IHD and HF, along with cardiovascular mortality. Epidemiological
studies reporting robust associations in copollutant models are
supported by direct evidence from controlled human exposure and animal
toxicologic studies reporting independent effects of PM2.5
exposures on endothelial dysfunction as well as endpoints indicating
impaired cardiac function, increased risk of arrhythmia, changes in
HRV, increases in BP, and increases in indicators of systemic
inflammation, oxidative stress, and coagulation (U.S. EPA, 2019,
section 6.1.16). Epidemiological panel studies, although not entirely
consistent, provide some evidence that PM2.5 exposures are
associated with cardiovascular effects, including increased risk of
arrhythmia, decreases in HRV, increases in BP, and ST segment
depression. Overall, the results from epidemiological panel, controlled
human exposure, and animal toxicologic studies (in particular those
related to endothelial dysfunction, impaired cardiac function, ST
segment depression, thrombosis, conduction abnormalities, and changes
in blood pressure) provide coherence and biological plausibility for
the consistent results from epidemiological studies reporting positive
associations between short-term PM2.5 exposures and IHD and
HF, and ultimately cardiovascular mortality. The 2019 ISA concludes
that, overall, ``there continues to be sufficient evidence to conclude
that a causal relationship exists between short-term PM2.5
exposure and cardiovascular effects'' (U.S. EPA, 2019, p. 6-138).
iii. Respiratory Effects
Long-Term PM2.5 Exposures
    The 2009 ISA concluded that ``a causal relationship is likely to
exist between long-term PM2.5 exposure and respiratory
effects'' (U.S. EPA, 2009c). This conclusion was based mainly on
epidemiological evidence demonstrating associations between long-term
PM2.5 exposure and changes in lung function or lung function
growth in children. Biological plausibility was provided by a single
animal toxicologic study examining pre- and post-natal exposure to
PM2.5 CAPs, which found impaired lung development.
Epidemiological evidence for associations between long-term
PM2.5 exposure and other respiratory outcomes, such as the

development of asthma, allergic disease, and COPD; respiratory
infection; and the severity of disease was limited, both in the number
of studies available and the consistency of the results. Experimental
evidence for other outcomes was also limited, with one animal
toxicologic study reporting that long-term exposure to PM2.5
CAPs results in morphological changes in the nasal airways of healthy
animals. Other animal studies examined exposure to mixtures, such as
motor vehicle exhaust and woodsmoke, and effects were not attributed
specifically to the particulate components of the mixture.
    Recent cohort studies provide additional support for the
relationship between long-term PM2.5 exposure and decrements
in lung function growth (as a measure of lung development), indicating
a robust and consistent association across study locations, exposure
assessment methods, and time periods (U.S. EPA, 2019, section 5.2.13).
This relationship is further supported by a recent retrospective study
that reports an association between declining PM2.5
concentrations and improvements in lung function growth in children
(U.S. EPA, 2019, section 5.2.11). Epidemiological studies also examined
asthma development in children (U.S. EPA, 2019, section 5.2.3), with
recent prospective cohort studies reporting generally positive
associations, though several are imprecise (i.e., they report wide
confidence intervals). Supporting evidence is provided by studies
reporting associations with asthma prevalence in children, with
childhood wheeze, and with exhaled nitric oxide, a marker of pulmonary
inflammation (U.S. EPA, 2019, section 5.2.13). A recent animal
toxicologic study showing the development of an allergic phenotype and
an increase in a marker of airway responsiveness supports the
biological plausibility of the development of allergic asthma (U.S.
EPA, 2019, section 5.2.13). Other epidemiological studies report a
PM2.5-related acceleration of lung function decline in
adults, while improvement in lung function was observed with declining
PM2.5 concentrations (U.S. EPA, 2019, section 5.2.11). A
recent longitudinal study found declining PM2.5
concentrations are also associated with an improvement in chronic
bronchitis symptoms in children, strengthening evidence reported in the
2009 ISA for a relationship between increased chronic bronchitis
symptoms and long-term PM2.5 exposure (U.S. EPA, 2019,
section 5.2.11). A common uncertainty across the epidemiological
evidence is the lack of examination of copollutants to assess the
potential for confounding. While there is some evidence that
associations remain robust in models with gaseous pollutants, a number
of these studies examining copollutant confounding were conducted in
Asia, and thus have limited generalizability due to high annual
pollutant concentrations.
    When taken together, the 2019 ISA concludes that ``the collective
evidence is sufficient to conclude a likely to be causal relationship
between long-term PM2.5 exposure and respiratory effects''
(U.S. EPA, 2019, p. 5-220).
Short-Term PM2.5 Exposures
    The 2009 ISA (U.S. EPA, 2009c) concluded that a ``causal
relationship is likely to exist'' between short-term PM2.5
exposure and respiratory effects. This conclusion was based mainly on
the epidemiological evidence demonstrating positive associations with
various respiratory effects. Specifically, the 2009 ISA described
epidemiological evidence as consistently showing PM2.5-
associated increases in hospital admissions and emergency department
visits for COPD and respiratory infection among adults or people of all
ages, as well as increases in respiratory mortality. These results were
supported by studies reporting associations with increased respiratory
symptoms and decreases in lung function in children with asthma, though
the available epidemiological evidence was inconsistent for hospital
admissions or emergency department visits for asthma. Studies examining
copollutant models showed that PM2.5 associations with
respiratory effects were robust to inclusion of CO or SO2 in
the model, but often were attenuated (though still positive) with
inclusion of O3 or NO2. In addition to the
copollutant models, evidence supporting an independent effect of
PM2.5 exposure on the respiratory system was provided by
animal toxicologic studies of PM2.5 CAPs demonstrating
changes in some pulmonary function parameters, as well as inflammation,
oxidative stress, injury, enhanced allergic responses, and reduced host
defenses. Many of these effects have been implicated in the
pathophysiology for asthma exacerbation, COPD exacerbation, or
respiratory infection. In the few controlled human exposure studies
conducted in individuals with asthma or COPD, PM2.5 exposure
mostly had no effect on respiratory symptoms, lung function, or
pulmonary inflammation. Available studies in healthy people also did
not clearly find respiratory effects following short-term
PM2.5 exposures.
    Recent epidemiological studies provide evidence for a relationship
between short-term PM2.5 exposure and several respiratory-
related endpoints, including asthma exacerbation (U.S. EPA, 2019,
section <IP_ADDRESS>), COPD exacerbation (U.S. EPA, 2019, section <IP_ADDRESS>),
and combined respiratory-related diseases (U.S. EPA, 2019, section
5.1.6), particularly from studies examining emergency department visits
and hospital admissions. The generally positive associations between
short-term PM2.5 exposure and asthma and COPD emergency
department visits and hospital admissions are supported by
epidemiological studies demonstrating associations with other
respiratory-related effects such as symptoms and medication use that
are indicative of asthma and COPD exacerbations (U.S. EPA, 2019,
sections <IP_ADDRESS> and <IP_ADDRESS>). The collective body of epidemiological
evidence for asthma exacerbation is more consistent in children than in
adults. Additionally, epidemiological studies examining the
relationship between short-term PM2.5 exposure and
respiratory mortality provide evidence of consistent positive
associations, demonstrating a continuum of effects (U.S. EPA, 2019,
section 5.1.9).
    Building on the studies evaluated in the 2009 ISA, recent
epidemiological studies expand the assessment of potential copollutant
confounding. There is some evidence that PM2.5 associations
with asthma exacerbation, combined respiratory-related diseases, and
respiratory mortality remain relatively unchanged in copollutant models
with gaseous pollutants (i.e., O3, NO2,
SO2, with more limited evidence for CO) and other particle
sizes (i.e., PM10-2.5) (U.S. EPA, 2019, section <IP_ADDRESS>).
    Insight into whether there is an independent effect of
PM2.5 on respiratory health is provided by findings from
animal toxicologic studies. Specifically, short-term exposure to
PM2.5 has been shown to enhance asthma-related responses in
an animal model of allergic airways disease and lung injury and
inflammation in an animal model of COPD (U.S. EPA, 2019, sections
<IP_ADDRESS>.4 and <IP_ADDRESS>.3). The experimental evidence provides biological
plausibility for some respiratory-related endpoints, including limited
evidence of altered host defense and greater susceptibility to
bacterial infection as well as consistent evidence of respiratory
irritant effects. Animal toxicologic evidence for other respiratory
effects is inconsistent and controlled human exposure studies

provide limited evidence of respiratory effects (U.S. EPA, 2019,
section 5.1.12).
    The 2019 ISA concludes that ``[t]he strongest evidence of an effect
of short-term PM2.5 exposure on respiratory effects is
provided by epidemiological studies of asthma and COPD exacerbation.
While animal toxicologic studies provide biological plausibility for
these findings, some uncertainty remains with respect to the
independence of PM2.5 effects'' (U.S. EPA, 2019, p. 5-155).
When taken together, the ISA concludes that this evidence ``is
sufficient to conclude a likely to be causal relationship between
short-term PM2.5 exposure and respiratory effects'' (U.S.
EPA, 2019, p. 5-155).
iv. Cancer
    The 2009 ISA concluded that the overall body of evidence was
``suggestive of a causal relationship between relevant PM2.5
exposures and cancer'' (U.S. EPA, 2009c). This conclusion was based
primarily on positive associations observed in a limited number of
epidemiological studies of lung cancer mortality. The few
epidemiological studies that had evaluated PM2.5 exposure
and lung cancer incidence or cancers of other organs and systems
generally did not show evidence of an association. Toxicologic studies
did not focus on exposures to specific PM size fractions, but rather
investigated the effects of exposures to total ambient PM, or other
source-based PM such as wood smoke. Collectively, results of in vitro
studies were consistent with the larger body of evidence demonstrating
that ambient PM and PM from specific combustion sources are mutagenic
and genotoxic. However, animal inhalation studies found little evidence
of tumor formation in response to chronic exposures. A small number of
studies provided preliminary evidence that PM exposure can lead to
changes in methylation of DNA, which may contribute to biological
events related to cancer.
    Since the 2009 ISA, additional cohort studies provide evidence that
long-term PM2.5 exposure is positively associated with lung
cancer mortality and with lung cancer incidence, and provide initial
evidence for an association with reduced cancer survival (U.S. EPA,
2019, section 10.2.5), with limited evidence of cancer in other organ
systems. Reanalyses of the ACS cohort using different years of
PM2.5 data and follow-up, along with various exposure
assignment approaches, provide consistent evidence of positive
associations between long-term PM2.5 exposure and lung
cancer mortality (U.S. EPA, 2019, Figure 10-3). Additional support for
positive associations with lung cancer mortality is provided by recent
epidemiological studies using individual-level data to control for
smoking status, in studies of people who have never smoked), and in
analyses of cohorts that relied upon proxy measures to account for
smoking status (U.S. EPA, 2019, section <IP_ADDRESS>.1). Although studies
that evaluate lung cancer incidence, including studies of people who
have never smoked, are limited in number, recent studies generally
report positive associations with long-term PM2.5 exposures
(U.S. EPA, 2019, section <IP_ADDRESS>.2). In addition, a subset of the
studies focusing on lung cancer incidence also examined histological
subtypes, providing some evidence of positive associations for
adenocarcinomas, the predominate subtype of lung cancer observed in
people who have never smoked (U.S. EPA, 2019, section <IP_ADDRESS>.2).
Associations between long-term PM2.5 exposure and lung
cancer incidence were found to remain relatively unchanged, though in
some cases confidence intervals widened, in analyses that attempted to
reduce exposure measurement error by accounting for length of time at
residential address or by examining different exposure assignment
approaches (U.S. EPA, 2019, section <IP_ADDRESS>.2).
    To date, relatively few studies have evaluated the potential for
copollutant confounding of the relationship between long-term
PM2.5 exposure and lung cancer mortality or incidence. The
small number of such studies have generally focused on O3
and report that PM2.5 associations remain relatively
unchanged in copollutant models (U.S. EPA, 2019, section <IP_ADDRESS>.3).
However, available studies have not systematically evaluated the
potential for copollutant confounding by other gaseous pollutants or by
other particle size fractions (U.S. EPA, 2019, section <IP_ADDRESS>.3).
Compared to total (non-accidental) mortality (discussed above), fewer
studies have examined the shape of the concentration-response curve for
cause-specific mortality outcomes, including lung cancer. Several of
these studies have reported no evidence of deviations from linearity in
the shape of the concentration-response relationship (Lepeule et al.,
2012; Raaschou-Nielsen et al., 2013; Puett et al., 2014), though
authors provided only limited discussions of results (U.S. EPA, 2019,
section <IP_ADDRESS>.4).
    In support of the biological plausibility of an independent effect
of PM2.5 on cancer, the 2019 ISA notes evidence from recent
experimental studies demonstrating that PM2.5 exposure can
lead to a range of effects indicative of mutagenicity, genotoxicity,
and carcinogenicity, as well as epigenetic effects (U.S. EPA, 2019,
section 10.2.7). For example, both in vitro and in vivo toxicologic
studies have shown that PM2.5 exposure can result in DNA
damage (U.S. EPA, 2019, section 10.2.2). Although such effects do not
necessarily equate to carcinogenicity, the evidence that PM exposure
can damage DNA, and elicit mutations, provides support for the
plausibility of epidemiological associations with lung cancer mortality
and incidence. Additional supporting studies indicate the occurrence of
micronuclei formation and chromosomal abnormalities (U.S. EPA, 2019,
section <IP_ADDRESS>), and differential expression of genes that may be
relevant to cancer pathogenesis, following PM exposures. Experimental
and epidemiological studies that examine epigenetic effects indicate
changes in DNA methylation, providing some support for PM2.5
exposure contributing to genomic instability (U.S. EPA, 2019, section
10.2.3).
    Epidemiological evidence for associations between PM2.5
exposure and lung cancer mortality and incidence, together with
evidence supporting the biological plausibility of such associations,
contributes to the 2019 ISA's conclusion that the evidence ``is
sufficient to conclude there is a likely to be causal relationship
between long-term PM2.5 exposure and cancer'' (U.S. EPA,
2019, p. 10-77).
    In its letter to the Administrator on the draft ISA, the CASAC
states that ``the Draft ISA does not present adequate evidence to
conclude that there is likely to be a causal relationship between long-
term PM2.5 exposure and . . . cancer'' (Cox, 2019a, p. 1 of
letter). The CASAC specifically states that this causality
determination ``relies largely on epidemiology studies that . . . do
not provide exposure time frames that are appropriate for cancer
causation and that there are no animal studies showing direct effects
of PM2.5 on cancer formation'' (Cox, 2019a, p. 20 of
consensus responses).
    With respect to the latency period, it is well recognized that
``air pollution exposures experienced over an extended historical time
period are likely more relevant to the etiology of lung cancer than air
pollution exposures experienced in the more recent past'' (Turner et
al. 2011). However, many epidemiological studies conducted within the
U.S. that examine long-term

PM2.5 exposure and lung cancer incidence and lung cancer
mortality rely on more recent air quality data because routine
PM2.5 monitoring did not start until 1999-2000. An exception
to this is the ACS study that had PM2.5 concentration data
from two time periods, 1979-1983 and from 1999-2000. Turner et al.
(2011), conducted a comparison of PM2.5 concentrations
between these two time periods and found that they were highly
correlated (r >0.7), with the relative rank order of metropolitan
statistical areas (MSAs) by PM2.5 concentrations being
``generally retained over time.'' Therefore, areas where
PM2.5 concentrations were high remained high over decades
(or were low and remained low) relative to other locations. Long-term
exposure epidemiological studies rely on spatial contrasts between
locations; therefore, if a location with high PM2.5
concentrations continues to have high concentrations over decades
relative to other locations a relationship between the PM2.5
exposure and cancer should persist. This was confirmed in a sensitivity
analysis conducted by Turner et al. (2011), where the authors reported
a similar hazard ratio (HR) for lung cancer mortality for participants
assigned exposure to PM2.5 (1979-1983) and PM2.5
(1999-2000) in two separate analyses.
    While experimental studies showing a direct effect of
PM2.5 on cancer formation were limited to an animal model of
urethane-induced tumor initiation, a large number of experimental
studies report that PM2.5 exhibits several key
characteristics of carcinogens, as indicated by genotoxic effects,
oxidative stress, electrophilicity, and epigenetic alterations, all of
which provide biological plausibility that PM2.5 exposure
can contribute to cancer development. The experimental evidence, in
combination with multiple recent and previously evaluated
epidemiological studies examining the relationship between long-term
PM2.5 exposure and both lung cancer incidence and lung
cancer mortality that reported generally positive associations across
different cohorts, exposure assignment methods, and in analyses of
never smokers further addresses uncertainties identified in the 2009
ISA. Therefore, upon re-evaluating the causality determination for
cancer, when considering CASAC comments on the draft ISA and applying
the causal framework as described (U.S. EPA, 2015; U.S. EPA, 2019,
section A.3.2.1), the EPA continues to conclude in the 2019 ISA that
the evidence for long-term PM2.5 exposure and cancer
supports a ``likely to be causal relationship'' (U.S. EPA, 2019, p. 10-
77).
v. Nervous System Effects
    Reflecting the very limited evidence available in the last review,
the 2009 ISA did not make a causality determination for long-term
PM2.5 exposures and nervous system effects (U.S. EPA,
2009c). Since the last review, this body of evidence has grown
substantially (U.S. EPA, 2019, section 8.2). Recent studies in adult
animals report that long-term PM2.5 exposures can lead to
morphologic changes in the hippocampus and to impaired learning and
memory. This evidence is consistent with epidemiological studies
reporting that long-term PM2.5 exposure is associated with
reduced cognitive function (U.S. EPA, 2019, section 8.2.5). Further,
while the evidence is limited, early markers of Alzheimer's disease
pathology have been reported in rodents following long-term exposure to
PM2.5 CAPs. These findings support reported associations
with neurodegenerative changes in the brain (i.e., decreased brain
volume), all-cause dementia, and hospitalization for Alzheimer's
disease in a small number of epidemiological studies (U.S. EPA, 2019,
section 8.2.6). Additionally, loss of dopaminergic neurons in the
substantia nigra, a hallmark of Parkinson's disease, has been reported
in mice following long-term PM2.5 exposures (U.S. EPA, 2019,
section 8.2.4), though epidemiological studies provide only limited
support for associations with Parkinson's disease (U.S. EPA, 2019,
section 8.2.6). Overall, the lack of consideration of copollutant
confounding introduces some uncertainty in the interpretation of
epidemiological studies of nervous system effects, but this uncertainty
is partly addressed by the evidence for an independent effect of
PM2.5 exposures provided by experimental animal studies.
    In addition to the findings described above, which are most
relevant to older adults, several recent studies of neurodevelopmental
effects in children have also been conducted. Epidemiological studies
provided limited evidence of an association between PM2.5
exposure during pregnancy and childhood on cognitive and motor
development (U.S. EPA, 2019, section <IP_ADDRESS>). While some studies
report positive associations between long-term exposure to
PM2.5 during the prenatal period and autism spectrum
disorder (ASD) (U.S. EPA, 2019, section <IP_ADDRESS>). Interpretation of
these epidemiological studies is limited due to the small number of
studies, their lack of control for potential confounding by
copollutants, and uncertainty regarding the critical exposure windows.
Biological plausibility is provided for the ASD findings by a study in
mice that found inflammatory and morphologic changes in the corpus
collosum and hippocampus, as well as ventriculomegaly (i.e., enlarged
lateral ventricles) in young mice following prenatal exposure to
PM2.5 CAPs.
    Taken together, the 2019 ISA concludes that the strongest evidence
of an effect of long-term exposure to PM2.5 on the nervous
system is provided by toxicologic studies that show inflammation,
oxidative stress, morphologic changes, and neurodegeneration in
multiple brain regions following long-term exposure of adult animals to
PM2.5 CAPs. These findings are coherent with epidemiological
studies reporting consistent associations with cognitive decrements and
with all-cause dementia. The ISA determines that ``[o]verall, the
collective evidence is sufficient to conclude a likely to be causal
relationship between long-term PM2.5 exposure and nervous
system effects'' (U.S. EPA, 2019, p. 8-61).
    In its letter to the Administrator on the draft ISA, the CASAC
states that ``the Draft ISA does not present adequate evidence to
conclude that there is likely to be a causal relationship between long-
term PM2.5 exposure and nervous system effects'' (Cox,
2019a, p. 1 of letter). The CASAC specifically states that ``[f]or a
likely causal conclusion, there would have to be evidence of health
effects in studies where results are not explained by chance,
confounding, and other biases, but uncertainties remain in the overall
evidence'' (Cox, 2019a, p. 20 of consensus responses). These
uncertainties in the eyes of CASAC reflect that animal toxicologic
studies ``have largely been done by a single group,'' and for
epidemiological studies that examined brain volume that ``brain volumes
can vary . . . between normal people'' and the results from studies of
cognitive function were ``largely non-statistically significant'' (Cox,
2019a, p. 20 of consensus responses).
    With these concerns in mind, and as noted in the proposed rule (85
FR 24114, April 30, 2020), the EPA re-evaluated the evidence and note
that animal toxicologic studies were conducted in ``multiple research
groups [and show a range of effects including] inflammation, oxidative
stress, morphologic changes, and neurodegeneration in multiple brain
regions following long-term exposure of adult animals to
PM2.5 CAPs'' (U.S. EPA, 2019, p. 8-61). The results from the

animal toxicologic studies ``are coherent with a number of
epidemiological studies reporting consistent associations with
cognitive decrements and with all-cause dementia'' (U.S. EPA, 2019, p.
8-61). Additionally, as discussed in the Preamble to the ISAs (U.S.
EPA, 2015):

``. . . the U.S. EPA emphasizes the importance of examining the
pattern of results across various studies and does not focus solely
on statistical significance or the magnitude of the direction of the
association as criteria of study reliability. Statistical
significance is influenced by a variety of factors including, but
not limited to, the size of the study, exposure and outcome
measurement error, and statistical model specifications. Statistical
significance . . . is just one of the means of evaluating confidence
in the observed relationship and assessing the probability of chance
as an explanation. Other indicators of reliability such as the
consistency and coherence of a body of studies as well as other
confirming data may be used to justify reliance on the results of a
body of epidemiologic studies, even if results in individual studies
lack statistical significance . . . [Therefore, the U.S. EPA] . . .
does not limit its focus or consideration to statistically
significant results in epidemiologic studies.''

Therefore, upon re-evaluating the causality determination, when
considering the CASAC comments on the draft ISA and applying the causal
framework as described (U.S. EPA, 2015; U.S. EPA, 2019, section
A.3.2.1), the EPA continues to conclude in the 2019 ISA that the
evidence for long-term PM2.5 exposure and nervous system
effects supports a ``likely to be causal relationship'' (U.S. EPA,
2019, p. 8-61).
vi. Other Effects
    For other categories of health effects and PM2.5
exposures,\40\ the currently available evidence is ``suggestive of, but
not sufficient to infer, a causal relationship,'' mainly due to
inconsistent evidence across specific outcomes and uncertainties
regarding exposure measurement error, the potential for confounding,
and potential modes of action (U.S. EPA, 2019, sections 7.1.4, 7.2.10,
8.1.6, and 9.1.5). These causality determinations are revised from
``inadequate to infer a causal relationship'' or not evaluated in the
2009 ISA this review; however, the ``suggestive of, but not sufficient
to infer, a causal relationship'' causality determinations reflect
continued uncertainties in the evidence.
---------------------------------------------------------------------------

    \40\ The other categories evaluated in the ISA include nervous
system effects and short-term exposures; metabolic effects;
reproduction and fertility; and pregnancy and birth outcomes (U.S.
EPA, 2019, Table ES-1).
---------------------------------------------------------------------------

b. At-Risk Populations
    In this review, we use the term ``at-risk populations'' to describe
populations with a quality or characteristic in common (e.g., a
specific pre-existing illness or specific lifestage) that contributes
to them having a greater likelihood of experiencing PM2.5-
related health effects. In the current review, consistent with the last
review, the 2019 ISA cites extensive evidence indicating that ``both
the general population as well as specific populations and lifestages
are at risk for PM2.5-related health effects'' (U.S. EPA,
2019, p. 12-1). For example, in support of its ``causal'' and ``likely
to be causal'' determinations, the ISA cites substantial evidence for:
PM-related mortality and cardiovascular effects in older adults (U.S.
EPA, 2019, sections 11.1, 11.2, 6.1, and 6.2); PM-related
cardiovascular effects in people with pre-existing cardiovascular
disease (U.S. EPA, 2019, section 6.1); PM-related respiratory effects
in people with pre-existing respiratory disease, particularly asthma
exacerbations in children (U.S. EPA, 2019, section 5.1); and PM-related
impairments in lung function growth and asthma development in children
(U.S. EPA, 2019, sections 5.1 and 5.2; <IP_ADDRESS>).
    The ISA additionally notes that stratified analyses (i.e., analyses
that directly compare PM-related health effects across groups) provide
support for racial and ethnic differences in PM2.5 exposures
and in PM2.5-related health risk (U.S. EPA, 2019, section
12.5.4). Drawing from such studies, the ISA concludes that ``[t]here is
strong evidence demonstrating that black and Hispanic populations, in
particular, have higher PM2.5 exposures than non-Hispanic
white populations'' and that ``there is consistent evidence across
multiple studies demonstrating an increase in risk for nonwhite
populations'' (U.S. EPA, 2019, p. 12-38). Stratified analyses focusing
on other groups also suggest that populations with pre-existing
cardiovascular or respiratory disease, populations that are overweight
or obese, populations that have particular genetic variants,
populations that are of low socioeconomic status, and current/former
smokers could be at increased risk for PM2.5-related adverse
health effects (U.S. EPA, 2019, Chapter 12).
    Thus, the groups at greater risk of PM2.5-related health
effects represent a substantial portion of the total U.S. population.
In evaluating the primary PM2.5 standards, an important
consideration is the potential for additional public health
improvements in these populations.
c. Evidence-Based Considerations
    The sections below summarize the PA's evaluation of the
PM2.5 exposure concentrations that have been examined in
controlled human exposure studies, animal toxicology studies, and
epidemiological studies.
i. PM2.5 Concentrations Evaluated in Experimental Studies
    Evidence for a particular PM2.5-related health outcome
is strengthened when results from experimental studies demonstrate
biologically plausible mechanisms through which adverse human health
outcomes could occur (U.S. EPA, 2015, p. 20). Two types of experimental
studies are of particular importance in understanding the effects of PM
exposures: Controlled human exposure and animal toxicologic studies. In
such studies, investigators expose human volunteers or laboratory
animals, respectively, to known concentrations of air pollutants under
carefully regulated environmental conditions and activity levels. Thus,
controlled human exposure and animal toxicology studies can provide
information on the health effects of experimentally administered
pollutant exposures under well-controlled laboratory conditions (U.S.
EPA, 2015, p. 11).
    Controlled human exposure studies have reported that
PM2.5 exposures lasting from less than one hour up to five
hours can impact cardiovascular function (U.S. EPA, 2019, section 6.1).
The most consistent evidence from these studies is for impaired
vascular function (U.S. EPA, 2019, section <IP_ADDRESS>). Table 3-2 in the
PA (U.S. EPA, 2020) summarizes information from the ISA on available
controlled human exposure studies that evaluate effects on markers of
cardiovascular function following exposures to PM2.5. Most
of the controlled human exposure studies in Table 3-2 of the PA have
evaluated average PM2.5 exposure concentrations at or above
about 100 [micro]g/m\3\, with exposure durations typically up to about
two hours. Statistically significant effects on one or more indicators
of cardiovascular function are often, though not always, reported
following 2-hour exposures to average PM2.5 concentrations
at and above about 120 [micro]g/m\3\, with less consistent evidence for
effects following exposures to lower concentrations. Impaired vascular
function, the effect identified in the ISA as the most consistent
across studies (U.S. EPA, 2019, section <IP_ADDRESS>), is shown following
2-hour

exposures to PM2.5 concentrations at and above 149 [micro]g/
m\3\. Mixed results are reported in the few studies that evaluate
longer exposure durations (i.e., longer than 2 hours) and lower
PM2.5 concentrations (U.S. EPA, 2020, section <IP_ADDRESS>).
    To provide some insight into what these studies may indicate
regarding the primary PM2.5 standards, analyses in the PA
examine monitored 2-hour PM2.5 concentrations at sites
meeting the current standards (U.S. EPA, 2020, section <IP_ADDRESS>). At
these sites, most 2-hour concentrations are below 11 [mu]g/m\3\, and
they almost never exceed 32 [mu]g/m\3\. Even the highest 2-hour
concentrations remain well-below the exposure concentrations
consistently shown to cause effects in controlled human exposure
studies (i.e., 99.9th percentile of 2-hour concentrations is 68 [mu]g/
m\3\ during the warm season). Thus, while controlled human exposure
studies support the plausibility of the serious cardiovascular effects
that have been linked with ambient PM2.5 exposures (U.S.
EPA, 2019, Chapter 6), the PA notes that the PM2.5 exposures
evaluated in most of these studies are well-above the ambient
concentrations typically measured in locations meeting the current
primary standards (U.S. EPA, 2020, section <IP_ADDRESS>.1).
    With respect to animal toxicology studies, the ISA relies on animal
toxicology studies to support the plausibility of a wide range of
PM2.5-related health effects. While animal toxicology
studies often examine more severe health outcomes and longer exposure
durations than controlled human exposure studies, there is uncertainty
in extrapolating the effects seen in animals, and the PM2.5
exposures and doses that cause those effects, to human populations.
    As with controlled human exposure studies, most of the animal
toxicology studies assessed in the ISA have examined effects following
exposures to PM2.5 concentrations well-above the
concentrations likely to be allowed by the current PM2.5
standards. Such studies have generally examined short-term exposures to
PM2.5 concentrations from 100 to >1,000 [mu]g/m\3\ and long-
term exposures to concentrations from 66 to >400 [mu]g/m\3\ (e.g., see
U.S. EPA, 2019, Table 1-2). Two exceptions are a study reporting
impaired lung development following long-term exposures (i.e., 24 hours
per day for several months prenatally and postnatally) to an average
PM2.5 concentration of 16.8 [mu]g/m\3\ (Mauad et al., 2008)
and a study reporting increased carcinogenic potential following long-
term exposures (i.e., 2 months) to an average PM2.5
concentration of 17.7 [mu]g/m\3\ (Cangerana Pereira et al., 2011).
These two studies report serious effects following long-term exposures
to PM2.5 concentrations close to the ambient concentrations
reported in some PM2.5 epidemiological studies (U.S. EPA,
2019, Table 1-2), though still above the ambient concentrations likely
to occur in areas meeting the current primary standards. Thus, as is
the case with controlled human exposure studies, animal toxicology
studies support the plausibility of various adverse effects that have
been linked to ambient PM2.5 exposures (U.S. EPA, 2019), but
have not evaluated PM2.5 exposures likely to occur in areas
meeting the current primary standards.
ii. Ambient Concentrations in Locations of Epidemiological Studies
    As summarized above in section II.A.2.a, epidemiological studies
examining associations between daily or annual average PM2.5
exposures and mortality or morbidity represent a large part of the
evidence base supporting several of the ISA's ``causal'' and ``likely
to be causal'' determinations for cardiovascular effects, respiratory
effects, cancer, and mortality. The PA considers what information from
these epidemiological studies may indicate regarding primary
PM2.5 standards. The use of information from epidemiological
studies to inform conclusions on the primary PM2.5 standards
is complicated by the fact that such studies evaluate associations
between distributions of ambient PM2.5 and health outcomes,
but do not identify the specific exposures that cause reported effects.
Rather, health effects can occur over the entire distributions of
ambient PM2.5 concentrations evaluated, and epidemiological
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, 2020, section <IP_ADDRESS>). Therefore, the PA evaluates
the PM2.5 air quality distributions over which
epidemiological studies support health effect associations. As
discussed further in the PA (U.S. EPA, 2020, section <IP_ADDRESS>.1),
studies of daily PM2.5 exposures examine associations
between day-to-day variation in PM2.5 concentrations and
health outcomes, often over several years. While there can be
considerable variability in daily exposures over a multi-year study
period, most of the estimated exposures reflect days with ambient
PM2.5 concentrations around the middle of the air quality
distributions examined (i.e., ``typical'' days rather than days with
extremely high or extremely low concentrations). Similarly, for studies
of annual PM2.5 exposures, most of the estimated exposures
reflect annual average PM2.5 concentrations around the
middle of the air quality distributions examined. In both cases,
epidemiological studies provide the strongest support for reported
health effect associations for this middle portion of the
PM2.5 air quality distribution, which corresponds to the
bulk of the underlying data, rather than the extreme upper or lower
ends of the distribution. Consistent with this, and as noted in the PA
(U.S. EPA, 2020, section <IP_ADDRESS>), several epidemiological studies
report that associations persist in analyses that exclude the upper
portions of the distributions of estimated PM2.5 exposures,
indicating that ``peak'' PM2.5 exposures are not
disproportionately responsible for reported health effect associations.
    Thus, in considering PM2.5 air quality data from
epidemiological studies, the PA evaluates study-reported means (or
medians) of daily and annual average PM2.5 concentrations as
proxies for the middle portions of the air quality distributions that
support reported associations. In Figure 3-7, the PA highlights the
overall mean (or median) PM2.5 concentrations reported in
key U.S. and Canadian epidemiological studies that use ground-based
monitors alone to estimate long- or short-term PM2.5
exposures. In Figure 3-8, the PA also considers the emerging body of
studies that use hybrid modeling methods to estimate long- or short-
term PM2.5 exposures. Hybrid methods incorporate data from
several sources, often including satellites and models, in addition to
ground-based monitors.
    Epidemiological studies using hybrid methods are generally new in
this review. These modeling methods have improved the ability to
estimate PM2.5 exposure for populations throughout the
conterminous U.S. compared with the earlier approaches based on
monitoring data alone. Excellent performance in cross-validation tests
suggests that hybrid methods are reliable for estimating
PM2.5 exposure in many applications. As discussed in Chapter
3 of the PA, good agreement in health study results between monitor-
and model-based methods for urban areas (McGuinn et al., 2017) and
general consistency in results for the conterminous U.S. (Jerrett et
al., 2017; Di et al., 2016) also suggests that the fields are reliable
for use in health studies. However, there are also important
limitations associated with the modeled fields that should be kept in
mind. First, performance evaluations

for the methods are weighted toward densely monitored urban areas at
the scales of representation of the monitoring networks. Predictions at
different scales or in sparsely monitored areas are relatively
untested. Second, studies have reported heterogeneity in performance
with relatively weak performance in parts of the western U.S., at low
concentrations, at greater distance to monitors, and under conditions
where the reliability and availability of key input datasets (e.g.,
satellite retrievals and air quality modeling) are limited. Lastly,
differences in predictions among different hybrid methods have also
been reported and tend to be most important under conditions with the
performance issues just noted. Differences in predictions can be
related to the different approaches used to create long-term
PM2.5 fields (e.g., averaging daily PM2.5 fields
vs. developing long-term average fields), which can be impacted by
variability in monitoring schedules, and the spatial scale at which
these fields are created. Future work to further characterize the
performance of modeled fields will be useful in informing our
understanding of the implications of using these fields to estimate
PM2.5 exposures in health studies (U.S. EPA, 2020, section
<IP_ADDRESS>.4).
    In assessing how the overall mean (or median) PM2.5
concentrations reported in key epidemiological studies can inform
conclusions on the primary PM2.5 standards, there are some
important considerations. As noted in the PA, study-reported
PM2.5 concentrations reflect the averages of daily or annual
PM2.5 air quality concentrations or exposure estimates in
the study population over the years examined by the study, and are not
the same as the PM2.5 design values used by the EPA to
determine whether areas meet or violate the PM NAAQS (U.S. EPA, 2020,
section <IP_ADDRESS>.1). Overall mean PM2.5 concentrations in key
studies reflect averaging of short- or long-term PM2.5
exposure estimates across locations (i.e., across multiple monitors or
across modeled grid cells) and over time (i.e., over several years). In
contrast, to determine whether areas meet or violate the NAAQS, the EPA
measures air pollution concentrations at individual monitors (i.e.,
concentrations are not averaged across monitors) and calculates design
values at monitors meeting appropriate data quality and completeness
criteria. For the annual PM2.5 standard, design values are
calculated as the annual arithmetic mean PM2.5
concentration, averaged over 3 years (described in Appendix N of 40 CFR
part 50). For an area to meet the NAAQS, all valid design values in
that area, including the highest monitored values, must be at or below
the level of the standard.
    In the context of epidemiological studies that use ground-based
monitors, analyses of recent air quality in U.S. CBSAs indicate that
maximum annual PM2.5 design values for a given three-year
period are often 10% to 20% higher than average monitored
concentrations (i.e., averaged across multiple monitors in the same
CBSA) (U.S. EPA, 2020, Appendix B, section B.7). This comparison is
more difficult for epidemiological studies that use hybrid methods. To
try to address this issue, the PA also considered a second approach to
evaluating information from epidemiological studies. In this approach,
the PA calculated study area air quality metrics similar to
PM2.5 design values (i.e., referred to in the PA as pseudo-
design values; U.S. EPA, 2020, section <IP_ADDRESS>.2) and considered the
degree to which such metrics indicate that study area air quality would
likely have met or violated the current standards during study periods.
This approach was generally not well received by commenters during the
review of the PA.
3. Overview of Risk and Exposure Assessment Information
    Beyond the consideration of the scientific evidence, discussed
above in section II.A.2, the EPA also considers the extent to which new
or updated quantitative analyses of PM2.5 air quality,
exposure, or health risks could inform conclusions on the adequacy of
the public health protection provided by the current primary
PM2.5 standards. Conducting such quantitative analyses, if
appropriate, could inform judgments about the potential for additional
public health improvements associated with PM2.5 exposure
and related health effects and could help to place the evidence for
specific effects into a broader public health context.
    To this end, the PA includes a risk assessment that estimates
population-level health risks associated with PM2.5 air
quality that has been adjusted to simulate air quality scenarios of
policy interest (e.g., ``just meeting'' the current standards). The
general approach to estimating PM2.5-associated health risks
combines concentration-response functions from epidemiological studies
with model-based PM2.5 air quality surfaces, baseline health
incidence data, and population demographics for 47 urban study areas
(U.S. EPA, 2020, section 3.3, Figure 3-10 and Appendix C).
    The risk assessment estimates that the current primary
PM2.5 standards could allow a substantial number of
PM2.5-associated deaths in the U.S. For example, when air
quality in the 47 study areas is adjusted to simulate just meeting the
current standards, the risk assessment estimates from about 16,000 to
17,000 long-term PM2.5 exposure-related deaths from ischemic
heart disease in a single year (i.e., confidence intervals range from
about 12,000 to 21,000 deaths).\41\ Compared to the current annual
standard, meeting a revised annual standard with a lower level is
estimated to reduce PM2.5-associated health risks by about 7
to 9% for a level of 11.0 [micro]g/m\3\, 14 to 18% for a level of 10.0
[micro]g/m\3\, and 21 to 27% for a level of 9.0 [micro]g/m\3\.
---------------------------------------------------------------------------

    \41\ For the only other cause-specific mortality endpoint
evaluated (i.e., lung cancer), substantially fewer deaths were
estimated (U.S. EPA, 2020, section 3.3.2, e.g., Figure 3-5). Risk
estimates were not generated for other ``likely to be causal''
outcome categories (i.e., respiratory effects, nervous system
effects).
---------------------------------------------------------------------------

    Uncertainty in risk estimates (e.g., in the size of risk estimates)
can result from a number of factors, including assumptions about the
shape of the concentration-response relationship with mortality at low
ambient PM concentrations, the potential for confounding and/or
exposure measurement error in the underlying epidemiological studies,
and the methods used to adjust PM2.5 air quality. The PA
characterizes these and other sources of uncertainty in risk estimates
using a combination of quantitative and qualitative approaches (U.S.
EPA, 2020, Appendix C, section C.3). As detailed further below in
II.B.1, some members of CASAC advised that the risk assessment
estimates did not provide useful information about whether the current
standard is protective, while other members thought they were useful to
understand potential impacts of alternative standards.

B. Conclusions on the Primary PM2.5 Standards

    In drawing conclusions on the adequacy of the current primary
PM2.5 standards, in view of the advances in scientific
knowledge and additional information now available, the Administrator
has considered the evidence base, information, and policy judgments
that were the foundation of the last review and reflects upon the body
of evidence and information newly available in this review. In so
doing, he considered the large body of evidence presented and assessed
in the ISA (U.S.

EPA, 2019), the policy-relevant and risk-based conclusions and
rationales as presented in the PA (U.S. EPA, 2020), views expressed by
CASAC, and public comments. The Administrator has taken into account
both evidence- and risk-based considerations in developing final
conclusions on the adequacy of the current primary PM2.5
standards. Evidence-based considerations include the assessment of
epidemiological, animal toxicologic, and controlled human exposure
studies evaluating long- or short-term exposures to PM2.5
and the integration of evidence across each of these disciplines. These
considerations, as assessed in the ISA (U.S. EPA, 2019), focus on the
policy-relevant considerations, as discussed in II.A.2 above and in the
PA (U.S. EPA, 2020, section 3.2.1). Risk-based considerations draw from
the results of the quantitative analyses and policy-relevant
considerations as discussed in II.A.3 above and in the PA (U.S. EPA,
2020, section 3.3.2).
    Section II.B.1 summarizes the advice and recommendations of the
CASAC. Section II.B.2 below summarizes the basis for the
Administrator's proposed decision, drawing from section II.C.3 of the
proposal, and section II.B.3 addresses public comments on the proposed
decision. The Administrator's conclusions in this review regarding the
adequacy of the current primary standard and whether any revisions are
appropriate are described in section II.B.4.
1. CASAC Advice in This Review
    With regard to the process for reviewing the PM NAAQS, the CASAC
requested the opportunity to review a second draft ISA (Cox, 2019b, p.
1 of letter) and recommended that ``the EPA reappoint the previous
CASAC PM panel (or appoint a panel with similar expertise)'' (Cox,
2019b, p. 2 of letter). As discussed above in section I.D, the Agency's
responses to these recommendations were described in a letter from the
Administrator to the CASAC chair (Wheeler, 2019).
    As part of its review of the draft PA, the CASAC provided advice on
the adequacy of the public health protection afforded by the current
primary PM2.5 standards.\42\ Its advice is documented in a
letter sent to the EPA Administrator (Cox, 2019a). In this letter, the
committee recommended retaining the current 24-hour PM2.5
standard but did not reach consensus on whether the scientific and
technical information support retaining or revising the current annual
standard. In particular, though the CASAC agreed that there is a long-
standing body of health evidence supporting relationships between
PM2.5 exposures and various health outcomes, including
mortality and serious morbidity effects, individual CASAC members
``differ[ed] in their assessments of the causal and policy significance
of these associations'' (Cox, 2019a, p. 8 of consensus responses).
Drawing from this evidence, ``some CASAC members'' expressed support
for retaining the current annual standard while ``other members''
expressed support for revising that standard in order to increase
public health protection (Cox, 2019a, p.1 of letter). These views are
summarized below.
---------------------------------------------------------------------------

    \42\ The CASAC also provided advice on the draft ISA's
assessment of the scientific evidence (Cox, 2019b). That advice, and
the resulting changes made in the final ISA and final PA, are
summarized in section II.B.3 of the proposal (85 FR 24114, April 30,
2020).
---------------------------------------------------------------------------

    The CASAC members who supported retaining the current annual
standard expressed the view that substantial uncertainty remains in the
evidence for associations between PM2.5 exposures and
mortality or serious morbidity effects. These committee members
asserted that ``such associations can reasonably be explained in light
of uncontrolled confounding and other potential sources of error and
bias'' (Cox, 2019a, p. 8 of consensus responses). They noted that
associations do not necessarily reflect causal effects, and they
contended that recent epidemiological studies reporting positive
associations at lower estimated exposure concentrations mainly confirm
what was anticipated or already assumed in setting the 2012 NAAQS. In
particular, they concluded that such studies have some of the same
limitations as prior studies and do not provide new information calling
into question the existing standard. They further asserted that
``accountability studies provide potentially crucial information about
whether and how much decreasing PM2.5 causes decreases in
future health effects'' (Cox, 2019a, p. 10), and they cited recent
reviews (i.e., Henneman et al., 2017; Burns et al., 2019) to support
their position that in such studies, ``reductions of PM2.5
concentrations have not clearly reduced mortality risks'' (Cox, 2019a,
p. 8 of consensus responses). Thus, the committee members who supported
retaining the current annual standard advise that, ``while the data on
associations should certainly be carefully considered, this data should
not be interpreted more strongly than warranted based on its
methodological limitations'' (Cox, 2019a, p. 8 of consensus responses).
    These members of the CASAC further concluded that the
PM2.5 risk assessment does not provide a valid basis for
revising the current standards. This conclusion was based on concerns
that (1) ``the risk assessment treats regression coefficients as causal
coefficients with no justification or validation provided for this
decision;'' (2) the estimated regression concentration-response
functions ``have not been adequately adjusted to correct for
confounding, errors in exposure estimates and other covariates, model
uncertainty, and heterogeneity in individual biological (causal)
[concentration-response] functions;'' (3) the estimated concentration-
response functions ``do not contain quantitative uncertainty bands that
reflect model uncertainty or effects of exposure and covariate
estimation errors;'' and (4) ``no regression diagnostics are provided
justifying the use of proportional hazards . . . and other modeling
assumptions'' (Cox, 2019a, p. 9 of consensus responses). These
committee members also contended that details regarding the derivation
of concentration-response functions, including specification of the
beta values and functional forms, were not well-documented, hampering
the ability of readers to evaluate these design details. Thus, these
members ``think that the risk characterization does not provide useful
information about whether the current standard is protective'' (Cox,
2019a, p. 11 of consensus responses).
    Drawing from their evaluation of the evidence and the risk
assessment, these committee members concluded that ``the Draft PM PA
does not establish that new scientific evidence and data reasonably
call into question the public health protection afforded by the current
2012 PM2.5 annual standard'' (Cox, 2019a, p.1 of letter).
    In contrast, ``[o]ther members of CASAC conclude[d] that the weight
of the evidence, particularly reflecting recent epidemiology studies
showing positive associations between PM2.5 and health
effects at estimated annual average PM2.5 concentrations
below the current standard, does reasonably call into question the
adequacy of the 2012 annual PM2.5 [standard] to protect
public health with an adequate margin of safety'' (Cox, 2019a, p.1 of
letter). The committee members who supported this conclusion noted that
the body of health evidence for PM2.5 not only includes the
repeated demonstration of associations in epidemiological studies, but
also includes support for biological

plausibility established by controlled human exposure and animal
toxicology studies. They pointed to recent studies demonstrating that
the associations between PM2.5 and health effects occur in a
diversity of locations, in different time periods, with different
populations, and using different exposure estimation and statistical
methods. They concluded that ``the entire body of evidence for PM
health effects justifies the causality determinations made in the Draft
PM ISA'' (Cox, 2019a, p. 8 of consensus responses).
    The members of the CASAC who supported revising the current annual
standard particularly emphasized recent findings of associations with
PM2.5 in areas with average long-term PM2.5
concentrations below the level of the annual standard and studies that
show positive associations even when estimated exposures above 12
[mu]g/m\3\ are excluded from analyses. They found it ``highly
unlikely'' that the extensive body of evidence indicating positive
associations at low estimated exposures could be fully explained by
confounding or by other non-causal explanations (Cox, 2019a, p. 8 of
consensus responses). They additionally concluded that ``the risk
characterization does provide a useful attempt to understand the
potential impacts of alternate standards on public health risks'' (Cox,
2019a, p. 11 of consensus responses). These committee members concluded
that the evidence available in this review reasonably calls into
question the protection provided by the current primary
PM2.5 standards and supports revising the annual standard to
increase that protection (Cox, 2019a).
2. Basis for Proposed Decision
    On April 14, 2020, the Administrator proposed to retain the current
primary PM2.5 standards. This proposal was published in the
Federal Register on April 30, 2020 (85 FR 24094, April 30, 2020). In
reaching his proposed decision to retain the current PM2.5
standards (i.e., annual and 24-hour PM2.5 standards), the
Administrator considered the assessment of the available evidence and
conclusions reached in the ISA (U.S. EPA, 2019); the analyses in the PA
(U.S. EPA, 2020), including uncertainties in the evidence and analyses;
and the advice and recommendations from the CASAC. These considerations
are summarized briefly below and discussed in detail in the proposal
notice (85 FR 24094, April 30, 2020).
    As described further in section II.A.2 of the proposal, the
Administrator's consideration of the public health protection provided
by the current primary PM2.5 standards were based on his
consideration of the combination of the annual and 24-hour standards,
including the indicators (PM2.5), averaging times, forms
(arithmetic mean and 98th percentile, averaged over three years), and
levels (12.0 [micro]g/m\3\, 35 [micro]g/m\3\) of those standards.
    The Administrator's proposed decision noted that one of the
methodological limitations highlighted by the CASAC members who support
retaining the annual standard (see section II.B.1 above) is that
associations reported in epidemiological studies are not necessarily
indicative of causal relationships and such associations ``can
reasonably be explained in light of uncontrolled confounding and other
potential sources of error and bias'' (Cox, 2019a, p.8). In the
proposed decision, the Administrator recognized that epidemiological
studies examine associations between distributions of PM2.5
air quality and health outcomes, and they do not identify particular
PM2.5 exposures that cause effects, as noted in the PA (U.S.
EPA, 2020, section 3.1.2). The Administrator's proposed decision noted
that experimental studies do provide evidence for health effects
following particular PM2.5 exposures under carefully
controlled laboratory conditions and further notes that the evidence
for a given PM2.5-related health outcome is strengthened
when results from experimental studies demonstrate biologically
plausibility mechanisms through which such an outcome could occur. In
the proposed decision, therefore, the Administrator expressed greatest
confidence in the potential for PM2.5 exposures to cause
adverse effects at concentrations supported by multiple types of
studies, including experimental studies as well as epidemiological
studies.
    In the proposed decision, in light of this approach to considering
the evidence, the Administrator recognized that controlled human
exposure and animal toxicology studies report a wide range of effects,
many of which are plausibly linked to the serious cardiovascular and
respiratory outcomes reported in epidemiological studies (including
mortality), though he noted that the PM2.5 exposures
examined in these studies are above the concentrations typically
measured in areas meeting the current annual and 24-hour standards
(U.S. EPA, 2020, section <IP_ADDRESS>). The Administrator was cautious about
placing too much weight on reported PM2.5 health effect
associations for air quality meeting the current annual and 24-hour
standards. He concluded in the proposed decision that such associations
alone, without supporting experimental evidence at similar
PM2.5 considerations, left important questions unanswered
regarding the degree to which the typical PM2.5 exposures
likely to occur in areas meeting the current standard could cause the
mortality and morbidity outcomes reported in epidemiological studies.
Given this concern, the Administrator noted in the proposal that he did
not think that recent epidemiological studies reporting health effect
associations at PM2.5 air quality concentrations likely to
have met the current primary standards support revising those
standards. Rather, he judged that the overall body of evidence,
including controlled human exposure and animal toxicologic studies, in
addition to epidemiological studies, indicated continuing uncertainty
in the degree to which adverse effects could result from
PM2.5 exposure in areas meeting the current annual and 24-
hour standards.
    The Administrator also considered the emerging body of evidence
from accountability studies examining past reductions in ambient
PM2.5, and the degree to which those reductions resulted in
public health improvements, but also recognized that interpreting such
studies in the context of the current primary PM2.5
standards was complicated by the fact that some of the available
accountability studies have not evaluated PM2.5
specifically, did not show changes in PM2.5 air quality, or
have not been able to disentangled health impacts of the interventions
from background trends in health. The Administrator also recognized
that the small number of available studies that do report public health
improvements following past declines in ambient PM2.5 have
not examined air quality meeting the current standard. Together with
the Administrator's concerns regarding the lack of experimental studies
examining PM2.5 exposures typical of areas meeting the
current standards, the lack of demonstrated health improvements in
areas with air quality meeting the current standards led him to
conclude, at the time of proposal, that there was considerable
uncertainty in the potential for increased public health protection
from further reductions in ambient PM2.5 concentrations
beyond those achieved under the current primary PM2.5
standards.
    In addition to the evidence, the Administrator also considered the
potential implications of the risk assessment for his proposed
decision, noting that all risk assessments have limitations. He noted
that such limitations in risk estimates can result

from uncertainty in the shapes of concentration-response functions,
particularly at low concentrations; uncertainties in the methods used
to adjust air quality; and uncertainty in estimating risks for
populations, locations and air quality distributions different from
those examined in the underlying epidemiological study. The
Administrator noted agreement with some members of the CASAC who
expressed concerns regarding limitations in the epidemiological
evidence, which provides key inputs to the risk assessment. Thus, he
judged it appropriate to place little weight on quantitative estimates
of PM2.5-associated mortality risk in reaching proposed
conclusions on the primary PM2.5 standards.
    In reaching his proposed decision to retain the current primary
PM2.5 standards, the Administrator concluded that the
scientific evidence assessed in the ISA (U.S. EPA, 2019), and the
analyses based on that evidence in the PA (U.S. EPA, 2020), do not call
into question the public health protection provided by the current
annual and 24-hour PM2.5 standards. In particular, the
Administrator judged that there is considerable uncertainty in the
potential for additional public health improvements from reducing
ambient PM2.5 below the concentrations achieved under the
current primary standards and, therefore, that standards more stringent
than the current standards (e.g., with lower levels) are not supported.
That is, he judged that such standards would be more than requisite to
protect the public health with an adequate margin of safety. This
judgment reflected his consideration of the uncertainties in the
potential implications of recent epidemiological studies due in part to
the lack of supporting evidence from experimental studies and
accountability studies conducted at PM2.5 concentrations
meeting the current standards.
    In addition, based on the Administrator's review of the science,
including experimental and accountability studies conducted at levels
just above the current standard, he judged that the degree of public
health protection provided by the current standard is not greater than
warranted. This judgment, together with the fact that no CASAC member
expressed support for a less stringent standard, led the Administrator
to conclude that standards less stringent than the current standards
(e.g., with higher levels) are also not supported.
    Thus, based on his consideration of the available scientific
evidence and technical information and his consideration of advice from
the CASAC, the Administrator proposed to conclude that the current
suite of primary standards, including the current indicators
(PM2.5), averaging times (annual and 24-hour), forms
(arithmetic mean and 98th percentile, averaged over three years) and
levels (12.0 [micro]g/m\3\, 35 [micro]g/m\3\), remain requisite to
protect the public health. As discussed in detail in the proposal (85
FR 24094, April 30, 2020), this proposed conclusion reflected his
judgment that limitations in the science lead to considerable
uncertainty regarding the potential public health implications of
revising the existing suite of PM2.5 standards. Therefore,
the Administrator proposed to retain the current standards, without
revision.
3. Comments on the Proposed Decision
    Overall, the EPA received a large number of unique public comments
on the proposed decision to retain the annual and 24-hour
PM2.5 standards. These comments generally fall into one of
two broad groups that expressed sharply divergent views. The first
group is comprised of the many commenters, representing industries and
industry groups, some state and local governments, and independent
organizations, that support the Administrator's proposed decision to
retain the primary PM2.5 standards. The second group of
commenters are those who asserted that the current primary
PM2.5 standards are not sufficient to protect public health
with an adequate margin of safety. These commenters disagree with the
EPA's proposed decision to retain the current PM2.5
standards and generally recommend a revised annual standard of between
8-10 [micro]g/m\3\ and a revised 24-hour standard between a range of
25-30 [micro]g/m\3\. Among those calling for revisions to the current
primary PM2.5 standards were commenters representing
national public health, medical, and environmental nongovernmental
organization, tribes and tribal groups, some state and local
governments and independent organizations and individuals.
    We address the key public comments received on the proposal (85 FR
24094, April 30, 2020) and present the EPA's responses to those
comments below. A more detailed summary of all significant comments,
along with the EPA's responses (henceforth ``Response to Comments''),
can be found in the docket for this rulemaking (Docket No. EPA-HQ-OAR-
2015-0072). This document is available for review in the docket for
this rulemaking and through the EPA's NAAQS website (https://www.epa.gov/naaqs/particulate-matter-pm-air-quality-standards).
    With respect to the various elements of the standards, the EPA
received very few comments related to indicator and none advocate for
revising the current PM2.5 indicator for fine particles.
Those who express explicit support for retaining the current
PM2.5 indicator generally endorse the rationale put forward
in the PA. The EPA agrees with these commenters, noting that the
scientific evidence in this review, as in the last review, continues to
provide strong support for health effects following short- and long-
term PM2.5 exposures and that the available information
remains too limited to support a distinct standard for any specific
PM2.5 component or group of components or to support a
distinct standard for the ultrafine fraction.
    The EPA also received very few comments on averaging time and form.
Those who did provide comments are mostly affiliated with public health
organizations and environmental advocacy groups and generally discuss
the need for future evaluation of the form and averaging time of the
current 24-hour standard (98th percentile, averaged over three years).
These commenters, acknowledging the current limitations and
uncertainties in the available evidence, suggest that in future reviews
the EPA should evaluate how well the current form of the 24-hour
standard protects against potential sub-daily exposures based on new
epidemiological and experimental evidence that considers sub-daily
exposures, but these commenters support retaining the current
indicators, averaging times, and forms.
    The EPA acknowledges the comments related to averaging time and
form of the 24-hour standard and agrees that the current information
does not support a revision to the averaging time or form. The EPA will
continue to evaluate the form and averaging time of the current 24-hour
standard in future reviews based on any new relevant information.
    With respect to the level of the 24-hour standard, commenters
supporting revision generally support a revised level in the range of
25-30 [micro]g/m\3\. They contend the available scientific evidence
supports that lower levels within this range are required to protect
public health, including the health of at-risk populations, with an
adequate margin of safety, and that lower levels within this range will
provide additional margin of safety. The commenters cite controlled
human exposure studies that assess short-term exposures (i.e., 2 to 5
hours) and epidemiological studies that report

associations between adverse health effects and concentrations below
the current standard level as supporting the need for this revision.
They further add that while revising the 24-hour level to 25 [micro]g/
m\3\ would offer more health protection than 30 [micro]g/m\3\, it would
still not reduce the risk of adverse health outcomes to zero.
    With respect to the level of the annual PM2.5 standard,
numerous comments were received that specifically focus on the
Administrator's consideration of epidemiological evidence in this
review. Commenters who support revision generally disagree with the
Administrator's conclusions and judgments about the uncertainties in
the epidemiological evidence and suggest that these studies support
revision of the PM2.5 annual standard to a level of 8-10
[micro]g/m\3\. These commenters state that uncertainties in the
epidemiological studies, alone, do not negate positive associations
seen in studies using diverse study designs and capturing large
geographic and population domains. These commenters note that the
possibility of confounders and the other referenced uncertainties have
been investigated and found not to be material given the overall
strength and consistency of results from varying approaches. The
commenters who support revising the primary PM2.5 standards
generally place substantial weight on epidemiologic evidence from
multi-city U.S. and Canadian studies that captured a larger geographic
domain and population size, and were included in the ISA and in the
study-related analyses in the PA (U.S. EPA, 2020). Further, they also
cite epidemiological studies in the ISA (U.S. EPA, 2019) that performed
restricted/truncated analyses with populations living in areas of lower
PM2.5 concentrations and contend that associations still
exist in these studies at the concentrations below the levels of the
current annual and daily standards. Moreover, they state that there was
no evidence for an ambient concentration threshold for adverse health
effects at the lowest observed levels of either annual or 24-hour
PM2.5 concentrations.
    The EPA disagrees with these commenters. First, the EPA notes that,
consistent with past practices, the foremost consideration is the
adequacy of the public health protection as provided by the combination
of the annual and 24-hour standards together. The annual standard
limits ``typical'' daily PM2.5 concentrations that make up
the bulk of the distribution, while the 24-hour standard adds
supplemental protection against ``peak'' daily PM2.5
concentrations. In the judgment of the Administrator, therefore, the
current annual standard (arithmetic mean, averaged over three years)
remains appropriate for targeting protection against the annual and
daily PM2.5 exposures around the middle portion of the
PM2.5 air quality distribution, while the current 24-hour
standard (98th percentile, averaged over three years) continues to
provide 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, 2020, section <IP_ADDRESS>).
Further, the Administrator notes that changes in PM2.5 air
quality 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. Similarly, the
Administrator recognizes that changes in air quality to meet a 24-hour
standard, would result not only in fewer and lower peak 24-hour
PM2.5 concentrations, but also in lower annual average
PM2.5 concentrations.
    Thus, in considering the adequacy of the 24-hour standard, an
important consideration is whether additional protection is needed
against short-term exposures to peak PM2.5 concentrations.
In examining the scientific evidence, the EPA notes that controlled
human exposure studies do provide evidence for health effects following
single, short-term PM2.5 exposures to concentrations. These
types of exposures correspond best to those to ambient exposures that
might be experienced in the upper end of the PM2.5 air
quality distribution in the U.S. (i.e., ``peak'' concentrations).
However, and as noted above in section II.A.2.c.i, most of these
studies examine exposure concentrations considerably higher than are
typically measured in areas meeting the current standards (U.S. EPA,
2020, section <IP_ADDRESS>). In particular, controlled human exposure
studies often 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\ (at and
above 149 [mu]g/m\3\ for vascular impairment, the effect shown to be
most consistent across studies). Commenters did specifically note one
study (Hemmingsen et al., 2015b) and contend that this study shows
significant effects on some outcomes at lower concentrations, following
5-hour exposures to 24 [mu]g/m\3\. The PA notes that this study does
not report effects consistent with other studies in the ISA that
evaluate longer exposure durations (i.e., longer than 2 hours) and
lower PM2.5 concentrations (e.g., Br[auml]uner et al., 2008
and Hemmingsen et al., 2015a). Furthermore, analyses in the PA show
that the exposure concentrations included in this study are not
observed in areas meeting the current standards (U.S. EPA, 2020, Figure
A-2), suggesting that the current standards provide protection against
these exposure concentrations. To provide insight into what these
studies may indicate regarding the primary PM2.5 standards,
the PA (U.S. EPA, 2020, p.3-49) notes that 2-hour ambient
concentrations of PM2.5 at monitoring sites meeting the
current standards almost never exceed 32 [mu]g/m\3\. In fact, even the
extreme upper end of the distribution of 2-hour PM2.5
concentrations at sites meeting the current standards remains well-
below the PM2.5 exposure concentrations consistently shown
in controlled human exposure studies to elicit effects (i.e., 99.9th
percentile of 2-hour concentrations at these sites is 68 [mu]g/m\3\
during the warm season). Thus, available PM2.5 controlled
human exposure studies do not indicate the need for additional
protection against exposures to peak PM2.5 concentrations,
beyond the protection provided by the combination of the current 24-
hour standard and the current annual standard (U.S. EPA, 2020, section
<IP_ADDRESS>). With respect to the epidemiological evidence and as noted
above in section II.A.2.c.ii, the information from such studies is most
applicable to examining potential health impacts associated with
typical (i.e., average or mean) exposures and thus are most applicable
in informing decisions on the annual standard (with its arithmetic mean
form). Furthermore, as noted above, the available epidemiological
studies do not indicate that associations in these studies are strongly
influenced by exposures to peak concentrations in the air quality
distribution, and thus do not indicate the need for additional
protection against short-term exposures to peak PM2.5
concentrations. As discussed above, the annual standard provides
protection against the typical 24-hour and annual PM2.5
exposures. Thus, in the context of a 24-hour standard that is meant to
provide supplemental protection (i.e., beyond that provided by the
annual standard alone) against short-term exposures to peak
PM2.5 concentrations, the available evidence supports the
Administrator's proposed conclusion to retain the current 24-hour
standard with its level of 35 [micro]g/m\3\.
    With respect to commenters that support revision of the annual
standard,

the EPA recognizes that there are a large number of studies, many of
which include a variety of study populations and geographic locations,
that show positive associations between mortality and morbidity and
short-term and long-term PM2.5 exposure. Furthermore, the
EPA recognizes that while uncertainties exist, when the epidemiological
evidence is viewed together in the context of the full body of
evidence, the scientific information supports that exposure to
PM2.5 may cause adverse health effects (U.S.EPA, 2019,
section 1.7.3, Table 1-4). Therefore, the EPA does not dispute
commenters that note epidemiological studies support the conclusion
that exposure to PM2.5 is associated with morbidity and
mortality.
    However, while the epidemiological evidence when considered
together with the full body of evidence supports health effects
associated with PM2.5 exposure, the EPA recognizes that
important uncertainties and limitations in the health effects evidence
remain. Epidemiological studies evaluating health effects associated
with long- and short-term PM2.5 exposures have reported
heterogeneity in associations between cities and geographic regions
within the U.S. Heterogeneity in the associations observed across
PM2.5 epidemiological studies may be due in part to exposure
error related to measurement-related issues, the use of central fixed-
site monitors to represent population exposure to PM2.5,
models used in lieu of or to supplement ambient measurements,
limitations in hybrid models and our limited understanding of factors
that may influence exposures (e.g., topography, the built environment,
weather, source characteristics, ventilation usage, personal activity
patterns, photochemistry) (U.S. EPA, 2020, p.3-25), all of which can
introduce bias and/or increased uncertainty is associated health
effects estimates. Heterogeneity is expected when the methods or
underlying distribution of covariates vary across studies (U.S. EPA,
2019, p. 6-221). In addition, where PM2.5 and other
pollutants (e.g., ozone, nitrogen dioxide, and carbon monoxide) are
correlated, it can be difficult to distinguish whether attenuation of
effects in some studies results from copollutant confounding or
collinearity with other pollutants in the ambient mixture (U.S. EPA,
2019, section 1.5.1). The EPA also recognizes that methodological study
designs to address confounding, such as causal inference methods, are
an emerging field of study (U.S. EPA, 2019, section <IP_ADDRESS> or U.S.
EPA, 2020, p. 3-24). The Administrator weighs these uncertainties in
the reported associations of PM2.5 concentrations in the
studies and considers them in the context of the entire body of
evidence before the Agency when reviewing the standards.
    Additionally, while epidemiological studies indicate associations
between exposure to PM2.5 and health effects, they do not
identify particular PM2.5 exposures that cause effects
(section II.A.2.c.ii above and U.S. EPA, 2020, section 3.1.2). Further,
using information from epidemiological studies to inform decisions on
PM2.5 standards is complicated by the recognition that no
population threshold, below which it can be concluded with confidence
that PM2.5-related effects do not occur, can be discerned
from the available evidence. As a result, any general approach to
reaching decisions on what standards are appropriate necessarily
requires judgments about how to translate the information available
from the epidemiological studies into a basis for appropriate
standards. This includes consideration of how to weigh the
uncertainties in the reported associations in the epidemiological
studies and the uncertainties in quantitative estimates of risk, in the
context of the entire body of evidence before the Agency. Such
approaches are consistent with setting standards that are neither more
nor less stringent than necessary, recognizing that a zero-risk
standard is not required by the CAA.
    Commenters who support revising the PM2.5 standards
further contend that the Administrator has arbitrarily rejected an
established practice of relying on epidemiological studies and of
setting the standard below the long-term mean PM2.5
concentrations reported in each of the studies that provide evidence of
an array of serious health effects. The commenters state that in
declaring that the latest epidemiological studies cannot justify a
decision to strengthen the PM NAAQS, the Administrator has rejected--
without acknowledgment or explanation--the EPA's long history of
relying on such research as the basis for its primary standards.
    As recognized in this and previous PM NAAQS reviews, including
those completed in 2006 and 2012, evidence of an association in any
epidemiological study is ``strongest at and around the long-term
average where the data in the study are most concentrated.'' In the PA
(U.S. EPA, 2020, section <IP_ADDRESS>.1), the EPA assessed air quality
distributions reported in key epidemiological studies included in the
ISA, with a focus on characterizing the long-term average or mean
PM2.5 concentrations. In doing this, key studies \43\ were
identified that examined short- and long-term exposure and showed
positive associations with either mortality or morbidity health
outcomes. The studies either estimated PM2.5 exposure using
ground-based monitored data or using hybrid modeling data, which
incorporate data from several sources, often including satellites and
models, as well as ground-based monitors (U.S. EPA, 2020, section
2.3.3). The PA notes some important considerations in using study
reported concentrations to inform conclusions on the primary
PM2.5 standards. In particular, it notes that the overall
mean PM2.5 concentrations reported by key epidemiological
studies are not the same as the ambient concentrations used by the EPA
to determine whether areas meet or violate the PM NAAQS. Mean
PM2.5 concentrations in key studies reflect averaging of
short- or long-term PM2.5 exposure estimates across
locations (i.e., across multiple monitors or across modeled grid cells)
and over time (i.e., over several years). In contrast, to determine
whether areas meet or violate the PM NAAQS, the EPA measures air
pollution concentrations at individual monitors (i.e., concentrations
are not averaged across monitors) and calculates design values \44\ at
monitors meeting appropriate data quality and completeness
criteria.\45\ For an area to meet the NAAQS, all valid design values in
that area, including the highest annual and highest 24-hour monitoring
values, must be at or below the standards. As a result, study reported
mean concentration values are generally lower than the design value of
the highest monitor in an area, which determines compliance.
---------------------------------------------------------------------------

    \43\ Studies included were multi-city studies in Canada and the
U.S. that examined health endpoints with `causal' or `likely to be
causal' determinations in the ISA.
    \44\ A design value is a statistic that summarizes the air
quality data for a given area in terms of the indicator, averaging
time, and form of the standard. Design values can be compared to the
level of the standard and are typically used to designate areas as
meeting or not meeting the standard and assess progress towards
meeting the NAAQS.
    \45\ For the annual PM2.5 standard, design values are
calculated as the annual arithmetic mean PM2.5
concentration, averaged over 3 years (described in appendix N of 40
CFR part 50). For the 24-hour standard, design values are calculated
as the 98th percentile of the annual distribution of the 24-hour
PM2.5 concentrations, averaged over three years.
---------------------------------------------------------------------------

    The PA first presents results from key epidemiological studies that
used ground-based monitoring data to estimate population exposure (U.S.
EPA, 2020, section <IP_ADDRESS>.1). Study reported mean (or medians) \46\
were

examined from the air quality distributions reported in key
epidemiological studies included in the ISA exposures (U.S. EPA, 2020,
Figure 3-7). The PA noted that these values are most useful in the
context of considering the level of the primary PM2.5 annual
standard. This is because the mean concentration values from these
studies, which include studies examining both short- and long-term
exposures, represent ``typical'' or mean exposures, which are most
relevant to the form and averaging time of the annual standard, and not
as relevant to the daily standard, whose form and averaging time
focuses on protecting against peak concentrations. Further, the PA
noted that in using these data it should be recognized that these mean
concentrations are generally below the design values in the
corresponding areas. In fact, analyses included in the PA of recent air
quality in U.S. CBSAs indicate that maximum annual PM2.5
design values for a given three-year period are often 10% to 20% higher
than average monitored concentrations (i.e., averaged across multiple
monitors in the same CBSA) (U.S. EPA, 2020, Appendix B, section B.7).
As noted in the PA, the difference between the maximum annual design
value and the average concentrations in an area will depend on a number
of factors including the numbers of monitors, monitor citing
characteristics, and the distribution of ambient PM2.5
concentrations. The PA also recognized that the recent requirement for
PM2.5 monitoring at near-road locations in large urban areas
may further increase the ratios of maximum annual design values to
average concentrations in some areas (U.S. EPA, 2020, section
<IP_ADDRESS>.1).
---------------------------------------------------------------------------

    \46\ Some epidemiological studies report median versus mean air
quality concentrations offering that median is a better metric since
it is less skewed by outlying concentrations. In most studies, the
mean and median concentrations are very similar and are generally
used here interchangeably.
---------------------------------------------------------------------------

    As detailed more in section II.A.2.c.ii, the PA next presents data
from the epidemiological studies that used hybrid modeling approaches
to estimate exposures (U.S. EPA, 2020, Figure 3-8). While studies using
hybrid modeling approaches provide valid methods to estimate exposures
in epidemiological studies and can expand the characterization of
PM2.5 exposures in areas with sparse monitoring networks,
these exposure estimation methods provide additional challenges to
comparing study reported mean concentrations to the annual standard
level. In these studies, PM2.5 concentrations are typically
estimated based on a hybrid approach of ``fusing'' data from air
quality models, satellites and ground-based monitors. As such, the
reported mean concentrations in an area (e.g., county or zip-code) from
these studies are calculated using the estimated concentrations from
thousands of grid cells across the area. Generally, this means a larger
number of lower concentration grid cells being included in the
calculation of the mean, resulting in a mean concentration even further
below the design value of the highest monitor in the area (which is
used for determining whether the area is meeting the current standard)
and even further below the mean concentration reported in
epidemiological studies utilizing ground-based monitors to estimate
exposure.
    It is also important to note that the performance of these hybrid
modeling approaches in estimating PM2.5 concentrations,
which are being used as surrogates for population exposure in the
epidemiological study, depends on the availability of monitoring data,
air quality model and the ability of the satellite to estimate ground
level concentration and, thus, varies by location. Factors that
contribute to poorer model performance often coincide with relatively
low ambient PM2.5 concentrations (U.S. EPA 2020, 2.3.3)
Thus, uncertainty in hybrid model predictions becomes an increasingly
important issue as lower predicted concentrations are considered. This
additional source of uncertainty is an important consideration,
particularly when all grid cell estimates are being used to calculate
the study mean concentration, and further adds to why using study
reported mean concentrations from epidemiological studies that use
hybrid approaches to inform conclusions on the primary PM2.5
standards is a challenge.
    Given all of this, the EPA concludes that the overall mean
PM2.5 concentrations in hybrid modeling studies are more
difficult to directly compare to design values than ground-based
monitoring concentrations in the context of setting a standard level.
In fact, recognizing this challenge, the PA tried to assess information
from hybrid modelling studies by calculating ``pseudo-design values''
in locations of the key epidemiological studies (U.S. EPA, 2020,
section <IP_ADDRESS>.2), as noted above in section II.A.2.c.ii and detailed
further in section II.C.1.a.ii of the proposal (85 FR 24117, April 30,
2020). However, this analysis and the associated approach were highly
criticized by most commenters, with none suggesting the methodology be
carried forward in the review. While the EPA believes that the PA's
``pseudo-design value'' approach was a step in the right direction, the
specific methodology itself needs further development.
    Given these considerations, and in light of the comments received,
the EPA believes it is reasonable to focus on study reported mean (or
median) concentrations \47\ from key U.S.\48\ epidemiological studies
that used ground-based monitors when considering information most
comparable to the current annual standard, while also weighing the
uncertainties associated with these studies and considering support
provided by other lines of evidence. Based on the information shown in
Figure 3-7 of the PA (U.S. EPA, 2020), the mean concentrations in 19 of
the 21 these studies were equal to or greater than the level of the
current annual standard of 12 [micro]g/m\3\. There were two studies,
both included in last review, for which the mean concentration (11.8
[micro]g/m\3\; Peng et al., 2009) or median concentration (10.7
[micro]g/m\3\ (Central Region); Zeger et al., 2008 \49\) was somewhat
below 12 [micro]g/m\3\. While these studies were included in the last
review, the air quality distributions were not used by the prior
Administrator in making a judgment on the level of the standard. The
reported study mean concentration for one other study was 12 [micro]g/
m\3\ (Kioumourtzoglou et al., 2016). The mean \50\ of the study
reported means (or medians) of these 21 studies is 13.5 [micro]g/m\3\,
a concentration level above the current level of the primary annual
standard of 12 [micro]g/m\3\. Additionally, based on analyses in the
PA, it would be expected that most of the design values (the metric
most relevant for comparison to the standard level) in the areas
included in these studies would be greater than 12 [micro]g/m\3\ \51\
(section II.A.2.c.ii above and U.S.

EPA 2020, Appendix B, section B.7). This is also supported by the
pseudo-design value analysis in Figure 3-9 of the PA (U.S. EPA, 2020).
---------------------------------------------------------------------------

    \47\ Some epidemiological studies report median versus mean air
quality concentrations offering that median is a better metric since
it is less skewed by outlying concentrations. In most studies, the
mean and median concentrations are very similar and are generally
used here interchangeably.
    \48\ Given how air quality monitors in other countries differ
from the U.S. EPA FRM monitors discussed here, a focus on U.S.
studies ensures that the results most closely compare to the data
being used for calculating the design values and for compliance of
the standard.
    \49\ We note that in this study the population was divided into
regions of the country, with statistically significant associations
in the Central and Eastern Regions and with median long-term
PM2.5 concentrations of: Central: 10.7 [micro]g/m\3\;
Western: 13.1 [micro]g/m\3\ and Eastern: 14.0 [micro]g/m\3\.
    \50\ The median of the study reported mean (or median)
PM2.5 concentrations is 13.3 [micro]g/m\3\.
    \51\ Recent air quality in U.S. CBSAs in the PA indicate that
maximum annual PM2.5 design values for a given three-year
period are often 10% to 20% higher than average monitored
concentrations (i.e., averaged across multiple monitors in the same
CBSA) (U.S. EPA, 2020, Appendix B, section B.7).
---------------------------------------------------------------------------

    Therefore, although recognizing that the proposal identified
certain concerns about the proper weight to be placed on
epidemiological studies, the EPA finds that its assessment of the mean
concentrations of the key short-term and long-term epidemiological
studies in the U.S. that use ground-based monitoring (i.e., those
studies that can provide information most directly comparable to the
current annual standard) is fundamentally consistent with the
assessment in the last review, which established the current primary
PM2.5 standards.
    Some commenters supporting revision of the primary PM2.5
standards contend that the quantitative risk assessment finds the
number of avoided deaths resulting from retention of the standards will
likely number in the many thousands, and a substantial reduction in
these events could be achieved by a more stringent PM2.5
standard. While commenters who support revising the PM2.5
standards support the recommendation of the PA to use the evidence-
based approach, as opposed to the risk-based approach, as a basis for
ascertaining whether and how to revise the primary standards, the
commenters state that the risk assessment does provide qualitative
support to revise the standards.
    With regard to the quantitative risk assessment described by some
commenters as showing health impacts that would be avoided by a more
stringent standard, the EPA notes that these analyses utilize
epidemiological study effect estimates as concentration-response
functions to predict the occurrence of primarily premature mortality
under different air quality conditions (characterized by the metric
used in the epidemiological study). While the epidemiological studies
that are inputs to the quantitative risk assessment are part of the
evidence base that supports the conclusion of a ``causal'' or ``likely
to be causal'' determination in the ISA (U.S. EPA, 2019), there are
uncertainties inherent in the derivation of estimates of health effects
(e.g., total mortality or ischemic heart disease mortality) ascribed to
PM2.5 exposures using effect estimates from these studies.
For example, the PA recognized several important uncertainties
associated with aspects of the quantitative risk assessment approach
and that the EPA concluded to have a medium or greater magnitude on
risk estimates (U.S. EPA, 2020, section C.3.1 and table C-32). These
uncertainties limit the applicability of the risk results for selecting
a specific standard. Uncertainties in the shapes of concentration-
response functions, particularly at low concentrations; uncertainties
in the methods used to adjust air quality; and uncertainty in
estimating risks for populations, locations and air quality
distributions different from those examined in the underlying
epidemiological study all limit utility (U.S. EPA, 2020, section
<IP_ADDRESS>). Further, the approach to weighing evidence-based and risk-
based considerations is not a new approach and as in previous reviews,
the selection of a specific approach to reaching final decisions on the
primary PM2.5 standards will reflect the judgments of the
Administrator as to what weight to place on the various types of
information available in the current review. The EPA notes that in the
previous review, evidence-based considerations were given greater
weight in the selection of standard levels than risk-based approaches
(e.g., 78 FR 3086, 3098-99, January 15, 2013) due to a recognition of
similar limitations.
    Some commenters who support the Administrator's rationale to retain
the PM2.5 standards contend that, due to uncertainties in
extrapolating health effects observed in animal toxicology studies to
humans, animal toxicology studies are of limited regarding the adequacy
of the current standard. On the other hand, commenters who support
revisions to the current suite of PM2.5 standards generally
contend that for experimental studies the Administrator: (1)
Inappropriately tied the concept of biological plausibility to a
specific concentration; (2) incorrectly interpreted animal/controlled
human exposure studies; (3) ignored the limitations of experimental
studies in relation to informing NAAQS levels and (4) gave inadequate
weight to all of the evidence because the Administrator saw no absolute
corroboration from clinical and accountability studies. The commenters
emphasize their view that experimental studies provide important
information regarding biological plausibility of numerous health
effects (e.g., cardiovascular, respiratory, nervous system, and cancer
effects) associated with PM2.5 exposure. Therefore, the
commenters contend that experimental studies provide biological
plausibility for human health effects linked to PM exposure in
epidemiological studies and when viewed together, support revision of
the current PM2.5 standards.
    The EPA notes that controlled human exposures studies provide
crucial evidence in assessing whether protection is provided for short-
term exposure concentrations consistently shown to elicit effects. In
examining the controlled human exposure studies, the PA notes these
studies provide evidence for health effects following single, short-
term PM2.5 exposures to concentrations, and thus, can be
useful to assess whether these effects are likely to occur in the upper
end of the PM2.5 air quality distribution in the U.S. (i.e.,
``peak'' concentrations) (U.S. EPA, 2020, section <IP_ADDRESS>). As noted by
the commenters, most of these studies examine exposure concentrations
considerably higher than are typically measured in areas meeting the
current standards (U.S. EPA, 2020, section <IP_ADDRESS>). As detailed in
section II.A.2.c.i above, even the extreme upper end of the
distribution of 2-hour PM2.5 concentrations at sites meeting
the current standards remains well-below the PM2.5 exposure
concentrations consistently shown to elicit effects. Further, human
exposure studies have not reported health effects at PM2.5
air quality concentrations likely to be seen in areas meeting the
current primary PM2.5 standards. As such, these studies do
not call into question the protection provided by the current primary
PM2.5 standards.
    Additionally, with respect to the experimental evidence, the EPA
agrees that animal toxicologic studies can be useful in understanding
and supporting the biological plausibility of various effects linked to
PM2.5 exposures. However, it is important to remember that
for this body of evidence there is uncertainty in extrapolating from
effects in animals to those in human populations. As such, animal
toxicology studies are of limited utility in directly informing
conclusions on the appropriate level of the standard. Thus, the
available evidence from animal toxicologic studies do not call into
question the protection provided by the current primary
PM2.5 standards.
    Further, the ISA assesses both human exposures studies and animal
toxicologic studies to evaluate the biological plausibility of various
effects linked to PM2.5 exposures, and thus, we agree with
the commenters on the importance of experimental evidence on this
account. Within the ISA's weight of evidence evaluation, which is based
on the integration of findings from various lines of evidence,
considerations in making causality determinations

include: ``determining whether laboratory studies of humans and
animals, in combination with epidemiological studies, inform the
biological mechanisms by which PM can impart health effects and provide
evidence demonstrating that PM exposure can independently cause a
health effect'' (U.S. EPA, 2019, p. ES-8). However, the ISA also notes
that the strength of the PM2.5 exposure-health effects
relationship varies depending on the exposure duration (i.e., short- or
long-term) and broad health effects category (e.g., cardiovascular
effects, respiratory effects) examined, and that across the broad
health effects categories examined, the evidence supporting biological
plausibility varies. Additionally, while assessing plausible biological
pathways is an important step in evaluating causality determinations,
the degree of biological plausibility for different mechanisms and end
points can also vary depending on the evidence available. As a result,
without a more clear linkage between concentrations below the current
standard levels and adverse health effects, the Administrator noted in
the proposal that he was ``cautious about placing too much weight on
reported PM2.5 health effect associations'' observed in
epidemiological studies (85 FR 24119, April 30, 2020). As discussed in
the proposal, the Administrator's proposed decision was based on his
evaluation of ``the overall body of evidence, including controlled
human exposure and animal toxicologic studies, in addition to
epidemiological studies'' (85 FR 24120, April 30, 2020). Thus, the
experimental evidence does not suggest that the epidemiological
evidence must be viewed differently than the Administrator has viewed
such evidence in his proposed decision to retain the current primary
standards.
    Some commenters who support retaining the current primary
PM2.5 standards assert that the currently available
accountability studies do not demonstrate that further reduction of the
PM NAAQS would achieve a measurable improvement in public health. In
contrast, commenters opposing the Administrator's proposed decision to
retain the PM2.5 standards criticize the Administrator's
heavy reliance on accountability studies to guide his decision, while
emphasizing that accountability studies are just one line of evidence
to inform causality. The commenters acknowledge the importance of well-
designed and conducted accountability studies but warn that
accountability studies measuring past interventions that are highly
localized may have actual effects too small to be reliably measured.
Considering the limitations of the accountability studies, including
findings leading to false negative results, such studies are not
considered essential for the proof of evidence required by statute,
according to these commenters.
    The EPA agrees with the commenters that well-designed and conducted
accountability studies can be informative and should be considered as
one line of evidence, recognizing that that these studies offer insight
into examples of how public health has responded to implementation of
PM2.5 reduction strategies. As discussed in the PA (U.S.
EPA, 2020, section <IP_ADDRESS>.1) and in section III.C.3 of the proposal
(85 FR 24120, April 30, 2020), the EPA notes the availability of
several such accountability studies and other retrospective health
studies examining periods of declining PM2.5 concentrations.
As indicated in Table 3-3 of the PA (U.S. EPA, 2020), these studies
conducted in the U.S. indicate 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. When considering the
overall means in these studies (i.e., the part of the air quality
distribution over which the studies provide the strongest support for
reported health effect associations), we find that ``starting'' annual
average PM2.5 concentrations (i.e., mean concentration prior
to reductions being evaluated) range from 13.2-31.5 [micro]g/m\3\ and
``ending'' concentrations ranging from 11.6-17.8 [micro]g/m\3\. As
such, the EPA notes that these retrospective studies tend to focus on
time periods during which ambient PM2.5 concentrations were
substantially higher than those measured more recently, as well as
``starting'' annual average PM2.5 concentrations above those
allowed by the current primary PM2.5 standards. As a result,
the EPA believes that while these studies do provide evidence of public
health improvements as ambient PM2.5 has declined over time,
no current studies have examined public health improvements following
reductions in ambient PM2.5 concentrations in areas where
the ``starting'' concentration met the current primary standards. Thus,
while acknowledging that this is an emerging field of study for
PM2.5-related health effects, the available evidence
supports the Administrator's recognition that currently, there is a
lack of accountability studies that clearly demonstrate that revising
the current primary PM2.5 standards would result in public
health improvements.
    Commenters opposed to the Administrator's proposed decision to
retain the PM2.5 standards contend that the EPA's proposed
decision is a violation of the CAA because it fails to consider
sensitive populations and contains no margin of safety for them, as
required under the CAA. In particular, these commenters pointed to
evidence drawn from epidemiological studies that included specific at-
risk groups in their study design and results.
    The EPA disagrees with these comments. As discussed above, the
Administrator's proposed decision to retain the current primary
PM2.5 standards followed the same general approach used in
previous reviews for reaching conclusions on what standards are
appropriate. As such, the Administrator recognized that judgments of
how to translate information available from epidemiological studies
into a basis for appropriate standards must be considered in
conjunction with the uncertainties in the epidemiological studies and
in the context of the entire body of evidence before the Agency. This
approach recognizes that the Administrator's judgment is particularly
important for a pollutant where a population threshold cannot be
clearly discerned with confidence from the evidence and where clinical
evidence does not demonstrate health effects at typical ambient
concentrations that meet the current standards. This approach is also
consistent with the CAA requirement to set standards that are neither
more nor less stringent than necessary, recognizing that a zero-risk
standard is not required by the CAA.
    With respect to protection of at-risk populations, the EPA has
carefully evaluated and considered evidence of effects in at-risk
populations. Unlike some of the other NAAQS reviews where the
epidemiological evidence may be less complete, this PM NAAQS review has
the benefit of having an ISA that considered many epidemiological
studies that assessed impacts for populations considered at-risk (e.g.,
populations of older adults, children, or those with preexisting
conditions, like cardiovascular disease). In addition, some of the key
epidemiology studies that the EPA assessed (included in Figure 3-7 of
the PA) also specifically focused on and evaluated at-risk populations,
including epidemiology studies that assessed morbidity and mortality
associations for age-specific

populations (e.g., Medicare populations), as well as epidemiology
studies that evaluated associations between PM2.5 exposure
and specific health endpoints, like hospital admissions for
cardiovascular effects in populations age 65 and older. The Agency
takes note that it considered these studies to inform its review of the
primary PM2.5 standards, which include at-risk populations,
as well as other studies in the full body of scientific evidence in
evaluating effects associated with long or short-term PM2.5
exposures (i.e., premature mortality, cardiovascular effects, cancer,
and respiratory effects).
    More specifically, in weighing the scientific evidence to inform
his decision on requisite PM2.5 standards with an adequate
margin of safety, including protection for at-risk populations, the
Administrator's proposed conclusions recognized that epidemiological
studies, many of which by design include at-risk populations, examine
associations between distributions of PM2.5 air quality and
health outcomes. Further, in noting that epidemiological studies do not
identify particular PM2.5 exposures that cause effects, the
PA focused on the reported mean concentrations from key epidemiological
studies with the aim of providing a potential translation of
information from epidemiological studies into the basis for
consideration on standard levels (U.S. EPA, 2020, section 3.1.2). As
discussed in more detail above, for the mean concentrations of the key
epidemiological studies in the U.S. that use ground-based monitoring
(i.e., those studies that can provide information most directly
comparable to the current annual standard), the majority of studies
have long-term mean (or median) concentrations above the current NAAQS
(12.0 [micro]g/m\3\), with the mean of the study reported means or
medians equal to 13.5 [micro]g/m\3\, a concentration level above the
current level of the primary annual standard of 12 [micro]g/m\3\. The
EPA notes that study reported mean (or median) concentration values are
generally 10-20% lower than the design value of the highest monitor in
an area, which determines compliance, and suggesting that that the
current level of the standard provides even more protection than is
suggested by the reported means.\52\ In the proposal, the Administrator
recognized that important uncertainties and limitations do remain in
the epidemiological evidence and the Administrator weighed these
uncertainties, while also considering support provided by other lines
of evidence, in judging whether the current standards are requisite
with an adequate margin of safety. The Administrator further considered
the emerging body of evidence from accountability studies examining
past reductions in ambient PM2.5 and the degree to which
those reductions have resulted in public health improvements. As
discussed above, such studies have focused on time periods during which
ambient PM2.5 concentrations were substantially higher than
those measured more recently and therefore do not demonstrate public
health improvements attributable to reduction in ambient
PM2.5 at concentrations below the current standard.
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    \52\ Analyses of recent air quality in U.S. CBSAs indicate that
maximum annual PM2.5 design values for a given three-year
period are often 10% to 20% higher than average monitored
concentrations (i.e., averaged across multiple monitors in the same
CBSA) (U.S. EPA, 2020, Appendix B, section B.7).
---------------------------------------------------------------------------

    Thus, the Administrator judged that the overall body of evidence
indicates continued uncertainty in the degree to which adverse effects
could result from PM2.5 exposures in areas meeting the
current annual and 24-hour standards. Additionally, the current annual
standard is below the lowest ``starting'' concentration in the
available accountability studies (i.e., 13.2 [micro]g/m\3\) and below
the reported mean concentration in the majority of the key U.S.
epidemiological studies using ground-based monitoring data \53\ (i.e.,
mean of the reported means was 13.5 [micro]g/m\3\). In addition,
concentrations in areas meeting the current 24-hour and annual
standards remain well-below the PM2.5 exposure
concentrations consistently shown to elicit effects in controlled human
exposure studies. In specifically assessing his proposed decision, the
Administrator noted that more stringent standards would be more than
requisite to protect public health with an adequate margin of safety.
---------------------------------------------------------------------------

    \53\ As discussed above, the means from these studies are most
relatable to the level of the annual standard. However, because the
reported means in these studies are based on averaging the monitored
concentration across an area, they are lower than the design value
for that same area, since attainment of the standard is based on the
measurements at the highest monitor (and not the average across
multiple monitors.)
---------------------------------------------------------------------------

4. Administrator's Conclusions
    This section summarizes the Administrator's conclusions and final
decisions related to the current primary PM2.5 standards and
presents his decision to retain those standards, without revision. As
described above (section I.D) and in section II.A.2 of the proposal (85
FR 24105, April 30, 2020), the Administrator's approach to considering
the adequacy of the current standards focuses on evaluating the public
health protection afforded by the annual and 24-hour standards, taken
together, against mortality and morbidity 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
and that the protection provided by the suite of standards results from
the combination of all of the elements of those standards (i.e.,
indicator, averaging time, form, level). Thus, the Administrator's
consideration of the public health protection provided by the current
primary PM2.5 standards is based on his consideration of the
combination of the annual and 24-hour standards, including the
indicators (PM2.5), averaging times, forms (arithmetic mean
and 98th percentile, averaged over three years), and levels (12.0
[mu]g/m\3\, 35 [mu]g/m\3\) of those standards.
    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 review is 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 is 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 is informed by the Administrator's consideration of advice from the
CASAC and public comments received on the proposal notice.
    As an initial matter, the Administrator recognizes that, with
regard to effects classified as having evidence of a causal

or likely causal relationship with long or short-term PM2.5
exposures (i.e., premature mortality, cardiovascular effects, cancer,
and respiratory effects), the EPA considered the full range of studies
evaluating these effects, including studies of at-risk populations, to
inform its review of the primary PM2.5 standards. Thus, the
Administrator notes that his judgment in this final decision reflects
placing the greatest weight on evidence of effects for which the ISA
determined there is a causal or likely causal relationship with long-
and short-term PM2.5 exposures.
    With respect to the indicator, the Administrator recognizes that
the scientific evidence in this review, as in the last review,
continues to provide strong support for health effects following short-
and long-term PM2.5 exposures. 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. Further, the Administrator notes that the
EPA received very few comments on the indicator, with no commenters
advocating for revising the current PM2.5 indicator for fine
particles. Thus, as proposed, the Administrator concludes that it is
appropriate to retain PM2.5 as the indicator for the primary
standards for fine particulates.
    With respect to averaging time and form, the Administrator notes
that the scientific evidence continues to provide strong support for
health effects associations with both long-term (e.g., annual or multi-
year) and short-term (e.g., mostly 24-hour) exposures to
PM2.5 and, consistent with the conclusions in the PA, judges
that the current evidence does not support considering alternatives
(U.S. EPA, 2020, section 3.5.2). The Administrator also notes that very
few comments were received related to averaging time and form and none
directly advocated for changing the form or averaging time. In the
current review, epidemiological and controlled human exposure studies
have examined a variety of PM2.5 exposure durations.
Epidemiological 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, 2019, section <IP_ADDRESS>; U.S. EPA,
2020, section <IP_ADDRESS>). In addition, controlled human exposure and
panel-based studies of sub-daily exposures typically examine
subclinical effects, as the commenters acknowledge, 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 ISA concludes that epidemiological studies do not
indicate that sub-daily averaging periods are more closely associated
with health effects than the 24-hour average exposure metric (U.S. EPA,
2019, 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, 2020, section <IP_ADDRESS>). Thus,
these studies also do not suggest the need for additional protection
against sub-daily PM2.5 exposures, beyond that provided by
the current primary standards. Therefore, the Administrator's judgment
is that the current 24-hour averaging time remains appropriate.
    In relation to the form of the 24-hour standard (98th percentile,
averaged over three years), the Administrator notes that
epidemiological studies continue to provide strong support for health
effect associations with short-term (e.g., mostly 24-hour)
PM2.5 exposures (U.S. EPA, 2020, section <IP_ADDRESS>) 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, 2020, section <IP_ADDRESS>). As such, the Administrator
concludes, as proposed, to retain the form and averaging time of the
current 24-hour standard (98th percentile, averaged over three years)
and annual standard (annual average, averaged over three years).
    The Administrator also proposed to retain the current levels of the
24-hour standard (98th percentile, averaged over three years) at 35
[micro]g/m\3\ and annual standard (annual average, averaged over 3
years) at 12 [micro]g/m\3\. The majority of the comments received
focused on this proposed decision to retain the current levels of both
standards. In reaching his final decision regarding the level of the
standards, the Administrator considered the large body of evidence
presented and assessed in the ISA (U.S. EPA, 2019), the policy-relevant
and risk-based conclusions and rationales as presented in the PA (U.S.
EPA, 2020), views expressed by the CASAC, and public comments. In
particular, in considering the ISA and PA, he considers key
epidemiological studies that evaluate associations between
PM2.5 air quality distributions and mortality and morbidity,
including key ``accountability studies''; the availability of
experimental studies to support biological plausibility; controlled
human exposure studies examining effects following short-term
PM2.5 exposures; air quality analyses; and the important
uncertainties and limitations associated with this information.
    As an initial matter, the Administrator recognizes that the current
annual standard is most effective in controlling PM2.5
concentrations near the middle of the air quality distribution (i.e.,
around the mean of the distribution), but can also provide some control
over short-term peak PM2.5 concentrations. On the other
hand, the 24-hour standard, with its 98th percentile form, is most
effective at limiting peak 24-hour PM2.5 concentrations, but
in doing so will also have an effect on annual average PM2.5
concentrations. Thus, while either standard could be viewed as
providing some measure of protection against both average exposures and
peak exposures, the 24-hour and annual standards are not expected to be
equally effective at limiting both types of exposures. Thus, consistent
with previous reviews, the Administrator's consideration of the public
health protection provided by the current primary PM2.5
standards is based on his consideration of the combination of the
annual and 24-hour standards. Specifically, he recognizes that the
annual standard is more likely to appropriately limit the ``typical''
daily and annual exposures that are most strongly associated with the
health effects observed in epidemiological studies. The Administrator
concludes that an annual standard (arithmetic mean, averaged over three
years) remains appropriate for targeting protection against the annual
and daily PM2.5 exposures around the middle portion of the
PM2.5 air quality distribution. Further, recognizing that
the 24-hour standard (with its 98th percentile form) is more directly
tied to short-term peak PM2.5 concentrations, and thus more
likely to appropriately limit exposures to such concentrations, the
Administrator concludes that the

current 24-hour standard (98th percentile, averaged over three years)
remains appropriate to provide a balance between limiting the
occurrence of peak 24-hour PM2.5 concentrations and
identifying a stable target for risk management programs. However, the
Administrator recognizes that changes in PM2.5 air quality
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. The Administrator further recognizes
that changes in air quality to meet a 24-hour standard, with a 98th
percentile form, would result not only in fewer and lower peak 24-hour
PM2.5 concentrations, but also in lower annual average
PM2.5 concentrations.