In addition, the CASAC also provided advice on areas for additional
research based on key areas of uncertainty that came up during the
review cycle (Diez Roux and Sheppard, 2017, p. 10-12). As part of this
advice, the CASAC stated that ``[t]here is an ongoing need for research
in multipollutant exposure and epidemiology to attempt to distinguish
the contribution to NO2 exposure to human health risk''
(Diez Roux and Sheppard, 2017, p. 10). More specifically, the CASAC
pointed to the importance of further understanding the effects of co-
pollutant exposures and the variability in ambient NO2
concentrations, particularly considering ``locations of peak exposure
occurrences (e.g., on road in vehicles, roadside for active commuters,
in street canyons, near other non-road facilities such as rail yards or
industrial facilities)'' (Diez Roux and Sheppard, 2017, p. 11). In
particular, the CASAC recognized the importance of the new near-road
monitoring data in reducing those uncertainties, stating that ``[t]he
amount of data from near-road monitoring will increase between now and
the next review cycle and should be analyzed and evaluated'' (Diez Roux
and Sheppard, 2017, p. 11).
3. Comments on the Proposed Decision
    This section presents the responses of the EPA to the public
comments received on the 2017 NO2 NAAQS proposal (82 FR
34792, July 26, 2017). All significant issues raised in timely public
comments have been addressed in this document, as the EPA is not
preparing a separate Response to Comments document. We have
additionally considered comments submitted after the close of the
public comment period, to the extent practicable.
    Overall, the EPA received 17 sets of comments, with the majority
expressing support for the Administrator's proposed decision to retain
the current primary standards, without revision. Comments supporting
the Administrator's proposed decision were received from various
industry groups,\99\ individuals, and state environmental or health
agencies.\100\ These commenters generally note their agreement with the
Administrator's rationale provided in the proposal and many note the
CASAC concurrence with the EPA that the current evidence does not
support revision to the standards. Some of the commenters also agree
with the EPA and the CASAC statements that the information in this
review has not substantially altered our previous understanding of the
concentrations at which effects can occur, and that the scientific
evidence does not support standards more protective than the current 1-
hour and annual standards.
---------------------------------------------------------------------------

    \99\ Comments were received from the following industry groups:
The NAAQS Implementation Coalition, the Utility Air Regulatory
Group, Edison Electric Institute, Interstate National Gas
Associations of America, Cleco Power, the American Fuel and
Petrochemical Manufacturers, the American Petroleum Institute, The
Tri-state Generation and Transmission Association, and the Class of
'85 Regulatory Response Group.
    \100\ Comments were received from the following state
environmental or health agencies: Texas Commission on Environmental
Quality (TCEQ) and Arkansas Department of Environmental Quality
(ADEQ).
---------------------------------------------------------------------------

    Several groups, including some that support the Administrator's
proposed decision to retain the current standards, provided additional
comments, including on the EPA's causal determinations in the 2016
NOX ISA, the margin of safety provided by the current
standards, and the potential for the scientific information to support
alternative standards that are less stringent than the current
standards. In addition, one organization (The American Lung
Association) argues for more stringent primary NO2
standards, noting the strong evidence for respiratory effects following
both short- and long-term NO2 exposures.
    The following sections discuss the public comments on the proposal
and the EPA's responses to those comments. Section II.B.3.a discusses
comments on the EPA's assessment of the scientific evidence. Section
II.B.3.b discusses comments on the degree of protection provided by the
current standards and on the potential for the available scientific
information to support standards that are less stringent than the
current standards. Section II.B.3.c discusses comments recommending
that the EPA revise the current standards to be more stringent. Section
II.B.3.d briefly explains the EPA's approach to comments related to
implementation of the NAAQS, which are outside the scope of this
action.
a. Comments on the Assessment of the Scientific Evidence
    There were several comments submitted related to the EPA's
assessment of the scientific evidence. Some commenters agree with the
causal framework used in the 2016 NOX ISA and with the ISA's
conclusions regarding the strength of the evidence for various health
outcomes and for at-risk populations. Other commenters, while agreeing
with the overall proposed decision to retain the existing primary
standards, assert that the ISA framework for causal determinations does
not result in a systematic, balanced, and rigorous evaluation of the
evidence. As discussed below, these commenters generally claim that the
2016 NOX ISA does not adequately address uncertainties and
biases in the evidence and recommend that the EPA should strengthen its
causal framework.
    Some comments received on the proposed decision express an overall

objection to ISA conclusions that the evidence linking NO2
exposures with a variety of health effects has become stronger in this
review. A subset of these comments further imply that the 2016
NOX ISA's conclusions on the strength of evidence, and the
corresponding discussions in the PA, are not entirely consistent with
the uncertainties noted by the Administrator throughout the discussion
of his proposed decision on the primary NO2 standards.
    In responding to these comments, the EPA notes that the ISA's
causal framework has been implemented and refined over multiple NAAQS
reviews, drawing from extensive interactions with the CASAC and from
the public input received as part of the CASAC review process. Based on
application of that framework in the current review, the 2016
NOX ISA has made causal determinations for a variety of
health outcomes. The ISA provides a careful and detailed rationale for
all of its causal determinations, explicitly characterizing the key
evidence, the reason for the change from the 2008 NOX ISA
(if a change occurred), and the uncertainties remaining in the body of
evidence (see, e.g., U.S. EPA, 2016a, Table 1-1). In most cases where
the causal determination has changed since the 2008 NOX ISA,
the change has been due to the availability, in the current review, of
additional studies that reduce uncertainty or bias in the evidence
(U.S. EPA, 2016a, Table 1-1).\101\ The causal determinations in the
NOX ISA underwent extensive CASAC review, which included
multiple opportunities for public input. The EPA considered the CASAC
advice and the public input in making final causal determinations. The
CASAC concurred with the 2016 NOX ISA's causal
determinations and explained the reasons for its concurrence (Diez Roux
and Frey, 2015a, p.1; Diez Roux and Sheppard, 2017, p. 7).
---------------------------------------------------------------------------

    \101\ The exception to this is the 2016 NOX ISA
determination that a causal relationship exists between short-term
NO2 exposure and respiratory effects. This conclusion is
strengthened from the ``likely to be causal'' relationship
determined in the 2008 NOX ISA for Oxides of Nitrogen.
Rather than new evidence, the 2016 NOX ISA notes that
integrated experimental and epidemiologic evidence for asthma
exacerbation, with due weight to controlled human exposure studies,
supports a causal relationship between short-term NO2
exposure and respiratory effects. Specifically, the 2016
NOX ISA explains that the conclusion is strengthened from
the previously determined ``likely to be causal'' relationship
because the combined controlled human exposure and epidemiologic
evidence can be linked in a coherent and biologically plausible
pathway to explain how NO2 exposure can trigger an asthma
exacerbation. (U.S. EPA, 2016a, pp. 1-17 to 1-19).
---------------------------------------------------------------------------

    For example, in concluding that a ``causal relationship exists
between short-term NO2 exposure and respiratory effects
based on evidence for asthma exacerbation'' (U.S. EPA, 2016a, p. 1-17),
the ISA cites ``epidemiologic evidence for NO2-associated
asthma exacerbation and biological plausibility from NO2-
induced increases in [AR] and allergic inflammation in adults with
asthma'' (U.S. EPA, 2016a, p. 5-247). In agreement with this causal
determination, the CASAC states the following (Diez Roux and Sheppard,
2017, p. 7):

    The CASAC concurs with the finding that short-term exposures to
NO2 are causal for respiratory effects based on evidence
for asthma exacerbation. The strongest evidence is for an increase
in airway responsiveness based on controlled human exposure studies,
with supporting evidence from epidemiologic studies.

    In addition, in concluding that ``[t]here is likely to be a causal
relationship between long-term NO2 exposure and respiratory
effects based on evidence for the development of asthma'' (U.S. EPA,
2016a, p. 1-20), the ISA notes that ``[r]ecent epidemiologic studies
consistently indicate increases in asthma incidence in children
particularly in association with NO2 exposures estimated at
or near children's homes or schools'' and that experimental evidence
``provides biological plausibility by characterizing a potential mode
of action by which long-term NO2 exposure may lead to asthma
development'' (U.S. EPA, 2016a, p. 6-67). In agreement with this causal
determination, the CASAC states the following (Diez Roux and Sheppard,
2017, p. 7):

    Long-term exposures to NO2 are likely to be causal
for respiratory effects, based on asthma development. The strongest
evidence is for asthma incidence in children in epidemiologic
studies, with supporting evidence from experimental animal studies.
Current scientific evidence for respiratory effects related to long-
term exposures is stronger since the last review, although
uncertainties remain related to the influence of co-pollutants on
the association between NO2 and asthma incidence.

    Thus, based on the evidence considered in the 2016 NOX
ISA, and consistent with the CASAC advice, we disagree with comments
that the strengthening of the causal determinations in the 2016
NOX ISA is not justified.
    The EPA further disagrees with comments claiming that, in his
consideration of the levels of the primary standards, the
Administrator's discussion of uncertainties and limitations in the
scientific evidence is inconsistent with the conclusions of the 2016
NOX ISA that the evidence for several health endpoints is
stronger now than in the last review. As an initial matter, we note
that the issues faced by the EPA in drawing causal determinations in
the 2016 NOX ISA differ from EPA's considerations in
evaluating the public health protection provided by the standards. In
drawing the causal determinations, the ISA focuses on the degree to
which the available evidence indicates that NO2 exposures
can cause specific health effects. These causal determinations reflect
the ISA's assessment of studies spanning a relatively wide range of
exposure concentrations, encompassing the full body of evidence
relevant for the review. In contrast, in the proposal and in this final
action, the EPA is additionally tasked with determining what the
evidence can tell us about the adequacy of the public health protection
provided by a particular standard or standards. This step typically
involves focusing on the subset of studies that, together with risk and
exposure information, can best inform the EPA's consideration of the
public health impacts associated with particular air quality
concentrations. Consideration of uncertainties is important for both
tasks, but the nature of those uncertainties, and exactly how the
various uncertainties factor into each aspect of the review, may
differ. For example, strengthening of a causal determination in the ISA
may be based on studies that clarify a proposed mode of action linking
exposures with an observed effect, despite being conducted at exposure
concentrations that would not be allowed by the current standards. Such
studies may reduce uncertainties in a way that supports strengthening a
causal determination, but not revising the standard. Thus, the
Administrator's consideration of uncertainties in the evidence when
reaching conclusions on the standards is not inconsistent with the ISA
conclusions that the evidence supports strengthening some causal
determinations in this review.
    We further note that, in reaching his proposed and final decisions,
the Administrator's consideration of the evidence, including its
limitations and uncertainties, draws directly from the 2016
NOX ISA's assessment of that evidence and from the PA's
considerations and conclusions related to the adequacy of the public
health protection provided by the current standards. Both the ISA and
PA include extensive discussion and consideration of the scientific
evidence and its uncertainties. As noted above, Table 1-1 in the ISA
summarizes the key evidence for various NO2-related health

outcomes, including the remaining uncertainties inherent in that
evidence. In addition, drawing from the ISA, the PA includes extensive
consideration of uncertainties and limitations in the evidence as they
relate to conclusions on the adequacy of the public health protection
provided by the current primary NO2 NAAQS (U.S. EPA, 2017a,
sections <IP_ADDRESS>, <IP_ADDRESS>, <IP_ADDRESS>). Contrary to the comments noted
above, the Administrator's proposed and final decisions draw from the
characterization in those documents of uncertainties and limitations in
the evidence (e.g., sections II.A.2, II.A.3, II.B.4 of this final
action). The Administrator's proposed and final decisions to retain the
current primary NO2 standards are consistent with the PA's
conclusions (U.S. EPA, 2017a, section 5.4). Moreover, these decisions
are consistent with recommendations of the CASAC to retain the current
standards (Diez Roux and Sheppard, 2017).
    Some comments further criticize the Agency's characterization of
the evidence by asserting that the EPA places too much emphasis on
epidemiologic studies that are methodologically flawed and insufficient
for determining a standard. While we agree that there are uncertainties
inherent in epidemiologic studies, these uncertainties, which have been
extensively considered as part of the assessment of the evidence in the
ISA and the evaluation of policy options in the PA, as well as in the
proposal and this final action (e.g., summarized in sections II.A.2 and
II.B.1 above), do not make the epidemiologic evidence insufficient for
informing decisions on the primary NO2 standards. Rather,
conclusions in this review draw from the consideration of scientific
evidence from a range of disciplines, each with its own strengths and
limitations.\102\ In particular, the 2016 NOX ISA's causal
determinations are based on the integration of evidence across
controlled human exposure, epidemiologic, and animal toxicological
studies. The focus of the ISA's integration is on evaluating the
consistency and inconsistency in the pattern of effects across studies
and endpoints as well as the strengths and limitations of the evidence
across the various disciplines (U.S. EPA, 2016a, p. 1). For each study,
the 2016 NOX ISA systematically evaluates study design,
populations evaluated, approach to exposure assessment/assignment,
approach to outcome assessment, potential for confounding, and
statistical methodology (U.S. EPA, 2016a, Table A-1). As described
below, and more fully in the ISA (see e.g., U.S. EPA, 2016a, Table 1-
1), uncertainties and limitations in the evidence, including in the
evidence from epidemiologic studies, are explicitly considered in the
ISA's causal determinations and can affect how various aspects of the
evidence are weighed in making those determinations.
---------------------------------------------------------------------------

    \102\ In fact, relative to other types of evidence, strengths of
epidemiologic studies can include providing information on the most
serious pollutant-associated effects in human populations, including
populations with pre-existing conditions, or at particular life
stages, that put them at increased risk of such effects.
---------------------------------------------------------------------------

    For example, while the ISA concludes that epidemiologic studies do
indicate the occurrence of NO2-associated asthma
exacerbation, it further concludes that ``epidemiologic evidence on its
own does not rule out the influence of other traffic-related
pollutants'' (U.S. EPA, 2016a, p. 1-18). The ISA further concludes that
``[t]he key evidence that NO2 exposure can independently
exacerbate asthma are the findings from previous controlled human
exposure studies for increases in airway responsiveness in adults with
asthma'' (U.S. EPA, 2016a, p. 1-18). Thus, based in part on
uncertainties in the available epidemiologic evidence, the ISA's
conclusion that ``[a] causal relationship exists between short-term
NO2 exposure and respiratory effects'' (U.S. EPA, 2016a, p.
1-17) places the greatest emphasis on information from controlled human
exposure studies (e.g., U.S. EPA, 2016a, p. 5-247). As noted above, the
CASAC endorsed this emphasis, stating that ``[t]he strongest evidence
is for an increase in airway responsiveness based on controlled human
exposure studies, with supporting evidence from epidemiologic studies''
(Diez Roux and Sheppard, 2017, p. 7). In fact, the CASAC recommended
that the controlled human exposure studies, alone, are sufficient to
justify the causal determination for short term NO2
exposures and respiratory effects (Diez Roux and Frey, 2015a, cover
letter at p. 2).\103\ Consistent with this, information from controlled
human exposure studies is emphasized in the PA's conclusions on the
public health protection provided by the current standards against
short-term NO2 exposures (U.S. EPA, 2017a, sections 3.2 and
5.4) and in the Administrator's conclusion to retain those standards in
this final decision (section II.B.4, below).
---------------------------------------------------------------------------

    \103\ Specifically, the CASAC recommended that ``the evidence
supporting changes to the causal determination status for oxides of
nitrogen for associations with short-term exposures be based
primarily on the findings from the controlled human exposure
studies, as they alone are sufficient to justify the change'' (Diez
Roux and Frey, 2015a, cover letter at p.2).
---------------------------------------------------------------------------

    In addition, the 2016 NOX ISA's conclusion on long-term
NO2 exposure and respiratory effects recognizes uncertainty
in epidemiologic studies due to potential confounding by other traffic-
related pollutants. The ISA specifically concludes that uncertainty
remains ``in identifying an independent effect of NO2
exposure from traffic-related copollutants because evidence from
experimental studies for effects related to asthma development is
limited, and epidemiologic analysis of confounding is lacking'' (U.S.
EPA, 2016a, p. 1-32).\104\ However, in making its overall determination
that ``there is likely to be a causal relationship between long-term
NO2 exposure and respiratory effects'' the ISA also notes
that support for biological plausibility comes from experimental
studies in animals (e.g., U.S. EPA, 2016a, Table 1-1). While
recognizing remaining uncertainties in the evidence, the CASAC agreed
with this ISA causal determination, observing that ``[t]he strongest
evidence is for asthma incidence in children in epidemiologic studies,
with supporting evidence from experimental animal studies'' (Diez Roux
and Sheppard, 2017, p. 7).
---------------------------------------------------------------------------

    \104\ Such uncertainties also informed the PA's conclusions on
the public health protection provided by the current standards (U.S.
EPA, 2017a, section 5.4).
---------------------------------------------------------------------------

    Thus, the 2016 NOX ISA's conclusions reflect the
consideration of information from all lines of evidence, not only
epidemiologic studies, including appropriate consideration of the
uncertainties and limitations in that evidence. The CASAC reviewed and
endorsed the 2016 NOX ISA's approach to assessing the
evidence, including uncertainties and limitations in that evidence, and
its key conclusions based on the application of that approach (e.g.,
Diez Roux and Frey, 2015a; Diez Roux and Sheppard, 2017, p. 7).
Additionally, the ISA's careful consideration of scientific evidence
from multiple disciplines, and the uncertainties and limitations in
that evidence, including in epidemiologic studies, informed the PA's
conclusions on the public health protection provided by the current
standards and the Administrator's decision to retain those standards,
without revision, in this review. Thus, the EPA does not agree with
comments that undue emphasis was placed on epidemiologic studies.
    Several comments further contend that the 2016 NOX ISA
overstates the consistency of results across

epidemiologic studies and that it does not adequately capture
uncertainties in the epidemiologic evidence. The EPA disagrees with
these comments. As noted above, the 2016 NOX ISA
appropriately characterizes the uncertainties and limitations in the
epidemiologic evidence, including uncertainties resulting from
inconsistent results across studies (e.g., U.S. EPA, 2016a, Tables 5-39
and 6-5). For endpoints where the epidemiologic evidence is not
consistent, the 2016 NOX ISA discusses the inconsistencies.
For example, the ISA states that ``[e]pidemiologic evidence for
NO2-related decreases in lung function in populations with
asthma is inconsistent as a whole'' (U.S. EPA, 2016a, p. 5-241). In
contrast, the ISA appropriately characterizes the consistent results of
epidemiologic studies that evaluate asthma-related outcomes. In
particular, the 2016 NOX ISA notes that ``[r]ecent studies
that examined the association between short-term NO2
exposure and asthma hospital admissions and ED visits consistently
report positive associations and support the results of U.S. and
Canadian studies evaluated in the 2008 ISA for Oxides of Nitrogen.''
(U.S. EPA, 2016a, p. 5-91). Figures 5-16 and 5-17 in the 2016
NOX ISA illustrate the consistent, positive associations
reported in studies that have evaluated the potential for confounding
of the NO2 association by co-occurring pollutants, a key
potential uncertainty in NO2 epidemiologic studies (U.S.
EPA, 2016a, pp. 5-248 to 5-249). Based on its assessment of such
studies of short-term NO2 exposure and asthma-related
effects, the 2016 NOX ISA concludes that ``the pattern of
association observed for NO2 supports the consistency of
evidence and does not indicate a high probability of associations found
by chance alone'' (U.S. EPA, 2016a, p. 5-241).
    Some comments criticizing the 2016 NOX ISA's
characterization of consistency of results across epidemiologic
studies, and the ISA's consideration of uncertainties in those studies,
focus specifically on studies of long-term NO2 exposures.
Such comments claim that the EPA overstates the consistency of the
epidemiologic evidence, particularly given the potential for
copollutant confounding and exposure measurement error in studies of
long-term NO2 exposures. As discussed below, the EPA
disagrees with these comments.
    Figure 6-1 in the 2016 NOX ISA illustrates the
consistently positive associations between long-term exposures and
asthma incidence in children. Based on such studies, the ISA concludes
the following (U.S. EPA, 2016a, p. 6-63):

    Multiple longitudinal studies demonstrate associations between
higher ambient NO2 concentrations measured in the first
year of life, in the year of diagnosis, or over a lifetime and
asthma incidence in children. Results are consistent across
locations based on various study designs and cohorts.

    In reaching this conclusion, the 2016 NOX ISA also
thoroughly discusses the uncertainties and limitations in these
studies, including uncertainties and limitations stemming from the
potential for copollutant confounding and exposure measurement error
(U.S. EPA, 2016a, section <IP_ADDRESS>). For example, with respect to
studies of long-term exposures, the ISA notes that ``[e]pidemiologic
studies of asthma development in children have not clearly
characterized potential confounding by PM2.5 or traffic-
related pollutants'' (U.S. EPA, 2016a, p. 6-64). Drawing from this
discussion in the ISA, the potential for such confounding is a key
consideration in the PA's conclusions on the adequacy of the public
health protection provided by the current primary NO2 NAAQS
(U.S., EPA, 2017, section 5.4). The Administrator has further
considered such uncertainty in reaching his proposed and final
decisions in this review (82 FR 34792, July 26, 2017, section II.F.4;
and see section II.B.4 below). The 2016 NOX ISA also
characterizes the potential for exposure measurement error in these
studies and uncertainties related to reliability of asthma diagnosis
and age of children and temporality between diagnosis and exposures
(U.S. EPA, 2016a, section 6.2). Based on the broader body of evidence
(i.e., including controlled human exposure and animal toxicological
studies), the 2016 NOX ISA concludes that uncertainty in the
epidemiologic evidence base ``is partly reduced by the biological
plausibility provided by findings from experimental studies'' (U.S.
EPA, 2016a, p. 6-64). When taken together, the 2016 NOX ISA
concludes that the evidence supports a relationship between long-term
NO2 exposure and respiratory effects that is ``likely to be
causal,'' and the CASAC supported this conclusion in its review of
drafts of the 2016 NOX ISA and the PA (Diez Roux and Frey,
2015a; Diez Roux and Sheppard, 2017, p. 7).
    Some comments additionally contend that the ISA provides a skewed
and unbalanced picture of the scientific record by failing to discuss
null associations in epidemiologic studies and by focusing on results
at the lag that had the most positive and statistically significant
association. These comments assert that the ISA ignores temporal
differences in the lag at which the strongest association was found.
    With regard to reporting null associations, the EPA agrees that the
assessment of the scientific evidence should consider all relevant,
well-conducted studies that meet the ISA's criteria for inclusion,
regardless of whether results are positive, null, or negative.
Accordingly, the EPA employs a comprehensive approach to ensure that
all of the relevant literature is identified for consideration and
evaluation in the ISA (U.S. EPA, 2015a, Figure III, p. 6). As an
initial step in the development of the 2016 NOX ISA, a call
for information was published in the Federal Register (77 FR 7149,
February 2, 2012). This call for information invited members of the
public to provide information relevant to the assessment, including the
identification of publications that evaluate potential relationships
between pollutant exposures and health effects or data from the fields
of atmospheric or exposure science. Subsequent to this call for
information, the EPA conducted a comprehensive literature search and an
evaluation and integration of evidence from the identified studies. As
part of this process, the EPA evaluated study quality according to
predefined criteria that are consistent with widely established methods
in the field (U.S. EPA, 2016a, Table A-1, p. A2). This evaluation and
assessment of the evidence, which included studies that reported null
or negative results, was presented in two drafts of the ISA, each of
which was reviewed by the CASAC at a public meeting where there were
opportunities for members of the public to provide comments. As
discussed above, in its advice to the Administrator, the CASAC
concurred with key conclusions in the ISA regarding the strength of the
evidence linking NO2 exposures with various health outcomes
(Diez Roux and Frey, 2015a, cover letter at p. 1; Diez Roux and
Sheppard, 2017, p. 7).
    In addition, we note that there is ample discussion throughout the
ISA of null and negative results when they are reported in the studies,
including epidemiologic studies (e.g., U.S. EPA, 2016a, Figures 5-7 and
6-1, and accompanying text).\105\ Summary tables

of key evidence in the ISA for each causal determination discuss
outcomes for which negative or inconsistent results are observed (see
Table ES-1 of the 2016 NOX ISA for a comprehensive list of
summary tables included in the ISA). Additionally, the EPA notes that
while these comments criticized the EPA's assessment of the evidence,
they did not identify well-conducted studies, regardless of association
observed, or lack thereof, that were not included in the 2016
NOX ISA. Thus, given the extensive public process that the
EPA has used to identify and assess the relevant scientific evidence,
including multiple opportunities for CASAC to provide advice and for
members of the public to provide input, together with the ISA's
discussion of all relevant, well-conducted studies, regardless of
results, we do not agree with comments claiming that the ISA provides
an unbalanced picture of the scientific record by failing to account
for studies reporting null or negative associations.
---------------------------------------------------------------------------

    \105\ The 2016 NOX ISA also recognizes the potential
for publication bias, stating that ``[p]ublication bias is another
source of uncertainty that can impact the magnitude of estimated
health or welfare effects. It is well understood that studies
reporting non-null findings are more likely to be published than
reports of null findings'' (U.S. EPA, 2016a p. li).
---------------------------------------------------------------------------

    Additionally, the EPA does not agree with comments criticizing the
2016 NOX ISA's approach to identifying the most appropriate
lags in epidemiologic studies of short-term NO2 exposures.
We note that lag structure can vary within the population according to
differences among individuals in time-activity patterns, pre-existing
disease, or other factors that influence exposure and responses to
exposure. The ISA specifically notes that ``[t]he lag structure for
associations with NO2 exposure may vary among health effects
depending on differences in the time course by which underlying
biological processes occur'' (U.S. EPA, 2016a, p. 1-39). In addition,
differences in associations among exposure lags may be influenced by
``differences in the extent to which single-day and multiday average
ambient NO2 concentrations represent people's actual
exposures'' (U.S. EPA, 2016a, p. 1-39).
    In assessing the support for specific lags in epidemiologic studies
of short-term NO2 exposures and asthma-related effects, the
ISA notes support for same-day exposures and for exposures averaged
over multiple days (U.S. EPA, 2016a, section 1.6.2). The ISA further
notes support for these lags from experimental studies (U.S. EPA,
2016a, section 1.6.2). Specifically, controlled human exposure studies
found airway responsiveness in adults with asthma to increase
immediately after, or 20 minutes to 4 hours after, a single
NO2 exposure and over 4 days of repeated exposure (U.S. EPA,
2016a, section <IP_ADDRESS>). In experimental studies, NO2
exposure enhanced allergic inflammation 30 minutes up to 19 hours after
a single- or 2-day exposure in humans and 7 days after exposure in rats
(U.S. EPA, 2016a, section <IP_ADDRESS>). Thus, based on its assessment of
the evidence, the ISA concludes that ``findings from experimental
studies provide biological plausibility for the asthma-related effects
observed in epidemiologic studies in association with 2- or 5-hour
exposures, same-day NO2 exposures, as well as exposures
averaged over multiple days'' (U.S. EPA, 2016a, p. 1-40). Accordingly,
when assessing epidemiologic studies of short-term NO2
exposures, the ISA focuses on the lags that are best supported in the
evidence, with a recognition that the most appropriate lag can vary
according to the specific endpoint evaluated, time-activity patterns of
members of the study population, the prevalence of pre-existing disease
in the study population, and other factors that influence pollutant
exposures or the responses to those exposures.
    Some comments recommend that the EPA conduct quantitative analyses
of uncertainty whenever possible. As discussed above and elsewhere in
this document (e.g., sections II.A.2, II.A.3, II.B.1, II.B.4), the EPA
has thoroughly considered uncertainties in the evidence and in
available quantitative analyses throughout this review of the primary
NO2 NAAQS. Uncertainties have been evaluated through a
combination of qualitative and quantitative approaches, with the
specific approach depending on the uncertainty being evaluated and the
data available for its evaluation. For example, the 2016 NOX
ISA's conclusions are based on an evaluation of the strengths and
weaknesses in the overall collection of studies across disciplines. The
ISA's approach to evaluating the evidence and drawing causal
determinations generally involves qualitative consideration of
uncertainties in the various lines of evidence (U.S EPA, 2016a,
preamble). As noted above, this framework has been implemented and
refined over multiple NAAQS reviews, drawing from extensive
interactions with the CASAC and from the public input received as part
of the CASAC review process. The CASAC has reviewed the causal
determinations in the NOX ISA, including the ISA's
consideration of uncertainties in the evidence, and has concurred with
those determinations (Diez Roux and Frey, 2015a, cover letter at p.1;
Diez Roux and Sheppard, 2017, p. 7).
    With regard to analyses comparing NO2 air quality and
health-based benchmarks, the PA includes both quantitative and
qualitative evaluation of uncertainties. For example, quantitative
sensitivity analyses were used to evaluate the degree to which study
areas adequately reflect influential factors that could contribute to
variability in NO2 concentrations and potential exposures
(U.S. EPA, 2017a, Appendix B, section 2.3.2) and to examine the
potential impacts of NO2 exposures on or near roadways (U.S.
EPA, 2017a, Appendix B, section 2.4.2). In addition, the PA includes
extensive qualitative discussion of uncertainties in air quality-
benchmark comparisons, and the implications of these uncertainties for
the interpretation of analysis results (U.S. EPA, 2017a, section
<IP_ADDRESS>). This includes consideration of uncertainties in evidence
underlying the health-based benchmarks, in the approach to adjusting
ambient NO2 concentrations to simulate just meeting the
current standard, and in the degree to which monitored NO2
concentrations reflect the highest potential NO2 exposures.
Thus, as part of this review, the EPA has thoroughly considered
uncertainties in the evidence and in available quantitative analyses,
with the specific approach depending on the uncertainty being evaluated
and the data available for its evaluation.
b. Comments Relating to Consideration of Less Stringent Standards
    Though most commenters express support for the proposed decision to
retain the current primary NO2 standards, some of these
commenters additionally encourage the identification and consideration
of less stringent standards. Such comments are often based on
criticisms of the EPA's approach to assessing the scientific evidence,
as discussed in section II.B.3.a above, with some comments contending
that the proposal understates the margin of safety provided by the
current 1-hour and annual standards. Some comments further conclude
that limitations and uncertainties in the body of scientific evidence
support the possibility that the current standards are more protective
than is requisite, claiming that, in its consideration of the adequacy
of the protection provided by the current standards, the EPA failed to
consider whether the NO2 NAAQS should be made less
stringent. One comment additionally asserts that the failure to
identify alternative, less stringent standards is arbitrary and
capricious, stating that the EPA has not adequately examined whether
the uncertainties in the evidence call into question the proposed
decision to retain the current standards or whether the standard
level(s) should be less stringent. This

comment contends that the EPA must examine the possibility that the
current standards may be too stringent and that, without such an
examination, there is not adequate foundation in the record to support
the proposed decision to retain those standards.
    The Administrator has carefully considered whether standards less
stringent than the current standards would be sufficient to protect
public health with an adequate margin of safety and, thus, whether
retaining the current standards would not be requisite (see discussion
in proposal at 82 FR 34792, July 26, 2017, section II.F.4, and below).
This consideration is informed by the thorough discussions of the
uncertainties in the scientific evidence in the 2016 NOX
ISA, the PA, and elsewhere in this document (U.S. EPA, 2016a, table 1-
1; U.S. EPA, 2017a, section 3; and section II.A.3, above). The
Administrator is not required to identify or evaluate specific
alternative standards in order to make a determination than an existing
standard or suite of standards provide the requisite protection. To the
contrary, where the record supports a judgment that the current
standards are requisite to protect public health with an adequate
margin of safety, and that more or less stringent standards would not
be requisite, the EPA may conclude, as it has here, that detailed
evaluation of specific alternative standards is not warranted.\106\
---------------------------------------------------------------------------

    \106\ For example, in the final decision in the recently
completed review of the National Ambient Air Quality Standards for
Lead (81 FR 71906, October 18, 2016), the standards were retained
without consideration of potential alternative levels.
---------------------------------------------------------------------------

    Further, we disagree with the suggestion that, by focusing on
whether the current standards adequately protect public health, the EPA
has failed to consider the possibility that those standards should be
revised to be less stringent in order to provide the requisite level of
protection. Comments making this claim mistakenly presume that, in
considering the adequacy the current primary NO2 NAAQS and
the public health protection they provided, the EPA has not considered
whether the current standards should be revised to be less stringent.
In fact, the EPA's consideration of the adequacy of the current
standards and the public health protection they provide is intended to
inform, and therefore substantively overlaps with, the Administrator's
consideration of whether more or less stringent standards would, in his
judgment, be requisite under the Clean Air Act. Accordingly, in
considering the adequacy of the current standards to satisfy the CAA's
requirements, the EPA also evaluates whether identification of
potential alternative standards, either more or less stringent, is
warranted. As described below, several considerations support the EPA
conclusion in this review that standards less stringent than the
current standards would not be requisite.
    First, compared to the current standards, less stringent standards
would be more likely to allow NO2 exposures that could
exacerbate respiratory effects in people with asthma. The current
NO2 standards are expected to allow virtually no potential
for exposures to the NO2 concentrations that have been shown
most consistently to increase AR in people with asthma (i.e., 250 ppb
and above). In addition, the current standards provide a margin of
safety, in part by limiting the potential for exposures to 1-hour
NO2 concentrations at or above 100 ppb, an exposure
concentration with the potential to exacerbate asthma symptoms but for
which the evidence indicates uncertainty in the risk of such effects
occurring (U.S. EPA, 2017a, sections 5.2, 5.4). Although limitations in
this evidence take on increased importance when considering the
potential public health implications of such exposures to 100 ppb, as
discussed in greater detail below (e.g, sections II.B.3.c and II.B.4),
the CAA requires that a primary NAAQS protect the public health even
where, as here, the risks from the pollutant cannot be quantified or
``precisely identified as to nature or degree.'' API v. EPA, 684 F.3d
at 1350 (internal citation omitted). Further, in setting a standard
with an adequate margin of safety, the EPA is to ``err on the side of
caution.'' Id. at 1352. Thus, EPA places weight on the consideration
that less stringent standards would be expected to be less effective
than the current standards at protecting against these short-term
exposures to NO2 concentrations at or above health-based
benchmarks.
    Second, less stringent standards would be more likely to allow the
ambient NO2 concentrations that have been reported in
epidemiologic studies to be associated with clearly adverse effects.
For example, such standards would be more likely to allow the short-
term ambient NO2 concentrations that have been shown in
epidemiologic studies conducted in the U.S. or Canada to be associated
with asthma-related hospitalizations. In addition, recognizing that the
current 1-hour standard contributes substantially to protection against
long-term NO2 exposures, less stringent standards would also
be more likely to allow the long-term ambient concentrations that have
been reported in epidemiologic studies to be associated with asthma
development in children. While the EPA recognizes the limitations and
uncertainties in these studies, they provide evidence for associations
with asthma-related effects in locations likely to have violated the
current standards (U.S. EPA, 2017a, sections <IP_ADDRESS> and <IP_ADDRESS>).
Therefore, the EPA also places weight on the consideration that,
compared to the current standards, less stringent standards would allow
greater risk of the serious health effects reported in these studies.
    Finally, the CASAC advice also supports the EPA conclusion that a
detailed evaluation of less stringent potential alternative standards
is not warranted in the current review. Specifically, the CASAC advised
that the current primary NO2 standards, but not less
stringent standards, provide protection against adverse effects
associated with both short- and long-term NO2 exposures.
Based on its consideration of the evidence, the CASAC concluded that
``there are notable adverse effects at levels that exceed the current
standard, but not at the level of the current standard'' (Diez Roux and
Sheppard, 2017 p. 9) and that it is ``the suite of the current 1-hour
and annual standards, together, that provide protection against adverse
effects'' (Diez Roux and Sheppard, 2017, p. 9). Therefore, for the
reasons discussed above, we disagree with comments advocating for a
detailed evaluation of potential alternative standards that would be
less stringent than the current standards and with comments contending
that EPA has not considered whether the current standards are too
stringent and, thus, should not be retained.
    Comments advocating for the identification of less stringent
standards often focus on specific uncertainties in the available health
evidence, claiming that, because of these uncertainties, the margin of
safety provided by the current primary NO2 standards is
larger than acknowledged in the proposal. For example, some comments
question the EPA's interpretation of controlled human exposure studies
examining AR, claiming that these studies do not demonstrate adverse
effects at exposure concentrations below 300 ppb. Such comments contend
that the EPA should clearly articulate the limitations in controlled
human exposure studies of AR following NO2 exposures, and in
the Brown (2015) meta-analysis of individual-level data from these
studies.
    The EPA agrees that there are uncertainties in the evidence from

controlled human exposure studies of NO2-induced changes in
AR. These uncertainties have been discussed and considered extensively
throughout this review, including in the 2016 NOX ISA and
the PA (U.S. EPA, 2016a; U.S. EPA, 2017a), and in the Administrator's
consideration of the evidence in both the proposal (82 FR 34792, July
26, 2017, section II.F.4) and this final action (section II.B.4,
below). Specifically, important limitations in the evidence for
increased AR following NO2 exposures include the lack of an
apparent dose-response relationship, which limits our ability to fully
characterize the health risks associated with these exposures, and
uncertainty in the adversity of the reported increases in AR (e.g., see
U.S. EPA, 2017a, section <IP_ADDRESS>, and section II.A.2.a.iii above).
While we agree that it is appropriate to consider these uncertainties
in reaching decisions on the primary NO2 NAAQS, as described
below, we disagree that such uncertainties indicate that the reported
effects do not have the potential to be adverse to public health.
    In particular, as discussed in the ISA, increases in AR are
considered to be a hallmark of asthma and can lead to poorer control of
symptoms in people with the disease. Drawing on guidelines from the ATS
and the ERS, analyses discussed in the 2016 NOX ISA indicate
that the increases in AR reported following exposures to NO2
concentrations from 100 to 530 ppb have the potential to be clinically
relevant in some people with asthma (82 FR 34804, July 26, 2017; U.S.,
EPA, 2016a section <IP_ADDRESS>). While there are no universally agreed upon
criteria for determining whether such increases should be considered
adverse, they represent respiratory effects that could be of particular
concern for people with more severe cases of asthma than have typically
been evaluated in the available studies of NO2 exposures.
These studies have generally evaluated people with mild asthma, while
people with moderate or severe asthma could be more susceptible to
NO2-induced increases in AR, and thus more likely to exhibit
adverse responses following NO2 exposures (Brown,
2015).\107\ Therefore, the uncertainty over the adversity of the
response reported in controlled human exposure studies and the Brown
(2015) meta-analysis does not mean that the NO2-induced
increase in AR is not adverse to any population. Rather, the evidence
indicates a risk of adversity for some people, especially for those
with more than mild asthma, though this risk cannot be fully
characterized based on existing studies. When considered at a
population level, these risks are amplified and take on public health
significance.
---------------------------------------------------------------------------

    \107\ Furthermore, the potential for such effects in other at-
risk populations that have generally not been evaluated in
NO2 controlled human exposure studies (i.e., children and
older adults) cannot be well-characterized based on the available
studies.
---------------------------------------------------------------------------

    In light of these observations, we disagree with the assertion that
controlled human exposure studies do not demonstrate effects that could
be adverse to public health following exposures to NO2
concentrations below 300 ppb and with comments that the proposal
overstates the margin of safety provided by the current standards.
Rather, while acknowledging uncertainties in the evidence, and that the
risk cannot be fully characterized based on existing studies, the EPA
remains concerned about the potential for adverse respiratory effects
following exposures to such NO2 concentrations, particularly
in people with more severe cases of asthma than have generally been
evaluated in the available studies of NO2 exposures.
Further, given the large percentage of people with asthma that
experienced an NO2-induced increase in AR in these studies,
including at exposures at and below 300 ppb,\108\ and the large size of
the asthmatic population in the United States, the EPA concludes that
it is appropriate to place weight on NO2-induced increases
in AR in considering the potential for adverse public health effects
following NO2 exposures.
---------------------------------------------------------------------------

    \108\ For example, as discussed elsewhere in this document
(e.g., section II.A.2 above), the Brown (2015) meta-analysis
reported that following resting NO2 exposure in the range
of 200 ppb to 300 ppb, increased non-specific AR was reported in 78%
of study participants.
---------------------------------------------------------------------------

    Additionally, some comments support placing more emphasis on a
meta-analysis of information from controlled human exposure studies by
Goodman et al. (2009). These comments assert that Goodman et al.
concluded that exposures to NO2 concentrations up to 600 ppb
are not associated with clinically relevant effects.
    The particular basis for these comments appears to be the
conclusions reached by Goodman et al. (2009) that there is no dose-
response relationship between NO2 exposures and increased
AR, and that the magnitude of any NO2 effect on airway
responsiveness is too small to be considered adverse. While the EPA
acknowledges the lack of an apparent dose-response relationship between
NO2 exposures and increased AR, potentially due to
differences in study protocols in the NO2-airway response
literature (U.S. EPA, 2016a, section <IP_ADDRESS>), the EPA disagrees with
the approach taken in the Goodman study to use existing data to attempt
to evaluate whether a dose-response relationship exists. Specifically,
the EPA notes that while Goodman et al., (2009) did not observe a dose-
response relationship, this could be due to a variety of factors
inherent to the study design rather than a true absence of a dose-
response relationship.\109\ Examples of such differences between
studies include the NO2 exposure method (i.e., mouthpiece
versus chamber), subject activity level (i.e., rest versus exercise)
during NO2 exposure, choice of airway challenge agent, and
physiological endpoint used to quantify airway responses.
---------------------------------------------------------------------------

    \109\CF. API v. EPA, 684 F.3d at 1350 (nothing in the context of
the last NO2 NAAQSreview that ``the [Goodman] study did
not establish there was `no dose-response relationship'''). In a
decision upholding the 2010 primary NO2 NAAQS , the court
held that EPA was ``justified in revising the NAAQS considering the
evidence of a statistically significant relationship between
relevant health conditions and NO2 exposure at various
concentrations, even if the agency did not know the precise dose-
response relationship between V and airway responsiveness, among
other health effects.'' Id. at 1351.
---------------------------------------------------------------------------

    As a result of these differences in study protocols, the 2016
NOX ISA judged it appropriate to assess only the fraction of
study participants who experienced increased or decreased airway
responsiveness following NO2 exposures. The CASAC endorsed
this approach of comparing the fractions of study participants, which
was adopted in the meta-analysis by Brown (2015) and was the focus of
discussion in the 2016 NOX ISA (U.S. EPA, 2016a, section
<IP_ADDRESS>). When commenting on Brown (2015) in the draft ISA, the CASAC
noted that it was ``impressed with the meta-analysis of controlled
human exposure studies'' and found that ``this analysis facilitates the
inferences that can be drawn from the studies contained in the
analysis'' (Diez Roux and Frey, 2015a, p. 2 of cover letter, p. 7 of
consensus comments).
    When the fraction of study participants who experienced increased
or decreased airway responsiveness was analyzed, both Brown (2015) and
Goodman et al. (2009) reported that exposures to NO2
concentrations at and above 100 ppb increased airway responsiveness in
the majority of people with asthma. Specifically, Table 4 of the
Goodman et al. (2009) study reports that 64% (95% CI: 58%, 71%) of
resting asthmatics exposed to NO2 experienced an increase in
airway responsiveness. Furthermore, Figure 2a of the Goodman et al.
(2009) study reports that for exposures less than 200 ppb, 61%

experienced an increase in AR (95% CI: 52%, 70%), while for exposures
of 200 to 300 ppb, 66% experienced an increase (95% CI: 59%, 74%).
These findings are consistent with those reported by Brown (2015) and
discussed in the 2016 NOX ISA (U.S. EPA, 2016a, section
<IP_ADDRESS>).
    Thus, both Goodman et al. (2009) and Brown (2015) report that the
majority of study subjects experienced increased AR following resting
NO2 exposures. As discussed further above, increases in AR
can lead to poorer control of symptoms in people with asthma and
analyses in the 2016 NOX ISA indicate that the increases in
AR reported following resting exposures to NO2
concentrations from 100 to 530 ppb have the potential to be clinically
relevant in some people with asthma. In addition, people with more
severe cases of asthma than have typically been evaluated in the
available studies of NO2 exposures could be more likely to
exhibit adverse responses following such exposures. Therefore, while we
agree with comments that it is appropriate to consider the meta-
analysis by Goodman et al. (2009), in addition to that by Brown (2015),
we do not agree that such consideration supports the conclusion that
exposures to NO2 concentrations up to 600 ppb are not
associated with clinically relevant effects.
    Some comments assert that the EPA should place more emphasis on
controlled human exposure studies that employ allergen challenge,
rather than those that use non-specific challenge agents, because the
commenters view such studies as more relevant to real world exposures.
These comments claim that the lack of effects in studies that used
allergen challenge increases the uncertainty that NO2 in
ambient air causes effects of concern.
    As an initial matter, we note that the ATS and the ERS recognize
increased AR following exposure to non-specific challenge agents (e.g.,
methacholine) as a primary feature in the clinical definition and
characterization of asthma severity (U.S. EPA, 2016a, section <IP_ADDRESS>;
Reddel et al., 2009). Thus, we do not agree with the implication of
these comments that non-specific challenge agents are inherently less
relevant to the evaluation of NO2-induced changes in AR.
    We further disagree that people would not have real world exposures
to all of the non-specific challenge agents used in controlled human
exposure studies. Specifically, both cold dry air and SO2,
which have been evaluated in studies of non-specific AR following
NO2 exposures, are nonspecific stimuli that people may
encounter in the environment.\110\ Thus, when viewed from a public
health perspective, a member of the public has the potential to be
exposed to a non-specific challenge agent just as they have the
potential to be exposed to an allergen to which they have been
sensitized.
---------------------------------------------------------------------------

    \110\ Of the studies included in the meta-analysis by Brown
(2015), SO2 was used as a challenge agent in a study of
resting exposures to 250 ppb NO2 (Table 1 of Brown, 2015)
and cold dry air was used in several studies of NO2
exposures during exercise (Table 2 of Brown, 2015).
---------------------------------------------------------------------------

    In addition, while we agree with the potential public health
significance of increased AR to allergen challenges (e.g., see U.S. EPA
2016a, pp. 5-24 and 5-25), relatively little individual-level data on
changes in AR following NO2 exposures was available from
studies using specific allergen challenges (i.e., about 30% of the AR
data). With regard to the allergen challenge studies that were
available, the 2016 NOX ISA (U.S. EPA 2016a, p. 5-25)
additionally notes that, ``. . . the response to an allergen is not
only a function of the concentration of inhaled allergen, but also the
degree of sensitization as measured by the level of allergen-specific
IgE and responsiveness to nonspecific agents,'' making it difficult to
predict the level of responsiveness to an allergen. The relatively
small amount of individual-level data from allergen challenge studies,
together with the greater difficulty in predicting allergen
responsiveness, limits the degree to which these studies, by
themselves, can inform conclusions on the potential public health
implications of NO2 exposures. Given this, in addition to
considering results of individual studies, we consider the data from
studies of allergen challenge, together with data from studies of non-
specific challenge, as part of the meta-analysis by Brown (2015). When
data from studies of non-specific challenge were combined with data
from studies of allergen challenge, Brown (2015) reported that the
majority of study participants experienced increased AR following
resting exposures from 100 to 200 ppb, 200 to 300 ppb, and above 300
ppb (Table 5 in Brown, 2015). Thus, based on the larger body of
information available, including information from studies that
evaluated AR following allergen challenge, NO2 exposures at
and above 100 ppb have the potential to increase AR in people with
asthma.
    Some comments additionally point out the inconsistent results
reported in controlled human exposure studies conducted in people who
are exercising, claiming that such inconsistency calls into question
the plausibility of a causal association between NO2 and
increased AR. With regard to these comments, the EPA agrees that
individual studies conducted with exercise have not consistently
reported NO2-induced increases in AR. However, the EPA does
not agree with commenters' conclusion that these inconsistencies call
into question the causal association between NO2 and
increased AR.
    As noted above, the 2016 NOX ISA has extensively
considered all available studies that have evaluated the potential for
NO2 to increase AR in people with asthma. This includes
studies conducted with participants at rest as well as studies with
participants engaged in exercise (U.S. EPA, 2016a, section 5.2). As
discussed in the ISA (U.S. EPA, 2016a, p. 5-23), the presence of a
response in study participants at rest, but not while engaged in
exercise, is not enough, in itself, to dismiss the causal association
between NO2 and airway responsiveness. This issue is
discussed in detail in the Brown (2015) meta-analysis, and in other
publications on NO2 by Folinsbee (1992) and Bylin (1993),
which were considered in the ISA. As discussed in those publications,
the act of exercising may create a refractory period which may lead to
diminished airway responsiveness to a challenge. Therefore, observing a
response in participants at rest, but not exercising, does not indicate
that there is no causal relationship between NO2 exposures
and increased airway responsiveness. The CASAC was aware of this
difference in results across study protocols, but still agreed with
EPA's determination that there was a causal relationship between
NO2 exposures and increased airway responsiveness,
concluding that the Brown (2015) meta-analysis ``provides confirmation
of causality for short-term effects'' (Diez Roux and Frey, 2015a, p.
6).
    Some comments supporting the consideration of less stringent
standards additionally focus on the epidemiologic evidence.
Specifically, some industry groups comment that the EPA overstates the
consistency of the epidemiologic evidence, particularly given the
potential for co-pollutant confounding and exposure measurement error
in studies of long-term NO2 exposures, and given the results
of a U.S. multicity study that reported no association between short-
term NO2 exposures and ED visits (Stieb et al., 2009).
    As discussed in greater detail above (Section II.B.3.a), we do not
agree with comments criticizing the 2016 NOX ISA's
assessment of the epidemiologic evidence, including comments
criticizing the ISA's characterization of the consistency of results
across studies or comments criticizing the assessment

of uncertainties in those studies. Contrary to these comments, the ISA
thoroughly considers uncertainties and limitations in the evidence,
including the potential for co-pollutant confounding and exposure
measurement error in epidemiologic studies (see e.g., U.S. EPA, 2016a,
sections <IP_ADDRESS> and <IP_ADDRESS>). The PA additionally considers such
uncertainties, and their implications for conclusions on the degree of
public health protection provided by the current primary NO2
standards (U.S. EPA, 2017a, sections <IP_ADDRESS>, <IP_ADDRESS>, 5.4).
    With regard to comments on the study by Stieb et al. (2009) in
particular, commenters correctly point out that this study reported no
association between short-term NO2 and ED visits. This lack
of a positive association was discussed in the 2016 NOX ISA
(U.S. EPA, 2016a, p. 5-84). However, the ISA's conclusion regarding the
overall consistency of the broader body of available epidemiologic
studies is based on the generally positive health effect associations
reported in studies conducted across the U.S., Canada, Europe, and Asia
(e.g., U.S. EPA, 2016a, Figure 5-7). The relatively small number of
studies in this group that did not report such positive associations,
including the study by Stieb et al. (2009), were appropriately
considered in reaching this broader ISA conclusion and do not call it
into question. The lack of a positive association in the study by Stieb
et al. (2009) was also specifically discussed in the PA (U.S. EPA,
2017a, p. 5-8), which noted that ``the only recent multicity study
evaluated (Stieb et al., 2009) . . . did not report a positive
association between NO2 and ED visits'' (U.S. EPA, 2017a, p.
5-8). This observation, together with information from other key
epidemiologic studies conducted in the U.S. or Canada,\111\ informed
the PA's conclusion that ``available U.S. and Canadian epidemiologic
studies of hospital admissions and ED visits do not indicate the
occurrence of NO2-associated effects in locations and time
periods with NO2 concentrations that would clearly have met
the current 1-hour NO2 standard'' (U.S. EPA, 2017a, p. 5-9).
Thus, the lack of a positive association with ED visits in the study by
Stieb et al. (2009) was discussed in the ISA and informed the PA's
conclusions on the adequacy of the public health protection provided by
the current primary NO2 NAAQS. Accordingly, we disagree with
the comments arguing, based on Stieb et al. (2009) or on uncertainties
and limitations in the epidemiologic evidence, as described more fully
above (II.B.3.a), that EPA has overstated the consistency of the
epidemiologic evidence.
---------------------------------------------------------------------------

    \111\ In considering the public health protection provided by
the current standards, the PA focused on key studies assessed in the
ISA that were conducted in the U.S. or Canada. Such studies are
likely to reflect air quality and exposure patterns that are
generally more applicable to the U.S. In addition, air quality data
corresponding to study locations and study time periods is often
readily available for studies conducted in the U.S. and Canada (U.S.
EPA, 2017a, p. 3-20).
---------------------------------------------------------------------------

    Some comments additionally note that current ambient NO2
concentrations are low, particularly compared to concentrations that
would be of concern based on the health evidence, and are showing a
downward trend. These comments contend that current monitoring,
including available near-road monitoring, shows that NO2
concentrations remain well below the levels of current standards,
calling into question the EPA's analysis comparing NO2 air
quality with health-based benchmarks and its resulting impact on the
Administrator's determinations in the proposed decision. They further
assert that the lack of real-world exposures above benchmarks, together
with the downward trend in NO2 concentrations, contradicts
EPA's rationale that the level of the current NAAQS must be maintained
to protect against exposures at 100 ppb or 250 ppb. Based on current
ambient NO2 concentrations, these commenters argue that the
EPA should consider how the monitoring data, including from near-road
monitors, impacts its assessment of exposures and should also examine
whether alternative, less stringent standards are appropriate.
    Insofar as these comments are premised on the notion that exposure-
and risk-related considerations in the NAAQS reviews should rely only
on actual air quality, we disagree. We recognize that available
monitoring data indicates that recent ambient NO2
concentrations are below the NO2 exposure concentrations
shown in controlled human exposure studies to increase AR. For example,
the PA notes that analyses based on recent NO2 air quality
``estimate almost no potential for 1-hour exposures to NO2
concentrations at or above benchmarks, even at the lowest benchmark
examined (i.e., 100 ppb)'' (U.S. EPA, 2017a, p. 4-19). However, the
observation that recent NO2 air quality concentrations,
including from the near-road monitors, are lower than the exposure
concentrations shown to cause effects does not, in and of itself,
answer the question whether the current standards are more protective
than necessary or whether the EPA should consider less stringent
standards. Rather, it is important to consider the potential
NO2 exposures that would be permissible under the current
standards to inform these questions.
    In order to accomplish this, the PA further considers the potential
for exposures to NO2 concentrations at or above health-based
benchmarks based on analyses where air quality has been adjusted
upwards to simulate areas that would ``just meet'' the current primary
NO2 NAAQS. These analyses provide information on the public
health protection associated with allowable NO2 air quality
under the current standards and, therefore, are clearly useful for
informing a decision on the issue before the EPA. See American
Petroleum Institute v. EPA, 684 F.3d at 1353 (upholding EPA's approach
``comparing the benefits of the one-hour standard against not only a
scenario based upon existing air quality but also upon an alternate
scenario in which areas just meet the [existing standard].''); American
Trucking Associations v. EPA, 283 F.3d 355, 370-71 (D.C. Cir. 2002)
(existence of evidence showing adverse effects occurring at levels
allowed by the current standards justifies finding that it is
appropriate to revise the existing NAAQS). This is a reasonable
approach to informing judgments regarding the current standards, and it
is consistent with section 109 of the CAA, which requires the EPA to
review whether the current primary standards--not current air quality--
are requisite to protect public health with an adequate margin of
safety. CAA section 109(b)(1) and 109(d)(1); see also NEDA/CAP v. EPA,
686 F.3d 803, 813 (D.C. Cir. 2012) (rejecting the notion that it would
be inappropriate for EPA to revise a NAAQS if current air quality does
not warrant revision, stating ``[n]othing in the CAA requires EPA to
give the current air quality such a controlling role in setting
NAAQS''). Furthermore, although NO2 air quality has been
improving and is expected to continue improving, there are inherent
uncertainties in predicting future air quality. Accordingly, it is
reasonable to consider the NO2 exposures that could occur
under a pattern of air quality that just meets the current standards.
API v. EPA, 684 F.3d at 1352.
    In addition, the CASAC agreed with considering analyses based on
adjusted air quality, stating that ``[t]he EPA has made a reasonable
choice in looking both at the number of [benchmark] exceedances of the
unadjusted data as well as the level of exceedance of the

adjusted data'' (Diez Roux and Sheppard, 2017, p. 5). Therefore, for
all of the reasons described above, relatively low recent ambient
NO2 concentrations, including those at near-road monitors,
do not call into question analyses comparing NO2 air quality
to health-based benchmarks or the role those analyses play in the
Administrator's decision to retain the existing standards.
c. Comments Supporting More Stringent Standards
    One commenter argues that the current NAAQS do not protect public
health with an adequate margin of safety, and that the standards should
be revised to be more stringent. Specifically, these comments recommend
that the level of the 1-hour NO2 standard be set at 50 ppb,
with a 99th percentile form, and that the level of the annual standard
should be set at 30 ppb. These comments, and the EPA's responses, are
discussed below. \112\
---------------------------------------------------------------------------

    \112\ These comments also refer, for the full discussion, to an
attached comment letter submitted during the 2010 review of the
primary NO2 NAAQS. This reference suggests that the
commenter believed the comments submitted as part of the 2010 review
are still relevant in the current review, given that the 2016
NOX ISA focused much of its assessment on studies that
were also included in the 2008 NOX ISA. We note that, to
the extent a separate response to those comments is required, we
have already responded to the prior comments in the 2010 final
decision on the primary NO2 NAAQS (75 FR 6474, February
9, 2010; U.S. EPA, 2010).
---------------------------------------------------------------------------

    Comments asserting that the current 1-hour standard does not
protect public health or provide any margin of safety cite the meta-
analysis by Brown (2015) to support this position, arguing that this
meta-analysis clearly shows that the majority of individuals with
asthma were adversely affected by a concentration of NO2
that would meet the current 1-hour standard. To support this point,
these comments state that Brown (2015) reported increased AR following
1-hour exposures to 100 ppb NO2, and they point to several
uncertainties in the individual studies (i.e., that no studies examined
1-hour concentrations below 100 ppb, that study subjects generally had
mild asthma rather than more severe cases of disease, and that the
studies do not provide information about potential effects of such
exposures on children and seniors, two groups EPA recognizes as being
particularly at risk). These comments disagree with the weight that EPA
placed on the lack of consistency in the individual controlled human
exposures studies at lower concentrations, contending that the Brown
meta-analysis has greater statistical power than the individual
studies. These comments further disagree with EPA's citation of
uncertainties related to lack of exposures below 100 ppb as a rationale
for retaining the current level of the 1-hour standard, contending that
the CAA's requirement for an adequate margin of safety is intended to
protect the population when information is limited.
    As discussed above (Sections II.A.2, II.B.1), while the Brown meta-
analysis shows that most study participants (i.e., generally adults
with mild asthma) experienced increased AR following resting
NO2 exposures from 100 to 530 ppb,\113\ there are important
limitations in the underlying studies, particularly in studies that
evaluated NO2 exposure concentrations at or near 100 ppb. Of
the five studies included in the meta-analysis that evaluated resting
exposures to 100 ppb NO2, a statistically significant
increase in AR following exposure to NO2 was only observed
in one (U.S. EPA, 2017a, section <IP_ADDRESS>). Of the four studies that did
not report statistically significant increases in AR following
exposures to 100 ppb NO2, three reported trends towards
decreased AR (U.S. EPA, 2017a, section <IP_ADDRESS>). Thus, individual
controlled human exposure studies have generally not reported
statistically significant increases in AR following resting exposures
to NO2 concentrations at 100 ppb (U.S. EPA, 2017a, section
<IP_ADDRESS>), indicating a greater uncertainty in the risk of such effects
at 100 ppb.\114\ When considering this general lack of consistent,
statistically significant results across these five individual studies,
limitations in the broader body of evidence from controlled human
exposure studies (i.e., uncertainty in adversity of reported responses
and the lack of an apparent dose-response relationship), which are
discussed above and have been considered throughout this review (e.g.,
U.S. EPA, 2017a, section <IP_ADDRESS>), take on increased importance when
considering the risk of adverse effects and the potential public health
implications of exposures to 100 ppb NO2.
---------------------------------------------------------------------------

    \113\ As discussed above, the most consistent evidence for
NO2-induced increases in AR comes from studies of resting
exposures.
    \114\ In addition, studies that evaluated resting exposures to
140 ppb and 200 ppb NO2 did not generally report
statistically significant increases in AR. Thus, individual
controlled human exposure studies have generally not reported
statistically significant increases in AR following resting
exposures to NO2 concentrations from 100 to 200 ppb,
though this evidence suggests a trend toward increased AR following
NO2 exposures from 140 to 200 ppb (U.S. EPA, 2017a,
section <IP_ADDRESS>).
---------------------------------------------------------------------------

    In light of the above information from the Brown (2015) meta-
analysis and from the individual studies included in that meta-
analysis, the Administrator's judgment in the proposal was that while
it is appropriate to consider the degree of protection provided by the
current 1-hour standard against exposures to NO2
concentrations as low as 100 ppb,\115\ emphasis should be placed on
protecting against the potential for exposures to higher NO2
concentrations, where individual studies generally report statistically
significant increases in AR (i.e., at or above 250 ppb, as discussed in
U.S. EPA, 2017a, section <IP_ADDRESS>). The more consistent results across
studies at such higher exposure concentrations indicate greater concern
for the risk of an NO2-induced effect.
---------------------------------------------------------------------------

    \115\ Uncertainties in this evidence are of even greater concern
for NO2 exposure concentrations below 100 ppb, for which
there are no data available in these studies. On this point, the
CASAC noted that ``the lack of a clear dose-response model based on
available data is another source of uncertainty that makes it
difficult to extrapolate a dose-response relationship at levels
lower than those measured in the controlled human studies.'' (Diez
Roux and Sheppard, 2017, pp. 7-8).
---------------------------------------------------------------------------

    To this end, based on the results of the NO2-air quality
benchmark comparisons reported in the PA (U.S. EPA, 2017a, section
4.2.1), the current 1-hour standard is estimated to allow virtually no
potential for 1-hour exposures to NO2 concentrations at or
above 200 ppb, even under worst-case conditions across a variety of
study areas with among the highest NOX emissions in the
United States. Such NO2 concentrations were not estimated to
occur, even at monitoring sites adjacent to some of the most heavily
trafficked roadways. In addition, the current 1-hour standard limits,
but does not eliminate, 1-hour exposures to NO2
concentrations at or above 100 ppb (U.S. EPA, 2017a, section 4.2.1), an
exposure concentration where uncertainties in the evidence take on
increased importance. Despite the importance of uncertainties in the
evidence for increased AR following exposures to NO2
concentrations at or near 100 ppb, as summarized above, a focus on
limiting such exposures gives weight to the results of Brown (2015) at
100 ppb and to the possibility that other at-risk groups (e.g., people
with more severe asthma, children, older adults) could experience more
serious effects than reported in available studies. As such, the
current 1-hour standard provides a margin of safety by virtually
eliminating the potential for 1-hour exposures to NO2
concentrations that have been consistently shown to increase AR in
people with asthma and by limiting exposures to NO2
concentrations that have the potential to exacerbate asthma

symptoms, but for which the evidence indicates greater uncertainty in
the risk of such effects.
    While the EPA recognizes, as discussed in section I.A. above, that
CAA section 109's requirement for a primary NAAQS to provide an
adequate margin of safety is intended to address uncertainties
associated with inconclusive scientific and technical information, it
also notes that the CAA does not require a primary NAAQS to be
established at a zero-risk level, or to protect the most sensitive
individual, but rather at a level that avoids unacceptable risks to
public health. See Lead Industries Association v. EPA, 647 F.2d at
1154, 1156 n.51. This approach to considering the degree of protection
provided by the current NAAQS is consistent with the governing case
law. The EPA further notes that under CAA section 109, a primary
standard must be ``requisite''--i.e., neither more nor less stringent
than necessary--to protect public health with an adequate margin of
safety. See Whitman v. American Trucking Associations, 531 U.S. at 465-
472, 475-76. Additionally, the selection of any particular approach to
providing an adequate margin of safety is a policy choice left to the
Administrator's judgment. See Lead Industries Association v. EPA, 647
F.2d at 1161-62. As discussed above, the EPA's approach to the margin
of safety in this review reasonably considers both the potential for
adverse public health effects following exposures to 100 ppb
NO2 and the uncertainties in the public health implications
of such exposures. Thus, the EPA's approach here comports with CAA
section 109 and the case law described in section I.A above.
    The EPA's approach to considering the degree of protection provided
by the current NO2 NAAQS is also consistent with advice from
the CASAC, which recognized that ``there is uncertainty regarding the
severity of adverse effects at a level of 100 ppb NO2, and
thus some potential for maximum daily levels to exceed this benchmark
with limited frequency may nonetheless be protective of public health''
(Diez Roux and Sheppard, 2017, p. 10). The CASAC additionally concluded
that ``there is not a scientific basis for a standard lower than the
current 1-hour standard'' (Diez Roux and Sheppard, 2017 p. 9). Thus,
for the reasons discussed above, the EPA disagrees with comments
claiming that the Brown (2015) meta-analysis indicates adverse effects
at NO2 concentrations meeting the current 1-hour standard
and with comments claiming that the Brown (2015) meta-analysis shows
that the 1-hour standard provides no margin of safety.
    Comments advocating for a more stringent 1-hour standard further
state that the current 98th percentile form allows too many days with
NO2 concentrations above 100 ppb, undermining protection for
people with asthma, including children. These comments contend that the
EPA's rationale that the 98th percentile provides more stability than
the 99th percentile has no substantive evidence behind it.
    In reviewing the NAAQS, the Administrator's foremost consideration
is the adequacy of the public health protection provided by the
combination of all of the elements of the standard, including the form.
In particular, the EPA notes that the benchmark analysis presented in
the PA, which informed the Administrator's proposed decision, evaluates
the potential for NO2 exposures with air quality just
meeting the current 1-hour standard, including the 98th percentile
form, and that analysis found that there were no exceedances of 200
ppb, and very few exceedances of 100 ppb (1 to 10 annually, on
average). Thus, as described in more detail above, even under worst-
case conditions across a variety of study areas with among the highest
NOX emissions in the U.S., the current 1-hour standard, with
its 98th percentile form, virtually eliminates the potential for
exposures to the NO2 concentrations that have been shown
most consistently to increase AR in people with asthma and to which the
Administrator gives most weight, and greatly limits the potential for
exposures to lower NO2 concentrations with the potential to
exacerbate symptoms in some people with asthma, but for which
uncertainties in the evidence take on increased importance.
    In addition, the CASAC advice provides further support for the 98th
percentile form. The CASAC accepted the protection provided by the
current 98th percentile form, together with the other elements of the
1-hour standard, in recommending retention of the current standard
without revision. In doing so, it provided the following advice (Diez
Roux and Sheppard, 2017, p. 9):

    For the 1-hour current standard, the form is based on the 98th
percentile of daily maximum 1-hour concentrations, which corresponds
to the 7th or 8th highest daily maximum 1-hour concentration in a
year. This form limits but does not eliminate exposures at or above
100 ppb NO2. A scientific rationale for this form is
there is uncertainty regarding the severity of adverse effects at a
level of 100 ppb NO2, and thus some potential for maximum
daily levels to exceed this benchmark with limited frequency may
nonetheless be protective of public health.

    Thus, in providing its advice to retain the existing 1-hour
standard, without revision, the CASAC clearly considered the
implications of the 98th percentile form of that standard.
    With regard to stability, the proposal explained that greater
regulatory stability was one consideration supporting the selection of
a 98th percentile form in the last review. In that review, the EPA
established the 98th percentile form, noting ``the limited available
information on the variability in peak NO2 concentrations
near important sources of NO2 such as major roadways'' and
``the recommendation from the CASAC that the potential for instability
in the 99th percentile concentration is cause for supporting a 98th
percentile form'' (75 FR 6493, February 9, 2010).\116\ However, in the
proposal and in this final action, the Administrator's judgments focus
primarily on his consideration of the public health protection provided
by the current standards: A 1-hour standard with a level of 100 ppb and
a 98th percentile form, and an annual average standard with a level of
53 ppb. The degree of public health protection provided by the current
standards is a function of the combination of all elements of these
standards (i.e., indicator, averaging times, forms, levels). Thus,
while judgments on stability can be a legitimate consideration, his
decision to retain the current primary NO2 NAAQS in this
review (see below) reflects his judgments regarding public health
protection provided by these standards. Given this, the EPA disagrees
with comments contending that the form of the 1-hour standard should be
revised to the 99th percentile.\117\
---------------------------------------------------------------------------

    \116\ As noted in the last review, a less stable form could
result in more frequent year-to-year shifts between meeting and
violating the standard, potentially disrupting ongoing air quality
planning without achieving public health goals (75 FR 6493, February
9, 2010).
    \117\ These comments also note that EPA established a 99th
percentile form when it revised the SO2 primary NAAQS in
2010. The fact that EPA concluded that the 99th percentile was
appropriate for one NAAQS, based on the combined elements of that
revised standard and the evidence and information in the supporting
record, does not mean that such a form should be used for a
different NAAQS for a different pollutant. Rather, in reviewing each
NAAQS, EPA makes a determination specific to the pollutant and
standard in question, in the course of which it evaluates the public
health protection it provides based on the combination of all the
elements of the standard and based on the evidence and information
in the record for that review.
---------------------------------------------------------------------------

    Comments advocating for more stringent standards also assert that
the EPA should adopt an annual standard

level of 30 ppb. These comments note the strengthened evidence linking
long-term NO2 exposures with various health effects,
particularly asthma development, arguing that it expands the range of
potential effects and at-risk populations. They further note the
recognition by the EPA and the CASAC, based on its review of analyses
in the PA, that the current 1-hour standard and annual standard
together are estimated to maintain annual NO2 concentrations
well below 53 ppb. These comments assert that both the EPA and the
CASAC recognized that the annual standard was not sufficiently
protective and, based on the degree of control associated with the 1-
hour standard, in effect used 30 ppb as the effective standard for
annual exposure. These comments thus conclude that EPA should lower the
level of the annual standard level to 30 ppb.
    We agree with comments that the evidence supporting associations
between long-term NO2 exposures and a variety of effects,
particularly the development of asthma in children, has become stronger
in this review.\118\ While this evidence supports associations with a
clearly adverse health outcome, given uncertainties in key studies and
the protection provided by the 1-hour standard against long-term
NO2 exposures, we disagree with comments that this
strengthened evidence supports a revised annual standard with a level
of 30 ppb. Our consideration of these factors is described below.
---------------------------------------------------------------------------

    \118\ The ISA additionally concludes that, compared to the last
review, stronger evidence is available in this review linking
various non-respiratory effects with long-term NO2
exposures (see, e.g., U.S. EPA, 2016a, section 1.5.2). These include
cardiovascular effects and diabetes, mortality, birth outcomes, and
cancer. However, compared to the evidence linking NO2
exposures with the development of asthma, there is greater
uncertainty in the evidence for these non-respiratory effects.
Therefore, in considering the public health protection provided by
the current standards, the focus in this review is on respiratory
effects (e.g., see U.S. EPA, 2017a, section 5.1). More specifically,
as noted in the PA ``we consider the full body of health evidence,
placing the greatest emphasis on the effects for which the evidence
has been judged in the ISA to demonstrate a `causal' or a `likely to
be a causal' relationship with NO2 exposures [i.e.,
respiratory effects]'' (U.S. EPA, 2017a, p. 3-2).
---------------------------------------------------------------------------

    As discussed in the proposal (82 FR 34792, July 26, 2017, section
II.F.4), and in the Administrator's final decision below, uncertainties
in studies of long-term NO2 exposures, and in the
NO2 air quality present in the locations of those studies,
limit their utility in identifying a specific revised annual standard
that would provide the requisite protection. Important uncertainties in
key U.S. and Canadian epidemiologic studies of long-term NO2
exposures include the potential for confounding by highly correlated
co-occurring pollutants and for exposure measurement error (see, e.g.,
sections II.A.2, II.B.1, II.B.4 of this document).
    With regard to potential confounding by co-occurring pollutants,
the 2016 NOX ISA concludes that ``[e]pidemiologic studies of
asthma development in children have not clearly characterized potential
confounding by PM2.5 or traffic-related pollutants [e.g.,
CO, BC/EC, volatile organic compounds (VOCs)]'' (U.S. EPA, 2016a, p. 6-
64). The 2016 NOX ISA further notes that ``[i]n the
longitudinal studies, correlations with PM2.5 and BC were
often high (e.g., r = 0.7-0.96), and no studies of asthma incidence
evaluated copollutant models to address copollutant confounding, making
it difficult to evaluate the independent effect of NO2''
(U.S. EPA, 2016a, p. 6-64).
    With regard to exposure measurement error, while some studies used
well-validated estimates of NO2 exposure (U.S. EPA, 2016a,
section <IP_ADDRESS>), most of the key epidemiologic studies conducted in
the U.S. or Canada, which are the studies relevant for informing
decisions on the standard, employed exposure models ``with unknown
validation'' or used ``central-site measurements that have well-
recognized limitations in reflecting variability in ambient
NO2 concentrations in a community and may not well represent
variability in NO2 exposure among subjects'' (U.S. EPA,
2017a, p. 3-35). Thus, it is unclear the extent to which most of the
key studies conducted in the U.S. or Canada provide reliable estimates
of asthma incidence for particular NO2 concentrations that
could be used in identifying a specific revised annual standard that
would provide the requisite protection.
    In addition, as discussed in detail in the PA, while epidemiologic
studies conducted in the U.S. or Canada provide evidence for
associations with asthma-related effects in locations likely to have
violated the current standards, they do not indicate associations of
asthma incidence with exposures to long-term NO2 in
locations that would have clearly met the current standards (U.S. EPA,
2017a, section 5.1). This is particularly the case given that
NO2 concentrations near the most heavily trafficked roadways
are not likely reflected by monitors in operation during study years.
Had such monitors been in place, NO2 design values in these
study areas may have been higher than indicated by the monitors that
were in operation during study periods.
    Thus, uncertainties in studies of long-term NO2
exposures, together with uncertainties in the NO2 air
quality present in the study locations, limit the degree to which these
studies can inform the identification of a specific revised annual
standard that would provide the requisite protection. Taken together,
these uncertainties limit what studies of long-term NO2 and
asthma development can tell us with regard to the adequacy of the
public health protection provided by the current NO2
standards.
    Beyond the uncertainties discussed above, the EPA further
recognizes that, as noted in comments, the current 1-hour standard is
expected to provide substantial protection against long-term
NO2 exposures. Support for considering protection provided
by the 1-hour standard against long-term NO2 exposures comes
from the ISA's integrated mode of action information describing the
biological plausibility for development of asthma. In particular, the
ISA states that ``findings for short-term NO2 exposure
support an effect on asthma development by describing a potential role
for repeated exposures to lead to recurrent inflammation and allergic
responses,'' which are ``identified as key early events in the proposed
mode of action for asthma development'' (U.S. EPA, 2016a, pp. 6-66 and
6-64).\119\ Given this, we note that meeting the 1-hour standard with
its level of 100 ppb is expected to maintain annual average
NO2 concentrations well below the 53 ppb level of the
current annual standard. With regard to this protection, the CASAC
notes that the PA's analyses of historical data indicate that
``attainment of the 1-hour standard corresponds with annual design
value averages of 30 ppb NO2'' (Diez Roux and Sheppard,
2017). While the CASAC did not endorse the degree of public health
protection provided by the annual standard alone (Diez Roux and
Sheppard, 2017, p. 9), based on these air quality relationships it
concluded that ``it is the suite of the current 1-hour and annual
standards, together, that provide protection against adverse effects''
(Diez Roux and Sheppard, 2017, p. 9). Thus, to the degree the evidence
supports additional protection against long-term NO2

exposures, beyond that provided by the current annual standard alone,
the 1-hour standard is expected to result in substantial additional
protection against such exposures.
---------------------------------------------------------------------------

    \119\ The ISA additionally recognizes that because the
experimental evidence is limited, there remains some uncertainty as
to whether long-term NO2 exposures have an independent
effect on asthma development or whether these health effects are due
to repeated short-term exposures, or a mixture of long-term and
short-term exposures (see U.S. EPA, 2016a, p. 6-67).
---------------------------------------------------------------------------

    Based on the above information, when taken together, the EPA
disagrees with comments that the level of the annual standard should be
revised to 30 ppb. In particular, based on the uncertainties in the
available key studies of NO2 and asthma incidence conducted
in the U.S. or Canada, uncertainty in the NO2 concentrations
present in locations of these key studies, and the substantial
protection against long-term NO2 exposures that is provided
by the current 1-hour standard, we conclude that the evidence does not
support a revised annual standard with a level of 30 ppb.
d. Other Comments
    In addition to the comments presented above, the EPA received
several comments related to implementation of the NO2 NAAQS,
including various comments on AERMOD and its use in permitting, as well
as on the historical difficulty of facilities demonstrating compliance
with the 1-hour NO2 standard in permitting. As described in
section I.A above, this action is being taken pursuant to CAA section
109(d)(1) and relevant case law. Consistent with this case law, the EPA
has not considered costs, including the costs or economic impacts
related to permitting or other implementation concerns, in this action.
Under CAA section 109(d)(1) the EPA has the obligation to periodically
review the air quality criteria and the existing primary NAAQS and make
such revisions as may be appropriate. Thus, the scope of this action is
to evaluate whether the existing NO2 primary standards are
requisite to protect public health with an adequate margin of safety,
not to address concerns related to implementation of the existing
standards. State and federal NO2 control programs such as
those discussed in section I.B may provide an opportunity for
permitting and other implementation concerns to be addressed.
4. Administrator's Conclusions
    Having carefully considered the public comments, as discussed
above, and taking into consideration the large body of evidence
concerning NO2-related health effects and available
estimates of the potential for NO2 exposures, including the
uncertainties and limitations inherent in the evidence and those
estimates, the Administrator concludes that the current primary
NO2 standards are requisite to protect the public health,
with an adequate margin of safety, and should be retained. The
Administrator's conclusions are based on a careful consideration of the
full body of information available in this review, giving weight to the
assessment of the available policy-relevant scientific evidence and the
conclusions contained in the 2016 NOX ISA; the PA's
consideration of this evidence and of analyses comparing NO2
air quality with health-based benchmarks; the PA's conclusions
regarding the public health protection provided by the current primary
NO2 NAAQS and the rationale supporting those conclusions;
the advice and recommendations from the CASAC; the scientific and
policy judgments and conclusions discussed in the proposal; and public
comments on the proposed action. The basis for the Administrator's
conclusions on the current primary NO2 standards is
discussed further below.
    As an initial matter, the Administrator takes note of the well-
established body of scientific evidence supporting the occurrence of
respiratory effects following NO2 exposures, as described in
detail in the 2016 NOX ISA (U.S. EPA, 2016a, chapter 5 and
chapter 6) and summarized in the PA (U.S. EPA, 2017a, chapter 3). As in
the last review, the clearest evidence indicates the occurrence of
respiratory effects following short-term NO2 exposures. The
strongest support for this relationship comes from controlled human
exposure studies demonstrating NO2-induced increases in AR
in individuals with asthma. As discussed above (section II.A.2), the
Administrator notes that most of the controlled human exposure studies
assessed in the 2016 NOX ISA were available in the last
review, with the addition in this review of an updated meta-analysis
that synthesizes data from these studies. He also notes that these
studies provided an important part of the body of evidence supporting
the decision in the last review to establish the 1-hour NO2
standard with its level of 100 ppb. Beyond the controlled human
exposure studies, additional supporting evidence comes from
epidemiologic studies reporting associations between short-term
NO2 exposures and a range of asthma-related respiratory
effects, including effects serious enough to result in emergency room
visits or hospital admissions. While there is some new evidence in the
current review from such epidemiologic studies, the results of these
newer studies are generally consistent with the epidemiologic studies
that were available in the last review.
    With regard to respiratory effects of long-term NO2
exposures, the Administrator notes that the evidence supporting
associations with asthma development in children has become stronger
since the last review, though uncertainties remain regarding the degree
to which estimates of long-term NO2 concentrations in these
studies are serving as surrogates for exposures to the broader mixture
of traffic-related pollutants (U.S. EPA, 2016a, table 1-1 and section
6.2.2). Supporting evidence also includes studies indicating a
potential role for repeated short-term NO2 exposures in the
development of asthma (U.S. EPA, 2016a, pp. 6-64 and 6-65).
    In addition, the Administrator acknowledges that the evidence for
some non-respiratory effects has strengthened since the last review. In
particular, based on the assessment of the evidence in the 2016
NOX ISA, he notes the stronger evidence for NO2-
associated cardiovascular effects (short- and long-term exposures),
premature mortality (long-term exposures), and certain reproductive
effects (long-term exposures) (U.S. EPA, 2016a, table 1-1). As detailed
in the 2016 NOX ISA, while this evidence has generally
become stronger since the last review, it remains subject to greater
uncertainty than the evidence of asthma-related respiratory effects
(U.S. EPA, 2016a, table 1-1 and section 6.2.2). Thus, as described
above (section II.B.1), and consistent with CASAC advice (Diez Roux and
Sheppard, 2017), the Administrator places the greatest emphasis on the
evidence for respiratory effects attributable to either short- or long-
term NO2 exposures, which the ISA has determined
demonstrates a ``causal'' and a ``likely to be causal'' relationship
with NO2 exposures, respectively.
    The Administrator's evaluation of the public health protection
provided against ambient NO2 exposures also involves
consideration of populations and lifestages that may be at greater risk
of experiencing NO2-attributable health effects. In the
current review, the Administrator's consideration of potential at-risk
populations draws from the 2016 NOX ISA's assessment of the
evidence (U.S. EPA, 2016a, Chapter 7). Based on the ISA's systematic
approach to evaluating factors that may increase risks in a particular
population or during a particular lifestage, the Administrator places
greatest weight on the potential effects of NO2 exposures in
people with asthma, children, and older adults (U.S. EPA, 2016a, Table
7-27). Support for potentially higher risks in these populations is
based primarily on evidence for asthma exacerbation or

asthma development. Evidence for other health effects is subject to
greater uncertainty (U.S. EPA, 2017a, Section 3.4).
    The Administrator further uses the scientific evidence outlined
above, and described in detail in the 2016 NOX ISA, to
directly inform his consideration of the adequacy of the public health
protection provided by the current primary NO2 standards.
Adopting the approach taken in the PA, which has been reviewed by the
CASAC (Diez Roux and Sheppard, 2017, pp. 6 to 9), the Administrator
specifically considers the evidence within the context of the degree of
public health protection provided by the current 1-hour and annual
standards together, including the combination of all elements of these
standards (i.e., indicator, averaging times, forms, levels).
    In doing so, the Administrator focuses on the results of controlled
human exposure studies of AR in people with asthma and on the results
of U.S. and Canadian epidemiologic studies of asthma-related hospital
admissions, asthma-related ED visits, and asthma development in
children. He particularly emphasizes the results of controlled human
exposure studies, which were identified in the 2016 NOX ISA
as providing ``[t]he key evidence that NO2 exposure can
independently exacerbate asthma'' (U.S. EPA, 2016a, p. 1-18). The
Administrator's decision to focus on these studies is in agreement with
the CASAC, which advised that, of the evidence for asthma exacerbation,
``[t]he strongest evidence is for an increase in AR based on controlled
human exposure studies, with supporting evidence from epidemiologic
studies'' (Diez Roux and Sheppard, 2017, p. 7).
    In considering the controlled human exposure studies of AR, the
Administrator focuses both on the results of an updated meta-analysis
of data from these studies (Brown, 2015) and on the consistency of
findings across individual studies. As discussed in sections II.A.2 and
II.B.1 above, and consistent with the evidence in the last review, the
Brown (2015) meta-analysis indicates that statistically significant
majorities of study volunteers, generally with mild asthma, experienced
increased AR following 30-minute to 1-hour resting exposures to
NO2 concentrations from 100 to 530 ppb. In some affected
individuals, the magnitudes of these increases were large enough to
have potential clinical relevance (sections II.A.2.a.i and II.B.3,
above).\120\ Based on these results, the Administrator notes the
potential for people with asthma to experience NO2-induced
respiratory effects following exposures in this range, and that people
with more severe asthma could experience more serious effects. The
Administrator further notes that individual studies consistently report
statistically significant increases in AR following exposures to
NO2 concentrations at or above 250 ppb, with less consistent
results across studies conducted at lower exposure concentrations,
particularly 100 ppb (section II.A.2.a).\121\
---------------------------------------------------------------------------

    \120\ As discussed in section II.A.2.a.i of this final action,
the consideration of clinical relevance by Brown (2015) is based on
the fraction of exposed individuals who experienced a halving of the
PD of challenge agent following NO2 exposures. This
magnitude of change has been recognized by the ATS and the ERS as a
``potential indicator, although not a validated estimate, of
clinically relevant changes in [AR]'' (Reddel et al., 2009) (U.S.
EPA, 2016a, p. 5-12). Although there is uncertainty in using this
approach to characterize whether a particular response in an
individual is ``adverse,'' it can provide insight into the potential
for adversity, particularly when applied to a population of exposed
individuals.
    \121\ In addition, studies that evaluated resting exposures to
140 ppb and 200 ppb NO2 did not report statistically
significant increases in AR, though group mean responses in these
studies suggest a trend towards such an increase.
---------------------------------------------------------------------------

    Uncertainties in this evidence, discussed in sections II.A.2.a,
II.A.3, and II.B.1 above, include the lack of an apparent dose-response
relationship between NO2 exposures and increased AR, which
limits the degree to which the health risks of these exposures can be
fully characterized, and uncertainty regarding the potential adversity
of the reported responses. These uncertainties take on increased
importance when considering the potential public health implications of
exposures to lower NO2 concentrations (i.e., at and near 100
ppb), where individual studies generally do not report NO2-
induced increases in AR.
    While the Administrator recognizes uncertainty in the extent to
which NO2-induced increases in AR may be adverse, he also
notes the risk that such increases could be adverse for some people
with asthma, particularly those with more severe asthma than have
typically been evaluated in available studies. He further notes that
this risk cannot be fully characterized based on existing studies.
However, given that the majority of people with asthma experienced an
NO2-induced increase in AR in the controlled human exposure
studies included in the Brown (2015) meta-analysis,\122\ and given the
large size of the asthmatic population in the United States, the
Administrator recognizes the potential for effects that are adverse to
public health following the types of NO2 exposures evaluated
in the studies analyzed by Brown (2015). Thus, while the Administrator
is not able to definitively determine whether the increased AR reported
in these studies would be adverse for a given individual, he concludes
that, from a public health perspective, it is appropriate to provide
protection from the risk of adversity associated with such increases.
As noted above, this is especially true for people with more severe
asthma and for other at-risk populations that have generally not been
evaluated in available controlled human exposure studies of
NO2 and AR (i.e., children and older adults).
---------------------------------------------------------------------------

    \122\ As described above (II.A.2, II.B.1, II.B.3), this is the
case for individuals exposed while at rest.
---------------------------------------------------------------------------

    Based on information from controlled human exposure studies, which
is discussed in more detail in sections II.A.2, II.B.1, and II.B.3 of
this final action, the Administrator is most concerned about the
potential for people with asthma to experience adverse respiratory
effects following exposures to NO2 concentrations at or
above 250 ppb. As noted above, 250 ppb is an exposure concentration
where the potential for NO2-induced respiratory effects is
supported both by results of the meta-analysis and by consistent
results reported across individual studies. Therefore, in reaching
decisions on the primary NO2 NAAQS, the Administrator
emphasizes the importance of protecting against such exposures.
    Because results are less consistent across individual studies that
evaluated lower exposure concentrations, the Administrator places
greater weight on the uncertainties in the evidence as he considers the
potential public health implications of such exposures. However, the
Administrator also recognizes the potential for adverse respiratory
effects following exposures to NO2 concentrations as low as
100 ppb, particularly in people with more severe cases of asthma than
have generally been evaluated in the available NO2
controlled human exposure studies. Available studies have generally
evaluated people with mild asthma, while people with moderate or severe
asthma could be more susceptible to NO2-induced increases in
AR, and thus more likely to exhibit adverse responses following
NO2 exposures (Brown, 2015). As discussed above, such
effects have the potential to be adverse to public health, in light of
the large size of the asthmatic population in the United States.
Further, as noted above, the Administrator also recognizes the

potential for such effects in other at-risk populations that have
generally not been evaluated in NO2 controlled human
exposure studies (i.e., children and older adults). Thus, when the
evidence and uncertainties are taken together, the Administrator judges
that, from a public health perspective, while it is appropriate to
emphasize the degree of protection against the potential for exposures
at or above 250 ppb, it is also appropriate to consider the degree of
protection provided against potential exposures to NO2
concentrations as low as 100 ppb.
    In further considering the potential public health implications of
the controlled human exposure studies, the Administrator looks to the
results of quantitative comparisons between NO2 air quality
and health-based benchmarks. As discussed in the PA (U.S. EPA, 2017a,
section 4.2 and section 5.2), these comparisons can help to place the
results of the controlled human exposure studies, which provide the
basis for the benchmark concentrations, into a broader public health
context. In considering the results of the analyses comparing
NO2 air quality to specific health-based benchmarks, the
Administrator first recognizes that all areas of the U.S. presently
meet the current primary NO2 standards. When based on recent
unadjusted NO2 air quality, these analyses estimate almost
no days with the potential for 1-hour exposures to NO2
concentrations at or above health-based benchmarks, including the
lowest benchmark examined (i.e., 100 ppb).
    To inform his consideration of the public health protection
associated with allowable NO2 air quality under the current
standards, the Administrator takes note of the analyses in the PA
examining the potential for exposures to NO2 concentrations
at or above health-based benchmarks when air quality has been adjusted
upwards to simulate areas that would ``just meet'' the current primary
NO2 NAAQS. Drawing on the discussion of these analyses in
the PA (U.S. EPA, 2017a, section 5.2), the Administrator recognizes
that, even when ambient NO2 concentrations are adjusted
upward to just meet the existing 1-hour standard, the analyses estimate
no days with the potential for exposures to the NO2
concentrations that have been shown most consistently to increase AR in
people with asthma (i.e., above 250 ppb \123\). Such NO2
concentrations were not estimated to occur, even under worst-case
conditions across a variety of study areas with among the highest
NOX emissions in the U.S. and at monitoring sites adjacent
to some of the most heavily trafficked roadways in the U.S. In
addition, analyses with adjusted air quality indicate a limited number
of days with the potential for exposures to 1-hour NO2
concentrations at or above 100 ppb (i.e., about one to 10 days per
year, on average) (U.S. EPA, 2017a, section 4.2.1). As discussed above,
100 ppb represents an exposure concentration with the potential to
exacerbate asthma-related respiratory effects in some people, but for
which uncertainties in the evidence take on increased importance.
---------------------------------------------------------------------------

    \123\ As discussed above, analyses in the PA estimate no
occurrences of 1-hour NO2 concentrations at or above 200
ppb.
---------------------------------------------------------------------------

    Based on his consideration of these results, the Administrator
concludes that evidence from controlled human exposure studies,
together with analyses comparing ambient NO2 concentrations
to health-based benchmarks, supports his overall judgment that the
current primary NO2 NAAQS are requisite to protect public
health with an adequate margin of safety. In particular, as discussed
above, he is most concerned about exposures to NO2
concentrations at and above 250 ppb, where the potential for
NO2-induced respiratory effects is supported both by results
of the meta-analysis and by consistent results reported across
individual studies. With regard to this, the Administrator notes that
NO2 air quality that just meets the current standards is
estimated to allow no potential for exposures to such 1-hour
NO2 concentrations. The Administrator also recognizes the
potential for effects that are adverse to public health with exposures
to lower NO2 concentrations, including as low as 100 ppb,
although he places greater weight on the uncertainties in the evidence
at these lower exposure concentrations. In light of these
uncertainties, the Administrator judges it appropriate to limit, but
not to eliminate, the potential for 1-hour exposures to NO2
concentrations as low as 100 ppb. With regard to this, he notes that
the current standard is estimated to restrict the potential for
exposures to 1-hour NO2 concentrations at or above 100 ppb
to a limited number of days per year.
    Thus, given that the current standards are estimated to allow no
exposures to 1-hour NO2 concentrations at or above 250 ppb,
and only limited potential for such exposures to concentrations as low
as 100 ppb, the Administrator concludes that the scientific evidence,
together with the information from analyses comparing NO2
air quality with health-based benchmarks, supports his judgment that
that the current 1-hour and annual NO2 primary standards,
together, are requisite to protect public health with an adequate
margin of safety. In reaching this conclusion, the Administrator finds
that retaining the 1-hour NO2 standard with the level of 100
ppb reflects a cautious approach, which is warranted given the CAA's
requirement to for an adequate margin of safety. However, uncertainties
in the evidence, especially those relating to the adversity of the
effect and its likelihood to occur at exposures at or below 100 ppb,
support the Administrator's conclusion that it is not necessary to
eliminate the potential for exposures to 100 ppb NO2.
    The Administrator also considers what the available epidemiologic
studies indicate with regard to the adequacy of the public health
protection provided by the current NO2 standards, noting
that these studies often examine more serious health effects than the
controlled human exposure studies. In particular, he considers analyses
of NO2 air quality in the locations, and during the time
periods, of available U.S. or Canadian epidemiologic studies of asthma-
related hospital admissions or ED visits. Although the NO2
epidemiologic evidence is subject to greater uncertainty than the
controlled human exposure studies of NO2-induced changes in
AR, as discussed in section II.B.1 above, these analyses can provide
insights into the extent to which NO2-health effect
associations are present for distributions of ambient NO2
concentrations that would be allowed by the current standards. The
presence of such associations would support the potential for the
current standards to allow the NO2-associated effects
indicated by epidemiologic studies. To the degree studies have not
reported associations in locations meeting the current NO2
standards, there is greater uncertainty regarding the potential for
reported effects to occur following the NO2 exposures that
are associated with air quality meeting those standards.
    With regard to studies of short-term NO2 exposures, as
discussed in greater detail in section II.B.1 above, the Administrator
notes that epidemiologic studies provide evidence for asthma-related ED
visits and hospital admissions with exposure to NO2 in
locations likely to have violated the current standards over at least
parts of study periods. In contrast, studies have not consistently
shown such NO2-associated outcomes in areas that would have
clearly met the current standards. In this regard, the Administrator
recognizes that the NO2 concentrations identified in the
locations of these epidemiologic studies are based on an

NO2 monitoring network that, during study periods, did not
include monitors meeting the current near-road monitoring requirements.
This is particularly important given that NO2 concentrations
near the most heavily trafficked roadways were likely to have been
higher than those reflected by the NO2 concentrations
measured at monitors in operation during study years. As such, the
estimated DVs associated with the areas at the times of the studies
could have been higher had a near-road monitoring network been in
place. Thus, while these epidemiologic studies provide evidence for
associations with asthma-related effects in locations likely to have
violated the current standards, supporting the decision to not set less
stringent standards (see section II.B.3, above), they do not provide
support for such associations in locations that would have clearly met
those standards. As a result, these studies additionally support the
decision to not set more stringent standards.
    With regard to studies of long-term NO2 exposures, the
Administrator notes that the preponderance of evidence for respiratory
health effects comes from epidemiologic studies evaluating asthma
development in children. While recognizing important uncertainties
related to potential copollutant confounding and exposure measurement
error (e.g., see U.S. EPA, 2017a, section <IP_ADDRESS>), the Administrator
considers what these studies could indicate with regard to the public
health protection provided by the current standards. As discussed in
section II.A.2 above, these studies report associations with long-term
average NO2 concentrations, while the broader body of
evidence indicates the potential for repeated short-term NO2
exposures to contribute to the development of asthma. Because of this,
and because air quality analyses indicate that meeting the current 1-
hour standard can also limit annual NO2 concentrations (U.S.
EPA, 2017a, figure 2-11), when considering these studies of asthma
development, the Administrator considers the protection provided by the
combination of both the annual and 1-hour standards.
    In doing so, he notes that key epidemiologic studies conducted in
the U.S. or Canada consistently report associations between long-term
NO2 exposures and asthma development in children in
locations likely to have violated the current standards over at least
parts of study periods, but that those studies do not indicate such
associations in locations that would have clearly met the current
annual and 1-hour standards (U.S. EPA, 2017a, section 5.1). As
discussed above for epidemiologic studies of short-term NO2
exposures, this is particularly the case given that NO2
concentrations near the most heavily trafficked roadways are not likely
reflected by monitors in operation during study years. Thus, while the
Administrator recognizes the public health significance of asthma
development in children, he concludes that the available evidence
supports his decision to not revise the current standards to be more
stringent. In addition, while there are important uncertainties in
these studies of long-term NO2 exposures, the Administrator
also concludes that, in light of the requirement for an adequate margin
of safety, reported associations in locations likely to have violated
the current standards support his decision to not revise the current
standards to be less stringent.
    Based on the above considerations, with their attendant
uncertainties and limitations, and with consideration of advice from
CASAC and public comment, the Administrator concludes that the current
body of scientific evidence, in combination with the results of the
quantitative analyses comparing NO2 air quality with health-
based benchmarks, supports his judgment that the current 1-hour and
annual NO2 primary standards, together, are requisite to
protect public health with an adequate margin of safety, and does not
call into question any of the four basic elements of those standards
(i.e., indicator, averaging time, level, and form). The Administrator
considers these four elements collectively in evaluating the public
health protection afforded by the current primary NO2
standards, as discussed above (section II.B.1.a). Based on this
consideration, and consistent with the CASAC advice (see, e.g., Diez
Roux and Sheppard, 2017, pp. 6-9), the Administrator judges that each
of the elements of the current standards should be retained. In
particular, taking note of the more detailed discussions elsewhere in
this document and in the proposal, he judges the following:
     NO2 continues to be the appropriate indicator
for both the current annual and 1-hour standards, and no alternative to
NO2 has been advanced as a more appropriate surrogate for
ambient oxides of nitrogen (section II.B.1.a.i above; 82 FR 34792, July
26, 2017, section II.F.1.a).
     The 1-hour and annual averaging times of the current
standards, together, can provide protection against short- and long-
term NO2 exposures and should be retained (section
II.B.1.a.ii above; 82 FR 34792, July 26, 2017, section II.F.1.b).
     The levels and the forms of the current short-term and
long-term standards should be retained (sections II.B.1.a.iii and
II.B.3 above; 82 FR 34792, July 26, 2017, section II.F.1.c).
    In considering the requirement for an adequate margin of safety,
the Administrator notes that the determination of what constitutes an
adequate margin of safety is expressly left to the judgment of the EPA
Administrator. See Lead Industries Association v. EPA, 647 F.2d at
1161-62; Mississippi, 744 F.3d at 1353. He further notes that in
evaluating how particular standards address the requirement to provide
an adequate margin of safety, it is appropriate to consider such
factors as the nature and severity of the health effects, the size of
sensitive population(s) at risk, and the kind and degree of the
uncertainties present. Consistent with past practice and long-standing
judicial precedent, and as described in this section, the Administrator
takes the need for an adequate margin of safety into account as an
integral part of his decision-making on a standard. See, e.g., NRDC v.
EPA, 902 F. 2d 962, 973-74 (D.C. Cir. 1990).
    In reaching the conclusion that the current primary NO2
standards, together, are requisite to protect public health with an
adequate margin of safety, the Administrator notes the following with
regard to effects attributable to short-term NO2 exposures:
     Meeting the current 1-hour NO2 standard is
expected to allow virtually no potential for exposures to
NO2 concentrations that have been shown most consistently to
increase AR in people with asthma (i.e., at or above 250 ppb), even
under worst-case conditions across a variety of study areas with among
the highest NOX emissions in the U.S. Based on analyses of
air quality adjusted upwards to just meet the current 1-hour standard,
such NO2 concentrations were not estimated to occur, even at
monitoring sites adjacent to some of the most heavily trafficked
roadways (U.S. EPA, 2017a, section 4.2.1).
     Meeting the current 1-hour standard limits the potential
for exposures to 1-hour concentrations at or above 100 ppb. Thus, the
current standard protects against NO2 exposures with the
potential to exacerbate symptoms in some people with asthma, but for
which uncertainties in the evidence take on increased importance (U.S.
EPA, 2017a, section 4.2.1).

     Meeting the current 1-hour standard is expected to
maintain ambient NO2 concentrations below those likely to
have been present in locations where key epidemiologic studies
conducted in the U.S. or Canada have reported relatively precise and
statistically significant associations between short-term
NO2 and asthma-related hospitalizations (U.S. EPA, 2017a,
section <IP_ADDRESS>).
    In addition, with regard to long-term NO2 exposures, the
Administrator notes that the evidence supporting associations with
asthma development in children has become stronger since the last
review, though important uncertainties remain. As discussed in section
II.B.1 above, meeting the current annual and 1-hour standards is
expected to maintain ambient NO2 concentrations below those
likely to have been present in locations where key U.S. and Canadian
epidemiologic studies have reported associations between long-term
NO2 and asthma development (U.S. EPA, 2017a, section
<IP_ADDRESS>). In considering the protection provided against exposures that
could contribute to asthma development, the Administrator recognizes
the air quality relationship between the current 1-hour standard and
the annual standard, and that analyses of historical ambient
NO2 concentrations suggest that meeting the 1-hour standard