symptoms, and related serious indicators of respiratory
morbidity including emergency department visits and hospital admissions
for respiratory causes.
    Specifically, the Administrator proposes to set a new short-term
primary NO2 standard, with a 1-hour (daily maximum)
averaging time, a form defined as the 3-year average of the 99th
percentile or the 4th highest daily maximum concentration. The level
for the new standard is proposed to be within the range of 80 to 100
ppb, reflecting maximum allowable concentrations anywhere in an area.
In conjunction with this proposed standard, the Administrator also
solicits comment on levels as low as 65 ppb and as high as 150 ppb, and
on alternative forms including the 3-year average of the 98th
percentile or the 7th or 8th highest daily maximum concentration.
    In addition, the Administrator also solicits comment on an
alternative approach to setting a new 1-hour standard. Under this
alternative, the NO2 NAAQS would reflect the maximum
allowable area-wide NO2 concentration, which would be
measured away from major roads. With regard to this approach, the
Administrator solicits comment on a level within the range from 50 to
75 ppb and on the same alternative forms as noted above.
    In addition to setting a new 1-hour standard, the Administrator
proposes to retain the current annual standard. The current annual
standard together with a new 1-hour standard would provide protection
against health effects potentially associated with long-term exposures
to NO2. The Administrator solicits comment on this approach.

III. Proposed Amendments to Ambient Monitoring and Reporting
Requirements

    The EPA is proposing changes to the ambient air monitoring,
reporting, and network design requirements for the NO2
NAAQS. This section discusses the changes we are proposing which are
intended to support the proposed 1-hour NAAQS and proposed retention of
the current annual NAAQS in Section II. Ambient NO2
monitoring data are used to determine whether an area is in violation
of the NO2 NAAQS. Ambient NO2 monitoring data are
collected by state, local, and Tribal monitoring agencies (``monitoring
agencies'') in accordance with the monitoring requirements contained in
40 CFR parts 50, 53, and 58.

A. Monitoring Methods

    To be used in a determination of compliance with the NO2
NAAQS, NO2 data must be collected using a Federal Reference
Method (FRM) or a Federal Equivalent Method (FEM) analyzer. The current
monitoring method in use by most State and local monitoring agencies is
the gas-phase chemiluminescence FRM (40 CFR Part 50, Appendix F), which
was implemented into the NO2 monitoring network in the early
1980s. The current list of all approved FRMs and FEMs capable of
providing ambient NO2 data for use in attainment
designations may be found on the EPA Web site (http://www.epa.gov/ttn/
amtic/files/ambient/criteria/reference-equivalent-methods-list.pdf). It
must be noted, however, that due to the proposal of a new 1-hour NAAQS,
wet chemical based FEMs would not be appropriate for use in determining
compliance of the proposed 1-hour NAAQS, since such methods are
incapable of providing hourly averaged data. Therefore, we propose that
any NO2 FRM or FEM used for making primary NAAQS decisions
must be capable of providing hourly averaged concentration data. We
propose to only allow FRM or FEMs capable of providing hourly averaged
concentration data to be used to produce data for comparison to the
NAAQS, and solicit comment on this proposed requirement.
    The sum of nitric oxide (NO) and NO2 is commonly called
NOX. Nitrogen oxides, technically the total reactive
nitrogen oxide family, known as NOY, is defined as the sum
of NO, NO2, and the higher nitrogen oxides collectively

termed NOZ. Important components of ambient NOZ
include nitrous acid (HNO2), nitric acid (HNO3),
and the peroxyacetyl nitrates (PANs). However, NO2 is the
indicator for the nitrogen oxides NAAQS. In the ambient monitoring
network, very nearly all measurements of NO2 are collected
by the chemiluminescence FRM. However, this technique directly measures
only NO by the principle of gas-phase chemiluminescence induced by the
reaction of NO with O3 at low pressure. NO2
concentrations are determined indirectly by the analyzer in two steps:
(1) By first measuring the ambient NO concentration, and (2)
determining total NOX, including NO2, by
measuring a second NO concentration after reducing the NO2
in the sample air stream to NO (most often through the use of a
molybdenum oxide (MoOX) substrate heated to between 300
[deg]C and 400 [deg]C in the sample flow path). The difference between
the second concentration (NO plus the NO2 reduced to NO) and
the first concentration (ambient NO only) is reported as the
NO2 concentration.
    One issue of note with the chemiluminescence FRM is that the
reduction of NO2 to NO on the MoOX converter
substrate is not specific to NO2; hence, chemiluminescence
method analyzers are subject to varying interferences produced by the
presence in the air sample of the NOZ species listed above
and others occurring in trace amounts in ambient air. This interference
is often termed a ``positive artifact'' in the reported NO2
concentration since the presence of NOZ results in an over-
estimate in the reported measurement of the actual ambient
NO2 concentration. This interference by NOZ
compounds has long been known and evaluated (Fehsenfeld et al., 1987;
Nunnermacker et al., 1998; Parrish and Fehsenfeld, 2000; McClenny et
al., 2002; U.S. Environmental Protection Agency, 1993, 2006a). The
sensitivity of the chemiluminescence FRM to potential interference by
individual NOZ compounds is variable and depends in part on
characteristics of individual monitors, such as the design of the
instrument inlet, the temperature and composition of the reducing
substrate, and the interactions of atmospheric species with the
reducing substrate. Furthermore, the concentrations of NOZ
compounds in ambient air are variable with time and distance from the
sources of NO and NO2, chiefly the point source and both on-
road and non-road mobile source combustion of fossil fuels. Nearer to
these sources, the potential interference is lower than it is farther
away because more of the measured nitrogen oxides are present as the
emitted NO and quickly formed NO2, rather than
NOZ. This is because oxidation to the NOZ
compounds from NO and NO2 requires time and the presence of
other atmospheric compounds like the hydroxyl radical.
    Overall, as noted in the ISA, it appears that interference by
NOZ on chemiluminescence FRMs is not more than 10 percent of
the reported NO2 concentration during most or all of the day
during winter (cold temperatures), but larger interference ranging up
to 70 percent can be found during summer (warm temperatures) in the
afternoon at sites away and downwind from strong emission sources. In
general, the NOZ interference in the reported NO2
concentrations collected downwind of source areas and NO2
concentrations collected in relatively remote areas away from
concentrated point, area, or mobile sources is larger than the
NOZ interference in NO2 measurements taken in
urban cores or other areas with fresh NOX emissions.
    The chemiluminescence FRM is well established, comprising a large
majority of the current operating network, and has served as the
principal monitoring method in the NO2 network for more than
thirty years. Many of the epidemiologic studies referenced in the REA
as the health basis for the proposed primary NO2 NAAQS
utilized ambient NO2 data obtained from chemiluminescence
FRMs, and subsequently, the uncertainties that may occur from the
potential positive influence of NOZ species on
NO2 values provided by the ambient FRM monitoring network
are already reflected in those studies. Therefore, for purposes of
comparing NO2 monitoring data to the NO2 NAAQS,
the EPA believes that the chemiluminescence FRMs are appropriate for
continued use under the current standard and under any of the options
being considered for a new 1-hour averaged primary NO2
NAAQS.
    EPA is aware of the more recent development of an alternative
method in determining NO2 concentrations by
chemiluminescence, specifically through the use of a photolytic
converter, which uses specific wavelengths of ultraviolet light to
reduce NO2 to NO in lieu of the FRM's MoOX
substrate converter. The advantage of the photolytic-chemiluminescence
method is that the photolytic converter is more specific to
NO2, as compared to a MoOX substrate converter,
and does not reduce many NOZ species to NO (Ryerson et al.,
2000), reducing the potential influence of NOZ
concentrations on the reported NO2 concentration. The
photolytic-chemiluminescence method is currently deployed within
certain research networks, but the EPA has not approved this method as
an FRM or an FEM. If this technique is to be advanced to an FRM or FEM,
the method may require additional research and development to ensure
the stability of the photolytic converter rates in a variety of ambient
conditions and monitor set-ups that might be experienced in the field
and a consistent method of mathematically correcting for the known
converter efficiencies.
    EPA also recognizes that, although not widely used by state and
local monitoring agencies, the existing FRM and FEM path-integrated
optical remote sensing techniques, also known as open-path and remote
sensing methods, which use spectrometers to detect pollutant
concentrations by light absorption over an optical path length, are
suitable for continued use in the ambient monitoring network as they
can provide NO2 measurements with reduced influences of
NOZ species on the reported NO2 concentrations,
relative to the chemiluminescence FRM. However, these methods do not
provide point specific concentrations like those provided by
chemiluminescence FRMs that are typically expected and seen in the
monitoring network, and may be one of the reasons these methods are not
more widely used.
    In recognition of the existence of alternative methods that may be
useful in the measurement of NO2 for NAAQS compliance
purposes, as well as other objectives, EPA solicits comment on the
advantages and disadvantages of advancing technology, such as the
photolytic-chemiluminescence method, or the use of existing open-path
or remote sensing FRM and FEM technology, as alternative methods to
supplement the approved chemiluminescence FRMs already deployed across
the U.S. at NO2 monitoring sites.

B. Network Design

1. Background
    The basic objectives of an ambient monitoring network, as noted in
40 CFR Part 58 Appendix D, include (1) providing air pollution data to
the general public in a timely manner, (2) supporting compliance with
ambient air quality standards and emissions strategy development, and
(3) providing support for air pollution research. Section II.A.1 notes
that there are currently no minimum monitoring requirements for
NO2 in 40 CFR part 58 Appendix D,

other than the requirement for EPA Regional Administrator approval
before removing any existing monitors, and that any ongoing
NO2 monitoring must have at least one monitor sited to
measure the maximum concentration of NO2 in that area. As
discussed in Section II.A.2, an analysis of the approximately 400 \19\
monitors comprising the current NO2 monitoring network
(Watkins and Thompson, 2008) indicates that the most frequently stated
monitor objectives for sites in the current NO2 network are
for the assessment of concentrations for general population exposure
and maximum (highest) concentrations typically at the neighborhood and
urban scales. Spatial scales are defined in 40 CFR Part 58 Appendix D,
Section 1.2, where the scales of representativeness of most interest
for the monitoring site types include:
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    \19\ It should be noted that the ISA Section 2.4.1 references a
different number of active monitors in the NO2 network.
The difference stems from how `currently operating monitors' were
defined when extracting data from AQS. The ISA only references
SLAMS, NAMS, and PAMS sites with defined montoring objectives, while
the Watkins and Thompson, 2008 value represents all NO2
sites reporting data at any point during the year.
---------------------------------------------------------------------------

    1. Microscale--Defines the concentration in air volumes associated
with area dimensions ranging from several meters up to about 100
meters.
    2. Middle scale--Defines the concentration typical of areas up to
several city blocks in size, with dimensions ranging from about 100
meters to 0.5 kilometers.
    3. Neighborhood scale--Defines concentrations within some extended