addition, the CASAC members recognized that the available evidence has
not identified a threshold concentration, below which an association no
longer remains, pointing to the conclusion in the draft ISA Supplement
that the ``evidence remains clear and consistent in supporting a no-
threshold relationship, and in supporting a linear relationship for
PM2.5 concentrations >8 [mu]g/m\3\'' (Sheppard, 2022a, p. 16
of consensus responses). Finally, these CASAC members placed weight on
the at-risk analysis as providing support for protection of at-risk
demographic groups, including minority populations.
    In reaching conclusions on a recommended range of 10-11 [mu]g/m\3\
for the primary annual PM2.5 standard, the minority of the
CASAC emphasized that there were few key epidemiologic studies that
reported positive and statistically significant health effects
associations for PM2.5 air quality distributions with
overall mean concentrations below 9.6 [mu]g/m\3\ (Sheppard, 2022a, p.
17 of consensus responses). In so doing, the minority of the CASAC
specifically noted the variability in the relationship between study-
reported means and area annual design values based on the methods
utilized in the studies, noting that design values are generally higher
than area average exposure levels. Further, the minority of the CASAC
stated that ``uncertainties related to copollutants and confounders
make it difficult to justify a recommendation below 10-11 [mu]g/m\3\''
(Sheppard, 2022a, p. 17 of consensus responses). Finally, the minority
of the CASAC placed less weight on the risk assessment results, noting
large uncertainties, including the approaches used for adjusting air
quality to simulate just meeting the current and alternative standards.
    With regard to the current primary 24-hour PM2.5
standard, the CASAC did not reach consensus regarding the adequacy of
the public health protection provided by the current standard. The
majority of the CASAC members concluded ``that the available evidence
calls into question the adequacy of the current 24-hour standard''
(Sheppard, 2022a, p. 3 of consensus letter), while the minority of the
CASAC members agreed with ``the EPA's preliminary conclusion [in the
draft PA] to retain the current 24-hour PM2.5 standard
without revision'' (Sheppard, 2022a, p. 4 of consensus letter). The
CASAC recommended that in future reviews, the EPA also consider
alternative forms for the primary 24-hour PM2.5 standard.
Specifically, the CASAC ``suggests considering a rolling 24-hour
average and examining alternatives to the 98th percentile of the 3-year
average,'' pointing to concerns that computing 24-hour average
PM2.5 concentrations using the current midnight-to-midnight
timeframe could potentially underestimate the effects of high 24-hour
exposures, especially in areas with wood-burning stoves and wintertime
stagnation (Sheppard, 2022a, p. 18 of consensus responses).
    The majority of the CASAC favored revising the level of the primary
24-hour PM2.5 standard and suggested that a range of 25-30
[mu]g/m\3\ would be adequately protective. In so doing, the CASAC
placed weight on the available epidemiologic evidence, including
epidemiologic studies that restricted analyses to 24-hour
PM2.5 concentrations below 25 [mu]g/m\3\. These members also
placed weight on results of controlled human exposure studies with
exposures close to the current standard, which they note provide
support for the epidemiologic evidence to lower the standard. These
members noted the limitations in using controlled human exposure
studies alone in considering adequacy of the 24-hour standard,
recognizing that controlled

human exposure studies preferentially recruit less susceptible
individuals and have a typical exposure duration much shorter than 24
hours. These members also placed ``greater weight on the scientific
evidence than on the values estimated by the risk assessment,'' citing
their concerns that the risk assessment ``may not adequately capture
areas with wintertime stagnation and residential wood-burning where the
annual standard is less likely to be protective'' (Sheppard, 2022a, p.
17 of consensus responses). Furthermore, these CASAC members ``also are
less confident that the annual standard could adequately protect
against health effects of short-term exposures'' (Sheppard, 2022a, p.
17 of consensus responses).
    The minority of the CASAC agreed with the EPA's preliminary
conclusion in the draft PA to retain the current primary 24-hour
PM2.5 standard, without revision. In so doing, the minority
of the CASAC placed greater weight on the risk assessment, noting that
the risk assessment accounts for both the level and the form of the
current standard and the way attainment with the standard is
determined. Further, the minority of the CASAC stated that the ``risk
assessment indicates that the annual standard is the controlling
standard across most of the urban study areas evaluated and revising
the level of the 24-hour standard is estimated to have minimal impact
on the PM2.5-associated risks'' and that, because of this,
``the annual standard can be used to limit both long- and short-term
PM2.5 concentrations'' (Sheppard, 2022a, p. 18 of consensus
responses). Further, the minority of the CASAC placed more weight on
the controlled human exposure studies, which show ``effects at
PM2.5 concentrations well above those typically measured in
areas meeting the current standards'' and which suggest that ``the
current standards are providing adequate protection against these
exposures'' (Sheppard, 2022a, p. 18 of consensus responses).
    While the CASAC members expressed differing opinions on the
appropriate revisions to the current standards, they did ``find that
both primary standards, 24-hour and annual, are critical to protect
public health given the evidence on detrimental health outcomes at both
short-term and long-term exposures including peak events'' (Sheppard,
2022a, p. 13 of consensus responses). The comments from the CASAC also
took note of uncertainties that remain in this reconsideration of the
primary PM2.5 standards and they identified a number of
additional areas for future research and data gathering that would
inform future reviews of the primary PM2.5 NAAQS (Sheppard,
2022a, pp. 14-15 of consensus responses).
2. Evidence- and Risk-Based Considerations in the Policy Assessment
    The main focus of the policy-relevant considerations in the PA is
consideration of the question: Does the currently available scientific
evidence- and exposure/risk-based information support or call into
question the adequacy of the protection afforded by the current primary
PM2.5 standards? The PA response to this overarching
question takes into account discussions that address the specific
policy-relevant questions for this reconsideration, focusing first on
consideration of the scientific evidence, as evaluated in the 2019 ISA
and ISA Supplement, including that newly available in this
reconsideration (section II.D.2.a). The PA also considers the
quantitative risk estimates drawn from the risk assessment (presented
in detail in section 3.4 and Appendix C of the PA; U.S. EPA, 2022b)
including associated limitations and uncertainties, and the extent to
which they may indicate different conclusions from those in previous
reviews regarding the magnitude of risk, as well as the level of
protection from adverse effects, associated with the current and
alternative standards (section II.D.2.b). The PA additionally considers
the key aspects of the evidence and exposure/risk estimates that were
emphasized in previous reviews of the current standards, as well as the
associated public health policy judgments and judgments about the
uncertainties inherent in the scientific evidence and quantitative
analyses that are integral to consideration of whether the currently
available information supports or calls into question the adequacy of
the current primary PM2.5 standards (U.S. EPA, 2022b,
section 3.6).
a. Evidence-Based Considerations
    The currently available evidence on the health effects of
PM2.5, including evidence newly available in this
reconsideration, is largely consistent with the evidence that was
available in previous reviews regarding health effects causally related
to PM2.5 exposures. Specifically, as in the 2012 review,
mortality and cardiovascular effects are concluded to be causally
related to long- and short-term exposures to PM2.5, while
respiratory effects are concluded to likely be causally related to
long- and short-term PM2.5 exposures. Also, since the 2012
review, recent evidence provides additional support that is sufficient
to conclude that the relationship between long-term PM2.5
exposures and nervous system effects and cancer are likely to be causal
(U.S. EPA, 2019a, Table ES-1). These determinations are based on
evidence from experimental and epidemiologic studies that is newly
available since the completion of the 2009 ISA (U.S. EPA, 2019, Table
ES-1). The current evidence base is concluded to be suggestive of, but
not sufficient to infer, causal relationships between nervous system
effects and short-term PM2.5 exposures; metabolic effects,
reproduction and fertility, and pregnancy and birth outcomes and long-
and short-term PM2.5 exposures (U.S. EPA, 2019a, Table ES-
1). Additionally, the current evidence base supports a suggestive of,
but not sufficient to infer, a causal relationship for cardiovascular
effects and short-term UFP exposures; respiratory effects and short-
term UFP exposures; and nervous system effects and long- and short-term
exposures (U.S. EPA, 2019a, Table ES-1).
    The available evidence in the 2019 ISA continues to provide support
for factors that may contribute to increased risk of PM2.5-
related health effects including lifestage (children and older adults),
pre-existing diseases (cardiovascular disease and respiratory disease),
race/ethnicity, and SES. Other factors that have the potential to
contribute to increased risk, but for which the evidence is less clear,
include obesity, diabetes, genetic factors, smoking status, sex, diet,
and residential location (U.S. EPA, 2019a, chapter 12). In addition to
these population groups, the 2019 ISA and ISA Supplement conclude that
there is strong evidence for racial and ethnic differences in
PM2.5 exposures and PM2.5-related health risk.
There is strong evidence demonstrating that Black and Hispanic
populations, in particular, have higher PM2.5 exposures than
non-Hispanic White populations (U.S. EPA, 2019a, Figure 12-2; U.S. EPA,
2022a, Figure 3-38). Further, there is consistent evidence across
multiple studies that demonstrate increased risk of PM2.5-
related health effects for Black populations, with the strongest
evidence for health risk disparities for mortality (U.S. EPA, 2019a,
section 12.5.4). In addition, studies assessed in the 2019 ISA and ISA
Supplement also provide evidence of exposure and health risk
disparities based on SES. The evidence indicates that lower SES
communities are exposed to higher concentrations of PM2.5
compared to higher SES communities (U.S. EPA, 2019a, section 12.5.3;
U.S. EPA, 2022b, section <IP_ADDRESS>.1). Additionally, evidence supports
the conclusions that lower SES

is associated with cause-specific mortality and certain health
endpoints (i.e., MI and CHF), but less so for all-cause or total (non-
accidental) mortality (U.S. EPA, 2019a, section 12.5.3; U.S. EPA,
2022b, section <IP_ADDRESS>).
    Consistent with the evidence available in the 2009 ISA, controlled
human exposure studies have demonstrated effects on cardiovascular
function following 1- to 5-hour exposures to PM2.5, with the
most consistent evidence for impaired vascular function. The PA notes
that most of the controlled human exposure studies have evaluated
average PM2.5 concentrations at or above about 100 [mu]g/
m\3\, with exposure durations up to two hours. These studies have
often, though not always, reported statistically significant effects on
one or more indicators of cardiovascular function following 2-hour
exposures to average PM2.5 concentrations at and above about
120 [mu]g/m\3\, with less consistent effects following exposures to
concentrations lower than 120 [mu]g/m\3\.
    In considering the controlled human exposure studies in reaching
conclusions on the primary PM2.5 standards, the PA notes
that air quality analyses indicate that 2-hour PM2.5
concentrations to which individuals were exposed in most of these
studies, including those that report the most consistent results, are
well-above the ambient PM2.5 concentrations typically
measured in locations meeting the current primary standards.
Additionally, the PA recognizes that the results are variable across
controlled human exposure studies that evaluated near-ambient
PM2.5 concentrations.
    Furthermore, the PA recognizes that controlled human exposure
studies often include small numbers of individuals and do not include
populations that are at increased risk of PM2.5-related
health effects (e.g., children). While the PA recognizes that the
controlled human exposure studies are important in establishing
biological plausibility, it emphasizes that it is unclear how the
results from these studies alone, particularly in studies conducted at
near-ambient PM2.5 concentrations, and the importance of the
effects observed in the studies should be interpreted with respect to
adversity to public health.
    With regard to the animal toxicological studies, the PA recognizes
that, unlike the controlled human exposure studies that provide insight
on the exposure concentrations that directly elicit health effects in
humans, there is uncertainty associated with translating the
observations in the animal toxicological studies to potential adverse
health effects in humans. The PA notes that the interpretation of these
studies is complicated by the fact that PM2.5 concentrations
in animal toxicological studies are much higher than those shown to
elicit effects in human populations. Moreover, the PA recognizes that
there are also significant anatomical and physiological difference
between animal models and humans. In considering the information from
the animal toxicological studies, the PA specifically notes two
studies, one of which is newly available in the 2019 ISA, that report
serious effects following long-term exposures to PM2.5
concentrations close to the ambient concentrations reported in some
epidemiologic studies, although still above the ambient concentrations
likely to occur in areas meeting the current primary standards (U.S.
EPA, 2022b, section <IP_ADDRESS>).
    Since the 2012 review, a large number of epidemiologic studies have
become available that report generally positive, and often
statistically significant, associations between long- and short-term
PM2.5 exposures and mortality and morbidity. Available
studies additionally indicate that PM2.5 health effect
associations are robust across various approaches to estimating
PM2.5 exposures and across various exposure windows. Since
the 2012 review, there are also a number of studies that employ
alternative methods for confounder control that further inform the
causal nature of the relationship between long- or short-term term
PM2.5 exposure and mortality, and these studies provide
support for the findings from the broad body of epidemiologic studies.
    In addition to broadening our understanding of the health effects
that can result from exposures to PM2.5 and strengthening
support for some key effects (e.g., nervous system effects, cancer, and
metabolic effects), recent epidemiologic studies strengthen support for
health effect associations at relatively low ambient PM2.5
concentrations. Studies that examine the shapes of C-R functions over
the full distribution of ambient PM2.5 concentrations have
not identified a threshold concentration below which associations no
longer exist (U.S. EPA, 2019a, section 1.5.3; U.S. EPA, 2022a, sections
<IP_ADDRESS> and <IP_ADDRESS>). While such analyses are complicated by the
relatively sparse data available at the lower end of the air quality
distribution (U.S. EPA, 2019a, section 1.5.3), the evidence remains
consistent in supporting a no-threshold relationship, and in supporting
a linear relationship for PM2.5 concentrations >8 [mu]g/
m\3\. However, uncertainties remain about the shape of the C-R curve at
PM2.5 concentrations <8 [mu]g/m\3\, with some recent studies
providing evidence for either a sublinear, linear, or supralinear
relationship at these lower concentrations.
    Consistent with previous reviews, the PA notes that the use of
information from epidemiologic studies to inform conclusions on the
current standards is complicated by the fact that such studies evaluate
associations between distributions of ambient PM2.5 and
health outcomes, and do not identify the specific exposures that can
lead to the reported effects. Rather, health effects can occur over the
entire distribution of ambient PM2.5 concentrations
evaluated, and epidemiologic studies do not identify a population-level
threshold below which it can be concluded with confidence that PM-
associated health effects do not occur (U.S. EPA, 2019a, section
1.5.3). However, the study-reported ambient PM2.5
concentrations reflecting estimated exposure in the middle portion of
the PM2.5 air quality distribution, which corresponds to the
bulk of the underlying data, provide the strongest support for reported
health effect associations and can inform conclusions on the current
and potential alternative standards. In considering this information,
the PA recognizes that the mean PM2.5 concentrations
reported by key epidemiologic studies differ in how mean concentrations
were calculated, as well as their interpretation in what means
represent in the context of the current standards.
    In identifying key epidemiologic studies for consideration, the PA
places the greatest emphasis on studies conducted in the U.S. and
Canada, although recognizes a number of limitations associated with
interpreting the results of Canadian studies compared to studies
conducted in the U.S. Generally, there are differences in the exposure
environments and population characteristics between the U.S. and other
countries, including Canada, that can affect the study-reported mean
PM2.5 concentration and its comparability with the annual
standard level. A number of other differences, including sources and
pollutant mixtures, concentration gradients, and populations densities,
can make it challenging to interpret the mean PM2.5
concentrations in Canadian studies in the context of a U.S.-based
standard. Specifically, it may be difficult to use such studies to
directly and quantitatively inform questions regarding the adequacy of
the current or potential alternative levels of the annual standard.
Therefore, while the PA considers the mean PM2.5

concentrations from U.S. and Canadian studies in reaching conclusions,
it notes that the U.S.-based epidemiologic studies are most informative
for comparisons with the annual standard metric and for reaching
conclusions on the current standards and for informing potential
alternative levels of the standard.
    Consistent with previous reviews, in considering information that
can be used from the available epidemiologic evidence to inform
proposed decisions on the current standards, the PA focuses on
PM2.5 concentrations near or somewhat below long-term mean
concentrations reported in epidemiologic studies. In so doing, the PA
notes that, in previous reviews, the epidemiologic studies used ground-
based monitors to estimate exposures, and that, in addition to newly
available monitor-based studies, there are also newly available
epidemiologic studies estimate exposures using hybrid modeling
approaches. In considering how the study-reported mean PM2.5
concentrations reported in studies using hybrid modeling approaches
compare to studies using ground-based monitors, the PA notes that the
hybrid modeling approaches provide a broader estimation of
PM2.5 exposures compared to monitor-based studies (i.e.,
because hybrid modeling studies include PM2.5 concentrations
estimated in areas without monitors). However, compared to monitor-
based studies, the PA recognizes that it is more difficult to relate
these means to an annual standard metric which relies on maximum
monitor design values to assess compliance. Further complicating the
comparison is the variability in how PM2.5 concentrations
are estimated between studies that use hybrid modeling approaches. Two
important variations across studies include: (1) variability in spatial
scale used (i.e., averages computed across the national (or large
portions of the country) versus a focus on only CBSAs) and (2)
variability in exposure assignment methods (i.e., averaging across all
grid cells, averaging across a scaled-up area like a ZIP code, and
population weighting).
    As described in more detail in section I.D.5 above, the PA included
analyses that considered how the study-reported mean PM2.5
concentrations were computed and how the means compare to the annual
standard metric (including the level, averaging time, and form) and the
use of the monitor with the highest PM2.5 design value in an
area for compliance. In so doing, the PA included a comparison of
PM2.5 fields in estimating exposure relative to design
values using two hybrid modeling surface with annual average
PM2.5 concentrations estimated per year at a 1 km x 1 km
spatial resolution. The PA notes that the means vary when
PM2.5 concentrations are estimated in urban areas only
(CBSAs) versus when the averages were calculated with all or most grid
cells nationwide. This is likely indicative of the fact that areas
included outside of CBSAs tend to be more rural and have lower
estimated PM2.5 concentrations. The PA acknowledges that
this is an important consideration since the study areas included in
the calculation of the mean, and more specifically whether a study is
focused on nationwide, regional, or urban areas, will affect the
calculation of the study mean based on how many rural areas are
included with lower estimated PM2.5 concentrations. While
the determination of what spatial scale to use to estimate
PM2.5 concentrations does not inherently affect the quality
of the epidemiologic study, the spatial scale can influence the
calculated long-term mean concentration across the study area and
period.
    Additionally, the PA analyses indicate that for the studies using
the hybrid modeling approaches, the use of population weighting in
calculating study-reported mean PM2.5 concentrations, and
not a difference in estimates of exposures in the study itself, can
produce substantially different study-reported mean PM2.5
concentrations compared to an approach that does not utilize population
weighting. In studies that do not apply population weighting in the
calculation of the mean PM2.5 concentrations, study-reported
means are lower, as a result of including areas with lower estimated
PM2.5 concentrations that may not be as densely populated,
as well as areas that may not include health events. To elaborate, in
hybrid modeling approaches that present mean PM2.5
concentrations based on an average PM2.5 concentration
across all grid cells (i.e., do not apply aspects of population
weighting), health events may not exist in each grid cell, and thus the
mean reported PM2.5 concentration is not necessarily based
on the mean PM2.5 concentrations assigned as the exposure in
the health study. In other words, the mean PM2.5
concentration that is reported and based on an average of all grid
cells is not necessarily the same as the mean PM2.5
concentration for each person assigned an exposure in the study. This
is an important consideration, as the purpose of the epidemiologic
study is to evaluate whether an association between PM2.5
exposure and health outcomes exists. As such, it is unclear whether the
mean concentration reported using each grid cell is associated with a
health outcome (i.e., not all grid cells have health events). This
leads to uncertainty in evaluating how the mean concentration can be
used in the context of the approach above to evaluate the adequacy of
the standard as well as potential alternative levels of the annual
standard.
    In considering the variability in how exposure in estimated between
studies that use hybrid modeling approaches, the PA focuses on the key
epidemiologic studies that use hybrid modeling approaches and apply
population weighting in calculating the study-reported mean, as well as
those studies that use monitors to estimate exposure, as described in
more detail in section II.B.3.b above. For key U.S. epidemiologic
studies that use monitors to estimate PM2.5 exposures,
overall mean PM2.5 concentrations range between 9.9 [mu]g/
m\3\ \92\ to 16.5 [mu]g/m\3\ (U.S. EPA, 2022b, Figure 3-8). For U.S.
studies that use hybrid model-predicted exposures and apply aspects of
population weighting, mean PM2.5 concentrations range from
9.3 [mu]g/m\3\ to 12.2 [mu]g/m\3\ (U.S. EPA, 2022b, Figure 3-14). In
U.S. studies that average up from the grid cell level to the ZIP code
or census tract level, mean PM2.5 concentrations range from
9.8 [mu]g/m\3\ to 12.2 [mu]g/m\3\. In the one U.S. study that
population-weighted the grid cells prior to averaging up to the ZIP
code or census tract level, the reported mean PM2.5
concentration is 9.3 [mu]g/m\3\. As described above, the PA also
considers the study-reported means from the key Canadian epidemiologic
studies, which are consistently much lower than those reported for key
U.S. epidemiologic studies, while noting that for the reasons described
above, there are uncertainties and limitations associated with
comparisons between Canadian studies and the annual standard metric.
For the key Canadian epidemiologic studies that use monitors to
estimate PM2.5 exposures, overall mean PM2.5
concentrations range from 6.9 [mu]g/m\3\ to 13.3 [mu]g/m\3\, while the
range of mean PM2.5 concentrations in Canadian studies that
use hybrid modeling (all of which average up to postal codes and thus
include some aspects of population weighting) is 5.9 [mu]g/m\3\ to 9.8
[mu]g/m\3\.
---------------------------------------------------------------------------

    \92\ This is generally consistent with, but slightly below, the
lowest study-reported mean PM2.5 concentration from
monitor-based studies available in the 2020 PA, which was 10.7
[mu]g/m\3\ (U.S. EPA, 2020a, Figure 3-7).

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

    As described in more detail in section II.B.3.b above, in assessing
the range of reported exposure concentrations for which the strongest
support exists for adverse health effects occurring, the PA evaluates
whether the available evidence supports or calls into question the
adequacy of public health protection afforded by the current primary
annual PM2.5 standard against these exposure concentrations.
This means, as in past reviews, the application of a decision framework
based on assessing means reported in key epidemiologic studies must
also consider how the study means were computed and how these values
compare to the annual standard metric (including the level, averaging
time and form) and the use of the monitor with the highest
PM2.5 design value in an area for compliance. Based on the
air quality analyses in presented in the PA and discussed above
(section I.D.5.a and section I.D.5.b), design values associated with
the study-reported means in these key U.S. based epidemiologic studies
are only somewhat higher: 10-20% for monitor-based studies and 15-18%
higher for the studies that include hybrid modeling approaches and
utilize population weighting. Based on these results, it can generally
be concluded that the study-reported mean concentrations in the studies
are associated with air quality conditions that would be achieved by
meeting annual standard levels that are 10-20% higher and 15-18% higher
than study-reported means for monitor-based studies and hybrid
modeling-based studies that use population weighting, respectively.
Therefore, an annual standard level that is no more than 10-20% higher
than the study-reported means in the monitor-based studies (i.e., 9.9-
16.5 [mu]g/m\3\), and no more than 15-18% higher than the study-
reported means in the studies that include hybrid modeling approaches
and utilize population weighting (i.e., 9.3-12.2 [mu]g/m\3\), would
generally maintain air quality exposures at or below those associated
with the study-reported mean PM2.5 concentrations, exposures
for which we have the strongest support for adverse health effects
occurring. This relationship is indicative of the fact that
PM2.5 exposures in an area are represented by a distribution
of concentrations across that area, with the annual standard level at
the design value monitor being associated with the highest annual
average exposure concentration for that area.
    In addition to the study-reported mean concentrations, in
considering the level of the annual standard, the PA uses an approach
consistent with that used in previous reviews and also considers
reported PM2.5 concentrations corresponding to the 25th and
10th percentiles of health data or exposure estimates when available in
the key epidemiologic studies. In using such an approach, the PA
recognized that there is an interrelatedness of the distributional
statistics in epidemiologic studies (e.g., 10th and 25th percentiles of
PM2.5 concentrations) and a range of one standard deviation
around the mean which contains approximately 68% of normally
distributed data, in that one standard deviation below the mean falls
between the 25th and 10th percentiles (U.S. EPA, 2022b, p. 2-71).
Further, the PA notes that in past reviews, some weight was placed on
studies that provided mean PM2.5 concentrations around the
25th percentile of the distributions of deaths and cardiovascular-
related hospitalizations and the Administrator judged the region around
the 25th percentile as a reasonable part of the distribution to guide
the decision on the appropriate standard level (78 FR 3161, January 15,
2013).
    As such, the PA concludes that focusing on concentrations somewhat
below the means (e.g., 25th and 10th percentiles), when such
information is available from epidemiologic studies, is a reasonable
approach for considering lower portions of the air quality
distribution. However, the PA recognizes that the health data are
appreciably more sparse and an understanding of the magnitude and
significance of the associations correspondingly become more uncertain
in the lower part of the air quality distribution. While health effects
can occur over the entire distribution of ambient PM2.5
concentrations evaluated, and epidemiologic studies do not identify a
population-level threshold below which it can be concluded with
confidence that PM-associated health effects do not occur (U.S. EPA,
2019a, section 1.5.3), using values below the 10th percentile would
lead to even greater uncertainties and diminished confidence in the
magnitude and significance of the associations.
    In considering the available key U.S. epidemiologic studies, the PA
notes that a small number of studies report PM2.5
concentrations corresponding to the 25th and 10th percentiles of health
data or exposure estimates that can be considered to provide insight
into the concentrations that comprise the lower quartiles of the air
quality distributions is examined below. In studies that use monitors
to estimate PM2.5 exposures, 25th percentiles of health
events correspond to PM2.5 concentrations (i.e., averaged
over the study period for each study city) at or above 11.5 [mu]g/m\3\
and 10th percentiles of health events correspond to PM2.5
concentrations at or above 9.8 [mu]g/m\3\ (i.e., 25% and 10% of health
events, respectively, occur in study locations with PM2.5
concentrations below these values) (U.S. EPA, 2022b, Figure 3-8). Of
the key U.S. epidemiologic studies that use hybrid modeling approaches
to estimate long-term PM2.5 exposures, the ambient
PM2.5 concentrations corresponding to 25th percentiles of
estimated exposures are 9.1 [mu]g/m\3\ (U.S. EPA, 2022b, Figure 3-14).
In key U.S. epidemiologic studies that use hybrid modeling approaches
to estimate short-term PM2.5 exposures, the ambient
concentrations corresponding to 25th percentiles of estimated
exposures, or health events, are 6.7 [mu]g/m\3\ and the ambient
PM2.5 concentration corresponding to that 10th percentile
range from 4.7 [mu]g/m\3\ to 7.3 [mu]g/m\3\ (U.S. EPA, 2022b, Figure 3-
14).
    As with the mean PM2.5 concentrations, in considering
these values relative to an area annual design value, the PA notes the
25th and 10th percentiles provide information about the lower quartiles
of the air quality distributions, while the study-reported mean
provides information about the average or typical exposures, and the
corresponding area annual design value provides the highest average
annual PM2.5 concentration being measured. In this way, the
PA recognizes that all of these metrics (i.e., lower percentiles, study
mean, annual design value) have a relationship relative to the other,
and each of these metrics can be used to inform the consideration of
the level of the current annual standard. Further, the PA recognizes
that the air quality analyses described above (section I.D.5) and in
the PA (U.S. EPA, 2022b, section <IP_ADDRESS> and section <IP_ADDRESS>.4) that
evaluated the relationship between a mean PM2.5
concentration in an area and the design value focuses on mean
PM2.5 concentrations and similar analyses were not conducted
for other PM2.5 concentrations in the lower portion of the
air quality distribution. Therefore, given the lack of additional
information regarding the relationship between percentiles of the air
quality distribution other than the mean and the annual design value,
the PA concludes that any direct comparison of study-reported
PM2.5 concentrations corresponding to lower percentiles
(e.g., 25th and/or 10th) and annual design values is more uncertain
than such comparisons with the mean.
    Since the completion of the 2009 ISA, a number of epidemiologic
studies have become available that can provide

additional consideration to inform conclusions regarding the adequacy
of the current standards. Studies that examine health effect
associations in analyses that exclude the highest exposures (i.e.,
studies that restrict analyses below certain PM2.5
concentrations), and which report positive and statistically
significant associations in analyses restricted to annual average
PM2.5 exposures at or below 12 [mu]g/m\3\ and/or to daily
exposures below 35 [mu]g/m\3\ (section II.B.3.b above and U.S. EPA,
2022b, Table 3-10). The PA notes that these restricted analyses provide
additional support for effects at lower concentrations, exhibiting
associations for mean concentrations presumably below the mean
concentrations for the main analyses. While mean PM2.5
concentrations for these restricted analyses may not be reported in
most studies, the PA asserts that it would not be unreasonable to
presume that the mean PM2.5 concentrations in the restricted
analyses are less than the study-reported mean PM2.5
concentrations in the main analyses. The two studies (Di et al., 2017b,
and Dominici et al., 2019) which report means in their restricted
analyses (restricting annual average PM2.5 exposure below 12
[mu]g/m\3\) and used population-weighted approaches to estimate
PM2.5 exposures report mean PM2.5 concentrations
of 9.6 [mu]g/m\3\. However, it is important to note that, even if the
other studies had reported the mean PM2.5 concentrations for
the restricted analysis, these means would not necessarily have been
useful in the context of the decision framework as was used in past
reviews (above in section II.B.3.b.), given uncertainties associated
with identifying the relationship between a calculated mean
concentration that excludes specific daily or annual average
concentrations above a certain threshold and the design value used to
determine compliance with a standard (either the annual or 24-hour
standard). Moreover, the PA emphasizes there is uncertainty in how
studies exclude concentrations (e.g., at what spatial resolution are
concentrations being excluded), which would make any comparisons of
mean concentrations in restricted analyses difficult to compare to
design values.
    The PA also takes note of studies that restrict 24-hour average
PM2.5 concentrations to values of less than 35 [mu]g/m\3\
and again recognizes that these studies do not report the mean
PM2.5 concentration for the restricted analysis, as noted
above, although the mean of the restricted analysis is presumably less
than the mean PM2.5 concentration in the main analysis.
However, in some studies, the majority of PM2.5
concentrations from the main study are already less than the restricted
concentration (e.g., in Di et al., 2017a, where of all case and control
days, 93.6% had PM2.5 concentrations below 25 [mu]g/m\3\),
which contributes to the uncertainty in how much lower a mean
concentration in a restricted study is compared to the mean
PM2.5 concentration in the main analysis. As a result, the
PA recognizes that there are limitations in how this information can be
used in evaluating the adequacy of the current or potential alternative
levels of the 24-hour standard. Additionally, the PA further recognizes
that it is difficult to use the means, when reported, from studies of
restricted analyses to evaluate the level of protection afforded by the
current or potential alternative levels of the primary 24-hour
PM2.5 standard because the relationship between the study-
reported mean concentration and the 98th percentile form of the 24-hour
standard is not well understood, in particular for a short-term
standard designed to limit exposures to peak PM2.5
concentrations.
    Finally, the PA notes the availability of accountability studies,
which evaluate whether environmental policies or air quality
interventions led to changes in air quality and are also associated
with improvements in public health, including a number of recent
studies evaluated in the ISA Supplement (summarized above in section
II.B.3.b and U.S. EPA, 2022b, Table 3-12). These studies report
positive and significant associations, including some studies with
annual PM2.5 concentrations below 12.0 [micro]g/m\3\ at the
start of the study period, indicating that public health improvements
may occur following PM2.5 reductions in areas that already
meet the current annual PM2.5 standard. For example, the PA
notes that the studies by Corrigan et al. (2018) and Sanders et al.
(2020a) and both found improvements in mortality rates due to
improvements in air quality in both attainment and nonattainment areas
following implementation of the 1997 primary annual PM2.5
NAAQS. Additionally, the PA notes that an accountability study by
Henneman et al. (2019a) evaluated the changes in modeled
PM2.5 concentrations following the retirement of coal fired
power plants in the U.S found that reductions in PM2.5
concentrations resulted in reductions of cardiovascular-related
hospital admissions.\93\ Other recent studies additionally report that
declines in ambient PM2.5 concentrations over a period of
years have been associated with decreases in mortality rates and
increases in life expectancy, improvements in respiratory development,
and decreased incidence of respiratory disease in children, further
supporting the robustness of PM2.5 health effect
associations reported in the epidemiologic evidence.
---------------------------------------------------------------------------

    \93\ We note that the studies by Corrigan et al. (2018) and
Sanders et al. (2020a) report monitor-based average PM2.5
concentrations, and the study by reports model-based average
PM2.5 concentrations, and that these studies do not
report design values.
---------------------------------------------------------------------------

    In considering the available scientific evidence, the PA recognizes
that there are a number of uncertainties associated with the evidence
that persist from previous reviews. The PA notes that, for controlled
human exposures studies, there are uncertainties related to
inconsistent results observed at concentrations near ambient
PM2.5 levels. Additionally, the PA recognizes that it is
unclear how the results of controlled human exposure studies alone and
the importance of the effects observed in these studies, particularly
in studies conducted at near-ambient PM2.5 concentrations,
should be interpreted with respect to adversity to public health. With
respect to animal toxicological studies, the PA notes that while these
studies also help establish biological plausibility, uncertainty exists
in extrapolating the effects observed in animal toxicological studies,
and the PM2.5 concentrations that cause those effects, to
human populations.
    Furthermore, the PA recognizes that uncertainties associated with
the epidemiologic evidence (e.g., the potential for copollutant
confounding and exposure measurement error) remain, although new
studies evaluated in the ISA Supplement employ statistical methods such
as alternative methods for confounder control, to more extensively
account for confounders, which are more robust to model
misspecification. With regard to controlling for potential confounders
in particular, the PA notes that the key epidemiologic studies use a
wide array of approaches to control for potential confounders. Time-
series studies control for potential confounders that vary over short
time intervals (e.g., including temperature, humidity, dew point
temperature, and day of the week), while cohort studies control for
community- and/or individual-level confounders that vary spatially
(e.g., including income, race, age, SES,

smoking, body mass index, and annual weather variables such as
temperature and humidity) (U.S. EPA, 2022b, Table B-4). Sensitivity
analyses indicate that adding covariates to control for potential
confounders can either increase or decrease the magnitude of
PM2.5 effect estimates, depending on the covariate, and that
none of the covariates examined can fully explain the association with
mortality (e.g., Di et al., 2017b, Figure S2 in Supplementary
Materials). Thus, while no individual study adjusts for all potential
confounders, a broad range of approaches have been adopted across
studies to examine confounding, supporting the robustness of reported
associations. Available studies additionally indicate that
PM2.5 health effect associations are robust across various
approaches to estimating PM2.5 exposures and across various
exposure windows. This includes recent studies that estimate exposures
using ground-based monitors alone and studies that estimate exposures
using data from multiple sources (e.g., satellites, land use
information, modeling), in addition to monitors. While none of these
approaches eliminates the potential for exposure error in epidemiologic
studies, the PA concludes that such error does not call into question
the fundamental findings of the broad body of PM2.5
epidemiologic evidence.
    Additionally, the PA notes the uncertainties associated with the
studies that examine the shapes of C-R functions over the full
distribution of ambient PM2.5 concentrations have not
identified a threshold concentration, below which associations no
longer exist (section II.B.4 above, U.S. EPA, 2019a, section 1.5.3;
U.S. EPA, 2022a, sections <IP_ADDRESS> and <IP_ADDRESS>). While such analyses are
complicated by the relatively sparse data available at the lower end of
the air quality distribution (U.S. EPA, 2019a, section 1.5.3), the
evidence remains consistent in supporting a no-threshold relationship,
and in supporting a linear relationship for PM2.5
concentrations >8 [mu]g/m\3\. However, uncertainties remain about the
shape of the C-R curve at PM2.5 concentrations <8 [mu]g/
m\3\, with some recent studies providing evidence for either a
sublinear, linear, or supralinear relationship at these lower
concentrations.
    While studies using hybrid modeling methods have demonstrated
reduced exposure measurement error and reduced uncertainty in the
health effect estimates, these methodologies have inherent limitations
and uncertainties, as described in more detail above in section
II.B.3.b and in sections <IP_ADDRESS>.5 and 3.3.4 of the PA, and the
performance of the modeling approaches depends on the availability of
monitoring data which varies by location. Factors likely contributing
to poorer model performance often coincide with relatively low ambient
PM2.5 concentrations, in areas where predicted exposures are
at a greater distance to monitors, and under conditions where the
reliability and availability of key datasets (e.g., air quality
modeling) are limited. Thus, the PA concludes that the uncertainty in
hybrid model predictions becomes an increasingly important
consideration as lower predicted concentrations are considered.
    In addition, the PA recognizes that there are uncertainties and
limitations in the analysis evaluating the comparison of estimated
PM2.5 concentrations using hybrid modeling surfaces and
their relationship to design values that should be considered (section
II.B.3.b above; U.S. EPA, 2022b, section <IP_ADDRESS>.4). While design
values in general are higher than estimated PM2.5
concentrations using these two hybrid modeling approaches (DI2019 and
HA2020), the PA recognizes that these are just two hybrid modeling
approaches to estimating PM2.5 concentrations and other
models/approaches/spatial scales may result in somewhat different
PM2.5 concentrations and relationships with design values.
The analysis evaluating the relationship between two different hybrid
modeling surfaces and design values estimates PM2.5
concentrations by CBSAs, but not every health study uses
PM2.5 estimates at this spatial scale, and spatial scales
for exposure estimates can vary by study (section I.D.5 above; U.S.
EPA, 2022b, section <IP_ADDRESS>.4). The analysis completed was a nationwide
analysis and ratios between design values and mean concentrations are
based on national estimates. However, not all health studies are
national studies (i.e., some studies are completed in different regions
of the country, like the southeast or northeast) and ratios in
different parts of the country could be higher or lower, depending on
factors like population, as well as the proportion of rural versus
urban areas. This analysis used specific air quality years (2000-2016)
and the use of other air quality years could result in higher or lower
ratios.
    Regardless of whether an epidemiologic study uses monitoring data
or a hybrid modeling approach when estimating PM2.5
exposures, the PA recognizes that it is challenging to interpret the
study-reported mean PM2.5 concentrations and how they
compare to design values. This is particularly true given the
variability that exists across the various approaches to estimate
exposure and to calculate the study-reported mean. The PA also
acknowledges that these types of challenges are also present in using
information from Canadian studies to directly and quantitatively inform
questions on the level of the annual standard given the difficulty of
interpreting what the Canadian study means represent relative to U.S.
design values.
b. Risk-Based Considerations
    As in previous reviews, consideration of the scientific evidence in
this reconsideration is informed by results from a quantitative
analysis of risk. The overarching PA consideration regarding these
results is whether they alter the overall conclusions from previous
reviews regarding health risk associated with exposure to
PM2.5 in ambient air and associated judgments on the
adequacy of public health protection provided by the current primary
PM2.5 standards. The risk assessment conducted for this
reconsideration develops exposure and risk estimates for populations in
47 urban study areas, as well as subsets of those study areas depending
on which of the primary PM2.5 standards is controlling in a
given study area. The primary analyses focus on exposure and risk
associated with air quality that might occur in an area under air
quality conditions that just meet the current and potential alternative
standards. These study areas include nearly 60 million people ages 30
years or older and illustrate the differences likely to occur across
various locations with such air quality as a result of area-specific
differences in emissions, meteorological, and population
characteristics. While the same conceptual air quality scenarios are
simulated in all study areas (i.e., conditions that just meet the
existing or alternate standards), source, meteorological and population
characteristics in the study areas contribute to variability in the
estimated magnitude of risk across study areas (U.S. EPA, 2022b,
section <IP_ADDRESS>). In this way, the 47 areas provide a variety of
examples of exposure patterns that can be informative to the
Administrator's consideration of potential exposures and risks that may
be associated with air quality conditions occurring under the current
and potential alternative PM2.5 standards.
    In considering the risk assessment in this reconsideration, the PA
notes a number of ways in which the current analyses update and improve
upon

those available in previous reviews. As an initial matter, the PA notes
that, consistent with the overall approach for this reconsideration,
the risk assessment has a targeted scope that focuses on all-cause or
nonaccidental mortality associated with long- and short-term
PM2.5 exposures (U.S. EPA, 2022b, section <IP_ADDRESS>). As noted
in section II.B.1 above, the evidence assessed in the 2019 ISA and ISA
Supplement support a causal relationship between long- and short-term
PM2.5 exposures and mortality. Concentration-response
functions used in the risk assessment are from large, multicity U.S.
epidemiologic studies that evaluate the relationship between
PM2.5 exposures and mortality and were identified using
criteria that take into account factors such as study design,
geographic coverage, demographic populations, and health endpoints
(U.S. EPA, 2022b, section 2.1).
    The risk assessment also includes updates and improvements to input
data and modeling approaches, summarized in section II.C above and in
section 3.4 of the PA (U.S. EPA, 2022b). As in previous reviews,
exposure and risk are estimated from air quality scenarios defined by
the highest design value in the study area, which is the monitor
location with the highest 3-year average of the annual mean
PM2.5 concentrations (e.g., equal to 12.0 [mu]g/m\3\ for the
current standard scenario) for the annual PM2.5 standard and
with the highest 3-year average of the 98th percentile 24-hour
PM2.5 concentrations (e.g., equal to 35 [mu]g/m\3\ for the
current standard scenario) for the 24-hour PM2.5 standard.
As described in more detail in section II.C above and in section 3.4 of
the PA (U.S. EPA, 2022b), air quality modeling was used to simulate
just meeting the existing annual and 24-hour standards of 12.0 [mu]g/
m\3\ and 35 [mu]g/m\3\ and to just meeting potential alternative annual
and 24-hour standards of 10.0 [mu]g/m\3\ and 30 [mu]g/m\3\. In addition
to the air quality modeling approach, linear interpolation and
extrapolation were used to simulate just meeting alternative annual
standards with levels of 11.0 (interpolated between 12.0 and 10.0
[mu]g/m\3\), 9.0 [mu]g/m\3\, and 8.0 [mu]g/m\3\ (both extrapolated from
12.0 and 10.0 [mu]g/m\3\) in the subset of study areas controlled by
the annual standard.
    In addition to the risk assessment described above, the PA presents
quantitative analyses that also assess long-term PM2.5-
attributable exposure and mortality risk, stratified by racial/ethnic
demographics. As described in more detail in section II.B.2 above, the
evidence suggests that different racial and ethnic groups, such as
Black and Hispanic populations residing in the study areas, have higher
PM2.5 exposures than White and non-Hispanic populations also
residing in the study areas, respectively, thus contributing to
increased risk of PM-related effects. Of the available studies, Di et
al. (2017b) was identified as best characterizing populations
potentially at increased risk of long-term exposure-attributable all-
cause mortality effects and provides race- and ethnicity-stratified C-R
functions for ages 65 and over (U.S. EPA, 2022b, section <IP_ADDRESS> and
Appendix C). Risk and exposure are quantitatively assessed within
racial and ethnic minority populations of older adults in the full set
of 47 areas and the subset of 30 areas controlled by the annual
PM2.5 standard. This analysis, when considered alongside
estimates of risk across all populations in the 47 study areas, can
help to inform conclusions on the annual primary PM2.5
standards that would be requisite to protect the public health of
demographic populations potentially at increased risk of long-term
PM2.5-related mortality effects.
    In considering the risk results, the PA focuses first on estimates
for the full set of 47 urban study areas. The risk assessment estimates
that the current primary PM2.5 standards could allow a
substantial number of deaths in the U.S., with the large majority of
those deaths associated with long-term PM2.5 exposures. For
example, when air quality in the 47 study areas is adjusted to just
meet the current standards, the risk assessment estimates about 41,000
to 45,000 deaths from all-cause mortality in a single year (e.g., for
long-term exposures; confidence intervals range from about 30,000 to
59,000) (U.S. EPA, 2022b, section <IP_ADDRESS>). For the 30 study areas \94\
where just meeting the current standards is controlled by the annual
standard,\95\ long-term PM2.5 exposures are estimated to be
associated with as many as 39,000 (confidence intervals range from
about 26,000 to 51,000) deaths from all-cause mortality in a single
year (U.S. EPA, 2022b, section <IP_ADDRESS>). For the 11 study areas \96\
where just meeting the current standards is controlled by the daily
standard,\97\ long-term PM2.5 exposures are estimated to be
associated with as many as 2,600 (confidence intervals ranging from
1,700 to 3,400) deaths in a single year (U.S. EPA, 2022b, section
<IP_ADDRESS>). The risk assessment estimates far fewer deaths in a single
year for short-term PM2.5 exposures as compared to long-term
PM2.5 exposures, across all of the study area subsets (U.S.
EPA, 2022b, section <IP_ADDRESS>).
---------------------------------------------------------------------------

    \94\ These 30 areas controlled by the annual standard under all
scenarios evaluated include a population of approximately 48 million
adults aged 30-99, or about 75% of the population included in the
full set of 47 areas.
    \95\ For these areas, the annual standard is the ``controlling
standard'' because when air quality is adjusted to simulate just
meeting the current or potential alternative annual standards, that
air quality also would meet the 24-hour standard being evaluated.
    \96\ These 11 areas controlled by the 24-hour standard under all
scenarios evaluated include a population of approximately 10 million
adults aged 30-99, or about 17% of the population included in the
full set of 47 areas.
    \97\ For these areas, the 24-hour standard is the controlling
standard because when air quality is adjusted to simulate just
meeting the current or potential alternative 24-hour standards, that
air quality also would meet the annual standard being evaluated.
Some areas classified as being controlled by the 24-hour standard
also violate the annual standard.
---------------------------------------------------------------------------

    While the absolute numbers of estimated deaths vary across exposure
durations, populations, and C-R functions, the general magnitude of
risk estimates supports the potential for significant public health
impacts in locations meeting the current primary PM2.5
standards. This is particularly the case given that the large majority
of PM2.5-associated deaths for air quality just meeting the
current standards are estimated at annual average PM2.5
concentrations from about 10 to 12 [mu]g/m\3\. These annual average
PM2.5 concentrations fall within the range of long-term
average concentrations over which key epidemiologic studies provide
strong support for reported positive and statistically significant
health effect associations (U.S. EPA, 2022b, section <IP_ADDRESS>).
    In the 47 urban study areas, when air quality is simulated to just
meet alternative standards, the PA notes that there are substantially
larger risk reductions associated with lowering the annual standard
than with lowering the 24-hour standard. Risks are estimated to
decrease by 13-17% when air quality is adjusted to just meet an
alternative annual standard with a level of 10.0 [mu]g/m\3\ or by 1-2%
when adjusted to just meet an alternative 24-hour standard with a level
of 30 [mu]g/m\3\ (U.S. EPA, 2022b, section <IP_ADDRESS>). The percentage
decrease when just meeting an alternative annual standard with a level
of 10.0 [mu]g/m\3\ corresponds to approximately 7,400 fewer deaths per
year (confidence intervals ranging from about 4,100 to 9,800)
attributable to long-term PM2.5 exposures (U.S. EPA, 2022b,
section <IP_ADDRESS>).
    In the 30 study areas where just meeting the current and
alternative standards is controlled by the annual standard, air quality
adjusted to meet alternative annual standards with lower

levels is associated with reductions in estimated all-cause mortality
risk. These reductions in risk for alternative annual levels are as
follows: 7-9% reduction for an alternative annual level of 11.0
[micro]g/m\3\, 15-19% reduction for a level of 10.0 [micro]g/m\3\, 22-
28% reduction for a level of 9.0 [micro]g/m\3\, and 30-37% reduction
for a level of 8.0 [micro]g/m\3\ (U.S. EPA, 2022b, section <IP_ADDRESS>).
For each of these standards, most of the risk remaining is estimated at
annual average PM2.5 concentrations that fall somewhat below
the alternative standard levels (U.S. EPA, 2022b, section <IP_ADDRESS>).
    In considering the at-risk analysis, the PA notes that across all
simulated air quality for both the full set of 47 and the subset of 30
study areas, Blacks experience the highest average PM2.5
concentrations of the demographic groups analyzed. Native Americans
experienced the lowest average PM2.5 concentrations,
particularly in the full set of 47 study areas. White, Hispanic, and
Asian populations were exposed to similar average PM2.5
concentrations. Additionally, as the levels of potential alternative
annual PM2.5 standards decrease, there is comparatively less
disproportionate exposure between demographic populations (U.S. EPA,
2022b, section <IP_ADDRESS>).
    The PA recognizes that the risk estimates can provide additional
information beyond the exposure information to inform our understanding
of potentially disproportionate impacts, in this instance by including
demographic-specific information on baseline incidence and the
relationship between exposure and health effect. Across all air quality
scenarios and demographic groups evaluated, Black populations in the
study areas are associated with the largest PM2.5-
attributable mortality risk rate per 100,000 people, while White
populations in the study areas are associated with the smallest
PM2.5-attributative mortality risk rate (U.S. EPA, 2022b,
section <IP_ADDRESS>, Figure 3-20). Generally, as the levels of potential
alternative annual PM2.5 standards decrease in the 30 areas
controlled by the annual standard, the average reductions in
PM2.5 concentration and mortality risk rates increase across
all demographic populations (U.S. EPA, 2022b, section <IP_ADDRESS>, Figure
3-21).
    In comparing the reductions in average national PM2.5
concentrations and risk rates within each demographic population, the
average percent PM2.5 concentrations and risk reductions are
slightly greater in the Black population than in the White population
for each alternative standard evaluated (11.0 [micro]g/m\3\, 10.0
[micro]g/m\3\, 9.0 [micro]g/m\3\, and 8.0 [micro]g/m\3\), when shifting
from the current annual PM2.5 standard (12.0 [micro]g/m\3\)
in the full set of 47 areas and the subset of 30 areas controlled by
the annual standard. Furthermore, the difference in average percent
risk reductions increases slightly more in Blacks than in Whites as the
level of the potential alternative annual standard decreases (U.S. EPA,
2022b, section <IP_ADDRESS>, Table 3-19 and Table 3-20).
    The PA also recognizes that there are several particularly
important uncertainties that affect the quantitative estimates of risk
rates and exposure in the at-risk analysis and their interpretation in
the context of considering the current primary PM2.5
standards. These include uncertainties related to the modeling and
adjustment methods for simulating air quality scenarios; the potential
influence of confounders on the relationship between PM2.5
exposure and mortality; and the interpretation of the shapes of C-R
functions, particularly at lower concentrations. It is also important
to recognize the limited availability of studies to inform the at-risk
analysis. As noted in section II.C above and in section 3.4 of the PA,
the at-risk analysis included C-R functions from one study, Di et al.
(2017b), which reported associations between long-term PM2.5
exposures and mortality, stratified by race/ethnicity, in populations
age 65 and older. Of the studies available from the 2019 ISA, Di et al.
(2017b) was identified as best characterizing potentially at-risk
minority populations across the U.S.\98\ While the at-risk analyses
provide additional insight on the estimated exposures and risks for
certain demographic groups, it is not clear how the results would vary
if: (1) analyses included populations that were younger than 65 years
old, (2) the analyses were conducted areas that are demographically
different than the 47 study areas included in this analysis, and (3)
the air quality adjustments reflected source-specific emissions
reduction strategies. Therefore, in light of the limitations and
uncertainties associated with the at-risk analyses, the results should
be considered within the context of the full risk assessment. The
uncertainties associated with the quantitative risk assessment and at-
risk analyses are described in more detail in the PA (U.S. EPA, 2022b,
section <IP_ADDRESS> and Appendix C) and are summarized in section II.C.2
above.
---------------------------------------------------------------------------

    \98\ Additional details on concentration-response function
identification can be found in Appendix C, section C.3.2 of the PA.
---------------------------------------------------------------------------

    In considering the public health implications of the risk
assessment, the PA notes that the purpose for the study areas is to
illustrate circumstances that may occur in areas that just meet the
current or potential alternative standards, and not to estimate risk
associated with conditions occurring in those specific locations
currently. The PA notes that some areas across the U.S. have air
quality for PM2.5 that is near or above the existing
standards. Risks associated with air quality above the current
standards are not informative to decisions about the adequacy of the
current standards. This is because the risk assessment uses an approach
to adjust air quality to just meet the current standards, which means
that areas that have air quality that is above the current standards
would be adjusted to just meet the current standards such that the
evaluation of changes in risk and risk remaining would be associated
with those areas meeting the current standards. The same is true for
air quality adjusted to simulate just meeting alternative standard
levels as well. Thus, the air quality and exposure circumstances
assessed in the study areas in the risk assessment are specifically
designed to inform whether the currently available information calls
into question the adequacy of the public health protection afforded by
the current standards, as well as to provide information regarding
potential alternative standard levels.
    The risk estimates for the study areas assessed in this
reconsideration reflect differences in exposure circumstances among
those areas and illustrate the exposures and risks that might be
expected to occur in other areas with such circumstances under air
quality conditions that just meet the current standards or the
alternative standards assessed. Thus, the exposure and risk estimates
indicate the magnitude of exposure and risk that might be expected in
many areas of the U.S. with PM2.5 concentrations at or near
the current or alternative standards. Although the methodologies and
data used to estimate risks in this reconsideration differ in several
ways from what was used in the 2020 review, the findings and
considerations summarized in the PA present a pattern of exposure and
risk that is generally similar to that considered in the 2020 review,
and indicate a level of protection generally consistent with that
described in the 2020 PA.
    The PA notes that the considerations related to the potential
public health implications of the risk assessment and at-risk analysis
are important to informing the Administrator's proposed

decisions regarding the public health significance of the risk
assessment results. Specifically, the PA notes that available evidence
and information suggests that both long- and short-term
PM2.5 exposures are associated with adverse health effects,
including more severe effects such as mortality. In addition, the PA
further notes that such effects impact large segments of the U.S.
population, including those populations that may have other factors
that influence risk (i.e., lifestage, pre-existing cardiovascular and
respiratory diseases, race/ethnicity), as well as disparities in
PM2.5 exposures and health risks based on race and ethnicity
(U.S. EPA, 2022b, section <IP_ADDRESS>). Therefore, the PA recognizes that
the air quality allowed by the current primary PM2.5
standards could be judged to be associated with significant public
health risk. The PA also recognizes that such conclusions also depend
in part on public health policy judgments that will weigh in the
Administrator's decision in this reconsideration with regard to the
adequacy of protection afforded by the current standards. Such
judgments that are common to NAAQS decisions include those related to
public health implications of effects of differing severity. Such
judgments also include those concerning the public health significance
of effects at exposures for which evidence is limited or lacking, such
as effects at lower concentrations than those demonstrated in the key
epidemiologic studies and in those population groups for which
population-specific information, such as C-R functions, are not
available from the epidemiologic literature.
3. Administrator's Proposed Conclusions on the Primary PM2.5
Standards
    This section summarizes the Administrator's considerations and
proposed conclusions related to the adequacy of the current primary
PM2.5 standards and presents his proposed decision to revise
the primary annual PM2.5 standard and retain the primary 24-
hour PM2.5 standard. In establishing primary standards under
the Act that are ``requisite'' to protect public health with an
adequate margin of safety, the Administrator is seeking to establish
standards that are neither more nor less stringent than necessary for
this purpose. He recognizes that the requirement to provide an adequate
margin of safety was intended to address uncertainties associated with
inconclusive scientific and technical information and to provide a
reasonable degree of protection against hazards that research has not
yet identified. However, the Act does not require that primary
standards be set at a zero-risk level; rather, the NAAQS must be
sufficiently protective, but not more stringent than necessary.
    Given these requirements, the Administrator's final decision in
this reconsideration will be a public health policy judgment drawing
upon scientific and technical information examining the health effects
of PM2.5 exposures, including how to consider the range and
magnitude of uncertainties inherent in that information. This public
health policy judgment will be based on an interpretation of the
scientific and technical information that neither overstates nor
understates its strengths and limitations, nor the appropriate
inferences to be drawn, and will be informed by the Administrator's
consideration of advice from the CASAC and public comments received on
this proposal document.
a. Adequacy of the Current Primary PM2.5 Standards
    In considering whether the currently available scientific evidence
and quantitative risk-based information support or call into question
the adequacy of the public health protection afforded by the current
primary PM2.5 standards, and as is the case with NAAQS
reviews in general, the extent to which the current primary
PM2.5 standards are judged to be adequate will depend on a
variety of factors, including science policy and public health policy
judgments to be made by the Administrator on the strength and
uncertainties of the scientific evidence. The factors relevant to
judging the adequacy of the standards also include the interpretation
of, and decisions as to the weight to place on, different aspects of
the results of the risk assessment for the study areas included and the
associated uncertainties. Thus, the Administrator's proposed
conclusions regarding the adequacy of the current standards will depend
in part on judgments regarding aspects of the evidence and risk
estimates, and judgments about the degree of protection that is
requisite to protect public health with an adequate margin of safety.
i. Proposed Conclusions on the Adequacy of the Current Primary
PM2.5 Standards
    In reaching proposed conclusions on the adequacy of the current
primary PM2.5 standards, the Administrator has considered
the scientific evidence, including that assessed in the 2019 ISA and
the ISA Supplement. The Administrator has also considered the
quantitative estimates of risk developed in this reconsideration,
including associated uncertainties and limitations, and the extent to
which they indicate differing conclusions regarding the magnitude of
risk, as well as level of protection from adverse effects, associated
with the current standards. The Administrator has additionally
considered the key aspects of the evidence and risk estimates
emphasized in establishing the current standards, and the associated
public health policy judgments and judgments about the uncertainties
inherent in the scientific evidence and quantitative analyses that are
integral to the proposed conclusions on the adequacy of the current
primary PM2.5 standards.
    First, as described above in section II.A.2, the Administrator's
approach recognizes that the current annual standard (based on
arithmetic mean concentrations) and 24-hour standard (based on 98th
percentile concentrations), together, are intended to provide public
health protection against the full distribution of short- and long-term
PM2.5 exposures. In evaluating the adequacy of the current
standards, the Administrator focuses on evaluating the public health
protection afforded by the annual and 24-hour standards, taken
together, against adverse health effects associated with long- or
short-term PM2.5 exposures. This approach recognizes that
changes in PM2.5 air quality designed to meet either the
annual or the 24-hour standard would likely result in changes to both
long-term average and short-term peak PM2.5 concentrations.
    In general, the Administrator recognizes that the annual standard
is most effective at controlling exposures to ``typical'' daily
PM2.5 concentrations that are experienced over the year,
while the 24-hour standard, with its 98th percentile form, is most
effective at limiting peak daily or 24-hour PM2.5
concentrations. In considering the combined effects of these standards,
the Administrator recognizes that changes in PM2.5 air
quality designed to meet an annual standard would likely result not
only in lower short- and long-term PM2.5 concentrations near
the middle of the air quality distribution, but also in fewer and lower
short-term peak PM2.5 concentrations. Additionally, changes
designed to meet a lower 24-hour standard, with a 98th percentile form,
would most effectively result in fewer and lower peak 24-hour
PM2.5 concentrations, but also have an effect on lowering
the annual average PM2.5 concentrations. Thus, the
Administrator acknowledges the focus in evaluating

the current primary standards is on the protection provided by the
combination of the annual and 24-hour standards against the
distribution of both short- and long-term PM2.5 exposures.
    The Administrator recognizes the longstanding body of health
evidence supporting relationships between PM2.5 exposures
(short- and long-term) and mortality or serious morbidity effects. The
evidence available in this reconsideration (i.e., that assessed in the
2019 ISA (U.S. EPA, 2019a) and ISA Supplement (U.S. EPA, 2022a) and
summarized above in section II.B.1 and section II.D.2.a reaffirms, and
in some cases strengthens, the conclusions from the 2009 ISA regarding
the health effects of PM2.5 exposures (U.S. EPA, 2009a). As
noted above, epidemiologic studies demonstrate generally positive, and
often statistically significant, PM2.5 health effect
associations. Such studies report associations between estimated
PM2.5 exposures and non-accidental, cardiovascular, or
respiratory mortality; cardiovascular or respiratory hospitalizations
or emergency room visits; and other mortality/morbidity outcomes (e.g.,
lung cancer mortality or incidence, asthma development). Recent
experimental evidence, as well as evidence from panel studies,
strengthens support for potential biological pathways through which
PM2.5 exposures could lead to the serious effects reported
in many population-level epidemiologic studies, including support for
pathways that could lead to cardiovascular, respiratory, nervous
system, and cancer-related effects. The Administrator also recognizes
that the PA notes that while the full body of health effects evidence
is considered in this reconsideration of the PM NAAQS, the greatest
emphasis in the PA is placed on the health effects for which the
evidence has been judged in the 2019 ISA to demonstrate a ``causal'' or
``likely to be causal'' relationship with PM2.5 exposures
(i.e., mortality, cardiovascular effects, respiratory effects, cancer,
and nervous system effects). In considering the available scientific
evidence, consistent with approaches employed in past NAAQS reviews,
the Administrator places the most weight on evidence supporting
``causal'' or ``likely to be causal'' relationship with long or short-
term PM2.5 exposures. In addition, the Administrator also
takes note of those populations identified to be at greater risk of
PM2.5-related health effects, as characterized in the 2019
ISA and ISA Supplement, and the potential public health implications.
    In evaluating the public health protection afforded by the current
primary PM2.5 standards against long- and short-term
PM2.5 exposures, the Administrator considers the four basic
elements of the NAAQS (indicator, averaging time, form, and level)
collectively. With respect to indicator, the Administrator recognizes
that the scientific evidence in this reconsideration, as in previous
reviews, continues to provide strong support for health effects
associated with PM2.5 mass. He notes the PA conclusion that
the available information continues to support the PM2.5
mass-based indicator and remains too limited to support a distinct
standard for any specific PM2.5 component or group of
components, and too limited to support a distinct standard for the
ultrafine fraction (U.S. EPA, 2022b, section <IP_ADDRESS>.1). In its advice
on the adequacy of the current primary PM2.5 standards, the
CASAC reached consensus that the PM2.5 mass-based indicator
should be retained, without revision (Sheppard, 2022a, p. 2 of
consensus letter). Thus, as in the 2020 review (85 FR 82715, December
18, 2020) and consistent with the advice from the CASAC, the
Administrator proposes to conclude that it is appropriate to consider
retaining PM2.5 mass as the indicator for the primary
standards for fine particles.
    With respect to averaging time and form, the Administrator notes
that the scientific evidence continues to provide strong support for
health effect associations with both long-term (e.g., annual or multi-
year) and short-term (e.g., mostly 24-hour exposures to
PM2.5) (U.S. EPA, 2022b, section <IP_ADDRESS>.2). In this
reconsideration, the epidemiologic and controlled human exposure
studies have examined a variety of PM2.5 exposure durations.
Epidemiologic studies continue to provide strong support for health
effects associated with short-term PM2.5 exposures based on
24-hour PM2.5 averaging periods, and the EPA notes that
associations with sub-daily estimates are less consistent and, in some
cases, smaller in magnitude (U.S. EPA, 2019a, section <IP_ADDRESS>; U.S.
EPA, 2022b, section <IP_ADDRESS>.2). In addition, controlled human exposure
and panel-based studies of sub-daily exposures typically examine
subclinical effects rather than the more serious population-level
effects that have been reported to be associated with 24-hour exposures
(e.g., mortality, hospitalizations). Taken together, the 2019 ISA
concludes that epidemiologic studies do not indicate that subdaily
averaging periods are more closely associated with health effects than
the 24-hour average exposure metric (U.S. EPA, 2019a, section <IP_ADDRESS>).
Additionally, while recent controlled human exposure studies provide
consistent evidence for cardiovascular effects following
PM2.5 exposures for less than 24 hours (i.e., <30 minutes to
5 hours), exposure concentrations in these studies are well-above the
ambient concentrations typically measured in locations meeting the
current standards (U.S. EPA, 2022b, section <IP_ADDRESS>). Therefore, these
studies do not provide support for additional protection against sub-
daily PM2.5 exposures, beyond that provided by the current
primary standards. In its advice on the adequacy of the current primary
PM2.5 standards, the CASAC reached consensus that averaging
times for the standards should be retained, without revision (Sheppard,
2022a, p. 2 of consensus letter). Thus, as in the 2020 review (85 FR
82715, December 18, 2020), and consistent with the advice from the
CASAC, the Administrator reaches the proposed conclusion that the
currently available evidence does not support considering alternatives
to the annual and 24-hour averaging times for standards meant to
protect against long- and short-term PM2.5 exposures.
    With regard to form, the Administrator proposes to conclude that it
is appropriate to consider retaining the current form of both the
annual and the 24-hour standards. In so doing, he first notes that, in
the 1997 review, the EPA set both an annual standard, to provide
protection from health effects associated with both long- and short-
term exposures to PM2.5, and a 24-hour standard to a
supplement the protection afforded by the annual standard (62 FR 38667,
July 18, 1997). With regard to the form of the annual standard, the
Administrator recognizes that a large majority of the recently
available epidemiologic studies continue to report associations between
health effects and annual average PM2.5 concentrations.
These studies of annual average PM2.5 concentrations provide
support for retaining the current form of the annual standard to
provide protection against long- and short-term PM2.5
exposures. In its advice on the adequacy of the current standards, the
CASAC reached consensus that the form of the annual standard (i.e.,
annual mean, averaged over 3 years) should be retained, without
revision (Sheppard, 2022a, p. 2 of consensus letter). In relation to
the form of the 24-hour standard (98th percentile, averaged over three
years), the Administrator notes that epidemiologic studies continue to
provide strong support for health effect associations with short-term
(e.g., mostly 24-hour) PM2.5 exposures (U.S.

EPA, 2022b, section <IP_ADDRESS>.3) and that controlled human exposure
studies provide evidence for health effects following single short-term
``peak'' PM2.5 exposures. Thus, the evidence supports
retaining a standard focused on providing supplemental protection
against short-term peak exposures and supports a 98th percentile form
for a 24-hour standard. The Administrator further notes that this form
also provides an appropriate balance between limiting the occurrence of
peak 24-hour PM2.5 concentrations and identifying a stable
target for risk management programs (U.S. EPA, 2022b, section
<IP_ADDRESS>.3). While the CASAC provided recommendations regarding the
adequacy of the current 24-hour standard conditional on the current
form (i.e., 98th percentile, averaged over three years), they
recommended that in future reviews, the EPA also consider alternative
forms for the primary 24-hour PM2.5 standard (Sheppard,
2022a, p. 18 of consensus responses). Furthermore, the Administrator
notes that the multi-year percentile form (i.e., averaged over three
years) offers greater stability to the air quality management process
by reducing the possibility that statistically unusual indicator values
will lead to transient violations of the standard. Thus, in considering
the information summarized above, and consistent with the advice from
the CASAC, the Administrator reaches the preliminary conclusion that it
is appropriate to consider retaining the forms of the current annual
and 24-hour PM2.5 standards. The Administrator solicits
public comment on the proposed decision to retain the current form
(98th percentile, averaged over three years) of the primary 24-hour
PM2.5 standard. The Administrator acknowledges that the
CASAC recommended retaining the current form at this time but also
recommended that the EPA consider alternatives to the current form in
future reviews. The EPA agrees that it would be appropriate to gather
additional air quality and scientific information and further consider
these issues in future reviews. This information will not be utilized
for this reconsideration process.
    With regard to the level of the current standards, the
Administrator first considers the scientific evidence evaluated in the
2019 ISA and ISA Supplement, and considerations regarding the evidence
as presented in the PA. The Administrator recognizes that the PA places
greater weight on epidemiologic studies conducted in the U.S. and
Canada, as these studies are more directly applicable for quantitative
considerations compared to studies conducted in other countries.
Studies conducted in other countries outside of the U.S. and Canada
generally reflect different populations, exposure characteristics, air
pollution mixtures, and higher PM2.5 concentrations in
ambient air than are currently found in the U.S. Therefore, consistent
with approaches in previous reviews, the Administrator judges that it
is appropriate to place greater weight on the U.S. and Canadian
epidemiologic studies in reaching conclusions regarding the adequacy of
the current standards. In so doing, the Administrator notes that the
epidemiologic studies in the U.S. and Canada report health effect
associations with mortality and/or morbidity across multiple cities and
in diverse populations, including in studies examining populations and
lifestages that may be at increased risk of experiencing a
PM2.5-related health effect (e.g., older adults, children,
populations with pre-existing cardiovascular and respiratory disease,
minority populations, and low SES communities). Further, he notes the
epidemiologic studies that use a variety of statistical designs and
employ a variety of methods to examine exposure measurement error as
well as to control for confounding effects, and he acknowledges that
results of these analyses support the robustness of the reported
associations. Additionally, the Administrator notes findings from an
expanded body of studies that employ alternative methods for confounder
control and accountability methods further inform the causal nature of
the relationship between long or short-term term PM2.5
exposure and mortality as described in the 2019 ISA and ISA Supplement
(U.S. EPA, 2019, sections <IP_ADDRESS>, <IP_ADDRESS>; U.S. EPA, 2022a, sections
<IP_ADDRESS>, <IP_ADDRESS>, <IP_ADDRESS>, and <IP_ADDRESS>). These studies, summarized
above in II.B.3 above and in Table 3-11 and Table 3-12 of the PA (U.S.
EPA, 2022b) examine both short- and long-term PM2.5 exposure
and cardiovascular effects and mortality, and, using a variety of
statistical methods to control for confounding bias, consistently
report positive associations, which further supports the broader body
of epidemiologic evidence for both cardiovascular effects and
mortality. Moreover, the Administrator notes that recent epidemiologic
studies strengthen support for health effect associations at
PM2.5 concentrations lower than in those evaluated in
epidemiologic studies available at the time of previous reviews.
Lastly, the Administrator notes that studies that examine the shape of
the C-R relationship over the full distribution of ambient
PM2.5 concentrations have not identified a threshold
concentration, below which associations no longer exist (U.S. EPA,
2019a, section 1.5.3; U.S. EPA, 2022a, sections <IP_ADDRESS>.1 and
<IP_ADDRESS>.2). However, the Administrator also notes that uncertainties
remain about the shape of the C-R curve at PM2.5
concentrations <8 [mu]g/m\3\, with some recent studies providing
evidence for either a sublinear, linear, or supralinear relationship at
these lower concentrations (section II.B.4 above; U.S. EPA, 2019a,
section 11.2.4; U.S. EPA, 2022a, section <IP_ADDRESS>).
    In considering the available scientific evidence to inform proposed
decisions on the adequacy of the current level of the annual standard,
the Administrator acknowledges that the evidence available in this
reconsideration provides support for adverse health effect associations
at lower ambient PM2.5 concentrations than in previous
reviews. The Administrator notes that in previous reviews (including
1997, 2006 and 2012 reviews), evidence-based approaches focused on
identifying standard levels near or somewhat below long-term mean
concentrations reported in key epidemiologic studies. These approaches
were supported by the CASAC in previous reviews and are supported in
this reconsideration by the current CASAC, who also referenced the
potential for considering other lines of epidemiologic evidence.\99\
The Administrator notes that in this reconsideration, a large number of
key U.S. epidemiologic studies report positive and statistically
significant associations for air quality distributions with overall
mean PM2.5 concentrations that are well below the current
level of the annual standard of 12 [mu]g/m\3\ (i.e., Figure 1 and
Figure 2 above with concentrations ranging down as low as 9.9 [mu]g/
m\3\ in U.S.-based monitor-based studies and 9.3 [mu]g/m\3\ in U.S.-
based hybrid model-based studies). The Administrator also recognizes
that, while Canadian studies can be more difficult to directly compare
to the annual design value used to determine in compliance in the U.S.,
the overall mean PM2.5 concentrations from the key Canadian
epidemiologic studies are

close to, though somewhat lower than, those from the U.S. studies. The
range of monitor-based mean PM2.5 concentrations is from 6.9
[mu]g/m\3\ to 13.3 [mu]g/m\3\ while the range of mean PM2.5
concentrations in studies that use hybrid modeling is 5.9 [mu]g/m\3\ to
9.8 [mu]g/m\3\.
---------------------------------------------------------------------------

    \99\ The Administrator notes that some members of the CASAC
advised that ``for the purpose of informing the adequacy of the
standards'' (Sheppard, 2022a, p. 8 of consensus responses) that the
EPA in future reviews include evaluation of other metrics, including
the distribution of concentrations reported in epidemiologic studies
and in analyses restricting concentrations to below the current
standard level.
---------------------------------------------------------------------------

    In assessing the adequacy of the current annual standard, the
Administrator also examines additional epidemiologic studies,
consistent with CASAC advice, that provide supplementary information
for consideration in reaching conclusions regarding the current annual
standard. These studies include analyses that restrict annual average
PM2.5 concentrations to values below level the annual
standard (described above in section II.B.3.b and in Table 3-10 of the
PA) and the CASAC advised that ``for the purpose of informing the
adequacy of the standards'' that the EPA evaluate the means from these
studies. In this reconsideration, there are two key studies available
that restrict average annual PM2.5 concentrations to less
than 12 [mu]g/m\3\ (Di et al., 2017a, and Dominici et al., 2019). These
restricted analyses report positive and statistically significant
associations with all-cause mortality and report mean PM2.5
concentrations of 9.6 [mu]g/m\3\. Thus, these two epidemiologic studies
provide support for positive and statistically significant associations
at lower mean PM2.5 concentrations. The Administrator does
note that uncertainties exist in these analyses (described in more
detail in sections II.B.3.b and II.D.2.a above), including uncertainty
in how studies exclude concentrations (e.g., at what spatial resolution
are concentrations being excluded), which would make any comparisons of
concentrations in restricted analyses difficult to compare directly to
design values.
    In considering the available key U.S. epidemiologic studies, the
Administrator also notes that CASAC recommended looking at the
distribution of concentrations reported in epidemiologic studies for
purposes of informing the adequacy of the standards and notes that a
small number of studies report PM2.5 concentrations
corresponding to the 25th and 10th percentiles of health data or
exposure estimates. He observes that in studies that use monitors to
estimate PM2.5 exposures, 25th percentiles of health events
correspond to PM2.5 concentrations (i.e., averaged over the
study period for each study city) at or above 11.5 [mu]g/m\3\ and 10th
percentiles of health events correspond to PM2.5
concentrations at or above 9.8 [mu]g/m\3\ (i.e., 25% and 10% of health
events, respectively, occur in study locations with PM2.5
concentrations below these values) (Figure 1 above and U.S. EPA, 2022b,
Figure 3-8). The Administrator further observes that of the key U.S.
epidemiologic studies that use hybrid modeling approaches to estimate
long-term PM2.5 exposures, the ambient PM2.5
concentrations corresponding to 25th percentiles of estimated exposures
are 9.1 [mu]g/m\3\ (Figure 2 above and U.S. EPA, 2022b, Figure 3-14).
In key U.S. epidemiologic studies that use hybrid modeling approaches
to estimate short-term PM2.5 exposures, the ambient
concentrations corresponding to 25th percentiles of estimated
exposures, or health events, are 6.7 [mu]g/m\3\ and the ambient
PM2.5 concentration corresponding to that 10th percentile
range from 4.7 [mu]g/m\3\ to 7.3 [mu]g/m\3\ (Figure 2 above and U.S.
EPA, 2022b, Figure 3-14). While the Administrator places less weight on
the limited number of studies that report these lower quartiles of the
air quality distributions, he notes these concentrations are generally
below the level of the annual standard of 12 [mu]g/m\3\.
    In further assessing the adequacy of the current annual standard,
the Administrator also evaluates what the accountability studies may
indicate with respect to potential for improvements in public health
with improvements in air quality. In so doing, he takes note of three
accountability studies (Sanders et al., 2020b; Corrigan et al., 2018;
and Henneman et al., 2019a) newly available in this reconsideration
with starting concentrations at or below 12.0 [mu]g/m\3\ that indicate
positive and significant associations with mortality and morbidity and
reductions in ambient PM2.5 (described above in section
II.B.3.b and in Table 3-12 of the PA) and notes that these studies
suggest public health improvements may occur at concentrations below 12
[mu]g/m\3\.
    Thus, in considering the available scientific evidence to inform
proposed decisions on the adequacy of the current primary annual
PM2.5 standard, the Administrator recognizes that there is a
long-standing body of epidemiologic evidence that provides support for
associations between PM2.5 exposures and health effects
across a distribution of air quality that includes concentrations near
(i.e., at, above, and below) the current standards. As such, the
Administrator recognizes that the available scientific evidence, as
assessed in the 2019 ISA and ISA Supplement, including the newly
available epidemiologic studies and the supplemental information from
specific types of epidemiologic studies, provides a strong scientific
foundation for consideration of the adequacy of the level of the
current annual standard.
    In considering the available scientific evidence to inform proposed
decisions on the adequacy of the current 24-hour standard, the
Administrator finds that there is less information available to support
decisions on the 24-hour standard than that summarized above for the
annual standard. When looking to the experimental studies, he notes
that controlled human exposure studies provide evidence for health
effects following single, short-term exposures to PM2.5
concentrations that are greater than those typically present in ambient
air. In the controlled human exposure studies, the Administrator
observes that results are inconsistent, particularly at lower
PM2.5 concentrations, but that studies do report
statistically significant effects on one or more indicators of
cardiovascular function following 2-hour exposures to PM2.5
concentrations at and above 120 [mu]g/m\3\ (and at and above 149 [mu]g/
m\3\ for vascular impairment, the effect shown to be most consistent
across studies). As noted in the 2019 ISA, these studies are important
in establishing biological plausibility for PM2.5 exposures
causing more serious health effects, such as those seen in short-term
exposure epidemiologic studies. However, as noted in the PA, the
observed effects in these controlled human exposures studies are ones
that signal an intermediate effect in the body, likely due to short-
term exposure to PM2.5, and which may provide support that
more adverse effects may be experienced following longer exposure
durations and/or exposure to higher concentrations but such
intermediate effects typically would not, by themselves, be judged as
adverse. Additionally, he acknowledges, as noted by the CASAC, that
these controlled human exposure studies generally do not include
populations with substantially increased risk from exposure to
PM2.5, such as children, older adults, or those with more
severe underlying illness. So, noting these points and balancing these
limitations (i.e., that the health outcomes observed in these
controlled human exposure studies are not clearly adverse and that the
studies generally do not include those at increased risk from
PM2.5 exposure), the Administrator examines the air quality
analyses, described in more detail in section II.B.3.a above, to assess
whether during recent air quality conditions, areas meeting the current

standards would experience the concentrations reported in these
controlled human exposure studies. He observes that these air quality
analyses demonstrate that the PM2.5 exposures shown to cause
consistent effects in the controlled human exposure studies are well-
above the ambient concentrations typically measured in locations
meeting the current primary standards, thus suggesting that the current
primary PM2.5 standards provide protection against these
``peak'' concentrations. In fact, at air quality monitoring sites
meeting the current primary PM2.5 standards (i.e., the 24-
hour standard and the annual standard), the 2-hour concentrations
generally remain below 10 [mu]g/m\3\, and rarely exceed 30 [mu]g/m\3\.
Two-hour concentrations are higher at monitoring sites violating the
current standards, but generally remain below 16 [mu]g/m\3\ and rarely
exceed 80 [mu]g/m\3\. Based on this information, the Administrator
finds that the current suite of standards maintains sub-daily
concentrations far below the current concentrations in controlled human
exposure studies where consistent effects have been observed, and notes
that while these studies generally do not include the most at-risk
individuals, the exposure concentrations in these studies also do not
elicit adverse effects.
    In addition, the Administrator also notes that the majority of the
CASAC provide support for their advice to revise the current daily
standard by pointing to ``substantial epidemiologic evidence from both
morbidity and mortality studies'' which ``includes three U.S. air
pollution studies with analyses restricted to 24-hour concentrations
below 25 [mu]g/m\3\'' (Sheppard, 2022a, p. 17 consensus responses). In
considering this advice from the majority of the CASAC, the
Administrator notes that the substantial epidemiologic evidence
available in this reconsideration, including the studies that restrict
short-term (24-hour average PM2.5 concentrations)
PM2.5 exposures below 25 [mu]g/m\3\, provides support for
positive and statistically significant associations between exposure to
short-term PM2.5 concentrations and all-cause mortality (Di
et al., 2017a) and CVD hospital admissions (deSouza et al., 2021, and
Di et al., 2017a). In particular, for the available epidemiologic
studies that employ restricted analyses of short-term exposure studies,
multicity studies indicate that positive and statistically significant
associations with mortality persist in analyses restricted to short-
term (24-hour average PM2.5 concentrations) PM2.5
exposures below 35 [mu]g/m\3\ (Lee et al., 2015), below 30 [mu]g/m\3\
(Shi et al., 2016), and below 25 [mu]g/m\3\ (Di et al., 2017a). Thus,
the Administrator agrees that these studies help to provide additional
support for reaching conclusions on causality in the 2019 ISA.
Additionally, when considering these studies, the restricted approach
in these short-term studies most clearly indicates that risks
associated with short-term PM2.5 exposures are not
disproportionately driven by the peaks of the air quality distribution.
While this is useful information, it does not help to inform questions
on the adequacy of the current 24-hour standard given that the 24-hour
standard focuses on reducing ``peak'' exposures (with its 98th
percentile form). In further evaluating these studies, the
Administrator notes that the fact that there are positive and
significant associations in these analyses does not mean that one can
conclude that there would be short-term effects occurring in areas that
meet a 24-hour standard at these levels. This is true for multiple
reasons. First, there are uncertainties with respect to the
methodologies used in these studies to exclude concentrations and the
specific methodology used (e.g., are individual days with
concentrations above the concentration of interest in the restricted
analyses excluded at the modeled grid cell level or the ZIP code level
rather than removing entire areas with day(s) that exceed that
concentration) has direct implications for the resulting air quality
scenario(s). This in turn affects how the adjusted air quality
scenarios in these studies can be related to air quality distributions
and exposures to PM2.5 concentrations in ambient air and
thus how the data can be interpreted with regard to the current
standard level. Second, given that these studies are only evaluating
daily or annual average PM2.5 concentrations that would
correspond to the levels of the standards, they do not consider these
levels along with the forms and averaging times of the standards. This
is quite limiting for use in judging the adequacy of the 24-hour
standard given that the study-reported mean concentration is not useful
in informing the level of a standard with a 98th percentile form that
is designed to limit exposures to peak PM2.5 concentrations.
Further, as noted in the PA, the study-reported means from these
studies, are not useful in identifying a level at which we can say with
some confidence that effects are occurring due to impacts from ``peak''
exposures (i.e., those most closely aligned with the protection provide
by the 24-hour standard, with its 98th percentile form) but are instead
more useful in informing questions about impacts from ``typical'' or
average 24-hour exposures (i.e., those most closely aligned with the
protection provided by the annual standard). These uncertainties and
lack of information available from these studies are quite limiting and
as such, the Administrator concludes that it is unclear how to apply
these studies to a decision framework that could inform whether the
level of the current 24-hour standard is or is not adequate. However,
the Administrator notes this uncertainty may not be quite as limiting
for using restricted analyses studies to inform conclusions regarding
the adequacy of the annual standard, given that the study-reported
means could be evaluated in the context of the decision framework
described above for informing proposed decisions on the level of the
annual standard. However, in considering the available evidence with
regard to the current 24-hour PM2.5 standard, while the
Administrator agrees with the majority of the CASAC's comment that the
controlled human exposure studies have significant limitations which
must be considered when reaching conclusions on the adequacy of the
current 24-hour standard, he finds that restricted analyses studies
have significant limitations and do not provide a stronger line of
evidence with which to inform his proposed decisions on the current 24-
hour standard.
    In addition to the evidence above, the Administrator also considers
what the risk assessment indicates with regard to the adequacy of the
current primary annual and 24-hour PM2.5 standards. These
analyses provide estimates of PM2.5-attributable mortality
which are estimated based on input data that include C-R functions from
epidemiologic studies that have no threshold and a linear C-R
relationship down to zero, as well an air quality adjustment approach
that incorporates proportional decreases in PM2.5
concentrations to meet lower standard levels. The Administrator
observes that the risk assessment estimates that the current primary
annual PM2.5 standard could allow a substantial number of
deaths in the U.S. For example, when air quality in 30 study areas is
adjusted to simulate just meeting the current annual standard, the risk
assessment estimates long-term PM2.5 exposures to be
associated with as many as 39,000 total deaths, with confidence
intervals ranging from 26,000-51,000. The Administrator notes that
these estimates do not reflect uncertainties in associations of health
effects at lower

concentrations and simulated air quality improvements will always lead
to proportional decreases in risk (i.e., each additional [mu]g/m\3\
reduction produces additional benefits with no clear stopping point).
Noting these limitations and noting that the absolute numbers of
estimated deaths vary across exposure durations, populations, and C-R
functions, he also observes that the general magnitude of risk
estimates supports the potential for significant public health impacts
in locations meeting the current primary annual PM2.5
standard. He observes that this is particularly the case given that the
large majority of PM2.5-associated deaths for air quality
just meeting the current annual standard are estimated at annual
average PM2.5 concentrations from about 10 to 12 [mu]g/m\3\,
annual average PM2.5 concentrations that fall well within
the range of long-term average concentrations over which key
epidemiologic studies provide strong support for reported positive and
statistically significant PM2.5 health effect associations.
With respect to the CASAC's advice on the risk assessment, the
Administrator notes that the majority of the CASAC agreed that ``[t]he
results support the conclusion that the current primary annual
PM2.5 standard does not adequately protect public health''
(Sheppard, 2022a, p. 2 of consensus letter) and that ``[t]he CASAC
concurs with the EPA's assessment that meaningful risk reductions will
result from lowering the annual PM2.5 standard'' (Sheppard,
2022a, p. 3 of consensus letter). Additionally, the minority of CASAC
also agreed that the risk assessment results support revision to the
annual standard but commented that there were important uncertainties
in the analyses and interpretation of the analyses for annual standard
levels below 10 [mu]g/m\3\ (Sheppard, 2022a, p. 3 of consensus letter).
    The Administrator also recognizes that the risk assessment was able
to include a new analysis based on the availability of a new study in
this reconsideration that provided mortality risk coefficients for
older adults (i.e., 65 years and older) based on PM2.5
exposure and stratified by racial and ethnic demographics. This at-risk
analysis provided estimates of potential long-term PM2.5-
attributable exposure and mortality risk in older adults, stratified by
racial/ethnic demographics, when meeting a revised annual standard with
a lower level. The Administrator recognizes that this analysis is
subject to the same uncertainties as those associated with the main
risk assessment estimates, including being limited to a subset of areas
across the U.S. and influenced by air quality adjustment methodologies
that may not produce estimates of PM2.5 concentration
exposures that match those that can result from control strategies
implemented to meet more stringent standards, and that the results are
based on the risk coefficients of only one epidemiologic study. Taking
into account these uncertainties and limitations, he does judge that
the analysis supports that a lower annual standard level (i.e., below
12 [mu]g/m\3\ and down as low as 8 [mu]g/m\3\) will help to reduce
PM2.5 exposure and may also help to mitigate risk
disparities. The Administrator notes that what urban areas are included
in the risk assessment analysis will greatly influence the results but
notes that based on the areas included in the analyses, the results
show the largest impact is on reducing exposure and risk in Black
populations, who were estimated in the risk assessment case study areas
to have the highest levels of exposures and the greatest rates of
premature mortality risk.
    With respect to the 24-hour standard, the risk assessment indicates
that the annual standard is the controlling standard across most of the
urban study areas evaluated. When air quality is adjusted to just meet
an alternative 24-hour standard level of 30 [mu]g/m\3\ in the areas
where the 24-hour standard is controlling, the risk assessment
estimates reductions in PM2.5-associated risks across a more
limited population and number of areas compared to when air quality is
adjusted to simulate alternative levels for the annual standard, and
these predictions are largely confined to areas located in the western
U.S., several of which are also likely to experience risk reductions
upon meeting a revised annual standard. With respect to CASAC advice,
the Administrator notes that the minority of CASAC advised that these
results suggest that the annual standard can be used to limit both
long- and short-term PM2.5 concentrations and views these
risk assessment results as supporting the conclusion that the current
24-hour standard is adequate (Sheppard, 2022a, p. 4 of consensus
letter). In contrast, the majority of CASAC members commented that they
placed greater weight on the evidence-based considerations than on the
values estimated by the risk assessment, noting the potential for
uncertainties in how the risk assessment was able to ``capture areas
with wintertime stagnation and residential wood-burning where the
annual standard is less likely to be protective'' (Sheppard, 2022a, p.
4 of consensus letter). The majority of the CASAC members further state
that ``[t]here is also less confidence that the annual standard could
adequately protect against health effects of short-term exposures. A
range of 25-30 [mu]g/m\3\ for the 24-hour PM2.5 standard
would be adequately protective'' (Sheppard, 2022a, p. 4 of consensus
letter). The majority of the CASAC members further state that ``[t]here
is also less confidence that the annual standard could adequately
protect against health effects of short-term exposures. A range of 25-
30 [mu]g/m\3\ for the 24-hour PM2.5 standard would be
adequately protective'' (Sheppard, 2022a, p.4 of consensus letter).
    In considering the application of the risk assessment in a decision
framework assessing the adequacy of the current 24-hour standard, the
Administrator again notes that the risk assessment analyses of
PM2.5-attributable mortality use input data that include C-R
functions from epidemiologic studies that have no threshold and a
linear C-R relationship down to zero, as well an air quality adjustment
approach that incorporates proportional decreases in PM2.5
concentrations to meet lower standard levels, and that this
quantitative approach does not incorporate any elements of uncertainty
in associations of health effects at lower concentrations and simulated
air quality improvements will always lead to proportional decreases in
risk (i.e., each additional [mu]g/m\3\ reduction produces additional
benefits with no clear stopping point). Therefore, the Administrator
recognizes that the risk estimates can help to place the evidence for
specific health effects into a broader public health context but should
be considered along with the inherent uncertainties and limitations of
such analyses when informing judgments about the potential for
additional public health protection associated with PM2.5
exposure and related health effects. The Administrator also notes that
in the U.S., current air quality shows that the 24-hour standard is
controlling in very few areas and thus, it is understandable that there
are very few areas that would be included in the study areas in the
risk assessment. The Administrator also recognizes that the risk
assessment did not provide quantitative information on risk impacts
associated with an alternative 24-hour standard level of 25 [mu]g/m\3\.
    Based on the above considerations, the Administrator reaches the
proposed conclusion that the available scientific evidence (summarized
above in section II.B) and quantitative risk assessment

(summarized above in section II.C), can reasonably be viewed as calling
into question the adequacy of the public health protection afforded by
the current annual standard. In reaching this conclusion, the
Administrator places weight on the extensive epidemiologic evidence
available in this reconsideration, strengthened from previous reviews,
showing associations between adverse health effects (particularly
cardiovascular effects and mortality) and long-term mean
PM2.5 concentrations, and notes the number and strength of
studies available showing associations with mean PM2.5
concentrations well below the current annual standard of 12.0 [mu]g/
m\3\. The Administrator also takes note of the evidence supporting the
biological plausibility of these associations, including toxicological
studies and controlled human exposure studies. When turning to
additional information from the epidemiologic evidence base, he notes
the advice from CASAC to also consider the 25th percentile of the data
that is available and the study reported means from long-term studies
that restrict concentrations to below 12 [mu]g/m\3\. When considering
the 25th percentile of the data, the Administrator notes that it is
available from a limited number of epidemiologic studies and that the
current level of the annual standard is above most of the 25th
percentile values reported in the key epidemiologic studies. When
looking to the restricted analyses studies, he notes that there are two
studies that report positive and statistically significant associations
with all-cause mortality, and report a study mean PM2.5
concentration of 9.6 [mu]g/m\3\. While noting the limited nature of
these two lines of evidence and the associated uncertainties, the
Administrator does judge that these data support the need to revise the
annual standard level. Lastly, with respect to the epidemiologic
evidence, the Administrator also takes into account accountability
studies newly available in this reconsideration with starting
concentrations at or below 12.0 [mu]g/m\3\ that indicate positive and
significant associations with mortality and morbidity and reductions in
ambient PM2.5 and notes that these studies suggest public
health improvements may occur at concentrations below 12 [mu]g/m\3\.
    The Administrator also considers the results of the risk assessment
in light of the information it provides on risks associated with the
current and more stringent levels of the annual standard. While he
recognizes a number of uncertainties and limitations associated with
the quantitative estimates of the risk assessment, he judges that the
estimated risks remaining under air quality adjusted to just meet the
current suite of standards are too high to be considered requisite to
protect public health with an adequate margin of safety, noting in
particular the large number of premature deaths estimated to remain
with air quality that just meets the current annual standard. The
Administrator also recognizes that the risk assessment was able to
include a new analysis (at-risk analysis) that provided estimates of
potential long-term PM2.5-attributable exposure and
mortality risk in older adults, stratified by racial/ethnic
demographics, when meeting a revised annual standard with a lower
level. While the Administrator recognizes that this analysis is subject
to multiple uncertainties and limitations (as noted above in sections
II.C.2 and II.D.2.b), he does judge that the analysis suggests that a
lower annual standard level (i.e., below 12 [mu]g/m\3\ and down as low
as 8 [mu]g/m\3\) will help to reduce PM2.5 exposure and may
also help to mitigate exposure and risk disparities. Finally, the
Administrator considers the advice from the CASAC, who unanimously
recommended revising the annual standard.
    The Administrator finds it is less clear whether the available
scientific evidence and quantitative information call into question the
adequacy of the public health protection afforded by the current 24-
hour standard, particularly when considered in conjunction with the
protection provided by the suite of standards and the proposed decision
to revise the annual standard. In considering the scientific evidence,
he notes that the controlled human exposure studies do not provide a
threshold below which no effects occur and they do not include the most
at-risk populations. However, the concentrations reported in these
studies are for observed effects that signal a change in the body
likely due to short-term exposure to PM2.5 and which may be
the prelude to more adverse effects following longer duration and/or
higher concentration exposures but typically would not, by themselves,
be judged as adverse. Balancing this with the observation that the air
quality concentrations in areas meeting the current standards are well
below the PM2.5 concentrations shown to elicit effects in
these studies, the Administrator does not judge that these studies call
into question the adequacy of the current 24-hour standard. With
respect to the epidemiologic evidence, the Administrator notes that the
body of epidemiologic evidence provides limited support for judging
adequacy of the level of the 24-hour standard. As discussed in detail
above (section II.B.3.b), epidemiologic studies provide the strongest
support for reported health effect associations for the part of the air
quality distribution corresponding to the bulk of the underlying data
(i.e., estimated exposures and/or health events), often around the
overall mean concentrations evaluated rather than near the upper end of
the distribution. While there are three studies available in this
reconsideration that restricted 24-hour concentrations to
concentrations below 25 [mu]g/m\3\ and while some members of CASAC
pointed to these studies as the basis for their recommendation to
revise the 24-hour standard, the Administrator preliminarily concludes
that the results from these studies, particularly in light of the
uncertainties associated with these studies (as discussed above), are
an inadequate basis for revising the level of the 24-hour
PM2.5 standard.
    When evaluating the risk assessment information, the Administrator
notes that the risk assessment estimates a reduction of 9-13%
PM2.5 attributable mortality in areas where the 24-hour
standard is controlling when the 24-hour PM2.5 standard is
reduced from a level of 35 [mu]g/m\3\ to 30 [mu]g/m\3\. The
Administrator notes that this estimated reduction in PM2.5-
associated risks is across a more limited population and is largely
confined to a small number of areas located in the western U.S. Other
areas included in the risk assessment were shown to experience risk
reductions that were driven primarily by meeting a lower annual
standard level (though the associated change in air quality also
resulted in lower 24-hour standard concentrations). With respect to
CASAC advice, the Administrator notes that the majority of CASAC
advised that less weight be placed, while the minority of CASAC advised
that these risk assessment results support the conclusion that the
current 24-hour standard is adequate (Sheppard, 2022a, p. 4 of
consensus letter), the majority of CASAC advised that less weight be
placed on the risk assessment results and noted the potential for
uncertainties in how the risk assessment was able to ``capture areas
with wintertime stagnation and residential wood-burning where the
annual standard is less likely to be protective'' (Sheppard, 2022a, p.
4 of consensus letter).
    Based on the current evidence and quantitative information, as well
as consideration of CASAC advice and

public comment thus far in this reconsideration, the Administrator
proposes to conclude that the current primary PM2.5
standards are not adequate to protect public health with an adequate
margin of safety. While he notes that the scientific evidence and
quantitative information clearly call into question the adequacy of the
public health protection afforded by the current annual standard, the
Administrator finds it is less clear whether the available scientific
evidence and quantitative information calls into question the adequacy
of the public health protection afforded by the current 24-hour
standard. In considering how to revise the suite of standards to
provide the requisite degree of protection, he recognizes that changes
in PM2.5 air quality designed to meet either the annual or
the 24-hour standard would likely result in changes to both long-term
average and short-term peak PM2.5 concentrations. He also
recognizes that the current annual standard and 24-hour standard,
together, are intended to provide public health protection against the
full distribution of short- and long-term PM2.5 exposures.
As noted above, the annual standard is targeted at controlling the
typical exposures for which the evidence of adverse health effects is
strongest. The Administrator places the most weight on the large number
and strength of epidemiologic studies that report positive, and often
statistically significant, associations with long-term mean reported
PM2.5 concentrations well below the current level of the
annual standard of 12.0 [mu]g/m\3\, as well as corroborating evidence
from U.S. accountability studies with starting concentrations below 12
[mu]g/m\3\ and studies that found positive and statistically
significant associations in analyses restricted to concentrations less
than 12 [mu]g/m\3\. In considering the risk assessment information, he
notes that, for most of the U.S., the annual standard is the
controlling standard and that the risk assessment estimates reductions
in PM2.5-associated risks across more of the population and
in more areas with alternative annual standard levels compared to
estimates for alternative 24-hour standard levels. Moreover, the
Administrator notes that a more stringent annual standard has been
shown to effectively reduce both average (annual) concentrations and
peak (daily) concentrations, ensuring the broadest protection of public
health. Finally, the Administrator notes that the CASAC was unanimous
in its advice regarding the need to revise the annual standard,
although they did not reach consensus on what range of alternative
levels would be most appropriate to consider. Thus, in considering how
to revise the suite of standards to provide the requisite degree of
protection, the Administrator proposes to conclude it is appropriate to
focus on revising the annual standard.
b. Consideration of Alternative Primary Annual PM2.5
Standard Levels
    This section summarizes the Administrator's conclusions and
proposed decisions related to the current primary annual
PM2.5 standard and presents his proposed decision to revise
the level of the current annual standard within the range of 9.0 to
10.0 [mu]g/m\3\, in conjunction with retaining the current indicator,
averaging time, and form of that standard. The EPA is also soliciting
public comment on alternative annual standard levels down to 8.0 [mu]g/
m\3\ and up to 11.0 [mu]g/m\3\, on an alternative 24-hour standard
level as low as 25 [mu]g/m\3\ and on the combination of annual and 24-
hour standards that commenters may believe is appropriate, along with
the approaches and rationales used to support such levels.
    In establishing primary standards under the Act that are
``requisite'' to protect public health with an adequate margin of
safety, the Administrator is seeking to establish standards that are
neither more nor less stringent than necessary for this purpose. He
recognizes that the requirement to provide an adequate margin of safety
was intended to address uncertainties associated with inconclusive
scientific and technical information and to provide a reasonable degree
of protection against hazards that research has not yet identified.
However, the Act does not require that primary standards be set at a
zero-risk level; rather, the NAAQS must be sufficiently protective, but
not more stringent than necessary.
    Having reached the conclusion that the current indicator, averaging
time, and form of the standard are appropriate for the reasons outlined
above, the Administrator next considers the range of potential
alternative standard levels that could be reasonably supported by the
available scientific evidence and risk-based information to increase
public health protection against short-term and long-term
PM2.5 exposures. The evidence available in this
reconsideration regarding PM2.5 exposures associated with
health effects affirms and strengthens the evidence available at the
completion of the 2009 ISA, taking into account studies evaluated in
the 2019 ISA and ISA Supplement. The Administrator recognizes that the
weight of evidence is strongest for health effects for which the 2019
ISA concludes that the evidence provides support for a causal
relationship between PM2.5 exposures and health effects,
including those between long- and short-term PM2.5 exposures
and mortality and cardiovascular effects. He recognizes that the weight
of evidence is also strong for health effects for which the 2019 ISA
concludes that the evidence supports a likely to be causal
relationship, which include long- and short-term PM2.5
exposures and respiratory effects and long-term PM2.5
exposures and cancer, and nervous system effects.
    In considering the available scientific evidence that could inform
conclusions regarding potential alternative levels of the annual
PM2.5 standard, the Administrator notes that in past
reviews, the decision framework used to judge adequacy of the existing
PM2.5 standards, and what levels of any potential
alternative standards should be considered, placed significant weight
on epidemiologic studies that assessed associations between
PM2.5 exposure and health outcomes that were most strongly
supported by the body of scientific evidence (i.e., causal or likely to
be causal determinations). In so doing, the Administrator recognizes
that the number of epidemiologic studies has expanded since the
completion of the 2009 ISA and the epidemiologic studies evaluated in
the 2019 ISA and the ISA Supplement continue to report positive and
statistically significant associations between long- and short-term
exposure to PM2.5 and mortality and morbidity.