term (warm season) exposure to O3 and elevated risk of
mortality in the cohort that had previously experienced an emergency
hospital admission due to chronic obstructive pulmonary disease (COPD).
A key limitation of this study is the inability to control for
PM2.5, because data were not available in these cities until
1999.
iii. Cardiovascular Effects--Short-Term Exposure
    A relatively small number of studies have examined the potential
effect of short-term O3 exposure on the cardiovascular
system. The 2006 AQCD (U.S. EPA, 2006a, p. 8-77) concluded that
``O3 directly and/or indirectly contributes to
cardiovascular-related morbidity,'' but added that the body of evidence
was limited. This conclusion was based on a controlled human exposure
study that included hypertensive adult males; a few epidemiologic
studies of physiologic effects, heart rate variability, arrhythmias,
myocardial infarctions, and hospital admissions; and toxicological
studies of heart rate, heart rhythm, and blood pressure.
    More recently, the body of scientific evidence available that has
examined the effect of O3 on the cardiovascular system has
expanded. There is an emerging body of animal toxicological evidence
demonstrating that short-term exposure to O3 can lead to
autonomic nervous system alterations (in heart rate and/or heart rate
variability) and suggesting that proinflammatory signals may mediate
cardiovascular effects. Interactions of O3 with respiratory
tract components result in secondary oxidation product formation and
subsequent production of inflammatory mediators, which have the
potential to penetrate the epithelial barrier and to initiate toxic
effects systemically. In addition, animal toxicological studies of
long-term exposure to O3 provide evidence of enhanced
atherosclerosis and ischemia/reperfusion (I/R) injury, corresponding
with development of a systemic oxidative, proinflammatory environment.
Recent experimental and epidemiologic studies have investigated
O3-related cardiovascular events and are summarized in the
ISA (U.S. EPA, 2013, section 6.3).
    Controlled human exposure studies discussed in previous reviews
have not demonstrated any consistent extrapulmonary effects. In this
review, evidence from controlled human exposure studies suggests
cardiovascular effects in response to short-term O3 exposure
(U.S. EPA, 2013, section 6.3.1) and provides some coherence with
evidence from animal toxicology studies. Controlled human exposure
studies also support the animal toxicological studies by demonstrating
O3-induced effects on blood biomarkers of systemic
inflammation and oxidative stress, as well as changes in biomarkers
that can indicate the potential for increased clotting following
O3 exposures. Increases and decreases in high frequency
heart rate variability (HRV) have been reported. These changes in
cardiac function observed in animal and human studies provide
preliminary evidence for O3-induced modulation of the
autonomic nervous system through the activation of neural reflexes in
the lung (U.S. EPA, 2013, section 5.3.2).
    Overall, the ISA concludes that the available body of epidemiologic
evidence examining the relationship between short-term exposures to
O3 concentrations and cardiovascular morbidity is
inconsistent (U.S. EPA, 2013, section <IP_ADDRESS>).
    Despite the inconsistent evidence for an association between
O3 concentration and cardiovascular disease (CVD) morbidity,
mortality studies indicate a consistent positive association between
short-term O3 exposure and cardiovascular mortality in
multicity studies and in a multi-continent study. When examining
mortality due to CVD, epidemiologic studies consistently observe
positive associations with short-term exposure to O3.
Additionally, there is some evidence for an association between long-
term exposure to O3 and mortality, although the association
between long-term ambient O3 concentrations and
cardiovascular mortality can be confounded by other pollutants (U.S.
EPA, 2013). The ISA (U.S. EPA, 2013, section 6.3.4) states that taken
together, the overall body of evidence across the animal and human
studies is sufficient to conclude that there is likely to be a causal
relationship between relevant short-term exposures to O3 and
cardiovascular system effects.
iv. Premature Mortality--Short-Term Exposure
    The 2006 AQCD concluded that the overall body of evidence was
highly suggestive that short-term exposure to O3 directly or
indirectly contributes to nonaccidental and cardiopulmonary-related
mortality in adults, but additional research was needed to more fully
establish underlying mechanisms by which such effects occur (U.S. EPA,
2006a; U.S. EPA, 2013, p. 2-18). In building on the evidence for
mortality from the last review, the ISA states (U.S. EPA, 2013, p. 6-
261):

    The evaluation of new multicity studies that examined the
association between short-term O3 exposures and mortality
found evidence that supports the conclusions of the 2006 AQCD. These
new studies reported consistent positive associations between short-
term O3 exposure and all-cause (nonaccidental) mortality,
with associations persisting or increasing in magnitude during the
warm season, and provide additional support for associations between
O3 exposure and cardiovascular and respiratory mortality.

    The 2006 AQCD reviewed a large number of time-series studies of
associations between short-term O3 exposures and total
mortality including single- and multicity studies, and meta-analyses.
Available studies reported some evidence for heterogeneity in
O3 mortality risk estimates across cities and across
studies. Studies that conducted seasonal analyses reported larger
O3 mortality risk estimates during the warm or summer
season. Overall, the 2006 AQCD identified robust associations between
various measures of daily ambient O3 concentrations and all-
cause mortality, which could not be readily explained by confounding
due to time, weather, or copollutants. With regard to cause-specific
mortality, consistent positive associations were reported between
short-term O3 exposure and cardiovascular mortality, with
less consistent evidence for associations with respiratory mortality.
The majority of the evidence for associations between O3 and
cause-specific mortality were from single-city studies, which had small
daily mortality counts and subsequently limited statistical power to
detect associations. The 2006 AQCD concluded that ``the overall body of
evidence is highly suggestive that O3 directly or indirectly
contributes to nonaccidental and cardiopulmonary-related mortality''
(U.S. EPA, 2013, section 6.6.1).

    Recent studies have strengthened the body of evidence that supports
the association between short-term O3 concentrations and
mortality in adults. This evidence includes a number of studies
reporting associations with nonaccidental as well as cause-specific
mortality. Multi-continent and multicity studies have consistently
reported positive and statistically significant associations between
short-term O3 concentrations and all-cause mortality, with
evidence for larger mortality risk estimates during the warm or summer
months (79 FR 75262; U.S. EPA, 2013 Figure 6-27; Table 6-42).
Similarly, evaluations of cause-specific mortality have reported
consistently positive associations with O3, particularly in
analyses restricted to the warm season (79 FR 75262; U.S. EPA, 2013
Fig. 6-37; Table 6-53).
    In the previous review, multiple uncertainties remained regarding
the relationship between short-term O3 concentrations and
mortality, including the extent of residual confounding by
copollutants; characterization of the factors that modify the
O3-mortality association; the appropriate lag structure for
identifying O3-mortality effects; and the shape of the
O3-mortality concentration-response function and whether a
threshold exists. Many of the studies, published since the last review,
have attempted to address one or more of these uncertainties and are
described in more detail in the proposal (79 FR 75262 and in the ISA
(U.S. EPA, 2013, section 6.6.2).
    In particular, recent studies have evaluated different statistical
approaches to examine the shape of the O3-mortality
concentration-response relationship and to evaluate whether a threshold
exists for O3-related mortality. These studies are detailed
in the proposal (79 FR 75262) and in the ISA (U.S. EPA, 2013, p. 2-32).
The ISA reaches the following overall conclusions that the
epidemiologic studies identified in the ISA indicated a generally
linear C-R function with no indication of a threshold but that there is
a lack of data at lower O3 concentrations and therefore,
less certainty in the shape of the C-R curve at the lower end of the
distribution (U.S. EPA, 2013, p. 2-32).
c. Adversity of Effects
    In making judgments as to when various O3-related
effects become regarded as adverse to the health of individuals, in
previous NAAQS reviews, the EPA has relied upon the guidelines
published by the ATS and the advice of CASAC. In 2000, the ATS
published an official statement on ``What Constitutes an Adverse Health
Effect of Air Pollution?'' (ATS, 2000a), which updated and built upon
its earlier guidance (ATS, 1985). The earlier guidance defined adverse
respiratory health effects as ``medically significant physiologic
changes generally evidenced by one or more of the following: (1)
Interference with the normal activity of the affected person or
persons, (2) episodic respiratory illness, (3) incapacitating illness,
(4) permanent respiratory injury, and/or (5) progressive respiratory
dysfunction,'' while recognizing that perceptions of ``medical
significance'' and ``normal activity'' may differ among physicians,
lung physiologists and experimental subjects (ATS, 1985). The more
recent guidance concludes that transient, reversible loss of lung
function in combination with respiratory symptoms should be considered
adverse.\33\ However, the committee also recommended ``that a small,
transient loss of lung function, by itself, should not automatically be
designated as adverse'' (ATS, 2000a, p. 670).
---------------------------------------------------------------------------

    \33\ ``In drawing the distinction between adverse and nonadverse
reversible effects, this committee recommended that reversible loss
of lung function in combination with the presence of symptoms should
be considered as adverse'' (ATS, 2000a).
---------------------------------------------------------------------------

    There is also a more specific consideration of population risk in
the 2000 guidance. Specifically, the committee considered that a shift
in the risk factor distribution, and hence the risk profile of the
exposed population, should be considered adverse, even in the absence
of the immediate occurrence of frank illness (ATS, 2000a, p. 668). For
example, a population of asthmatics could have a distribution of lung
function such that no individual has a level associated with clinically
important impairment. Exposure to air pollution could shift the
distribution to lower levels of lung function that still do not bring
any individual to a level that is associated with clinically relevant
effects. However, this would be considered to be adverse because
individuals within the population would already have diminished reserve
function, and therefore would be at increased risk to further
environmental insult (ATS, 2000a, p. 668).
    The ATS also concluded in its guidance that elevations of
biomarkers such as cell numbers and types, cytokines, and reactive
oxygen species may signal risk for ongoing injury and more serious
effects or may simply represent transient responses, illustrating the
lack of clear boundaries that separate adverse from nonadverse events.
More subtle health outcomes also may be connected mechanistically to
health effects that are clearly adverse, so that small changes in
physiological measures may not appear clearly adverse when considered
alone, but may be part of a coherent and biologically plausible chain
of related health outcomes that include responses that are clearly
adverse, such as mortality (U.S. EPA, 2014c, section <IP_ADDRESS>).
    Application of the ATS guidelines to the least serious category of
effects \34\ related to ambient O3 exposures, which are also
the most numerous and, therefore, are also important from a public
health perspective, involves judgments about which medical experts on
CASAC panels and public commenters have in the past expressed diverse
views. To help frame such judgments, in past reviews, the EPA has
defined gradations of individual functional responses (e.g., decrements
in FEV1 and airway responsiveness) and symptomatic responses
(e.g., cough, chest pain, wheeze), together with judgments as to the
potential impact on individuals experiencing varying degrees of
severity of these responses. These gradations were used by the EPA in
the 1997 O3 NAAQS review and slightly revised in the 2008
review (U.S. EPA, 1996b, p. 59; U.S. EPA, 2007, p. 3-72; 72 FR 37849,
July 11, 2007). These gradations and impacts are summarized in Tables
3-2 and 3-3 in the 2007 O3 Staff Paper (U.S. EPA, 2007, pp.
3-74 to 3-75).
---------------------------------------------------------------------------

    \34\ These include, for example, the transient and reversible
effects demonstrated in controlled human exposure studies, such as
lung function decrements or respiratory symptoms.
---------------------------------------------------------------------------

    For the purpose of estimating potentially adverse lung function
decrements in active healthy people, the CASAC panel in the 2008
O3 NAAQS review indicated that a focus on the mid to upper
end of the range of moderate levels of functional responses is most
appropriate (e.g., FEV1 decrements >=15% but <20%)
(Henderson, 2006; U.S. EPA, 2007, p. 3-76). In this review, CASAC
reiterated that the ``[e]stimation of FEV1 decrements of
>=15% is appropriate as a scientifically relevant surrogate for adverse
health outcomes in active healthy adults'' (Frey, 2014c, p. 3).
    For the purpose of estimating potentially adverse lung function
decrements in people with lung disease, the CASAC panel in the 2008
O3 NAAQS review indicated that a focus on the lower end of
the range of moderate levels of functional responses is most
appropriate (e.g., FEV1 decrements >=10%) (Henderson, 2006;
U.S. EPA, 2007, p. 3-76). In their letter

advising the Administrator on the reconsideration of the 2008 final
decision, CASAC stated that ``[a] 10% decrement in FEV1 can
lead to respiratory symptoms, especially in individuals with pre-
existing pulmonary or cardiac disease. For example, people with chronic
obstructive pulmonary disease have decreased ventilatory reserve (i.e.,
decreased baseline FEV1) such that a >= 10% decrement could
lead to moderate to severe respiratory symptoms'' (Samet, 2011). In
this review, CASAC provided similar advice, stating that ``[a]n
FEV1 decrement of >= 10% is a scientifically relevant
surrogate for adverse health outcomes for people with asthma and lung
disease'', and that such decrements ``could be adverse for people with
lung disease'' (Frey, 2014c, pp. 3, 7).
    In judging the extent to which these impacts represent effects that
should be regarded as adverse to the health status of individuals, in
previous NAAQS reviews, the EPA has also considered whether effects
were experienced repeatedly during the course of a year or only on a
single occasion (U.S. EPA, 2007). While some experts would judge single
occurrences of moderate responses to be a ``nuisance,'' especially for
healthy individuals, a more general consensus view of the adversity of
such moderate responses emerges as the frequency of occurrence
increases. In particular, not every estimated occurrence of an
O3-induced FEV1 decrement will be adverse.\35\
However, repeated occurrences of moderate responses, even in otherwise
healthy individuals, may be considered to be adverse since they could
set the stage for more serious illness (61 FR 65723). The CASAC panel
in the 1997 NAAQS review expressed a consensus view that these
``criteria for the determination of an adverse physiological response
were reasonable'' (Wolff, 1995). In the review completed in 2008, as in
the current review (II.B, II.C below), estimates of repeated
occurrences continued to be an important public health policy factor in
judging the adversity of moderate lung function decrements in healthy
and asthmatic people (72 FR 37850, July 11, 2007).
---------------------------------------------------------------------------

    \35\ As noted above, the ATS recommended ``that a small,
transient loss of lung function, by itself, should not automatically
be designated as adverse'' (ATS, 2000a, p. 670).
---------------------------------------------------------------------------

d. Ozone-Related Impacts on Public Health
    The currently available evidence expands the understanding of
populations that were identified to be at greater risk of
O3-related health effects at the time of the last review
(i.e., people who are active outdoors, people with lung disease,
children and older adults and people with increased responsiveness to
O3) and supports the identification of additional factors
that may lead to increased risk (U.S. EPA, 2006a, section 6.3; U.S.
EPA, 2013, Chapter 8). Populations and lifestages may be at greater
risk for O3-related health effects due to factors that
contribute to their susceptibility and/or vulnerability to
O3. The definitions of susceptibility and vulnerability have
been found to vary across studies, but in most instances
``susceptibility'' refers to biological or intrinsic factors (e.g.,
lifestage, sex, preexisting disease/conditions) while ``vulnerability''
refers to non-biological or extrinsic factors (e.g., socioeconomic
status [SES]) (U.S. EPA, 2013, p. 8-1; U.S. EPA, 2010, 2009b). In some
cases, the terms ``at-risk'' and ``sensitive'' have been used to
encompass these concepts more generally. In the ISA, PA, and proposal,
``at-risk'' is the all-encompassing term used to define groups with
specific factors that increase their risk of O3-related
health effects.
    There are multiple avenues by which groups may experience increased
risk for O3-induced health effects. A population or
lifestage \36\ may exhibit greater effects than other populations or
lifestages exposed to the same concentration or dose, or they may be at
greater risk due to increased exposure to an air pollutant (e.g., time
spent outdoors). A group with intrinsically increased risk would have
some factor(s) that increases risk through a biological mechanism and,
in general, would have a steeper concentration-risk relationship,
compared to those not in the group. Factors that are often considered
intrinsic include pre-existing asthma, genetic background, and
lifestage. A group of people could also have extrinsically increased
risk, which would be through an external, non-biological factor, such
as socioeconomic status (SES) and diet. Some groups are at risk of
increased internal dose at a given exposure concentration, for example,
because of breathing patterns. This category would include people who
work or exercise outdoors. Finally, there are those who might be placed
at increased risk for experiencing greater exposures by being exposed
to higher O3 concentrations. This would include, for
example, groups of people with greater exposure to ambient
O3 due to less availability or use of home air conditioners
such that they are more likely to be in locations with open windows on
high O3 days. Some groups may be at increased risk of
O3-related health effects through a combination of factors.
For example, children tend to spend more time outdoors when
O3 levels are high, and at higher levels of activity than
adults, which leads to increased exposure and dose, and they also have
biological, or intrinsic, risk factors (e.g., their lungs are still
developing) (U.S. EPA, 2013, Chapter 8). An at-risk population or
lifestage is more likely to experience adverse health effects related
to O3 exposures and/or, develop more severe effects from
exposure than the general population. The populations and lifestages
identified by the ISA (U.S. EPA, 2013, section 8.5) identified that
have ``adequate'' evidence for increased O3-related health
effects are people with certain genotypes, people with asthma, younger
and older age groups, people with reduced intake of certain nutrients,
and outdoor workers. These at-risk populations and lifestages are
described in more detail in section II.B.4 of the proposal (79 FR
75264-269).
---------------------------------------------------------------------------

    \36\ Lifestages, which in this case includes childhood and older
adulthood, are experienced by most people over the course of a
lifetime, unlike other factors associated with at-risk populations.
---------------------------------------------------------------------------

    One consideration in the assessment of potential public health
impacts is the size of various population groups for which there is
adequate evidence of increased risk for health effects associated with
O3-related air pollution exposure (U.S. EPA, 2014c, section
<IP_ADDRESS>). The factors for which the ISA judged the evidence to be
``adequate'' with respect to contributing to increased risk of
O3-related effects among various populations and lifestages
included: Asthma; childhood and older adulthood; diets lower in
vitamins C and E; certain genetic variants; and working outdoors (U.S.
EPA, 2013, section 8.5). No statistics are available to estimate the
size of an at-risk population based on nutritional status or genetic
variability.
    With regard to asthma, Table 3-7 in the PA (U.S. EPA, 2014c,
section <IP_ADDRESS>) summarizes information on the prevalence of current
asthma by age in the U.S. adult population in 2010 (Schiller et al.
2012; children--Bloom et al., 2011). Individuals with current asthma
constitute a fairly large proportion of the population, including more
than 25 million people. Asthma prevalence tends to be higher in
children than adults. Within the U.S., approximately 8.2% of adults
have reported currently having asthma (Schiller et al., 2012) and 9.5%
of

children have reported currently having asthma (Bloom et al.,
2011).\37\
---------------------------------------------------------------------------

    \37\ As noted below (II.C.3.a.ii), asthmatics can experience
larger O3-induced respiratory effects than non-asthmatic,
healthy adults. The responsiveness of asthmatics to O3
exposures could depend on factors that have not been well-evaluated
such as asthma severity, the effectiveness of asthma control, or the
prevalence of medication use.
---------------------------------------------------------------------------

    With regard to lifestages, based on U.S. census data from 2010
(Howden and Meyer, 2011), about 74 million people, or 24% of the U.S.
population, are under 18 years of age and more than 40 million people,
or about 13% of the U.S. population, are 65 years of age or older.
Hence, a large proportion of the U.S. population (i.e., more than a
third) is included in age groups that are considered likely to be at
increased risk for health effects from ambient O3 exposure.
    With regard to outdoor workers, in 2010, approximately 11.7% of the
total number of people (143 million people) employed, or about 16.8
million people, worked outdoors one or more days per week (based on
worker surveys).\38\ Of these, approximately 7.4% of the workforce, or
about 7.8 million people, worked outdoors three or more days per week.
---------------------------------------------------------------------------

    \38\ The O*NET program is the nation's primary source of
occupational information. Central to the project is the O*NET
database, containing information on hundreds of standardized and
occupation-specific descriptors. The database, which is available to
the public at no cost, is continually updated by surveying a broad
range of workers from each occupation. http://www.onetcenter.org/overview.html. http://www.onetonline.org/find/descriptor/browse/Work_Context/4.C.2/.
---------------------------------------------------------------------------

    While it is difficult to estimate the total number of people in
groups that are at greater risk from exposure to O3, due to
the overlap in members of the different at-risk population groups, the
proportion of the total population at greater risk is large. The size
of the at-risk population combined with the estimates of risk of
different health outcomes associated with exposure to O3 can
give an indication of the magnitude of O3 impacts on public
health.
2. Overview of Human Exposure and Health Risk Assessments
    To put judgments about health effects into a broader public health
context, the EPA has developed and applied models to estimate human
exposures to O3 and O3-associated health risks.
Exposure and risk estimates that are output from such models are
presented and assessed in the HREA (U.S. EPA, 2014a). Section II.C of
the proposal discusses the quantitative assessments of O3
exposures and O3-related health risks that are presented in
the HREA (79 FR 75270). Summaries of these discussions are provided
below for the approach used to adjust air quality for quantitative
exposure and risk analyses in the HREA (II.A.2.a), the HREA assessment
of exposures to ambient O3 (II.A.2.b), and the HREA
assessments of O3-related health risks (II.A.2.c).
a. Air Quality Adjustment
    As discussed in section II.C.1 of the proposal (79 FR 75270), the
HREA uses a photochemical model to estimate sensitivities of
O3 to changes in precursor emissions in order to estimate
ambient O3 concentrations that would just meet the current
and alternative standards (U.S. EPA, 2014a, Chapter 4).\39\ For the 15
urban study areas evaluated in the HREA,\40\ this model-based
adjustment approach estimates hourly O3 concentrations at
each monitor location when modeled U.S. anthropogenic precursor
emissions (i.e., NOX, VOC) \41\ are reduced. The HREA
estimates air quality that just meets the current and alternative
standards for the 2006-2008 and 2008-2010 periods.\42\
---------------------------------------------------------------------------

    \39\ The HREA uses the Community Multi-scale Air Quality (CMAQ)
photochemical model instrumented with the higher order direct
decoupled method (HDDM) to estimate O3 concentrations
that would occur with the achievement of the current and alternative
O3 standards (U.S. EPA, 2014a, Chapter 4).
    \40\ The urban study areas assessed are Atlanta, Baltimore,
Boston, Chicago, Cleveland, Dallas, Denver, Detroit, Houston, Los
Angeles, New York, Philadelphia, Sacramento, St. Louis, and
Washington, DC.
    \41\ Exposure and risk analyses for most of the urban study
areas focus on reducing U.S. anthropogenic NOX emissions
alone. The exceptions are Chicago and Denver. Exposure and risk
analyses for Chicago and Denver are based on reductions in emissions
of both NOX and VOC (U.S. EPA, 2014a, section <IP_ADDRESS>;
Appendix 4D).
    \42\ These estimates thus reflect design values--8 hour values
using the form of the NAAQS that meet the level of the current or
alternative standards. These simulations are illustrative and do not
reflect any consideration of specific control programs designed to
achieve the reductions in emissions required to meet the specified
standards. Further, these simulations do not represent predictions
of when, whether, or how areas might meet the specified standards.
---------------------------------------------------------------------------

    As discussed in Chapter 4 of the HREA (U.S. EPA, 2014a), this
approach to adjusting air quality models the physical and chemical
atmospheric processes that influence ambient O3
concentrations. Compared to the quadratic rollback approach used in
previous reviews, it provides more realistic estimates of the spatial
and temporal responses of O3 to reductions in precursor
emissions. Because ambient NOX can contribute both to the
formation and destruction of O3 (U.S. EPA, 2014a, Chapter
4), the response of ambient O3 concentrations to reductions
in NOX emissions is more variable than indicated by the
quadratic rollback approach. This improved approach to adjusting
O3 air quality is consistent with recommendations from the
National Research Council of the National Academies (NRC, 2008). In
addition, CASAC strongly supported the new approach as an improvement
and endorsed the way it was utilized in the HREA, stating that ``the
quadratic rollback approach has been replaced by a scientifically more
valid Higher-order Decoupled Direct Method (HDDM)'' and that ``[t]he
replacement of the quadratic rollback procedure by the HDDM procedure
is important and supported by the CASAC'' (Frey, 2014a, pp. 1 and 3).
    Within urban study areas, the model-based air quality adjustments
show reductions in the O3 levels at the upper ends of
ambient concentrations and increases in the O3 levels at the
lower ends of those distributions (U.S. EPA, 2014a, section <IP_ADDRESS>,
Figures 4-9 and 4-10).\43\ Seasonal means of daily O3
concentrations generally exhibit only modest changes upon model
adjustment, reflecting the seasonal balance between daily decreases in
relatively higher concentrations and increases in relatively lower
concentrations (U.S. EPA, 2014a, Figures 4-9 and 4-10). The resulting
compression in the seasonal distributions of ambient O3
concentrations is evident in all of the urban study areas evaluated,
though the degree of compression varies considerably across areas (U.S.
EPA, 2014a, Figures 4-9 and 4-10).
---------------------------------------------------------------------------

    \43\ It is important to note that sensitivity analyses in the
HREA indicate that the increases in low O3 concentrations
are smaller when NOX and VOC emissions are reduced than
when only NOX emissions are reduced (U.S. EPA, 2014a,
Appendix 4-D, section 4.7).
---------------------------------------------------------------------------

    As discussed in the PA (U.S. EPA, 2014c, section 3.2.1), adjusted
patterns of O3 air quality have important implications for
exposure and risk estimates in urban case study areas. Estimates
influenced largely by the upper ends of the distribution of ambient
concentrations (i.e., exposures of concern and lung function risk
estimates, as discussed in sections 3.2.2 and <IP_ADDRESS> of the PA) will
decrease with model-adjustment to the current and alternative
standards. In contrast, seasonal risk estimates influenced by the full
distribution of ambient O3 concentrations (i.e.,
epidemiology-based risk estimates, as discussed in section <IP_ADDRESS> of
the PA) either increase or decrease in response to air quality
adjustment, depending on the balance between the daily decreases in
high O3

concentrations and increases in low O3 concentrations.\44\
---------------------------------------------------------------------------

    \44\ In addition, because epidemiology-based risk estimates use
``area-wide'' average O3 concentrations, calculated by
averaging concentrations across multiple monitors in urban case
study areas (section <IP_ADDRESS> below), risk estimates on a given day
depend on the daily balance between increasing and decreasing
O3 concentrations at individual monitors.
---------------------------------------------------------------------------

    To evaluate uncertainties in air quality adjustments, the HREA
assessed the extent to which the modeled O3 response to
reductions in NOX emissions appropriately represent the
trends observed in monitored ambient O3 following actual
reductions in NOX emissions, and the extent to which the
O3 response to reductions in precursor emissions could
differ with emissions reduction strategies that are different from
those used in HREA to generate risk estimates.
    To evaluate the first issue, the HREA conducted a national analysis
evaluating trends in monitored ambient O3 concentrations
during a time period when the U.S. experienced large-scale reductions
in NOX emissions (i.e., 2001 to 2010). Analyses of trends in
monitored O3 indicate that over such a time period, the
upper end of the distribution of monitored O3 concentrations
(i.e., indicated by the 95th percentile) generally decreased in urban
and non-urban locations across the U.S. (U.S. EPA, 2014a, Figure 8-29).
During this same time period, median O3 concentrations
decreased in suburban and rural locations, and in some urban locations.
However, median concentrations increased in some large urban centers
(U.S. EPA, 2014a, Figure 8-28). As discussed in the HREA, these
increases in median concentrations likely reflect the increases in
relatively low O3 concentrations that can occur near
important sources of NOX upon reductions in NOX
emissions (U.S. EPA, 2014a, section <IP_ADDRESS>). These patterns of
monitored O3 during a period when the U.S. experienced large
reductions in NOX emissions are qualitatively consistent
with the modeled responses of O3 to reductions in
NOX emissions.
    To evaluate the second issue, the HREA assessed the O3
air quality response to reducing both NOX and VOC emissions
(i.e., in addition to assessing reductions in NOX emissions
alone) for a subset of seven urban study areas. As discussed in the PA
(U.S. EPA, 2014c, section 3.2.1), the addition of VOC reductions
generally resulted in larger decreases in mid-range O3
concentrations (25th to 75th percentiles) (U.S. EPA, 2014a, Appendix
4D, section 4.7).\45\ In addition, in all seven of the urban study
areas evaluated, the increases in low O3 concentrations were
smaller for the NOX/VOC scenarios than the NOX
alone scenarios (U.S. EPA, 2014a, Appendix 4D, section 4.7). This was
most apparent for Denver, Houston, Los Angeles, New York, and
Philadelphia. Given the impacts on total risk estimates of increases in
low O3 concentrations (discussed below), these results
suggest that in some locations optimized emissions reduction strategies
could result in larger reductions in O3-associated mortality
and morbidity than indicated by HREA estimates.
---------------------------------------------------------------------------

    \45\ This was the case for all of the urban study areas
evaluated, with the exception of New York (U.S. EPA, 2014a, Appendix
4-D, section 4.7). In this analysis, emissions of NOX and
VOC were reduced by equal percentages, a scenario not likely to
reflect the optimal combination for reducing risks. In most of the
urban study areas the inclusion of VOC emissions reductions did not
alter the NOX emissions reductions required to meet the
current or alternative standards. The exceptions are Chicago and
Denver, for which the HREA risk estimates are based on reductions in
both NOX and VOC (U.S. EPA, 2014a, section <IP_ADDRESS>).
---------------------------------------------------------------------------

b. Exposure Assessment
    As discussed in section II.C.2 of the proposal, the O3
exposure assessment presented in the HREA (U.S. EPA, 2014a, Chapter 5)
provides estimates of the number and percent of people exposed to
various concentrations of ambient O3 while at specified
exertion levels. The HREA estimates exposures in the 15 urban study
areas for four study groups, all school-age children (ages 5 to 18),
asthmatic school-age children, asthmatic adults (ages 19 to 95), and
all older adults (ages 65 to 95), reflecting the evidence indicating
that these populations are at increased risk for O3-
attributable effects (U.S. EPA, 2013, Chapter 8; II.A.1.d, above). An
important purpose of these exposure estimates is to provide perspective
on the extent to which air quality adjusted to just meet the current
O3 NAAQS could be associated with exposures to O3
concentrations reported to result in respiratory effects.\46\ These
analyses of exposure assessment incorporate behavior patterns,
including estimates of physical exertion, which are critical in
assessing whether ambient concentrations of O3 may pose a
public health risk.\47\ In particular, exposures to ambient or near-
ambient O3 concentrations have only been shown to result in
potentially adverse effects if the ventilation rates of people in the
exposed populations are raised to a sufficient degree (e.g., through
physical exertion) (U.S. EPA, 2013, section <IP_ADDRESS>). Estimates of such
``exposures of concern'' provide perspective on the potential public
health impacts of O3-related effects, including effects that
cannot currently be evaluated in a quantitative risk assessment.\48\
---------------------------------------------------------------------------

    \46\ In addition, the range of modeled personal exposures to
ambient O3 provide an essential input to the portion of
the health risk assessment based on exposure-response functions (for
lung function decrements) from controlled human exposure studies.
The health risk assessment based on exposure-response information is
discussed below (II.C.3).
    \47\ See 79 FR 75269 ``The activity pattern of individuals is an
important determinant of their exposure. Variation in O3
concentrations among various microenvironments means that the amount
of time spent in each location, as well as the level of activity,
will influence an individual's exposure to ambient O3.
Activity patterns vary both among and within individuals, resulting
in corresponding variations in exposure across a population and over
time'' (internal citations omitted).
    \48\ In this review, the term ``exposure of concern'' is defined
as a personal exposure, while at moderate or greater exertion, to 8-
hour average ambient O3 concentrations at and above
specific benchmarks levels. As discussed below, these benchmark
levels represent exposure concentrations at which O3-
induced health effects are known to occur, or can reasonably be
anticipated to occur, in some individuals.
---------------------------------------------------------------------------

    The HREA estimates 8-hour exposures at or above benchmark
concentrations of 60, 70, and 80 ppb for individuals engaged in
moderate or greater exertion (i.e., to approximate conditions in the
controlled human exposure studies on which benchmarks are based).
Benchmarks reflect exposure concentrations at which O3-
induced respiratory effects are known to occur in some healthy adults
engaged in moderate, quasi-continuous exertion, based on evidence from
controlled human exposure studies (U.S. EPA, 2013, section 6.2; U.S.
EPA, 2014c, section <IP_ADDRESS>). The amount of weight to place on the
estimates of exposures at or above specific benchmark concentrations
depends in part on the weight of the scientific evidence concerning
health effects associated with O3 exposures at those
benchmark concentrations. It also depends on judgments about the
importance, from a public health perspective, of the health effects
that are known or can reasonably be inferred to occur as a result of
exposures at benchmark concentrations (U.S. EPA, 2014c, sections 3.1.3,
3.1.5).
    In considering estimates of O3 exposures of concern at
or above benchmarks of 60, 70, and 80 ppb, the PA focuses on modeled
exposures for school-age children (ages 5-18), including asthmatic
school-age children, which are key at-risk populations identified in
the ISA (U.S. EPA, 2014c, section 3.1.5). The percentages of children
estimated to experience exposures of concern are considerably larger
than the percentages estimated for adult populations (i.e.,
approximately 3-fold larger across urban

study areas) \49\ (U.S. EPA, 2014a, section 5.3.2 and Figures 5-5 to 5-
8). The larger exposure estimates for children are due primarily to the
larger percentage of children estimated to spend an extended period of
time being physically active outdoors when O3 concentrations
are elevated (U.S. EPA, 2014a, sections 5.3.2 and 5.4.1).
---------------------------------------------------------------------------

    \49\ HREA exposure estimates for all children and asthmatic
children are virtually indistinguishable, in terms of the percent
estimated to experience exposures of concern (U.S. EPA, 2014a,
Chapter 5). Consistent with this, HREA analyses indicate that
activity data for people with asthma is generally similar to non-
asthmatic populations (U.S. EPA, 2014a, Appendix 5G, Tables 5G2-to
5G-5).
---------------------------------------------------------------------------

    Although exposure estimates differ between children and adults, the
patterns of results across the urban study areas and years are similar
among all of the populations evaluated (U.S. EPA, 2014a, Figures 5-5 to
5-8). Therefore, while the PA highlights estimates in children,
including asthmatic school-age children, it also notes that the
patterns of exposures estimated for children represent the patterns
estimated for adult asthmatics and older adults.
    Table 1 of the proposal (79 FR 75272 to 75273) summarizes key
results from the exposure assessment. This table is reprinted below.
---------------------------------------------------------------------------

    \50\ Estimates for each urban case study area were averaged for
the years evaluated in the HREA (2006 to 2010). Ranges reflect the
ranges across urban study areas. Estimates smaller than 0.05% were
rounded downward to zero (from U.S. EPA, 2014a, Tables 5-11 and 5-
12). Numbers in parentheses reflect averages across urban study
areas, as well as over the years evaluated in the HREA.
    \51\ Numbers of children exposed in each urban case study area
were averaged over the years 2006 to 2010. These averages were then
summed across urban study areas. Numbers were rounded to nearest
thousand unless otherwise indicated. Estimates smaller than 50 were
rounded downward to zero (from U.S. EPA, 2014a, Appendix 5F Table
5F-5).
    \52\ As discussed in section 4.3.3 of the HREA, the model-based
air quality adjustment approach used to estimate exposures and lung
function decrements associated with the current and alternative
standards was unable to estimate the distribution of ambient
O3 concentrations in New York City upon just meeting an
alternative standard with a level of 60 ppb. Therefore, for the 60
ppb standard level, the numbers of children and asthmatic children,
and the ranges of percentages, reflect all of the urban study areas
except New York.

Table 1--Summary of Estimated Exposures of Concern in All School-age Children for the Current and Alternative O3
                                         Standards in Urban Study Areas
----------------------------------------------------------------------------------------------------------------
                                                                         Average number of
                                                       Average %          children exposed     % Children--worst
    Benchmark concentration       Standard level   children  exposed     [average number of      year and worst
                                      (ppb)               \50\          asthmatic children]           area
                                                                                \51\
----------------------------------------------------------------------------------------------------------------
                                   One or more exposures of concern per season
----------------------------------------------------------------------------------------------------------------
>= 80 ppb.....................                 75        0-0.3 (0.1)           27,000 [3,000]                1.1
                                               70          0-0.1 (0)              3,700 [300]                0.2
                                               65              0 (0)                  300 [0]                  0
                                               60              0 (0)             100 \52\ [0]                  0
>= 70 ppb.....................                 75      0.6-3.3 (1.9)         362,000 [40,000]                8.1
                                               70      0.1-1.2 (0.5)          94,000 [10,000]                3.2
                                               65        0-0.2 (0.1)           14,000 [2,000]                0.5
                                               60              0 (0)              1,400 [200]                0.1
>= 60 ppb.....................                 75      9.5-17 (12.2)      2,316,000 [246,000]               25.8
                                               70     3.3-10.2 (6.2)      1,176,000 [126,000]               18.9
                                               65        0-4.2 (2.1)         392,000 [42,000]                9.5
                                               60        0-1.2 (0.4)           70,000 [8,000]                2.2
----------------------------------------------------------------------------------------------------------------
                                   Two or more exposures of concern per season
----------------------------------------------------------------------------------------------------------------
>= 80 ppb.....................                 75              0 (0)                600 [100]                0.1
                                               70              0 (0)                    0 [0]                  0
                                               65              0 (0)                    0 [0]                  0
                                               60              0 (0)                    0 [0]                  0
>= 70 ppb.....................                 75      0.1-0.6 (0.2)           46,000 [5,000]                2.2
                                               70          0-0.1 (0)              5,400 [600]                0.4
                                               65              0 (0)                300 [100]                  0
                                               60              0 (0)                    0 [0]                  0
>= 60 ppb.....................                 75      3.1-7.6 (4.5)         865,000 [93,000]               14.4
                                               70      0.5-3.5 (1.7)         320,000 [35,000]                9.2
                                               65        0-0.8 (0.3)           67,000 [7,500]                2.8
                                               60          0-0.2 (0)              5,100 [700]                0.3
----------------------------------------------------------------------------------------------------------------

    Uncertainties in exposure estimates are summarized in section
II.C.2.b of the proposal (79 FR 75273). For example, due to variability
in responsiveness, only a subset of individuals who experience
exposures at or above a benchmark concentration can be expected to
experience health effects.\53\ In addition, not all of these effects
will be adverse. Given the lack of sufficient exposure-response
information for most of the health effects that informed benchmark
concentrations, estimates of the number of people likely to experience
exposures at or above benchmark concentrations generally cannot be
translated into quantitative estimates of the number of people likely
to experience specific health effects.\54\ The PA views health-relevant
exposures as a continuum with greater confidence and less uncertainty
about the existence of adverse health effects at higher O3
exposure concentrations, and less confidence and greater uncertainty as
one considers lower exposure concentrations (e.g., U.S. EPA, 2014c,

sections 3.1 and 4.6). This view draws from the overall body of
available health evidence, which indicates that as exposure
concentrations increase, the incidence, magnitude, and severity of
effects increases.
---------------------------------------------------------------------------

    \53\ As noted below (II.C.3.a.ii), in the case of asthmatics,
responsiveness to O3 could depend on factors that have
not been well-evaluated, such as asthma severity, the effectiveness
of asthma control, or the prevalence of medication use.
    \54\ The exception to this is lung function decrements, as
discussed below (and in U.S. EPA, 2014c, section <IP_ADDRESS>).
---------------------------------------------------------------------------

    Another important uncertainty is that there is very limited
evidence from controlled human exposure studies, which provided the
basis for health benchmark concentrations for both exposures of concern
and lung function decrements, related to clinical responses in at-risk
populations. Compared to the healthy young adults included in the
controlled human exposure studies, members of at-risk populations could
be more likely to experience adverse effects, could experience larger
and/or more serious effects, and/or could experience effects following
exposures to lower O3 concentrations.\55\
---------------------------------------------------------------------------

    \55\ ``The CASAC further notes that clinical studies do not
address sensitive subgroups, such as children with asthma, and that
there is a scientific basis to anticipate that the adverse effects
for such subgroups are likely to be more significant at 60 ppb than
for healthy adults'' (Frey 2014a, p. 7).
---------------------------------------------------------------------------

    There are also uncertainties associated with the exposure
modelling. These are described most fully, and their potential impact
characterized, in section 5.5.2 of the HREA (U.S. EPA, 2013, pp. 5-72
to 5-79). These include interpretation of activity patterns set forth
in diaries which do not typically distinguish the basis for activity
patterns and so may reflect averting behavior,\56\ and whether the HREA
underestimates exposures for groups spending especially large
proportion of time being active outdoors during the O3
season (outdoor workers and especially active children).
---------------------------------------------------------------------------

    \56\ See EPA 2014a pp. 5-53 to 54 describing EPA's sensitivity
analysis regarding impacts of potential averting behavior for
school-age children on the exposure and lung function decrement
estimate, and see also section B.2.a.i below.
---------------------------------------------------------------------------

c. Quantitative Health Risk Assessments
    As discussed in section II.C.3 of the proposal (79 FR 75274), for
some health endpoints, there is sufficient scientific evidence and
information available to support the development of quantitative
estimates of O3-related health risks. In the current review,
for short-term O3 concentrations, the HREA estimates lung
function decrements; respiratory symptoms in asthmatics; hospital
admissions and emergency department visits for respiratory causes; and
all-cause mortality (U.S. EPA, 2014a). For long-term O3
concentrations, the HREA estimates respiratory mortality (U.S. EPA,
2014a).\57\ Estimates of O3-induced lung function decrements
are based on exposure modeling using the MSS model (see section
II.1.b.i.(1) above, and 79 FR 75250), combined with exposure-response
relationships from controlled human exposure studies (U.S. EPA, 2014a,
Chapter 6). Estimates of O3-associated respiratory symptoms,
hospital admissions and emergency department visits, and mortality are
based on concentration-response relationships from epidemiologic
studies (U.S. EPA, 2014a, Chapter 7). As with the exposure assessment
discussed above, O3-associated health risks are estimated
for recent air quality and for ambient concentrations adjusted to just
meet the current and alternative O3 standards, based on
2006-2010 air quality and adjusted precursor emissions. The following
sections summarize the discussions from the proposal on the lung
function risk assessment (II.A.2.c.i) and the epidemiology-based
morbidity and mortality risk assessments (II.A.2.c.ii).
---------------------------------------------------------------------------

    \57\ Estimates of O3-associated respiratory mortality
are based on the study by Jerrett et al. (2009). This study used
seasonal averages of 1-hour daily maximum O3
concentrations to estimate long-term concentrations.
---------------------------------------------------------------------------

i. Lung Function Risk Assessment
    The HREA estimates risks of lung function decrements in school-aged
children (ages 5 to 18), asthmatic school-aged children, and the
general adult population for the 15 urban study areas. The results
presented in the HREA are based on an updated dose-threshold model that
estimates FEV1 responses for individuals following short-
term exposures to O3 (McDonnell et al., 2012), reflecting
methodological improvements since the last review (II.B.2.a.i (1),
above; U.S. EPA, 2014a, section 6.2.4). The impact of the dose
threshold is that O3-induced FEV1 decrements
result primarily from exposures on days with average ambient
O3 concentrations above about 40 ppb (U.S. EPA, 2014a,
section 6.3.1, Figure 6-9).\58\
---------------------------------------------------------------------------

    \58\ Analysis of this issue in the HREA is based on risk
estimates in Los Angeles for 2006 unadjusted air quality. The HREA
shows that more than 90% of daily instances of FEV1
decrements >=10% occur when 8-hr average ambient concentrations are
above 40 ppb for this modeled scenario. The HREA notes that the
distribution of responses will be different for different study
areas, years, and air quality scenarios (U.S. EPA, 2014c, Chapter
6).
---------------------------------------------------------------------------

    Table 2 in the proposal (79 FR 75275), and reprinted below,
summarizes key results from the lung function risk assessment. Table 2
presents estimates of the percentages of school-aged children estimated
to experience O3-induced FEV1 decrements
10, 15, or 20% when air quality was adjusted to just meet
the current and alternative 8-hour O3 standards. Table 2
also presents the numbers of children, including children with asthma,
estimated to experience such decrements.

 Table 2--Summary of Estimated O3-Induced Lung Function Decrements for the Current and Potential Alternative O3
                                       Standards in Urban Case Study Areas
----------------------------------------------------------------------------------------------------------------
                                                                       Number of children (5
                                   Alternative         Average %      to 18 years) [number of   % Children worst
    Lung function decrement       standard level     children \59\      asthmatic children]      year and area
                                                                                \60\
----------------------------------------------------------------------------------------------------------------
                                        One or more decrements per season
----------------------------------------------------------------------------------------------------------------
>=10%.........................                 75              14-19      3,007,000 [312,000]                 22
                                               70              11-17      2,527,000 [261,000]                 20
                                               65               3-15      1,896,000 [191,000]                 18
                                               60               5-11  \61\1,404,000 [139,000]                 13
>=15%.........................                 75                3-5         766,000 [80,000]                  7
                                               70                2-4         562,000 [58,000]                  5
                                               65                0-3         356,000 [36,000]                  4
                                               60                1-2         225,000 [22,000]                  3
>=20%.........................                 75                1-2         285,000 [30,000]                2.8
                                               70                1-2         189,000 [20,000]                2.1
                                               65                0-1         106,000 [11,000]                1.4
                                               60                0-1           57,000 [6,000]                0.9
----------------------------------------------------------------------------------------------------------------

                                        Two or more decrements per season
----------------------------------------------------------------------------------------------------------------
>=10%.........................                 75             7.5-12      1,730,000 [179,000]                 14
                                               70             5.5-11      1,414,000 [145,000]                 13
                                               65            1.3-8.8      1,023,000 [102,000]                 11
                                               60            2.1-6.4         741,000 [73,000]                7.3
>=15%.........................                 75            1.7-2.9         391,000 [40,000]                3.8
                                               70            0.9-2.4         276,000 [28,000]                3.1
                                               65            0.1-1.8         168,000 [17,000]                2.3
                                               60            0.2-1.0         101,000 [10,000]                1.4
>=20%.........................                 75            0.5-1.1         128,000 [13,000]                1.5
                                               70            0.3-0.8           81,000 [8,000]                1.1
                                               65              0-0.5           43,000 [4,000]                0.8
                                               60              0-0.2           21,000 [2,000]                0.4
----------------------------------------------------------------------------------------------------------------

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

    \59\ Estimates in each urban case study area were averaged for
the years evaluated in the HREA (2006 to 2010). Ranges reflect the
ranges across urban study areas.
    \60\ Numbers of children estimated to experience decrements in
each study urban case study area were averaged over 2006 to 2010.
These averages were then summed across urban study areas. Numbers
are rounded to nearest thousand unless otherwise indicated.
    \61\ As discussed in section 4.3.3 of the HREA, the model-based
air quality adjustment approach used to estimate risks associated
with the current and alternative standards was unable to estimate
the distribution of ambient O3 concentrations in New York
City upon just meeting an alternative standard with a level of 60
ppb. Therefore, for the 60 ppb standard level, the numbers of
children and asthmatic children experiencing decrements, and the
ranges of percentages of such children across study areas, reflect
all of the urban study areas except New York City. Because of this,
in some cases (i.e., when New York City provided the smallest risk
estimate), the lower end of the ranges in Table 2 are higher for a
standard level of 60 ppb than for a level of 65 ppb.
---------------------------------------------------------------------------

    Uncertainties in estimates of lung function risks are summarized in
section II.C.3.a.ii of the proposal (79 FR 75275). In addition to the
uncertainties noted for exposure estimates, an uncertainty which
impacts lung function risk estimates stems from the lack of exposure-
response information in children. In the near absence of controlled
human exposure data for children, risk estimates are based on the
assumption that children exhibit the same lung function response
following O3 exposures as healthy 18 year olds (i.e., the
youngest age for which controlled human exposure data is generally
available) (U.S. EPA, 2014a, section 6.5.3). This assumption is
justified in part by the findings of McDonnell et al. (1985), who
reported that children (8-11 years old) experienced FEV1
responses similar to those observed in adults (18-35 years old) (U.S.
EPA, 2014a, p. 3-10). In addition, as discussed in the ISA (U.S. EPA,
2013, section 6.2.1), summer camp studies of school-aged children
reported O3-induced lung function decrements similar in
magnitude to those observed in controlled human exposure studies using
adults. In extending the risk model to children, the HREA thus fixes
the age term in the model at its highest value, the value for age 18.
Notwithstanding the information just summarized supporting this
approach, EPA acknowledges the uncertainty involved, and notes that the
approach could result in either over- or underestimates of
O3-induced lung function decrements in children, depending
on how children compare to the adults used in controlled human exposure
studies (U.S. EPA, 2014a, section 6.5.3).
    A related source of uncertainty is that the risk assessment
estimates of O3-induced decrements in asthmatics used the
exposure-response relationship developed from data collected from
healthy individuals. Although the evidence has been mixed (U.S. EPA,
2013, section <IP_ADDRESS>), several studies have reported statistically
larger, or a tendency toward larger, O3-induced lung
function decrements in asthmatics than in non-asthmatics (Kreit et al.,
1989; Horstman et al., 1995; Jorres et al., 1996; Alexis et al., 2000).
On this issue, CASAC noted that ``[a]sthmatic subjects appear to be at
least as sensitive, if not more sensitive, than non-asthmatic subjects
in manifesting O3-induced pulmonary function decrements''
(Frey, 2014c, p. 4). To the extent asthmatics experience larger
O3-induced lung function decrements than the healthy adults
used to develop exposure-response relationships, the HREA could
underestimate the impacts of O3 exposures on lung function
in asthmatics, including asthmatic children. The implications of this
uncertainty for risk estimates remain unknown at this time (U.S. EPA,
2014a, section 6.5.4), and could depend on a variety of factors that
have not been well-evaluated, including the severity of asthma and the
prevalence of medication use. However, the available evidence shows
responses to O3 increase with severity of asthma (Horstman
et al., 1995) and corticosteroid usage does not prevent O3
effects on lung function decrements or respiratory symptoms in people
with asthma (Vagaggini et al., 2001, 2007).
ii. Mortality and Morbidity Risk Assessments
    As discussed in section II.C.3.b of the proposal (79 FR 75276), the
HREA estimates O3-associated risks in 12 urban study areas
\62\ using concentration-response relationships drawn from
epidemiologic studies. These concentration-response relationships are
based on ``area-wide'' average O3 concentrations.\63\ The
HREA estimates risks for the years 2007 and 2009 in order to provide
estimates of risk for a year with generally higher O3

concentrations (2007) and a year with generally lower O3
concentrations (2009) (U.S. EPA, 2014a, section 7.1.1).
---------------------------------------------------------------------------

    \62\ The 12 urban areas evaluated are Atlanta, Baltimore,
Boston, Cleveland, Denver, Detroit, Houston, Los Angeles, New York,
Philadelphia, Sacramento, and St. Louis.
    \63\ In the epidemiologic studies that provide the health basis
for HREA risk assessments, concentration-response relationships are
based on daytime O3 concentrations, averaged across
multiple monitors within study areas. These daily averages are used
as surrogates for the spatial and temporal patterns of exposures in
study populations. Consistent with this approach, the HREA
epidemiologic-based risk estimates also utilize daytime
O3 concentrations, averaged across monitors, as
surrogates for population exposures. In this notice, we refer to
these averaged concentrations as ``area-wide'' O3
concentrations. Area-wide concentrations are discussed in more
detail in section 3.1.4 of the PA (U.S. EPA, 2014c).
---------------------------------------------------------------------------

    In considering the epidemiology-based risk estimates, the proposal
focuses on mortality risks associated with short-term O3
concentrations. The proposal considers estimates of total risk (i.e.,
based on the full distributions of ambient O3
concentrations) and estimates of risk associated with O3
concentrations in the upper portions of ambient distributions. Both
estimates are discussed to provide information that considers risk
estimates based on concentration-response relationships being linear
over the entire distribution of ambient O3 concentrations,
and thus have the greater potential for morbidity and mortality to be
affected by changes in relatively low O3 concentrations, as
well as risk estimates that are associated with O3
concentrations in the upper portions of the ambient distribution, thus
focusing on risk from higher O3 concentrations and placing
greater weight on the uncertainty associated with the shapes of
concentration-response curves for O3 concentrations in the
lower portions of the distribution. These results for O3-
associated mortality risk are summarized in Table 3 in the proposal (79
FR 75277).
    Important uncertainties in epidemiology-based risk estimates, based
on their consideration in the HREA and PA, are discussed in section
II.C.3.b.ii of the proposal (79 FR 75277). Compared to estimates of
O3 exposures of concern and estimates of O3-
induced lung function decrements (discussed above), the HREA
conclusions reflect lower confidence in epidemiologic-based risk
estimates (U.S. EPA, 2014a, section 9.6). In particular, the HREA
highlights the heterogeneity in effect estimates between locations, the
potential for exposure measurement errors, and uncertainty in the
interpretation of the shape of concentration-response functions at
lower O3 concentrations (U.S. EPA, 2014a, section 9.6). The
HREA also concludes that lower confidence should be placed in the
results of the assessment of respiratory mortality risks associated
with long-term O3, primarily because that analysis is based
on only one study, though that study is well-designed, and because of
the uncertainty in that study about the existence and identification of
a potential threshold in the concentration-response function (U.S. EPA,
2014a, section 9.6).\64,65\ This section further discusses some of the
key uncertainties in epidemiologic-based risk estimates, as summarized
in the PA (U.S. EPA, 2014c, section <IP_ADDRESS>), with a focus on
uncertainties that can have particularly important implications for the
Administrator's consideration of epidemiology-based risk estimates.
---------------------------------------------------------------------------

    \64\ The CASAC also concluded that ``[i]n light of the potential
nonlinearity of the C-R function for long-term exposure reflecting a
threshold of the mortality response, the estimated number of
premature deaths avoidable for long-term exposure reductions for
several levels need to be viewed with caution'' (Frey, 2014a, p. 3).
    \65\ There is also uncertainty about the extent to which
mortality estimates based on the long-term metric used in the study
by Jerrett et al. (2009) (i.e., seasonal average of 1-hour daily
maximum concentrations) reflects associations with long-term average
O3 versus repeated occurrences of elevated short-term
concentrations.
---------------------------------------------------------------------------

    The PA notes that reducing NOX emissions generally
reduces O3-associated mortality and morbidity risk estimates
in locations and time periods with relatively high ambient
O3 concentrations and increases risk estimates in locations
and time periods with relatively low concentrations (II.A, above). When
evaluating uncertainties in epidemiologic risk estimates, the PA
considered (1) the extent to which the modeled O3 response
to reductions in NOX emissions appropriately represents the
trends observed in monitored ambient O3 following actual
reductions in NOX emissions, (2) the extent to which the
O3 response to reductions in precursor emissions could
differ with emissions reduction strategies that are different from
those used in HREA to generate risk estimates, and (3) the extent to
which estimated changes in risks in urban study areas are
representative of the changes that would be experienced broadly across
the U.S. population. The first two of these issues are discussed in
section II.A.2.c above. The third issue is discussed below.
    The HREA conducted national air quality modeling analyses that
estimated the proportion of the U.S. population living in locations
where seasonal averages of daily O3 concentrations are
estimated to decrease in response to reductions in NOX
emissions, and the proportion living in locations where such seasonal
averages are estimated to increase. Given the close relationship
between changes in seasonal averages of daily O3
concentrations and changes in seasonal mortality and morbidity risk
estimates, this analysis informs consideration of the extent to which
the risk results in urban study areas represent the U.S. population as
a whole. This ``representativeness analysis'' indicates that the
majority of the U.S. population lives in locations where reducing
NOX emissions would be expected to result in decreases in
warm season averages of daily maximum 8-hour ambient O3
concentrations. Because the HREA urban study areas tend to
underrepresent the populations living in such areas (e.g., suburban,
smaller urban, and rural areas), risk estimates for the urban study
areas are likely to understate the average reductions in O3-
associated mortality and morbidity risks that would be experienced
across the U.S. population as a whole upon reducing NOX
emissions (U.S. EPA, 2014a, section <IP_ADDRESS>).
    Section 7.4 of the HREA also highlights some additional
uncertainties associated with epidemiologic-based risk estimates (U.S.
EPA, 2014a). This section of the HREA identifies and discusses sources
of uncertainty and presents a qualitative evaluation of key parameters
that can introduce uncertainty into risk estimates (U.S. EPA, 2014a,
Table 7-4). For several of these parameters, the HREA also presents
quantitative sensitivity analyses (U.S. EPA, 2014a, sections 7.4.2 and
7.5.3). Of the uncertainties discussed in Chapter 7 of the HREA, those
related to the application of concentration-response functions from
epidemiologic studies can have particularly important implications for
consideration of epidemiology-based risk estimates, as discussed below.
    An important uncertainty is the shape of concentration-response
functions at low ambient O3 concentrations (U.S. EPA, 2014a,
Table 7-4).\66\ In recognition of the ISA's conclusion that certainty
in the shape of O3 concentration-response functions
decreases at low ambient concentrations, the HREA provides estimates of
epidemiology-based mortality risks for entire distributions of ambient
O3 concentrations, as well as estimates of total mortality
associated with various ambient O3 concentrations. The PA
considers both types of risk estimates, recognizing greater public
health concern for adverse O3-attributable effects at higher
ambient O3 concentrations (which drive higher exposure
concentrations, section 3.2.2 of the PA (U.S. EPA, 2014c)), as compared
to lower concentrations.
---------------------------------------------------------------------------

    \66\ A related uncertainty is the existence, or not, of a
threshold. The HREA addresses this issue for long-term O3
by evaluating risks in models that include potential thresholds
(II.D.2.c).
---------------------------------------------------------------------------

    A related consideration is associated with the public health
importance of the increases in relatively low O3
concentrations following air quality adjustment. There is uncertainty
that relates to the assumption that the concentration response function
for O3 is linear, such that total risk estimates are equally
influenced by decreasing

high concentrations and increasing low concentrations, when the
increases and decreases are of equal magnitude. Even on days with
increases in relatively low area-wide average concentrations, resulting
in increases in estimated risks, some portions of the urban study areas
could experience decreases in high O3 concentrations. To the
extent adverse O3-attributable effects are more strongly
supported for higher ambient concentrations (which, as noted above, are
consistently reduced upon air quality adjustment), the impacts on risk
estimates of increasing low O3 concentrations reflect an
important source of uncertainty. In addition to the uncertainties
discussed above, the proposal also notes uncertainties related to (1)
using concentration-response relationships developed for a particular
population in a particular location to estimate health risks in
different populations and locations; (2) using concentration-response
functions from epidemiologic studies reflecting a particular air
quality distribution to adjusted air quality necessarily reflecting a
different (simulated) air quality distribution; (3) using a national
concentration-response function to estimate respiratory mortality
associated with long-term O3; and (4) unquantified
reductions in risk that could be associated with reductions in the
ambient concentrations of pollutants other than O3,
resulting from control of NOX (79 FR 75277 to 75279).

B. Need for Revision of the Primary Standard

    The initial issue to be addressed in the current review of the
primary O3 standard is whether, in view of the advances in
scientific knowledge and additional information, it is appropriate to
revise the existing standard. This section presents the Administrator's
final decision on whether it is ``appropriate'' to revise the current
standard within the meaning of section 109 (d)(1) of the CAA. Section
II.B.1 contains a summary discussion of the basis for the proposed
conclusions on the adequacy of the primary standard. Section II.B.2
discusses comments received on the adequacy of the primary standard.
Section II.B.3 presents the Administrator's final conclusions on the
adequacy of the current primary standard.
1. Basis for Proposed Decision
    In evaluating whether it is appropriate to retain or revise the
current standard, the Administrator's considerations build upon those
in the 2008 review, including consideration of the broader body of
scientific evidence and exposure and health risk information now
available, as summarized in sections II.A to II.C (79 FR 75246-75279)
of the proposal and section II.A above.
    In developing conclusions on the adequacy of the current primary
O3 standard, the Administrator takes into account both
evidence-based and quantitative exposure- and risk-based
considerations. Evidence-based considerations include the assessment of
evidence from controlled human exposure, animal toxicological, and
epidemiologic studies for a variety of health endpoints. The
Administrator focuses on health endpoints for which the evidence is
strong enough to support a ``causal'' or a ``likely to be causal''
relationship, based on the ISA's integrative synthesis of the entire
body of evidence. The Administrator's consideration of quantitative
exposure and risk information draws from the results of the exposure
and risk assessments presented in the HREA.
    The Administrator's consideration of the evidence and exposure/risk
information is informed by the considerations and conclusions presented
in the PA (U.S. EPA, 2014c). The purpose of the PA is to help ``bridge
the gap'' between the scientific and technical information assessed in
the ISA and HREA, and the policy decisions that are required of the
Administrator (U.S. EPA, 2014c, Chapter 1); see also American Farm
Bureau Federation, 559 F. 3d at 516, 521 (``[a]lthough not required by
the statute, in practice EPA staff also develop a Staff Paper, which
discusses the information in the Criteria Document that is most
relevant to the policy judgments the EPA makes when it sets the
NAAQS''). The PA's evidence-based and exposure-/risk-based
considerations and conclusions are briefly summarized below in sections
II.B.1.a (evidence-based considerations), II.B.1.b (exposure- and risk-
based considerations), and II.B.1.c (PA conclusions on the current
standard). Section II.B.1.d summarizes CASAC advice to the
Administrator and public commenter views on the current standard.
Section II.B.1.e presents a summary of the Administrator's proposed
conclusions concerning the adequacy of the public health protection
provided by the current standard, and her proposed decision to revise
that standard.
a. Evidence-Based Considerations From the PA
    In considering the available scientific evidence, the PA evaluates
the O3 concentrations in health effects studies (U.S. EPA,
2014c, section 3.1.4). Specifically, the PA characterizes the extent to
which health effects have been reported for the O3 exposure
concentrations evaluated in controlled human exposure studies, and
effects occurring over the distributions of ambient O3
concentrations in locations where epidemiologic studies have been
conducted. These considerations, as they relate to the adequacy of the
current standard, are presented in detail in section 3.1.4 of the PA
(U.S. EPA, 2014c) and are summarized in the proposal (79 FR 75279-
75287). The PA's considerations are summarized briefly below for
controlled human exposure, epidemiologic panel studies, and
epidemiologic population-based studies.
    Section II.D.1.a of the proposal discusses the PA's consideration
of the evidence from controlled human exposure and panel studies. This
evidence is assessed in section 6.2 of the ISA (U.S. EPA, 2013) and is
summarized in section 3.1.2 of the PA (U.S. EPA, 2014c). A large number
of controlled human exposure studies have reported lung function
decrements, respiratory symptoms, air inflammation, airway
hyperresponsiveness, and/or impaired lung host defense in young,
healthy adults engaged in moderate quasi-continuous exertion, following
6.6-hour O3 exposures. These studies have consistently
reported such effects following exposures to O3
concentrations of 80 ppb or greater. In addition to lung function
decrements, available studies have evaluated respiratory symptoms or
airway inflammation following exposures to O3 concentrations
below 75 ppb. Table 3-1 in the PA highlights the group mean results of
individual controlled human exposure studies that evaluated exposures
to O3 concentrations below 75 ppb. These studies observe the
combination of lung function decrements and respiratory symptoms
following exposures to O3 concentrations as low as 72 ppb,
and lung function decrements and airway inflammation following
exposures to O3 concentrations as low as 60 ppb (based on
group means).
    Based on this evidence, the PA notes that controlled human exposure
studies have reported a variety of respiratory effects in young,
healthy adults following exposures to a wide range of O3
concentrations for 6.6 hours, including exposures to concentrations
below 75 ppb. In particular, the PA further notes that a recent
controlled human exposure study reported the combination of lung
function decrements and respiratory symptoms in healthy adults engaged
in quasi-

continuous, moderate exertion following 6.6 hour exposures to 72 ppb
O3, a combination of effects that have been classified as
adverse based on ATS guidelines for adversity (ATS, 2000a). In
addition, a recent study has also reported lung function decrements and
pulmonary inflammation following exposure to 60 ppb O3.
Sixty ppb is the lowest exposure concentration for which inflammation
has been evaluated and reported to occur, and corresponds to the lowest
exposure concentration demonstrated to result in lung function
decrements large enough to be judged an abnormal response by ATS (ATS,
2000b). The PA also notes, and CASAC agreed, that these controlled
human exposure studies were conducted in healthy adults, while at-risk
groups (e.g., children, people with asthma) could experience larger
and/or more serious effects. Therefore, the PA concludes that the
evidence from controlled human exposure studies provide support that
the respiratory effects experienced following exposures to
O3 concentrations lower than 75 ppb would be adverse in some
individuals, particularly if experienced by members of at-risk
populations (e.g., people with asthma, children).
    The PA also notes consistent results in some panel studies of
O3-associated lung function decrements. In particular, the
PA notes that epidemiologic panel studies in children and adults
consistently indicate O3-associated lung function decrements
when on-site, ambient monitored concentrations were below 75 ppb
(although the evidence becomes less consistent at low O3
concentrations, and the averaging periods involved ranged from 10
minutes to 12 hours (U.S. EPA, 2014c, section <IP_ADDRESS>)).
    Section II.D.1.b of the proposal summarizes the PA's analyses of
monitored O3 concentrations in locations of epidemiologic
studies. While the majority of the epidemiologic study areas evaluated
would have violated the current standard during study periods, the PA
makes the following observations with regard to health effect
associations at O3 concentrations likely to have met the
current standard:
    (1) A single-city study reported positive and statistically
significant associations with asthma emergency department visits in
children and adults in Seattle, a location that would have met the
current standard over the entire study period (Mar and Koenig, 2009).
    (2) Additional single-city studies support associations with
respiratory morbidity at relatively low ambient O3
concentrations, including when virtually all monitored concentrations
were below the level of the current standard (Silverman and Ito, 2010;
Strickland et al., 2010).
    (3) Canadian multicity studies reported positive and statistically
significant associations with respiratory morbidity or mortality when
the majority of study cities, though not all study cities, would have
met the current standard over the study period in each of these studies
(Cakmak et al., 2006; Dales et al., 2006; Katsouyanni et al., 2009;
Stieb et al., 2009).
    (4) A U.S. multicity study reported positive and statistically
significant associations with mortality when ambient O3
concentrations were restricted to those likely to have met the current
O3 standard (Bell et al., 2006).
    The PA also takes into account important uncertainties in these
analyses of air quality in locations of epidemiologic study areas.
These uncertainties are summarized in section II.D.1.b.iii of the
proposal. Briefly, they include the following: (1) Uncertainty in
conclusions about the extent to which multicity effect estimates
reflect associations with air quality meeting the current standard,
versus air quality violating that standard; (2) uncertainty regarding
the potential for thresholds to exist, given that regional
heterogeneity in O3 health effect associations could obscure
the presence of thresholds, should they exist; (3) uncertainty in the
extent to which the PA appropriately recreated the air quality analyses
in the published study by Bell et al. (2006); and (4) uncertainty in
the extent to which reported health effects are caused by exposures to
O3 itself, as opposed to other factors such as co-occurring
pollutants or pollutant mixtures, particularly at low ambient
O3 concentrations.\67\
---------------------------------------------------------------------------

    \67\ As noted above (section II.A.1.B.i), the ISA concludes that
studies that examined the potential confounding effects of
copollutants found that O3 effect estimates remained
relatively robust upon the inclusion of PM and gaseous pollutants in
two-pollutant models (U.S. EPA, 2013, section <IP_ADDRESS>).
---------------------------------------------------------------------------

    In considering the analyses of monitored O3 air quality
in locations of epidemiologic studies, as well as the important
uncertainties in these analyses, the PA concludes that these analyses
provide support for the occurrence of morbidity and mortality
associated with short-term ambient O3 concentrations likely
to meet the current O3 standard.\68\ In considering the
evidence as a whole, the PA concludes that (1) controlled human
exposure studies provide strong support for the occurrence of adverse
respiratory effects following exposures to O3 concentrations
below the level of the current standard and (2) epidemiologic studies
provide support for the occurrence of adverse respiratory effects and
mortality under air quality conditions that would meet the current
standard.
---------------------------------------------------------------------------

    \68\ Unlike for the studies of short-term O3, the
available U.S. and Canadian epidemiologic studies evaluating long-
term ambient O3 concentration metrics have not been
conducted in locations likely to have met the current 8-hour
O3 standard during the study period, and have not
reported concentration-response functions that indicate confidence
in health effect associations at O3 concentrations
meeting the current standard (U.S. EPA, 2014c, section <IP_ADDRESS>).
---------------------------------------------------------------------------

b. Exposure- and Risk-Based Considerations in the PA
    In order to further inform judgments about the potential public
health implications of the current O3 NAAQS, the PA
considers the exposure and risk assessments presented in the HREA (U.S.
EPA, 2014c, section 3.2). Overviews of these exposure and risk
assessments, including brief summaries of key results and
uncertainties, are provided in section II.A.2 above. Section II.D.2 of
the proposal summarizes key observations from the PA related to the
adequacy of the current O3 NAAQS, based on consideration of
the HREA exposure assessment, lung function risk assessment, and
mortality/morbidity risk assessments (79 FR 75283).
    Section II.D.2.a of the proposal summarizes key observations from
the PA regarding estimates of O3 exposures of concern (79 FR
75283). Given the evidence for respiratory effects from controlled
human exposure studies, the PA considers the extent to which the
current standard would be estimated to protect at-risk populations
against exposures of concern to O3 concentrations at or
above the health benchmark concentrations of 60, 70, and 80 ppb (i.e.,
based on HREA estimates of one or more and two or more exposures of
concern). In doing so, the PA notes the CASAC conclusion that (Frey,
2014c, p. 6):

    The 80 ppb-8hr benchmark level represents an exposure level for
which there is substantial clinical evidence demonstrating a range
of ozone-related effects including lung inflammation and airway
responsiveness in healthy individuals. The 70 ppb-8hr benchmark
level reflects the fact that in healthy subjects, decreases in lung
function and respiratory symptoms occur at concentrations as low as
72 ppb and that these effects almost certainly occur in some people,
including asthmatics and others with low lung function who are less
tolerant of such effects, at levels of 70 ppb and below. The 60 ppb-
8hr benchmark level represents the lowest exposure level at which
ozone-

related effects have been observed in clinical studies of healthy
individuals.

    For exposures of concern at or above 60 ppb, the proposal
highlights the following key observations for air quality adjusted to
just meet the current standard:
    (1) On average over the years 2006 to 2010, the current standard is
estimated to allow approximately 10 to 18% of children in urban study
areas to experience one or more exposures of concern at or above 60
ppb. Summing across urban study areas, these percentages correspond to
almost 2.5 million children experiencing approximately 4 million
exposures of concern at or above 60 ppb during a single O3
season. Of these children, almost 250,000 are asthmatics.\69\
---------------------------------------------------------------------------

    \69\ As discussed in section II.C.2.b of the proposal, due to
variability in responsiveness, only a subset of individuals who
experience exposures at or above a benchmark concentration can be
expected to experience adverse health effects.
---------------------------------------------------------------------------

    (2) On average over the years 2006 to 2010, the current standard is
estimated to allow approximately 3 to 8% of children in urban study
areas to experience two or more exposures of concern to O3
concentrations at or above 60 ppb. Summing across the urban study
areas, these percentages correspond to almost 900,000 children
(including almost 90,000 asthmatic children).
    (3) In the worst-case years (i.e., those with the largest exposure
estimates), the current standard is estimated to allow approximately 10
to 25% of children to experience one or more exposures of concern at or
above 60 ppb, and approximately 4 to 14% to experience two or more
exposures of concern at or above 60 ppb.

    For exposures of concern at or above 70 ppb, the PA highlights the
following key observations for air quality adjusted to just meet the
current standard:
    (1) On average over the years 2006 to 2010, the current standard is
estimated to allow up to approximately 3% of children in urban study
areas to experience one or more exposures of concern at or above 70
ppb. Summing across urban study areas, almost 400,000 children
(including almost 40,000 asthmatic children) are estimated to
experience O3 exposure concentrations at or above 70 ppb
during a single O3 season.
    (2) On average over the years 2006 to 2010, the current standard is
estimated to allow less than 1% of children in urban study areas to
experience two or more exposures of concern to O3
concentrations at or above 70 ppb.
    (3) In the worst-case location and year, the current standard is
estimated to allow approximately 8% of children to experience one or
more exposures of concern at or above 70 ppb, and approximately 2% to
experience two or more exposures of concern, at or above 70 ppb.

For exposures of concern at or above 80 ppb, the PA highlights the
observation that the current standard is estimated to allow about 1% or
fewer children in urban study areas to experience exposures of concern
at or above 80 ppb, even in years with the highest exposure estimates.
    Uncertainties in exposure estimates are summarized in section
II.C.2.b of the proposal (79 FR 75273), and discussed more fully in the
HREA (U.S. EPA, 2014a, section 5.5.2) and the PA (U.S. EPA, 2014c,
section 3.2.2). Key uncertainties include the variability in
responsiveness following O3 exposures, resulting in only a
subset of exposed individuals experiencing health effects, adverse or
otherwise, and the limited evidence from controlled human exposure
studies conducted in at-risk populations. In addition, there are a
number of uncertainties in the exposure modelling approach used in the
HREA, contributing to overall uncertainty in exposure estimates.
    Section II.D.2.b of the proposal summarizes key observations from
the PA regarding the estimated risk of O3-induced lung
function decrements (79 FR 75283 to 75284). With respect to the lung
function decrements that have been evaluated in controlled human
exposure studies, the PA considers the extent to which standards with
revised levels would be estimated to protect healthy and at-risk
populations against one or more, and two or more, moderate (i.e.,
FEV1 decrements >=10% and >=15%) and large (i.e.,
FEV1 decrements >=20%) lung function decrements. As
discussed in section 3.1.3 of the PA (U.S. EPA, 2014c), although some
experts would judge single occurrences of moderate responses to be a
nuisance, especially for healthy individuals, a more general consensus
view of the adversity of moderate lung function decrements emerges as
the frequency of occurrence increases.
    With regard to decrements >=10%, the PA highlights the following
key observations for air quality adjusted to just meet the current
standard:
    (1) On average over the years 2006 to 2010, the current standard is
estimated to allow approximately 14 to 19% of children in urban study
areas to experience one or more lung function decrements >=10%. Summing
across urban study areas, this corresponds to approximately 3 million
children experiencing 15 million O3-induced lung function
decrements >=10% during a single O3 season. Of these
children, about 300,000 are asthmatics.
    (2) On average over the years 2006 to 2010, the current standard is
estimated to allow approximately 7 to 12% of children in urban study
areas to experience two or more O3-induced lung function
decrements >=10%. Summing across the urban study areas, this
corresponds to almost 2 million children (including almost 200,000
asthmatic children) estimated to experience two or more O3-
induced lung function decrements greater than 10% during a single
O3 season.
    (3) In the worst-case years, the current standard is estimated to
allow approximately 17 to 23% of children in urban study areas to
experience one or more lung function decrements >=10%, and
approximately 10 to 14% to experience two or more O3-induced
lung function decrements >=10%.

With regard to decrements >=15%, the PA highlights the following key
observations for air quality adjusted to just meet the current
standard:
    (1) On average over the years 2006 to 2010, the current standard is
estimated to allow approximately 3 to 5% of children in urban study
areas to experience one or more lung function decrements <=15%. Summing
across urban study areas, this corresponds to approximately 800,000
children (including approximately 80,000 asthmatic children) estimated
to experience at least one O3-induced lung function
decrement <=15% during a single O3 season.
    (2) On average over the years 2006 to 2010, the current standard is
estimated to allow approximately 2 to 3% of children in urban study
areas to experience two or more O3-induced lung function
decrements <=15%.
    (3) In the worst-case years, the current standard is estimated to
allow approximately 4 to 6% of children in urban study areas to
experience one or more lung function decrements <=15%, and
approximately 2 to 4% to experience two or more O3-induced
lung function decrements <=15%.

    With regard to decrements <=20%, the PA highlights the following
key observations for air quality adjusted to just meet the current
standard:
    (1) On average over the years 2006 to 2010, the current standard is
estimated to allow approximately 1 to 2% of children in urban study
areas to experience one or more lung function decrements >=20%. Summing
across

urban study areas, this corresponds to approximately 300,000 children
(including approximately 30,000 asthmatic children) estimated to
experience at least one O3-induced lung function decrement
>=20% during a single O3 season.
    (2) On average over the years 2006 to 2010, the current standard is
estimated to allow less than 1% of children in urban study areas to
experience two or more O3-induced lung function decrements
>=20%.
    (3) In the worst-case years, the current standard is estimated to
allow approximately 2 to 3% of children to experience one or more lung
function decrements >=20%, and less than 2% to experience two or more
O3-induced lung function decrements >=20%.

Uncertainties in lung function risk estimates are summarized in section
II.C.3.a of the proposal, and discussed more fully in the HREA (U.S.
EPA, 2014a, section 6.5) and the PA (U.S. EPA, 2014c, section <IP_ADDRESS>).
In addition to the uncertainties noted above for exposure estimates,
the key uncertainties associated with estimates of O3-
induced lung function decrements include the paucity of exposure-
response information in children and in people with asthma.
    Section II.D.2.c of the proposal summarizes key observations from
the PA regarding risk estimates of O3-associated mortality
and morbidity (79 FR 75284 to 75285). With regard to total mortality or
morbidity associated with short-term O3, the PA notes the
following for air quality adjusted to just meet the current standard:
    (1) When air quality was adjusted to the current standard for the
2007 model year (the year with generally ``higher'' O3-
associated risks), 10 of 12 urban study areas exhibited either
decreases or virtually no change in estimates of the number of
O3-associated deaths (U.S. EPA, 2014a, Appendix 7B).
Increases were estimated in two of the urban study areas (Houston, Los
Angeles)\70\ (U.S. EPA, 2014a, Appendix 7B).\71\
---------------------------------------------------------------------------

    \70\ As discussed above (II.C.1), in locations and time periods
when NOX is predominantly contributing to O3
formation (e.g., downwind of important NOX sources, where
the highest O3 concentrations often occur), model-based
adjustment to the current and alternative standards decreases
estimated ambient O3 concentrations compared to recent
monitored concentrations (U.S. EPA, 2014a, section <IP_ADDRESS>). In
contrast, in locations and time periods when NOX is
predominantly contributing to O3 titration (e.g., in
urban centers with high concentrations of NOX emissions,
where ambient O3 concentrations are often suppressed and
are thus relatively low), model-based adjustment increases ambient
O3 concentrations compared to recent monitored
concentrations (U.S. EPA, 2014a, section <IP_ADDRESS>). Changes in
epidemiology-based risk estimates depend on the balance between the
daily decreases in high O3 concentrations and increases
in low O3 concentrations following the model-based air
quality adjustment. Commenting on this issue, CASAC noted that
``controls designed to reduce the peak levels of ozone (e.g., the
fourth-highest annual MDA8) may not be effective at reducing lower
levels of ozone on more typical days and may actually increase ozone
levels on days where ozone concentrations are low'' (Frey 2014a, p.
2). CASAC further noted that risk results ``suggest that the ozone-
related health risks in the urban cores can increase for some of the
cities as ozone NAAQS alternatives become more stringent. This is
because reductions in nitrogen oxides emissions can lead to less
scavenging of ozone and free radicals, resulting in locally higher
levels of ozone'' (Frey 2014c, p. 10).
    \71\ For the 2009 adjusted year (i.e., the year with generally
lower O3 concentrations), changes in risk were generally
smaller than in 2007 (i.e., most changes about 2% or smaller).
Increases were estimated for Houston, Los Angeles, and New York
City.
---------------------------------------------------------------------------

    (2) In focusing on total risk, the current standard is estimated to
allow thousands of O3-associated deaths per year in the
urban study areas. In focusing on the risks associated with the upper
portions of distributions of ambient concentrations (area-wide
concentrations <= 40, 60 ppb), the current standard is estimated to
allow hundreds to thousands of O3-associated deaths per year
in the urban study areas.
    (3) The current standard is estimated to allow tens to thousands of
O3-associated morbidity events per year (i.e., respiratory-
related hospital admissions, emergency department visits, and asthma
exacerbations).

With regard to respiratory mortality associated with long-term
O3, the PA notes the following for air quality adjusted to
just meet the current standard:
    (1) Based on a linear concentration-response function, the current
standard is estimated to allow thousands of O3-associated
respiratory deaths per year in the urban study areas.
    (2) Based on threshold models, HREA sensitivity analyses indicate
that the number of respiratory deaths associated with long-term
O3 concentrations could potentially be considerably lower
(i.e., by more than 75% if a threshold exists at 40 ppb, and by about
98% if a threshold exists at 56 ppb) (U.S. EPA, 2014a, Figure 7-9).\72\
---------------------------------------------------------------------------

    \72\ Risk estimates for respiratory mortality associated with
long-term O3 exposures are based on the study by Jerrett
et al. (2009) (U.S. EPA, 2014a, Chapter 7). As discussed above
(II.B.2.b.iv) and in the PA (U.S. EPA, 2014c, section <IP_ADDRESS>),
Jerrett et al. (2009) reported that when seasonal averages of 1-hour
daily maximum O3 concentrations ranged from 33 to 104
ppb, there was no statistical deviation from a linear concentration-
response relationship between O3 and respiratory
mortality across 96 U.S. cities (U.S. EPA, 2013, section 7.7).
However, the authors reported ``limited evidence'' for an effect
threshold at an O3 concentration of 56 ppb (p=0.06). In
communications with EPA staff (Sasser, 2014), the study authors
indicated that it is not clear whether a threshold model is a better
predictor of respiratory mortality than the linear model, and that
``considerable caution should be exercised in accepting any specific
threshold.''
---------------------------------------------------------------------------

    Compared to the weight given to HREA estimates of exposures of
concern and lung function risks, and the weight given to the evidence,
the PA places relatively less weight on epidemiologic-based risk
estimates. In doing so, the PA notes that the overall conclusions from
the HREA likewise reflect less confidence in estimates of
epidemiologic-based risks than in estimates of exposures and lung
function risks. The determination to attach less weight to the
epidemiologic-based estimates reflects the uncertainties associated
with mortality and morbidity risk estimates, including the
heterogeneity in effect estimates between locations, the potential for
exposure measurement errors, and uncertainty in the interpretation of
the shape of concentration-response functions at lower O3
concentrations (U.S. EPA, 2014a, section 9.6).
    Uncertainty in the shape of concentration-response functions at
lower O3 concentrations is particularly important to
interpreting risk estimates given the approach used to adjust air
quality to just meet the current standard, and potential alternative
standards, and the resulting compression in the air quality
distributions (i.e., decreasing high concentrations and increasing low
concentrations) (II.A.2.a, above). Total risk estimates in the HREA are
based on the assumption that the concentration response function for
O3 is linear, such that total risk estimates are equally
influenced by decreasing high concentrations and increasing low
concentrations, when the increases and decreases are of equal
magnitude. However, consistent with the PA's consideration of risk
estimates, in the proposal the Administrator notes that the overall
body of evidence provides stronger support for the occurrence of

O3-attributable health effects following exposures to
O3 concentrations corresponding to the upper ends of typical
ambient distributions (II.E.4.d of the proposal). In addition, even on
days with increases in relatively low area-wide average concentrations,
resulting in increases in estimated risks, some portions of the urban
study areas could experience decreases in high O3
concentrations. Therefore, to the extent adverse O3-
attributable effects are more strongly supported for higher ambient
concentrations (which, as noted above, are consistently reduced upon
air quality adjustment), the PA notes that the impacts on risk
estimates of increasing low O3 concentrations reflect an
important source of uncertainty.
c. PA Conclusions on the Current Standard
    Section II.D.3 of the proposal summarizes the PA conclusions on the
adequacy of the existing primary O3 standard (79 FR 75285).
As an initial matter, the PA concludes that reducing precursor
emissions to achieve O3 concentrations that meet the current
standard will provide important improvements in public health
protection. This initial conclusion is based on (1) the strong body of
scientific evidence indicating a wide range of adverse health outcomes
attributable to exposures to O3 concentrations commonly
found in the ambient air and (2) estimates indicating decreased
occurrences of O3 exposures of concern and decreased health
risks upon meeting the current standard, compared to recent air
quality.
    In particular, the PA concludes that strong support for this
initial conclusion is provided by controlled human exposure studies of
respiratory effects, and by quantitative estimates of exposures of
concern and lung function decrements based on information in these
studies. Analyses in the HREA estimate that the percentages of children
(i.e., all children and children with asthma) in urban study areas
experiencing exposures of concern, or experiencing abnormal and
potentially adverse lung function decrements, are consistently lower
for air quality that just meets the current O3 standard than
for recent air quality. The HREA estimates such reductions consistently
across the urban study areas evaluated and throughout various portions
of individual urban study areas, including in urban cores and the
portions of urban study areas surrounding urban cores. These reductions
in exposures of concern and O3-induced lung function
decrements reflect the consistent decreases in the highest
O3 concentrations following reductions in precursor
emissions to meet the current standard. Thus, populations in both urban
and non-urban areas would be expected to experience important
reductions in O3 exposures and O3-induced lung
function risks upon meeting the current standard.
    The PA further concludes that support for this initial conclusion
is also provided by estimates of O3-associated mortality and
morbidity based on application of concentration-response relationships
from epidemiologic studies to air quality adjusted to just meet the
current standard. These estimates are based on the assumption that
concentration-response relationships are linear over entire
distributions of ambient O3 concentrations, an assumption
which has uncertainties that complicate interpretation of these
estimates (II.A.2.c.ii). However, risk estimates for effects associated
with short- and long-term O3 exposures, combined with the
HREA's national analysis of O3 responsiveness to reductions
in precursor emissions and the consistent reductions estimated for the
highest ambient O3 concentrations, suggest that
O3-associated mortality and morbidity would be expected to
decrease nationwide following reductions in precursor emissions to meet
the current O3 standard.
    After reaching the initial conclusion that meeting the current
primary O3 standard will provide important improvements in
public health protection, and that it is not appropriate to consider a
standard that is less protective than the current standard, the PA
considers the adequacy of the public health protection that is provided
by the current standard. In considering the available scientific
evidence, exposure/risk information, advice from CASAC (II.B.1.d,
below), and input from the public, the PA reaches the conclusion that
the available evidence and information clearly call into question the
adequacy of public health protection provided by the current primary
standard. In reaching this conclusion, the PA notes that evidence from
controlled human exposure studies provides strong support for the
occurrence of adverse respiratory effects following exposures to
O3 concentrations below the level of the current standard.
Epidemiologic studies provide support for the occurrence of adverse
respiratory effects and mortality under air quality conditions that
would likely meet the current standard. In addition, based on the
analyses in the HREA, the PA concludes that the exposures and risks
projected to remain upon meeting the current standard are indicative of
risks that can reasonably be judged to be important from a public
health perspective. Thus, the PA concludes that the evidence and
information provide strong support for giving consideration to revising
the current primary standard in order to provide increased public
health protection against an array of adverse health effects that range
from decreased lung function and respiratory symptoms to more serious
indicators of morbidity (e.g., including emergency department visits
and hospital admissions), and mortality. In consideration of all of the
above, the PA draws the conclusion that it is appropriate for the
Administrator to consider revision of the current primary O3
standard to provide increased public health protection.
d. CASAC Advice
    Section II.D.4 of the proposal summarizes CASAC advice regarding
the adequacy of the existing primary O3 standard. Following
the 2008 decision to revise the primary O3 standard by
setting the level at 0.075 ppm (75 ppb), CASAC strongly questioned
whether the standard met the requirements of the CAA. In September
2009, the EPA announced its intention to reconsider the 2008 standards,
issuing a notice of proposed rulemaking in January 2010 (75 FR 2938).
Soon after, the EPA solicited CASAC review of that proposed rule and in
January 2011, solicited additional advice. This proposal was based on
the scientific and technical record from the 2008 rulemaking, including
public comments and CASAC advice and recommendations. As further
described above (I.D), in the fall of 2011, the EPA did not revise the
standard as part of the reconsideration process but decided to defer
decisions on revisions to the O3 standards to the next
periodic review, which was already underway. Accordingly, in this
section we describe CASAC's advice related to the 2008 final decision
and the subsequent reconsideration, as well as its advice on this
current review of the O3 NAAQS that was initiated in
September 2008.
    In April 2008, the members of the CASAC Ozone Review Panel sent a
letter to EPA stating ``[I]n our most-recent letters to you on this
subject--dated October 2006 and March 2007--the CASAC unanimously
recommended selection of an 8-hour average Ozone NAAQS within the range
of 0.060 to 0.070 parts per million [60 to 70 ppb] for the primary
(human health-based) Ozone NAAQS'' (Henderson, 2008). In 2010, in
response to the EPA's solicitation of advice on the EPA's

proposed rulemaking as part of the reconsideration, CASAC again stated
that the current standard should be revised to provide additional
protection to the public health (Samet, 2010):

    CASAC fully supports EPA's proposed range of 0.060-0.070 parts
per million (ppm) for the 8-hour primary ozone standard. CASAC
considers this range to be justified by the scientific evidence as
presented in the Air Quality Criteria for Ozone and Related
Photochemical Oxidants (March 2006) and Review of the National
Ambient Air Quality Standards for Ozone: Policy Assessment of
Scientific and Technical Information, OAQPS Staff Paper (July 2007).
As stated in our letters of October 24, 2006, March 26, 2007 and
April 7, 2008 to former Administrator Stephen L. Johnson, CASAC
unanimously recommended selection of an 8-hour average ozone NAAQS
within the range proposed by EPA (0.060 to 0.070 ppm). In proposing
this range, EPA has recognized the large body of data and risk
analyses demonstrating that retention of the current standard would
leave large numbers of individuals at risk for respiratory effects
and/or other significant health impacts including asthma
exacerbations, emergency room visits, hospital admissions and
mortality.

    In response to the EPA's request for additional advice on the
reconsideration in 2011, CASAC reaffirmed their conclusion that ``the
evidence from controlled human and epidemiological studies strongly
supports the selection of a new primary ozone standard within the 60-70
ppb range for an 8-hour averaging time'' (Samet, 2011, p ii). As
requested by the EPA, CASAC's advice and recommendations were based on
the scientific and technical record from the 2008 rulemaking. In
considering the record for the 2008 rulemaking, CASAC stated the
following to summarize the basis for their conclusions (Samet, 2011,
pp. ii to iii):
    (1) The evidence available on dose-response for effects of
O3 shows associations extending to levels within the range
of concentrations currently experienced in the United States.
    (2) There is scientific certainty that 6.6-hour exposures with
exercise of young, healthy, non-smoking adult volunteers to
concentrations >=80 ppb cause clinically relevant decrements of lung
function.
    (3) Some healthy individuals have been shown to have clinically
relevant responses, even at 60 ppb.
    (4) Since the majority of clinical studies involve young, healthy
adult populations, less is known about health effects in such
potentially ozone sensitive populations as the elderly, children and
those with cardiopulmonary disease. For these susceptible groups,
decrements in lung function may be greater than in healthy volunteers
and are likely to have a greater clinical significance.
    (5) Children and adults with asthma are at increased risk of acute
exacerbations on or shortly after days when elevated O3
concentrations occur, even when exposures do not exceed the NAAQS
concentration of 75 ppb.
    (6) Large segments of the population fall into what the EPA terms a
``sensitive population group,'' i.e., those at increased risk because
they are more intrinsically susceptible (children, the elderly, and
individuals with chronic lung disease) and those who are more
vulnerable due to increased exposure because they work outside or live
in areas that are more polluted than the mean levels in their
communities.

With respect to evidence from epidemiologic studies, CASAC stated
``while epidemiological studies are inherently more uncertain as
exposures and risk estimates decrease (due to the greater potential for
biases to dominate small effect estimates), specific evidence in the
literature does not suggest that our confidence on the specific
attribution of the estimated effects of ozone on health outcomes
differs over the proposed range of 60-70 ppb'' (Samet, 2011, p. 10).
    Following its review of the second draft PA in the current review,
which considers an updated scientific and technical record since the
2008 rulemaking, CASAC concluded that ``there is clear scientific
support for the need to revise the standard'' (Frey, 2014c, p. ii). In
particular, CASAC noted the following (Frey, 2014c, p. 5):

    [T]he scientific evidence provides strong support for the
occurrence of a range of adverse respiratory effects and mortality
under air quality conditions that would meet the current standard.
Therefore, CASAC unanimously recommends that the Administrator
revise the current primary ozone standard to protect public
health.\73\
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    \73\ CASAC provided similar advice in their letter to the
Administrator on the HREA, stating that ``The CASAC finds that the
current primary NAAQS for ozone is not protective of human health
and needs to be revised'' (Frey, 2014a, p. 15).

    In supporting these conclusions, CASAC judged that the strongest
evidence comes from controlled human exposure studies of respiratory
effects. The Committee specifically noted that ``the combination of
decrements in FEV1 together with the statistically
significant alterations in symptoms in human subjects exposed to 72 ppb
ozone meets the American Thoracic Society's definition of an adverse
health effect'' (Frey, 2014c, p. 5). CASAC further judged that ``if
subjects had been exposed to ozone using the 8-hour averaging period
used in the standard, adverse effects could have occurred at lower
concentration'' and that ``the level at which adverse effects might be
observed would likely be lower for more sensitive subgroups, such as
those with asthma'' (Frey, 2014c, p. 5). With regard to 60 ppb
exposures, CASAC noted that ``a level of 60 ppb corresponds to the
lowest exposure concentration demonstrated to result in lung function
decrements large enough to be judged an abnormal response by ATS and
that could be adverse in individuals with lung disease'' (Frey, 2014c,
p. 7). The CASAC further noted that ``a level of 60 ppb also
corresponds to the lowest exposure concentration at which pulmonary
inflammation has been reported'' (Frey, 2014c, p. 7).
    In their advice, CASAC also took note of estimates of O3
exposures of concern and the risk of O3-induced lung
function decrements. With regard to the benchmark concentrations used
in estimating exposures of concern, CASAC stated the following (Frey,
2014c, p. 6):

    The 80 ppb-8hr benchmark level represents an exposure level for
which there is substantial clinical evidence demonstrating a range
of ozone-related effects including lung inflammation and airway
responsiveness in healthy individuals. The 70 ppb-8hr benchmark
level reflects the fact that in healthy subjects, decreases in lung
function and respiratory symptoms occur at concentrations as low as
72 ppb and that these effects almost certainly occur in some people,
including asthmatics and others with low lung function who are less
tolerant of such effects, at levels of 70 ppb and below. The 60 ppb-
8hr benchmark level represents the lowest exposure level at which
ozone-related effects have been observed in clinical studies of
healthy individuals. Based on its scientific judgment, the CASAC
finds that the 60 ppb-8hr exposure benchmark is relevant for
consideration with respect to adverse effects on asthmatics.

    With regard to lung function risk estimates, CASAC concluded that
``estimation of FEV1 decrements of >=15% is appropriate as a
scientifically relevant surrogate for adverse health outcomes in active
healthy adults, whereas an FEV1 decrement of >=10% is a
scientifically relevant surrogate for adverse health outcomes for
people with asthma and lung disease'' (Frey, 2014c, p. 3). The
Committee further concluded that ``[a]sthmatic subjects appear to be at
least as sensitive, if not more sensitive, than non-asthmatic subjects
in manifesting O3-induced pulmonary function decrements''
(Frey, 2014c, p. 4).
    Although CASAC judged that controlled human exposure studies of
respiratory effects provide the strongest

evidence supporting their conclusion on the current standard, the
Committee judged that there is also ``sufficient scientific evidence
based on epidemiologic studies for mortality and morbidity associated
with short-term exposure to ozone at the level of the current
standard'' (Frey, 2014c, p. 5) and noted that ``[r]ecent animal
toxicological studies support identification of modes of action and,
therefore, the biological plausibility associated with the
epidemiological findings'' (Frey, 2014c, p. 5).
e. Administrator's Proposed Decision
    Section II.D.5 in the proposal (79 FR 75287-75291) discusses the
Administrator's proposed conclusions related to the adequacy of the
public health protection provided by the current primary O3
standard, resulting in her proposed decision to revise that standard.
These proposed conclusions and her proposed decision, summarized below,
were based on the Administrator's consideration of the available
scientific evidence, exposure/risk information, the comments and advice
of CASAC, and public input that had been received by the time of
proposal.
    As an initial matter, the Administrator concluded that reducing
precursor emissions to achieve O3 concentrations that meet
the current primary O3 standard will provide important
improvements in public health protection, compared to recent air
quality. In reaching this initial conclusion, she noted the discussion
in section 3.4 of the PA (U.S. EPA, 2014c). In particular, the
Administrator noted that this initial conclusion is supported by (1)
the strong body of scientific evidence indicating a wide range of
adverse health outcomes attributable to exposures to O3
concentrations commonly measured in the ambient air and (2) estimates
indicating decreased occurrences of O3 exposures of concern
and decreased O3-associated health risks upon meeting the
current standard, compared to recent air quality. Thus, she concluded
that it would not be appropriate in this review to consider a standard
that is less protective than the current standard.\74\
---------------------------------------------------------------------------

    \74\ Although the Administrator noted that reductions in
O3 precursor emissions (e.g., NOX; VOC) to
achieve O3 concentrations that meet the current standard
could also increase public health protection by reducing the ambient
concentrations of pollutants other than O3 (e.g.,
PM2.5, NO2), we did not quantitatively analyze
these effects, consistent with CASAC advice (Frey, 2014a, p.10).
However, the Administrator is not setting the standard to address
risks from pollutants other than O3.
---------------------------------------------------------------------------

    After reaching the initial conclusion that meeting the current
primary O3 standard will provide important improvements in
public health protection, and that it is not appropriate to consider a
standard that is less protective than the current standard, the
Administrator next considered the adequacy of the public health
protection that is provided by the current standard. In doing so, the
Administrator first noted that studies evaluated since the completion
of the 2006 AQCD support and expand upon the strong body of evidence
that, in the last review, indicated a causal relationship between
short-term O3 exposures and respiratory health effects, the
strongest determination under the ISA's hierarchical system for
classifying weight of evidence for causation. Together, experimental
and epidemiologic studies support conclusions regarding a continuum of
O3 respiratory effects ranging from small reversible changes
in pulmonary function, and pulmonary inflammation, to more serious
effects that can result in respiratory-related emergency department
visits, hospital admissions, and premature mortality. The Administrator
further noted that recent animal toxicology studies support
descriptions of modes of action for these respiratory effects and
provide support for biological plausibility for the role of
O3 in reported effects. With regard to mode of action,
evidence indicates that antioxidant capacity may modify the risk of
respiratory morbidity associated with O3 exposure, and that
the inherent capacity to quench (based on individual antioxidant
capacity) can be overwhelmed, especially with exposure to elevated
concentrations of O3. In addition, based on the consistency
of findings across studies and evidence for the coherence of results
from different scientific disciplines, evidence indicates that certain
populations are at increased risk of experiencing O3-related
effects, including the most severe effects. These include populations
and lifestages identified in previous reviews (i.e., people with
asthma, children, older adults, outdoor workers) and populations
identified since the last review (i.e., people with certain genotypes
related to antioxidant and/or anti-inflammatory status; people with
reduced intake of certain antioxidant nutrients, such as Vitamins C and
E).
    The Administrator further noted that evidence for adverse
respiratory health effects attributable to long-term \75\ O3
exposures is much stronger than in previous reviews, and noted the
ISA's conclusion that there is ``likely to be'' a causal relationship
between such O3 exposures and adverse respiratory health
effects (the second strongest causality determination). She noted that
the evidence available in this review includes new epidemiologic
studies using a variety of designs and analysis methods, conducted by
different research groups in different locations, evaluating the
relationships between long-term O3 exposures and measures of
respiratory morbidity and mortality. New evidence supports associations
between long-term O3 exposures and the development of asthma
in children, with several studies reporting interactions between
genetic variants and such O3 exposures. Studies also report
associations between long-term O3 exposures and asthma
prevalence, asthma severity and control, respiratory symptoms among
asthmatics, and respiratory mortality.
---------------------------------------------------------------------------

    \75\ Based on the exposure surrogates used in recent
epidemiologic studies of long-term O3 exposure, it is not
possible to distinguish between the impacts of long-term
O3 exposure and exposure to repeated short-term peaks
over an O3 season.
---------------------------------------------------------------------------

    In considering the O3 exposure concentrations reported
to elicit respiratory effects, the Administrator agreed with the
conclusions of the PA and with the advice of CASAC (Frey, 2014c) that
controlled human exposure studies provide the most certain evidence
indicating the occurrence of health effects in humans following
exposures to specific O3 concentrations. In particular, she
noted that the effects reported in controlled human exposure studies