morbidity that could not be included in the risk assessment (e.g.,
school absences, increased medication use, emergency department visits)
and which primarily affect members of at-risk groups. Moreover, the
Administrator noted that the CASAC Panel supported a qualitative
consideration of the much broader array of O3-related health
endpoints, and specifically referred to respiratory emergency
department visits in asthmatics and people with other lung diseases,
increased medication use, and increased respiratory symptoms reported
at exposure levels well below the current standard.
    The Administrator expressed the view in the proposal that the
exposure and risk estimates discussed in the Staff Paper and summarized
above are important from a public health perspective and indicative of
potential exposures and risks to at-risk groups. In reaching this
proposed judgment, the Administrator considered the following factors:
(1) The estimates of numbers of persons exposed at and above the 0.070
ppm benchmark level; (2) the risk estimates of the proportion of the
population and number of occurrences of various health effects in areas
upon just meeting the current standard; (3) the year-to-year and city-
to-city variability in both the exposure and risk estimates; (4) the
uncertainties in these estimates; and (5) recognition that there is a
broader array of O3-related adverse health outcomes for
which risk estimates could not be quantified (that are part of a
broader ``pyramid of effects'') and that the scope of the assessment
was limited to just a sample of urban areas and to some but not all at-
risk populations, leading to an incomplete estimation of public health
impacts associated with O3 exposures across the country. The
Administrator also noted that it was the unanimous conclusion of the
CASAC Panel that there is no scientific justification for retaining the
current primary O3 standard, that the current standard is
not sufficiently health-protective with an adequate margin of safety,
and that the standard needs to be substantially reduced to protect
human health, particularly in at-risk subpopulations.
    Based on all of these considerations, the Administrator proposed
that the current O3 standard is not requisite to protect
public health with an adequate margin of safety because it does not
provide sufficient protection and that revision would result in
increased public health protection, especially for members of at-risk
groups.
2. Comments on the Need for Revision
    The above section outlines the health effects evidence and
assessments used by the Administrator to inform his proposed judgments
about the adequacy of the current O3 primary standard.
General comments received on the proposal that either supported or
opposed the proposed decision to revise the current O3
primary standard are addressed in this section. Comments on the health
effects evidence, which includes evidence from controlled human
exposure and epidemiological studies, are considered in section
II.B.2.a below. Comments on human exposure and health risk assessments
are considered in section II.B.2.b, and comments on other policy-
related issues are considered in section II.B.2.c, below. Comments on
specific issues, health effects evidence, or the human exposure and
health risk assessments that relate to consideration of the appropriate
averaging time, form, or level of the O3 standard are
addressed below in sections II.C.3 and II.C.4. General comments based
on implementation-related factors that are not a permissible basis for
considering the need to revise the current standard are noted in the
Response to Comments document.
a. Consideration of Health Effects Evidence
    With regard to the need to revise the current primary O3
standard, sharply divergent comments were received from two general
sets of commenters. Many public comments received on the proposal
asserted that the current O3 standard is insufficient to
protect public health, especially the health of sensitive groups, with
an adequate margin of safety and revisions to the standard are
appropriate. Among those calling for revisions to the current primary
standard were medical groups, including for example, the American
Medical Association (AMA), the American Thoracic Society (ATS), the
American Academy of Pediatrics (AAP), and the American College of Chest
Physicians (ACCP), as well as medical doctors and academic researchers.
For example, the ATS stated:

    We believe that the Administrator has correctly stated that,
beyond any degree of scientific uncertainty, convincing and
compelling evidence has demonstrated that exposure to ozone at
levels below the current standard is responsible for measurable and
significant adverse health effects, both in terms of morbidity and
mortality. * * * The known respiratory, cardiac and perinatal
effects of ozone pollution are each in their own right major public
health issues. In combination they provide immediate, actionable
information and require a meaningful public health policy response
from the EPA. [ATS et al. pp. 1, 11]

    Similar conclusions were also reached in comments by many national,
State, and local public health organizations, including, for example,
the American Lung Association (ALA) in a joint set of comments with
several environmental groups, the American Heart Association (AHA), the
American Nurses Association (ANA), the American Public Health
Association (APHA), and the National Association of County and City
Health Officials (NACCHO), as well as in letters to the Administrator
from EPA's advisory panel on children's environmental health
(Children's Health Protection Advisory Committee; Marty et al., 2007a,
2007b). Environmental groups also commented in support of revising the
standard, including the Sierra Club, Environmental Defense, the Natural
Resources Defense Council (NRDC), Earthjustice, and the U.S. Public
Interest Research Group (US PIRG). All of these medical, environmental
and public health commenters stated that the current O3
standard needs to be revised and that an even more protective standard
than proposed by EPA is needed to protect the health of sensitive
population

groups. Many individual commenters also expressed such views.
    The majority of State and local air pollution control authorities
who commented on the O3 standard supported revision of the
current O3 standard, as did the National Tribal Air
Association (NTAA). Environmental agencies that supported revising the
standard include agencies from: Arkansas; California; Delaware; Iowa;
Illinois; Michigan; North Carolina; New Mexico; New York; Oklahoma;
Oregon; Pennsylvania; Utah; Wisconsin; and Washington, DC. State
organizations, including the National Association of Clean Air Agencies
(NACAA), Northeast States for Coordinated Air Use Management (NESCAUM),
and the Ozone Transport Commission (OTC) urged that EPA revise the
O3 standard. All of these commenters supported revisions to
the current standard, with most supporting a standard consistent with
CASAC's recommendations.
    In general, the commenters noted above primarily based their views
on the body of evidence assessed in the Criteria Document, finding it
to be stronger and more compelling than in the last review. Some
specifically agreed with the weight of evidence approach taken by the
Criteria Document. These commenters generally placed much weight on
CASAC's interpretation of the body of available evidence and the
results of EPA's exposure and risk assessments, both of which formed
the basis for CASAC's recommendation to revise the O3
standard to provide increased public health protection.

    In recent years, a broad scientific consensus has emerged that
EPA's current air quality standards for ozone are not sufficient to
protect public health, and that the levels and form must be greatly
tightened. This consensus is evidenced by the by the strong
unanimous comments of the CASAC, which was backed by the endorsement
of over 100 leading independent air quality scientists, EPA's
Children's Health Protection Advisory Committee, and many others. In
the face of this strong consensus, it is untenable to cite
``uncertainty'' as a rationale for failing to propose tighter
standards. [ALA et al., p. 15]

Medical and public health commenters also expressed the view that EPA
must not use uncertainty in the scientific evidence as justification
for retaining the current O3 standard.
    EPA generally agrees with these commenters' conclusion regarding
the need to revise the current primary O3 standard. The
scientific evidence-related health effects to O3 exposure
noted by these commenters was generally the same as that assessed in
the Criteria Document and the proposal. EPA agrees that this
information provides a basis for concluding that the current
O3 standard is not adequately protective of public health.
For reasons discussed below in sections II.C.3 and II.C.4, however, EPA
disagrees with aspects of these commenters' views on the level of
protection that is appropriate and supported by the available
scientific information.
    Another group of commenters representing industry associations and
businesses opposed revising the current primary O3 standard.
These views were extensively presented in comments from the Utility Air
Regulatory Group (UARG), representing a group of electric generating
companies and organizations and several national trade associations,
and in comments from other industry and business associations
including, for example: Exxon Mobil Corporation; the Alliance of
Automobile Manufacturers (AAM); the National Association of
Manufacturers (NAM), the American Petroleum Institute (API). The API
sponsored a workshop at the University of Rochester in June 2007 to
review the scientific information and health risk assessment considered
by EPA during the review of the O3 NAAQS. Although the
report (hereafter, ``Rochester Report'') from this workshop does not
offer judgments on the specific elements of the current or proposed
standard, it has been cited in a number of public comments that opposed
revision of the current 8-hour standard. The Annapolis Center for
Science-Based Public Policy issued a report (hereafter, ``Annapolis
Center'') on the science and health effects of O3, which
explicitly opposed revising the current O3 primary standard.
Several State environmental agencies also opposed revising the current
O3 primary standard, including agencies from: Georgia;
Indiana; Kentucky; Louisiana; Nevada; and Texas.
    As discussed more fully below in sections dealing with specific
comments, these and other commenters in this group generally mentioned
many of the same studies from the body of evidence in the Criteria
Document that were cited by the commenters who supported revising the
standards, but highlighted different aspects of these studies in
reaching substantially different conclusions about their strength and
the extent to which progress has been made in reducing uncertainties in
the evidence since the last review. They then considered whether the
evidence that has become available since the last review has
established a more certain risk or a risk of effects that is
significantly different in character from those that provided a basis
for the current standards, or whether the evidence demonstrates that
the risk to public health upon attainment of the current standards
would be greater than was understood when EPA established the current
O3 standard in 1997. These commenters generally expressed
the view that the current standard provides the requisite degree of
public health protection.
    In supporting their view that the present primary O3
standard continues to provide the requisite public health protection
and should not be revised, UARG and others generally stated: That the
effects of concern have not changed significantly since 1997; that the
uncertainties in the underlying health science are as great or greater
than in 1997; that the estimated number of exposures of concern and
health risks upon attainment of the current O3 standard has
not changed or decreased since 1997; and that ``new'' studies not
included in the Criteria Document continue to demonstrate uncertainties
about possible health risks associated with exposure to O3
at levels below the current standard. As noted above, EPA disagrees
with this general assessment, and agrees with the general position that
the available information provides a basis for concluding that the
current O3 standard is not adequately protective of public
health. The rationale for this position is discussed more fully in the
responses to specific comments that are presented below.
    More specific comments on the evidence and EPA's responses are
discussed below. Section II.B.2.a.i contains comments on evidence from
controlled human exposure studies; section II.B.2.a.ii contains
comments on evidence from epidemiological studies, including
interpretation of the evidence and specific methodological issues.
Comments on evidence pertaining to at-risk subgroups for O3-
related effects can be found in section II.B.2.a.iii below. EPA notes
here that most of the issues and concerns raised by commenters
concerning the health effects evidence, including both the
interpretation of the evidence and specific technical or methodological
issues, were essentially restatements of issues raised during the
review of the Criteria Document and the Staff Paper. Most of these
issues were highlighted and thoroughly discussed during the review of
these documents by the CASAC. More detailed responses related to the
interpretation of the health effects evidence and its role in the
decision on the O3 NAAQS are contained in the Response to
Comments document.

i. Evidence from Controlled Human Exposure Studies
    As noted in the overview of health effects evidence, section II.A.2
above, two new controlled human-exposure studies (Adams 2002, 2006) are
now available that examine respiratory effects associated with
prolonged O3 exposures at levels at and below 0.080 ppm,
which was the lowest exposure level that had been examined in the last
review. One group of commenters that included national medical (e.g.,
ATS, AMA, ACCP) and national environmental and public health
organizations (e.g., ALA in a joint set of comments with Environmental
Defense, Sierra Club), agreed with EPA's reanalysis of the Adams' data
while disagreeing with EPA's characterization of the evidence from the
Adams studies as ``very limited'' (72 FR 37870). These commenters
expressed the view that the Adams studies provide evidence of effects
at lower concentrations than had previously been reported. They noted
that Adams, while finding small group mean changes at 0.060 ppm,
reported total subjective symptom scores reached statistical
significance (relative to pre-exposure) at 5.6 and 6.6 hours, with the
triangular exposure scenario, and that pain on deep inspiration values
followed a similar pattern to total subjective symptoms scores. In
addition, Adams (2002) reports that ``some sensitive subjects
experience notable effects at 0.060 ppm,'' based on a greater than 10%
reduction in FEV1. These commenters made the point that the
responses of individuals are more important than group mean responses
and that when the Adams (2002, 2006) study data are corrected for the
effects of exercise in clean air, 7 percent of subjects experience
FEV1 decrements greater than 10% at the 0.040 and 0.060 ppm
exposure levels. They expressed the view that while 2 of 30 tested
subjects responding at the 0.060 ppm level may seem like a small
number, a 7 percent response rate is far from trivial. Seven percent of
the U.S. population is 21.2 million people (ALA et al., p. 51). Noting
that the subjects in the Adams' studies were all healthy adults, these
groups expressed concern that ``in some vulnerable populations the
magnitude of the response would be greater and the exposure level at
which responses are observed to occur would be lower'' (ATS, p. 4).
    These commenters generally supported EPA's reanalysis of the Adams'
data, stating that EPA has undertaken a careful reanalysis of the
underlying data in the Adams studies to assess the change in
FEV1 following exposure to 0.060 ppm O3 and
filtered air, and concluding that ``the reanalysis employs the standard
approach used by other researchers, and supported by CASAC'' (ALA et
al., p. 49), and ``we believe that the Adams study shows significant
health effects at 0.06 ppm exposure levels'' (ATS, p. 5). The American
Thoracic Society, AMA and other medical organizations conclude:

    The Adams study confirms our understanding that in healthy
populations, an important fraction of the population will experience
larger-than-average decrements in FEV1 when exposed to
low levels of ozone. It is reasonable to assume that these effects
would be even greater when extrapolated to other populations known
to have sensitivities to ozone (children, asthmatics, COPD
patients). We feel the correct conclusion to draw from the Adams
study is that there is a significant fraction of the population that
will express significant responses to low levels of ozone. [ATS, p.
5]

    EPA generally agrees with most of the comments summarized above,
while placing more emphasis on the limited nature of the evidence
addressing O3-related lung function and respiratory symptom
responses at the 0.060 and 0.040 ppm exposure levels. As characterized
in the proposal notice, EPA's reanalysis of the data from the most
recent Adams study shows small group mean decrements in lung function
responses to be statistically significant at the 0.060 ppm exposure
level, while acknowledging that the author's analysis did not yield
statistically significant lung function responses. The Adams studies
report a small percentage of subjects experiencing lung function
decrements ([gteqt]10 percent) at the 0.060 ppm exposure level. EPA
disagrees with these commenters that the percent of subjects that
experienced FEV1 decrements greater than 10% in this study
of 30 subjects can appropriately be generalized to the U.S. population.
The Administrator concludes that these studies provide very limited
evidence of O3-related lung function decrements and
respiratory symptoms at this lower exposure level.
    The second group of commenters, who opposed revision of the
standard, raised many concerns about the role of the Adams studies and
EPA's reanalysis of the Adams data in the decision. With regard to the
results reported by Adams, these commenters expressed the view that the
group mean FEV1 decrement measured at 0.060 ppm was small,
less than 3%, which is within the 3 to 5% range of normal measurement
variability for an individual (UARG, p. 12). Moreover even the reported
group mean FEV1 decrements in Adams subjects when exposed to
an O3 concentration of 0.080 ppm were described as quite
minimal, likely non-detectable by the subjects and within the range
that the EPA would consider to be normal or mild (UARG, p. 13); With
respect to the larger decrements in FEV1 ([gteqt] 10%)
experienced by some subjects in the Adams studies, these commenters
stated the view that such decrements would not be considered adverse in
healthy individuals, and that ``reliance on the individual responses of
such a miniscule number of subjects (2 of 30) is woefully inadequate as
any basis for a nationwide O3 standard'' (UARG, p.14). Some
of these commenters put the results of the Adams studies (2002, 2006)
in the context of the 1997 decision on the O3 standard to
reach the conclusion that there is no basis for revising that standard.
They stated that the data from Adams (2002, 2006) on O3
levels below 0.080 ppm was too limited to support a revised standard,
and noted that responses reported in the Adams studies at 0.080 ppm
were similar to responses reported previously (Horstmann et al., 1990
and McDonnell et al., 1991), and therefore, provided no new information
on O3 that was not known at the time of EPA's last review
(Exxon Mobil, pp. 5-6).
    These commenters raised one or more of the following concerns about
EPA's reanalysis of the Adams data: (1) EPA's re-analysis was not
published or peer-reviewed, and therefore neither the scientific
community nor the public was afforded opportunity to appropriately
review the analysis (Exxon Mobil, p. 6); (2) EPA has misinterpreted the
studies of Dr. Adams, and over his objections used a different
analytical methodology to reach a different conclusion; (3) EPA's
reanalysis did not employ an appropriate statistical test; the ANOVA
statistical test employed by Adams was preferred over the statistical
test used in EPA's reanalysis (paired t-test); and (4) the reanalysis
of the Adams data is evidence that EPA interpreted and presented
scientific information in a systematically biased manner, reflecting
purposeful bias because the reanalysis supported staff policy
recommendations and Adams' own analysis did not, and the 10% decrement
in FEV1 was a post-hoc threshold chosen for compatibility
with EPA staff policy recommendations (NAM, p. 19).
    First, EPA agrees that the group mean lung function decrement
observed in the Adams study at the 0.060 ppm exposure level is
relatively small. However, EPA and the CASAC Panel observed that the
study showed some individuals experienced lung function decrements >=
10 percent, which is the most

important finding from this study in terms of public health
implications. The magnitude of changes in the group mean do not address
whether a subset of the population is at risk of health effects. The
clinical evidence to date makes it clear that there is significant
variability in responses across individuals, so it is important to look
beyond group mean to the response of subsets of the group to evaluate
the potential impact for sensitive or susceptible parts of the
population. The Administrator also agrees with both EPA staff and
CASAC's views that this level of response may not represent an adverse
health effect in healthy individuals but does represent a level that
should be considered adverse for asthmatic individuals.
    Second, EPA notes that its reanalysis of the Adams (2006) study was
prepared in response to the issues and analysis raised by a public
commenter who made a presentation to the CASAC Panel at its March 5,
2007 teleconference. EPA replicated the analysis and addressed issues
raised in these public comments concerning the statistical significance
of 0.060 ppm O3 exposure on lung function response in the Adams (2006)
publication. EPA documented its response in a technical memorandum
(Brown, 2007), which was placed in the rulemaking docket prior to
publication of the proposal. EPA has clearly stated that the additional
statistical analyses conducted by both the public commenter and by EPA
staff do not contradict or undercut the statistical analysis presented
by Dr. Adams in his published study, as EPA and the author were
addressing different questions. While the author of the original study
was focused on determining whether the changes observed on an hour-by-
hour basis were statistically significant for different exposure
protocols, EPA's reanalysis was focused on the different question of
whether there was a statistically significant difference in lung
function decrement before and after the entire 6.6 hour exposure period
between the 0.060 ppm exposure protocol and filtered air.
    Third, with respect to the concerns raised by Dr. Adams and other
commenters that EPA had used an inappropriate statistical approach to
address the question regarding statistical significance of the average
lung function response at 0.060 ppm, members of the CASAC Panel noted
on the March 5, 2007 teleconference the very conservative nature of the
approach used by Adams to evaluate the research questions posed by the
author. These same CASAC Panel members also supported the use of the
statistical approach (i.e., paired-t test) used in the analysis
prepared by the public commenter, which was the same approach later
used in EPA's reanalysis, as the preferred method for analyzing the
pre-minus post-exposure lung function responses reported in this study.
EPA agrees with the characterization of the Adams (2006) study in the
Rochester Report, which stated, ``Although these findings have not been
confirmed or replicated, the responses to 0.06 ppm ozone in this
[Adams] study are consistent with the presence of an exposure-response
curve with responses that do not end abruptly below 0.08 ppm.'' This
same report also concluded,

    The statistical test used in Adams (2006) did not identify the
response of the 0.06 ppm exposure as statistically different from
that of the filtered air exposure. However, alternative statistical
tests suggest that the observed small group mean response in
FEV1 induced by exposure to 0.06 ppm compared to filtered
air is not the result of chance alone. [Rochester Report, p. 56].

    Fourth, EPA rejects the contention that the conduct and
presentation of its reanalysis of the Adams (2006) study to address
issues raised by public commenters represents purposeful bias and was
developed only to support a pre-determined policy position. As
discussed above, EPA's reanalysis addressed a different question than
the author's analysis contained in the publication. Other controlled
human exposure studies had routinely examined the same question EPA's
reanalysis addressed, whether or not there was a statistically
significant group mean response for the entire exposure period compared
to filtered air.
ii Evidence from Epidemiological Studies
    This section contains major comments on EPA's assessment of
epidemiological studies in the proposal and the Agency's general
responses to those comments. Many of the issues discussed below are
addressed in more detail in the Response to Comments document. Comments
on EPA's interpretation and assessment of the body of epidemiological
evidence are discussed first and then comments on methodological issues
and particular study designs are discussed. EPA notes here that most of
the issues and concerns raised by commenters on the interpretation of
the epidemiological evidence and methodological issues are essentially
restatements of issues raised during the review of the Criteria
Document and Staff Paper. EPA presented and the CASAC Panel reviewed
the interpretation of the epidemiological evidence in the Criteria
Document and the integration of the evidence with policy considerations
in the development of the policy options presented in the Staff Paper
for consideration by the Administrator. CASAC reviewed both the O3
Criteria Document and O3 Staff Paper and approved of the scientific
content and accuracy of both documents. The CASAC chairman sent to the
Administrator one letter (Henderson, 2006a) for the O3 Criteria
Document and another letter for the O3 Staff Paper (Henderson, 2006c)
indicating that these documents provided an appropriate basis for use
in regulatory decision making regarding the O3 NAAQS.
    As with evidence from controlled human exposure studies, sharply
divergent comments were received on the evidence from epidemiological
studies, including EPA's interpretation of the evidence. One group of
commenters from medical, public health and environmental organizations,
in general, supported EPA's interpretation of the epidemiological
evidence (72 FR 37838, section II.a.3.a-c) with regard to whether the
evidence for associations is consistent and coherent and whether there
is biological plausibility for judging whether exposure to O3 is
causally related to respiratory and cardiovascular morbidity and
mortality effects. Comments of public health and environmental groups,
including a joint set of comments from ALA and several environmental
groups, note that more than 250 new epidemiological studies, published
from 1996 to 2005, were included in the Criteria Document and point to
a figure from the Staff Paper and proposal (72 FR 37842, Figure 1) of
short-term O3 exposures and respiratory health outcome showing
consistency in an array of positive effects estimates and health
endpoints observed in multiple locations in Canada and the U.S. Medical
commenters, including ATS and AMA, stated that these ``real world''
studies support the findings of chamber studies to show adverse
respiratory health effects at levels below the current 8-hour O3
standard. These commenters generally expressed agreement with the
weight of evidence approach taken by the Criteria Document and the
conclusions reached, which were reviewed by CASAC, that the effects of
O3 on respiratory symptoms, lung function changes, emergency department
visits for respiratory and cardiovascular effects, and hospital
admissions can be considered causal.
    EPA generally agrees with this interpretation of the
epidemiological evidence. The Criteria Document concludes that positive
and robust

associations were found between ambient O3 concentrations and various
respiratory disease hospitalization outcomes and emergency department
visits for asthma, when focusing particularly on results of warm-season
analyses. These positive and robust associations are supported by the
human clinical, animal toxicological, and epidemiological evidence for
lung function decrements, increased respiratory symptoms, airway
inflammation, and increased airway responsiveness. Taken together, the
overall evidence supports a causal relationship between acute ambient
O3 exposures and increased respiratory morbidity outcomes resulting in
increased emergency department visits and hospitalizations during the
warm season (EPA, 2006a, p. 8-77).
    However, in contrast with EPA, these commenters from ALA and other
environmental, medical and public health groups asserted that the
causal associations extend down to the lowest ambient O3 concentrations
reported in these studies. These commenters also expressed the view
that the respiratory and cardiovascular system effects are well-
supported by the Hill criteria\19\ of judging causality: strength of
association, consistency between studies, coherence among studies, and
biological plausibility (ALA et al., pp. 51-52). They also noted that
recent studies provide compelling evidence that exposure to O3 results
in adverse cardiovascular health effects (ATS, p. 6-7).
---------------------------------------------------------------------------

    \19\ The Hill criteria, published by Sir Bradford Hill (1965),
are commonly used criteria for reaching judgments about causality
from observed associations, and these criteria were the basis for
the critical assessment of the epidemiological evidence presented in
the Criteria Document (pp. 7-3-7-4).
---------------------------------------------------------------------------

    EPA disagrees with the assertion of these commenters that the
causal associations extend down to the lowest ambient O3 concentrations
reported in these studies. The biological plausibility of the
epidemiological associations is generally supported by controlled human
exposure and toxicological evidence of respiratory morbidity effects
for levels at and below 0.080 ppm, but that biological plausibility
becomes increasingly uncertain at much lower levels. Further, at much
lower levels, it becomes increasingly uncertain as to whether the
reported associations are related to O3 alone rather than to the
broader mix of air pollutants present in the ambient air. With regard
to cardiovascular health outcomes, the Criteria Document concludes that
the generally limited body of evidence from animal toxicology, human
controlled exposure, and epidemiologic studies is suggestive that O3
can directly and/or indirectly contribute to cardiovascular-related
morbidity, and that for cardiovascular mortality the Criteria Document
suggests that effects estimates are more consistently positive and
statistically significant in warm season analyses but that additional
research is needed to more fully establish the underlying mechanisms by
which such mortality effects occur (EPA, 2006a, pp. 8-77-78).
    The second group of commenters, mostly representing industry
associations and some businesses opposed to revising the primary O3
standard, disagreed with EPA's interpretation of the epidemiological
evidence. These commenters expressed the view that while many new
epidemiological studies have been published since the current primary
O3 standard was promulgated, the inconsistencies and uncertainties
inherent in these studies as a whole should preclude any reliance on
them as justification for a more stringent primary O3 NAAQS. They
contend that the purported consistency is the result of inappropriate
selectivity in focusing on specific studies and specific results within
those studies (UARG, p. 15). With regard to daily mortality, the
proposal emphasizes the multi-city studies, suggesting that they have
the statistical power to allow the authors to reliably distinguish even
weak relationships from the null hypothesis with statistical
confidence. However, these commenters note that these studies are not
consistent, with regard to the findings concerning individual cities
analyzed in the multi-city analyses. One commenter asserted that each
of the multi-city studies and meta-analyses cited by EPA involves
cities for which the city-specific estimates of O3 effects have been
observed to vary over a wide range that includes negative [i.e.,
beneficial] effects (API, p. 15). To illustrate this point, many
commenters point to EPA's use of the study by Bell et al., 2004. They
note that in focusing on the national estimate from Bell of the
association between 24-hour average O3 levels and daily mortality, the
Administrator overlooks the very significant and heterogeneous
information of the individual analyses of the 95 cities used to produce
the national estimate and, based on this inconsistency, question
whether what is being seen is actually an O3 mortality association at
all (UARG, p. 16).
    EPA has accurately characterized the inconsistencies and
uncertainties in the epidemiological evidence and strongly denies that
it has inappropriately focused on specific positive studies or specific
positive results within those studies. EPA's assessment of the health
effects evidence in the Criteria Document has been reviewed by the
CASAC Panel. EPA has appropriately characterized the heterogeneity in
O3 health effects in assessing the results of the single-city and
multi-city studies and the meta-analyses, as discussed in section 7.6.6
of the Criteria Document. In general, in the proposal, the
Administrator recognized that in the body of epidemiological evidence,
many studies reported positive and statistically significant
associations, while others reported positive results that were not
statistically significant, and a few did not report any positive O3-
related associations. In addition, the Administrator judged that
evidence of a causal relationship between adverse health outcomes and
O3 exposures became increasingly uncertain at lower levels of exposure.
    More specifically, the Bell et al. (2004) study observed a
statistically significant, positive association between short-term O3
concentrations (24-hour average) and all-cause mortality using data
from 95 U.S. National Morbidity, Mortality, and Air Pollution Study
(NMMAPS) communities. The objective of the NMMAPS was to develop an
overall national effect estimate using multi-city time-series analyses,
by drawing on information from all of the individual cities. The
strength of this approach is the use of a uniform analytic methodology,
avoidance of selection bias, and larger statistical power. Significant
intercity heterogeneity was noted in the Bell et al. and other multi-
city studies, probably due to many factors, including city-specific
differences in pollution characteristics, the use of air conditioning,
time spent indoors versus outdoors, and socioeconomic factors. Levy et
al. (2005) found suggestive evidence that air conditioning prevalence
was a predictor of heterogeneity in O3 risk estimates in their meta-
analysis.
    Several commenters argued that EPA overstates the probability of
causal links between health effects and exposure to O3, especially at
the lower concentrations examined, and that the statistical
associations found in the cited epidemiological studies do not
automatically imply that a causal relationship exists. These commenters
expressed the view that the correlation between health effects and O3
exposure must be rigorously evaluated according to a standard set of
criteria before concluding that there is a causal link and that EPA
fails to articulate and

follow the weight of the evidence or established causality criteria for
evaluating epidemiological studies in drawing conclusion regarding
causality (Exxon Mobil, pp. 10-11).
    In the proposal, EPA explicitly stated that epidemiological studies
are not themselves direct evidence of a causal link between exposure to
O3 and the occurrence of effects (72 FR 37879). Throughout the O3
review, a standard set of criteria have been used to evaluate evidence
of a causal link. The critical assessment of epidemiological evidence
presented in the Criteria Document was conceptually based upon
consideration of salient aspects of the evidence of associations so as
to reach fundamental judgments as to the likely causal significance of
the observed associations in accordance with the Hill criteria
(Criteria Document, pp. 7-3--7-4). Moreover, consistent with the
proposal the Administrator has specifically considered evidence from
epidemiological studies in the context of all the other available
evidence in evaluating the degree of certainty that O3-related adverse
health effects occur at various levels at and below 0.080 ppm,
including the strong evidence from controlled human exposure studies
and the toxicological studies that demonstrate biological plausibility
and mechanisms for effects. More detailed discussion of the criteria
used to evaluate evidence with regard to judgments about causality can
be found in the Response to Comments document.
    Several commenters made the point that the results of the new
epidemiological studies included in this review are not coherent. They
state that although EPA notes that estimates of risk from
cardiovascular mortality are higher than those for total mortality and
indicates that these findings are highly suggestive that short-term O3
exposure directly or indirectly contributes to cardiovascular
mortality, the Agency fails to contrast the mortality studies to
studies of hospital admissions for cardiovascular causes. Most studies
of cardiovascular causes have not found statistically significant
associations with O3 exposures (UARG, pp. 16-17).
    EPA strongly disagrees that it has failed to appropriately
characterize the association between O3 exposure and potential
cardiovascular morbidity and mortality effects. As noted above, the
Criteria Document characterizes the overall body of evidence as
limited, but highly suggestive, and concludes that much needs to be
done to more fully integrate links between ambient O3 exposures and
adverse cardiovascular outcomes (EPA, 2006a, p. 8-77). Some field/panel
studies that examined associations between O3 and various cardiac
physiologic endpoints have yielded limited epidemiological evidence
suggestive of a potential association between acute O3 exposure and
altered HRV, ventricular arrhythmias, and incidence of myocardial
infarction (Criteria Document, section 7.2.7). In addition, there were
approximately 20 single-city studies of emergency department visits and
hospital admissions for all cardiovascular diseases or specific
diseases (i.e., myocardial infarction, congestive heart failure,
ischemic heart disease, dysrhythmias). In the studies using all year
data, many showed positive results but few were statistically
significant. Given the strong seasonal variations in O3 concentrations
and the changing relationship between O3 and other copollutants by
season, inadequate adjustment for seasonal effects might have masked or
underestimated the associations. In the limited number of studies that
analyzed data by season (6 studies), statistically significant
associations were observed in all but one study (Criteria Document,
section 7.3.4). Newly available animal toxicology data provide some
plausibility for the observed associations between O3 and
cardiovascular outcomes. EPA believes that its characterization of the
evidence for O3-related cardiovascular system effects is appropriate.
It is clear that coherence is stronger in the much larger body of
evidence of O3-related respiratory morbidity and mortality effects.
    Many commenters who did not support revising the current O3 primary
standard also submitted comments on specific methodological issues
related to the epidemiological evidence, including: The adequacy of
exposure data; confounding by copollutants; model selection; evidence
of mortality; and, new studies not included in the Criteria Document.
Some of the major comments on methodological issues raised by these
commenters are discussed below. The Response to Comments document
contains more detailed responses to many of these comments, as well as
responses to other comments not considered here.
    (1) Adequacy of exposure data. Many commenters expressed concern
about the adequacy of exposure data both for time-series and panel
studies. These commenters argued that almost all of the epidemiological
studies on which EPA relies in recommending a more stringent O3
standard are based on data from ambient monitors for which there is a
poor correlation with the actual personal exposure subjects receive
during their daily activities. They questioned the Administrator's
conclusion that in the absence of available data on personal O3
exposure, the use of routinely monitored ambient O3 concentrations as a
surrogate for personal exposures is not generally expected to change
the principal conclusions from epidemiological studies. These
commenters also note that, in its June 2006 letter, the CASAC Panel
raised the issue of exposure error, concluding that it called into
question whether observed associations could be attributed to O3 alone
(API, p. 17). One of these commenters cited studies (e.g., Sarnat et
al., 2001; Sarnat et al., 2005) that show a lack of correlation between
personal exposures and ambient concentrations (NAM, p. 22). Another
cited studies (Sarnat et al., 2001, 2005, and 2006; and Koutrakis et
al., 2005) that have found that the ability of ambient gas monitors to
represent personal exposure to such gases is similarly quite limited,
including: (1) Most personal exposures are so low as to be not
detectable at a level of 5 parts per billion (ppb), resulting in very
low correlation between concentrations reported from central ambient
monitors and personal monitors; (2) O3 measurements from ambient
monitors are a better surrogate for personal exposure to
PM2.5 than to O3; and (3) populations expected to be
potentially susceptible to O3, including children, the elderly, and
those with COPD, are at the low end of the population exposure
distribution (Exxon Mobil, pp. 15-16). These commenters contended that
without such a correlation there is no legitimate way for EPA to
conclude that O3 exposure has caused the reported health effects, or to
conclude that use of routinely monitored ambient O3 concentrations as a
surrogate for personal exposures is adequate. Some of these commenters
also contended that EPA incorrectly concludes that the exposure error
in epidemiological studies results in an underestimate of risk (Exxon
Mobil, p. 20).
    With regard to the views on exposure measurement error expressed by
CASAC, while the commenter is correct that the CASAC Panel raised the
question of exposure error and whether observed associations could be
attributed to O3 alone, the commenter failed to note that CASAC's
comment was focused on the association between O3 and mortality, at
very low O3 concentrations and in the group of people most susceptible
to premature mortality. The CASAC Panel in its June 2006 letter stated:

    The population that would be expected to be potentially
susceptible to dying from exposure to ozone is likely to have ozone
exposures that are at the lower end of the ozone population
distribution, in which case the population would be exposed to very
low ozone concentrations, and especially so in winter. Therefore it
seems unlikely that the observed associations between short-term
ozone concentrations and daily mortality are due solely to ozone
itself. [Henderson 2006b, pp. 3-4]

    This section of the quote, which was not addressed in the comment
submitted by API, together with the conclusions in the final CASAC
letter (Henderson, 2007), leads EPA to conclude that contrary to the
commenters' assertion, the CASAC Panel was not calling into question
the association between O3 exposure and the full range of
morbidity effects found in panel or time-series studies that rely on
ambient monitoring data as a surrogate for personal exposure data. It
is important to note that EPA agrees that the evidence is only highly
suggestive that O3 directly or indirectly contributes to
mortality, as compared to the stronger evidence of causality for
respiratory morbidity effects.
    EPA agrees that exposure measurement error may result from the use
of stationary ambient monitors as an indicator of personal exposure in
population studies. There is a full discussion of measurement error and
its effect on the estimates of relative risk in section <IP_ADDRESS> of the
Criteria Document. However, the possibility of measurement error does
not preclude the use of ambient monitoring data as a surrogate for
personal exposure data in time-series or panel studies. It simply means
that in some situations where the likelihood of measurement error is
greatest, effects estimates must be evaluated carefully and that
caution must be used in interpreting the results from these studies.
Throughout this review, EPA has recognized this concern. The Criteria
Document states that there is supportive evidence that ambient
O3 concentrations from central monitors may serve as valid
surrogate measures for mean personal O3 exposures
experienced by the population, which is of most relevance to time-
series studies, in which individual variations in factors affecting
exposure tend to average out across the study population. This is
especially true for respiratory hospital admission studies for which
much of the response is attributable to O3 effects on
asthmatics. In children, for whom asthma is more prevalent than for
adults, ambient monitors are more likely to correlate reasonably well
with personal exposure to O3 of ambient origin because
children tend to spend more time outdoors than adults in the warm
season. EPA does not agree that the correlation between personal
exposure and ambient monitoring data is necessarily poor, especially in
children. Moreover, the CASAC Panel supported this view as they noted
that ``[p]ersonal exposures most likely correlate better with central
site values for those subpopulations that spend a good deal of time
outdoors, which coincides, for example, with children actively engaged
in outdoor activities, and which happens to be a group that the ozone
risk assessment focuses upon.'' (Henderson, 2006c. p. 10). However, the
Criteria Document notes that there is some concern in considering
certain mortality and hospitalization time-series studies regarding the
extent to which ambient O3 concentrations are representative
of personal O3 exposures in another particularly susceptible
group of individuals, the debilitated elderly, as the correlation
between the two measurements has not been examined in this population.
A better understanding of the relationship between ambient
concentrations and personal exposures, as well as of the factors that
affect the relationship, will improve the interpretation of observed
associations between ambient concentration and population health
response.
    With regard to the specific comments that reference the findings of
studies by Sarnat et al. (2001, 2005, 2006) and Koutrakis et al.
(2005), the fact that personal exposure monitors cannot detect
O3 levels of 5 ppb and below may in part explain why there
was a poor correlation between personal exposure measurements and
ambient monitoring data in the winter relative to the correlation in
the warm season, along with differences in activity patterns and
building ventilation. In one study conducted in Baltimore, Sarnat et
al. (2001) observed that ambient O3 concentrations showed
stronger associations with personal exposure to PM2.5 than
to O3; however, in a later study conducted in Boston (Sarnat
et al., 2005), ambient O3 concentrations and personal
O3 exposures were found to be significantly associated in
the summer. Another study cited by the commenter, but not included in
the Criteria Document, conducted in Steubenville (Sarnat et al., 2006),
also observed significant associations between ambient O3
concentrations and personal O3. The authors noted that the
city-specific discrepancy in the results may be attributable to
differences in ventilation. Though the studies by Sarnat et al. (2001,
2005, and 2006) included senior citizens, the study selection criteria
required them to be nonsmoking and physically healthy. EPA is not
relying on studies that are not in the Criteria Document, such as
Sarnat et al. (2006), to refute the commenters. However, EPA notes that
Sarnat et al. (2006) does not support the conclusion drawn by the
commenters that this study shows very limited associations between
ambient O3 concentrations and personal exposures.
    Existing epidemiologic models may not fully take into consideration
all the biologically relevant exposure history or reflect the
complexities of all the underlying biological processes. Using ambient
concentrations to determine exposure generally overestimates true
personal O3 exposures (by approximately 2- to 4-fold in the
various studies described in the Criteria Document, section 3.9), which
assuming the relationship is causal, would result in biased
descriptions of underlying concentration-response relationships (i.e.,
in attenuated effect estimates). From this perspective, the implication
is that the effects being estimated in relationship to ambient levels
occur at fairly low personal exposures and the potency of O3
is greater than these effect estimates indicate. On the other hand, as
very few studies evaluating O3 health effects with personal
O3 exposure measurements exist in the literature, effect
estimates determined from ambient O3 concentrations must be
evaluated and used with caution to assess the health risks of
O3 (Criteria Document, pp. 7-8 to 7-10). Nonetheless, as
noted in section II.C.3 of the proposal, the use of routinely monitored
ambient O3 concentrations as a surrogate for personal
exposures is not generally expected to change the principal conclusions
from O3 epidemiologic studies. Therefore, population risk
estimates derived using ambient O3 concentrations from
currently available observational studies, with appropriate caveats
about personal exposure considerations, remain useful (72 FR 37839).
    (2) Confounding by copollutants. Many commenters argued that known
confounders are inadequately controlled in the epidemiological studies
of O3 and various health outcomes and that the health
effects of O3 are often not statistically significant when
epidemiological studies consider the effects of confounding air
pollutants (e.g., PM2.5, CO, nitrogen dioxide
(NO2) in multi-pollutant models. For example, Mortimer et
al. (2002), a large multi-city asthma panel study, found that when

other pollutants, i.e., sulfur dioxide (SO2),
NO2, and particles with an aerodynamic diameter less than or
equal to a nominal 10 micrometers (PM10), were placed in a
multi-pollutant model with O3, the O3-related
associations with respiratory symptoms and lung function became non-
significant.
    The National Cooperative Inner-City Asthma Study (Mortimer et al.,
2002) evaluated air pollution health effects in 846 asthmatic children
in 8 urban areas. The pollutants evaluated included O3,
PM10, SO2, and NO2. Three effects were
evaluated: (1) Daily percent change in lung function, measured as peak
expiratory flow rate (PEFR); (2) incidence of (>= 10% reduction in lung
function (PEFR); and, (3) incidence of symptoms (i.e., cough, chest
tightness, and wheeze). EPA notes that in this study, O3 was
the only pollutant associated with reduction in lung function. Nitrogen
dioxide had the strongest effect on morning symptoms, and the authors
concluded it ``* * * may be a better marker for the summer-pollutant
mix in these cities'' but had no association with morning lung
function. In a two-pollutant model with NO2, the
O3 effect on morning symptoms remained relatively unchanged.
Sulfur dioxide had statistically significant effects on morning
symptoms but no association with morning lung function. Particulate
matter (PM10), which was measured daily in 3 cities, had no
statistically significant effect on morning lung function. In a two-
pollutant model with O3, the PM10 estimate for
morning symptoms was slightly reduced and there was a larger reduction
in the O3 estimate, which remained positive but not
statistically significant. A more general discussion and response to
this issue concerning confounding by copollutants is presented in the
Response to Comments document.
    (3) Model selection. Commenters who did not support revision of the
primary O3 standard raised issues regarding the adequacy of
model specification including control of temporal and weather variables
in the time-series epidemiological studies that EPA has claimed support
the finding of O3-related morbidity and mortality health
outcomes. Specifically, concerns were expressed regarding the following
issues: (i) Commenters noted that recent meta-analyses have confirmed
the important effects of model selection in the results of the time-
series studies, including the choice of models to address weather and
the degree of smoothing, in direct contradiction of the Staff Paper's
conclusion on the robustness of the models used in the O3
time-series studies (Exxon Mobil, p. 41); (ii) commenters contended
that there were no criteria for how confounders such as temperature or
other factors were to be addressed, resulting in arbitrary model
selection potentially impacting the resulting effect estimates; and
(iii) commenters expressed the view that to appropriately address
concerns about model selection in the O3 time-series
studies, EPA should rely on an alternative statistical approach,
Bayesian model averaging, that incorporates a range of models
addressing confounding variables, pollutants, and lags rather than a
single model.
    In response to the first issue, EPA agrees that the results of the
meta-analyses do support the conclusion that there are important
effects of model selection and that, for example, alternative models to
address weather might make a difference of a factor of two in the
effect estimates. However, as noted in the Criteria Document, one of
the meta-analyses (Ito et al., 2005) suggested that the stringent
weather model used in the Bell et al. (2004) NMMAPS study may tend to
yield smaller effect estimates than those used in other studies
(Criteria Document, p. 7-96), and, thus concerns about appropriate
choice of models could result in either higher or lower effect
estimates than reported. In addressing this issue, the Criteria
Document concluded,

    Considering the wide variability in possible study designs and
statistical model specification choices, the reported O3
risk estimates for the various health outcomes are in reasonably
good agreement. In the case of O3-mortality time-series
studies, combinations of choices in model specifications * * * alone
may explain the extent of difference in O3 risk estimates
across studies. (Criteria Document, p. 7-174)

    Second, the issues surrounding sensitivity to model specifications
were thoroughly discussed in the Criteria Document (see section
<IP_ADDRESS>) and evaluated in some of the meta-analyses reviewed in the
Criteria Document and Staff Paper. As stated in the Criteria Document,
O3 effect estimates ``were generally more sensitive to
alternative weather models than to varying degrees of freedom for
temporal trend adjustment'' (Criteria Document, p. 7-176). The Criteria
Document also concluded that ``although there is some concern regarding
the use of multipollutant models * * * results generally suggest that
the inclusion of copollutants into the models do not substantially
affect O3 risk estimates'' and the results of the time-
series studies are ``robust and independent of the effects of other
copollutants'' (Criteria Document, p. 7-177). Overall, EPA continues to
believe that based on its integrated assessment, the time-series
studies provide strong support for concluding there are O3-
related morbidity effects, including respiratory-related hospital
admissions and emergency department visits during the warm season, and
that the time-series studies provide findings that are highly
suggestive that short-term O3 exposure directly or
indirectly contributes to non-accidental and cardiorespiratory-related
mortality.
    The Administrator acknowledges that uncertainties concerning
appropriate model selection are an important source of uncertainty
affecting the specific risk estimates included in EPA's risk assessment
and that these quantitative risk estimates must be used with
appropriate caution, keeping in mind these important uncertainties, as
discussed above in section II.A.3. As discussed later in this notice,
the Administrator is not relying on any specific quantitative effect
estimates from the time-series studies or any risk estimates based on
the time-series studies in reaching his judgment about the need to
revise the current 8-hour O3 standard.
    Third, in response to commenters who suggested that EPA adopt an
alternative statistical approach, i.e., Bayesian model averaging, to
address concerns about potential arbitrary selection of models, the
Criteria Document evaluated the strengths and weaknesses of such
methods in the context of air pollution epidemiology. The Criteria
Document noted several limitations, especially where there are many
interaction terms and meteorological variables and where variables are
highly correlated, as is the case for air pollution studies, which
makes it very difficult to interpret the results using this alternative
approach. EPA believes further research is needed to address concerns
about model selection and to develop appropriate methods addressing
these concerns.
    (4) Evidence of mortality. Many commenters, including those that
argued for revising the current O3 standard as well as those
that argued against revisions, focused on the new evidence from multi-
city time-series analyses and meta-analyses linking O3
exposure with mortality. Again, the comments were highly polarized. One
set of commenters, including medical, public health, and environmental
organizations argued that recent published research has provided more
robust, consistent evidence linking O3 to cardiovascular and
respiratory

mortality. The ATS, AMA, and others stated that data from single-city
studies, multiple-city studies, and meta-analyses show a consistent
relationship between O3 exposure and mortality from
respiratory and cardiovascular causes. These commenters noted that this
effect was observed after controlling for co-pollutants and seasonal
impacts. These commenters stated that research has demonstrated that
exposure to O3 pollution is causing premature deaths, and
has also provided clues on the possible mechanisms that lead to
premature mortality (ATS, p. 4). These commenters noted that people may
die from O3 exposure even when the concentrations are well
below the current standard. They pointed to a study (Bell et al., 2006)
in which the authors followed up on their 2004 multi-city study to
estimate the exposure-response curve for O3 and the risk of
mortality and to evaluate whether a threshold exists below which there
is no effect. The authors applied several statistical models to data on
air pollution, weather, and mortality for 98 U.S. urban communities for
the period 1987 to 2000. The study reported that O3 and
mortality results did not appear to be confounded by temperature or PM
and showed that any threshold, if it existed, would have to be at very
low concentrations, far below the current standard (ALA et al., p. 74).
Another approach also indicated that the mortality effect is unlikely
to be confounded by temperature. A case-crossover study (Schwartz 2005)
of over one million deaths in 14 U.S. cities, designed to control for
the effect of temperature on daily deaths attributable to
O3, found that the association between O3 and
mortality risk reported in the multi-city studies is unlikely to be due
to confounding by temperature (ALA et al., p. 76). These commenters
argue that meta-analyses also provide compelling evidence that the
O3-mortality findings are consistent. They point to three
independent analyses conducted by separate research groups at Johns
Hopkins University, Harvard University and New York University, using
their own methods and study criteria, which reported a remarkably
consistent link between daily O3 levels and total mortality.
    In response, EPA notes that the Criteria Document states that the
results from the U.S. multi-city time-series studies provide the
strongest evidence to date for O3 effects on acute
mortality. Recent meta-analyses also indicate positive risk estimates
that are unlikely to be confounded by PM; however, future work is
needed to better understand the influence of model specifications on
the risk coefficient (EPA, 2006a, p. 7-175). The Criteria Document
concludes that these findings are highly suggestive that short-term
O3 exposure directly or indirectly contributes to non-
accidental and cardiorespiratory-related mortality but that additional
research is needed to more fully establish the underlying mechanisms by
which such effects occur (72 FR 37836). Thus while EPA generally agrees
with the direction of the comment, EPA believes the evidence supports a
view as noted above. In addition, it must be noted that the
Administrator did not focus on mortality as a basis for proposing that
the current O3 standard was not adequate. In the proposal,
the Administrator focused on the very strong evidence of respiratory
morbidity effects in healthy people at the 0.080 ppm exposure level and
new evidence that people with asthma are likely to experience larger
and more serious effects than healthy people at the same level of
exposure (72 FR 37870). With regard to the ambient concentrations at
which O3-related mortality effects may be occurring, EPA
recognized in the proposal that evidence of a causal relationship
between adverse health effects and O3 exposures becomes
increasingly uncertain at lower levels of exposure (72 FR 37880). This
is discussed more fully in section (b) below.
    Several industry organizations argued against placing any reliance
on the time-series epidemiological studies, especially those studies
related to mortality effects. The Annapolis Center (p. 46) makes the
point that although there may be somewhat more positive associations
than negative associations, there is so much noise or variability in
the data that identifying which positive associations may be real
health effects and which are not is beyond the capability of current
methods. They cite the view that the CASAC Panel expressed in a June
2006 letter (Henderson, 2006b), noting that ``Because results of time-
series studies implicate all of the criteria pollutants, findings of
mortality time-series studies do not seem to allow us to confidently
attribute observed effects specifically to individual pollutants.''
    Because of the importance of the O3 mortality multi-city
studies in EPA's analysis of this issue, several of these commenters
focused on them in particular, arguing that, although these studies
have the statistical power to distinguish weak relationships between
daily O3 and mortality, they do not provide reliable or
consistent evidence implicating O3 exposures as a cause of
mortality. Several reasons were given, including: (a) The multi-city
studies cited by EPA involve a wide range of city-specific effects
estimates, including some large cities that have very slight or
negligible effects (e.g., Los Angeles) (Bell et al., 2004), thus
causing several commenters to question the relevance of a ``national''
effect of O3 on mortality and argue that a single national
O3 concentration-mortality coefficient should be used and
interpreted with caution (Rochester Report p. 4); (b) the multi-city
mortality studies did not sufficiently account for other pollutants,
for example, Bell et al. (2004) adjusted for PM10 but did
not have the necessary air quality data to adequately adjust for
PM2.5, which EPA has concluded also causes mortality and is
correlated with O3, especially in the summer months
(Annapolis Center, p. 42); and (c) these studies contain several
findings that are inconsistent or implausible, such as premature
mortality reported at such low levels as to imply that O3-
related mortality is occurring at levels well within natural
background, which is not biologically plausible (Annapolis Center, p.
42).
    Evidence supporting an association between short-term O3
exposure and premature mortality is not limited to multi-city time-
series studies. Most single-city studies show elevated risk of total,
non-accidental mortality, cardiorespiratory, and respiratory mortality
(> 20 studies), including one study in an area that would have met
current standard (Vedal et al., 2003). Three large meta-analyses, which
pool data from many single-city studies to increase statistical power,
reported statistically significant associations and examined sources of
heterogeneity in those associations (Bell et al., 2005; Ito et al.,
2005; Levy et al. 2005). These studies found: (1) Larger and more
significant effects in the warm season than in the cool season or all
year; (2) no strong evidence of confounding by PM; and (3) suggestive
evidence of publication bias, but significant associations remain even
after adjustment for the publication bias.
    Moreover, EPA asserts that the biological plausibility of the
epidemiological mortality associations is generally supported by
controlled human exposure and toxicological evidence of respiratory
morbidity effects for levels at and below 0.080 ppm, but that
biological plausibility becomes increasingly uncertain especially below
0.060 ppm, the lowest level at which effects were observed in
controlled human exposure studies. Further, at lower levels, it becomes
increasingly

uncertain as to whether the reported associations are related to
O3 alone rather than to the broader mix of air pollutants
present in the ambient air. EPA agrees that the multi-city times series
studies evaluated in this review do not completely resolve this issue.
It also becomes increasingly uncertain as to whether effect thresholds
exist but cannot be clearly discerned by statistical analyses. Thus,
when considering the epidemiological evidence in light of the other
available information, it is reasonable to judge that at some point the
epidemiological associations cannot be interpreted with confidence as
providing evidence that the observed health effects can be attributed
to O3 alone.
    In the letter cited, the CASAC Panel did raise the issue of the
utility of time-series studies in the standard setting process with
regard to time-series mortality studies. Nevertheless, in a subsequent
letter to the Administrator, CASAC noted these mortality studies as
evidence to support a recommendation to revise the current primary
O3 standard. ``Several new single-city studies and large
multi-city studies designed specifically to examine the effects of
ozone and other pollutants on both morbidity and mortality have
provided more evidence for adverse health effects at concentrations
lower than the current standard (Henderson, 2006c, p. 3).''
    With regard to the specific issues raised in the comments as to why
the times-series mortality studies do not provide reliable or
consistent evidence implicating O3 exposure as a cause of
mortality, EPA has the following responses:
    (a) The purpose of the NMMAPS approach is not to single out
individual city results but rather to estimate the overall effect from
the 95 communities. It was designed to provide a general, nationwide
estimate. With regard to the very slight or negligible effects
estimates for some large cities (e.g., Los Angeles), an important
factor to consider is that the Bell et al. (2004) study used all
available data in their analyses. Bell et al., reported that the effect
estimate for all available (including 55 cities with all year data) and
warm season (April-October) analyses for the 95 U.S. cities were
similar in magnitude; however, in most other studies, larger excess
mortality risks were reported in the summer season (generally June-
August when O3 concentrations are the highest) compared to
all year or the cold season. Though the effect estimate for Los Angeles
is small compared to some of the other communities, it should be noted
that all year data (combined warm and cool seasons) was used in the
analyses for this city, which likely resulted in a smaller effect
estimate. Because all year data was used for Los Angeles, the median
O3 concentration for Los Angeles is fairly low compared to
the other communities, ranked 23rd out of 95 communities. The median
24-hour average O3 concentration for Los Angeles in this
dataset was 22 ppb, with a 10th percentile of 8 ppb to a 90th
percentile of 38 ppb. The importance of seasonal differences in
O3-related health outcomes has been well documented.
    (b) In section 7.4.6, O3 mortality risk estimates
adjusting for PM exposure, the Criteria Document states that the main
confounders of interest for O3, especially for the northeast
U.S., are ``summer haze-type'' pollutants such as acid aerosols and
sulfates. Since very few studies included these chemical measurements,
PM (especially PM2.5) data, may serve as surrogates.
However, due to the expected high correlation among the constituents of
the ``summer haze mix,'' multipollutant models including these
pollutants may result in unstable coefficients; and, therefore,
interpretation of such results requires some caution.
    In this section, Figure 7-22 shows the O3 risk estimates
with and without adjustment for PM indices using all-year data in
studies that conducted two-pollutant analyses. Approximately half of
the O3 risk estimates increased slightly, whereas the other
half decreased slightly with the inclusion of PM in the models. In
general, the O3 mortality risk estimates were robust to
adjustment for PM in the models.
    The U.S. 95 communities study by Bell et al. (2004) examined the
sensitivity of acute O3-mortality effects to potential
confounding by PM10. Restricting analysis to days when both
O3 and PM10 data were available, the community-
specific O3-mortality effect estimates as well as the
national average results indicated that O3 was robust to
adjustment for PM10 (Bell et al., 2004). As commenters
noted, there were insufficient data available to examine potential
confounding by PM2.5. One study (Lipfert et al., 2000)
reported O3 risk estimates with and without adjustment for
sulfate, a component of PM2.5. Lipfert et al. (2000)
calculated O3 risk estimates based on mean (45 ppb) less
background (not stated) levels of 1-hour max O3 in seven
counties in Pennsylvania and New Jersey. The O3 risk
estimate was not substantially affected by the addition of sulfate in
the model (3.2% versus 3.0% with sulfate) and remained statistically
significant.
    Several O3 mortality studies examined the effect of
confounding by PM indices in different seasons (Figure 7-23, section
7.4.6, Criteria Document). In analyses using all-year data and warm-
season only data, O3 risk estimates were once again fairly
robust to adjustment for PM indices, with values showing both slight
increases and decreases with the inclusion of PM in the model. In the
analyses using cool season data only, the O3 risk estimates
all increased slightly with the adjustment of PM indices, although none
reached statistical significance.
    The three recent meta-analyses (Bell et al., 2005; Ito et al.,
2005; Levy et al., 2005) all examined the influence of PM on
O3 risk estimates. No substantial influence was observed in
any of these studies. In the analysis by Bell et al. (2005), the
combined estimate without PM adjustment was 1.75% (95% PI: 1.10, 2.37)
from 41 estimates, and the combined estimate with PM adjustment was
1.95% (95% PI: -0.06, 4.00) from 11 estimates per 20 ppb increase in
24-hour average O3. In the meta-analysis of 15 cities by Ito
et al. (2005), the combined estimate was 1.6% (95% CI: 1.1, 2.2) and
1.5% (95% CI: 0.8, 2.2) per 20 ppb in 24-hour average O3
without and with PM adjustment, respectively. The additional time-
series analysis of six cities by Ito et al. found that the influence of
PM by season varied across alternative weather models but was never
substantial. Levy et al. (2005) examined the regression relationships
between O3 and PM indices (PM10 and
2.5) with O3-mortality effect estimates for all
year and by season. Positive slopes, which might indicate potential
confounding, were observed for PM2.5 on O3 risk
estimates in the summer and all-year periods, but the relationships
were weak. The effect of one causal variable (i.e., O3) is
expected to be overestimated when a second causal variable (e.g., PM)
is excluded from the analysis, if the two variables are positively
correlated and act in the same direction. However, EPA notes that the
results from these meta-analyses, as well as several single- and
multiple-city studies, indicate that copollutants, including PM,
generally do not appear to substantially confound the association
between O3 and mortality.
    (c) With regard to the biological plausibility of O3-
related mortality occurring at levels well within natural background,
EPA concluded in the proposal that additional research is needed to
more fully establish underlying mechanisms by which mortality effects
occur (72 FR 37836). Such research would likely also help determine
whether it is plausible that mortality would occur at such low levels.
As noted above, the multi-city

times series studies evaluated in this review can not resolve the issue
of whether the reported associations at such low levels are related to
O3 alone rather than to the broader mix of air pollutants
present in the ambient air.
    (5) ``New'' studies not included in the Criteria Document. Many
commenters identified ``new'' studies that were not included in the
Criteria Document that they stated support arguments both for and
against the revision of the current O3 standard. Commenters
who supported revising the current O3 standard identified
new studies that generally supported EPA's conclusions about the
associations between O3 exposure and a range of respiratory
and cardiovascular health outcomes. These commenters also identified
new studies that provide evidence for associations with health outcomes
that EPA has not linked to O3 exposure, such as cancer, and
populations that EPA has not identified as being susceptible or
vulnerable to O3 exposure, including African-American men
and women. Commenters who did not support revision of the current
O3 standard often submitted the same ``new'' studies, but
focused on different aspects of the findings. Commenters who did not
support revision of the current O3 standard stated that
these ``new'' studies provide inconsistent and sometimes conflicting
findings that do little to resolve uncertainties regarding whether
O3 has a causal role in the reported associations with
adverse health outcomes, including premature mortality and various
morbidity outcomes. More detail about the topic areas covered in the
``new'' studies can be found in the Response to Comments document.
    To the extent that these commenters included ``new'' scientific
studies, studies that were published too late to be considered in the
Criteria Document, in support of their arguments for revising or not
revising the standards, EPA notes, as discussed in section I above,
that as in past NAAQS reviews, it is basing the final decisions in this
review on the studies and related information included in the
O3 air quality criteria that have undergone CASAC and public
review and will consider newly published studies for purposes of
decision making in the next O3 NAAQS review. In
provisionally evaluating commenters' arguments, as discussed in the
Response to Comments document, EPA notes that its provisional
consideration of ``new'' science found that such studies did not
materially change the conclusions in the Criteria Document.
iii. Evidence Pertaining to At-Risk Subgroups for O3-Related
Effects
    This section contains major comments on EPA's assessment of the
body of evidence, including controlled human exposure and
epidemiological studies, related to the effects of O3
exposure on sensitive subpopulations. Since new information about the
increased responsiveness of people with lung disease, especially
children and adults with asthma, was an important consideration in the
Administrator's proposed decision that the current O3
standard is not adequate, many of the comments focused on this
information and the conclusions drawn from it. There were also comments
on other sensitive groups identified by EPA, as well as comments
suggesting that additional groups should be considered at increased
risk from O3 exposure. Many of the issues discussed below,
as well as other related issues, are addressed in more detail in the
Response to Comments document.
    As with the comments on controlled human exposure and
epidemiological studies, upon which judgments about sensitive
subpopulations were based, the comments about EPA's delineation of
these groups were highly polarized. In general, one group of commenters
who supported revising the current O3 primary standard,
including medical associations, public health and environmental groups,
agreed in part with EPA's assessment of the subpopulations that are at
increased risk from O3 exposure, but commented that there
are additional groups that need to be considered. A comment from ATS,
AMA and other medical associations noted:

    Within this population exists a number of individuals uniquely
at much higher risk for adverse health effects from ozone exposures,
including children, people with respiratory illness, the elderly,
outdoor workers and healthy children and adults who exercise
outdoors. [ATS, p. 2]

    These commenters agreed with EPA that, based on evidence from
controlled human exposure and epidemiology studies, people with asthma,
especially children, are likely to have greater lung function
decrements and respiratory symptoms in response to O3
exposure than people who do not have asthma, and are likely to respond
at lower levels. Because of this, these commenters make the point that
controlled human exposure studies that employ healthy subjects will
underestimate the effects of O3 exposures in people with
asthma.
    These commenters agreed with EPA's assessment that epidemiological
studies provide evidence of increased morbidity effects, including lung
function decrements, respiratory symptoms, emergency department visits
and hospital admissions, in people with asthma and that controlled
human exposure studies provide biological plausibility for these
morbidity outcomes. Further, the Rochester Report, funded by API,
evaluated some of the same the studies that EPA did and found similar
results with regard to the increased inflammatory responses and
increased airway responsiveness of people with asthma when exposed to
O3. The Rochester Report reached the same conclusion that
EPA did, that this increased responsiveness provides biological
plausibility for the respiratory morbidity effects found in
epidemiological studies.

    Several new studies have demonstrated that exposure of
individuals with atopic asthma to sufficient levels of ozone
produces an increase in specific airway responsiveness to inhaled
allergens* * * These findings, in combination with previously
observed effects of ozone on nonspecific airway responsiveness and
airway inflammation, supports the idea that ambient ozone exposure
could result in exacerbation of asthma several days following
exposure, and provides biological plausibility for the epidemiologic
studies in which ambient ozone concentration has been associated
with increased asthma symptoms, medication use, emergency room
visits, and hospitalizations for asthma. [Rochester Report, pp. 57-
58]

    Commenters also often mentioned the increased susceptibility of
people with COPD, and in this case cited new studies not considered in
the Criteria Document.
    They identify one potentially susceptible subpopulation that EPA
did not focus on in the proposal is infants. Commenters from medical
associations, and environmental and public health groups expressed the
view that O3 exposure can have important effects on infants,
including reduced birth weight, pre-term birth, and increased
respiratory morbidity effects in infants. Exposure to O3
during pregnancy, especially during the second and third trimesters,
was associated with reduced birth weight in full-term infants. Although
this effect was noted at relatively low O3 exposure levels,
the ATS notes that, ``* * * the reduced birth weight in infants in the
highest ozone exposures communities equaled the reduced birth weight
observed in pregnant women who smoke'' (ATS, p. 7).
    In general, EPA agrees with comments that there is very strong
evidence from controlled human exposure and epidemiological studies
that people with lung disease, especially children and adults with
asthma, are susceptible to O3 exposure and are likely to

experience more serious effects than those people who do not have lung
disease. This means that controlled human exposure studies that employ
subjects who do not have lung disease will likely underestimate effects
in those people that do have asthma or other lung diseases.
    In summarizing the epidemiological evidence related to birth-
related health outcomes, the Criteria Document (p. 7-133) concludes
that O3 was not an important predictor of several birth-
related outcomes including premature births and low birth weight.
Birth-related outcomes generally appeared to be associated with air
pollutants that tend to peak in the winter and are possibly traffic-
related. However, given that most of these studies did not analyze the
data by season, seasonal confounding may have therefore influenced the
reported associations. One study reported some results suggestive of
associations between exposures to O3 in the second month of
pregnancy and birth defects, but further evaluation of such potential
associations is needed. With regard to comments about effect in
infants, EPA notes that some of the studies cited by commenters were
not considered in the Criteria Document. More detailed responses to
studies submitted by commenters but not considered in the Criteria
Document can be found in the Response to Comments document.
    The second group of commenters, mostly representing industry
associations and some businesses opposed to revising the primary
O3 standard, asserted that EPA is wrong to claim that new
evidence indicates that the current standard does not provide adequate
health public health protection for people with asthma. In support of
this position, these commenters made the following major comments: (1)
Lung function decrements and respiratory symptoms observed in
controlled human exposure studies of asthmatics are not clinically
important; (2) EPA postulates that asthmatics would likely experience
more serious responses and responses at lower levels than the subjects
of controlled human exposure experiments, but that hypothesis is not
supported by scientific evidence; and, (3) EPA recognized asthmatics as
a sensitive subpopulation in 1997, and new information does not suggest
greater susceptibility than was previously believed.
    With regard to the first point, these commenters expressed the view
that asthmatics are not likely to experience medically significant lung
function changes or respiratory symptoms at ambient O3
concentrations at or even above the level of the current standard. Many
of these commenters cited the opinion of one physician who was asked on
behalf of a group of trade associations and companies to provide his
views on the health significance for asthmatics of the types of
responses that have been reported in controlled human exposure studies
of O3. This commenter (McFadden) reviewed earlier controlled
human exposure studies of asthmatics (from the last review) as well as
the recent controlled human exposure studies of healthy individuals
(Adams 2002, 2003a,b, and 2006) at 0.12, 0.08, 0.06, and 0.04 ppm and
expressed the view that ``* * * these studies on asthmatics indicate
that ozone exposures at ~ 0.12 ppm do not produce medically significant
functional changes and are right around the inflection point where one
begins to see an increase in symptoms; however, that increase is
small'' (McFadden, p. 3). This commenter went on to express the view
that responses to O3 exposure at levels < 0 .08 ppm would be
even less and that the available data are not sufficiently robust to
indicate that such exposures would present a significant health concern
even to sensitive people like asthmatics.
    EPA notes that this commenter based his comment on the group mean
functional and respiratory symptom changes in the studies he reviewed.
EPA agrees that group mean changes at these levels are relatively small
and has described them as such in both the previous review and this one
(72 FR 37828). The importance of group mean changes is to evaluate the
statistical significance of the association between the exposures and
the observed effects, to try to determine if the observed effects are
likely due to O3 exposure rather than chance. In the
previous review as well as in this one, EPA has also focused on the
fact that some individuals experience more severe effects that may be
clinically significant. With regard to the significance of individual
responses, this commenter (McFadden, p. 2) states ``* * * transient
decreases in FEV1 of 10-20% are not by themselves
significant or meaningful to asthmatics* * *. It has been my experience
from examining and studying thousands of patients for both clinical and
research purposes that asthmatics typically will not begin to sense
bronchoconstriction until their FEV1 falls about 50% from
normal.'' EPA strongly disagrees with this assessment. As stated in the
Criteria Document (Table 8-3, p. 8-68) for people with lung disease,
even moderate functional responses (e.g., FEV1 decrements >=
10% but < 20%) would likely interfere with normal activities for many
individuals, and would likely result in more frequent medication use.
EPA notes that in the context of standard setting, CASAC indicated
(Henderson, 2006c) that a focus on the lower end of the range of
moderate functional responses (e.g., FEV1 decrements >= 10%)
is most appropriate for estimating potentially adverse lung function
decrements in people with lung disease.
    With regard to the second point, whether asthmatics would likely
experience more serious responses and responses at lower levels than
the subjects of controlled human exposure experiments and EPA's
discussion of the relationship of increased airway responsiveness and
inflammation experienced by asthmatics to exacerbation of asthma, this
commenter stated that ``there simply are no data to support the
sequence described'' and that ``the assumption that these responses
would lead to clinical manifestations in terms of exacerbations of
asthma or other adverse health effects remains unproven theory''
(McFadden, p. 3).
    In these sections of the proposal (72 FR 37826 and 37846-37847),
EPA describes the evidence indicating that people with asthma are as
sensitive as, if not more sensitive than, normal subjects in
manifesting O3-induced pulmonary function decrements.
Controlled human exposure studies show that asthmatics present a
differential response profile for cellular, molecular, and biochemical
parameters that are altered in response to acute O3
exposure. Asthmatics have greater O3-induced inflammatory
responses and increased O3-induced airway responsiveness
(both incidence and duration) that could have important clinical
implications.
    There are two ways to interpret these comments. One way to
interpret them is that because these controlled human exposure studies
have not produced exacerbations of asthma in study subjects resulting
in the need for medical attention, there are no data to support the
clinical significance of the results. EPA rejects this interpretation
because it would be unethical to knowingly conduct a controlled human
exposure study that would lead to exacerbation of asthma. Controlled
human exposure studies are specifically designed to avoid these types
of responses. The other interpretation is that the commenter does not
agree that the differences in lung function, inflammation and increased
airway responsiveness found in these

controlled human exposure studies support the inference that asthmatics
are likely to have more serious responses than healthy subjects, and
that these responses could have important clinical implications. EPA
rejects this interpretation as well. EPA did not base its increased
concern for asthmatics solely on the results of the controlled human
exposure studies, but has appropriately used a weight of evidence
approach, integrating evidence from animal toxicological, controlled
human exposure and epidemiological studies as a basis for this concern.
The Criteria Document concludes that the positive and robust
epidemiological associations between O3 exposure and
emergency department visits and hospitalizations in the warm season are
supported by the human clinical, animal toxicological and
epidemiological evidence for lung function decrements, increased
respiratory symptoms, airway inflammation, and increased airway
responsiveness (72 FR 37832). The CASAC Panel itself expressed the view
that people with asthma, especially children, have been found to be
more sensitive to O3 exposure, and indicated that EPA should
place more weight on inflammatory responses and serious morbidity
effects, such as increased respiratory-related emergency department
visits and hospitalizations (Henderson, p. 4). Moreover, the Rochester
Report, cited above, reaches essentially the same conclusions as EPA
did, that the evidence from controlled human exposure studies provides
biological plausibility for the epidemiological studies in which
ambient O3 concentrations have been associated with
increased asthma symptoms, medication use, emergency room visits, and
hospitalizations for asthma. Therefore, EPA continues to assert that
there is strong evidence that asthmatics likely have more serious
responses to O3 exposure than people without asthma, and
that these responses have the potential to lead to exacerbation of
asthma as indicated by the serious morbidity effects, such as increased
respiratory-related emergency department visits and hospitalizations
found in epidemiological studies.
    With regard to the third point, commenters expressed the view that
there is no significant new evidence establishing greater risk to
asthmatics than was accepted in 1997, when EPA concluded that the
existing NAAQS was sufficiently stringent to protect public health--
including asthmatics--with an adequate margin of safety (UARG, pp. 22-
23). To support this view, these commenters noted the points made above
and expressed the view that epidemiological studies of asthmatics that
provide new evidence of respiratory symptoms and medication use in
asthmatic children are subject to the limitations of epidemiological
studies discussed above (e.g., confounding by co-pollutants,
heterogeneity of results). In addition, these commenters identified a
new, large multi-city panel study, not included in the Criteria
Document, by Schildcrout et al. (2006), which the commenters
characterize as reporting no association between O3
concentrations and exacerbation of asthma.
    At the time of the last review, EPA concluded that people with
asthma were at greater risk because the impact of O3-induced
responses on already-compromised respiratory systems would noticeably
impair an individual's ability to engage in normal activity or would be
more likely to result in increased self-medication or medical
treatment. At that time there was little evidence that people with pre-
existing disease were more responsive than healthy individuals in terms
of the magnitude of pulmonary function decrements or symptomatic
responses. The new results from controlled exposure and epidemiologic
studies indicate that individuals with preexisting lung disease,
especially people with asthma, are likely to have more serious
responses than people who do not have lung disease and therefore are at
greater risk for O3 health effects than previously judged in
the 1997 review. EPA notes that comments on the limitations of
epidemiological studies and evidence from ``new'' studies (not in the
Criteria Document) have been addressed above. As with other ``new''
studies, this study by Schildcrout et al. (2006) is specifically
discussed in the Response to Comments document.
b. Consideration of Human Exposure and Health Risk Assessments
    Section II.A.3 above provides a summary overview of the exposure
and risk assessment information used by the Administrator to inform
judgments about exposure and health risk estimates associated with
attainment of the current and alternative standards. EPA notes here
that most of the issues and concerns raised by commenters concerning
the methods used in the exposure and risk assessments are essentially
restatements of concerns raised during the review of the Criteria
Document and the development and review of these quantitative
assessments as part of the preparation and review of the Staff Paper
and the associated analyses. EPA presented and the CASAC Panel reviewed
in detail the approaches used to assess exposure and health risk, the
studies and health effect categories selected for which exposure-
response and concentration-response relationships were estimated, and
the presentation of the exposure and risk results summarized in the
Staff Paper. As stated in the proposal notice, EPA believes and CASAC
Panel concurred, that the model selected to estimate exposure represent
the state of the art and that the risk assessment was ``well done,
balanced and reasonably communicated'' and that the selection of health
endpoints for inclusion in the quantitative risk assessment was
appropriate (Henderson, 2006c). EPA does not believe that the exposure
or risk assessments are fundamentally biased in one direction or the
other as claimed in some of the comments.
    Comments received after proposal related to the development of
exposure and health risk assessments, interpretation of exposure and
risk results, and the role of the quantitative human exposure and
health risk assessments in considering the need to revise the current
8-hour O3 standard generally fell into two groups. One group
of commenters that included national environmental and public health
organizations (e.g., joint set of comments by ALA and several
environmental groups including Environmental Defense and Sierra Club),
NESCAUM, and some State and local health and air pollution agencies
argued that the exposure and health risk assessments underestimated
exposure and risks for several reasons including: (1) The geographic
scope was limited to at most only 12 urban areas and thus
underestimates national public health impacts due to exposures to
O3; (2) the assessments did not include all relevant at risk
population groups and excluded populations such as pre-school children,
outdoor workers, adults who exercise outdoors; and (3) the risk
assessment did not include all of the health effect endpoints for which
there is evidence that there are O3-related health effects
(e.g., increased medicine use by asthmatics, lung function decrements
and respiratory symptoms in adults, increased doctors' visits,
emergency department visits, school absences, inflammation, and
decreased resistance to infection among children and adults); and (4)
EPA's exposure assessment underestimates exposures since it considers
average children, not active children who spend more time outdoors and
repeated exposures are also underestimated. The joint set of

comments from ALA and several environmental groups contended that the
``exposures of concern'' metric presented in the Staff Paper and
proposal is ``an inappropriate basis for decisionmaking'' and urged EPA
to set the standard based on the concentrations shown by health studies
to cause adverse effects, not on how much O3 Americans
inhale. This same set of commenters stated that if exposures of concern
were to be considered then the benchmark level of 0.060 ppm should be
the focus, and not higher benchmark levels. These same commenters also
stated that EPA should have estimated and considered total risk without
excluding risks associated with PRB levels because there is no rational
basis for excluding natural and anthropogenic sources from outside
North America and that the NAAQS must protect against total exposure.
While disagreeing with EPA's approach of estimating risks only above
PRB, these same commenters supported the use of the GEOS-CHEM model as
the ``best tool available to derive background concentrations'' should
EPA continue to pursue this approach. These comments are discussed in
turn below.
    EPA agrees that the exposure and health risk assessments are
limited to certain urban areas and do not capture all of the
populations at risk for O3-related effects, and that the
risk assessment does not include all potential O3-related
health effects. The criteria and rationale for selecting the
populations and health outcomes included in the quantitative
assessments were presented in the draft Health Assessment Plan, Staff
Paper, and technical support documents for the exposure and health risk
assessments that were reviewed by the CASAC Panel and the public. The
CASAC Panel indicated in its letter that the health outcomes included
in the quantitative risk assessment were appropriate, while recognizing
that other health outcomes such as emergency department visits and
increased doctors' visits should be addressed qualitatively (Henderson,
2006c). The Staff Paper (and the CASAC Panel) clearly recognized that
the exposure and risk analyses could not provide a full picture of the
O3 exposures and O3-related health risks posed
nationally. The proposal notice made note of this important point and
stated that ``national-scale public health impacts of ambient
O3 exposures are clearly much larger than the quantitative
estimates of O3-related incidences of adverse health effects
and the numbers of children likely to experience exposures of concern
associated with recent air quality or air quality that just meets the
current or alternative standards'' (72 FR 37866).
    However, as stated in the proposal notice, EPA also recognizes that
inter-individual variability in responsiveness to O3 shown
in controlled human exposure studies for a variety of effects means
that only a subset of individuals in any population group estimated to
experience exposures exceeding a given benchmark exposure of concern
level would actually be expected to experience such adverse health
effects. The Administrator continues to recognize that there is a
broader array of O3-related adverse health outcomes for
which risk estimates could not be quantified (that are part of a
broader ``pyramid of effects'') and that the scope of the assessment
was limited to just a sample of urban areas and to some but not all at-
risk populations, leading to an incomplete estimation of public health
impacts associated with O3 exposures across the country. The
Administrator is fully mindful of these limitations, along with the
uncertainties in these estimates, in reaching his conclusion that
observations from the exposure and health risk assessments provide
additional support for his judgment that the current 8-hour standard
does not protect public health with an adequate margin of safety and
must be revised. For reasons discussed below in section II.C.4,
however, the Administrator disagrees with aspects of these commenters'
views on the level of the standard that is appropriate and supported by
the available health effects evidence and quantitative assessments
associated with just meeting alternative standards.
    EPA does not agree that consideration of exposure estimates is not
permitted or is somehow inappropriate in decisions concerning the
primary standard. EPA has considered population exposure estimates as a
consideration in prior NAAQS review decisions, including the 1997
revision of the O3 primary standard and the 1994 decision on
the carbon monoxide (CO) standard. As indicated in the proposal,
estimating exposures of concern is important because it provides some
indication of potential public health impacts of a range of
O3-related health outcomes, such as lung inflammation,
increased airway responsiveness, and changes in host defenses. These
particular health effects have been demonstrated to occur in some
individuals in controlled human exposure studies at levels as low as
0.080 ppm O3 but have not been evaluated at lower levels.
While there is very limited evidence addressing lung function and
respiratory symptom responses at 0.060 ppm, this evidence does not
address these other health effects.
    As noted in the proposal, EPA emphasized that although the analysis
of ``exposures of concern'' was conducted using three discrete
benchmark levels (0.080, 0.070, 0.060 ppm), the concept was more
appropriately viewed as a continuum, with greater confidence and less
uncertainty about the existence of health effects at the upper end and
less confidence and greater uncertainty as one considers increasingly
lower O3 exposure levels. EPA recognized that there was no
sharp breakpoint within the continuum ranging from at and above 0.080
ppm down to 0.060 ppm. In considering the concept of exposures of
concern, the proposal noted that it was important to balance concerns
about the potential for health effects and their severity with the
increasing uncertainty associated with our understanding of the
likelihood of such effects at lower levels.
    As noted above, environmental and public health group comments
expressed the view that if exposures of concern were considered, then
the Administrator should focus only on the 0.060 ppm benchmark based on
the contention that adverse health effects had been demonstrated down
to this level. In contrast, other commenters, primarily industry and
business groups focused on comparisons of the exposures of concern at
the 0.080 ppm benchmark level based on their view that there was no
convincing evidence demonstrating adverse health effects at levels
below this benchmark. In view of the comments received related to the
definition and use of the term ``exposure of concern'' at the time of
proposal, the Administrator recognizes that that there is a risk for
confusion, as it could be read to imply a determination that a certain
benchmark level of exposure has been shown to be causally associated
with adverse health effects. As a consequence, the Administrator
believes that it is more appropriate to consider such exposure
estimates in the context of a continuum rather than focusing on any one
discrete benchmark level, as was done at the time of proposal, since
the Administrator does not believe that the underlying scientific
evidence is certain enough to support a focus on any single bright-line
benchmark level. Thus, the Administrator believes it is appropriate to
consider a range of benchmark levels from 0.080 down to 0.060 ppm,
recognizing that exposures of concern must be considered in the

context of a continuum of the potential for health effects of concern,
and their severity, with increasing uncertainty associated with the
likelihood of such effects at lower O3 exposure levels.
    EPA recognizes that the 0.080 ppm benchmark level represents a
level at which several health outcomes including lung inflammation,
increased airway responsiveness, and decreased resistance to infection
have been shown to occur in healthy adults. The Administrator places
relatively great weight on the public health significance of exposures
at and above this benchmark level given these physiological effects
measured in healthy adults at O3 exposures of 0.080 ppm and
the evidence from controlled human exposure studies showing that people
with asthma have more serious responses than people without asthma.
However, the Administrator does not agree with those commenters who
would only consider this single benchmark level. While the
Administrator places less weight on exposures at and above the 0.070 pm
benchmark level, given the increased uncertainty about the fraction of
the population and severity of the health responses that might occur
associated with exposures at and above this level, he believes that it
is appropriate to consider exposures at and above this benchmark as
well in judging the adequacy of the current standard to protect public
health. Considering exposures at and above the 0.070 ppm benchmark
level provides some consideration for the fact that the effects
observed at 0.080 ppm were in healthy adult subjects but sensitive
population groups such as asthmatics are likely to respond at lower
O3 levels than healthy individuals. The Administrator
considered but placed very little weight on exposures at and above the
0.060 ppm benchmark given the very limited scientific evidence
supporting a conclusion that O3 is causally related to
various health outcomes at this exposure level.
    EPA does not agree that it is inappropriate or impermissible to
assess risks that are in excess of PRB or that EPA must focus on total
risks when using a risk assessment to inform decisions on the primary
standard. Consistent with the approach used in the risk assessment for
the prior O3 standard review and consistent with the
approach used in risk assessments for other prior NAAQS reviews,
estimating risks in excess of PRB is judged to be more relevant to
policy decisions regarding the ambient air quality standard than risk
estimates that include effects potentially attributable to
uncontrollable background O3 concentrations. EPA also notes
that with respect to the adequacy of the current standard taking total
risks into account would not impact the Administrator's decision, since
he judges that the current standard is not adequate even when risks in
excess of current PRB estimates are considered. In addition, EPA notes
that consideration of the evidence itself, as well as exposures at and
above benchmark levels in the range of 0.060 to 0.080 ppm, are not
impacted at all by consideration of current PRB estimates.
    EPA does agree with the ALA and environmental groups comment that
the GEOS-CHEM model represents the best tool currently available to
estimate PRB as recognized in the Criteria Document evaluation of this
issue and the CASAC Panel support expressed during the review of the
Criteria Document.
    The second group of commenters mostly representing industry
associations, businesses, and some State and local officials opposed to
revising the 8-hour standard, and most extensively presented in
comments from UARG, API, Exxon-Mobil, AAM, and NAM, raised one or more
of the following concerns: (1) That exposures of concern and health
risk estimates have not changed significantly since the prior review in
1997; (2) that uncertainties and limitations underlying the exposure
and risk assessments make them too speculative to be used in supporting
a decision to revise the standard; (3) that EPA should have defined PRB
differently and that EPA underestimated PRB levels which results in
health risk reductions associated with more stringent standards being
overestimated; (4) that exposures are overestimated based on specific
methodological choices made by EPA including, for example,
O3 measurements at fixed-site monitors can be higher than
other locations where individuals are exposed, the exposure estimates
do not account for O3 avoidance behaviors, and the exposure
model overestimates elevated breathing rates; and (5) that health risks
are overestimated based on specific methodological choices made by EPA
including, for example, selection of inappropriate effect estimates
from health effect studies and EPA's approach to addressing the shape
of exposure-response relationships and whether or not to incorporate
thresholds into its models for the various health effects analyzed.
These comments are discussed in turn below. Additional detailed
comments related to the development, presentation, and interpretation
of EPA's exposure and health risk assessments, along with EPA's
responses to the specific issues raised by these commenters can be
found in the Response to Comments document.
    (1) In asserting that the estimated exposures and risks associated
with air quality just meeting the current standard have not appreciably
changed since the prior review, comments from Exxon-Mobil, the
Annapolis Center and others have compared results of EPA's lung
function risk assessment done in the last review with those from the
Agency's risk assessment done as part of this review and have concluded
that lung function risks upon attainment of the current O3
standard are below those that were predicted in 1997 and that
uncertainties about other health effects based on epidemiological
studies remain the same. These commenters used this conclusion as the
basis for a claim that there is no reason to depart from the
Administrator's 1997 decision that the current 8-hour standard is
requisite to protect public health.
    EPA believes that this claim is fundamentally flawed for three
reasons, as discussed in turn below: (i) It is factually inappropriate
to compare the quantitative risks estimated in 1997 with those
estimated in the current rulemaking; (ii) it fails to take into account
that with similar risks, increased certainty in the risks presented by
O3 implies greater concern than in the last review, and
(iii) it fails to recognize that the Administrator has used these
estimates in a supportive role, in light of significant uncertainties
in the exposure and risk estimates, to inform the conclusions drawn
primarily from integrative assessment of the controlled human exposure
and epidemiological evidence on whether ambient O3 levels
allowed under the current standard present a serious public health
problem warranting revision of the O3 standard.
    With respect to the first point, the 1997 risk estimates, or any
comparison of the 1997 risk estimates to the current estimates, are
irrelevant for the purpose of judging the adequacy of the current 8-
hour standard, as the 1997 estimates reflect outdated analyses that
have been updated in this review to reflect the current science. Just
comparing the results for lung function decrements ignores these
differences. In particular, as discussed in section 4.6.1 of the Staff
Paper, there have been significant improvements to the exposure model
and the model inputs since the last review that make comparisons
inappropriate between the prior and current review. For example, the
geographic areas modeled are larger

than in the previous review and when modeling a larger area, extending
well beyond the urban core, there will be more people exposed, but a
smaller percentage of the modeled population will be exposed at high
levels, if O3 concentrations are lower in the extended
areas. In the prior review, only typical years, in terms of
O3 air quality were modeled, while the current review used
the most recent three-year period (i.e., 2002-2004). Also, the prior
review estimated exposures for children who spent more time outdoors,
while the assessment for the current review included all school age and
all asthmatic school age children. Therefore, the population groups
examined in the exposure assessment are different between those
considered in the 1997 and current review, making comparison of the
resulting estimates inappropriate. Another important difference making
comparison between the 1997 health risk assessment and the current
assessment inappropriate is that a number of additional health effects
were included in the current review (e.g., respiratory symptoms in
moderate/severe asthmatic children, non-accidental and
cardiorespiratory mortality) based on health effects observed in
epidemiological studies that were not included in the risk assessment
for the prior review. These commenters only compare the risk estimates
with respect to lung function decrement, and fail to account for
differences in additional and more severe health endpoints not covered
in the 1997 assessment, as well as the fact that there are somewhat
different and more urban areas included in the current assessment.
    Second, it is important to take into account EPA's increased level
of confidence in the associations between short-term O3
exposures and morbidity and mortality effects. In comparing the
scientific understanding of the risk presented by exposure to
O3 between the last and current reviews, one must examine
not only the quantitative estimate of risk from those exposures (e.g.
the numbers of increased hospital admissions at various levels) but
also the degree of confidence that the Agency has that the observed
health effects are causally linked to O3 exposure at those
levels. As documented in the Criteria Document and the recommendations
and conclusions of CASAC, EPA recognizes significant advances in our
understanding of the health effects of O3 based on new
epidemiological studies, new human and animal studies documenting
effects, new laboratory studies identifying and investigating
biological mechanisms of O3 toxicity, and new studies
addressing the utility of using ambient monitors to assess population
exposures to ambient O3. As a result of these advances, EPA
is now more certain that ambient O3 presents a significant
risk to public health at levels at or above the range of levels that
the Agency had considered for these standards in 1997. From this more
comprehensive perspective, since the risks presented by O3
are more certain and the current quantitative risk estimates include
additional important health effects, O3-related risks for a
wider range of health effects are now of greater concern at the current
level of the standard than in the last review.
    Third, quantitative risk estimates were not the only basis for
EPA's decision in setting a level for the O3 standard in
1997, and they do not set any quantified ``benchmark'' for the Agency's
decision to revise the O3 standard at this time. While EPA
believes that confidence in the causal relationships between short-term
exposures to O3 and various health effects reported in
epidemiological studies has increased markedly since 1997, the
Administrator also recognizes that the risk estimates for these effects
must be considered in the light of uncertainties about whether or not
these O3-related effects occur at very low O3
concentrations. The Administrator continues to believe that the
exposure and risk estimates associated with just meeting the current
standard discussed in the Staff Paper and summarized in the proposal
notice are important from a public health perspective and are
indicative of potential exposures and risks to at-risk groups. In
considering the exposure and risk estimates, the Administrator has
considered the year-to-year and city-to-city variability in both the
exposure and risk estimates, the uncertainties in these estimates, and
recognition that there is a broader array of O3-related
adverse health outcomes for which risk estimates could not be
quantified (that are part of a broader ``pyramid of effects'') and that
the scope of the assessment was limited to just a sample of urban areas
and to some, but not all, at-risk populations, leading to an incomplete
estimation of public health impacts associated with O3
exposures across the country.
    (2) In asserting that uncertainties and limitations associated with
the exposure and health risk assessments make them too speculative to
be used in supporting a decision to revise the standard, comments from
industry associations and others cited a number of issues including:
(i) Uncertainties about the air quality adjustment approach used to
simulate just meeting the current and alternative standards; (ii)
uncertainties and limitations associated with the definition and
estimation of PRB concentrations; (iii) uncertainties about whether the
respiratory symptoms, hospital admissions, and non-accidental and
cardiorespiratory mortality effects included in the health risk
assessment are actually causally related to ambient O3
concentrations, particularly at levels well below the current standard;
and (iv) uncertainties about the shape of the exposure-response
relationships for lung function responses and concentration-response
relationships for the health effects based on findings from
epidemiological studies and the assumption of a linear non-threshold
relationship for these responses. In summary, these commenters contend
that the substantial uncertainties present in the exposure and risk
assessments preclude the Administrator from using any of the results to
support a conclusion that the current 8-hour standard does not
adequately protect public health.
    Several of the issues raised, including whether EPA's judgments
about causality for the effects included in the risk assessment are
appropriate, the shape of concentration-response relationships, and use
of a linear non-threshold relationship for the health outcomes based on
the epidemiological evidence, have been discussed in the previous
section on health effects evidence. Concerns expressed about the
definition and estimation of PRB levels for O3 and the role
of PRB in the risk assessment are addressed as a separate item below.
These issues also are addressed in more detail in the Response to
Comments document.
    With respect to the air quality adjustment approach used in the
current review to simulate air quality just meeting the current and
alternative O3 standards, as discussed in the Staff Paper
(section 4.5.6) and in more detail in a staff memorandum (Rizzo, 2006),
EPA concluded that the quadratic air quality adjustment approach
generally best represented the pattern of reductions across the
O3 air quality distribution observed over the last decade in
areas implementing control programs designed to attain the
O3 NAAQS. While EPA recognizes that future changes in air
quality distributions are area-specific, and will be affected by
whatever specific control strategies are implemented in the future to
attain a revised NAAQS, there is no empirical evidence to suggest that
future reductions in ambient O3 will be significantly
different from past

reductions with respect to impacting the overall shape of the
O3 distribution.
    As discussed in the proposal notice, EPA recognizes that the
exposure and health risk assessments necessarily contain many sources
of uncertainty including those noted by these commenters, and EPA has
accounted for such uncertainties to the extent possible. EPA developed
and presented an uncertainty analysis addressing the most significant
uncertainties affecting the exposure estimates. With respect to the
health risk assessment, EPA conducted and presented sensitivity
analyses addressing the impact on risk estimates of different
assumptions about the shape of the exposure-response relationship for
lung function decrements and alternative assumptions about PRB levels.
EPA notes that most of the comments summarized above concerning
limitations and uncertainties in these assessments are essentially
restatements of concerns raised during the development and review of
these quantitative assessments as part of the preparation and review of
the Staff Paper and assessments. The CASAC Panel reviewed in detail the
approaches used to assess exposure and health risks and the
presentation of the results in the Staff Paper. EPA believes, and the
CASAC Panel concurred, that the model used to estimate exposures
represents a state-of-the-art approach and that ``there is an explicit
discussion of the limitations of the APEX model in terms of variability
and quality of the input data, which is appropriate and fine''
(Henderson, 2006c, p. 11). The CASAC Panel also found the risk chapter
in the Staff Paper and the risk assessment ``to be well done, balanced,
and reasonably communicated'' (Henderson, 2006c, p. 12). Although EPA
agrees that important limitations and uncertainties remain, and that
future research directed toward addressing these uncertainties is
warranted, EPA believes that overall uncertainties about population
exposure and possible health risks associated with short-term
O3 exposure have diminished since the last review. The
Administrator has carefully considered the limitations and
uncertainties associated with these quantitative assessments but
continues to believe that they provide general support for concluding
that exposures and health risks associated with meeting the current 8-
hour standard are important from a public health perspective and that
the 8-hour standard needs to be revised to provide additional
protection in order to protect public health with an adequate margin of
safety.
    (3) Comments from several industry organizations, businesses, and
others related to PRB included: (i) That EPA should have defined PRB
differently so as to include anthropogenic emissions from Canada and
Mexico; (ii) that EPA underestimated PRB levels by relying on estimates
from the GEOS-CHEM model using 2001 meteorology and EPA should instead
rely on O3 levels observed at remote monitoring locations or
sites that represent PRB conditions; and (iii) that the use of
underestimated PRB levels in the risk assessment results in
overestimated health risks associated with air quality just meeting the
current standard. Finally, some commenters cited concerns expressed by
the CASAC Panel that ``the current approach to determining PRB is the
best method to make this estimation'' (Henderson, 2007, p. 2). Each of
these concerns is addressed below and in more detail in the Response to
Comments document.
    First, the U.S. government has influence over emissions at our
borders that affect ambient O3 concentrations entering the
U.S. from Canada and Mexico through either regulations or international
agreements, and therefore EPA does not agree that these emissions are
uncontrollable. PRB is designed to identify O3 levels that
result from emissions that are considered uncontrollable because the
U.S. has little if any influence on their control, and in that context
anthropogenic emissions from Mexico or Canada should be excluded from
PRB. EPA has consistently defined PRB as excluding anthropogenic
emissions from Canada and Mexico in NAAQS reviews over more than two
decades and sees no basis in the comments to alter this definition.
    Second, the criticisms raised concerning the use of a modeling
approach (GEOS-CHEM using 2001 meteorology) and the alternative
approach of using remote monitoring data to estimate PRB were
considered by EPA's scientific staff and the CASAC Panel during the
course of reviewing the Criteria Document. Both EPA's experts and CASAC
endorsed the use of the peer-reviewed, thoroughly evaluated modeling
approach (GEOS-CHEM) described in the Criteria Document as the best
current approach for estimating PRB levels. The Criteria Document
reviewed detailed evaluations of GEOS-CHEM with O3
observations at U.S. surface sites (Fiore et al., 2002, 2003) and
comparisons of GEOS-CHEM predictions with observations at Trinidad
Head, CA (Goldstein et al., 2004) and found no significant differences
between the model predictions and observations for all conditions,
including those reflecting those given in the current PRB definition.
The Criteria Document states that the current model estimates indicate
that PRB in the U.S. is generally 0.015 to 0.035 ppm that declines from
spring to summer and is generally < 0.025 ppm under conditions
conducive to high O3 episodes. The Criteria Document
acknowledges that PRB can be higher, especially at elevated sites in
the spring due to stratospheric exchange. However, unusually high
springtime O3 episodes tied to stratospheric intrusion are
rare and generally occur at elevated locations and these can be readily
identified and excluded under EPA's exceptional events rule (72 FR
13560) to avoid any impact on attainment/non-attainment status of an
area.
    Third, many of the commenters who raised the concern that EPA's
estimates of PRB were too low and had the impact of exaggerating the
risks associated with the current standard ignored the fact that the