annual design values \31\ to understand the policy implications of the
alternative standard levels supported by the underlying science. In
particular, the Policy Assessment considers the extent to which
different combinations of alternative annual and 24-hour standards
would support the policy goal of focusing on a generally controlling
annual standard in conjunction with a 24-hour standard that would
provide supplemental protection. Based on the evidence-based
considerations outlined above, the Policy Assessment develops
integrated conclusions with regard to alternative suites of standards,
including both annual and 24-hour standards that are appropriate to
consider in this review based on the currently available evidence and
air quality information. In so doing, the Policy Assessment discusses
the roles that each standard might be expected to play in the
protection afforded by alternative suites of standards.
---------------------------------------------------------------------------

    \31\ Design values are the metrics (i.e., statistics) that are
compared to the NAAQS levels to determine compliance.
---------------------------------------------------------------------------

    Beyond these evidence-based considerations, the Policy Assessment
also considers the quantitative risk estimates and the key observations
presented in the Risk Assessment. This assessment includes an
evaluation of 15 urban case study areas and estimated risk associated
with a number of health endpoints associated with long- and short-term
PM2.5 exposures (U.S. EPA, 2010a). As part of the risk-based
considerations, the Policy Assessment considers estimates of the
magnitude of PM2.5-related risks associated with recent air
quality levels and air quality simulated to just meet the current and
alternative suites of standards using alternative simulation
approaches. The Policy Assessment also characterizes the risk
reductions, relative to the risks remaining upon just meeting the
current standards, associated with just meeting alternative suites of
standards. In so doing, the Policy Assessment recognizes the
uncertainties inherent in such risk estimates, and takes such
uncertainties into account by considering the sensitivity of the
``core'' risk estimates to alternative assumptions and methods likely
to have substantial impact on the estimates. In addition, the Policy
Assessment considers additional analyses characterizing the
representativeness of the urban study areas within a broader national
context to understand the roles that the annual and 24-hour standards
may play in affording protection against effects

related to both long- and short-term PM2.5 exposures.
    The Policy Assessment conclusions related to the primary
PM2.5 standards reflect an understanding of both evidence-
based and risk-based considerations to inform two overarching questions
related to: (1) The adequacy of the current suite of PM2.5
standards and (2) potential alternative standards, if any, that are
appropriate to consider in this review to protect against effects
associated with both long- and short-term exposures to fine particles.
In addressing these broad questions, the discussions included in the
Policy Assessment were organized around a series of more specific
questions reflecting different aspects of each overarching question
(U.S. EPA, 2011a, chapter 2, Figure 2-1). When evaluating the health
protection afforded by the current or any alternative suites of
standards considered, the Policy Assessment takes into account the four
basic elements of the NAAQS: the indicator, averaging time, form, and
level. The general approach for reviewing the primary PM2.5
standards described above provides a comprehensive basis to help inform
the judgments required of the Administrator in reaching decisions about
the current and potential alternative primary fine particle standards
and in responding to the remand of the 2006 primary annual
PM2.5 standard.

B. Health Effects Related to Exposure to Fine Particles

    This section outlines key information contained in the Integrated
Science Assessment (Chapters 2, 4, 5, 6, 7, and 8) and the Policy
Assessment (Chapter 2) related to health effects associated with fine
particle exposures. As was true in the last review, evidence from
epidemiologic studies plays a key role in the Integrated Science
Assessment's evaluation of the scientific evidence. The following
sections discuss available information on the health effects associated
with exposures to PM2.5, including the nature of such health
effects (section III.B.1) and associated limitations and uncertainties
(section III.B.2), at-risk populations (section III.B.3), and potential
PM2.5-related impacts on public health (section III.B.4).
1. Nature of Effects
    In considering the strength of the associations between long- and
short-term exposures to PM2.5 and health effects, the Policy
Assessment notes that in the PM NAAQS review completed in 2006 the
Agency concluded that there was ``strong epidemiological evidence'' for
linking long-term PM2.5 exposures with cardiovascular-
related and lung cancer mortality and respiratory-related morbidity and
for linking short-term PM2.5 exposures with cardiovascular-
related and respiratory-related mortality and morbidity (U.S. EPA,
2004, p. 9-46; U.S. EPA, 2005, p. 5-4). Overall, the epidemiological
evidence supported ``likely causal associations'' between
PM2.5 and both mortality and morbidity from cardiovascular
and respiratory diseases, based on ``an assessment of strength,
robustness, and consistency in results'' (U.S. EPA, 2004, p. 9-48).\32\
---------------------------------------------------------------------------

    \32\ The term ``likely causal association'' was used in the 2004
Criteria Document to summarize the strength of the available
epidemiological evidence available in the last review for
PM2.5. However, this terminology was not based on a
formal framework for evaluating evidence for inferring causation.
Since the last review, the EPA has developed a more formal framework
for reaching causal determinations with standardized language to
express evaluation of the evidence (U.S. EPA, 2009a, section 1.5).
---------------------------------------------------------------------------

    In looking across the extensive new scientific evidence available
in this review, our overall understanding of health effects associated
with fine particle exposures has been greatly expanded (U.S. EPA,
2009a, sections 2.3.1 and 2.3.2). The currently available evidence is
stronger in comparison to evidence available in the last review because
of its breadth and the substantiation of previously observed health
effects. A number of large multi-city epidemiological studies have been
conducted throughout the U.S., including extended analyses of studies
that were important to inform decision-making in the last review. These
studies have reported consistent increases in morbidity and/or
mortality related to ambient PM2.5 concentrations, with the
strongest evidence reported for cardiovascular-related effects. In
addition, the findings of new toxicological and controlled human
exposure studies greatly expand and provide stronger support for a
number of potential biologic mechanisms or pathways for cardiovascular
and respiratory effects associated with long- and short-term PM
exposures (U.S. EPA, 2009a, p. 2-17; chapter 5; Figures 5-4 and 5-5).
    With regard to causal inferences described in the Integrated
Science Assessment, the Policy Assessment notes that since the last
review, the Agency has developed a more formal framework for reaching
causal determinations that draws upon the assessment and integration of
evidence from across epidemiological, controlled human exposure, and
toxicological studies, and the related uncertainties, that ultimately
influence our understanding of the evidence (U.S. EPA, 2011a, p. 2-18;
U.S. EPA, 2009a, section 1.5). This framework employs a five-level
hierarchy that classifies the overall weight of evidence and causality
using the following categorizations: causal relationship, likely to be
a causal relationship, suggestive of a causal relationship, inadequate
to infer a causal relationship, and not likely to be a causal
relationship (U.S. EPA, 2009a, Table 1-3).\33\
---------------------------------------------------------------------------

    \33\ Causal inferences, as discussed in the Integrated Science
Assessment, are based not only on the more expansive epidemiological
evidence available in this review but also reflect consideration of
important progress that has been made to advance our understanding
of a number of potential biologic modes of action or pathways for
PM-related cardiovascular and respiratory effects (U.S. EPA, 2009a,
chapter 5).
---------------------------------------------------------------------------

    Using this causal framework, the Integrated Science Assessment
concludes that the collective evidence is largely consistent with past
studies and substantially strengthens what was known about fine
particles in the last review to reach the conclusion that a causal
relationship exists between both long- and short-term exposures to
PM2.5 and mortality and cardiovascular effects including
cardiovascular-related mortality. The Integrated Science Assessment
also concludes that the collective evidence continues to support a
likely causal relationship between long- and short-term
PM2.5 exposures and respiratory effects, including
respiratory-related mortality. Further, the Integrated Science
Assessment concludes that the currently available evidence is
suggestive of a causal relationship between long-term PM2.5
exposures and other health effects, including developmental and
reproductive effects (e.g., low birth weight, infant mortality) and
carcinogenic, mutagenic, and genotoxic effects (e.g., lung cancer
mortality) (U.S. EPA, 2009a, sections 2.3.1 and 2.6; Table 2-6; U.S.
EPA, 2011a, Table 2-1).
a. Health Effects Associated With Long-Term PM2.5 Exposures
    With regard to mortality, the Integrated Science Assessment
concludes that newly available evidence significantly strengthens the
link between long-term exposure to PM2.5 and mortality,
while providing indications that the magnitude of the PM2.5-
mortality association may be larger than previously estimated (U.S.
EPA, 2009a, sections 7.2.10, 7.2.11, and 7.6.1; Figures 7-6 and 7-7). A
number of large U.S. cohort studies have been published since the last
review, including extended analyses of the

American Cancer Society (ACS) and Harvard Six Cities studies (U.S. EPA,
2009a, pp. 7-84 to 7-85; Figure 7-6; Krewski et al., 2009; Pope et al.,
2004; Jerrett et al., 2005; Laden et al., 2006). In addition, new long-
term PM2.5 exposure studies evaluating mortality impacts in
additional cohorts are now available (U.S. EPA, 2009a, section 7.6).
For example, the Women's Health Initiative (WHI) Observational Study
reported effects of PM2.5 on cardiovascular-related
mortality in post-menopausal women with no previous history of cardiac
disease (Miller et al., 2007). The PM2.5 effect estimate in
this study remained positive and statistically significant in a multi-
pollutant model that included gaseous co-pollutants as well as coarse
particles. In addition, multiple studies observed PM2.5-
associated mortality among older adults using Medicare data (Eftim et
al., 2008; Zeger et al., 2007, 2008). Collectively, these new studies,
along with evidence available in the last review, provide consistent
and stronger evidence of associations between long-term exposure to
PM2.5 and mortality (U.S. EPA, 2009a, sections 2.3.1 and
7.6).
    The strength of the causal relationship between long-term
PM2.5 exposure and mortality also builds upon new studies
providing evidence of improvement in community health following
reductions in ambient fine particles. Pope et al. (2009) documented the
population health benefits of reducing ambient air pollution by
correlating past reductions in ambient PM2.5 concentrations
with increased life expectancy. These investigators reported that
reductions in ambient fine particles during the 1980s and 1990s account
for as much as 15 percent of the overall improvement in life expectancy
in 51 U.S. metropolitan areas, with the fine particle reductions
reported to be associated with an estimated increase in mean life
expectancy of approximately 5 to 9 months (U.S. EPA, 2009a, p. 7-95;
Pope et al., 2009). An extended analysis of the Harvard Six Cities
study found that as cities cleaned up their air, locations with the
largest reductions in PM2.5 saw the largest improvements in
reduced mortality rates, while those with the smallest decreases in
PM2.5 concentrations saw the smallest improvements (Laden et
al., 2006). Another extended follow-up to the Harvard Six Cities study
investigated the delay between changes in ambient PM2.5
concentrations and changes in mortality (Schwartz et al., 2008) and
reported that the effects of changes in PM2.5 were seen
within the 2 years prior to death (U.S. EPA, 2009a, p. 7-92; Figure 7-
9).
    With regard to cardiovascular effects, several new studies have
examined the association between cardiovascular effects and long-term
PM2.5 exposures in multi-city studies conducted in the U.S.
and Europe. The Integrated Science Assessment concludes that the
strongest evidence comes from recent studies investigating
cardiovascular-related mortality. This includes evidence from a number
of large, multi-city U.S. long-term cohort studies including extended
follow-up analyses of the ACS and Harvard Six Cities studies, as well
as the WHI study (U.S. EPA, 2009a, sections 7.2.10 and 7.6.1; Krewski
et al., 2009; Pope et al., 2004; Laden et al., 2006; Miller et al.,
2007). Pope et al. (2004) reported a positive association between
mortality and long-term PM2.5 exposure for a number of
specific cardiovascular diseases, including ischemic heart disease,
dysrhythmia, heart failure, and cardiac arrest (U.S. EPA, 2009a, p. 7-
84; Figure 7-7). Krewski et al. (2009) provides further evidence for
mortality related to ischemic heart disease associated with long-term
PM2.5 exposure (U.S. EPA, 2009a, p. 7-84, Figure 7-7).
    With regard to cardiovascular-related morbidity associated with
long-term PM2.5 exposures, studies were not available in the
last review. Recent studies, however, have provided new evidence
linking long-term exposure to PM2.5 with cardiovascular
outcomes that has ``expanded upon the continuum of effects ranging from
the more subtle subclinical measures to cardiopulmonary mortality''
(U.S. EPA, 2009a, p. 2-17). In the current review, studies are now
available that evaluated a number of endpoints ranging from subtle
indicators of cardiovascular health to serious clinical events
associated with coronary heart disease and cardiovascular and
cerebrovascular disease.\34\ The most important new evidence comes from
the WHI study which provides evidence of nonfatal cardiovascular events
including both coronary and cerebrovascular events (Miller et al.,
2007; U.S. EPA, 2009a, sections 7.2.9 and 7.6.1). Toxicological studies
provide supportive evidence that the cardiovascular morbidity effects
observed in long-term exposure epidemiological studies are biologically
plausible and coherent with studies of cardiovascular-related mortality
as well as with studies of cardiovascular-related effects associated
with short-term exposures to PM2.5, as described below (U.S.
EPA, 2009a, p. 7-19).
---------------------------------------------------------------------------

    \34\ Coronary and cerebrovascular events include myocardial
infarction, coronary artery revascularization (e.g., bypass graft,
angioplasty, stent, atherectomy), congestive heart failure and
stroke.
---------------------------------------------------------------------------

    With regard to respiratory effects, the Integrated Science
Assessment concludes that extended analyses of studies available in the
last review as well as new epidemiological studies conducted in the
U.S. and abroad provide stronger evidence of respiratory-related
morbidity associated with long-term PM2.5 exposure. The
strongest evidence for respiratory-related effects available in this
review is from studies that evaluated decrements in lung function
growth, increased respiratory symptoms, and asthma development (U.S.
EPA, 2009a, sections <IP_ADDRESS>, <IP_ADDRESS>, and <IP_ADDRESS>).\35\ Specifically,
extended analyses of the Southern California Children's Health Study
provide evidence that clinically important deficits in lung function
\36\ associated with long-term exposure to PM2.5 persist
into early adulthood (U.S. EPA, 2009a, p. 7-27; Gauderman et al.,
2004). Additional analyses of the Southern California Children's Health
Study cohort reported an association between long-term PM2.5
exposure and bronchitic symptoms (U.S. EPA, 2009a, p. 7-23 to 24;
McConnell et al., 2003) that remained positive in co-pollutant models,
with the PM2.5 effect estimates increasing in magnitude in
some models and decreasing in others, and a strong modifying effect of
PM2.5 on the association between lung function and asthma
incidence (U.S. EPA, 2009, 7-24; Islam et al., 2007). The outcomes
observed in these more recent reports from the Southern California
Children's Health Study, including evaluation of a broader range of
endpoints and longer follow-up periods, were larger in magnitude and
more precise than previously reported. Supporting these results are new
longitudinal cohort studies conducted by other researchers in varying
locations using different methods (U.S. EPA, 2009a, section <IP_ADDRESS>).
New evidence from a U.S. cohort of cystic fibrosis patients provided
evidence of association between long-term PM2.5 exposures
and exacerbations of respiratory symptoms

resulting in hospital admissions or use of home intravenous antibiotics
(U.S. EPA, 2009a, p. 7-25; Goss et al., 2004).
---------------------------------------------------------------------------

    \35\ Supporting evidence comes from studies ``that observed
associations between long-term exposure to PM10 and an
increase in respiratory symptoms and reductions in lung function
growth in areas where PM10 is dominated by
PM2.5'' (U.S. EPA, 2009a, p. 2-12).
    \36\ Clinical significance was defined as an FEV1
below 80 percent of the predicted value, a criterion commonly used
in clinical settings to identify persons at increased risk for
adverse respiratory conditions (U.S. EPA, 2009a, p. 7-29 to 7-30).
The primary NAAQS for sulfur dioxide (SO2) also includes
this interpretation for FEV1 (75 FR 35525, June 22,
2010).
---------------------------------------------------------------------------

    Toxicological studies provide coherence and biological plausibility
for the respiratory effects observed in epidemiological studies (U.S.
EPA, 2009a, p. 7-42). For example, pre- and postnatal exposure to
ambient levels of urban particles has been found to affect lung
development in an animal model (U.S. EPA, 2009a, section <IP_ADDRESS>; p. 7-
43). This finding is important because impaired lung development is one
mechanism by which PM exposure may decrease lung function growth in
children (U.S. EPA, 2009a, p. 2-12; section 7.3).
    With regard to respiratory-related mortality associated with long-
term PM2.5 exposure, the Integrated Science Assessment
concludes that ``when deaths due to respiratory causes are separated
from all-cause (nonaccidental) and cardiopulmonary deaths, there is
limited and inconclusive evidence for an effect of PM2.5 on
respiratory mortality, with one large cohort study finding a reduction
in deaths due to respiratory causes associated with reduced
PM2.5 concentrations, and another large cohort study finding
no PM2.5 associations with respiratory mortality'' (U.S.
EPA, 2009a, p. 7-41). The extended follow-up of the Harvard Six Cities
study reported a positive but statistically non-significant association
between long-term PM2.5 exposure and respiratory-related
mortality (Laden et al., 2006), whereas Pope et al. (2004) found no
association in the ACS cohort (U.S. EPA, 2009a, p. 7-84). There is
emerging but limited evidence for an association between long-term
PM2.5 exposure and respiratory mortality in post-neonatal
infants where long-term exposure was considered as approximately one
month to one year (U.S. EPA, 2009a, pp. 7-54 to 7-55). Emerging
evidence of short- and long-term exposure to PM2.5 and
respiratory morbidity and infant mortality provide some support for the
weak respiratory-related mortality effects observed.
    Beyond effects considered to have causal or likely causal
relationships with long-term PM2.5 exposure as discussed
above, the following health outcomes are classified in the Integrated
Science Assessment as having evidence suggestive of a causal
relationship with long-term PM2.5 exposure: (1) Reproductive
and developmental effects and (2) cancer, mutagenicity, and
genotoxicity effects (U.S. EPA, 2009a, Table 2-6). With regard to
reproductive and developmental effects, the Integrated Science
Assessment notes, ``[e]vidence is accumulating for PM2.5-
related effects on low birth weight and infant mortality, especially
due to respiratory causes during the post-neonatal period'' (U.S. EPA,
2009a, p. 2-13). New evidence available in this review reports
significant associations between exposure to PM2.5 during
pregnancy and lower birth weight and infant mortality, with less
consistent evidence for pre-term birth and intrauterine growth
restriction. (U.S. EPA, 2009a, section 7.4). The Integrated Science
Assessment further notes that ``[i]nfants and fetal development
processes may be particularly vulnerable to PM exposure, and although
the physical mechanisms are not fully understood, several hypotheses
have been proposed involving direct effects on fetal health, altered
placenta function, or indirect effects on the mother's health'' (U.S.
EPA, 2009a, section 7.4.1). Although toxicological studies provide some
evidence that supports an association between long-term
PM2.5 exposure and adverse reproductive and developmental
outcomes, there is ``little mechanistic information or biological
plausibility for an association between long-term PM exposure and
adverse birth outcomes (e.g., low birth weight, infant mortality)''
(U.S. EPA, 2009a, p. 2-13).
    With regard to cancer, mutagenic and genotoxic effects,
``[m]ultiple epidemiologic studies have shown a consistent positive
association between PM2.5 and lung cancer mortality, but
studies have generally not reported associations between
PM2.5 and lung cancer incidence'' (U.S. EPA, 2009a, p. 2-13
and sections <IP_ADDRESS> and 7.5; Table 7-7; Figures 7-6 and 7-7). The
extended follow-up to the ACS study reported an association between
long-term PM2.5 exposure and lung cancer mortality (U.S.
EPA, 2009a, p. 7-71; Krewski et al., 2009) as did the extended follow-
up to the Harvard Six Cities study when considering the entire 25-year
follow-up period (Laden et al., 2006). There is some evidence,
primarily from in vitro studies, providing biological plausibility for
the PM-lung cancer relationships observed in epidemiological studies
(U.S. EPA, 2009a, p. 7-80), although in vivo toxicological studies of
carcinogenicity generally reported mixed results (U.S. EPA, 2009a,
section 7.5).
b. Health Effects Associated With Short-Term PM2.5 Exposures
    In considering effects associated with short-term PM2.5
exposure, the body of currently available scientific evidence has been
expanded greatly by the publication of a number of new multi-city,
time-series studies that have used uniform methodologies to investigate
the effects of short-term fine particle exposures on public health.
This body of evidence provides a more expansive data base and considers
multiple locations representing varying regions and seasons that
provide evidence of the influence of climate and air pollution mixes on
PM2.5-associated health effects. These studies provide more
precise estimates of the magnitude of effects associated with short-
term PM2.5 exposure than most smaller-scale single-city
studies that were more commonly available in the last review (U.S. EPA
2009a, chapter 6).
    With regard to mortality, new U.S. and Canadian multi-city and
single-city PM2.5 exposure studies have found generally
consistent positive associations between short-term PM2.5
exposures and cardiovascular- and respiratory-related mortality as well
as all-cause (non-accidental) mortality (U.S. EPA, 2009a, sections
<IP_ADDRESS>, 6.2.11 and <IP_ADDRESS>; Figures 6-26, 6-27, and 6-28). In an
analysis of the National Morbidity, Mortality, and Air Pollution Study
(NMMAPS) data, Dominici et al. (2007) reported associations between
fine particle exposures and all-cause and cardiopulmonary-related
mortality (U.S. EPA, 2009a, p. 6-175, Figure 6-26). In a study of 112
U.S. cities, Zanobetti and Schwartz (2009) reported positive
associations (in 99 percent of the cities) and frequently statistically
significant associations (in 55 percent of the cities) between short-
term PM2.5 exposure and total (non-accidental) mortality
(U.S. EPA, 2009a, pp. 6-176 to 6-179; Figures 6-23 and 6-24).\37\ A
Canadian 12-city study (Burnett et al., 2004) is generally consistent
with an earlier Canadian 8-city study (Burnett and Goldberg, 2003).
Both studies reported a positive and statistically significant
association between short-term PM2.5 exposure and mortality
(U.S. EPA, 2009a, p. 6-182, Figure 2-1), although the influence of
nitrogen dioxide (NO2) and limited PM2.5 data for
several years during the study period somewhat diminished the findings
reported in the 12-city study. In addition to these multi-city studies,
evidence from available single-city studies suggests that gaseous
copollutants do not confound the PM2.5-mortality association
(U.S. EPA, 2009a, section <IP_ADDRESS>). Collectively, these studies provide
generally consistent and much stronger evidence for PM2.5-

associated mortality than the evidence available in the last review
(U.S. EPA, 2011a, p. 2-24).
---------------------------------------------------------------------------

    \37\ Single-city Bayes-adjusted effect estimates for the 112
cities analyzed in Zanobetti and Schwartz (2009) were provided by
the study author (personal communication with Dr. Antonella
Zanobetti, 2009; see also U.S. EPA, 2009a, Figure 6-24).
---------------------------------------------------------------------------

    With regard to cardiovascular effects, new multi-city as well as
single-city short-term PM2.5 exposure studies conducted
since the last review support a largely positive and frequently
statistically significant association between short-term exposure to
PM2.5 and cardiovascular-related morbidity and mortality,
substantiating prior findings. For example, among a multi-city cohort
of older adults participating in the Medicare Air Pollution Study
(MCAPS), investigators reported evidence of a positive association
between short-term PM2.5 exposures and hospital admissions
related to cardiovascular outcomes (U.S. EPA, 2009a, pp. 6-57 to 58;
Dominici et al, 2006a; Bell et al, 2008). The strongest evidence for
cardiovascular effects has been observed predominantly for hospital
admissions and emergency department visits for ischemic heart disease
and congestive heart failure, and cardiovascular-related mortality
(U.S. EPA, 2009a, Figure 2-1, p. 6-79, sections <IP_ADDRESS>, <IP_ADDRESS>, and
6.2.11; Bell et al., 2008; Dominici et al., 2006a; Tolbert et al.,
2007; Zanobetti and Schwartz, 2009). In studies that evaluated the
potential for confounding using co-pollutant models, PM2.5
effect estimates for cardiovascular-related hospital admissions and
emergency department visits generally remained positive, with the
magnitude of PM2.5 effect estimates increasing in some
models and decreasing in others (U.S. EPA, 2009a, Figure 6-5).
Furthermore, these findings are supported by a recent study of a multi-
city cohort of women participating in the WHI study that reported a
positive but statistically nonsignificant association between short-
term exposure to PM2.5 and electrocardiogram measures of
myocardial ischemia (Zhang et al., 2009).
    In focusing on respiratory effects, the strongest evidence from
short-term PM2.5 exposure studies has been observed for
respiratory-related emergency department visits and hospital admissions
for chronic obstructive pulmonary disease (COPD) and respiratory
infections (U.S. EPA, 2009a, sections <IP_ADDRESS> and <IP_ADDRESS>; Figures 2-1
and 6-13; Dominici et al., 2006a). In studies that employed co-
pollutant models to evaluate the potential for confounding,
PM2.5 effect estimates for respiratory-related hospital
admissions and emergency department visits generally remained positive,
with the magnitude of PM2.5 effect estimates increasing in
some models and decreasing in others (U.S. EPA, 2009a, Figure 6-15).
Evidence for PM2.5-related respiratory effects has also been
observed in panel studies, which indicate associations with respiratory
symptoms, pulmonary function, and pulmonary inflammation among
asthmatic children (U.S. EPA, 2009a, p. 2-10). Although not
consistently observed, some controlled human exposure studies have
reported small decrements in various measures of pulmonary function
following controlled exposures to PM2.5 (U.S. EPA, 2009a, p.
2-10). Furthermore, the comparatively larger body of toxicological
evidence since the last review is coherent with the evidence from
epidemiological and controlled human exposure studies that examined
short-term exposures to PM2.5 and respiratory effects (U.S.
EPA, 2009a, section <IP_ADDRESS>).
c. Summary
    In considering the extent to which newly available scientific
evidence strengthens or calls into question evidence of associations
identified in the last review between ambient fine particle exposures
and health effects, the Policy Assessment recognizes that much progress
has been made in assessing some key uncertainties related to our
understanding of health effects associated with long- and short-term
exposure to PM2.5. As briefly discussed above as well as in
the more complete discussion of the evidence as presented and assessed
in the Integrated Science Assessment, the Policy Assessment notes that
the newly available information combined with information available in
the last review provides substantially stronger confidence in a causal
relationship between long- and short-term exposures to PM2.5
and mortality and cardiovascular effects. In addition, the newly
available evidence reinforces and expands the evidence supporting a
likely causal relationship between long- and short-term exposure to
PM2.5 and respiratory effects. The body of scientific
evidence is somewhat expanded but is still limited with respect to
associations between long-term PM2.5 exposures and
developmental and reproductive effects as well as cancer, mutagenic,
and genotoxic effects. The Integrated Science Assessment concludes that
these data provide evidence that is suggestive of a causal relationship
for these effects. Thus, the Policy Assessment concludes there is
stronger and more consistent and coherent support for associations
between long- and short-term PM2.5 exposure and a broader
range of health outcomes than was available in the last review,
providing the basis for fine particle standards at least as protective
as the current PM2.5 standards.
2. Limitations and Uncertainties Associated With the Currently
Available Evidence
    With respect to understanding the nature and magnitude of
PM2.5-related risks, the Policy Assessment recognizes that
important uncertainties remain in the current review (U.S. EPA, 2011a,
p. 2-25). Epidemiological studies evaluating health effects associated
with long- and short-term PM2.5 exposures have reported
heterogeneity in responses both within and between cities and
geographic regions within the U.S. In particular, the Policy Assessment
notes that there are challenges with interpreting differences in health
effects observed in the eastern versus western parts of the U.S.,
including evaluating effects stratified by seasons.\38\ This
heterogeneity may be attributed, in part, to differences in the fine
particle composition or related to exposure measurement error.
---------------------------------------------------------------------------

    \38\ Seasonal differences in effects may be related to
PM2.5 composition as well as regional differences in
climate and infrastructure that may affect time spent outdoors or
indoors, housing characteristics including air conditioning usage,
and differences in baseline incidence rates (U.S. EPA, 2009a, p. 3-
182).
---------------------------------------------------------------------------

    In considering the relationships between PM composition and health
effects, the ISA notes that the scientific evidence continues to evolve
and concludes that, while many constituents of PM can be linked with
differing health effects, the evidence is not yet sufficient to allow
differentiation of those constituents or sources that may be more
closely related to specific health outcomes (U.S. EPA, 2009a, p. 2-17).
In particular, based on assessing the body of available evidence, the
ISA notes that (1) cardiovascular effects have been linked with
elemental carbon as well as with PM2.5 from crustal sources,
traffic, and wood smoke/vegetative burning; (2) respiratory effects
have been linked with secondary sulfate PM2.5 as well as
with PM2.5 from crustal/soil/road dust and traffic sources;
and (3) a few studies have reported associations between total
mortality and secondary sulfate/long-range transport, traffic, and
salt. While specific PM2.5 constituents have been linked
with various PM2.5-related health effects in a small number
of studies, research continues to focus on the identification of
specific constituents or sources that may be most closely related to
specific PM2.5-related health outcomes.

    Exposure measurement error is also an important source of
uncertainty (U.S. EPA, 2009a, section 3.8.6). Variability 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, and our limited understanding of factors that may
influence exposures (e.g., topography, the built environment, climate,
source characteristics, ventilation usage, personal activity patterns,
photochemistry). As noted in the Integrated Science Assessment,
exposure measurement error can introduce bias and increased uncertainty
in associated health effect estimates (U.S. EPA, 2009a, p. 2-17).
    In addition, where PM2.5 and other pollutants (e.g.,
ozone, nitrogen dioxide, and carbon monoxide) are correlated, it can be
difficult to distinguish the effects of the various pollutants in the
ambient mixture (i.e., co-pollutant confounding).\39\ As noted above,
although short-term studies of cardiovascular and respiratory hospital
admissions and emergency department visits generally reported that
PM2.5 effect estimates remained positive, the magnitude of
those effect estimates increased in some models and decreased in
others. In addition, although evidence from single-city studies
available in the last review suggests that gaseous copollutants do not
confound the PM2.5-related mortality association (U.S. EPA,
2004, section <IP_ADDRESS>), a conclusion that is supported by studies that
examined the PM10-mortality relationship (U.S. EPA, 2009a,
p. 6-182 and 6-201), many recent U.S. multi-city studies have not
analyzed multipollutant models. While uncertainties and limitations
still remain in the available health effects evidence, the
Administrator judges the currently available scientific data base to be
stronger and more consistent than in previous reviews providing a
strong basis for decision making in this review.
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    \39\ A copollutant meets the criteria for potential confounding
in PM-health associations if: (1) It is a potential risk factor for
the health effect under study; (2) it is correlated with PM; and (3)
it does not act as an intermediate step in the pathway between PM
exposure and the health effect under study (U.S. EPA, 2004, p. 8-
10).
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3. At-Risk Populations
    In identifying population groups or lifestages at greatest risk for
health risk from a specific pollutant, the terms susceptibility,
vulnerability, sensitivity, and at-risk are commonly employed. The
definition for these terms sometimes varies, but in most instances
``susceptibility'' refers to biological or intrinsic factors (e.g.,
lifestage, gender, preexisting disease/conditions) while
``vulnerability'' refers to nonbiological or extrinsic factors (e.g.,
socioeconomic factors). However, factors included in the terms
``susceptibility'' and ``vulnerability'' are intertwined and are
difficult to distinguish. In the Integrated Science Assessment, the
term ``susceptibility'' has been used broadly to recognize populations
that have a greater likelihood of experiencing effects related to
ambient PM exposure\40\, such that use of the term ``susceptible
populations'' in the Integrated Science Assessment is used as a term
that encompasses factors related both to susceptibility and
vulnerability.\41\ In the development of a more recent Integrated
Science Assessment, the Agency is using the term ``at-risk'' groups to
more broadly define the populations with characteristics that increase
the risk of pollutant-related health effects (U.S. EPA, 2011d, p. 8-1).
Therefore, in this proposal, the term ``at-risk'' is the broadly
encompassing term used for groups with specific factors that increase
the risk of PM-related health effects in a population. At-risk
populations could exhibit a greater risk of PM-related health effects
than the general population for a number of reasons including: being
affected by lower concentrations of PM, experiencing a larger health
impact at a given PM concentration or being exposed to higher PM
concentrations than the general population. Given the heterogeneity of
individual responses to PM exposures, the severity of the health
effects experienced by an at-risk population may be much greater than
that experienced by the population at large.
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    \40\ Although studies have primarily used exposures to
PM10 or PM2.5, the available evidence suggests
that the identified factors also increase risk from
PM10-2.5 (U.S. EPA, 2009a, section 8.1.8).
    \41\ The term ``susceptible population'' is defined in the
Integrated Science Assessment as ``[P]opulations that have a greater
likelihood of experiencing health effects related to exposure to an
air pollutant (e.g., PM) due to a variety of factors including, but
not limited to: Genetic or developmental factors, race, gender,
lifestage, lifestyle (e.g., smoking status and nutrition) or
preexisting disease; as well as population-level factors that can
increase an individual's exposure to an air pollutant (e.g., PM)
such as socioeconomic status [SES], which encompasses reduced access
to health care, low educational attainment, residential location,
and other factors (U.S. EPA, 2009a, p. 8-1).
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    As summarized below and presented in more detail in chapter 8 of
the Integrated Science Assessment and section 2.2.1 of the Policy
Assessment, the currently available epidemiological and controlled
human exposure evidence expands our understanding of previously
identified at-risk populations (i.e., children, older adults, and
individuals with pre-existing heart and lung disease) and supports the
identification of additional at-risk populations (e.g., persons with
lower socioeconomic status, genetic differences) (U.S. EPA, 2009a,
section 2.4.1, Table 8-2). In addition, toxicological studies provide
underlying support for the biological mechanisms that potentially lead
to increased susceptibility to PM-related health effects (U.S. EPA,
2009a, sections 2.4.1 and 8.1.8).
    Two different lifestages have been associated with increased risk
to PM-related health effects: childhood (i.e., less than 18 years of
age) and older adulthood (i.e., 65 years of age and older). Childhood
represents a lifestage where susceptibility to PM exposures may be
related to the following observations: children spend more time
outdoors; children have greater activity levels than adults; children
have exposures resulting in higher doses per body weight and lung
surface area; and the developing lung is prone to damage, including
irreversible effects, from environmental pollutants as it continues to
develop through adolescence (U.S. EPA, 2009a, section <IP_ADDRESS>). Older
adults represent a lifestage where susceptibility to PM-associated
health effects may be related to the higher prevalence of pre-existing
cardiovascular and respiratory diseases found in this age group
compared to younger age groups as well as the gradual decline in
physiological processes that occur as part of the aging process (U.S.
EPA, 2009a, section <IP_ADDRESS>). In addition, accumulating evidence
suggests that the developing fetus may also represent an additional
lifestage that is at greater risk to PM exposures (U.S. EPA, 2009a,
sections <IP_ADDRESS> and 7.4).
    With regard to mortality, recent epidemiological studies have
continued to find that older adults are at greater risk of all-cause
(non-accidental) mortality associated with short-term exposure to both
PM2.5 and PM10, providing consistent and stronger
evidence of effects in this at-risk population compared to the last
review (U.S. EPA, 2009a, Figure 7-7, section <IP_ADDRESS>, Zeger et al.,
2008). Evidence is accumulating for PM2.5-related infant
mortality, especially due to respiratory causes during the post-
neonatal period (U.S. EPA, 2009a, sections <IP_ADDRESS> and 7.4).

    With regard to morbidity effects, currently available studies
provide evidence that older adults have heightened responses,
especially for cardiovascular-related effects, and children have
heightened responses for respiratory-related effects (U.S. EPA, 2009a,
p. 2-23). In considering respiratory-related effects in children
associated with long-term PM exposures, the Policy Assessment
recognizes that our understanding of effects on lung development has
been strengthened based on newly available evidence that is consistent
and coherent across different study designs, locations, and research
groups (U.S. EPA, 2011a, p. 2-28). The strongest evidence comes from
the extended follow-up for the Southern California Children's Health
Study which includes several new studies that report positive
associations between long-term exposure to PM2.5 and
respiratory morbidity, particularly for such endpoints as lung function
growth, respiratory symptoms (e.g., bronchitic symptoms), and
respiratory disease incidence (U.S. EPA, 2009a, section 7.3; McConnell
et al, 2003; Gauderman et al., 2004; Islam et al., 2007). These
analyses provide evidence that PM2.5-related effects persist
into early adulthood and are more robust and larger in magnitude than
previously reported. With regard to respiratory effects in children
associated with short-term exposures to PM2.5, currently
available studies provide stronger evidence of respiratory-related
hospitalizations with larger effect estimates observed among children.
In addition, reductions in lung function (i.e., FEV1) and
increases in respiratory symptoms and medication use associated with PM
exposures have been reported among asthmatic children (U.S. EPA, 2009a,
sections 6.3.1, <IP_ADDRESS>, and 8.4.9).
    A number of health conditions have been found to put individuals at
greater risk for adverse effects following exposure to PM. The
currently available evidence confirms and strengthens evidence in the
last review that individuals with underlying cardiovascular and
respiratory diseases are more susceptible to PM exposures (U.S. EPA,
2009a, section 8.1.6; U.S. EPA, 2011a, section 2.2.1). There is also
emerging evidence that people with diabetes, who are at risk for
cardiovascular disease, as well as obese individuals, may have
increased susceptibility to PM exposures (U.S. EPA, 2009a, section
<IP_ADDRESS>). As discussed in section 8.1.6 of the Integrated Science
Assessment, this body of evidence includes findings from
epidemiological and human clinical studies that associations with
mortality or morbidity are greater in those with pre-existing
conditions, and also includes evidence from toxicological studies using
animal models of cardiopulmonary disease.
    Stronger evidence is available in this review than the last
indicating that people from lower socioeconomic strata are an at-risk
population relative to PM exposures (U.S. EPA, 2009a, section 8.1.7;
U.S. EPA, 2011a, section 2.2.1). Persons with lower socioeconomic
status (SES) \42\ have been generally found to have a higher prevalence
of pre-existing diseases; limited access to medical treatment; and
increased nutritional deficiencies, which can increase this
population's risk to PM-related effects.
---------------------------------------------------------------------------

    \42\ Socioeconomic status is a composite measure that usually
consists of economic status, measured by income; social status
measured by education; and work status measured by occupation (U.S.
EPA, 2009a, p. 8-14).
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    Investigation of potential genetic susceptibility has provided
evidence that individuals with specific genetic differences are more
susceptible to PM-related effects (U.S. EPA, 2009a, pp. 8-7 to 8-9).
More research is needed to better understand the relationship between
genetic effects and potential susceptibility to PM-related effects
(U.S. EPA, 2011a, p. 2-109).
    In summary, there are several at-risk populations that may be
especially susceptible or vulnerable to PM-related effects. These
groups include those with preexisting heart and lung diseases, specific
genetic differences, and lower socioeconomic status as well as the
lifestages of childhood and older adulthood. Evidence for PM-related
effects in these at-risk populations has expanded and is stronger than
previously observed. There is emerging, though still limited, evidence
for additional potentially at-risk populations, such as those with
diabetes, people who are obese, pregnant women, and the developing
fetus. The available evidence does not generally allow distinctions to
be drawn between the PM indicators in terms of whether populations are
more at-risk to a particular size fraction (i.e., PM2.5 and
PM10-2.5).
4. Potential PM2.5-Related Impacts on Public Health
    The population potentially affected by PM2.5 is large.
In addition, large subgroups of the U.S. population have been
identified as at-risk populations as described in section III.B.3.
While individual effect estimates from epidemiological studies may be
small in size, the public health impact of the mortality and morbidity
associations can be quite large. In addition, it appears that mortality
risks are not limited to the very frail. Taken together, these results
suggest that exposure to ambient PM2.5 concentrations can
have substantial public health impacts.
    With regard to at-risk populations in the United States,
approximately 7 percent of adults (approximately 16 million adults) and
9 percent of children (approximately 7 million children) have asthma
(U.S. EPA 2009a, Table 8-3; CDC, 2008 \43\). In addition, approximately
4 percent of adults have been diagnosed with chronic bronchitis and
approximately 2 percent with emphysema (U.S. EPA, 2009a, Table 8-3).
Approximately 11 percent of adults have been diagnosed with heart
disease, 6 percent with coronary heart disease, 23 percent with
hypertension, and 8 percent with diabetes (U.S. EPA, 2009a, Table 8-3).
In addition, approximately 3 percent of the U.S. adult population has
suffered a stroke (U.S. EPA, 2009a, Table 8-3). Therefore, large
portions of the United States population are in groups that may be at
increased risk to health effects associated with exposures to ambient
PM2.5. The size of the potentially at-risk population
suggests that exposure to ambient PM2.5 has significant
impact on public health in the United States.
---------------------------------------------------------------------------

    \43\ For percentages, see http://www.cdc.gov/ASTHMA/nhis/06/table4-1.htm. For population estimates, see http://www.cdc.gov/ASTHMA/nhis/06/table3-1.htm.
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C. Quantitative Characterization of Health Risks

1. Overview
    In this review, the quantitative risk assessment builds on the
approach used and lessons learned in the last review and focuses on
improving the characterization of the overall confidence in the risk
estimates, including related uncertainties, by incorporating a number
of enhancements, in terms of both the methods and data used in the
analyses. The goals of this quantitative risk assessment are largely
the same as those articulated in the risk assessment conducted for the
last review. These goals include: (1) To provide estimates of the
potential magnitude of premature mortality and/or selected morbidity
effects in the population associated with recent ambient level of
PM2.5 and with simulating just meeting the current and
alternative suites of PM2.5 standards in 15 selected urban
study areas, including, where data were available, consideration of
impacts on at-risk

populations; (2) to develop a better understanding of the influence of
various inputs and assumptions on the risk estimates to more clearly
differentiate among alternative suites of standards; and (3) to gain
insights into the distribution of risks and patterns of risk reductions
and the variability and uncertainties in those risk estimates. In
addition, the quantitative risk assessment included nationwide
estimates of the potential magnitude of premature mortality associated
with long-term exposure to recent ambient PM2.5
concentrations to more broadly characterize this risk on a national
scale and to support the interpretation of the more detailed risk
estimates generated for selected urban study areas.
    The risk assessment conducted for this review is more fully
described and presented in the Risk Assessment (U.S. EPA, 2010a) and
summarized in detail in the Policy Assessment (U.S. EPA, 2011a,
sections 2.2.2. and <IP_ADDRESS>). The scope and methodology for this risk
assessment were developed over the last few years with considerable
input from CASAC and the public as described in section I.B.3.
2. Summary of Design Aspects
    Based on a review of the evidence presented and assessed in the
Integrated Science Assessment and criteria for selecting specific
health effect endpoints discussed in the Risk Assessment (U.S. EPA,
2010a, section 3.3.1), the following broad categories of health
endpoints were included in the quantitative risk assessment: (1) All-
cause, ischemic heart disease-related, cardiopulmonary-related, and
lung cancer-related mortality associated with long-term
PM2.5 exposure; (2) non-accidental, cardiovascular-related,
and respiratory-related mortality associated with short-term
PM2.5 exposure; and (3) cardiovascular-related and
respiratory-related hospital admissions and asthma-related emergency
department visits associated with short-term PM2.5 exposure.
The evidence available for these selected health effect endpoints
generally focused on the entire population, although some information
was available to support analyses that considered differences in
estimated risk for at-risk populations including older adults and
persons with pre-existing cardiovascular and respiratory diseases (U.S.
EPA, 2010a, p. 3-29). The quantitative risk assessment estimates risks
for various health effects in 15 urban study areas. The selection of
urban study areas was based on a number of criteria including: (1)
Consideration of urban study areas evaluated in the last PM risk
assessment; (2) consideration of locations evaluated in key
epidemiological studies; (3) preference for locations with relatively
elevated annual and/or 24-hour PM2.5 monitored
concentrations; and (4) preference for including locations from
different regions across the country, reflecting potential differences
in PM2.5 sources, composition, and potentially other factors
which might impact PM2.5-related risk (U.S. EPA, 2010a,
section 3.3.2). Based on the results of several analyses examining the
representativeness of these 15 urban study areas in the broader
national context, the Risk Assessment concludes that these study areas
are generally representative of urban areas in the U.S. likely to
experience relatively elevated levels of risk related to ambient
PM2.5 exposure with the potential for better
characterization at the higher end of that distribution (U.S. EPA,
2011a, p. 2-42; U.S. EPA, 2010a, section 4.4, Figure 4-17).\44\
---------------------------------------------------------------------------

    \44\ The representativeness analysis also showed that the 15
urban study areas do not capture areas with the highest baseline
morality risks or the oldest populations (both of which can result
in higher PM2.5-related mortality estimates). However,
some of the areas with the highest values for these attributes have
relatively low PM2.5 concentrations (e.g., urban areas in
Florida) and, consequently, the Risk Assessment concludes failure to
include these areas in the set of urban study areas is unlikely to
exclude high PM2.5-risk locations (U.S. EPA, 2010a,
section 4.4.1).
---------------------------------------------------------------------------

    In order to estimate the incidence of a particular health effect
associated with recent ambient conditions in a specific urban study
area attributable to PM2.5 exposures, as well as the change
in incidence corresponding to a given change in PM2.5
concentrations resulting from simulating just meeting current or
alternative PM2.5 standards, three elements are required
(U.S. EPA, 2010a, section 3.1.1, Figures 3-2 and 3-3). These elements
are: (1) Air quality information (including recent air quality data for
PM2.5 from ambient monitors for the selected location,
estimates of background PM2.5 concentrations appropriate for
that location, and a method for adjusting the recent data to reflect
patterns of air quality estimated to occur when the area just meets a
given set of PM2.5 standards); (2) relative risk-based
concentration-response functions that provide an estimate of the
relationship between the health endpoints of interest and ambient
PM2.5 concentrations; and (3) baseline health effects
incidence rates and population data, which are needed to provide an
estimate of the incidence of health effects in an area before any
changes in PM2.5 air quality.\45\
---------------------------------------------------------------------------

    \45\ Incidence rates express the occurrence of a disease or
event (e.g., death, hospital admission) in a specific period of
time, usually per year. Rates are expressed either as a value per
population group (e.g., the number of cases in Philadelphia County)
or a value per number of people (e.g., the number of cases per
10,000 residents in Philadelphia County), and may be age- and/or
sex-specific. Incidence rates vary among geographic areas due to
differences in populations characteristics (e.g., age distribution)
and factors promoting illness (e.g., smoking rates, air pollution
concentrations). The baseline incidence rate provides an estimate of
the incidence rate (i.e., number of cases of the health effect per
year, usually per 10,000 or 100,000 general population) in the
assessment location unrelated to changes in ambient PM2.5
concentrations in that location (U.S. EPA, 2010a, section 3.4).
---------------------------------------------------------------------------

    The Risk Assessment includes a core set of risk estimates
supplemented by an alternative set of risk results generated using
single-factor and multi-factor sensitivity analyses. The core set of
risk estimates was developed using the combination of modeling elements
and input data sets identified in the Risk Assessment as having higher
confidence relative to inputs used in the sensitivity analyses. The
results of the sensitivity analyses provide information to evaluate and
rank the potential impacts of key sources of uncertainty on the core
risk estimates (U.S. EPA, 2010a, sections 3.5 and 4.3, Table 4-3). In
addition, the sensitivity analyses represent a set of reasonable
alternatives to the core set of risk estimates that fall within an
overall set of plausible risk estimates surrounding the core estimates
(U.S. EPA, 2010a, section 4.3.2).
    Recent air quality was characterized for the 15 urban study areas
based on 24-hour PM2.5 concentrations measured for 3 years
(i.e., 2005, 2006, and 2007) as described in section 3.2.1 of the Risk
Assessment. Different methodologies were then used to simulate
conditions for just meeting the current or alternative PM2.5
standards (U.S. EPA, 2010a, section 3.2.3). This included using the
single rollback approach used in the risk assessment conducted for the
last review which reflects a uniform regional pattern of reductions in
ambient PM2.5 concentrations across monitors (i.e.,
proportional rollback approach). The proportional rollback approach was
used in generating the core risk estimates (U.S. EPA, 2010a, section
<IP_ADDRESS>). In sensitivity analyses, the Risk Assessment also applied two
alternative rollback approaches (i.e., hybrid and locally-focused
rollback approaches)\46\ to better characterize

potential variability in the way air quality in urban areas responds to
programs put in place to meet the current or alternative
PM2.5 standards. In considering the three rollback
approaches collectively, the proportional and locally-focused methods
are approaches that are more likely to represent ``bounding'' scenarios
related to the spatial pattern of future reductions in ambient
PM2.5 concentrations. In contrast, the hybrid approach, in
principle, reflects a more plausible or representative rollback
strategy since it: (1) Reflects consideration for site-specific
information regarding larger PM2.5 sources and their
potential impact on source-oriented monitors and (2) combines elements
of more locally-focused and regionally-focused patterns of reductions
(U.S. EPA, 2010a, section 3.2.3).
---------------------------------------------------------------------------

    \46\ The hybrid rollback approach involves a combination of an
initial step of a more localized reduction in ambient
PM2.5 concentrations at source-oriented monitors followed
by a regional pattern of reduction across all monitors in a study
area (U.S. EPA, 2010a, section <IP_ADDRESS>). The locally-focused
rollback approach involves a focused reduction of concentrations
only at those monitors exceeding the current or alternative 24-hour
standard levels (U.S. EPA, 2010a, section <IP_ADDRESS>).
---------------------------------------------------------------------------

    The peak-to-mean ratio of ambient PM2.5 concentrations
within a study area informs the type of rollback approach used to
simulate just meeting the current or alternative suites of standards to
determine the magnitude of the reduction in annual mean
PM2.5 concentrations for that study area and consequently
the degree of risk reduction.\47\ For example, study areas with
relatively high peak-to-mean ratios are likely to have greater
estimated risk reductions for the current suite of standards (depending
on the combination of 24-hour and annual design values), and such
locations can be especially sensitive to the type of rollback approach
used, with the proportional rollback approach resulting in notably
greater estimated risk reduction compared with the locally-focused
rollback approach. In contrast, study areas with lower peak-to-mean
ratios typically experience greater risk reductions when simulating
just meeting the current or alternative annual-standard level than with
simulating just meeting the current or alternative 24-hour standard
level (again depending on the combination of 24-hour and annual design
values). In addition, the type of rollback approach used will tend to
have less of an impact on the magnitude of risk reductions for study
areas with lower peak-to-mean ratios. Consideration of these two
factors helps to inform an understanding of the nature and pattern of
estimated risk reductions and risk remaining upon simulation of just
meeting the current and alternative suites of standards across the
urban study areas (U.S. EPA, 2010a, section 5.2.1).
---------------------------------------------------------------------------

    \47\ The peak-to-mean ratio of ambient PM2.5
concentrations also has a direct bearing on whether the 24-hour or
annual standard will be the generally controlling standard for a
particular study area, with higher peak-to-mean ratios generally
being associated with locations where the 24-hour standard is likely
the controlling standard.
---------------------------------------------------------------------------

    The concentration-response functions used in the risk assessment
were based on findings from epidemiological studies that have relied on
fixed-site, population-oriented, ambient monitors as a surrogate for
actual ambient PM2.5 exposures. The risk assessment
addresses risks attributable to anthropogenic sources and activities
(i.e., risk associated with concentrations above policy-relevant
background).\48\ This approach of estimating risks in excess of
background was judged to be more relevant to policy decisions regarding
ambient air quality standards than risk estimates that include effects
potentially attributable to PM2.5 concentrations that are
not associated with North American anthropogenic emissions.
---------------------------------------------------------------------------

    \48\ Policy-relevant background estimates used in the risk
assessment model were based on information presented in the
Integrated Science Assessment (U.S. EPA, 2009a, section 3.7, Table
3-23) and discussed in the Risk Assessment (U.S. EPA, 2010a, section
3.2.2). These values were generated based on a combination of
Community Multiscale Air Quality model (CMAQ) and Goddard Earth
Observing System (GEOS)-Chem modeling (U.S. EPA, 2009a, section
<IP_ADDRESS>; U.S. EPA, 2010a, section 3.2.2).
---------------------------------------------------------------------------

    In modeling risk associated with long- and short-term
PM2.5 exposures, the Risk Assessment initially focused on
selecting concentration-response functions from multi-city studies.\49\
Concentration-response functions from two single-city studies provided
coverage for additional health effect endpoints (i.e., emergency
department visits for cardiovascular and/or respiratory effects)
associated with short-term PM2.5 exposures (U.S. EPA, 2010a,
p. 3-37).
---------------------------------------------------------------------------

    \49\ As noted in section 3.3.3 of the Risk Assessment, multi-
city studies have a number of advantages over single-city studies
including: increased statistical power providing effect estimates
with relatively greater precision and reduced problems with
publication bias (i.e., in which studies with statistically
insignificant or negative results are less likely to get published
than those with positive and/or statistically significant results).
---------------------------------------------------------------------------

    With regard to modeling risks associated with long-term
PM2.5 exposure, concentration-response functions used in the
risk model are all based on cohort studies, in which a cohort of
individuals is followed over time. In the core analysis, estimated
premature mortality risk associated with long-term PM2.5
concentrations used concentration-response functions from the extended
ACS study (Krewski et al., 2009). This study had a number of advantages
including: analyses that expanded upon previous publications presenting
evaluations of the ACS long-term cohort study and extending the follow-
up period to eighteen years; a rigorous examination of different model
forms for estimating effect estimates; coverage for a range of
ecological variables (e.g., social, economic, and demographic factors)
which allowed for consideration of whether these factors confound or
modify the relationship between PM2.5 exposure and
mortality; and updated and expanded data sets on incidence and exposure
(U.S. EPA, 2010a, p 2-9 and 3-38).
    As discussed in section III.B.3, persons of lower socioeconomic
status have been identified as an at-risk population. The ACS study
cohort does not provide representative coverage for persons of lower-
socioeconomic status and, thus, the Risk Assessment concludes that
using the concentration-response functions from this study may result
in risk estimates that are biased low (U.S. EPA, 2010a, p. 5-7).
Therefore, concentration-response functions from a reanalysis of the
Harvard Six Cities study (Krewski et al., 2000) were used in a
sensitivity analysis to better support generalizing the results of the
risk assessment across the broader national population.\50\
---------------------------------------------------------------------------

    \50\ As noted in the last review, the ACS study population has
persons generally representative of a higher SES (e.g., higher
educational status) relative to the Harvard Six Cities study
population (12 percent versus 28 percent of the cohort had less than
a high school education, respectively) (U.S. EPA, 2004, p. 8-118).
The Policy Assessment concludes that the Harvard Six Cities study
cohort may provide a more representative sample of the broader
national population than the ACS study cohort (U.S. EPA, 2011a, p.
2-40).
---------------------------------------------------------------------------

    While being mindful that the use of concentration-response
functions from Krewski et al. (2009) introduces potential for low bias
in the core risk estimates, the Policy Assessment also recognizes many
strengths of this study and reasons for its continued use for
generating the core risk estimates, including: consideration of a large
number of metropolitan statistical areas, inclusion of two time periods
for the air quality data which allowed us to consider different
exposure windows, and analysis of a wide range of concentration-
response function models. Therefore, the Risk Assessment concludes that
concentration-response functions obtained from this study had the
greatest overall support and were appropriate to incorporate in the
core risk model (U.S. EPA, 2010a, p. 3-38).

    In the core analysis, for modeling health endpoints associated with
long-term exposure, the Risk Assessment concluded that modeling risks
down to policy-relevant background would require substantial
extrapolation of the estimated concentration-response functions below
the range of the data on which they were estimated (i.e., the lowest
measured levels reported in the epidemiological studies were
substantially above policy-relevant background). Therefore, the Risk
Assessment concluded it was most appropriate in the core analysis to
estimate risk only down to the lowest measured level to avoid
introducing additional uncertainty into the analysis (U.S. EPA, 2010a,
3-1 to 3-3).\51\ A sensitivity analysis comparing the impact of
estimated risks down to policy-relevant background rather than down to
the lowest measured level (U.S. EPA, 2010a, section <IP_ADDRESS>) used
annual estimates of policy-relevant background values for specific
geographic regions (U.S. EPA, 2010a, section 3.2.2, Table 3-2).
---------------------------------------------------------------------------

    \51\ To provide consistency for the different concentration-
response functions selected from the long-term exposure studies,
and, in particular, to avoid the choice of lowest measured levels
unduly influencing the results of the risk assessment, the Risk
Assessment concluded it was appropriate to select a single lowest
measured level--5.8 [mu]g/m\3\ from the later exposure period
evaluated in Krewski et al. (2009)--to use in estimating risks
associated with long-term PM2.5 exposures (U.S. EPA,
2010a, p. 3-3).
---------------------------------------------------------------------------

    With regard to modeling risks associated with short-term
PM2.5 exposure, concentration-response functions from two
time-series studies were selected as the primary studies to support the
core analysis. Concentration-response functions from Zanobetti and
Schwartz (2009) were used in estimating premature non-accidental,
cardiovascular-related, and respiratory-related mortality.
Concentration-response functions from Bell et al. (2008) were used in
estimating cardiovascular-related and respiratory-related hospital
admissions. In addition, concentration-response functions from two
single-city studies were used to estimate emergency department visits
for cardiovascular and/or respiratory illnesses associated with short-
term PM2.5 exposure (Tolbert et al., 2007; Ito et al., 2007;
U.S. EPA, 2010a, p. 3-37).
    For modeling health endpoints associated with short-term
PM2.5 exposure, the Risk Assessment estimates risk down to
policy-relevant background exclusively using quarterly values to
represent the appropriate block of days within a simulated year (U.S.
EPA, 2010a, section 3.2.2, Table 3-2).
    To estimate the change in incidence of a health endpoint associated
with a given change in PM2.5 concentrations, information on
the baseline incidence of that endpoint is needed (U.S. EPA, 2010a,
section 3.4). In calculating a baseline incidence rate to be used with
a concentration-response function from a given epidemiological study,
the Risk Assessment matched the counties, age grouping, and
International Classification of Diseases (ICD) codes used in that study
(U.S. EPA, 2010a, section 3.4.2).
    An important component of a population health risk assessment is
the characterization of both uncertainty and variability.\52\ The
design of the risk assessment includes a number of elements to address
these issues, including using guidance from the World Health
Organization (WHO, 2008) as a framework for developing the approach
used for characterizing uncertainty in the analyses (U.S. EPA, 2010a,
section 3.5).
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    \52\ Variability refers to the heterogeneity of a variable of
interest within a population or across different populations.
Uncertainty refers to the lack of knowledge regarding the actual
values of inputs to an analysis (U.S. EPA, 2010a, p. 3-63).
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    The Risk Assessment considers key sources of variability that can
impact the nature and magnitude of risks associated with simulating
just meeting current and alternative standard levels across the urban
study areas (U.S. EPA, 2010a, section 3.5.2). These sources of
variability include those that contribute to differences in risk across
urban study areas, but do not directly affect the degree of risk
reduction associated with the simulation of just meeting current or
alternative standard levels (e.g., differences in baseline incidence
rates, demographics and population behavior). The Risk Assessment also
focuses on factors that not only introduce variability into risk
estimates across study areas, but also play an important role in
determining the magnitude of risk reductions upon simulation of just
meeting current or alternative standard levels (e.g., peak-to-mean
ratios of ambient PM2.5 concentrations within individual
urban study areas and the nature of the rollback approach used to
simulate just meeting the current or alternative standards). Key
sources of potential variability that are likely to affect population
risks and the degree to which they were (or were not) fully captured in
the design of the risk assessment are discussed in section 3.5.2 of the
Risk Assessment. These sources include: PM2.5 composition;
intra-urban variability in ambient PM2.5 concentrations;
variability in the patterns of reductions in PM2.5
concentrations associated with different rollback approaches when
simulating just meeting the current or alternative standards; co-
pollutant exposures; factors related to demographic and socioeconomic
status; behavioral differences across urban study areas (e.g., time
spent outdoors); baseline incidence rates; and longer-term temporal
variability in ambient PM2.5 concentrations reflecting
meteorological trends as well as future changes in the mix of
PM2.5 sources, including changes in air quality related to
future regulatory actions (U.S. EPA, 2010a, pp. 3-67 to 3-69).
    Single and multi-factor sensitivity analyses were combined with a
qualitative analysis to assess the impact of potential sources of
uncertainty on the core risk estimates (U.S. EPA, 2010a, sections 3.5.3
and 3.5.4). The quantitative sensitivity analyses informed our
understanding of sources of uncertainty that may have a moderate to
large impact on the core risk estimates including: (1) Characterizing
intra-urban population exposure in the context of epidemiology studies
linking PM2.5 to specific health effects; (2) statistical
fit of the concentration-response functions for short-term exposure-
related health endpoints; (3) shape of the concentration-response
functions; (4) specifying the appropriate lag structure for short-term
exposure studies; (5) transferability of concentration-response
functions from study locations to urban study area locations for long-
term exposure-related health endpoints; (6) use of single-city versus
multi-city studies in the derivation of concentration-response
functions; (7) impact of historical air quality on estimates of health
risk associate with long-term PM2.5 exposures; and (8)
potential variation in effect estimates reflecting compositional
differences in PM2.5 (U.S. EPA, 2011a, section 5.1.4). In
addition to identifying sources of uncertainty with a moderate to large
impact on the core risk estimates, the single and multi-element
sensitivity analyses also produced a set of reasonable alternative risk
estimates that allowed us to place the results of the core analysis in
context with regard to uncertainty and potential bias (U.S. EPA, 2010a,
section 5.1.4). The qualitative uncertainty analysis supplemented the
quantitative sensitivity analyses by allowing coverage for sources of
uncertainty that could not be readily included in the sensitivity
analysis (U.S. EPA, 2010a, section 3.5.3).
    With respect to the long-term exposure-related mortality risk

estimates,\53\ the most important sources of uncertainty identified in
the quantitative sensitivity analyses included: selection of
concentration-response functions; modeling risk down to policy-relevant
background versus lowest measured level; and the choice of rollback
approach used to simulate just meeting current or alternative standards
(U.S. EPA, 2011a, p. 2-39). With regard to the qualitative analysis of
uncertainty, the following sources were identified as potentially
having a large impact on the core risk estimates for the long-term
exposure-related mortality: characterization of intra-urban population
exposures; impact of historical air quality; and potential variation in
effect estimates reflecting differences in PM2.5 composition
(U.S. EPA, 2011a, p. 2-39).
---------------------------------------------------------------------------

    \53\ Given increased emphasis placed in this analysis on long-
term exposure-related mortality, the uncertainty analyses completed
for this health endpoint category were more comprehensive than those
conducted for analyses of short-term exposure-related mortality and
morbidity. This reflects, to some extent, limitations in the
epidemiological data available for addressing uncertainty in the
latter categories (U.S. EPA, 2010a, section <IP_ADDRESS>).
---------------------------------------------------------------------------

    Beyond characterizing uncertainty and variability, a number of
design elements were included in the risk assessment to increase the
overall confidence in the risk estimates generated for the 15 urban
study areas (U.S. EPA, 2011a, pp. 2-38 to 2-41). These elements
included: (1) Use of a deliberative process for specifying components
of the risk model that reflects consideration of the latest research on
PM2.5 exposure and risk (U.S. EPA, 2010a, section 5.1.1);
(2) integration of key sources of variability into the design as well
as the interpretation of risk estimates (U.S. EPA, 2010a, section
5.1.2); (3) assessment of the degree to which the urban study areas are
representative of areas in the U.S. experiencing higher
PM2.5-related risk (U.S. EPA, 2010a, section 5.1.3); and (4)
identification and assessment of important sources of uncertainty and
the impact of these uncertainties on the core risk estimates (U.S. EPA,
2010a, section 5.1.4). Two additional analyses examined potential bias
and overall confidence in the risk estimates. The first analysis
explored potential bias in the core risk estimates by considering a set
of alternative reasonable risk estimates generated as part of a
sensitivity analysis. The second analysis compared the annual mean
PM2.5 concentrations associated with simulating just meeting
the current and alternative suites of standards with the air quality
distribution used in deriving the concentration-response functions
applied in modeling mortality risk. Greater confidence is associated
with risk estimates based on simulated annual mean PM2.5
concentrations that are within the region of the air quality
distribution used in deriving the concentration-response functions
where the bulk of the data reside (e.g., within one standard deviation
around the long-term mean PM2.5 concentration) (U.S. EPA,
2011a, p. 2-38).
3. Risk Estimates and Key Observations
    As discussed below, three factors figure prominently in the
interpretation of the risk estimates associated with simulating just
meeting the current and alternative suites of standards, including: (1)
The importance of changes in annual mean PM2.5
concentrations for a specific study area in estimating changes in risks
related to both long- and short-term exposures associated with recent
air quality conditions and air quality simulated to just meet the
current and alternative suites of PM2.5 standards; (2) the
ratio of peak- to-mean ambient PM2.5 concentrations in a
study area; and (3) the spatial pattern of ambient PM2.5
reductions that result from using different approaches to simulate just
meeting the current standard levels (i.e., rollback approaches). The
latter two factors are interrelated and influence the degree of risk
reduction estimated under the current suite of standards.
    The magnitude of both long- and short-term exposure-related risk
estimated to remain upon just meeting the current suite of standards is
strongly associated with the simulated change in annual mean
PM2.5 concentrations. The role of annual mean
PM2.5 concentrations in driving long-term exposure-related
risk estimates is intuitive given that risks are modeled using the
annual mean air quality metric.\54\ The fact that short-term exposure-
related risk estimates are also driven by changes in long-term mean
PM2.5 concentrations is less intuitive, since changes in
mean 24-hour PM2.5 concentrations are used to estimate
changes in risk for this time period.\55\ Analyses show that short-term
exposure-related risks are not primarily driven by the small number of
days with PM2.5 concentrations in the upper tail of the air
quality distribution, but rather by the large number of days with
PM2.5 concentrations at and around the mean of the
distribution (U.S. EPA, 2010a, section <IP_ADDRESS>). Consequently, the
largest part of the estimates of short-term exposure-related risk is
related to the changes in the portion of the distribution of short term
PM2.5 exposures that are well represented by changes in the
annual mean. Therefore, the Policy Assessment focuses on changes in
annual mean PM2.5 concentrations to inform our understanding
of patterns of both long- and short-term exposure-related risk
estimates across the set of urban study areas evaluated in the
quantitative risk assessment (U.S. EPA, 2011a, pp. 2-36 to 2-37).
---------------------------------------------------------------------------

    \54\ As noted in section 3.2.1 of the Risk Assessment (U.S. EPA,
2010a), estimates of long-term exposure-related mortality are
actually based on an annual mean PM2.5 concentration that
is the average across monitors in a study area (i.e., based on the
composite monitor distribution). Therefore, in considering changes
in long-term exposure-related mortality, it is most appropriate to
compare composite monitor estimates generated for a study area under
each alternative suite of standards considered. The annual mean at
the highest reporting monitor (i.e., based on the maximum monitor
distribution) for a study area is the annual design value. The
annual design value is used to determine the percent reduction in
PM2.5 concentrations required to meet a particular
standard. Both types of air quality estimates are provided in Table
3-4 of the Risk Assessment (U.S. EPA, 2010a, pp. 3-25 to 3-27).
    \55\ Estimates of short-term PM2.5 exposure-related
mortality and morbidity are based on composite monitor 24-hour
PM2.5 concentrations. However, similar to the case with
long-term exposure-related mortality, under the current rules, it is
the 98th percentile 24-hour concentration estimated at the maximum
monitor (the 24-hour design value) that will determine the degree of
reduction required to meet a given 24-hour standard level (U.S. EPA,
2011a, p. 2-37).
---------------------------------------------------------------------------

    In estimating PM2.5-related risks likely to remain upon
simulation of just meeting the current annual and 24-hour standards in
the 15 urban study areas, the Risk Assessment focuses on the 13 areas
that would likely not have met the current suite of PM2.5
standards based on recent air quality (2005 to 2007). These 13 areas
have annual and/or 24-hour design values that are above the levels of
the current standards (U.S. EPA, 2010a, Table 3-3).\56\ Based on the
core risk estimates for these areas, using the proportional rollback
approach, the Policy Assessment makes the following key observations
regarding the magnitude of risk remaining upon simulation of just
meeting the current suite of standards:
---------------------------------------------------------------------------

    \56\ Of the 15 urban study areas, only Dallas and Phoenix have
both annual and 24-hour design values below the levels of the
current standards based on 2005-2007 air quality data (U.S. EPA,
2010a, Table 3-3).

    (1) Long-term exposure-related mortality risk estimated to
remain upon just meeting the current standards are significant:
Premature mortality related to ischemic heart disease attributable
to long-term PM2.5 exposure was estimated to range from
less than 100 to approximately 2,000 cases per year across the urban
study areas. The variability in these estimates reflects, to a

great extent, differences in the size of study area populations.
These estimates represent from 4 to 17% of all mortality related to
ischemic heart disease in a given year for the urban study areas
evaluated, representing a measure of risk that takes into account
differences in population size and baseline mortality rates (U.S.
EPA, 2011a, p. 2-43, Table 2-2). These estimates of risk for
mortality related to ischemic heart disease associated with long-
term PM2.5 exposure would likely be in a range of
thousands of deaths per year for the 15 urban study areas \57\ (U.S.
EPA, 2011a, pp. 2-46 to 2-47). Based on these risk estimates for
premature mortality related to ischemic heart disease alone, the
Policy Assessment concludes that risks estimated to remain upon
simulation of just meeting the current suite of standards are
important from a public health standpoint (U.S. EPA, 2011a, p. 2-
47). The Risk Assessment also includes estimated risks for premature
mortality related to cardiopulmonary effects and lung cancer, which
increase the total annual incidence of mortality attributable to
long-term PM2.5 exposure (see U.S. EPA, 2010a, section
4.2.1).
---------------------------------------------------------------------------

    \57\ Premature mortality for all causes attributed to
PM2.5 exposure was estimated to be in a range of tens of
thousands of deaths per year on a national scale based on 2005 air
quality data (U.S. EPA, 2010a, Appendix G, Table G-1).
---------------------------------------------------------------------------

    (2) Short-term exposure-related mortality risk estimated to
remain upon just meeting the current standards are much smaller than
long-term exposure-related mortality risks: Cardiovascular-related
mortality associated with short-term PM2.5 exposure was
estimated to range from less than 10 to 500 cases per year across
the urban study areas. These estimates represent approximately 1 to
2 percent of total cardiovascular-related mortality in a given year
for the urban study areas evaluated (U.S. EPA, 2011a, p. 2-43, Table
2-3). Although long- and short-term exposure-related mortality rates
have similar patterns in terms of the subset of urban study areas
experiencing risk reductions for the current suite of standard
levels, the magnitude of risk remaining is substantially lower, up
to an order of magnitude smaller, for short-term exposure-related
mortality (U.S. EPA, 2011a, p. 2-47).
    (3) Short-term exposure-related morbidity risk estimated to
remain upon just meeting the current standards indicate
hospitalizations are significantly larger for cardiovascular-related
rather than respiratory-related events and emergency department
visits for asthma-related events are significant: Cardiovascular-
related hospitalizations were estimated to range from approximately
10 to 800 cases per year across the study areas, which are less than
1 percent of total cardiovascular-related hospitalizations (U.S.
EPA, 2011a, p. 2-43, Table 2-3). Respiratory-related hospital
admissions attributable to short-term PM2.5 exposure were
significantly smaller than those related to cardiovascular events
(U.S. EPA, 2010a, Tables E-102 and E-111). Cardiovascular- and
respiratory-related hospital admissions together ranged up to
approximately 1,000 admissions per year across the urban study
areas. The estimated incidence of asthma-related emergency
department visits is several times larger than the estimates of
cardiovascular- and respiratory-related hospital admissions (U.S.
EPA, 2011a, p. 2-47; U.S. EPA, 2010a, Tables E-118 to E-123
    (4) Substantial variability exists in the magnitude of risk
remaining across urban study areas: Estimated risks remaining upon
just meeting the current suite of standards vary substantially
across study areas, even when considering risks normalized for
differences in population size and baseline incidence rates. This
variability is a consequence of the substantial differences in the
annual mean PM2.5 concentrations across study areas that
result from simulating just meeting the current standards. This is
important because, as discussed above, annual mean concentrations
are highly correlated with both long- and short-term exposure-
related risk. The variability in annual mean PM2.5
concentrations occurred primarily in those study areas in which the
24-hour standard was the generally controlling standard. In such
areas, the variability in estimated risks across study areas was
largest when regional patterns of reductions in PM2.5
concentrations were simulated, using the proportional rollback
approach, as was done in the core analysis. Less variability was
observed when more localized patterns of PM2.5 reductions
were simulated using the locally-focused rollback approach, as was
done in a sensitivity analysis. When simulations were done using the
locally-focused rollback approach, estimated risks remaining upon
just meeting the current suite of standards were appreciably larger
than those estimated in the core analysis (U.S. EPA, 2011a, p. 2-46;
U.S. EPA, 2010a, section <IP_ADDRESS>).
    (5) Simulation of just meeting the current suite of standards
results in annual mean PM2.5 concentrations well below
the current standard for some study areas: In simulating just
meeting the current suite of standards, the resulting composite
monitor annual mean PM2.5 concentrations ranged from
about 15 [micro]g/m\3\ (for those study areas in which the annual
standard was controlling) down to as low as about 8 [micro]g/m\3\
(for those study areas in which the 24-hour standard was the
generally controlling standard or the annual mean concentration was
well below 15 [micro]g/m\3\ based on recent air quality) (U.S. EPA,
2011a, p. 2-46).

    Reductions in risk associated with simulating air quality to just
meet alternative standard levels were also estimated in this review
(U.S. EPA, 2010a, sections 4.2.2, 5.2.2, and 5.2.3; U.S. EPA, 2011a,
section <IP_ADDRESS>). The estimated percent of risk reductions are depicted
graphically in the Policy Assessment (US 2011a, Figures 2-11 and 2-12),
showing patterns of estimated risk reductions associated with
alternative suites of standards.\58\ These figures also depict the
level of confidence associated with the risk estimates generated for
simulating just meeting the current standards as well as alternative
standard levels considered. As would be expected, patterns of
increasing estimated risk reductions are generally observed as either
the annual or 24-hour standard, or both, are reduced over the ranges
considered in the Risk Assessment. A number of the key observations
regarding the magnitude of risk remaining upon simulation of just
meeting the alternative suites of standards are analogous to the
observations identified above for simulation of just meeting the
current standards (U.S. EPA, 2011a, pp. 2-97 to 2-100).
---------------------------------------------------------------------------

    \58\ Patterns of risk reduction across alternative annual
standard levels, in terms of percent change relative to risk
estimates upon simulating just meeting the current standards, are
similar for all health endpoints modeled (i.e., all-cause, ischemic
heart disease-related, and cardiopulmonary-related mortality). This
similarity reflects the fact that the concentration-response
functions used in the quantitative risk assessment are close to
linear across the range of ambient PM2.5 concentrations
evaluated. However, estimated incidence will vary by health endpoint
(U.S. EPA, 2011a, pp. 2-93 to 2-94, footnote 70).
---------------------------------------------------------------------------

    With regard to characterizing estimates of PM2.5-related
risk associated with simulation of alternative standards, the Policy
Assessment recognizes that greater overall confidence is associated
with estimates of risk reduction than for estimates of absolute risk
remaining (U.S. EPA, 2011a, p. 2-94). Furthermore, the Policy
Assessment recognizes that estimates of absolute risk remaining for
each of the alternative standard levels considered, particularly in the
context of long-term exposure-related mortality, may be underestimated
(U.S. EPA, 2011a, p. 2-97). In addition, the Policy Assessment observes
that in considering the overall confidence associated with the
quantitative analyses, the Risk Assessment recognizes that: (1)
Substantial variability exists in the magnitude of risk remaining
across urban study areas and (2) in general, higher confidence is
associated with risk estimates based on PM2.5 concentrations
near the mean PM2.5 concentrations in the underlying
epidemiological studies providing the concentration-response functions.
    The variability in risk is a consequence of the substantial
differences in the annual mean PM2.5 concentrations across
urban study areas that result from simulating just meeting current or
alternative standards. As PM2.5 concentrations decrease from
the mean PM2.5 concentrations, the Risk Assessment concludes
there is decreasing confidence in the risk estimates (U.S. EPA, 2010a,
p. 5-16). As lower long-term mean PM2.5 concentrations are
simulated (i.e., ambient concentrations further from

recent air quality conditions), the potential variability in such
factors as the spatial pattern of ambient PM2.5 reductions
(i.e., rollback) increases, thereby introducing greater uncertainty
into the simulation of composite monitor annual mean PM2.5
concentrations, and, consequently, in the risk estimates (U.S. EPA,
2010a, Appendix J).
    Based on consideration of the composite monitor annual mean
PM2.5 concentrations involved in estimating long-term
exposure-related mortality, the Risk Assessment has higher confidence
in using those concentrations that generally fall well within the range
of ambient PM2.5 concentrations considered in fitting the
concentration-response functions used (i.e., within one standard
deviation of the mean PM2.5 concentration reported in
Krewski et al. (2009) for 1999-2000) as inputs to the risk model. For
example, with the exception of one urban study area, those areas
estimated to have risk reductions using alternative annual standard
levels of 13 and 14 [micro]g/m\3\ had simulated composite monitor
annual mean concentrations ranging from approximately 10.6 to 13.3
[micro]g/m\3\. With lower alternative annual standard levels of 12
[micro]g/m\3\ and 10 [micro]g/m\3\, the composite monitor annual mean
values ranged from approximately 9.0 to 11.4 [micro]g/m\3\ and 7.6 and
8.9 [micro]g/m\3\, respectively. These concentrations are towards the
lower end of the range of ACS data (in some cases approaching the
lowest measured level) used in fitting the concentration-response
functions, particularly for an annual standard level of 10 [micro]g/
m\3\, and, thus, the Policy Assessment concludes there is less
confidence in the risk estimates associated with these levels compared
with those for the higher alternative annual standard levels considered
(U.S. EPA, 2011a, p. 2-99). Thus, while simulation of risks for an
alternative annual standard level of 10 [micro]g/m\3\ suggests that
additional risk reductions could be expected with alternative annual
standards below 12 [micro]g/m\3\, the Policy Assessment recognizes that
there is potentially greater uncertainty associated with these risk
estimates compared with estimates generated for the higher alternative
annual standard levels considered in the quantitative risk assessment,
since these estimates required simulation of relatively greater
reductions in ambient PM2.5 concentrations (U.S. EPA, 2011a,
p. 2-98).
    The results of simulating alternative suites of PM2.5
standards including a combination of alternative annual and 24-hour
standard levels suggest that an alternative 24-hour standard level can
produce additional estimated risk reductions beyond that provided by an
alternative annual standard alone. However, the degree of estimated
risk reduction provided by the alternative 24-hour standard is highly
variable (U.S. EPA, 2010a, section 4.2.2). Thus, the Risk Assessment
concludes more consistent reductions in estimated risk and consequently
degrees of public health protection are estimated to result from
simulating just meeting the alternative annual standard levels
considered (U.S. EPA, 2010a, pp. 5-15 to 5-16). Furthermore, the Policy
Assessment concludes that the urban study areas with the greatest
degree of estimated reduction associated with simulating just meeting
alternative 24-hour standard levels of 30 and 25 [micro]g/m\3\ also had
the lowest estimated annual mean PM2.5 concentrations, and,
therefore, there was substantially lower confidence in these risk
estimates (U.S. EPA, 2011a, pp. 2-99 to 2-100).
    Based on the consideration of both the qualitative and quantitative
assessments of uncertainty, the Risk Assessment concludes it is
unlikely that the estimated risks are over-stated, particularly for
premature mortality related to long-term PM2.5 exposures. In
fact, the Policy Assessment and Risk Assessment conclude that the core
risk estimates for this category of health effects may well be biased
low based on consideration of alternative model specifications
evaluated in the sensitivity analyses \59\ (U.S. EPA, 2011a, p. 2-41;
U.S. EPA, 2010a, p. 5-16; Figures 4-7 and 4-8). In addition, the Policy
Assessment recognizes that the currently available scientific
information includes evidence for a broader range of health endpoints
and at-risk populations beyond those included in the quantitative risk
assessment, including lung function growth and respiratory symptoms in
children and reproductive and developmental effects (U.S. EPA, 2011a,
section 2.2.1).
---------------------------------------------------------------------------

    \59\ Most of the alternative model specifications supported by
the currently available scientific information produced risk
estimates that are higher (by up to a factor of 2 to 3) than the
core risk estimates (U.S. EPA, 2011a, pp. 2-40 and 2-41).
---------------------------------------------------------------------------

    In considering the set of quantitative risk estimates and related
uncertainties and limitations related to long- and short-term
PM2.5 exposure discussed above together with consideration
of the health endpoints which could not be quantified, the Policy
Assessment concludes this information provides strong evidence that
risks estimated to remain upon simulating just meeting the current
suite of PM2.5 standards are important from a public health
perspective, both in terms of severity and magnitude (U.S. EPA, 2011a,
p. 2-47). Furthermore, while the alternative 24-hour standard levels
considered (when controlling) did result in additional estimated risk
reductions beyond those estimated for alternative annual standards
alone, these additional estimated reductions are highly variable, in
part due to different rollback approaches. Conversely, the Risk
Assessment recognizes that alternative annual standard levels, when
controlling, resulted in more consistent risk reductions across urban
study areas, thereby potentially providing a more consistent degree of
public health protection (U.S. EPA, 2010a, p. 5-17).

D. Conclusions on the Adequacy of the Current Primary PM2.5 Standards

    The initial issue to be addressed in the current review of the
primary PM2.5 standards is whether, in view of the
additional information now available, the existing standards should be
retained or revised. In evaluating whether it is appropriate to retain
or revise the current suite of standards, the Administrator considered
the scientific information from the last review and the broader body of
evidence and information now available. The Administrator has taken
into account both evidence- and risk-based considerations in developing
conclusions on the adequacy of the current primary PM2.5
standards. Evidence-based considerations (section III.D.1) include the
assessment of epidemiological, toxicological, and controlled human
exposure studies evaluating long- or short-term exposures to
PM2.5, with supporting evidence related to dosimetry and
potential pathways/modes of action, as well as the integration of
evidence across each of these disciplines, as assessed in the
Integrated Science Assessment (U.S. EPA, 2009a) and focus on the
policy-relevant considerations as discussed in section III.B above and
in the Policy Assessment (U.S. EPA, 2011a, section 2.2.1). The risk-
based considerations (section III.D.2) draw from the results of the
quantitative analyses presented in the Risk Assessment (U.S. EPA,
2010a) and focus on the policy-relevant considerations as discussed in
section III.C above and in the Policy Assessment (U.S. EPA, 2011a,
section 2.2.2). The advice received from CASAC is discussed in section
III.D.3. Finally, the Administrator's proposed conclusion on the
adequacy of the current PM2.5 primary standards is provided
in section III.D.4.

1. Evidence-Based Considerations in the Policy Assessment
    In light of the health evidence described above, specifically with
regard to factors contributing to greater susceptibility to health
effects associated with ambient PM2.5 exposures, the Policy
Assessment considers the extent to which the currently available
scientific evidence reports associations between fine particle
exposures and health effects that extend to air quality concentrations
that are lower than had previously been observed or that have been
observed in areas that would likely meet the current suite of
PM2.5 standards (U.S. EPA, 2011a, section 2.2.1). As noted
above, the Integrated Science Assessment concludes there is no evidence
to support the existence of a discernible threshold below which effects
would not occur (U.S. EPA, 2009a, section 2.4.3).
a. Associations With Long-term PM2.5 Exposures
    With regard to associations observed in long-term PM2.5
exposure studies, the Policy Assessment recognizes that extended
follow-up analyses of the ACS and Harvard Six Cities studies provide
consistent and stronger evidence of an association with mortality at
lower air quality distributions than had previously been observed (U.S.
EPA, 2011a, pp. 2-31 to 2-32). The original and reanalysis of the ACS
study reported positive and statistically significant effects
associated with a long-term mean PM2.5 concentration of 18.2
[micro]g/m\3\ across 50 metropolitan areas for 1979-1983 (Pope et al.,
1995; Krewski et al., 2000).\60\ In extended analyses, positive and
statistically significant effects of approximately similar magnitude
were associated with declining PM2.5 concentrations, from an
aggregate long-term mean in 58 metropolitan areas of 21.2 [micro]g/m\3\
in the original monitoring period (1979-1983) to 14.0 [micro]g/m\3\ for
116 metropolitan areas in the most recent years evaluated (1999-2000),
with an overall average across the two study periods in 51 metropolitan
areas of 17.7 [micro]g/m\3\ (Pope et al., 2002; Krewski et al., 2009).
With regard to the Harvard Six Cities Study, the original and
reanalysis reported positive and statistically significant effects
associated with a long-term mean PM2.5 concentration of 18.0
[micro]g/m\3\ for 1980-1985 (Dockery et al., 1993; Krewski et al.,
2000). In an extended follow-up of this study, the aggregate long-term
mean concentration across all years evaluated was 16.4 [micro]g/m\3\
for 1980-1988 \61\ (Laden et al., 2006). In an additional analysis of
the extended follow-up of the Harvard Six Cities study, investigators
reported that the concentration-response relationship was linear and
``clearly continuing below the level'' of the current annual standard
(U.S. EPA, 2009a, p. 7-92; Schwartz et al., 2008).
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    \60\ The study periods referred to in the Policy Assessment
(U.S. EPA, 2011a) and in this proposed rule reflect the years of air
quality data that were included in the analyses, whereas the study
periods identified in the Integrated Science Assessment (U.S. EPA,
2009a) reflect the years of health status data that were included.
    \61\ Aggregate mean concentration provided by study author
(personal communication from Dr. Francine Laden, 2009).
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    New cohort studies provide additional evidence of mortality
associated with air quality distributions that are generally lower than
those reported in the ACS and Harvard Six Cities studies, with effect
estimates that were similar or greater in magnitude (U.S. EPA, 2011a,
pp. 2-32 to 2-33). The WHI study reported positive and most often
statistically significant associations between long-term
PM2.5 exposure and cardiovascular-related mortality, with
much larger relative risk estimates than in the ACS and Harvard Six
Cities studies, as well as morbidity effects at an aggregate long-term
mean PM2.5 concentration of 12.9 [mu]g/m\3\ for 2000 (Miller
et al., 2007).\62\ Using the Medicare cohort, Eftim et al. (2008)
reported somewhat higher effect estimates than in the ACS and Harvard
Six Cities studies with aggregate long-term mean concentrations of 13.6
[mu]g/m\3\ and 14.1 [mu]g/m\3\, respectively, for 2000-2002. The MCAPS
reported associations between long-term PM2.5 exposure and
mortality for the eastern region of the U.S. at an aggregated long-term
PM2.5 median concentration of 14.0 [micro]g/m\3\, although
no association was reported for the western region with an aggregate
long-term PM2.5 median concentration of 13.1 [micro]g/m\3\
(U.S. EPA, 2009a, p. 7-88; Zeger et al., 2008).\63\ Premature mortality
in children reported in a national infant mortality study as well as
mortality in a cystic fibrosis cohort including both children and
adults reported positive but statistically nonsignificant effects
associated with long-term aggregate mean concentrations of 14.8 [mu]g/
m\3\ and 13.7 [mu]g/m\3\, respectively (Woodruff et al., 2008; Goss et
al., 2004).
---------------------------------------------------------------------------

    \62\ Miller et al. (2007) studied postmenopausal women without
previous cardiovascular disease in 36 study areas from 1994 to 1998,
with a median follow-up period of six years. The ambient
PM2.5 monitor nearest to a study subject's residence
(within 30 miles or 48 kilometers) was identified and used to assign
long-term mean PM2.5 concentrations to each subject. The
annual average concentration in the year 2000 was the primary
exposure measure because of the substantially increased network of
monitors in that year, as compared with previous years. Miller et
al. (2007) reported a long-term mean PM2.5 concentration
across study areas of 13.5 [mu]g/m\3\. This concentration was
presented in the Integrated Science Assessment (U.S. EPA, 2009a,
Figure 2-2, Table 7-8) and discussed in the second draft Policy
Assessment (U.S. EPA, 2010f, Figure 2-4). In response to a request
from the EPA for additional information on the air quality data used
in selected epidemiological studies (Hassett-Sipple and Stanek,
2009), study investigators provided updated air quality data for the
study period. The updated long-term mean PM2.5
concentration provided by the study authors was 12.9 [mu]g/m\3\
(personal communication from Cynthia Curl, 2009; Stanek et al.,
2010). The EPA notes that this updated long-term mean concentration
matches the composite monitor approach annual mean calculated by
staff for the year of air quality data (i.e., 2000) considered by
the study investigators (Hassett-Sipple et al., 2010, Attachment A,
p. 6). The updated air quality data for the Women's Health
Initiative study was presented and considered in the final Policy
Assessment (U.S. EPA, 2011a, p. 2-32). The Policy Assessment notes
that in comparison to other long-term exposure studies, the WHI
study was more limited in that it was based on only one year of air
quality data (U.S. EPA, 2011a, p. 2-82).
    \63\ Zeger et al. (2008) also reported positive and
statistically significant effects for the central region, with an
aggregate long-term mean PM2.5 concentration of 10.7
[micro]g/m\3\. However, in contrast to the eastern and western risk
estimates, the central risk estimate increased with adjustment for
COPD (used as a proxy for smoking status). Due to the potential for
confounding bias influencing the risk estimate for the central
region, the Policy Assessment did not focus on the results reported
in the central region to inform the adequacy of the current suite of
standards or alternative annual standard levels (U.S. EPA, 2011a, p.
2-32).
---------------------------------------------------------------------------

    With respect to respiratory morbidity effects associated with long-
term PM2.5 exposure, the across-city mean of 2-week average
PM2.5 concentrations reported in the initial Southern
California Children's Health Study was approximately 15.1 [mu]g/m\3\
(Peters et al., 1999). These results were found to be consistent with
results of cross-sectional analyses of the 24-Cities Study (Dockery et
al., 1996; Raizenne et al., 1996), which reported a long-term cross-
city mean PM2.5 concentration of 14.5 [mu]g/m\3\. In this
review, extended analyses of the Southern California Children's Health
Study provide stronger evidence of PM2.5-related respiratory
effects, at lower air quality concentrations than had previously been
reported, with a four-year aggregate mean concentration of 13.8 [mu]g/
m\3\ across the 12 study communities (McConnell et al., 2003; Gauderman
et al., 2004, U.S. EPA, 2009a, Figure 7-4).
    In also considering health effects for which the Integrated Science
Assessment concludes evidence is suggestive of a causal relationship,
the Policy Assessment notes a limited number of birth outcome studies
that reported positive and statistically significant effects related to
aggregate long-term mean PM2.5 concentrations

down to approximately 12 [mu]g/m\3\ (U.S. EPA, 2011a, p. 2-33).
    Collectively, the Policy Assessment concludes that currently
available evidence provides support for associations between long-term
PM2.5 exposure and mortality and morbidity effects that
extend to air quality concentrations that are lower than had previously
been observed, with aggregate long-term mean PM2.5
concentrations extending to well below the level of the current annual
standard. These studies evaluated a broader range of health outcomes in
the general population and in at-risk populations than were considered
in the last review, and include extended follow-up for prospective
epidemiological studies that were important in the last review as well
as additional evidence in important new cohorts.
b. Associations With Short-term PM2.5 Exposures
    In light of the mixed findings reported in single-city, short-term
exposure studies, the Policy Assessment places comparatively greater
weight on the results from multi-city studies in considering the
adequacy of the current suite of standards (U.S. EPA, 2011a, pp. 2-34
to 2-35). With regard to associations reported in short-term
PM2.5 exposure studies, the Policy Assessment recognizes
that long-term mean concentrations reported in new multi-city U.S. and
Canadian studies provide evidence of associations between short-term
PM2.5 exposure and mortality at similar air quality
distributions than had previously been observed in an 8-cities Canadian
study (Burnett and Goldberg, 2003; aggregate long-term mean
PM2.5 concentration of 13.3 [mu]g/m\3\). In a multi-city
time-series analysis of 112 U.S. cities, Zanobetti and Schwartz (2009)
reported a positive and statistically significant association with all-
cause, cardiovascular-related (e.g., heart attacks, stroke), and
respiratory-related mortality and short-term PM2.5 exposure,
in which the aggregate long-term mean PM2.5 concentration
was 13.2 [mu]g/m\3\ (U.S. EPA, 2009a, Figure 6-24). Furthermore, city-
specific effect estimates indicate the association between short-term
exposure to PM2.5 and total mortality and cardiovascular-
and respiratory-related mortality is consistently positive for an
overwhelming majority (99 percent) of the 112 cities across a wide
range of air quality concentrations (long-term mean concentrations
ranging from 6.6 [mu]g/m\3\ to 24.7 [mu]g/m\3\; U.S. EPA, 2009a, Figure
6-24, p. 6-178 to 179). The EPA staff notes that for all-cause
mortality, city-specific effect estimates were statistically
significant for 55 percent of the 112 cities, with long-term city-mean
PM2.5 concentrations ranging from 7.8 [mu]g/m\3\ to 18.7
[mu]g/m\3\ and 24-hour PM2.5 city-mean 98th percentile
concentrations ranging from 18.4 to 64.9 [mu]g/m\3\ (personal
communication with Dr. Antonella Zanobetti, 2009).\64\
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    \64\ Single-city Bayes-adjusted effect estimates for the 112
cities analyzed in Zanobetti and Schwartz (2009) were provided by
the study authors (personal communication with Dr. Antonella
Zanobetti, 2009; see also U.S. EPA, 2009a, Figure 6-24).
---------------------------------------------------------------------------

    With regard to cardiovascular and respiratory morbidity effects, in
the first analysis of the MCAPS cohort conducted by Dominici et al.
(2006a) across 204 U.S. counties, investigators reported a
statistically significant association with hospitalizations for
cardiovascular and respiratory diseases and short-term PM2.5
exposure, in which the aggregate long-term mean PM2.5
concentration was 13.4 [mu]g/m\3\. Furthermore, a sub-analysis
restricted to days with 24-hour average concentrations of
PM2.5 at or below 35 [mu]g/m\3\ indicated that, in spite of
a reduced statistical power from a smaller number of study days,
statistically significant associations were still observed between
short-term exposure to PM2.5 and hospital admissions for
cardiovascular and respiratory diseases (Dominici, 2006b).\65\ In an
extended analysis of the MCAPS study, Bell et al. (2008) reported a
positive and statistically significant increase in cardiovascular
hospitalizations associated with short-term PM2.5 exposure,
in which the aggregate long-term mean PM2.5 concentration
was 12.9 [mu]g/m\3\. These results, along with the observation that
approximately 50 percent of the 204 county-specific mean 98th
percentile PM2.5 concentrations in the study aggregated
across all years were below the 24-hour standard of 35 [mu]g/m\3\, not
only indicate that effects are occurring in areas that would meet the
current standards but also suggest that the overall health effects
observed across the U.S. are not primarily driven by the higher end of
the PM2.5 air quality distribution (Bell, 2009a, personal
communication from Dr. Michelle Bell regarding air quality data for
Bell et al., 2008 and Dominici et al., 2006a).
---------------------------------------------------------------------------

    \65\ This sub-analysis was not included in the original
publication (Dominici et al., 2006a). Authors provided sub-analysis
results for the Administrator's consideration as a letter to the
docket following publication of the proposed rule in January 2006
(personal communication with Dr. Francesca Dominici, 2006b). As
noted in section III.A.3, this study is part of the basis for the
conclusion that there is no evidence suggesting that risks
associated with long-term exposures are likely to be
disproportionately driven by peak 24-hour concentrations.
---------------------------------------------------------------------------

    Collectively, the Policy Assessment concludes that the findings
from short-term PM2.5 exposure studies provide evidence of
PM2.5-associated health effects occurring in areas that
would likely have met the current suite of PM2.5 standards
(U.S. EPA, 2011a, p. 2-35). These findings are further bolstered by
evidence of statistically significant PM2.5-related health
effects occurring in analyses restricted to days in which 24-hour
average PM2.5 concentrations were below 35 [mu]g/m\3\
(Dominici, 2006b).
    In evaluating the currently available scientific evidence, as
summarized in section III.B, the Policy Assessment first concludes that
there is stronger and more consistent and coherent support for
associations between long- and short-term PM2.5 exposures
and a broad range of health outcomes than was available in the last
review, providing the basis for fine particle standards at least as
protective as the current PM2.5 standards (U.S. EPA, 2011a,
p. 2-26). Having reached this initial conclusion, the Policy Assessment
addresses the question of whether the available evidence supports
consideration of standards that are more protective than the current
standards. In so doing, the Policy Assessment considers whether there
is now evidence that health effect associations have been observed in
areas that likely met the current suite of PM2.5 standards.
As discussed above, long- and short-term PM2.5 exposure
studies provide evidence of associations with mortality and
cardiovascular and respiratory effects both at lower ambient
PM2.5 concentrations than had been observed in the previous
review and at concentrations allowed by the current standards (U.S.
EPA, 2011a, p. 2-35).
    In reviewing this information, the Policy Assessment recognizes
that important limitations and uncertainties associated with this
expanded body of scientific evidence, noted above in section III.B.2,
need to be carefully considered in determining the weight to be placed
on the body of studies available in this review. Taking these
limitations and uncertainties into consideration, the Policy Assessment
concludes that the currently available evidence clearly calls into
question whether the current suite of primary PM2.5
standards protects public health with an adequate margin of safety from
effects associated with long- and short-term exposures. Furthermore,
the Policy Assessment concludes this evidence provides strong support
for considering fine particle standards that would afford increased
protection beyond that

afforded by the current standards (U.S. EPA, 2011a, p. 2-35).
2. Summary of Risk-Based Considerations in the Policy Assessment
    In addition to evidence-based consideration, the Policy Assessment
also considers the extent to which health risks estimated to occur upon
simulating just meeting the current PM2.5 standards may be
judged to be important from a public health perspective, taking into
account key uncertainties associated with the quantitative health risk
estimates. In so doing, the Policy Assessment first notes that the
quantitative risk assessment addresses: (1) The core PM2.5-
related risk estimates; (2) the related uncertainty and sensitivity
analyses, including additional sets of reasonable risk estimates
generated to supplement the core analysis; (3) an assessment of the
representativeness of the urban study areas within a national context;
\66\ and (4) consideration of patterns in design values and air quality
monitoring data to inform interpretation of the risk estimates, as
discussed in section III.C above.
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    \66\ Based on analyses of the representativeness of the 15 urban
study areas in the broader national context, the Policy Assessment
concludes that these study areas are generally representative of
urban areas in the U.S. likely to experience relatively elevated
levels of risk related to ambient PM2.5 exposures (U.S.
EPA, 2011a, p. 2-42).
---------------------------------------------------------------------------

    In considering the health risks estimated to remain upon simulation
of just meeting the current suite of standards and considering both the
qualitative and quantitative assessment of uncertainty completed as
part of the assessment, the Policy Assessment concludes these risks are
important from a public health standpoint (U.S. EPA, 2011a, p. 2-47).
This conclusion reflects consideration of both the severity and the
magnitude of the effects. For example, the risk assessment indicates
the possibility that premature deaths related to ischemic heart disease
associated with long-term PM2.5 exposure alone would likely
be on the order of thousands of deaths per year in the 15 urban study
areas upon simulating just meeting the current standards \67\ (U.S.
EPA, 2011a, pp. 2-46 to 2-47). Moreover, additional risks are
anticipated for premature mortality related to cardiopulmonary effects
and lung cancer associated with long-term PM2.5 exposure as
well as mortality and cardiovascular- and respiratory-related morbidity
effects (e.g., hospital admissions, emergency department visits)
associated with short-term PM2.5 exposures. Based on the
consideration of both qualitative and quantitative assessments of
uncertainty completed as part of the quantitative risk assessment, the
Risk Assessment concludes that it is unlikely that the estimated risks
are over-stated, particularly for mortality related to long-term
PM2.5 exposure, and may well be biased low based on
consideration of alternative model specifications evaluated in the
sensitivity analyses (U.S. EPA, 2010a, p. 5-16; U.S. EPA, 2011a, p. 2-
41). Furthermore, the currently available scientific information
summarized in section III.B above provides evidence for a broader range
of health endpoints and at-risk populations beyond those included in
the quantitative risk assessment (U.S. EPA, 2011a, p. 2-47).
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    \67\ Premature mortality for all causes attributed to
PM2.5 exposure was estimated to be on the order of tens
of thousands of deaths per year on a national scale based on 2005
air quality data (U.S. EPA, 2010a, Appendix G, Table G-1).
---------------------------------------------------------------------------

    In considering the risks estimated to occur upon simulating just
meeting the current PM2.5 standards, the Policy Assessment
concludes that these estimated risks can reasonably be judged to be
important from a public health perspective and provide strong support
for consideration of alternative standards that would provide increased
protection beyond that afforded by the current PM2.5
standards (U.S. EPA, 2011a, p. 2-48).
3. CASAC Advice
    CASAC, based on their review of drafts of the Integrated Science
Assessment, the Risk Assessment, and the Policy Assessment, has
provided an array of advice both with regard to interpreting the
scientific evidence and quantitative risk assessment, as well as with
regard to consideration of the adequacy of the current PM2.5
standards (Samet, 2009a b,c,d,e,f; Samet 2010a,b,c,d). With regard to
the adequacy of the current standards, CASAC concluded that the
``currently available information clearly calls into question the
adequacy of the current standards'' (Samet, 2010d, p. i) and that the
current standards are ``not protective'' (Samet, 2010d, p. 1). Further,
in commenting on the first draft Policy Assessment, CASAC noted:

    With regard to the integration of evidence-based and risk-based
considerations, CASAC concurs with EPA's conclusion that the new
data strengthens the evidence available on associations previously
considered in the last round of the assessment of the
PM2.5 standard. CASAC also agrees that there are
significant public health consequences at the current levels of the
standard that justify consideration of lowering the PM2.5
NAAQS further (Samet, 2010c, p.12).
4. Administrator's Proposed Conclusions Concerning the Adequacy of the
Current Primary PM2.5 Standards
    In considering the adequacy of the current suite of
PM2.5 standards, the Administrator has considered the large
body of evidence presented and assessed in the Integrated Science
Assessment (U.S. EPA, 2009a), the staff conclusions and associated
rationales presented in the Policy Assessment, views expressed by
CASAC, and public comments. In particular, the Administrator recognizes
that the Integrated Science Assessment concludes that the results of
epidemiological and experimental studies form a plausible and coherent
data set that supports a causal relationship between long- and short-
term PM2.5 exposures and mortality and cardiovascular
effects, and a likely causal relationship between long- and short-term
PM2.5 exposures and respiratory effects. Moreover, the
Administrator reflects that these effects have been observed at lower
ambient PM2.5 concentrations than what had been observed in
the last review, including at ambient PM2.5 concentrations
in areas that likely met the current PM2.5 NAAQS. See
American Trucking Associations v. EPA, 283 F. 3d at 369, 376 (revision
of level of existing standards justified when effects are observed in
areas that meet those standards). With regard to the results of the
quantitative risk assessment, the Administrator notes that the Risk
Assessment concludes that the risks estimated to remain upon simulation
of just meeting the current standards are important from a public
health standpoint in terms of both the severity and magnitude of the
effects.
    Based on her consideration of these conclusions, as well as
consideration of CASAC's conclusion that the evidence and risk
assessment clearly call into question the adequacy of the public health
protection provided by the current PM2.5 NAAQS, the
Administrator provisionally concludes that the current primary
PM2.5 standards, taken together, are not requisite to
protect public health with an adequate margin of safety and that
revision is needed to provide increased public health protection. The
Administrator provisionally concludes that the scientific evidence and
information on risk provide strong support for consideration of
alternative standards that would provide increased public health