[Federal Register Volume 82, Number 142 (Wednesday, July 26, 2017)]
[Proposed Rules]
[Pages 34792-34834]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-15591]
[[Page 34791]]
Vol. 82
Wednesday,
No. 142
July 26, 2017
Part III
Environmental Protection Agency
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40 CFR Part 50
Review of the Primary National Ambient Air Quality Standards for Oxides
of Nitrogen; Proposed Rule
Federal Register / Vol. 82 , No. 142 / Wednesday, July 26, 2017 /
Proposed Rules
[[Page 34792]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 50
[EPA-HQ-OAR-2013-0146; FRL-9965-28-OAR]
RIN 2060-AR57
Review of the Primary National Ambient Air Quality Standards for
Oxides of Nitrogen
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: Based on the Environmental Protection Agency's (EPA's) review
of the air quality criteria addressing human health effects of oxides
of nitrogen and the primary national ambient air quality standards
(NAAQS) for nitrogen dioxide (NO2), the EPA is proposing to
retain the current standards, without revision.
DATES: Comments must be received on or before September 25, 2017.
Public Hearings: If, by August 2, 2017, the EPA receives a request
from a member of the public to speak at a public hearing concerning the
proposed decision, we will hold a public hearing, with information
about the hearing provided in a subsequent notice in the Federal
Register.
To request a hearing, to register to speak at a hearing or to
inquire if a hearing will be held, please contact Ms. Regina Chappell
at (919) 541-3650 or by email at [email protected]. The EPA will
post all information regarding any public hearing on this proposed
action, including whether a hearing will be held, its location, date,
and time if applicable and any updates online at https://www.epa.gov/naaqs/nitrogen-dioxide-no2-primary-air-quality-standards.
ADDRESSES: Submit your comments, identified by Docket ID No. EPA-HQ-
OAR-2013-0146 to the Federal eRulemaking Portal: http://www.regulations.gov. Follow the online instructions for submitting
comments. Once submitted, comments cannot be edited or withdrawn. The
EPA may publish any comment received to its public docket. Do not
submit electronically any information you consider to be Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Multimedia submissions (audio, video, etc.) must
be accompanied by a written comment. The written comment is considered
the official comment and should include discussion of all points you
wish to make. The EPA will generally not consider comments or comment
contents located outside of the primary submission (i.e., on the Web,
Cloud, or other file sharing system). For additional submission
methods, the full EPA public comment policy, information about CBI or
multimedia submissions, and general guidance on making effective
comments, please visit http://www2.epa.gov/dockets/commenting-epa-dockets.
Docket: All documents in the docket are listed on the
www.regulations.gov Web site. This includes documents in the docket for
the proposed decision (Docket ID No. EPA-HQ-OAR-2013-0146) and a
separate docket, established for the Integrated Science Assessment
(ISA) for this review (Docket ID No. EPA-HQ-ORD-2013-0232) that has
been incorporated by reference into the docket for this proposed
decision. All documents in these dockets are listed on the
www.regulations.gov Web site. Although listed in the index, some
information is not publicly available, e.g., CBI or other information
whose disclosure is restricted by statute. Certain other material, such
as copyrighted material, is not placed on the Internet and may be
viewed, with prior arrangement, at the EPA Docket Center. Publicly
available docket materials are available either electronically in
www.regulations.gov or in hard copy at the Air and Radiation Docket
Information Center, EPA/DC, WJC West Building, Room 3334, 1301
Constitution Ave. NW., Washington, DC. The Public Reading Room is open
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal
holidays. The telephone number for the Public Reading Room is (202)
566-1744 and the telephone number for the Air and Radiation Docket
Information Center is (202) 566-1742.
FOR FURTHER INFORMATION CONTACT: Ms. Breanna Alman, Health and
Environmental Impacts Division, Office of Air Quality Planning and
Standards, U.S. Environmental Protection Agency, Mail Code C504-06,
Research Triangle Park, NC 27711; telephone: (919) 541-2351; fax: (919)
541-0237; email: [email protected].
SUPPLEMENTARY INFORMATION:
General Information
Preparing Comments for the EPA
1. Submitting CBI. Do not submit this information to the EPA
through www.regulations.gov or email. Clearly mark the part or all of
the information that you claim to be CBI. For CBI information in a disk
or CD-ROM that you mail to the EPA, mark the outside of the disk or CD-
ROM as CBI and then identify electronically within the disk or CD-ROM
the specific information that is claimed as CBI. In addition to one
complete version of the comment that includes information claimed as
CBI, a copy of the comment that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 Code of Federal Regulations (CFR) part 2.
2. Tips for Preparing Your Comments. When submitting comments,
remember to:
Identify the action by docket number and other identifying
information (subject heading, Federal Register date and page number).
Follow directions--the agency may ask you to respond to
specific questions or organize comments by referencing a CFR part or
section number.
Explain why you agree or disagree, suggest alternatives,
and substitute language for your requested changes.
Describe any assumptions and provide any technical
information and/or data that you used.
Provide specific examples to illustrate your concerns, and
suggest alternatives.
Explain your views as clearly as possible, avoiding the
use of profanity or personal threats.
Make sure to submit your comments by the comment period
deadline identified.
Availability of Information Related to This Action
A number of the documents that are relevant to this proposed
decision are available through the EPA's Web site at https://www.epa.gov/naaqs/nitrogen-dioxide-no2-primary-air-quality-standards.
These documents include the Integrated Review Plan for the Primary
National Ambient Air Quality Standards for Nitrogen Dioxide (U.S. EPA,
2011a), available at https://www3.epa.gov/ttn/naaqs/standards/nox/data/201406finalirpprimaryno2.pdf, the Integrated Science Assessment for
Oxides of Nitrogen--Health Criteria (U.S. EPA, 2016a), available at
https://cfpub.epa.gov/ncea/isa/recordisplay.cfm?deid=310879, and the
Policy Assessment for the Review of the Primary National Ambient Air
Quality Standards for Oxides of Nitrogen (U.S. EPA, 2017a), available
at https://www.epa.gov/naaqs/policy-assessment-review-primary-national-ambient-air-quality-standards-oxides-nitrogen. These and other related
documents are also available for
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inspection and copying in the EPA docket identified above.
Table of Contents
The following topics are discussed in this preamble:
Executive Summary
I. Background
A. Legislative Requirements
B. Related NO2 Control Programs
C. Review of the Air Quality Criteria and Standards for Oxides
of Nitrogen
II. Rationale for Proposed Decisions on the Primary NO2
Standards
A. General Approach
1. Approach in the Last Review
2. Approach for the Current Review
B. Characterization of NO2 Air Quality
1. Atmospheric Chemistry
2. National Trends in NOX Emissions and Ambient
NO2 Concentrations
3. Near-Road NO2 Air Quality
4. Relationships Between Hourly and Annual NO2
Concentrations
C. Health Effects Information
1. Health Effects With Short-Term Exposure to NO2
2. Health Effects With Long-Term Exposure to NO2
3. Potential Public Health Implications
D. Human Exposure and Health Risk Characterization
1. Overview of Approach To Estimating Potential NO2
Exposures
2. Results of Updated Analyses
3. Uncertainties
4. Conclusions
E. Summary of CASAC Advice
F. Proposed Conclusions on the Adequacy of the Current Primary
NO2 Standards
1. Evidence-Based Considerations
2. Exposure and Risk-Based Considerations
3. CASAC Advice
4. Administrator's Proposed Conclusions Regarding the Adequacy
of the Current Primary NO2 Standards
III. Statutory and Executive Order Reviews
A. Executive Order 12866: Regulatory Planning and Review and
Executive Order 13563: Improving Regulation and Regulatory Review
B. Paperwork Reduction Act (PRA)
C. Regulatory Flexibility Act (RFA)
D. Unfunded Mandates Reform Act (UMRA)
E. Executive Order 13132: Federalism
F. Executive Order 13175: Consultation and Coordination With
Indian Tribal Governments
G. Executive Order 13045: Protection of Children From
Environmental Health and Safety Risks
H. Executive Order 13211: Actions That Significantly Affect
Energy Supply, Distribution or Use
I. National Technology Transfer and Advancement Act (NTTAA)
J. Executive Order 12898: Federal Actions To Address
Environmental Justice in Minority Populations and Low-Income
Populations
K. Determination Under Section 307(d)
References
Executive Summary
This section summarizes background information about this proposed
action and the Administrator's proposed decision to retain the current
primary NO2 standards.
Summary of Background Information
There are currently two primary standards for oxides of nitrogen.
NO2 is the component of oxides of nitrogen of greatest
concern for health and is the indicator for the primary NAAQS. The two
primary NO2 standards are: A 1-hour standard established in
2010 at a level of 100 parts per billion (ppb) and based on the 98th
percentile of the annual distribution of daily maximum 1-hour
NO2 concentrations, averaged over 3 years; and an annual
standard, originally set in 1971, at a level of 53 ppb and based on
annual average NO2 concentrations.
Sections 108 and 109 of the Clean Air Act (CAA) govern the
establishment, review, and revision, as appropriate, of the NAAQS to
protect public health and welfare. The CAA requires the EPA to
periodically review the air quality criteria--the science upon which
the standards are based--and the standards themselves. This review of
the primary (health-based) NO2 NAAQS is being conducted
pursuant to these statutory requirements. The schedule for completing
this review is established by a federal court order, which requires
signature of a proposed determination by July 14, 2017, and a final
determination by April 6, 2018.
The last review of the primary NO2 NAAQS was completed
in 2010. In that review, the EPA supplemented the existing primary
annual NO2 standard by establishing a new short-term
standard with a level of 100 ppb, based on the 3-year average of the
98th percentile of the annual distribution of daily maximum 1-hour
concentrations (75 FR 6474, February 9, 2010). Revisions to the NAAQS
were accompanied by revisions to the data handling procedures and the
ambient air monitoring and reporting requirements, including the
establishment of requirements for states to locate monitors near
heavily trafficked roadways in large urban areas and in other locations
where maximum NO2 concentrations can occur.
Consistent with the review completed in 2010, this review is
focused on the health effects associated with gaseous oxides of
nitrogen and on the protection afforded by the primary NO2
standards. The gaseous oxides of nitrogen include NO2 and
nitric oxide (NO), as well as their gaseous reaction products. Total
oxides of nitrogen include these gaseous species as well as particulate
species (e.g., nitrates). The EPA is separately considering the health
and non-ecological welfare effects of particulate species in the review
of the NAAQS for particulate matter (PM) (U.S. EPA, 2016b). In
addition, the EPA is separately reviewing the ecological welfare
effects associated with oxides of nitrogen, oxides of sulfur, and PM,
and the protection provided by the secondary NO2,
SO2 and PM standards. (U.S. EPA, 2017b).
Summary of Proposed Decision
In this notice, the EPA is proposing to retain the current primary
NO2 standards, without revision. This proposed decision has
been informed by a careful consideration of the full body of scientific
evidence and information available in this review, giving particular
weight to the assessment of the evidence in the ISA; analyses and
considerations in the Policy Assessment (PA); and the advice and
recommendations of the Clean Air Scientific Advisory Committee (CASAC).
As in the last review, the strongest evidence continues to come
from studies examining respiratory effects following short-term
NO2 exposures (e.g., typically minutes to hours). In
particular, the ISA concludes that ``[a] causal relationship exists
between short-term NO2 exposure and respiratory effects
based on evidence for asthma exacerbation'' (U.S. EPA, 2016a, pp. 1-
17). The strongest support for this conclusion comes from controlled
human exposure studies examining the potential for NO2-
induced increases in airway responsiveness (AR) (which is a hallmark of
asthma) in individuals with asthma. Most of these studies were
available in the last review and, consistent with the evidence in that
review, an updated meta-analysis indicates increased AR in some people
with asthma following resting exposures to NO2
concentrations from 100 to 530 ppb. However, there is not an apparent
dose-response relationship between NO2 exposure and
increased AR and there is uncertainty regarding the potential adversity
of reported responses. In addition, these studies are largely focused
on adults with mild asthma, rather than adults or children with more
severe cases of the disease.
Evidence supporting the ISA conclusion also comes from
epidemiologic studies reporting associations between short-term
NO2 exposures and an array of respiratory outcomes related
to asthma exacerbation. Such studies consistently
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report associations with several asthma-related outcomes, including
asthma-related hospital admissions and emergency department visits in
children and adults. The epidemiologic evidence that is newly available
in the current review is consistent with evidence from the last review
and does not fundamentally alter our understanding of respiratory
effects related to short-term NO2 exposures. While our
fundamental understanding of such effects has not changed, recent
epidemiologic studies do reduce some uncertainty from the last review
by reporting health effect associations with short-term NO2
exposures in copollutant models and by their use of improved exposure
metrics.
In addition to the effects of short-term exposures, the ISA
concludes that there is ``likely to be a causal relationship'' between
long-term NO2 exposures and respiratory effects, based on
the evidence for asthma development in children. The strongest evidence
supporting this conclusion comes from recent epidemiologic studies
demonstrating associations between long-term NO2 exposures
and asthma incidence. While these studies strengthen the evidence for
effects of long-term exposures, compared to the last review, they are
subject to uncertainties resulting from the methods used to assign
NO2 exposures, the high correlations between NO2
and other traffic-related pollutants, and the lack of information
regarding the extent to which reported effects are independently
associated with NO2 rather than the overall mixture of
traffic-related pollutants. Additional support comes from experimental
studies supporting the biological plausibility of a potential mode of
action by which NO2 exposures could cause asthma
development. These include studies that support a potential role for
repeated short-term NO2 exposures in the development of
asthma.
While the evidence supports the occurrence of adverse
NO2-related respiratory effects at ambient NO2
concentrations likely to have been above those allowed by the current
primary NO2 NAAQS, available studies do not call into
question the adequacy of the public health protection provided by the
current standards. In particular, compared to the last review when the
1-hour standard was set, evidence from controlled human exposure
studies has not altered our understanding of the NO2
exposure concentrations that cause increased AR. In addition, while
epidemiologic studies report relatively precise associations with
serious NO2-related health outcomes (i.e., emergency
department visits, hospital admissions, asthma incidence) in locations
likely to have violated the current 1-hour and/or annual standards
during portions of study periods, studies do not indicate such
associations in locations with NO2 concentrations that would
have clearly met those standards.
Beyond the scientific evidence, the EPA also considers the extent
to which quantitative analyses can inform conclusions on the adequacy
of the public health protection provided by the current primary
NO2 standards. In particular, the EPA considers analyses
estimating the potential for NO2 exposures of public health
concern that could be allowed by the current standards. Overall, these
analyses indicate that the current 1-hour standard provides substantial
protection against exposures to ambient NO2 concentrations
that have consistently been shown to increase AR in people with asthma,
even under worst-case conditions across a variety of study areas in the
U.S. Such NO2 concentrations were not estimated to occur,
even at monitoring sites adjacent to some of the most heavily
trafficked roads. In addition, the analyses indicate that meeting the
current 1-hour standard limits the potential for exposure to 1-hour
NO2 concentrations that have the potential to exacerbate
symptoms in some people with asthma, but for which uncertainties in the
evidence become increasingly important.
When taken together, the Administrator reaches the proposed
conclusion that the current body of scientific evidence and the results
of quantitative analyses support the degree of public health protection
provided by the current 1-hour and annual primary NO2
standards and do not call into question any of the elements of those
standards. He additionally reaches the proposed conclusion that the
current 1-hour and annual NO2 primary standards, together,
are requisite to protect public health with an adequate margin of
safety.
These proposed conclusions are consistent with CASAC
recommendations. In its advice to the Administrator, ``the CASAC
recommends retaining, and not changing the existing suite of
standards'' (Diez Roux and Sheppard, 2017). The CASAC further stated
that ``it is the suite of the current 1-hour and annual standards,
together, that provide protection against adverse effects'' (Diez Roux
and Sheppard, 2017, p. 9).
Therefore, in this review, the Administrator proposes to retain the
current primary NO2 standards, without revision. The
Administrator solicits comment on his proposed conclusions regarding
the public health protection provided by the current primary
NO2 standards and on his proposal to retain those standards
in this review. He invites comment on all aspects of these proposed
conclusions and their underlying rationales, as discussed in detail in
section II below.
I. Background
A. Legislative Requirements
Two sections of the Clean Air Act (CAA or the Act) govern the
establishment and revision of the NAAQS. Section 108 (42 U.S.C. 7408)
directs the Administrator to identify and list certain air pollutants
and then to issue air quality criteria for those pollutants. The
Administrator is to list those air pollutants that in his ``judgment,
cause or contribute to air pollution which may reasonably be
anticipated to endanger public health or welfare;'' ``the presence of
which in the ambient air results from numerous or diverse mobile or
stationary sources;'' and ``for which . . . [the Administrator] plans
to issue air quality criteria. . . .'' Air quality criteria are
intended to ``accurately reflect the latest scientific knowledge useful
in indicating the kind and extent of all identifiable effects on public
health or welfare which may be expected from the presence of [a]
pollutant in the ambient air . . . .'' 42 U.S.C. 7408(b). Section 109
(42 U.S.C. 7409) directs the Administrator to propose and promulgate
``primary'' and ``secondary'' NAAQS for pollutants for which air
quality criteria are issued. Section 109(b)(1) defines a primary
standard as one ``the attainment and maintenance of which in the
judgment of the Administrator, based on such criteria and allowing an
adequate margin of safety, are requisite to protect the public
health.'' \1\ A secondary standard, as defined in section 109(b)(2),
must ``specify a level of air quality the attainment and maintenance of
which, in the judgment of the Administrator, based on such criteria, is
requisite to protect the public welfare from any known or anticipated
adverse effects associated with the presence of [the] pollutant in the
ambient air.'' \2\
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\1\ The legislative history of section 109 indicates that a
primary standard is to be set at ``the maximum permissible ambient
air level . . . which will protect the health of any [sensitive]
group of the population,'' and that for this purpose ``reference
should be made to a representative sample of persons comprising the
sensitive group rather than to a single person in such a group.''
See S. Rep. No. 91-1196, 91st Cong., 2d Sess. 10 (1970).
\2\ As specified in section 302(h) (42 U.S.C. 7602(h)) effects
on welfare include, but are not limited to, ``effects on soils,
water, crops, vegetation, man-made materials, animals, wildlife,
weather, visibility and climate, damage to and deterioration of
property, and hazards to transportation, as well as effects on
economic values and on personal comfort and well-being.''
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The requirement that primary standards provide an adequate margin
of safety was intended to address uncertainties associated with
inconclusive scientific and technical information available at the time
of standard setting. It was also intended to provide a reasonable
degree of protection against hazards that research has not yet
identified. See Lead Industries Association v. EPA, 647 F.2d 1130, 1154
(DC Cir 1980), cert. denied, 449 U.S. 1042 (1980); American Petroleum
Institute v. Costle, 665 F.2d 1176, 1186 (D.C. Cir. 1981), cert.
denied, 455 U.S. 1034 (1982); American Farm Bureau Federation v. EPA,
559 F. 3d 512, 533 (D.C. Cir. 2009); Association of Battery Recyclers
v. EPA, 604 F. 3d 613, 617-18 (D.C. Cir. 2010). Both kinds of
uncertainties are components of the risk associated with pollution at
levels below those at which human health effects can be said to occur
with reasonable scientific certainty. Thus, in selecting primary
standards that provide an adequate margin of safety, the Administrator
is seeking not only to prevent pollution levels that have been
demonstrated to be harmful but also to prevent lower pollutant levels
that may pose an unacceptable risk of harm, even if the risk is not
precisely identified as to nature or degree. The CAA does not require
the Administrator to establish a primary NAAQS at a zero-risk level,
see Lead Industries v. EPA, 647 F.2d at 1156 n.51, but rather at a
level that reduces risk sufficiently so as to protect public health
with an adequate margin of safety.
In addressing the requirement for an adequate margin of safety, the
EPA considers such factors as the nature and severity of the health
effects involved, the size of sensitive population(s) at risk,\3\ and
the kind and degree of the uncertainties that must be addressed. The
selection of any particular approach to providing an adequate margin of
safety is a policy choice left specifically to the Administrator's
judgment. See Lead Industries Association v. EPA, 647 F.2d at 1161-62.
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\3\ As used here and similarly throughout this notice, the term
population (or group) refers to persons having a quality or
characteristic in common, such as a specific pre-existing illness or
a specific age or life stage. As discussed more fully in section
II.C.3 below, the identification of sensitive groups (called at-risk
groups or at-risk populations) involves consideration of
susceptibility and vulnerability.
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In setting primary and secondary standards that are ``requisite''
to protect public health and welfare, respectively, as provided in
section 109(b), the EPA's task is to establish standards that are
neither more nor less stringent than necessary for these purposes. In
so doing, the EPA may not consider the costs of implementing the
standards. See generally, Whitman v. American Trucking Associations,
531 U.S. 457, 465-472, 475-76 (2001). Likewise, ``[a]ttainability and
technological feasibility are not relevant considerations in the
promulgation of national ambient air quality standards.'' American
Petroleum Institute v. Costle, 665 F. 2d at 1185.
Section 109(d)(1) requires that ``not later than December 31, 1980,
and at 5-year intervals thereafter, the Administrator shall complete a
thorough review of the criteria published under section 108 and the
national ambient air quality standards . . . and shall make such
revisions in such criteria and standards and promulgate such new
standards as may be appropriate . . . . '' Section 109(d)(2) requires
that an independent scientific review committee ``shall complete a
review of the criteria . . . and the national primary and secondary
ambient air quality standards . . . and shall recommend to the
Administrator any new . . . standards and revisions of existing
criteria and standards as may be appropriate . . . .'' Since the early
1980s, this independent review function has been performed by the Clean
Air Scientific Advisory Committee (CASAC).\4\
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\4\ Lists of CASAC members and members of the NO2
Review Panel are available at: http://yosemite.epa.gov/sab/sabproduct.nsf/WebCASAC/CommitteesandMembership?OpenDocument.
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B. Related NO2 Control Programs
States are primarily responsible for ensuring attainment and
maintenance of ambient air quality standards once EPA has established
them. Under section 110 of the Act, 42 U.S.C. 7410, and related
provisions, states are to submit, for EPA approval, state
implementation plans (SIPs) that provide for the attainment and
maintenance of such standards through control programs directed to
sources of the pollutants involved. The states, in conjunction with
EPA, also administer the prevention of significant deterioration
program that covers these pollutants. See 42 U.S.C. 7470-7479. In
addition, federal programs provide for nationwide reductions in
emissions of these and other air pollutants under Title II of the Act,
42 U.S.C. 7521-7574, which involves controls for automobile, truck,
bus, motorcycle, nonroad engine and equipment, and aircraft emissions;
the new source performance standards (NSPS) under section 111 of the
Act, 42 U.S.C. 7411; and the national emission standards for hazardous
air pollutants under section 112 of the Act, 42 U.S.C. 7412.
Currently there are no areas in the United States that are
designated as nonattainment of the NO2 NAAQS (see 77 FR 9532
(February 17, 2012)). In addition, there are currently no monitors
where there are design values (DVs) \5\ above either the 1-hour or
annual standard (U.S. EPA, 2017 Figure 2-5), with the maximum DVs in
2015 being 30 ppb (annual) and 72 ppb (hourly) (U.S. EPA, 2017 Section
2.3.1).\6\
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\5\ The metric used to determine whether areas meet or exceed
the NAAQS is called a design value (DV). In the case of the primary
NO2 NAAQS, there are 2 types of DVs: the annual DV and
the hourly DV. The annual DV for a particular year is the average of
all hourly values within that calendar year. The hourly DV is the
three-year average of the 98th percentiles of the annual
distributions of daily maximum 1-hour NO2 concentrations.
These DVs are considered to be valid if the monitoring data used to
calculate them meet completeness criteria described in 40 CFR 50.11
and Appendix S to Part 50.
\6\ For more information on estimated DVs, see Section 2.3 of
the NO2 PA.
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While NOX (the sum of NO and NO2) is emitted
from a wide variety of source types, the top three categories of
sources of NOX emissions are highway vehicles, off-highway
vehicles, and stationary fuel combustion sources.\7\ The EPA
anticipates that NOX emissions will continue to decrease
over the next 20 years as a result of the ongoing implementation of
mobile source emissions standards.\8\ In particular, Tier 2 and Tier 3
emission standards for new light-duty vehicles, combined with the
reduction of gasoline sulfur content, will significantly reduce motor
vehicle emissions of NOX, with Tier 3 standards phasing in
from model year 2017 to model year 2025. For heavy-duty engines, new
NOX standards were phased in between the 2007 and 2010 model
years, following the introduction of ultra-low sulfur diesel fuel. More
stringent NOX standards for nonroad diesel engines,
locomotives, and certain marine engines are becoming effective
throughout the next decade. In future decades, these vehicles and
engines
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meeting more stringent NOX standards will become an
increasingly large fraction of in-use mobile sources, leading to large
NOX emission reductions.
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\7\ Highway vehicles include all on-road vehicles, including
light duty as well as heavy duty vehicles, both gasoline- and
diesel-powered. Off-highway vehicles and engines include aircraft,
commercial marine vessels, locomotives and non-road equipment. Fuel
combustion sources includes electric power generating units (EGUs),
which derive their power generation from all types of fuels.
\8\ Reductions in ambient NO2 concentrations could
also result from the implementation of NAAQS for other pollutants
(e.g., ozone, PM), to the extent NOX emissions are
reduced as part of the implementation of those standards.
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NOX emissions from stationary fuel combustion sources
are primarily from electric utility sources, both coal and gas-fired.
NOX emissions from these sources, as well as for some large
industrial combustion sources, are also expected to continue to
decrease over the next decade as newer replacement units come on-line
which will have to meet NSPS and SIP compliance limits, and as
additional existing sources opt-in to NOX trading programs
to maintain state emissions budget programs.
C. Review of the Air Quality Criteria and Standards for Oxides of
Nitrogen
In 1971, the EPA added oxides of nitrogen to the list of criteria
pollutants under section 108(a)(1) of the CAA and issued the initial
air quality criteria (36 FR 1515, January 30, 1971; U.S. EPA, 1971).\9\
Based on these air quality criteria, the EPA promulgated the
NO2 NAAQS (36 FR 8186, April 30, 1971). Both primary and
secondary standards were set at 53 ppb,\10\ annual average. Since then,
the Agency has completed multiple reviews of the air quality criteria
and primary NO2 standards. In the last review, the EPA made
revisions to the primary NO2 NAAQS in order to provide
requisite protection of public health. Specifically, the EPA
supplemented the existing primary annual NO2 standard by
establishing a new short-term standard with a level of 100 ppb, based
on the 3-year average of the 98th percentile of the annual distribution
of daily maximum 1-hour concentrations (75 FR 6474, February 9, 2010).
In addition, revisions to the NAAQS were accompanied by revisions to
the data handling procedures and the ambient air monitoring and
reporting requirements, including requirements for states to locate
monitors near heavily trafficked roadways in large urban areas and in
other locations where maximum NO2 concentrations can occur.
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\9\ In the 1971 proposal, the EPA used the term nitrogen oxides.
\10\ In 1971, primary and secondary NO2 NAAQS were
set at levels of 100 micrograms per cubic meter ([mu]g/m\3\), which
equals 0.053 parts per million (ppm) or 53 ppb.
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Industry groups filed petitions for judicial review of the 2010
rule in the U.S. Court of Appeals for the District of Columbia Circuit.
API v. EPA, 684 F.3d 1342 (D.C. Cir. 2012). The court upheld the 2010
rule, denying the petitions' challenges to the adoption of the 1-hour
NO2 NAAQS and dismissing, for lack of jurisdiction, the
challenges to statements regarding permitting in the preamble of the
2010 rule. Id. at 1354.
Subsequent to the 2010 rulemaking, the Agency revised the deadlines
by which the near-road monitors were to be operational in order to
implement a phased deployment approach (78 FR 16184, March 14, 2013),
with a majority of the network becoming operational by 2015. In 2016,
after analyzing available monitoring data, the Agency revised the size
requirements of the near-road network, reducing the network to only
operate in Core Based Statistical Areas (CBSAs) with populations of 1
million or more (81 FR 96381, December 30, 2016).
In February 2012, the EPA announced the initiation of the current
periodic review of the air quality criteria for oxides of nitrogen and
of the primary NO2 NAAQS and issued a call for information
in the Federal Register (77 FR 7149, February 10, 2012). A wide range
of external experts as well as EPA staff representing a variety of
areas of expertise (e.g., epidemiology, human and animal toxicology,
statistics, risk/exposure analysis, atmospheric science, and biology)
participated in a workshop held by the EPA on February 29 to March 1,
2012 in Research Triangle Park, NC. The workshop provided an
opportunity for a public discussion of the key policy-relevant issues
around which the Agency would structure this primary NO2
NAAQS review and the most meaningful new science that would be
available to inform the EPA's understanding of these issues.
Based in part on the workshop discussions, the EPA developed a
draft plan for the ISA and a draft Integrated Review Plan (IRP)
outlining the schedule, process, and key policy-relevant questions that
would guide the evaluation of the health-related air quality criteria
for NO2 and the review of the primary NO2 NAAQS.
The draft plan for the ISA was released in May 2013 (78 FR 26026) and
was the subject of a consultation with the CASAC on June 5, 2013 (78 FR
27234). Comments from the CASAC and the public were considered in the
preparation of the first draft ISA and the draft IRP. In addition,
preliminary draft materials for the ISA were reviewed by subject matter
experts at a public workshop hosted by the EPA's National Center for
Environmental Assessment (NCEA) in May 2013 (78 FR 27374). The first
draft ISA was released in November 2013 (78 FR 70040). During this
time, the draft IRP was also in preparation and was released in
February 2014 (79 FR 7184). Both the draft IRP and first draft ISA were
reviewed by the CASAC at a public meeting held in March 2014 (79 FR
8701), and the first draft ISA was further discussed at an additional
teleconference held in May 2014 (79 FR 17538). The CASAC finalized its
recommendations on the first draft ISA and the draft IRP in letters
dated June 10, 2014 (Frey, 2014a; Frey, 2014b), and the final IRP was
released in June 2014 (79 FR 36801).
The EPA released the second draft ISA in January 2015 (80 FR 5110)
and the Risk and Exposure Assessment (REA) Planning document in May
2015 (80 FR 27304). These documents were reviewed by the CASAC at a
public meeting held in June 2015 (80 FR 22993). A follow-up
teleconference with the CASAC was held in August 2015 (80 FR 43085) to
finalize recommendations on the second draft ISA. The final ISA was
released in January 2016 (81 FR 4910). The CASAC's recommendations on
the second draft ISA and the draft REA Plan were provided to the EPA in
letters dated September 9, 2015 (Diez Roux and Frey, 2015a; Diez Roux
and Frey 2015b), and the final ISA was released in January, 2016 (81 FR
4910).
After considering CASAC's advice and public comments, the EPA
prepared a draft Policy Assessment (PA), which was released on
September 23, 2016 (81 FR 65353). The draft PA was reviewed by the
CASAC on November 9-10, 2016 (81 FR 68414), and a follow-up
teleconference was held on January 24, 2017 (81 FR 95137). The CASAC's
recommendations, based on its review of the draft PA, were provided in
a letter to the EPA Administrator dated March 7, 2017 (Diez Roux and
Sheppard, 2017). The EPA staff took into account these recommendations,
as well as public comments provided on the draft PA, when developing
the final PA, which was released in April 2017.\11\
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\11\ This document may be found at: https://www.epa.gov/naaqs/policy-assessment-review-primary-national-ambient-air-quality-standards-oxides-nitrogen.
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In addition, in July 2016, a lawsuit was filed against the EPA and
included a claim that EPA had failed to complete its review of the
primary NO2 NAAQS within five years, as required by the CAA.
Center for Biological Diversity et al. v. McCarthy, (No. 4:16-cv-03796-
VC, N.D. Cal., July 7, 2016). Consistent with CAA section 113(g), a
notice of a proposed consent decree to resolve this litigation was
published in the Federal Register on January 17, 2017 (82 FR 4866). The
EPA received two public comments on the proposed consent decree,
neither of which disclosed facts or considerations indicating that the
Department of Justice or EPA should withhold consent. The parties to
the
[[Page 34797]]
litigation filed a joint motion asking the court to enter the consent
decree, and the court entered the consent decree as a consent judgment
on April 28, 2017. The consent judgment established July 14, 2017, as
the deadline for signature of a notice setting forth the proposed
decision in this review, and April 6, 2018, as the deadline for
signature of a notice setting forth the final decision.
Consistent with the review completed in 2010, this review is
focused on health effects associated with gaseous oxides of nitrogen
and the protection afforded by the primary NO2 standards.
The gaseous oxides of nitrogen include NO2 and NO as well as
their gaseous reaction products. Total oxides of nitrogen include these
gaseous species as well as particulate species (e.g., nitrates). Health
effects and non-ecological welfare effects associated with the
particulate species are addressed in the review of the NAAQS for PM
(U.S. EPA, 2016b).\12\ The EPA is separately reviewing the ecological
welfare effects associated with oxides of nitrogen, oxides of sulfur,
and PM, and the protection provided by the secondary NO2,
SO2 and PM standards. (U.S. EPA, 2017a).\13\
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\12\ Additional information on the PM NAAQS is available at:
https://www.epa.gov/naaqs/particulate-matter-pm-air-quality-standards.
\13\ Additional information on the ongoing and previous review
of the secondary NO2 and SO2 NAAQS is
available at: https://www.epa.gov/naaqs/nitrogen-dioxide-no2-and-sulfur-dioxide-so2-secondary-air-quality-standards.
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II. Rationale for Proposed Decisions on the Primary NO[bdi2] Standards
This section presents the rationale for the Administrator's
proposed decision to retain the existing NO2 primary
standards. This rationale is based on a thorough review of the latest
scientific information generally published through August 2014,\14\ as
presented in the ISA, on human health effects associated with
NO2 and pertaining to the presence of NO2 in the
ambient air. The Administrator's rationale also takes into account: (1)
The EPA staff's consideration of the scientific evidence and technical
information and staff's conclusions based on that evidence and
information, presented in the PA; (2) the CASAC's advice and
recommendations, as reflected in discussions at public meetings of
drafts of the various documents that were prepared for this review,
including the ISA and PA, and in the CASAC's letters to the
Administrator; and (3) public input received during the development of
these documents, either in connection with CASAC meetings or
separately.\15\
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\14\ In addition to the review's opening ``call for
information'' (77 FR 7149, February 10, 2012), ``the U.S. EPA
routinely conducted literature searches to identify relevant peer-
reviewed studies published since the previous ISA (i.e., from
January 2008 through August 2014)'' (U.S. EPA, 2016a p. 1-3).
References that are cited in the ISA, the references that were
considered for inclusion but not cited, and electronic links to
bibliographic information and abstracts can be found at: http://hero.epa.gov/oxides-of-nitrogen.
\15\ Public input during the review process, including on drafts
of the ISA and PA, and CASAC's advice in light of that public input,
were considered by the EPA staff in developing final documents.
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In presenting the rationale for the Administrator's proposed
decision and its foundations, Section II.A provides background on the
general approach for review of the primary NO2 NAAQS,
including a summary of the approach used in the last review (Section
II.A.1) and the general approach taken in the PA for the current review
(Section II.A.2). Section II.B characterizes ambient NO2
concentrations throughout the United States. Section II.C summarizes
the body of available scientific evidence, focusing on consideration of
key policy-relevant questions, and Section II.D summarizes the
available information from quantitative analyses evaluating the
potential for NO2 exposures that could be of public health
concern. Section II.E summarizes CASAC advice. Section II.F presents
the Administrator's proposed conclusions on adequacy of the current
standard, drawing on both evidence-based and exposure-/risk-based
considerations (Sections II.F.1 and II.F.2, respectively), and advice
from CASAC (Section II.F.3).
A. General Approach
The past and current approaches described below are both based,
most fundamentally, on using the EPA's assessment of the current
scientific evidence and associated quantitative analyses to inform the
Administrator's judgment regarding primary NO2 standards
that protect public health with an adequate margin of safety. As noted
in the PA (U.S. EPA, 2017a, section 1.4), in drawing conclusions with
regard to the primary standards, the final decision on the adequacy of
the current standards is largely a public health policy judgment to be
made by the Administrator. The Administrator's decisions draw upon
scientific information and analyses about health effects, population
exposure and risks, as well as judgments about how to consider the
range and magnitude of uncertainties that are inherent in the
scientific evidence and analyses. The PA's approach to informing these
judgments, discussed more fully below, is based on the recognition that
the available health effects evidence generally reflects a continuum,
consisting of higher concentrations at which scientists generally agree
that health effects are likely to occur, through lower concentrations
at which the likelihood and magnitude of the response become
increasingly uncertain. This approach is consistent with the
requirements of sections 108 and 109 of the Act and with how the EPA
and the courts have historically interpreted the Act. These provisions
require the establishment of primary standards that, in the judgment of
the Administrator, are requisite to protect public health with an
adequate margin of safety. In fulfilling this responsibility, the
Administrator seeks to establish standards that are neither more nor
less stringent than necessary for this purpose. The Act does not
require that primary standards be set at a zero-risk level, but rather
at a level that avoids unacceptable risks to public health including
the health of sensitive groups. The four basic elements of the NAAQS
(indicator, averaging time, level, and form) are considered
collectively in evaluating the health protection afforded by the
current standards.
1. Approach in the Last Review
The last review of the primary NO2 NAAQS was completed
in 2010 (75 FR 6474, February 9, 2010). In that review, the EPA
established a new 1-hour standard to provide increased public health
protection, including for people with asthma and other at-risk
populations,\16\ against an array of adverse respiratory health effects
that had been linked to short-term NO2 exposures (75 FR 6498
to 6502; U.S. EPA, 2008a, Sections 3.1.7 and 5.3.2.1; Table 5.3-1).
Specifically, the EPA established a short-term standard defined by the
3-year average of the 98th percentile of the annual distribution of
daily maximum 1-hour NO2 concentrations, with a level of 100
ppb. In addition to setting the new 1-hour standard, the EPA retained
the existing annual standard with its level of 53 ppb (75 FR 6502,
February 9, 2010). The Administrator in that review concluded that,
together, the two standards provide protection against adverse
respiratory health effects associated with short-term exposures to
NO2 and effects potentially associated with long-term
exposures. In conjunction with the revised primary NO2
NAAQS, the EPA also established a multi-tiered monitoring network
composed of (1) near-road monitors which would be placed near heavily
trafficked roads in urban areas; (2) monitors located to characterize
areas with the highest expected NO2 concentrations at the
neighborhood and
[[Page 34798]]
larger spatial scales (also referred to as ``area-wide'' monitors); and
(3) forty NO2 monitors to characterize air quality for
susceptible and vulnerable communities, nationwide (75 FR 6505 to
6511). Subsequent to the 2010 rulemaking, the Agency adopted a phased
implementation schedule for the near-road monitoring network and
removed the requirement for near-road NO2 monitoring in
CBSAs with population of less than 1 million (78 FR 16184, March 14,
2013; 81 FR 96381, December 30, 2016). Key aspects of the
Administrator's approach in the last review to reaching these decisions
are described below.
a. Approach to Considering the Need for Revision in the Last Review
The 2010 decision to revise the existing primary NO2
standard was based largely on the body of scientific evidence published
through early 2008 and assessed in the 2008 ISA (U.S. EPA, 2008a); the
quantitative exposure and risk analyses and the assessment of the
policy-relevant aspects of the evidence presented in the REA (U.S. EPA,
2008b); \17\ the advice and recommendations of the CASAC (Samet, 2008);
and public comments on the proposal.
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\17\ As discussed in the IRP for this review (U.S. EPA, 2014,
Section 1.3), due to changes in the NAAQS process, the last review
of the NO2 NAAQS did not include a separate PA document.
Rather, the REA for that review included a policy assessment
chapter.
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As an initial consideration in reaching that decision, the
Administrator noted that the evidence relating short-term (minutes to
weeks) NO2 exposures to respiratory morbidity was judged in
the ISA to be ``sufficient to infer a likely causal relationship'' (75
FR 6489, February 9, 2010; U.S. EPA, 2008a, Sections 3.1.7 and
5.3.2.1).\18\ The scientific evidence included controlled human
exposure studies providing evidence of increases in airway
responsiveness in people with asthma following short-term exposures to
NO2 concentrations as low as 100 ppb \19\ and epidemiologic
studies reporting associations between short-term NO2
exposures and respiratory effects in locations that would have met the
annual standard.
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\18\ In contrast, the evidence relating long-term (weeks to
years) NO2 exposures to health effects was judged to be
either ``suggestive of but not sufficient to infer a causal
relationship'' (respiratory morbidity) or ``inadequate to infer the
presence or absence of a causal relationship'' (mortality, cancer,
cardiovascular effects, reproductive/developmental effects) (75 FR
6478, February 9, 2010). The causal framework used in the ISA for
the current review is discussed in Chapter 3 of the PA (U.S. EPA,
2017a).
\19\ Transient increases in airway responsiveness have the
potential to increase asthma symptoms and worsen asthma control (74
FR 34415, July 15, 2009; U.S. EPA, 2008a, sections 5.3.2.1 and 5.4).
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The quantitative analyses presented in the 2008 REA included
exposure and risk estimates for air-quality adjusted to just meet the
annual standard. The Administrator took note of the REA conclusion that
risks estimated for air quality adjusted upward to simulate just
meeting the current standard could reasonably be concluded to be
important from a public health perspective, while additionally
recognizing the uncertainties associated with adjusting air quality in
such analyses (75 FR 6489, February 9, 2010). For air quality adjusted
to just meet the existing annual standard, the REA findings given
particular attention by the Administrator included the following: ``a
large percentage (8 to 9%) of respiratory-related [emergency
department] visits in Atlanta could be associated with short-term
NO2 exposures; most people with asthma in Atlanta could be
exposed on multiple days per year to NO2 concentrations at
or above 300 ppb; and most locations evaluated could experience on-/
near-road NO2 concentrations above 100 ppb on more than half
of the days in a given year'' (75 FR 6489, February 9, 2010; U.S. EPA,
2008b, Section 10.3.2).
In reaching the conclusion on adequacy of the annual standard
alone, the Administrator also considered advice received from the
CASAC. In its advice, the CASAC agreed that the primary concern in the
review was to protect against health effects that have been associated
with short-term NO2 exposures. The CASAC also agreed that
the annual standard alone was not sufficient to protect public health
against the types of exposures that could lead to these health effects.
As noted in its letter to the EPA Administrator, ``[The] CASAC concurs
with EPA's judgment that the current NAAQS does not protect the
public's health and that it should be revised'' (Samet, 2008, p. 2).
Based on the considerations summarized above, the Administrator
concluded that the annual NO2 NAAQS alone was not requisite
to protect public health with an adequate margin of safety and that the
standard should be revised in order to provide increased public health
protection against respiratory effects associated with short-term
exposures, particularly for at-risk populations and lifestages such as
people with asthma, children, and older adults (75 FR 6490, February 9,
2010). Upon consideration of approaches to revising the standard, the
Administrator concluded that it was appropriate to set a new short-term
standard, in addition to the existing annual standard with its level of
53 ppb, as described below.
b. Approach to Considering the Elements of a Revised Standard in the
Last Review
In considering appropriate revisions in the last review, each of
the four basic elements of the NAAQS (indicator, averaging time, level,
and form) were evaluated. The sections below summarize the approaches
used by the Administrator, and her final decisions, on each of those
elements.
i. Indicator
In the review completed in 2010, as well as in previous reviews,
the EPA focused on NO2 as the most appropriate indicator for
oxides of nitrogen because the available scientific information
regarding health effects was largely indexed by NO2.
Controlled human exposure studies and animal toxicological studies
provided specific evidence for health effects following exposures to
NO2. In addition, epidemiologic studies typically reported
effects associated with NO2 concentrations \20\ (75 FR 6490,
February 9, 2010; U.S. EPA 2008a, Section 2.2.3). Based on the
information available in the last review, and consistent with the views
of the CASAC (Samet, 2008, p. 2; Samet, 2009, p. 2), the EPA concluded
it was appropriate to continue to use NO2 as the indicator
for a standard that was intended to address effects associated with
exposure to NO2, alone or in combination with other gaseous
oxides of nitrogen. In so doing, the EPA recognized that measures
leading to reductions in population exposures to NO2 will
also reduce exposures to other oxides of nitrogen (75 FR 6490, February
9, 2010).
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\20\ The degree to which monitored NO2 reflected
actual NO2 concentrations, as opposed to NO2
plus other gaseous oxides of nitrogen, was recognized as an
uncertainty (75 FR 6490, February, 9, 2010; U.S. EPA 2008b, section
2.2.3).
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ii. Averaging Time
In considering the most appropriate averaging time(s) for the
primary NO2 NAAQS, the Administrator noted the available
scientific evidence as assessed in the ISA, the air quality analyses
presented in the REA, the conclusions of the policy assessment chapter
of the REA, and recommendations from the CASAC.\21\ Her key
considerations are summarized below.
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\21\ She also considered public comments received on the
proposal (75 FR 6490, February, 9, 2010).
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When considering averaging time, the Administrator first noted that
the evidence relating short-term (minutes to weeks) NO2
exposures to respiratory
[[Page 34799]]
morbidity was judged in the ISA to be ``sufficient to infer a likely
causal relationship'' (U.S. EPA, 2008a, section 5.3.2.1). The
Administrator concluded that this strength of evidence most directly
supported consideration of an averaging time that focused protection on
effects associated with short-term exposures to NO2. In
considering the level of support available for specific short-term
averaging times, the Administrator noted that the policy assessment
chapter of the REA considered evidence from both experimental and
epidemiologic studies. Controlled human exposure studies and animal
toxicological studies provided evidence that NO2 exposures
from less than 1 hour up to 3 hours can result in respiratory effects
such as increased AR and inflammation (U.S. EPA, 2008a, Section
5.3.2.7). The Administrator specifically noted the ISA conclusion that
exposures of adults with asthma to 100 ppb NO2 for 1-hour
(or 200 to 300 ppb for 30 minutes) can result in small but
statistically significant increases in nonspecific AR (U.S. EPA, 2008a,
Section 5.3.2.1). In addition, the epidemiologic evidence provided
support for short-term averaging times ranging from approximately 1
hour up to 24 hours (U.S. EPA, 2008a, Section 5.3.2.7). Based on this,
the Administrator concluded that a primary concern with regard to
averaging time is the degree of protection provided against effects
associated with 1-hour NO2 concentrations. Based on REA
analyses of ratios between 1-hour and 24-hour NO2
concentrations (U.S. EPA, 2008b, Section 10.4.2), she further concluded
that a standard based on 1-hour daily maximum NO2
concentrations could also be effective at protecting against effects
associated with 24-hour NO2 exposures (75 FR 6490).
Based on the above, the Administrator judged that it was
appropriate to set a new NO2 standard with a 1-hour
averaging time. She concluded that such a standard would be expected to
effectively limit short-term (e.g., 1- to 24-hours) exposures that have
been linked to adverse respiratory effects. She also retained the
existing annual standard to continue to provide protection against
effects potentially associated with long-term exposures to oxides of
nitrogen (75 FR 6502, February 9, 2010). These decisions were
consistent with CASAC advice to establish a short-term primary standard
for oxides of nitrogen based on using 1-hour maximum NO2
concentrations and to retain the current annual standard (Samet, 2008,
p. 2; Samet, 2009, p. 2).
iii. Level
With consideration of the available health effects evidence,
exposure and risk analyses, and air quality information, the
Administrator set the level of the new 1-hour NO2 standard
at 100 ppb. This standard was focused on limiting the maximum 1-hour
NO2 concentrations in ambient air (75 FR 6474, February 9,
2010).\22\ In establishing this new standard, the Administrator
emphasized the importance of protecting against short-term exposures to
peak concentrations of NO2, such as those that can occur
around major roadways. Available evidence and information suggested
that roadways account for the majority of exposures to peak
NO2 concentrations and, therefore, are important
contributors to NO2-associated public health risks (U.S.
EPA, 2008b, Figures 8-17 and 8-18).
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\22\ In conjunction with this new standard, the Administrator
established a multi-tiered monitoring network that included monitors
sited to measure the maximum NO2 concentrations near
major roadways, as well as monitors sited to measure maximum area-
wide NO2 concentrations and for the characterization of
NO2 exposure for susceptible and vulnerable populations.
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In setting the level of the new 1-hour standard at 100 ppb, the
Administrator noted that there is no bright line clearly directing the
choice of level. Rather, the choice of what is appropriate is largely a
public health policy judgment entrusted to the Administrator. This
judgment must include consideration of the strengths and limitations of
the evidence and the appropriate inferences to be drawn from the
evidence and the exposure and risk assessments.
The Administrator judged that the existing evidence from controlled
human exposure studies supported the conclusion that the
NO2-induced increase in AR at or above 100 ppb presented a
potential risk of adverse effects for some people with asthma,
especially those with more serious (i.e., more than mild) asthma. The
Administrator noted that the risks associated with increased AR could
not be fully characterized based on available controlled human exposure
studies. However, the Administrator concluded that people with asthma,
particularly those suffering from more severe asthma, warrant
protection from the risk of adverse effects associated with the
NO2-induced increase in AR. Therefore, the Administrator
concluded that the controlled human exposure evidence supported setting
a standard level no higher than 100 ppb to reflect a cautious approach
to the uncertainty regarding the adversity of the effect. However,
those uncertainties led her to also conclude that this evidence did not
support setting a standard level lower than 100 ppb (75 FR 6500-6501,
February 9, 2010).
The Administrator also considered the more serious health effects
reported in NO2 epidemiologic studies. She noted that a new
standard focused on protecting against maximum 1-hour NO2
concentrations in ambient air anywhere in an area, with a level of 100
ppb and an appropriate form (as discussed below), would be expected to
limit area-wide \23\ NO2 concentrations to below 85 ppb,
which was the lowest 98th percentile 1-hour daily maximum
NO2 concentration in the cluster of five key epidemiologic
studies which reported associations with respiratory-related hospital
admissions or emergency department visits and which the Administrator
gave substantial weight. The Administrator also concluded that such a
1-hour standard would be consistent with the REA conclusions based on
the NO2 exposure and risk information (75 FR 6501, February
9, 2010).
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\23\ Area-wide concentrations refer to those measured by
monitors that have been sited to characterize ambient concentrations
at the neighborhood and larger spatial scales.
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Given the above considerations and the comments received on the
proposal, and considering the entire body of evidence and information
before her, as well as the related uncertainties, the Administrator
judged it appropriate to set a 1-hour standard with a level of 100 ppb.
Specifically, she concluded that such a standard, with an appropriate
form as discussed below, would provide a substantial increase in public
health protection compared to that provided by the annual standard
alone and would be expected to protect against the respiratory effects
that have been linked with NO2 exposures in both controlled
human exposure and epidemiologic studies. This includes limiting
exposures at and above 100 ppb for the vast majority of people,
including those in at-risk groups, and maintaining maximum area-wide
NO2 concentrations below those in locations where key U.S.
epidemiologic studies had reported that ambient NO2 was
associated with clearly adverse respiratory health effects, as
indicated by increased hospital admissions and emergency department
visits. The Administrator also noted that a standard level of 100 ppb
was consistent with the consensus recommendation of the CASAC. (75 FR
6501, February 9, 2010).
In setting the standard level at 100 ppb rather than at a lower
level, the Administrator also acknowledged the
[[Page 34800]]
uncertainties associated with the scientific evidence. She noted that a
1-hour standard with a level lower than 100 ppb would only result in
significant further public health protection if, in fact, there is a
continuum of serious, adverse health risks caused by exposure to
NO2 concentrations below 100 ppb and/or associated with
area-wide NO2 concentrations well below those in locations
where key U.S. epidemiologic studies had reported associations with
respiratory-related emergency department visits and hospital
admissions. Based on the available evidence, the Administrator did not
believe that such assumptions were warranted. Taking into account the
uncertainties that remained in interpreting the evidence from available
controlled human exposure and epidemiologic studies, the Administrator
observed that the likelihood of obtaining benefits to public health
with a standard set below 100 ppb decreased, while the likelihood of
requiring reductions in ambient concentrations that go beyond those
that are needed to protect public health increased. (75 FR 6501-02,
February 9, 2010).
iv. Form
The ``form'' of a standard defines the air quality statistic that
is to be compared to the level of the standard in determining whether
an area attains the standard. The Administrator recognized that for
short-term standards, concentration-based forms that reflect
consideration of a statistical characterization of an entire
distribution of air quality data, with a focus on a single statistical
metric such as the 98th or 99th percentile, can better reflect
pollutant-associated health risks than forms based on expected
exceedances. This is the case because concentration-based forms give
proportionally greater weight to days when pollutant concentrations are
well above the level of the standard than to days when the
concentrations are just above the level of the standard.\24\ In
addition, she recognized that it is desirable from a public health
perspective to have a form that is reasonably stable and insulated from
the impacts of extreme meteorological events, and concluded that when
averaged over three years, these concentration-based forms provide an
appropriate balance between limiting peak pollutant concentrations and
providing a stable regulatory target (75 FR 6492, February 9, 2010).
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\24\ Compared to an exceedance-based form, a concentration-based
form reflects the magnitude of the exceedance of a standard level
not just the fact that such an exceedance occurred.
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In the last review, the EPA considered two specific concentration-
based forms (i.e., the 98th and 99th percentile concentrations),
averaged over 3 years, for the new 1-hour NO2 standard. The
focus on the upper percentiles of the distribution was based, in part,
on evidence of health effects associated with short-term NO2
exposures from experimental studies which provided information on
specific exposure concentrations that were linked to respiratory
effects. In a letter to the Administrator following issuance of the
Agency's proposed rule, the CASAC recommended a form based on the 3-
year average of the 98th percentile of the distribution of 1-hour daily
maximum NO2 concentrations (Samet, 2009, p. 2). In making
this recommendation, the CASAC noted the potential for instability in
the higher percentile concentrations and the absence of data from the
near-road monitoring network, which at that time had been proposed but
was not yet established.
Given the limited available information on the variability in peak
NO2 concentrations near important sources of NO2,
primarily near major roadways, and given the recommendation from the
CASAC regarding the potential for instability in the 99th percentile
concentrations, the Administrator judged it appropriate to set the form
based on the 3-year average of the 98th percentile of the annual
distribution of daily maximum 1-hour NO2 concentrations. In
addition, consistent with the CASAC's advice (Samet, 2008, p. 2; Samet,
2009, p. 2), the EPA retained the form of the annual standard (75 FR
6502, February 9, 2010).
c. Areas of Uncertainty in Last Review
While the available scientific information informing the last
review was stronger and more consistent than in previous reviews and
provided a strong basis for decision making in that review, the Agency
recognized that areas of uncertainty remained. These were generally
related to the following: (1) Understanding the role of NO2
in the complex ambient mixture which includes a range of co-occurring
pollutants (e.g., fine particulate matter (PM2.5),\25\
carbon monoxide (CO), and other traffic-related pollutants; ozone
(O3); and sulfur dioxide (SO2)) (e.g., 75 FR 6485
February 9, 2010); (2) understanding the extent to which monitored
ambient NO2 concentrations used in epidemiologic studies
reflect exposures in study populations and the range of ambient
concentrations over which the evidence indicates confidence in the
health effects observed in the epidemiologic studies (e.g., 75 FR 6501,
February 9, 2010); (3) understanding the magnitude and potential
adversity of NO2-induced respiratory effects reported in
controlled human exposure studies (e.g., 75 FR 6500, February 9, 2010);
and (4) understanding the NO2 concentration gradients around
important sources, such as major roads, and relating those gradients to
broader ambient monitoring concentrations (e.g., 75 FR 6479, February
9, 2010).
---------------------------------------------------------------------------
\25\ In general terms, particulate matter with a nominal mean
aerodynamic diameter less than or equal to 2.5 [mu]m; a measurement
of fine particles. In regulatory terms, particles with an upper 50%
cut -point of 2.5 [mu]m aerodynamic diameter (the 50% cut point
diameter is the diameter at which the sampler collects 50% of the
particles and rejects 50% of the particles) and a penetration curve
as measured by a reference method based on Appendix L of 40 CFR part
50 and designated in accordance with 40 CFR part 53, by an
equivalent method designated in accordance with 40 CFR part 53, or
by an approved regional method designated in accordance with
Appendix C of 40 CFR part 58.
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2. Approach for the Current Review
The approach in this review of the primary NO2 NAAQS
takes into consideration the approach used in the last review, and
addresses key policy-relevant questions in light of the currently
available scientific and technical information. To evaluate whether it
is appropriate to consider retaining the current primary NO2
standards, or whether consideration of revision is appropriate, the EPA
has adopted an approach that builds upon the general approach used in
the last review and reflects the body of evidence and information now
available. As summarized above, the decisions in the last review were
based on the integration of NO2 health effects information
with judgments on the adversity and public health significance of key
health effects, policy judgments as to when the standard is requisite
to protect public health with an adequate margin of safety,
consideration of CASAC advice, and consideration of public comments.
In the current review, the EPA's approach recognizes that the
available health effects evidence reflects a continuum from relatively
higher NO2 concentrations, at which scientists generally
agree that health effects are likely to occur, through lower
concentrations, at which the likelihood and magnitude of a response
become increasingly uncertain. In reaching a final decision on the
current primary NO2 standards, the Administrator will draw
upon the available scientific
[[Page 34801]]
evidence for NO2-attributable health effects and upon
information from available quantitative analyses, including judgments
about the appropriate weight to assign the range of uncertainties
inherent in the evidence and analyses. The Administrator will also
consider advice from CASAC and public comments received in response to
this proposed decision.
The final decision on the primary NO2 standards is
largely a public health policy judgment to be made by the EPA
Administrator. The weight to be given to various elements of the
evidence and the available quantitative analyses is part of the public
health policy judgments that the Administrator will make in reaching
decisions on the standards.
To inform the Administrator's judgments and decisions, the PA
presents evidence-based and exposure/risk-based considerations.
Evidence-based considerations focus on the findings of epidemiologic
studies, controlled human exposure studies, and experimental animal
studies evaluating health effects related to NO2 exposures.
The PA's consideration of such studies draws from the assessment of the
evidence presented in the ISA (U.S. EPA, 2016a). Exposure/risk-based
considerations draw upon the results of the PA's quantitative analyses
of potential NO2 exposures. The PA's consideration of the
evidence and quantitative information is framed by a series of key
policy-relevant questions (U.S. EPA, 2017a, Figure 1-1). These
questions focus on the strength of the evidence for various
NO2-related health effects and for potential at-risk
populations, the NO2 exposure concentrations at which
adverse effects occur, the potential for NO2 exposures and
health effects of public health concern with NO2
concentrations that meet the current standards, and uncertainties in
the available evidence and information. The PA's consideration of these
issues is intended to inform the Administrator's decisions as to
whether, and if so how, to revise the current NO2 standards.
These considerations are discussed below (II.C to II.F).
B. Characterization of NO2 Air Quality
This section presents information on NO2 atmospheric
chemistry and ambient concentrations, with a focus on information that
is most relevant for the review of the primary NO2
standards. This section is drawn from the more detailed discussion of
NO2 air quality in the PA (U.S. EPA, 2017a, Chapter 2) and
the ISA (U.S. EPA, 2016a, Chapter 2).\26\ It presents a summary of
NO2 atmospheric chemistry (II.B.1), trends in ambient
NO2 concentrations (II.B.2), ambient NO2
concentrations measured at monitors near roads (II.B.3), the
relationships between hourly and annual ambient NO2
concentrations (II.B.4), and background concentrations of
NO2 (II.B.5).
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\26\ The focus is on NO2 in this notice, as this is
the indicator for the current standards and is most relevant to the
evaluation of health evidence. Characterization of air quality for
the broader category of oxides of nitrogen is provided in the ISA
(U.S. EPA, 2016a, Chapter 2).
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1. Atmospheric Chemistry
Ambient concentrations of NO2 are influenced by both
direct NO2 emissions and by emissions of nitric oxide (NO),
with the subsequent conversion of NO to NO2 primarily though
reaction with ozone (O3). The initial reaction between NO
and O3 to form NO2 occurs fairly quickly during
the daytime, with reaction times on the order of minutes. However,
NO2 can also be photolyzed to regenerate NO, creating new
O3 in the process (U.S. EPA, 2016a, Section 2.2). A large
number of oxidized nitrogen species in the atmosphere are formed from
the oxidation of NO and NO2. These include nitrate radicals
(NO3), nitrous acid (HONO), nitric acid (HNO3),
dinitrogen pentoxide (N2O5), nitryl chloride
(ClNO2), peroxynitric acid (HNO4), peroxyacetyl
nitrate and its homologues (PANs), other organic nitrates, such as
alkyl nitrates (including isoprene nitrates), and pNO3. The
sum of these reactive oxidation products and NO plus NO2
comprise the oxides of nitrogen.27 28
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\27\ This follows usages in the Clean Air Act Section 108(c):
``Such criteria [for oxides of nitrogen] shall include a discussion
of nitric and nitrous acids, nitrites, nitrates, nitrosamines, and
other carcinogenic and potentially carcinogenic derivatives of
oxides of nitrogen.'' By contrast, within air pollution research and
control communities, the terms ``nitrogen oxides'' and
NOX are often restricted to refer only to the sum of NO
and NO2.
\28\ See Figure 2-1 of the NO2 PA for additional
information (U.S. EPA, 2017a).
---------------------------------------------------------------------------
Due to the close relationship between NO and NO2, and
their ready interconversion, these species are often grouped together
and referred to as NOX. The majority of NOX
emissions are in the form of NO. For example, 90% or more of tail-pipe
NOX emissions are in the form of NO, with only about 2% to
10% emitted as NO2 (Itano et al., 2014; Kota et al., 2013;
Jimenez et al., 2000; Richmond-Bryant et al., 2016). NOX
emissions require time and sufficient O3 concentrations for
the conversion of NO to NO2. Higher temperatures and
concentrations of reactants result in shorter conversion times (e.g.,
less than one minute under some conditions), while dispersion and
depletion of reactants result in longer conversion times. The time
required to transport emissions away from a roadway can vary from less
than one minute (e.g., under open conditions) to about one hour (e.g.,
for certain urban street canyons) (D[uuml]ring et al., 2011; Richmond-
Bryant and Reff, 2012). These factors can affect the locations where
the highest NO2 concentrations occur. In particular, while
ambient NO2 concentrations are often elevated near important
sources of NOX emissions, such as major roadways, the
highest measured ambient concentrations in a given urban area may not
always occur immediately adjacent to those sources.\29\
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\29\ Ambient NO2 concentrations around stationary
sources of NOX emissions are similarly impacted by the
availability of O3 and by meteorological conditions,
although surface-level NO2 concentrations can be less
impacted in cases where stationary source NOX emissions
are emitted from locations elevated substantially above ground
level.
---------------------------------------------------------------------------
2. National Trends in NOX Emissions and Ambient
NO2 Concentrations
Ambient concentrations of NO2 in the U.S. are due
largely to NOX emissions from anthropogenic sources.
Background NO2 is estimated to make up only a small fraction
of current ambient concentrations (U.S. EPA, 2016a, Section 2.5.6; U.S.
EPA, 2017, Section 2.3.4).\30\ Nationwide estimates indicate that there
has been a 61% reduction in total NOX emissions from 1980 to
2016 (U.S. EPA, 2017a, Section 2.1.2, Figure 2-2). These reductions
have been driven primarily by decreases in emissions from mobile
sources and fuel combustion (U.S., EPA, 2017, Section 2.1.2, Figure 2-
3).
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\30\ Background concentrations of a pollutant can be defined in
various ways, depending on context and circumstances. Background
concentrations of NO2 are discussed in the ISA (U.S. EPA,
2016a, Section 2.5.6) and the PA (U.S. EPA, 2017, Section 2.3.4).
---------------------------------------------------------------------------
Long-term trends in NO2 DVs across the U.S. show that
ambient concentrations of NO2 have been declining, on
average, since 1980 (U.S. EPA, 2017a, Figure 2-4). Data have been
collected for at least some part of the period since 1980 at 2099 sites
in the U.S., with individual sites having a wide range in duration and
continuity of operations across multiple decades. Overall, the majority
of sampling sites have observed statistically significant downward
trends in ambient NO2 concentrations (U.S. EPA, 2017a,
Figure 2-5).\31\ The annual and hourly DVs
[[Page 34802]]
trended upward in less than 4% of the sites.\32\ Even considering the
fact that there are a handful of sites where upward trends in
NO2 concentrations have occurred, the maximum DVs in 2015
across the whole monitoring network were well-below the NAAQS, with the
highest values being 30 ppb (annual) and 72 ppb (hourly) (U.S. EPA,
2017a, Section 2.3.1).
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\31\ Based on an analysis of data from sampling sites with
sufficient data to produce at least five valid DVs.
\32\ It is not clear whether specific sources may be responsible
for these upward trends in ambient NO2 concentrations. As
discussed in the PA (U.S. EPA, 2017a, Section 2.1.2), since 1980
increases in NOX emissions have been observed for several
types of sources, including oil and gas production, agricultural
field burning, prescribed fires and mining. Though relatively small
contributors nationally, emissions from these sources can be
substantial in some areas (e.g., see U.S. EPA, 2016a, Section
2.3.5).
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3. Near-Road NO2 Air Quality
The largest single source of NOX emissions is on-road
vehicles, and emissions are primarily in the form of NO, with
NO2 formation requiring both time and sufficient
O3 concentrations. Depending on local meteorological
conditions and O3 concentrations, ambient NO2
concentrations can be higher near roadways than at sites in the same
area but farther removed from the road (and from other sources of
NOX emissions).
When considering the historical relationships between
NO2 concentrations at monitors near roadways, and monitors
further away from roads, NO2 DVs are generally highest at
sampling sites nearest to the road (less than 50 meters) and decrease
as distance from the road increases (U.S. EPA, 2017a, Section 2.3.2,
Figure 2-6). This relationship is more pronounced for annual DVs than
for hourly DVs. The general pattern of decreasing DVs with increasing
distance from the road has persisted over time, though the absolute
difference (in terms of ppb) between NO2 concentrations
close to roads and those farther from roads has generally decreased
over time (U.S. EPA, 2017a, Section 2.3.2, Figure 2-6).
In addition, data from the recently deployed network \33\ of
dedicated near-road NO2 monitors indicate that daily maximum
1-hour NO2 concentrations are generally higher at near-road
monitors than at non-near-road monitors in the same CBSA (U.S. EPA,
2017a, Figures 2-7 to 2-10). The 98th percentiles of 1-hour daily
maximum concentrations (the statistic most relevant to the 2010
standard) were highest at near-road monitors (i.e., higher than all
non-near-road monitors in the same CBSA) in 58% to 77% of the CBSAs
evaluated, depending on the year (U.S. EPA, 2017a, Section 2.3.2,
Figures 2-7 to 2-10).\34\
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\33\ Prior to the 2010 rulemaking, monitors were ``not sited to
measure peak roadway-associated NO2 concentrations. . .
.'' (75 FR 6479).
\34\ The upper end of this range (i.e., 77%) reflects more
recent years during which most near-road monitors were in operation.
The lower end of this range (i.e., 58%) reflects the smaller number
of near-road monitors in operation during the early years of the
deployment of the near-road network.
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4. Relationships Between Hourly and Annual NO2
Concentrations
Control programs have resulted in substantial reductions in
NOX emissions since the 1980s. These reductions in
NOX emissions have decreased both short-term peak
NO2 concentrations and annual average concentrations (U.S.
EPA, 2017a, Section 2.3.1). When considering the change in
NO2 DVs since the 1980s, the median annual DV has decreased
by about 65% and the median 1-hour DV has decreased by about 50% (U.S.
EPA, 2017a, Section 2.3.3, Figure 2-10). These DVs were measured
predominantly by NO2 monitors located at area-wide
monitoring sites and data from the new near-road monitoring network
were not included in the analysis due to the limited amount of data
available.\35\ At various times in the past, a number of these area-
wide sites would have violated the 1-hour standard without violating
the annual standard; however, no sites would have violated the annual
standard without also violating the 1-hour standard (U.S. EPA, 2017a
p.2-21). Furthermore, examination of historical data indicate that 1-
hour DVs at or below 100 ppb generally correspond to annual DVs below
35 ppb (U.S. EPA, 2017a p.2-21). Based on this, meeting the 1-hour
standard with its level of 100 ppb would be expected to maintain annual
average NO2 concentrations well-below the 53 ppb level of
the annual standard (U.S. EPA, 2017a, Figure 2-11). It will be
important to reevaluate this relationship as more data become available
from recently deployed near-road monitors.
---------------------------------------------------------------------------
\35\ As noted above (II.A.1), area-wide sites are intended to
characterize ambient NO2 concentrations at the
neighborhood and larger spatial scales.
---------------------------------------------------------------------------
C. Health Effects Information
This section summarizes the available scientific evidence on the
health effects of NO2 exposures. These summaries are based
primarily on the assessment of the evidence in the ISA (U.S. EPA,
2016a) and on the PA's consideration of that evidence in evaluating the
public health protection provided by the current primary NO2
standards (U.S. EPA, 2017a).
In the current review of the primary NO2 NAAQS, the ISA
uses frameworks to characterize the strength of the available
scientific evidence for health effects attributable to NO2
exposures and to classify the evidence for factors that may increase
risk in some populations \36\ or lifestages (U.S. EPA, 2015, Preamble,
Section 6). These frameworks provide the basis for robust, consistent,
and transparent evaluation of the scientific evidence, including
uncertainties in the evidence, and for drawing conclusions on air
pollution-related health effects and at-risk populations.
---------------------------------------------------------------------------
\36\ The term ``population'' refers to people having a quality
or characteristic in common, including a specific pre-existing
illness or a specific age or lifestage.
---------------------------------------------------------------------------
With regard to characterization of the health effects evidence, the
ISA uses a five-level hierarchy to classify the overall weight of
evidence into one of the following categories: causal relationship;
likely to be a causal relationship; suggestive of, but not sufficient
to infer, a causal relationship; inadequate to infer a causal
relationship; and not likely to be a causal relationship (U.S. EPA,
2015, Preamble Table II). The PA considers the full body of health
evidence addressed in the ISA, placing the greatest emphasis on the
effects for which the evidence has been judged in the ISA to
demonstrate a ``causal'' or a ``likely to be a causal'' relationship
with NO2 exposures (U.S. EPA, 2017a).\37\ In the ISA, a
``causal'' relationship is supported when, ``the consistency and
coherence of evidence integrated across scientific disciplines and
related health outcomes are sufficient to rule out chance, confounding,
and other biases with reasonable confidence'' (U.S. EPA, 2016a, p. 1-
5). A ``likely to be a causal'' relationship is supported when ``there
are studies where results are not explained by chance, confounding, or
other biases, but uncertainties remain in the evidence overall. For
example, the influence of other pollutants is difficult to address, or
evidence among scientific disciplines may be limited or inconsistent''
(U.S. EPA, 2016a, p. 1-5). Many of the health effects evaluated in the
ISA, have complex etiologies. For instance, diseases such as asthma are
typically initiated by multiple agents. For example, outcomes depend on
a variety of factors such as age, genetic background, nutritional
status, immune competence, and social factors (U.S.
[[Page 34803]]
EPA, 2017a Preamble, Section 5.b). Thus, exposure to NO2 is
likely one of several contributors to the health effects evaluated in
the ISA.
---------------------------------------------------------------------------
\37\ In this review, as in past reviews, there were causal
determination changes for different endpoint categories. For more
information on changes in causal determinations from the previous
review, see below and Table 1-1 of the ISA (U.S. EPA, 2016a).
---------------------------------------------------------------------------
With regard to identifying specific populations or lifestages that
may be at increased risk of health effects related to NO2
exposures, the ISA characterizes the evidence for a number of
``factors'', including both intrinsic (i.e., biologic, such as pre-
existing disease or lifestage) and extrinsic (i.e., non-biologic, such
as diet or socioeconomic status) factors. The categories considered in
classifying the evidence for these potential at-risk factors are
``adequate evidence,'' ``suggestive evidence,'' ``inadequate
evidence,'' and ``evidence of no effect'' (U.S. EPA, 2016a, Section
5.c, Table II). Within the PA, the focus is on the consideration of
potential at-risk populations and lifestages for which the ISA judges
there is ``adequate'' evidence (U.S. EPA, 2016a, Table 7-27).
Section II.C.1 summarizes the evidence for effects related to
short-term NO2 exposures (e.g., minutes to weeks). Section
II.C.2 summarizes the evidence for effects related to long-term
NO2 exposures (e.g., months to years). Section II.C.3
discusses the potential public health implications of NO2
exposures, based on the evidence for populations and lifestages at
increased risk of NO2-related effects.
1. Health Effects With Short-Term Exposure to NO2
This section discusses the evidence for health effects following
short-term NO2 exposures. Section II.C.1.a discusses the
nature of the health effects that have been shown to occur following
short-term NO2 exposures and the strength of the evidence
supporting various effects, based on the assessment of that evidence in
the ISA. Section II.C.1.b discusses the NO2 concentrations
at which health effects have been demonstrated to occur, based on the
considerations and analyses included in the PA.\38\
---------------------------------------------------------------------------
\38\ When considering the NO2 concentrations at which
health effects have been demonstrated to occur, the EPA places the
greatest emphasis on evidence supporting health endpoints that the
ISA has determined to have a ``causal'' or ``likely to be a causal''
relationship with NO2 exposure.
---------------------------------------------------------------------------
a. Nature of Effects
Across previous reviews of the primary NO2 NAAQS (U.S.
EPA, 1993; U.S. EPA, 2008a), evidence has consistently demonstrated
respiratory effects attributable to short-term NO2
exposures. In the last review, the 2008 ISA concluded that evidence was
``sufficient to infer a likely causal relationship between short-term
NO2 exposure and adverse effects on the respiratory system''
based on the large body of epidemiologic evidence demonstrating
positive associations with respiratory symptoms and hospitalization or
emergency department (ED) visits as well as supporting evidence from
controlled human exposure and animal studies (U.S. EPA, 2008a, p. 5-6).
Evidence for cardiovascular effects and mortality attributable to
short-term NO2 exposures was weaker and was judged
``inadequate to infer the presence or absence of a causal
relationship'' and ``suggestive of, but not sufficient to infer, a
causal relationship,'' respectively. The 2008 ISA noted an overarching
uncertainty in determining the extent to which NO2 is
independently associated with effects or if NO2 is a marker
for the effects of another traffic-related pollutant or mix of
pollutants (U.S. EPA, 2008a, Section 5.3.2.2 to 5.3.2.6).
For the current review, there is newly available evidence for both
respiratory effects and other health effects critically evaluated in
the ISA as part of the full body of evidence informing the nature of
the relationship between health effects and short-term exposures to
NO2 (U.S. EPA, 2016a).\39\ In considering the available
evidence and the causal determinations presented in the ISA, consistent
with the PA (U.S. EPA, 2017a), this proposal focuses on respiratory
effects (II.C.1.a.i), cardiovascular effects (II.C.1.a.ii), and
mortality (II.C.1.a.iii).
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\39\ A list of the causal determinations from the ISA for the
current review, and those from the previous review, for respiratory
effects, cardiovascular effects, and mortality is presented in Table
3-1 of the NO2 PA (U.S. EPA, 2017a).
---------------------------------------------------------------------------
i. Respiratory Effects
The ISA concludes that evidence supports a causal relationship
between respiratory effects and short-term NO2 exposures,
primarily based on evidence for asthma exacerbation. In reaching this
conclusion, the ISA notes that ``epidemiologic, controlled human
exposure, and animal toxicological evidence together can be linked in a
coherent and biologically plausible pathway to explain how
NO2 exposure can trigger an asthma exacerbation'' (U.S. EPA,
2016a, p. 1-17). In the last review, the 2008 ISA described much of the
same evidence and determined it was ``sufficient to infer a likely
causal relationship'' with respiratory effects, citing uncertainty as
to whether the epidemiologic results for NO2 could be
disentangled from effects related to other traffic-related pollutants.
In contrast to the current review, the 2008 ISA evaluated evidence for
the broad category of respiratory effects and did not explicitly
evaluate the extent to which various lines of evidence supported
effects on more specific endpoints such as asthma exacerbation (i.e.,
asthma attacks). In the current review, the ISA states that ``the
determination of a causal relationship is not based on new evidence as
much as it is on the integrated findings for asthma attacks with due
weight given to experimental studies'' (U.S. EPA, 2016a, p.
1xxxiii).\40\
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\40\ Experimental studies, such as controlled human exposure
studies, provide support for effects of exposures to NO2
itself, and generally do not reflect the complex atmospheres to
which people are exposed. Thus, unlike epidemiologic studies,
experimental studies that evaluate exposures to NO2
itself are not subject to uncertainties related to the potential for
copollutant confounding.
---------------------------------------------------------------------------
Strong evidence supporting this causal determination in the ISA
comes from a meta-analysis of controlled human exposure studies that
evaluate the potential for increased AR \41\ following 20-minute to 1-
hour NO2 exposures (Brown, 2015).\42\ While individual
controlled human exposure studies can lack statistical power to
identify effects, the meta-analysis of individual-level data combined
from multiple studies has greater statistical power due to increased
sample size.\43\ AR has been the key respiratory outcome from
controlled human exposures in the previous and current reviews of the
primary NO2 NAAQS, and the ISA specifically notes that
``airway hyperresponsiveness can lead to poorer control of symptoms and
is a hallmark of asthma'' (U.S. EPA, 2016a, p. 1-18). Brown (2015)
examined the relationship between AR and NO2 exposures in
subjects with asthma across the large body of controlled human exposure
studies,\44\ most of which were available in the last review (U.S. EPA,
2017a, Tables 3-2 and 3-3). More specifically, the meta-analysis
[[Page 34804]]
identified the fraction of individuals having an increase in AR
following NO2 exposure, compared to the fraction having a
decrease, across studies.\45\ The meta-analysis also stratified the
data to consider the influence of factors that may affect results
including exercise versus rest and non-specific versus specific
challenge agents.\46\
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\41\ The ISA states that airway responsiveness is ``inherent
responsiveness of the airways to challenge by bronchoconstricting
agents'' (U.S. EPA, 2016a, p. 5-9). More specifically, airway
hyperresponsiveness refers to increased sensitivity of the airways
to an inhaled bronchoconstricting agent. This is often quantified as
the dose of challenge agent that results in a 20% reduction in
forced expiratory volume for 1 second (FEV1), but some
studies report the change in FEV1 for a specified dose of
challenge agent. The change in specific airways resistance (sRaw) is
also used to quantify AR.
\42\ These studies evaluate the effect of inhaled NO2
on the inherent responsiveness of the airways to challenge by
bronchoconstricting agents.
\43\ A meta-analyses synthesizes data from multiple studies
using statistical analyses.
\44\ These controlled human exposure studies were conducted in
people with asthma, a group at increased risk for NO2-
related effects. The severity of asthma varied across studies,
ranging from inactive asthma up to severe asthma. (Brown, 2015).
\45\ More information on the distribution of study subjects
across NO2 concentrations can be found below
(II.C.1.b.i). Information on the fraction of individuals who
experienced an increase versus a decrease stratified by
concentration can also be found in this section.
\46\ ``Bronchial challenge agents can be classified as
nonspecific (e.g., histamine; SO2; cold air) or specific
(i.e., an allergen). Nonspecific agents can be differentiated
between `direct' stimuli (e.g., histamine, carbachol, and
methacholine) which act on airway smooth muscle receptors and
`indirect' stimuli (e.g., exercise, cold air) which act on smooth
muscle through intermediate pathways, especially via inflammatory
mediators. Specific allergen challenges (e.g., house dust mite, cat
allergen) also act `indirectly' via inflammatory mediators to
initiate smooth muscle contraction and bronchoconstriction'' (U.S.
EPA, 2016a, p. 5-8).
---------------------------------------------------------------------------
The results from the meta-analysis demonstrate that the majority of
study volunteers with asthma experienced increased AR following resting
exposure to NO2 concentrations ranging from 100 to 530 ppb,
relative to filtered air. Limitations in this evidence result from the
lack of an apparent dose-response relationship, uncertainty in the
potential adversity of responses, and the general focus of available
studies on people with mild asthma, rather than more severe cases of
the disease. These controlled human exposure studies, the meta-
analysis, and uncertainties in this body of evidence are discussed in
greater detail below (II.C.1.b.i).
The ISA further characterizes the clinical relevance of these
increases in AR, using an approach that is based on guidelines from the
American Thoracic Society (ATS) and the European Respiratory Society
(ERS) for the assessment of therapeutic agents (Reddel et al., 2009).
Specifically, based on individual-level responses reported in a subset
of studies, the ISA considered a halving of the provocative dose (PD)
to indicate responses that may be clinically relevant.47 48
With regard to this approach, the ISA notes that ``in a joint statement
of the [ATS] and [ERS], one doubling dose change in PD is recognized as
a potential indicator, although not a validated estimate, of clinically
relevant changes in AR (Reddel et al., 2009)'' (U.S. EPA, 2016a, p. 5-
12).
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\47\ PD is the dose of challenge agent required to elicit a
specified change in a measure of lung function, typically a 20%
decrease in FEV1 or a 100% increase in specific airway
resistance (sRaw).
\48\ The ISA's characterization of a clinically relevant
response is based on evidence from controlled human exposure studies
evaluating the efficacy of inhaled corticosteroids that are used to
prevent bronchoconstriction and airway responsiveness as described
by Reddel et al. (2009). Generally, a change of at least one
doubling dose is considered to be an indication of clinical
relevance. Based on this, a halving of the PD is taken in the ISA to
represent an increase in AR that indicates a clinically relevant
response.
---------------------------------------------------------------------------
Based on a subset of the controlled human exposure studies
considered in the ISA, Brown (2015) shows that NO2 exposures
from 100 to 530 ppb resulted in a halving of the dose of a challenge
agent required to increase AR (i.e., a halving of the PD) for about a
quarter of study volunteers. While these results support the potential
for clinically relevant increases in AR in some individuals with asthma
following NO2 exposures within the range of 100 to 530 ppb,
uncertainty remains given that this analysis is limited to a small
subset of the studies included in the broader Brown et al. (2015) meta-
analysis and given the lack of an apparent dose-response
relationship.\49\ In addition, compared to conclusions based on the
entire range of NO2 exposure concentrations evaluated (i.e.,
100 to 530 ppb), there is greater uncertainty in reaching conclusions
about the potential for clinically relevant effects at any particular
NO2 exposure concentration within this range.
---------------------------------------------------------------------------
\49\ Section 3.2.2.1 of the PA (U.S. EPA, 2017a) includes
additional discussion of these uncertainties.
---------------------------------------------------------------------------
Controlled human exposure studies discussed in the ISA also
evaluated a range of other respiratory effects, including lung function
decrements, respiratory symptoms, and pulmonary inflammation. The
evidence does not consistently demonstrate these effects following
exposures to NO2 concentrations at or near those found in
the ambient air in the U.S. However, a subset of studies using
NO2 exposures to 260 ppb for 15-30 min or 400 ppb for up to
6 hours provide evidence that study volunteers with asthma and allergy
can experience increased inflammatory responses following allergen
challenge. Evidence for pulmonary inflammation was more mixed across
studies that did not use an allergen challenge following NO2
exposures ranging from 300-1,000 ppb (U.S. EPA, 2016a, Section
5.2.2.5).
In addition to this evidence for NO2-induced increases
in AR and allergic inflammation in controlled human exposure studies,
the ISA also describes consistent evidence from epidemiologic studies
for positive associations between short-term NO2 exposures
and an array of respiratory outcomes related to asthma. Thus, coherence
and biological plausibility is demonstrated in the evidence integrated
between controlled human exposure studies and the various asthma-
related outcomes examined in epidemiologic studies. The ISA indicates
that epidemiologic studies consistently demonstrate NO2-
health effect associations with asthma hospital admissions and ED
visits among subjects of all ages and children, and with asthma
symptoms in children (U.S. EPA, 2016a, Sections 5.2.2.4 and 5.2.2.3).
The robustness of the evidence is demonstrated by associations found in
studies conducted in diverse locations in the U.S., Canada, and Asia,
including several multicity studies. The evidence for asthma
exacerbation is substantiated by several recent studies with strong
exposure assessment characterized by measuring NO2
concentrations in subjects' location(s). Epidemiologic studies also
demonstrated associations between short-term NO2 exposures
and respiratory symptoms, lung function decrements, and pulmonary
inflammation, particularly for measures of personal total and ambient
NO2 exposures and NO2 measured outside schools.
This is important because there is considerable spatial variability in
NO2 concentrations, and measurements in subjects' locations
may better represent variability in ambient NO2 exposures,
compared to measurements at central site monitors (U.S. EPA, 2016a,
Sections 2.5.3 and 3.4.4). Epidemiologic studies also consistently
indicate ambient or personal NO2-associated increases in
exhaled nitric oxide (eNO, a marker of airway inflammation), which is
coherent with experimental findings for allergic inflammation (U.S.
EPA, 2016a, Section 5.2.2.6).
In assessing the evidence from epidemiologic studies, the ISA not
only considers the consistency of effects across studies, but also
evaluates other study attributes that affect study quality, including
potential confounding and exposure assignment. Regarding potential
confounding, the ISA notes that NO2 associations with
asthma-related effects persist with adjustment for temperature;
humidity; season; long-term time trends; and PM10,
SO2, or O3. Recent studies also add findings for
NO2 associations that generally persist with adjustment for
a key copollutant, including PM2.5 and traffic-related
copollutants such as elemental carbon (EC) or black carbon (BC), ultra-
fine particles (UFPs), or carbon monoxide (CO) (U.S. EPA, 2016a,
Figures 5-16 and 5-17, Table 5-38). Confounding by organic carbon (OC),
PM metal species, or volatile organic compounds (VOCs) is poorly
studied, but NO2 associations
[[Page 34805]]
with asthma exacerbation tend to persist in the few available
copollutant models. The ISA recognizes, however, that copollutant
models have inherent limitations and cannot conclusively rule out
confounding (U.S. EPA, 2015, Preamble, Section 4.b).
The ISA also notes that results based on personal exposures or
pollutants measured at people's locations provide support for
NO2 associations that are independent of PM2.5,
EC/BC, organic carbon (OC), or UFPs. Compared to ambient NO2
concentrations measured at central-site monitors, personal
NO2 exposure concentrations and indoor NO2
concentrations exhibit lower correlations with many traffic-related
copollutants (e.g., r = -0.37 to 0.31). Thus, these health effect
associations with personal and indoor NO2 may be less prone
to confounding by these traffic-related copollutants (U.S. EPA, 2016a,
Section 1.4.3).
Overall, the strongest evidence supporting the conclusion of the
causal relationship determined in the ISA comes from controlled human
exposure studies demonstrating NO2-induced increases in AR
in individuals with asthma, with supporting evidence for a range of
respiratory effects from epidemiologic studies. The conclusion of a
causal relationship in the ISA is based on this evidence, and its
explicit integration within the context of effects related to asthma
exacerbation. Most of the controlled human exposure studies assessed in
the ISA were available in the last review, particularly studies of non-
specific AR, and thus, do not themselves provide substantively new
information. However, by pooling data from a subset of studies, the
newly available meta-analysis (Brown, 2015) has partially addressed an
uncertainty from the last review by demonstrating the potential for
clinically relevant increases in AR following exposures to
NO2 concentrations in the range of 100 to 530 ppb.
Similarly, the epidemiologic evidence that is newly available in the
current review is consistent with evidence from the last review and
does not alter the understanding of respiratory effects related to
ambient NO2 exposures. New epidemiologic evidence does,
however, reduce some uncertainty from the last review regarding the
extent to which effects may be independently related to NO2
as there is more evidence from studies using measures that may better
capture personal exposure as well as a more robust evidence base
examining copollutant confounding. Some uncertainty remains in the
epidemiologic evidence regarding confounding by the most relevant
copollutants as it can be difficult to disentangle the independent
effects of highly correlated pollutants (i.e., NO2 and
traffic-related pollutants).
ii. Cardiovascular Effects
The evidence for cardiovascular health effects and short-term
NO2 exposures in the 2016 ISA was judged ``suggestive of,
but not sufficient to infer, a causal relationship'' (U.S. EPA, 2016a,
Section 5.3.11), which is stronger than the conclusion in the last
review that the evidence was ``inadequate to infer the presence or
absence of a causal relationship.'' The more recent causal
determination was primarily supported by consistent epidemiologic
evidence from multiple new studies indicating associations for
triggering of a myocardial infarction. However, further evaluation and
integration of evidence points to uncertainty related to exposure
measurement error and potential confounding by traffic-related
pollutants. There is consistent evidence demonstrating NO2-
associated hospital admissions and ED visits for ischemic heart
disease, myocardial infarction, and angina as well as all
cardiovascular diseases combined, which is coherent with evidence from
other studies indicating NO2-associated repolarization
abnormalities and cardiovascular mortality. There are experimental
studies that provide some evidence for effects on key events in the
proposed mode of action (e.g., systemic inflammation), but these
studies do not provide evidence that is sufficiently coherent with the
epidemiologic studies to help rule out chance, confounding, and other
biases. In particular, the ISA concludes that ``[t]here continues to be
a lack of experimental evidence that is coherent with the epidemiologic
studies to strengthen the inference of causality for NO2-
related cardiovascular effects, including [myocardial infarction]''
(U.S. EPA, 2016a, p. 5-335). Beyond evidence for myocardial infarction,
there were studies examining other cardiovascular health effects, but
results across these outcomes are inconsistent. Thus, while the
evidence is stronger in the current review than in the last review,
important uncertainties remain regarding the independent effects of
NO2.
iii. Mortality
The ISA concludes that the evidence for short-term NO2
exposures and total mortality is ``suggestive of, but not sufficient to
infer, a causal relationship'' (U.S. EPA, 2016a, Section 5.4.8), which
is the same conclusion reached in the last review (U.S. EPA, 2008a).
Several recent multicity studies add to the evidence base for the
current review and demonstrate associations that are robust in
copollutant models with PM10, O3, or
SO2. However, confounding by traffic-related copollutants,
which is of greatest concern, is not examined in the available
copollutant models for NO2-associated mortality. Overall,
the recent evidence assessed in the ISA builds upon and supports
conclusions in the last review, but key limitations across the evidence
include a lack of biological plausibility as experimental studies and
epidemiologic studies on cardiovascular morbidity, a major cause of
mortality, do not clearly provide a mechanism by which NO2-
related effects could lead to mortality. In addition, important
uncertainties remain regarding the independent effect of NO2
(i.e., independent of other traffic-related pollutants).
b. Short-Term NO2 Concentrations in Health Studies
In evaluating what the available health evidence indicates with
regard to the degree of public health protection provided by the
current standards, it is appropriate to consider the short-term
NO2 concentrations that have been associated with various
effects. The PA explicitly considers these NO2
concentrations within the context of evaluating the public health
protection provided by the current standards (U.S. EPA, 2017a, Section
3.2). This section summarizes those considerations from the PA.
In evaluating the NO2 exposure concentrations associated
with health effects within the context of considering the adequacy of
the current standards, the PA focuses on the evidence for asthma-
related effects (i.e., the strongest evidence supporting a causal
relationship, as discussed above). The PA specifically considers to
what extent the evidence indicates adverse asthma-related effects
attributable to short-term exposures to NO2 concentrations
lower than previously identified or below the existing standards (U.S.
EPA, 2017a p. 3-11). In addressing this issue, the PA considers the
extent to which NO2-induced adverse effects have been
reported over the ranges of NO2 exposure concentrations
evaluated in controlled human exposure studies and the extent to which
NO2-associated effects have been reported for distributions
of ambient NO2 concentrations in epidemiologic study
locations meeting existing standards. These considerations are
discussed below for controlled human exposure studies (II.C.1.b.i) and
epidemiologic studies (II.C.1.b.ii).
[[Page 34806]]
i. NO2 Concentrations in Controlled Human Exposure Studies
Controlled human exposure studies, most of which were available and
considered in the last review, have evaluated various respiratory
effects following short-term NO2 exposures. These include
AR, inflammation and oxidative stress, respiratory symptoms, and lung
function decrements. Generally, when considering respiratory effects
from controlled human exposure studies in healthy adults without
asthma, evidence does not indicate respiratory symptoms or lung
function decrements following NO2 exposures below 4,000 ppb
and limited evidence indicates airway inflammation following exposures
below 1,500 ppb (U.S. EPA, 2016a, Section 5.2.7).\50\ There is a
substantial body of evidence demonstrating increased AR in healthy
adults with exposures in the range of 1,500-3,000 ppb.
---------------------------------------------------------------------------
\50\ Exposure durations were from one to three hours in studies
evaluating AR and respiratory symptoms, and up to five hours in
studies evaluating lung function decrements.
---------------------------------------------------------------------------
Evidence for respiratory effects following exposures to
NO2 concentrations at or near those found in the ambient air
is strongest for AR in individuals with asthma (U.S. EPA, 2016a,
Section 5.2.2 p. 5-7). As discussed above, increased AR has been
reported in people with asthma following exposures to NO2
concentrations as low as 100 ppb. In contrast, controlled human
exposure studies evaluated in the ISA do not provide consistent
evidence for respiratory symptoms, lung function decrements, or
pulmonary inflammation in adults with asthma following exposures to
NO2 concentrations at or near those in ambient air (i.e.,
<1,000 ppb; U.S. EPA, 2016a, Section 5.2.2). There is some indication
of allergic inflammation in adults with allergy and asthma following
exposures to 260-1,000 ppb. However, the generally high exposure
concentrations make it difficult to interpret the likelihood that these
effects could potentially occur following NO2 exposures at
or below the level of the current standard.
Thus, in considering the exposure concentrations evaluated in
controlled human exposure studies, the PA focuses on the body of
evidence for NO2-induced increases AR in adults with asthma.
In evaluating the NO2 exposure concentrations at which
increased AR is observed, the PA considers both the group mean results
reported in individual studies and the results evaluated across studies
in the meta-analysis by Brown (2015; U.S. EPA, 2016a, Section 5.2.2.1).
Group mean responses in individual studies, and the variability in
those responses, can provide insight into the extent to which observed
changes in AR are due to NO2 exposures, rather than to
chance alone, and have the advantage of being based on the same
exposure conditions. The meta-analysis by Brown (2015) aids in
identifying trends in individual-level responses across studies and has
the advantage of increased power to detect effects, even in the absence
of statistically significant effects in individual studies.\51\
---------------------------------------------------------------------------
\51\ Tables 3-2 and 3-3 in the NO2 PA (adapted from
the ISA; U.S. EPA, 2016a, Tables 5-1 and 5-2) provide details for
the studies examining AR in individuals with asthma at rest and with
exercise, respectively. These tables note various study details
including the exposure concentration, duration of exposure, type of
challenge (nonspecific or specific), number of study subjects,
number of subjects having an increase or decrease in AR following
NO2 exposure, average provocative dose (PD; dose of
challenge agent required to elicit a particular magnitude of change
in FEV1 or other measure of lung function) across
subjects, and the statistical significance of the change in AR
following NO2 exposures.
---------------------------------------------------------------------------
Consideration of Group Mean Results From Individual Studies
In first considering controlled human exposure studies conducted at
rest, the PA notes that the lowest NO2 concentration to
which individuals with asthma have been exposed is 100 ppb, with an
exposure duration of 60 minutes in all studies. Of the five studies
conducted at 100 ppb, a statistically significant increase in AR
following exposure to NO2 was only observed in the study by
Orehek et al. (1976) (N=20). Of the four studies that did not report
statistically significant increases in AR following exposures to 100
ppb NO2, three reported weak trends towards decreased AR (n
= 20, Ahmed et al., 1983b; n=15, Hazucha et al., 1983; n=8, Tunnicliffe
et al., 1994), and one reported a trend towards increased AR (n=20,
Ahmed et al., 1983a). Resting exposures to 140 ppb NO2
resulted in increases in AR that reached marginal statistical
significance (n=20; Bylin et al., 1988). In addition, the one study
conducted at 200 ppb demonstrated a trend towards increased AR, but
this study was small and results were not statistically significant
(n=4; Orehek et al., 1976). Thus, individual controlled human exposure
studies have generally not reported statistically significant increases
in AR following resting exposures to NO2 concentrations from
100 to 200 ppb. Group mean responses in these studies suggest a trend
towards increased AR following exposures to 140 and 200 ppb
NO2, while trends in the direction of group mean responses
were inconsistent following exposures to 100 ppb NO2.
In next considering studies in individuals with asthma conducted
with exercise, the PA notes that three studies evaluated NO2
exposure concentrations between 150 and 200 ppb (n=19, Roger et al.,
1990; n=31, Kleinman et al., 1983; n=11, Jenkins et al., 1999). Of
these studies, only Kleinman et al. (1983) reported a statistically
significant increase in AR following NO2 exposure (i.e., at
200 ppb). Roger et al. (1990) and Jenkins et al. (1999) did not report
statistically significant increases, but showed weak trends for
increases in AR following exposures to 150 ppb and 200 ppb
NO2, respectively. Thus, as with studies of resting
exposures, studies that evaluated exposures to 150 to 200 ppb
NO2 with exercise report trends toward increased AR, though
results are generally not statistically significant.
Several studies evaluated exposures of individuals with asthma to
NO2 concentrations above 200 ppb. Of the five studies that
evaluated 30-minute resting exposures to NO2 concentrations
from 250 to 270 ppb, NO2-induced increases in AR were
statistically significant in three (n=14, J[ouml]rres et al., 1990;
n=18, Strand et al., 1988; n=20, Bylin et al., 1988). Statistically
significant increases in AR are also more consistently reported across
studies that evaluated resting exposures to 400-530 ppb NO2,
with three of four studies reporting a statistically significant
increase in AR following such exposures. However, studies conducted
with exercise do not indicate consistent increases in AR following
exposures to NO2 concentrations from 300 to 600 ppb (U.S.
EPA, 2017a, Table 3-3).\52\
---------------------------------------------------------------------------
\52\ There are eight additional studies with exercising
exposures to 300-350 ppb NO2 as presented in Table 3-3 of
the NO2 PA, with exposure durations ranging from 30-240
minutes. Results across these studies are inconsistent, with only
two of eight reporting significant results. Only one of four studies
with exercising exposures of 400 or 600 ppb reported statistically
significant increases in airway responsiveness.
---------------------------------------------------------------------------
Consideration of Results From the Meta-Analysis
As discussed above, the ISA assessment of the evidence for AR in
individuals with asthma also focuses on a recently published meta-
analysis (Brown, 2015) investigating individual-level data from
controlled human exposure studies. While individual controlled human
exposure studies can lack statistical power to identify effects, the
meta-analysis of individual-level data combined from multiple studies
(Brown, 2015) has greater statistical
[[Page 34807]]
power due to increased sample size. The meta-analysis considered
individual-level responses, specifically whether individual study
subjects experienced an increase or decrease in AR following
NO2 exposure compared to air exposure.\53\ Evidence was
evaluated together across all studies and also stratified for exposures
conducted with exercise and at rest, and for measures of specific and
non-specific AR. The ISA notes that these methodological differences
may have important implications with regard to results (U.S. EPA, 2016a
(discussing Brown, 2015; Goodman et al., 2009)), contributing to the
ISA's emphasis on studies of resting exposures and non-specific
challenge agents. Overall, the meta-analysis presents the fraction of
individuals having an increase in AR following exposure to various
NO2 concentrations (i.e., 100 ppb, 100 ppb to <200 ppb, 200
ppb up to and including 300 ppb, and above 300 ppb) (U.S. EPA, 2016a,
Section 5.2.2.1).\54\ \55\
---------------------------------------------------------------------------
\53\ The meta-analysis combined information from the studies
presented in Tables 3-2 and 3-3 of the PA.
\54\ Brown et al. (2015) compared the number of study
participants who experienced an increase in AR following
NO2 exposures to the number who experienced a decrease in
AR. Study participants who experienced no change in AR were not
included in comparisons. P-value refers to the significance level of
a two-tailed sign test.
\55\ The number of participants in each study and the number
having an increase or decrease in AR is indicated in Tables 3-2 and
3-3 of the NO2 PA.
---------------------------------------------------------------------------
When evaluating results from the meta-analysis, first the PA
considers results across all exposure conditions (i.e., resting,
exercising, non-specific challenge, and specific challenge). For 100
ppb NO2 exposures, Brown (2015) reported that, of the study
participants who experienced either an increase or decrease in AR
following NO2 exposures, 61% experienced an increase
(p=0.08). For 100 to <200 ppb NO2 exposures, 62% of study
subjects experienced an increase in AR following NO2
exposures (p=0.014). For 200 to 300 ppb NO2 exposures, 58%
of study subjects experienced an increase in AR following
NO2 exposures (p=0.008). For exposures above 300 ppb
NO2, 57% of study subjects experienced an increase in AR
following NO2 exposures, though this fraction was not
statistically different than the fraction experiencing a decrease.
The PA also considers the results of Brown (2015) for various
subsets of the available studies, based on the exposure conditions
evaluated (i.e., resting, exercising) and the type of challenge agent
used (specific, non-specific). For exposures conducted at rest, across
all exposure concentrations (i.e., 100-530 ppb NO2, n=139;
U.S. EPA, 2017a, Table 3-2), Brown (2015) reported that a statistically
significant fraction of study participants (71%, p <0.001) experienced
an increase in AR following NO2 exposures, compared to the
fraction that experienced a decrease in AR. The meta-analysis also
presented results for various concentrations or ranges of
concentrations. Following resting exposure to 100 ppb NO2,
66% of study participants experienced increased non-specific AR. For
exposures to concentrations of 100 ppb to <200 ppb, 200 ppb up to and
including 300 ppb, and above 300 ppb, increased non-specific AR was
reported in 67%, 78%, and 73% of study participants, respectively.\56\
For non-specific challenge agents, the differences between the
fractions of individuals who experienced increased AR following resting
NO2 exposures and the fraction who experienced decreased AR
reached statistical significance for all of the ranges of exposures
concentrations evaluated (p <0.05).
---------------------------------------------------------------------------
\56\ For the exposure category of ``above 300 ppb'', exposures
included 400, 480, 500, and 530 ppb. No studies conducted at rest
used concentrations between 300 and 400 ppb.
---------------------------------------------------------------------------
In contrast to the results from studies conducted at rest, the
fraction of individuals having an increase in AR following
NO2 exposures with exercise was not consistently greater
than 50%, and none of the results were statistically significant
(Brown, 2015). Across all NO2 exposures with exercise,
measures of non-specific AR were available for 241 individuals, 54% of
whom experienced an increase in AR following NO2 exposures
relative to air controls. There were no studies in this group conducted
at 100 ppb, and for exercising exposures to 150-200 ppb, 250-300 ppb,
and 350-600 ppb, the fraction of individuals with increased AR was 59%,
55%, and 49%, respectively.
In addition to examining results from studies of non-specific AR,
the meta-analysis also considered results from studies that evaluated
changes in specific AR (i.e., AR following an allergen challenge;
n=130; U.S. EPA, 2017a, Table 3-3) following NO2 exposures.
The results do not indicate statistically significant fractions of
individuals having an increase in specific AR following exposure to
NO2 at concentrations below 400 ppb, even when considering
resting and exercising exposures separately (Brown, 2015). Of the three
studies that evaluated specific AR at concentrations of 400 ppb, one
was conducted at rest (Tunnicliffe et al., 1994). This study reported
that all individuals experienced increased AR following 400 ppb
NO2 exposures (Brown, 2015, Table 4). In contrast, for
exposures during exercise, most study subjects did not experience
NO2-induced increases in specific AR.\57\ Overall, results
across studies are less consistent for increases in specific AR
following NO2 exposures.
---------------------------------------------------------------------------
\57\ Forty-eight percent experienced increased AR and 52%
experienced decreased AR, based on individual-level data for study
participants exposed to 350 ppb (Riedl et al., 2012) or 400 ppb
(Jenkins et al., 1999; Witten et al., 2005) NO2.
---------------------------------------------------------------------------
Uncertainties in Evidence for AR
When considering the evidence for NO2-induced increases
in AR in individuals with asthma, there are important uncertainties
that should be considered. One uncertainty is that available studies of
NO2 and AR have generally evaluated adults with mild asthma,
while people with more severe cases could experience more serious
effects and/or effects following exposures to lower NO2
concentrations.\58\ Additional uncertainties include the lack of an
apparent dose-response relationship and uncertainty in the potential
adversity of the reported effects. Each of these is discussed below.
---------------------------------------------------------------------------
\58\ Brown (2015) notes, however, that disease status varied,
ranging from ``inactive asthma up to severe asthma in a few
studies.''
---------------------------------------------------------------------------
Both the meta-analysis by Brown (2015) and an additional meta-
analysis and meta-regression by Goodman et al. (2009) conclude that
there is no indication of a dose-response relationship for exposures
between 100 and 500 ppb NO2 and increased AR in individuals
with asthma. A dose-response relationship generally increases
confidence that observed effects are due to pollutant exposures rather
than to chance; however, the lack of a dose-response relationship does
not necessarily indicate that there is no relationship between the
exposure and effect, particularly in these analyses based on between-
subject comparisons (i.e., as opposed to comparisons within the same
subject exposed to multiple concentrations). As discussed in the ISA,
there are a number of methodological differences across studies that
could contribute to between-subject differences and that could obscure
a dose-response relationship between NO2 and AR. These
include subject activity level (rest versus exercise) during
NO2 exposure, asthma medication usage, choice of airway
challenge agent, method of administering the bronchoconstricting
agents, and physiological endpoint used to assess AR. Such
methodological
[[Page 34808]]
differences across studies likely contribute to the variability and
uncertainty in results across studies and complicate interpretation of
the overall body of evidence for NO2-induced AR. Thus, while
the lack of an apparent dose-response relationship adds uncertainty to
the interpretation of controlled human exposure studies of AR, it does
not necessarily indicate the lack of an NO2 effect.
An additional uncertainty in interpreting these studies within the
context of considering the adequacy of the protection provided by the
NO2 NAAQS is the potential adversity of the reported
NO2-induced increases in AR. As discussed above, the meta-
analysis by Brown (2015) used an approach that is consistent with
guidelines from the ATS and the ERS for the assessment of therapeutic
agents (Reddel et al., 2009) to assess the potential for clinical
relevance of these responses. Specifically, based on individual-level
responses reported in a subset of studies, Brown (2015) considered a
halving of the PD to indicate responses that may be clinically
relevant. With regard to this approach, the ISA notes that ``one
doubling dose change in PD is recognized as a potential indicator,
although not a validated estimate, of clinically relevant changes in AR
(Reddel et al., 2009)'' (U.S. EPA, 2016a, p. 5-12). While there is
uncertainty in using this approach to characterize whether a particular
response in an individual is ``adverse,'' it can provide insight into
the potential for adversity, particularly when applied to a population
of exposed individuals.\59\
---------------------------------------------------------------------------
\59\ As noted above, the degree to which populations in U.S.
urban areas have the potential for such NO2 exposures is
evaluated in Chapter 4 of the PA and described in Section II.D
below.
---------------------------------------------------------------------------
Five studies provided data for each individual's provocative dose.
These five studies provided individual-level data for a total of 72
study participants (116 AR measurements) and eight NO2
exposure concentrations, for resting exposures and non-specific
bronchial challenge agents. Across exposures to 100, 140, 200, 250,
270, 480, 500, and 530 ppb NO2, 24% of study participants
experienced a halving of the provocative dose (indicating increased AR)
while 8% showed a doubling of the provocative dose (indicating
decreased AR). The relative distributions of the provocative doses at
different concentrations were similar, with no dose-response
relationship indicated (Brown, 2015). While these results support the
potential for clinically relevant increases in AR in some individuals
with asthma following NO2 exposures within the range of 100
to 530 ppb, uncertainty remains given that this analysis is limited to
a small subset of studies and given the lack of an apparent dose-
response relationship. In addition, compared to conclusions based on
the entire range of NO2 exposure concentrations evaluated
(i.e., 100 to 530 ppb), there is greater uncertainty in reaching
conclusions about the potential for clinically relevant effects at any
particular NO2 exposure concentration within this range.
PA Conclusions on Short-Term NO2 Concentrations in
Controlled Human Exposure Studies
As in the last review, a meta-analysis of individual-level data
supports the potential for increased AR in individuals with generally
mild asthma following 30 minute to 1 hour exposures to NO2
concentrations from 100 to 530 ppb, particularly for resting exposures
and measures of non-specific AR (N = 33 to 70 for various ranges of
NO2 exposure concentrations). In about a quarter of these
individuals, increases were large enough to be of potential clinical
relevance. Individual studies most consistently report statistically
significant NO2-induced increases in AR following exposures
to NO2 concentrations at or above 250 ppb. Individual
studies (N = 4 to 20) generally do not report statistically significant
increases in AR following exposures to NO2 concentrations at
or below 200 ppb, though the evidence suggests a trend toward increased
AR following NO2 exposures from 140 to 200 ppb. In contrast,
individual studies do not indicate a consistent trend towards increased
AR following 1-hour exposures to 100 ppb NO2. Important
limitations in this evidence include the lack of a dose-response
relationship between NO2 and AR and uncertainty in the
adversity of the reported increases in AR. These limitations become
increasingly important at the lower NO2 exposure
concentrations (i.e., at or near 100 ppb), where the evidence for
NO2-induced increases in AR is not consistent across
studies.
ii. Consideration of NO2 Concentrations in Locations of
Epidemiologic Studies
In addition to considering the exposure concentrations evaluated in
the controlled human exposure studies, the PA also considers
distributions of ambient NO2 concentrations in locations
where epidemiologic studies have examined NO2 associations
with asthma-related hospital admissions or ED visits. These outcomes
are clearly adverse and study results comprise a key line of
epidemiologic evidence in the determination of a causal relationship in
the ISA (U.S. EPA, 2016a, Section 5.2.9). As in other NAAQS reviews
(U.S. EPA, 2014; U.S. EPA, 2011), when considering epidemiologic
studies within the context of evaluating the adequacy of the current
standard, the PA emphasizes those studies conducted in the U.S. and
Canada.\60\ For short-term exposures to NO2, the PA
emphasizes studies reporting associations with effects judged in the
ISA to be robust to confounding by other factors, including exposure to
co-occurring air pollutants. In addition, the PA considers the
statistical precision of study results, and the inclusion of at-risk
populations for which the NO2-health effect associations may
be larger. These considerations help inform the range of ambient
NO2 concentrations over which the evidence indicates the
most confidence in NO2-associated health effects and the
range of concentrations over which confidence in such effects is
appreciably lower. In consideration of these issues, the PA
specifically focuses on the following question: To what extent have
U.S. and Canadian epidemiologic studies reported associations between
asthma-related hospital admissions or ED visits and short-term
NO2 concentrations in study areas that would have met the
current 1-hour NO2 standard during the study period?
---------------------------------------------------------------------------
\60\ Such studies are likely to reflect air quality and exposure
patterns that are generally applicable to the U.S. In addition, air
quality data corresponding to study locations and study time periods
is often readily available for studies conducted in the U.S. and
Canada. Nonetheless, the PA recognizes the importance of all
studies, including other international studies, in the ISA's
assessment of the weight of the evidence that informs the causal
determinations.
---------------------------------------------------------------------------
Addressing this question can provide important insights into the
extent to which NO2- associated health effect associations
are present for distributions of ambient NO2 concentrations
that would be allowed by the current primary standards. The presence of
such associations would support the potential for the current standards
to allow the NO2-associated effects indicated by
epidemiologic studies. To the degree studies have not reported
associations in locations meeting the current NO2 standards,
there is greater uncertainty regarding the potential for the reported
effects to occur following the NO2 exposures associated with
air quality meeting those standards.
In addressing the question above, the PA places the greatest
emphasis on studies reporting positive, and relatively precise (i.e.,
relatively narrow 95% confidence intervals), health effect
[[Page 34809]]
associations. In evaluating whether such associations are likely to
reflect NO2 concentrations meeting the existing 1-hour
standard, the PA considers the 1-hour ambient NO2
concentrations measured at monitors in study locations during study
periods. The PA also considers what additional information is available
regarding the ambient NO2 concentrations that could have
been present in the study locations during the study periods (e.g.,
around major roads). When considered together, this information can
provide important insights into the extent to which NO2
health effect associations have been reported for NO2 air
quality concentrations that likely would have met the current 1-hour
NO2 standard.
The PA evaluates U.S. and Canadian studies of respiratory-related
hospital admissions and ED visits, with a focus on studies of asthma-
related effects (studies identified from Table 5-10 in U.S. EPA,
2016a).\61\ For each NO2 monitor in the locations included
in these studies, and for the ranges of years encompassed by studies,
the PA identifies the 3-year averages of the 98th percentiles of the
annual distributions of daily maximum 1-hour NO2
concentrations.\62\ These concentrations approximate the DVs that are
used when determining whether an area meets the primary NO2
NAAQS.\63\ Thus, these estimated DVs can provide perspective on whether
study areas would likely have met or exceeded the primary 1-hour
NO2 NAAQS during the study periods. Based on this approach,
study locations would likely have met the current 1-hour standard over
the entire study period if all of the hourly DV estimates were at or
below 100 ppb.
---------------------------------------------------------------------------
\61\ Strong support was also provided by epidemiologic studies
for respiratory symptoms, but the majority of studies on respiratory
symptoms were only conducted over part of a year, complicating the
evaluation of a DV based on data from 3 years of monitoring data
relative to the respective health effect estimates. For more
information on these studies and the estimated DVs in the study
locations, see Appendix A of the PA (U.S. EPA, 2017a).
\62\ All study locations had maximum annual DVs below 53 ppb
(U.S. EPA, 2017a, Appendix A).
\63\ As described in I.B.2., a DV is a statistic that describes
the air quality status of a given area relative to the NAAQS and
that is typically used to classify nonattainment areas, assess
progress towards meeting the NAAQS, and develop control strategies.
For the 1-hour NO2 standard, the DV is calculated at
individual monitors and based on 3 consecutive years of data
collected from that site. In the case of the 1-hour NO2
standard, the design value for a monitor is based on the 3-year
average of the 98th percentile of the annual distribution of daily
maximum 1-hour NO2 concentrations. For more information
on these studies and the calculation of the study area DVs estimates
see Appendix A of the NO2 PA (U.S. EPA, 2017a).
---------------------------------------------------------------------------
A key limitation in these analyses of NO2 DV estimates
is that currently required near-road NO2 monitors were not
in place during study periods. The studies evaluated were based on air
quality from 1980-2006, with most studies spanning the 1990s to early
2000s. There were no specific near-road monitoring network requirements
during these years, and most areas did not have monitors sited to
measure NO2 concentrations near the most heavily-trafficked
roadways. In addition, mobile source NOX emissions were
considerably higher during the time periods of the available
epidemiologic studies than in more recent years (U.S. EPA, 2017a,
section 2.1.2), suggesting that the NO2 concentration
gradients around major roads could have been more pronounced than
indicated by data from recently deployed near-road monitors.\64\ This
information suggests that if the current near-road monitoring network
had been in operation during study periods, NO2
concentrations measured at near-road monitors would likely have been
higher than those identified in the PA (U.S. EPA, 2017a, Figure 3-1).
This uncertainty particularly limits the degree to which strong
conclusions can be reached based on study areas with DV estimates that
are at or just below 100 ppb.\65\
---------------------------------------------------------------------------
\64\ Recent data indicate that, for most near-road monitors,
measured 1-hour NO2 concentrations are higher than those
measured at all of the non-near-road monitors in the same CBSA
(Section II.B.3).
\65\ Epidemiologic studies that evaluate potential
NO2 health effect associations during time periods when
near-road monitors are operational could reduce this uncertainty in
future reviews.
---------------------------------------------------------------------------
With this key limitation in mind, the PA considers what the
available epidemiologic evidence indicates with regard to the adequacy
of the public health protection provided by the current 1-hour standard
against short-term NO2 exposures. To this end, the PA
highlights the epidemiologic studies examining associations between
asthma hospitalizations or ED visits and short-term exposures to
ambient NO2 that were conducted in the U.S. and Canada (U.S.
EPA, 2017a, Figure 3-1). These studies were identified and evaluated in
the ISA and include both the few recently published studies and the
studies that were available in the previous review.
In considering the epidemiologic information presented in the U.S.
and Canadian studies, the PA notes that multi-city studies tend to have
greater power to detect associations. The one multi-city study that has
become available since the last review (Stieb et al., 2009) reported a
null association with asthma ED visits, based on study locations with
maximum estimated DVs ranging from 67-242 ppb (six of seven study
cities had maximum estimated DVs at or above 85 ppb). Of the single
city studies identified, those reporting positive and relatively
precise associations were conducted in locations with maximum, and
often mean, estimated DVs at or above 100 ppb (i.e., Linn et al., 2000;
Peel et al., 2005; Ito et al., 2007; Villeneuve et al., 2007; Burnett
et al., 1999; Strickland et al., 2010). Maximum estimated DVs from
these study locations ranged from 100 to 242 ppb (U.S. EPA, Figure 3-
1). For the other single city studies, two reported more mixed results
in locations with maximum estimated DVs around 90 ppb (Jaffe et al.,
2003; ATSDR, 2006).\66\ Associations in these studies were generally
not statistically significant, were less precise (i.e., wider 95%
confidence intervals), and included a negative association (Manhattan,
NY). One single city study was conducted in a location with 1-hour
estimated DVs well-below 100 ppb (Li et al., 2011), though the reported
associations were not statistically significant and were relatively
imprecise. Thus, of the U.S. and Canadian studies that can most clearly
inform consideration of the adequacy of the current NO2
standards, the lone multicity study did not report a positive health
effect association and the single-city studies reporting positive, and
relatively precise, associations were generally conducted in locations
with maximum 1-hour estimated DVs at or above 100 ppb (i.e., up to 242
ppb). The evidence for associations in locations with maximum estimated
DVs below 100 ppb is more mixed, and reported associations are
generally less precise.
---------------------------------------------------------------------------
\66\ The study by the U.S. Agency for Toxic Substances and
Disease Registry (ATSDR) was not published in a peer-review journal.
Rather, it was a report prepared by New York State Department of
Health's Center for Environmental Health, the New York State
Department of Environmental Conservation and Columbia University in
the course of performing work contracted for and sponsored by the
New York State Energy Research and Development Authority and the
ATSDR.
---------------------------------------------------------------------------
An uncertainty in this body of evidence is the potential for
copollutant confounding. Copollutant (two-pollutant) models can be used
in epidemiologic studies in an effort to disentangle the independent
pollutant effects, though there can be limitations in these models due
to differential exposure measurement error and high correlations with
traffic-related copollutants. For NO2, the copollutants that
are most relevant to consider are those from traffic sources such as
CO, EC/BC, UFP, and VOCs such as benzene as well as PM2.5
and PM10 (U.S. EPA, 2016a, Section 3.5). Of the studies
[[Page 34810]]
examining asthma-related hospital admissions and ED visits in the U.S.
and Canada, three examined copollutant models (Ito et al., 2007;
Villeneuve et al., 2007; Strickland et al., 2010). Ito et al. (2007)
found that in copollutant models with PM2.5, SO2,
CO, or O3, NO2 consistently had the strongest
effect estimates that were robust to the inclusion of other pollutants.
Villeneuve et al. (2007) utilized a model including NO2 and
CO (r = 0.74) for ED visits in the warm season and reported that
associations for NO2 were robust to CO. Strickland et al.
(2010) found that the relationship between ambient NO2 and
asthma ED visits in Atlanta, GA was robust in models including
O3, but copollutant models were not analyzed for other
pollutants and the correlations between NO2 and other
pollutants were not reported. Taken together, these studies provide
some evidence for independent effects of NO2 for asthma ED
visits, but some important traffic-related copollutants (e.g. EC/BC,
VOCs) have not been examined in this body of evidence and the
limitations of copollutant models in demonstrating an independent
association are noted (U.S. EPA, 2016a).
Considering this evidence together, the PA notes the following
observations. First, the only recent multicity study evaluated, which
had maximum estimated DVs ranging from 67 to 242 ppb, did not report a
positive association between NO2 and ED visits (Stieb et
al., 2009). In addition, of the single-city studies reporting positive
and relatively precise associations between NO2 and asthma
hospital admissions and ED visits, most locations likely had
NO2 concentrations above the current 1-hour NO2
standard over at least part of the study period. Although maximum
estimated DVs for the studies conducted in Atlanta were 100 ppb, it is
likely that those DVs would have been higher than 100 ppb if currently
required near-road monitors had been in place. For the study locations
with maximum estimated DVs below 100 ppb, mixed results are reported
with associations that are generally not statistically significant and
imprecise, indicating that associations between NO2
concentrations and asthma-related ED visits are more uncertain in
locations that could have met the current standards. Given that near-
road monitors were not in operation during study periods, it is not
clear that these DVs below 100 ppb indicate study areas that would have
met the current 1-hour standard.
Thus, while epidemiologic studies provide support for
NO2-associated hospital admissions and ED visits at ambient
NO2 concentrations likely to have been above those allowed
by the current 1-hour standard, the PA reaches the conclusion that
available U.S. and Canadian epidemiologic studies do not provide
support for such NO2-associated outcomes in locations with
NO2 concentrations that would have clearly met that
standard.
2. Health Effects With Long-Term Exposure to NO2
This section discusses the evidence for health effects associated
with long-term NO2 exposures. Section II.C.2.a discusses the
nature of the health effects that have been shown to be associated with
long-term NO2 exposures and the strength of the evidence
supporting various effects, based on the assessment of that evidence in
the ISA. Section II.C.2.b discusses the NO2 concentrations
at which health effects have been demonstrated to occur, based on the
considerations and analyses included in the PA.
a. Nature of Effects
In the last review of the primary NO2 NAAQS, evidence
for health effects related to long-term ambient NO2 exposure
was judged ``suggestive of, but not sufficient to infer a causal
relationship'' for respiratory effects and ``inadequate to infer the
presence or absence of a causal relationship'' for several other health
effect categories. These included cardiovascular, and reproductive and
developmental effects as well as cancer and total mortality. In the
current review, new epidemiologic evidence, in conjunction with
explicit integration of evidence across related outcomes, has resulted
in strengthening of some of the causal determinations. Though the
evidence of health effects associated with long-term exposure to
NO2 is more robust than in previous reviews, there are still
a number of uncertainties limiting understanding of the role of long-
term NO2 exposures in causing health effects.
Chapter 6 of the ISA presents a detailed assessment of the evidence
for health effects associated with long-term NO2 exposures
(U.S. EPA, 2016a). This evidence is summarized briefly below for
respiratory effects (II.C.2.a.i), cardiovascular effects and diabetes
(II.C.2.a.ii), reproductive and developmental effects (II.C.2.a. iii),
premature mortality (II.C.2.a.iv), and cancer (II.C.2.a.v).
i. Respiratory Effects
The 2016 ISA concluded that there is ``likely to be a causal
relationship'' between long-term NO2 exposure and
respiratory effects, based primarily on evidence integrated across
disciplines for a relationship with asthma development in children.\67\
Evidence for other respiratory outcomes integrated across epidemiologic
and experimental studies, including decrements in lung function and
partially irreversible decrements in lung development, respiratory
disease severity, chronic bronchitis/asthma incidence in adults,
chronic obstructive pulmonary disease (COPD) hospital admissions, and
respiratory infections, is less consistent and has larger uncertainty
as to whether there is an independent effect of long-term
NO2 exposure (U.S. EPA, 2016a, Section 6.2.9). As noted
above, NO2 is only one of many etiologic agents that may
contribute to respiratory health effects such as the development of
asthma in children.
---------------------------------------------------------------------------
\67\ Asthma development is also referred to as ``asthma
incidence'' in this notice and elsewhere. Both asthma development
and asthma incidence refer to the onset of the disease rather than
the exacerbation of existing disease.
---------------------------------------------------------------------------
The conclusion of a ``likely to be a causal relationship'' in the
current review represents a change from 2008 ISA conclusion that the
evidence was ``suggestive of, but not sufficient to infer, a causal
relationship'' (U.S. EPA, 2008a, Section 5.3.2.4). This strengthening
of the causal determination is due to the epidemiologic evidence base,
which has expanded since the last review and biological plausibility
from some experimental studies (U.S. EPA, 2016 Table 1-1). This
expanded evidence includes several recently published longitudinal
studies that indicate positive associations between asthma incidence in
children and long-term NO2 exposures, with improved exposure
assessment in some studies based on NO2 modeled estimates
for children's homes or NO2 measured near children's homes
or schools. Associations were observed across various periods of
exposure, including first year of life, year prior to asthma diagnosis,
and cumulative exposure. In addition, the ISA notes several other
strengths of the evidence base including the general timing of asthma
diagnosis and relative confidence that the NO2 exposure
preceded asthma development in longitudinal studies, more reliable
estimates of asthma incidence based on physician-diagnosis in children
older than 5 years of age from parental report or clinical assessment,
as well as residential NO2 concentrations estimated from
land use regression (LUR) models with good NO2 prediction in
some studies.
While the causal determination has been strengthened in this
review,
[[Page 34811]]
important uncertainties remain. For example, the ISA notes that as in
the last review, a ``key uncertainty that remains when examining the
epidemiologic evidence alone is the inability to determine whether
NO2 exposure has an independent effect from that of other
pollutants in the ambient mixture'' (U.S. EPA, 2016a, Section 6.2.2.1,
p. 6-21). While a few studies have included copollutant models for
respiratory effects other than asthma development, the ISA states that
``[e]pidemiologic studies of asthma development in children have not
clearly characterized potential confounding by PM2.5 or
traffic-related pollutants [e.g., CO, BC/EC, volatile organic compounds
(VOCs)]'' (U.S. EPA, 2016a, p. 6-64). The ISA further notes that ``[i]n
the longitudinal studies, correlations with PM2.5 and BC
were often high (e.g., r = 0.7-0.96), and no studies of asthma
incidence evaluated models to address copollutant confounding, making
it difficult to evaluate the independent effect of NO2''
(U.S. EPA, 2016a, p. 6-64). High correlations between NO2
and other traffic-related pollutants were based on modeling, and
studies of asthma incidence that used monitored NO2
concentrations as an exposure surrogate did not report such
correlations (U.S. EPA, 2016a, Table 6-1). This uncertainty is
important to consider when interpreting the epidemiologic evidence
regarding the extent to which NO2 is independently related
to asthma development.
The ISA also evaluated copollutant confounding in long-term
exposure studies beyond asthma incidence to examine whether studies of
other respiratory effects could provide information on the potential
for confounding by traffic-related copollutants. Several studies
examined correlations between NO2 and traffic-related
copollutants and found them to be relatively high in many cases,
ranging from 0.54-0.95 for PM2.5, 0.54-0.93 for BC/EC, 0.2-
0.95 for PM10, and 0.64-0.86 for OC (U.S. EPA, 2016a, Tables
6-1 and 6-3). While these correlations are often based on model
estimates, some are based on monitored pollutant concentrations (i.e.,
McConnell et al. (2003) reported correlations of 0.54 with
PM2.5 and EC) (U.S. EPA, 2016a, Table 6-3). Additionally,
three studies (McConnell et al., 2003; MacIntyre et al., 2014; Gehring
et al., 2013) \68\ evaluated copollutant models with NO2 and
PM2.5, and some findings suggest that associations for
NO2 with bronchitic symptoms, lung function, and respiratory
infection are not robust because effect estimates decreased in
magnitude and became imprecise when a copollutant was added in the
model. Overall, examination of evidence from studies of other
respiratory effects indicates moderate to high correlations between
long-term NO2 concentrations and traffic-related
copollutants, with very limited evaluation of the potential for
confounding. Thus, when considering the collective evidence, it is
difficult to disentangle the independent effect of NO2 from
other traffic-related pollutants or mixtures in epidemiologic studies
(U.S. EPA, 2016a, Sections 3.4.4 and 6.2.9.5).
---------------------------------------------------------------------------
\68\ In single-pollutant models for various health endpoints,
the studies reported the following effect estimates (95% CI):
McConnell et al., 2003 (Bronchitic symptoms) 1.97 (1.22, 3.18);
MacIntyre et al., 2014 (Pneumonia) 1.30 (1.02, 1.65), (Otitis Media)
1.09 (1.02, 1.16), (Croup) 0.96 (0.83, 1.12); Gehring et al., 2013
(FEV1) -0.98 (-1.70, -0.26), (FVC) -2.14 (-4.20, -0.04), (PEF) -1.04
(-1.94, -0.13).
---------------------------------------------------------------------------
While this uncertainty continues to apply to the epidemiologic
evidence for asthma incidence in children, the ISA describes that the
uncertainty is partly reduced by the coherence of findings from
experimental studies and epidemiologic studies. Experimental studies
demonstrate effects on key events in the mode of action proposed for
the development of asthma and provide biological plausibility for the
epidemiologic evidence. For example, one study demonstrated that airway
hyperresponsiveness was induced in guinea pigs after long-term exposure
to NO2 [1,000-4,000 ppb; (Kobayashi and Miura, 1995)]. Other
experimental studies examining oxidative stress report mixed results,
but some evidence from short-term studies supports a relationship
between NO2 exposure and increased pulmonary inflammation in
healthy humans. The ISA also points to supporting evidence from studies
demonstrating that short-term exposure repeated over several days (260-
1,000 ppb) and long-term NO2 exposure (2,000-4,000 ppb) can
induce T helper (Th)2 skewing/allergic sensitization in healthy humans
and animal models by showing increased Th2 cytokines, airway
eosinophils, and immunoglobulin E (IgE)-mediated responses (U.S. EPA,
2016a, Sections 4.3.5 and 6.2.2.3). Epidemiologic studies also provide
some supporting evidence for these key events in the mode of action.
Some evidence from epidemiologic studies demonstrates associations
between short-term ambient NO2 concentrations and increases
in pulmonary inflammation in healthy children and adults, giving a
possible mechanistic understanding of this effect (U.S. EPA, 2016a,
Section 5.2.2.5). Overall, evidence from experimental and epidemiologic
studies provide support for a role of NO2 in asthma
development by describing a potential role for repeated exposures to
lead to recurrent inflammation and allergic responses.
Overall, the ISA notes that there is new evidence available that
strengthens conclusions from the last review regarding respiratory
health effects attributable to long-term ambient NO2-
exposure. The majority of new evidence is from epidemiologic studies of
asthma incidence in children with improved exposure assessment (i.e.,
measured or modeled at or near children's homes or schools), which
builds upon previous evidence for associations of long-term
NO2 and asthma incidence and also partly reduces
uncertainties related to measurement error. Explicit integration of
evidence for individual outcome categories (e.g., asthma incidence,
respiratory infection) provides improved characterization of biological
plausibility and mode of action, including some new evidence from
studies of short-term exposure supporting an effect on asthma
development. Although this partly reduces the uncertainty regarding
independent effects of NO2, the potential for confounding
remains a concern when interpreting these epidemiologic studies as a
result of the high correlation with other traffic-related copollutants
and the general lack of copollutant models including these pollutants.
In particular, it remains unclear the degree to which NO2
itself may be causing the development of asthma versus serving as a
surrogate for the broader traffic-pollutant mix.
ii. Cardiovascular Effects and Diabetes
In the previous review, the 2008 ISA stated that the evidence for
cardiovascular effects attributable to long-term ambient NO2
exposure was ``inadequate to infer the presence or absence of a causal
relationship.'' The epidemiologic and experimental evidence was
limited, with uncertainties related to traffic-related copollutant
confounding (U.S. EPA, 2008a). For the current review, the body of
epidemiologic evidence available is substantially larger than that in
the last review and includes evidence for diabetes. The conclusion on
causality is stronger in the current review with regard to the
relationship between long-term exposure to NO2 and
cardiovascular effects and diabetes, as the ISA judged the evidence to
be
[[Page 34812]]
``suggestive, but not sufficient to infer'' a causal relationship (U.S.
EPA, 2016a, Section 6.3). The strongest evidence comes from recent
epidemiologic studies reporting positive associations of NO2
with heart disease and diabetes with improved exposure assessment
(i.e., residential estimates from models that well predict
NO2 concentrations in the study areas), but the evidence
across experimental studies remains limited and inconsistent and does
not provide sufficient biological plausibility for effects observed in
epidemiologic studies. Specifically, the ISA concludes that
``[e]pidemiologic studies have not adequately accounted for confounding
by PM2.5, noise, or traffic-related copollutants, and there
is limited coherence and biological plausibility for NO2-
related development of heart disease'' (U.S. EPA, 2016a, p. 6-98) or
``for NO2-related development of diabetes'' (U.S. EPA,
2016a, p. 6-99). Thus, substantial uncertainty exists regarding the
independent effect of NO2 and the total evidence is
``suggestive of, but not sufficient to infer, a causal relationship''
between long-term NO2 exposure and cardiovascular effects
and diabetes (U.S. EPA, 2016a, Section 6.3.9).
iii. Reproductive and Developmental Effects
In the previous review, a limited number of epidemiologic and
toxicological studies had assessed the relationship between long-term
NO2 exposure and reproductive and developmental effects. The
2008 ISA concluded that there was not consistent evidence for an
association between NO2 and birth outcomes and that evidence
was ``inadequate to infer the presence or absence of a causal
relationship'' with reproductive and developmental effects overall
(U.S. EPA, 2008a). In the ISA for the current review, a number of
recent studies added to the evidence base, and reproductive effects
were considered as three separate categories: birth outcomes;
fertility, reproduction, and pregnancy; and postnatal development (U.S.
EPA, 2016a, Section 6.4). Overall, the ISA found the evidence to be
``suggestive of, but not sufficient to infer, a causal relationship''
between long-term exposure to NO2 and birth outcomes and
``inadequate to infer the presence or absence of a causal
relationship'' between long-term exposure to NO2 and
fertility, reproduction and pregnancy as well as postnatal development.
Evidence for effects on fertility, reproduction, and pregnancy and for
effects on postnatal development is inconsistent across both
epidemiologic and toxicological studies. Additionally, there are few
toxicological studies available. The ISA concludes the change in the
causal determination for birth outcomes reflects the large number of
studies that generally observed associations with fetal growth
restriction and the improved outcome assessment (e.g., measurements
throughout pregnancy via ultrasound) and exposure assessment (e.g.,
well-validated LUR models) employed by many of these studies (U.S. EPA,
2016a, Section 6.4.5). For birth outcomes, there is uncertainty in
whether the epidemiologic findings reflect an independent effect of
NO2 exposure.
iv. Total Mortality
In the 2008 ISA, a limited number of epidemiologic studies assessed
the relationship between long-term exposure to NO2 and
mortality in adults. The 2008 ISA concluded that the scarce amount of
evidence was ``inadequate to infer the presence or absence of a causal
relationship'' (U.S. EPA, 2008a). The ISA for the current review
concludes that evidence is ``suggestive of, but not sufficient to
infer, a causal relationship'' between long-term exposure to
NO2 and mortality among adults (U.S. EPA, 2016a, Section
6.5.3). This causal determination is based on evidence from recent
studies demonstrating generally positive associations between long-term
exposure to NO2 and total mortality from extended analyses
of existing cohorts as well as original results from new cohorts. In
addition, there is evidence for associations between long-term
NO2 exposures and mortality due to respiratory and
cardiovascular causes. However, there were several studies that did not
observe an association between long-term exposure to NO2 and
mortality.
Some recent studies examined the potential for copollutant
confounding by PM2.5, BC, or measures of traffic proximity
or density in copollutant models with results from these models
generally showing attenuation of the NO2 effect on total
mortality with the adjustment for PM2.5 or BC. It remains
difficult to disentangle the independent effect of NO2 from
the potential effect of the traffic-related pollution mixture or other
components of that mixture. Further, as described above, there is large
uncertainty whether long-term NO2 exposure has an
independent effect on the cardiovascular and respiratory morbidity
outcomes that are major underlying causes of mortality. Thus, it is not
clear by what biological pathways NO2 exposure could lead to
mortality. Considering the generally positive epidemiologic evidence
together with the uncertainty regarding an independent NO2
effect, the ISA judged the evidence to be ``suggestive of, but not
sufficient to infer, a causal relationship'' between long-term exposure
to NO2 and total mortality (U.S. EPA, 2016a, 6.5.3).
v. Cancer
The evidence evaluated in the 2008 ISA was judged ``inadequate to
infer the presence or absence of a causal relationship'' (U.S. EPA,
2008a) based on a few epidemiologic studies indicating associations
between long-term NO2 exposure and lung cancer incidence but
lack of toxicological evidence demonstrating that NO2
induces tumors. In the current review, the integration of recent and
older studies on long-term NO2 exposure and cancer yielded
an evidence base judged ``suggestive of, but not sufficient to infer, a
causal relationship'' (U.S. EPA, 2016a, Section 6.6.9). This conclusion
is based primarily on recent epidemiologic evidence, some of which
shows NO2-associated lung cancer incidence and mortality but
does not address confounding by traffic-related copollutants, and is
also based on some previous toxicological evidence that implicates
NO2 in tumor promotion (U.S. EPA, 2016a, Section 6.6.9).
b. Long-Term NO2 Concentrations in Health Studies
In evaluating what the available health evidence indicates with
regard to the degree of public health protection provided by the
current standards, it is appropriate to consider the long-term
NO2 concentrations that have been associated with various
effects. The PA explicitly considers these NO2
concentrations within the context of evaluating the public health
protection provided by the current standards (U.S. EPA, 2017a, Section
3.2). This section summarizes those considerations from the PA.
In evaluating the long-term NO2 concentrations
associated with health effects within the context of considering the
adequacy of the current standards, the PA focuses on the evidence for
asthma incidence (i.e., the strongest evidence supporting a likely to
be causal relationship, as discussed above). The PA specifically
considers (1) the extent to which epidemiologic studies indicate
associations between long-term NO2 exposures and asthma
development for distributions of ambient NO2 concentrations
that would likely have met the existing standards and (2) the extent to
which effects related to asthma development have been reported
following the range of NO2 exposure
[[Page 34813]]
concentrations examined in experimental studies. These considerations
are discussed below for epidemiologic studies (II.C.2.b.i) and
experimental studies (II.C.2.b.ii).
i. Ambient NO2 Concentrations in Locations of Epidemiologic
Studies
As discussed above for short-term exposures (Section II.C.1), when
considering epidemiologic studies of long term NO2 exposures
within the context of evaluating the adequacy of the current
NO2 standards, the PA emphasizes studies conducted in the
U.S. and Canada. The PA considers the extent to which these studies
report positive and relatively precise associations with long-term
NO2 exposures, and the extent to which important
uncertainties could impact the emphasis placed on particular studies.
For the studies with potential to inform conclusions on adequacy, the
PA also evaluates available air quality information in study locations,
focusing on estimated DVs over the course of study periods.
The epidemiologic studies available in the current review that
evaluate associations between long-term NO2 exposures and
asthma incidence are summarized in Table 6-1 of the ISA (U.S. EPA,
2016a, pp. 6-7). There are six longitudinal epidemiologic studies
conducted in the U.S. or Canada that vary in terms of the populations
examined and methods used. Of the six studies, the ISA identifies three
as key studies supporting the causal determination (Carlsten et al.,
2011; Clougherty et al., 2007; Jerrett et al., 2008). The other three
studies, not identified as key studies in the ISA causality
determination, had a greater degree of uncertainty inherent in their
characterizations of NO2 exposures (Clark et al., 2010;
McConnell et al., 2010, Nishimura et al., 2013). In evaluating the
adequacy of the current NO2 standards, the PA places the
greatest emphasis on the three U.S. and Canadian studies identified in
the ISA as providing key supporting evidence for the causal
determination. However, the PA also considers what the additional three
U.S. and Canadian studies can indicate about the adequacy of the
current standards, while noting the increased uncertainty in these
studies.
Effect estimates in U.S. and Canadian studies are generally
positive and, in some cases, statistically significant and relatively
precise (U.S. EPA, 2016a, Table 6-1; U.S. EPA, 2017a, Figure). However,
there are important uncertainties in this body of evidence for asthma
incidence, limiting the extent to which these studies can inform
consideration of the adequacy of the current NO2 standards
to protect against long-term NO2 exposures. For example,
there is uncertainty in the degree to which reported associations are
specific to NO2, rather than reflecting associations with
another traffic-related copollutant or the broader mix of pollutants.
Overall, the potential for copollutant confounding has not been well
studied in this body of evidence, as described above (Section
II.C.2.a). Of the U.S. and Canadian studies, Carlsten et al. (2011)
reported correlations between NO2 and traffic-related
pollutants (0.7 for PM2.5, 0.5 for BC based on land use
regression). Other U.S. and Canadian studies did not report
quantitative results, but generally reported ``moderate'' to ``high''
correlations between NO2 and other pollutants (U.S. EPA,
2016a, Table 6-1). Given the relatively high correlations for
NO2 with co-occurring pollutants, study authors often
interpreted associations with NO2 as reflecting associations
with traffic-related pollution more broadly (e.g., Jerrett et al.,
2008; McConnell et al., 2010).
Another important uncertainty is the potential for exposure
measurement error in these epidemiologic studies. The ISA states that
``a key issue in evaluating the strength of inference about
NO2-related asthma development from epidemiologic studies is
the extent to which the NO2 exposure assessment method used
in a study captured the variability in exposure among study subjects''
(U.S. EPA, 2016a, pp. 6-16). The ISA conclusion of a ``likely to be a
causal relationship'' is based on the total body of evidence, with the
strongest basis for inferring associations of NO2 with
asthma incidence coming from studies that ``estimated residential
NO2 from LUR models that were demonstrated to predict well
the variability in NO2 in study locations or examined
NO2 measured at locations [within] 1-2 km of subjects'
school or home'' (U.S. EPA, 2016a, pp. 6-21). The studies that meet
this criterion were mostly conducted outside of the U.S. or Canada,
with the exception of Carlsten et al. (2011), which used a LUR model
with good predictive capacity. The other U.S. and Canadian studies
employed LUR models with unknown validation, or central-site
measurements that have well-recognized limitations in reflecting
variability in ambient NO2 concentrations in a community and
may not well represent variability in NO2 exposure among
subjects. Thus, the extent to which these U.S. and Canadian studies
provide reliable estimates of asthma incidence for particular
NO2 concentrations is unclear.
Overall, in revisiting the first question posed above, the PA notes
that U.S. and Canadian epidemiologic studies report positive, and in
some cases relatively precise, associations between long-term
NO2 exposure and asthma incidence in children. While it is
appropriate to consider what these studies can tell us with regard to
the adequacy of the existing primary NO2 standards (see
below), the emphasis that is placed on these considerations will
reflect important uncertainties related to the potential for
confounding by traffic-related copollutants and for exposure
measurement error.
While keeping in mind these uncertainties, the PA next considers
the ambient NO2 concentrations present at monitoring sites
in locations and time periods of U.S. and Canadian epidemiologic
studies. Specifically, the PA considers the following question: To what
extent do U.S. and Canadian epidemiologic studies report associations
with long-term NO2 in locations likely to have met the
current primary NO2 standards?
As discussed above for short-term exposures (Section II.C.1),
addressing this question can provide important insights into the extent
to which NO2-health effect associations are present for
distributions of ambient NO2 concentrations that would be
allowed by the current primary standards. The presence of such
associations would support the potential for the current standards to
allow the NO2-associated asthma development indicated by
epidemiologic studies. To the degree studies have not reported
associations in locations meeting the current primary NO2
standards, there is greater uncertainty regarding the potential for the
development of asthma to result from the NO2 exposures
associated with air quality meeting those standards.
To evaluate this issue, the PA compares NO2 estimated
DVs in study areas to the levels of the current primary NO2
standards. In addition to comparing annual DVs to the level of the
annual standard, support for consideration of 1-hour DVs comes from the
ISA's integrated mode of action information describing the biological
plausibility for development of asthma (Section B.II.2., above). In
particular, studies demonstrate the potential for repeated short-term
NO2 exposures to induce pulmonary inflammation and
development of allergic responses. The ISA states that ``findings for
short-term NO2 exposure support an effect on asthma
development by describing a potential role for repeated exposures to
[[Page 34814]]
lead to recurrent inflammation and allergic responses,'' which are
``identified as key early events in the proposed mode of action for
asthma development'' (U.S. EPA, 2016a, p. 6-66 and p. 6-64). More
specifically, the ISA states the following (U.S. EPA, 2016a, p. 4-64):
The initiating events in the development of respiratory effects due
to long-term NO2 exposure are recurrent and/or chronic
respiratory tract inflammation and oxidative stress. These are the
driving factors for potential downstream key events, allergic
sensitization, airway inflammation, and airway remodeling, that may
lead to the endpoint [airway hyperresponsiveness]. The resulting
outcome may be new asthma onset, which presents as an asthma
exacerbation that leads to physician-diagnosed asthma.
Thus, when considering the protection provided by the current
standards against NO2-associated asthma development, the PA
considers the combined protection afforded by the 1-hour and annual
standards.\69\
---------------------------------------------------------------------------
\69\ It is also the case that broad changes in NO2
concentrations will affect both hourly and annual metrics. This is
discussed in more detail in Section II.B.4. above, and in CASAC's
letter to the Administrator (Diez Roux and Sheppard, 2017). Thus, as
in the recent review of the O3 NAAQS (80 FR 65292,
October 26, 2015), it is appropriate to consider the extent to which
a short-term standard could provide protection against longer-term
pollutant exposures.
---------------------------------------------------------------------------
To inform consideration of whether a study area's air quality could
have met the current primary NO2 standards during study
periods, the PA presents DV estimates based on the NO2
concentrations measured at existing monitors during the years over
which the epidemiologic studies of long-term NO2 exposures
were conducted.70 71
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\70\ As discussed above for short-term exposures, the DVs
estimates reported here are meant to approximate the values that are
used when determining whether an area meets the primary
NO2 NAAQS (U.S. EPA, 2017a, Appendix A).
\71\ The DV estimates for the epidemiologic studies of asthma
incidence conducted in the U.S. and Canada are presented in Figure
3-2 of the NO2 PA (U.S. EPA, 2017a).
---------------------------------------------------------------------------
In interpreting these comparisons of DV estimates with the
NO2 standards, the PA also considers uncertainty in the
extent to which identified DV estimates represent the higher
NO2 concentrations likely to have been present near major
roads during study periods (II.B.3, above). In particular, as discussed
above for short-term exposures, study area DV estimates are based on
NO2 concentrations from the generally area-wide
NO2 monitors that were present during study periods.
Calculated DV estimates could have been higher if the near-road
monitors that are now required in major U.S. urban areas had been in
place. On this issue, the PA notes that the published scientific
literature supports the occurrence of higher NO2
concentrations near roadways and that recent air quality information
from the new near-road NO2 monitoring network generally
indicates higher NO2 concentrations at near-road monitoring
sites than at non-near road monitors in the same CBSA (Section II.B.3).
In addition, mobile source NOX emissions were substantially
higher during the majority of study periods (1986-2006) than they are
today (Section II.B.2), and NO2 concentration gradients
around roadways were generally more pronounced during study periods
than indicated by recent air quality information. Thus, even in cases
where DV estimates during study periods are at or somewhat below the
levels of current primary standards, it is not clear that study areas
would have met the standards if the currently required near-road
monitors had been in place.\72\
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\72\ As noted above for studies of short-term NO2
exposures (II.C.1.b.ii), epidemiologic studies that evaluate
potential NO2 health effect associations during time
periods when near-road monitors are operational could reduce this
uncertainty in future reviews.
---------------------------------------------------------------------------
In considering the epidemiologic studies looking at long-term
NO2 exposure and asthma development (U.S. EPA, 2017a, Figure
3-2), the PA first notes the information from the key studies as
identified in the ISA (Jerrett et al., 2008; Carlsten et al., 2011,
Clougherty et al., 2007). Jerrett et al. (2008) reported positive and
relatively precise associations with asthma incidence, based on
analyses across several communities in Southern California. Of the 11
study communities evaluated by Jerrett et al. (2008), most (i.e.,
seven) had maximum annual estimated DVs that were near (i.e., 46 ppb
for the four communities represented by the Riverside estimated DVs) or
above (i.e., 60 ppb for the three communities represented by the Los
Angeles estimated DVs) 53 ppb.\73\ These seven communities also had 1-
hour estimated DVs (max and mean) that were well-above 100 ppb. The
other key studies (i.e., Carlsten et al., 2011; Clougherty et al.,
2007), conducted in single cities, reported positive but statistically
imprecise associations. The annual estimated DVs in locations of these
studies during study years were below 53 ppb, but maximum 1-hour
estimated DVs were near (Clougherty) \74\ or above (Carlsten) 100 ppb.
---------------------------------------------------------------------------
\73\ For the studies by Jerrett et al. (2008) and McConnell et
al. (2010), the majority of communities were located within the Los
Angeles and Riverside CBSAs. Because of this, and because community-
specific NO2 monitoring data were often not available in
these areas (U.S. EPA, 2017a, Appendix A), DV estimates for the Los
Angeles and Riverside CBSAs were used to represent multiple study
communities.
\74\ As noted above, even in cases where DV estimates during
study periods are at or somewhat below the levels of current
standards, it is not clear that study areas would have met the
standards if the currently required near-road monitors had been in
place.
---------------------------------------------------------------------------
The PA also considers the information from the other U.S. and
Canadian studies available that, due to additional uncertainties, were
not identified as key studies in the ISA (Clark et al., 2010; McConnell
et al., 2010; Nishimura et al., 2013). The multi-city study by
Nishimura et al. (2013) reports a positive and relatively precise
association with asthma incidence, based on five U.S. cities and Puerto
Rico (see ``combined'' estimate in Figure 3-2 of the NO2
PA). Annual estimated DVs in all study cities were below 53 ppb, while
maximum 1-hour estimated DVs were above 100 ppb in four of the five
study cities (mean 1-hour estimated DVs were also near or above 100 ppb
in most study cities). Nishimura et al. (2013) also reported mixed
results in city-specific effects estimates. McConnell et al. (2010)
also conducted a multi-community study in Southern California and
reported a positive and relatively precise association between asthma
incidence and long-term NO2 exposures based on central-site
measurements. This study encompasses some of the same communities as
Jerrett et al. (2008), and while the annual DV estimates for these
study years are more mixed, the 1-hour DV estimates representing 10 of
13 communities are near or above 100 ppb. Finally, Clark et al. (2010)
reported a relatively precise and statistically significant association
in a study conducted over a two-year period in British Columbia, with
annual and hourly DV estimates of 32 ppb and 67 ppb, respectively.
However, this result was based on central-site NO2
measurements that have well-recognized limitations in reflecting
variability in ambient NO2 concentrations in a community and
variability in NO2 exposure among subjects.
PA Conclusions on Ambient NO2 Concentrations in Locations of
Epidemiologic Studies
Based on the information discussed above, while epidemiologic
studies provide support for NO2-associated asthma
development at ambient NO2 concentrations likely to have
been above those allowed by the current standards,
[[Page 34815]]
these studies do not report such associations at ambient NO2
concentrations that would have clearly met the current standards. Thus,
in evaluating the adequacy of the public health protection provided by
the current 1-hour and annual NO2 standards, the PA
concludes that epidemiologic studies do not provide a clear basis for
concluding that ambient NO2 concentrations allowed by the
current standards are independently (i.e., independent of co-occurring
roadway pollutants) associated with the development of asthma (U.S.
EPA, 2017, section 3.3.2). This conclusion stems from consideration of
the available evidence from U.S. and Canadian studies for
NO2-associated asthma incidence, the ambient NO2
concentrations present in study locations during study periods, and the
uncertainties and limitations inherent in the evidence and in the
analysis of study area DV estimates.
With regard to uncertainties in the evidence, the PA particularly
notes the potential for confounding by co-occurring pollutants, as
described above, given the following: (1) The relatively high
correlations observed between long-term concentrations of
NO2 and long-term concentrations of other roadway-associated
pollutants; (2) the general lack of information from copollutant models
on the potential for NO2 associations that are independent
of another traffic-related pollutant or mix of pollutants. This
uncertainty is an important consideration in evaluating the potential
support for adverse effects occurring below the levels of the current
primary NO2 standards.
Furthermore, the analysis of study area estimated DVs does not
provide support for the occurrence of NO2-associated asthma
incidence in locations with ambient NO2 concentrations
clearly meeting the current NAAQS. In particular, for most of the study
locations evaluated in the lone key U.S. multi-community study (Jerrett
et al., 2008), 1-hour estimated DV were above 100 ppb and annual DVs
were near or above 53 ppb. In addition, the two key single-city studies
evaluated reported positive, but relatively imprecise, associations in
locations with 1-hour estimated DVs near (Clougherty et al., 2007 in
Boston) or above (Carlsten et al., 2011 in Vancouver) 100 ppb. Had
currently required near-road monitors been in operation during study
periods, estimated DVs in U.S. study locations would likely have been
higher. Other U.S. and Canadian studies evaluated were subject to
greater uncertainties in the characterization of NO2
exposures. Given this information and consideration of these
uncertainties, the degree to which these epidemiologic studies can
inform whether adverse NO2-associated effects are occurring
below the levels of the current primary NO2 standards is
limited.
ii. NO2 Concentrations in Experimental Studies of Long-Term
Exposure
In addition to the evidence from epidemiologic studies, the PA also
considers evidence from experimental studies in animals and humans.\75\
Experimental studies examining asthma-related effects attributable to
long-term NO2 exposures are largely limited to animals
exposed to NO2 concentrations well-above those found in the
ambient air (i.e., >= 1,000 ppb). As discussed above, the ISA indicates
evidence from these animal studies supports the causal determination by
characterizing ``a potential mode of action linking NO2
exposure with asthma development'' (U.S. EPA, 2016a, p. 1-20). In
particular, there is limited evidence for increased airway
responsiveness in guinea pigs with exposures to 1,000-4,000 ppb for 6-
12 weeks. There is inconsistent evidence for pulmonary inflammation
across all studies, though effects were reported following
NO2 exposures of 500-2,000 ppb for 12 weeks. Despite
providing support for the ``likely to be a causal'' relationship,
evidence from these experimental studies, by themselves, does not
provide insight into the occurrence of adverse health effects following
exposures below the levels of the existing primary NO2
standards.\76\
---------------------------------------------------------------------------
\75\ While there are not controlled human exposure studies for
long-term exposures, the ISA and the PA consider the extent to which
evidence from short-term studies can provide support for effects
observed in long-term exposure studies.
\76\ In addition, the ISA draws from experimental evidence for
short-term exposures to support the biological plausibility of
asthma development. Consideration of the NO2 exposure
concentrations evaluated in these studies is discussed in Section
II.C.1 above.
---------------------------------------------------------------------------
iii. Overall Conclusions
Taking all of the evidence and information together, including
important uncertainties, the PA revisits the extent to which the
evidence supports the occurrence of NO2-attributable asthma
development in children at NO2 concentrations below the
existing standards. Based on the considerations discussed above, the PA
concludes that the available evidence does not provide support for
asthma development attributable to long-term exposures to
NO2 concentrations that would clearly meet the existing
annual and 1-hour primary NO2 standards. This conclusion
recognizes the NO2 air quality relationships, which indicate
that meeting the 1-hour NO2 standard would be expected to
limit annual NO2 concentrations to well-below the level of
the current annual standard (Section II.B.4, above). This conclusion
also recognizes the uncertainties in interpreting the epidemiologic
evidence within the context of evaluating the existing standards due to
the lack of near-road monitors during study periods and due to the
potential for confounding by co-occurring pollutants. Thus, the PA
concludes that epidemiologic studies of long-term NO2
exposures and asthma development do not provide a clear basis for
concluding that ambient NO2 concentrations allowed by the
current primary NO2 standards are independently (i.e.,
independent of co-occurring roadway pollutants) associated with the
development of asthma. In addition, while experimental studies provide
support for NO2-attributable effects that are plausibly
related to asthma development, the relatively high NO2
exposure concentrations used in these studies do not provide insight
into whether such effects would occur at NO2 exposure
concentrations that would be allowed by the current standards.
3. Potential Public Health Implications
Evaluation of the public health protection provided against ambient
NO2 exposures requires consideration of populations and
lifestages that may be at greater risk of experiencing NO2-
attributable health effects. In the last review, the 2008 ISA for
Oxides of Nitrogen noted that a considerable fraction of the U.S.
population lives, works, or attends school near major roadways, where
ambient NO2 concentrations are often elevated (U.S. EPA,
2008a, Section 4.3). Of this population, the 2008 ISA concluded that
``those with physiological susceptibility will have even greater risks
of health effects related to NO2'' (U.S. EPA, 2008a, p. 4-
12). With regard to susceptibility, the 2008 ISA concluded that
``[p]ersons with preexisting respiratory disease, children, and older
adults may be more susceptible to the effects of NO2
exposure'' (U.S. EPA, 2008a, p. 4-12).
In the current review, the 2016 ISA again notes because of the
large populations attending school, living, working, and commuting on
or near roads, where ambient NO2 concentrations can be
higher than in many other locations (U.S. EPA, 2016a,
[[Page 34816]]
Section 7.5.6),\77\ there is widespread potential for elevated ambient
NO2 exposures. For example, Rowangould et al. (2013) found
that over 19% of the U.S. population lives within 100 m of roads with
an annual average daily traffic (AADT) of 25,000 vehicles, and 1.3%
lives near roads with AADT greater than 200,000. The proportion is much
larger in certain parts of the country, mostly coinciding with urban
areas. Among California residents, 40% live within 100 m of roads with
AADT of 25,000 (Rowangould, 2013). In addition, 7% of U.S. schools
serving a total of 3,152,000 school children are located within 100 m
of a major roadway, and 15% of U.S. schools serving a total of
6,357,000 school children are located within 250 m of a major roadway
(Kingsley et al., 2014). Thus, as in the last review, the available
information indicates that large proportions of the U.S. population
potentially have elevated NO2 exposures as a result of
living, working, attending school, or commuting on or near roadways.
---------------------------------------------------------------------------
\77\ The ISA specifically notes that a zone of elevated
NO2 concentrations typically extends 200 to 500 m from
roads with heavy traffic (U.S. EPA, 2016A, Section 2.5.3).
---------------------------------------------------------------------------
The impacts of exposures to elevated NO2 concentrations,
such as those that can occur around roadways, are of particular concern
for populations at increased risk of experiencing adverse effects. In
the current review, the PA's consideration of potential at-risk
populations draws from the 2016 ISA's assessment of the evidence (U.S.
EPA, 2016a, Chapter 7). The ISA uses a systematic approach to evaluate
factors that may increase risks in a particular population or during a
particular lifestage, noting that increased risk could be due to
``intrinsic or extrinsic factors, differences in internal dose, or
differences in exposure'' (U.S. EPA, 2016a, p. 7-1).
The ISA evaluates the evidence for a number of potential at-risk
factors, including pre-existing diseases like asthma (U.S. EPA, 2016a,
Section 7.3), genetic factors (U.S. EPA, 2016a, Section 7.4),
sociodemographic factors (U.S. EPA, 2016a, Section 7.5), and behavioral
and other factors (U.S. EPA, 2016a, Section 7.6). The ISA then uses a
systematic approach for classifying the evidence for each potential at-
risk factor (U.S. EPA, 2015, Preamble, Section 6.a, Table III). The
categories considered are ``adequate evidence,'' ``suggestive
evidence,'' ``inadequate evidence,'' and ``evidence of no effect''
(U.S. EPA, 2016a, Table 7-1). Consistent with other recent NAAQS
reviews (e.g., 80 FR 65292, October 26, 2015), the PA focuses the
consideration of potential at-risk populations on those factors for
which the ISA determines there is ``adequate'' evidence (U.S. EPA,
2016a, Table 7-27). In the case of NO2, this includes people
with asthma, children and older adults (U.S. EPA, 2016a, Table 7-27),
based primarily on evidence for asthma exacerbation or asthma
development as evidence for an independent relationship of
NO2 exposure with other health effects is more uncertain.
The PA's consideration of the evidence supporting these at-risk
populations specifically focuses on the following question: To what
extent does the currently available scientific evidence expand the
understanding of populations and/or lifestages that may be at greater
risk for NO2-related health effects?
In addressing this question, the PA considers the evidence for
effects in people with asthma, children, and older adults (U.S. EPA,
2016a, Chapter 7, Table 7-27). This section presents the PA's overall
conclusions regarding the populations at increased risk of
NO2-related effects.
a. People With Asthma
Approximately 8.0% of adults and 9.3% of children (age <18 years)
in the U.S. currently have asthma (Blackwell et al., 2014; Bloom et
al., 2013), and it is the leading chronic illness affecting children
(U.S. EPA, 2016a, Section 7.3.1). Individuals with pre-existing
diseases like asthma may be at greater risk for some air pollution-
related health effects if they are in a compromised biological state.
As in the last review, controlled human exposure studies
demonstrating NO2-induced increases in AR provide key
evidence that people with asthma are more sensitive than people without
asthma to the effects of short-term NO2 exposures. In
particular, a meta-analysis conducted by Folinsbee et al. (1992)
demonstrated that NO2 exposures from 100 to 300 ppb
increased AR in the majority of adults with asthma, while AR in adults
without asthma was increased only for NO2 exposure
concentrations greater than 1,000 ppb (U.S. EPA, 2016a, Section 7.3.1).
Brown (2015) showed that following resting exposures to NO2
concentrations in the range of 100 to 530 ppb, about a quarter of
individuals with asthma experience clinically relevant increases in AR
to non-specific bronchial challenge. Results of epidemiologic studies
are less clear regarding potential differences between populations with
and without asthma (U.S. EPA, 2016a, Section 7.3.1). Additionally,
studies of activity patterns do not clearly indicate difference in time
spent outdoors to suggest differences in NO2 exposure.
However, the meta-analysis of information from controlled human
exposure studies, which supported the ISA's determination of a causal
relationship between short-term exposures and respiratory effects,
clearly demonstrates increased sensitivity of adults with asthma
compared to healthy adults.\78\ Thus, consistent with observations made
in the 2008 ISA (U.S. EPA, 2008a), in the current review the ISA
determines that the ``evidence is adequate to conclude that people with
asthma are at increased risk for NO2-related health
effects'' (U.S. EPA, 2016a, p. 7-7).
---------------------------------------------------------------------------
\78\ Though, as discussed above (Section II.C.1), there is
uncertainty in the extent to which increases in AR following
exposures to NO2 concentrations near those found in the
ambient air (i.e., around 100 ppb) would be clearly adverse.
---------------------------------------------------------------------------
b. Children
According to the 2010 census, 24% of the U.S. population is less
than 18 years of age, with 6.5% less than age 6 years (Howden and
Meyer, 2011). The National Human Activity Pattern Survey shows that
children spend more time than adults outdoors (Klepeis et al., 1996),
and a longitudinal study in California showed a larger proportion of
children reported spending time engaged in moderate or vigorous outdoor
physical activity (Wu et al., 2011b). In addition, children have a
higher propensity than adults for oronasal breathing (U.S. EPA, 2016a,
Section 4.2.2.3) and the human respiratory system is not fully
developed until 18-20 years of age (U.S. EPA, 2016a, Section 7.5.1).
All of these factors could contribute to children being at higher risk
than adults for effects attributable to ambient NO2
exposures (U.S. EPA, 2016a, Section 7.5.1.1).
Epidemiologic evidence across diverse locations (U.S., Canada,
Europe, Asia, Australia) consistently demonstrates adverse effects of
both short- and long-term NO2 exposures in children. In
particular, short-term increases in ambient NO2
concentrations are consistently associated with larger increases in
asthma-related hospital admissions, ED visits or outpatient visits in
children than in adults (U.S. EPA, 2016a, Section 7.5.1.1, Table 7-13).
These results seem to indicate NO2-associated impacts that
are 1.8 to 3.4-fold larger in children (Son et al., 2013; Ko et al.,
2007; Atkinson et al., 1999; Anderson et al., 1998). In addition,
asthma development
[[Page 34817]]
in children has been reported to be associated with long-term
NO2 exposures, based on exposure periods spanning infancy to
adolescence (U.S. EPA, 2016a, Section 6.2.2.1). Given the consistent
epidemiologic evidence for associations between ambient NO2
and asthma-related outcomes, including the larger associations with
short-term exposures observed in children, the ISA concludes the
evidence ``is adequate to conclude that children are at increased risk
for NO2-related health effects'' (U.S. EPA, 2016a, p. 7-32).
c. Older Adults
According to the 2012 National Population Projections issued by the
U.S. Census Bureau, 13% of the U.S. population was age 65 years or
older in 2010, and by 2030, this fraction is estimated to grow to 20%
(Ortman et al., 2014). Recent epidemiologic findings expand on evidence
available in the 2008 ISA that older adults may be at increased risk
for NO2-related health effects. (U.S. EPA, 2016a Table 7-
15). While it is not clear that older adults experience greater
NO2 exposures or doses, epidemiologic evidence generally
indicates greater risk of NO2-related health effects in
older adults compared with younger adults. For example, comparisons of
older and younger adults with respect to NO2-related asthma
exacerbation generally show larger (one to threefold) effects in adults
ages 65 years or older than among individuals ages 15-64 years or 15-65
years (Ko et al., 2007; Villeneuve et al., 2007; Migliaretti et al.,
2005; Anderson et al., 1998). Results for all respiratory hospital
admissions combined also tend to show larger associations with
NO2 among older adults ages 65 years or older (Arbex et al.,
2009; Wong et al., 2009; Hinwood et al., 2006; Atkinson et al., 1999).
The ISA determined that, overall, the consistent epidemiologic evidence
for asthma-related hospital admissions and ED visits ``is adequate to
conclude that older adults are at increased risk for NO2-
related health effects'' (U.S. EPA, 2016a, p. 7-37).
d. PA Conclusions on At-Risk Populations
As described in the PA, and consistent with the last review, the
ISA determined that the available evidence is adequate to conclude that
people with asthma, children, and older adults are at increased risk
for NO2-related health effects. The large proportions of the
U.S. population that encompass each of these groups and lifestages
(i.e., 8% adults and 9.3% children with asthma, 24% children, 13% older
adults) underscores the potential for important public health impacts
attributable to NO2 exposures. These impacts are of
particular concern for members of these populations and lifestages who
live, work, attend school or otherwise spend a large amount of time in
locations of elevated ambient NO2, including near heavily
trafficked roadways.
D. Human Exposure and Health Risk Characterization
Beyond the consideration of the scientific evidence, discussed
above in Section II.C, the EPA also considers the extent to which new
or updated quantitative analyses of NO2 air quality,
exposures or health risks could inform conclusions on the adequacy of
the public health protection provided by the current primary
NO2 standards. Conducting such quantitative analyses, if
appropriate, could inform judgments about the public health impacts of
NO2-related health effects and could help to place the
evidence for specific effects into a broader public health context. To
this end, in the REA Planning document (U.S. EPA, 2015) and in the PA,
the staff evaluated the extent to which the available evidence and
information provide support for conducting new or updated analyses of
NO2 exposures and/or health risks, beyond the analyses
conducted in the 2008 REA (U.S. EPA, 2008b). In doing so, staff
carefully considered the assessments developed as part of the last
review of the primary NO2 NAAQS (U.S. EPA, 2008b) and the
newly available scientific and technical information, particularly
considering the degree to which updated analyses in the current review
are likely to substantially add to the understanding of NO2
exposures and/or health risks. The final PA also considers the CASAC
advice and public input received on the REA Planning document (U.S.
EPA, 2017a, Chapter 4), and on the draft PA (Diez Roux and Sheppard,
2017). Based on these considerations, the PA included updated analyses
examining the occurrence of NO2 air quality concentrations
(i.e., as surrogates for potential NO2 exposures) that may
be of public health concern (see below and Appendix B of U.S. EPA,
2017a). These analyses, summarized below and discussed in more detail
in Chapter 4 of the PA (U.S. EPA, 2017a), have been informed by advice
from the CASAC and input from the public on the REA Planning document
(Diez Roux and Frey, 2015b) and on the draft PA (Diez Roux and
Sheppard, 2017). Updated risk estimates based on information from
epidemiology studies were not conducted in the current review given
that these analyses would be subject to the same uncertainties
identified in the 2008 REA (U.S. EPA, 2017a, Section 4-1). The CASAC
agreed with this conclusion in its review of the REA Planning document
(Diez Roux and Frey, 2015b, p. 5).
1. Overview of Approach to Estimating Potential NO2
Exposures
To provide insight into the potential occurrence of NO2
air quality concentrations that may be of public health concern, the PA
included analyses comparing NO2 air quality to health-based
benchmarks in 23 study areas (U.S. EPA, 2017a Table 4-1). The selection
of study areas focused on CBSAs with near-road monitors in
operation,\79\ CBSAs with the highest NO2 design values, and
CBSAs with a relatively large number of NO2 monitors overall
(i.e., providing improved spatial characterization).\80\
---------------------------------------------------------------------------
\79\ As discussed above (Sections I.C and II.B.3), the
regulations require near-road monitors were required within 50 m of
major roads in large urban areas that met certain criteria for
population size or traffic volume. Most near-road monitors are sited
within about 30 m of the road, and in some cases they are sited
almost at the roadside (i.e., as close as 2 m from the road; http://www3.epa.gov/ttn/amtic/nearroad.html) (U.S. EPA, 2017a, Section
2.2.2).
\80\ Based on these criteria, a total of 23 CBSAs from across
the U.S. were selected as study areas (U.S. EPA, 2017a, Appendix B,
Figure B2-1). Further evaluation indicates that these 23 study areas
are among the most populated CBSAs in the U.S.; they have among the
highest total NOX emissions and mobile source
NOX emissions in the U.S.; and they include a wide range
of stationary source NOX emissions (U.S. EPA, 2017a,
Appendix B, Figures B2-2 to B2-8).
---------------------------------------------------------------------------
Air quality-benchmark comparisons were conducted in study areas
with unadjusted air quality and with air quality adjusted upward to
just meet the existing 1-hour standard.\81\ Upward adjustment was
required because all locations in the U.S. meet the current
NO2 NAAQS.
---------------------------------------------------------------------------
\81\ In all study areas, ambient NO2 concentrations
required smaller upward adjustments to just meet the 1-hour standard
than to just meet the annual standard. Therefore, when adjusting air
quality to just meet the current primary NO2 NAAQS, the
PA applied the adjustment needed to just meet the 1-hour standard.
For additional information on the air quality adjustment approach
see Appendix B, Section B2.4.1 in the PA (U.S. EPA, 2017a).
---------------------------------------------------------------------------
In identifying the range of NO2 health-based benchmarks
to evaluate, and the weight to place on specific benchmarks within this
range, the PA considered both the group mean responses reported in
individual studies of AR and the results of a meta-analysis that
combined individual-level data from multiple studies (Brown, 2015; U.S.
EPA, 2016a, Section 5.2.2.1). When taken together, the results of
controlled human exposure studies and of the meta-analysis by Brown
(2015) support consideration of NO2 benchmarks from
[[Page 34818]]
100 to 300 ppb, based largely on studies of non-specific AR in study
participants exposed at rest.\82\ Given uncertainties in the evidence,
including the lack of an apparent dose-response relationship and
uncertainty in the potential adversity of reported increases in AR,
caution is appropriate when interpreting the potential public health
implications of 1-hour NO2 concentrations at or above these
benchmarks. This is particularly the case for the 100 ppb benchmark,
given the less consistent results across individual studies at this
exposure concentration (see Section II.C.1 above and U.S. EPA, 2017a,
Section 4.2.1).
---------------------------------------------------------------------------
\82\ Benchmarks from the upper end of this range are supported
by the results of individual studies, the majority of which most
consistently reported statistically significant increases in AR
following NO2 exposures at or above 250 ppb, and by the
results of the meta-analysis by Brown (2015). Benchmarks from the
lower end of this range are supported by the results of the meta-
analysis, even though individual studies generally do not report
statistically significant NO2-induced increases in AR
following exposures below 200 ppb.
---------------------------------------------------------------------------
2. Results of Updated Analyses
In considering the results of these updated analyses, the EPA
focuses on the number of days per year that such 1-hour NO2
concentrations could occur at each monitoring site in each study area.
Based on the results of these analyses (U.S. EPA, 2017a, Tables 4-1
and 4-2), the EPA makes the following key observations for study areas
when air quality was unadjusted (``as-is'') and when air quality was
adjusted to just meet the current 1-hour NO2 standard \83\
(U.S. EPA, 2017a, Section 4.2.1.2).
---------------------------------------------------------------------------
\83\ As discussed in the PA (U.S. EPA, 2017a, Section 4.2.1), in
all study areas, ambient NO2 concentrations required
smaller upward adjustments to just meet the 1-hour standard than to
just meet the annual standard. Therefore, when adjusting air quality
to just meet the current NO2 NAAQS, the adjustment needed
to just meet the 1-hour standard was applied.
---------------------------------------------------------------------------
For unadjusted air quality:
One-hour ambient NO2 concentrations in study
areas, including those near major roadways, were always below 200 ppb,
and were virtually always below 150 ppb.
[cir] Even in the worst-case years (i.e., the years with the
largest number of days at or above benchmarks), no study areas had any
days with 1-hour NO2 concentrations at or above 200 ppb, and
only one area had any days (i.e., one day) with 1-hour concentrations
at or above 150 ppb.
One-hour ambient NO2 concentrations in study
areas, including those near major roadways, only rarely reached or
exceeded 100 ppb. On average in all study areas, 1-hour NO2
concentrations at or above 100 ppb occurred on less than one day per
year.
[cir] Even in the worst-case years, most study areas had either
zero or one day with 1-hour NO2 concentrations at or above
100 ppb (7 days in the single worst-case location and worst-case year).
For air quality adjusted to just meet the current primary 1-hour
NO2 standard:
The current standard is estimated to allow no days in
study areas with 1-hour ambient NO2 concentrations at or
above 200 ppb. This is true for both area-wide and near-road monitoring
sites, even in the worst-case years.
The current standard is estimated to allow almost no days
with 1-hour ambient NO2 concentrations at or above 150 ppb,
based on both area-wide and near-road monitoring sites (i.e., zero to
one day per year, on average).
[cir] In the worst-case years in most study areas, the current
standard is estimated to allow either zero or one day with 1-hour
ambient NO2 concentrations at or above 150 ppb. In the
single worst-case year and location, the current standard is estimated
to allow eight such days.
At area-wide monitoring sites in most of the study areas,
the current standard is estimated to allow from one to seven days per
year, on average, with 1-hour ambient NO2 concentrations at
or above 100 ppb. At near-road monitoring sites in most of the study
areas, the current standard is estimated to allow from about one to 10
days per year with such 1-hour concentrations.
[cir] In the worst-case years in most of the study areas, the
current standard is estimated to allow from about 5 to 20 days with 1-
hour NO2 concentrations at or above 100 ppb (30 days in the
single worst-case location and year).
3. Uncertainties
There are a variety of limitations and uncertainties in these
comparisons of NO2 air quality with health-based benchmarks.
In particular, there are uncertainties in the evidence underlying the
benchmarks themselves, as well as uncertainties in the upward
adjustment of NO2 air quality concentrations, and
uncertainty in the degree to which monitored NO2
concentrations reflect the highest potential NO2
concentrations. Each of these is discussed below.
a. Health-Based Benchmarks
The primary goal of this analysis is to inform conclusions
regarding the potential for the existing primary NO2
standards to allow exposures to ambient NO2 concentrations
that may be of concern for public health. As discussed in detail above
(Sections II.C.1), the meta-analysis by Brown (2015) indicates the
potential for increased AR in some people with asthma following
NO2 exposures from 100 to 530 ppb. While it is possible that
certain individuals could be more severely affected by NO2
exposures than indicated by existing studies, which have generally
evaluated adults with mild asthma,\84\ there remains uncertainty in the
degree to which the effects identified in these studies would be of
public health concern. In particular, both the lack of an apparent
dose-response relationship between NO2 exposure and AR and
the uncertainties in the magnitude and potential adversity of the
increase in AR following NO2 exposures complicate the
interpretation of comparisons between ambient NO2
concentrations and health-based benchmarks. When considered in the
context of the less consistent results observed across individual
studies following exposures to 100 ppb NO2, in comparison to
the more consistent results at higher exposure concentrations,\85\
these uncertainties have the potential to be of particular importance
for interpreting the public health implications of ambient
NO2 concentrations at or above the 100 ppb benchmark.\86\
---------------------------------------------------------------------------
\84\ Brown (2015, p. 3) notes, however, that one study included
in the meta-analysis (Avol et al., 1989) evaluated children aged 8
to 16 years and that disease status varied across studies, ranging
from ``inactive asthma up to severe asthma in a few studies.''
\85\ As discussed previously, while the meta-analysis indicates
that the majority of study volunteers experienced increased non-
specific AR following exposures to 100 ppb NO2, results
were marginally significant when specific AR was also included in
the analysis. In addition, individual studies do not consistently
indicate increases in AR following exposures to 100 ppb
NO2.
\86\ Sensitivity analyses included in Appendix B of the PA (U.S.
EPA, 2017a, Section 3.2, table B3-1) also evaluated 1-hour
NO2 benchmarks below 100 ppb (i.e., 85, 90, 95 ppb),
though the available health evidence does not provide a clear a
basis for determining what exposures to such NO2
concentrations might mean for public health.
---------------------------------------------------------------------------
With regard to the magnitude and clinical relevance of the
NO2-induced increase in AR in particular, the meta-analysis
by Brown (2015) attempts to address this uncertainty and inconsistency
across individual studies. Specifically, as discussed above (Section
II.C.1), the meta-analysis evaluates the available individual-level
data on the magnitude of the change in AR following resting
NO2 exposures. Brown (2015) reports that the magnitude of
the increases in AR observed following resting NO2 exposures
from 100 to 530 ppb were large enough to be of potential clinical
relevance in about a quarter of the 72 study volunteers with available
data. This is based on the fraction of exposed individuals who
[[Page 34819]]
experienced a halving of the provocative dose of challenge agent
following NO2 exposures. This magnitude of change has been
recognized by the American Thoracic Society (ATS) and the European
Respiratory Society as a ``potential indicator, although not a
validated estimate, of clinically relevant changes in [AR]'' (Reddel et
al., 2009) (U.S. EPA, 2016a, p. 5-12). Although there is uncertainty in
using this approach to characterize whether a particular response in an
individual is ``adverse,'' it can provide insight into the potential
for adversity, particularly when applied to a population of exposed
individuals. While this analysis by Brown (2015) indicates the
potential for some people with asthma to experience effects of clinical
relevance following resting NO2 exposures from 100 to 530
ppb, it is based on a relatively small subset of volunteers and the
interpretation of these results for any specific exposure concentration
within the range of 100 to 530 ppb is uncertain (see section II.C.1,
above).
b. Approach to Adjusting Ambient NO2 Concentrations
These analyses use historical air quality relationships as the
basis for adjusting ambient NO2 concentrations to just meet
the current 1-hour standard (U.S. EPA, 2017a, Appendix B). The adjusted
air quality is meant to illustrate a hypothetical scenario, and does
not represent expectations regarding future air quality trends. If
ambient NO2 concentrations were to increase in some
locations to the point of just meeting the current standards, it is not
clear that the spatial and temporal relationships reflected in the
historical data would persist. In particular, as discussed in Section
2.1.2 of the PA (U.S. EPA, 2017a), ongoing implementation of existing
regulations is expected to result in continued reductions in ambient
NO2 concentrations over much of the U.S. (i.e., reductions
beyond the ``unadjusted'' air quality used in these analyses). Thus, if
ambient NO2 concentrations were to increase to the point of
just meeting the existing 1-hour NO2 standard in some areas,
the resulting air quality patterns may not be similar to those
estimated in the PA's air quality adjustments.
There is also uncertainty in the upward adjustment of
NO2 air quality because three years of data are not yet
available from most near-road monitors. In most study areas, estimated
DVs were not calculated at near-road monitors and, therefore, near-road
monitors were generally not used as the basis for identifying
adjustment factors for just meeting the existing standard.\87\ In
locations where near-road monitors measure the highest NO2
DVs, reliance on those near-road monitors to identify air quality
adjustment factors would result in smaller adjustments being applied to
monitors in the study area. Thus, monitors in such study areas would be
adjusted upward by smaller increments, potentially reducing the number
of days on which the current standard is estimated to allow 1-hour
NO2 concentrations at or above benchmarks. Given that near-
road monitors in most areas measure higher 1-hour NO2
concentrations than the area-wide monitors in the same CBSA (U.S. EPA,
2017a, Figures 2-7 to 2-10), this uncertainty has the potential to
impact results in many of the study areas. While the magnitude of the
impact is unknown at present, the inclusion of additional years of
near-road monitoring information in the determination of air quality
adjustments could result in fewer estimated 1-hour NO2
concentrations at or above benchmarks in some study areas.
---------------------------------------------------------------------------
\87\ Though in a few study locations, near-road monitors did
contribute to the calculation of air quality adjustments, as
described in Appendix B of the PA (U.S. EPA, 2017a, Table B2-7).
---------------------------------------------------------------------------
c. Degree to Which Monitored NO2 Concentrations Reflect the
Highest Potential NO2 Exposures
To the extent there are unmonitored locations where ambient
NO2 concentrations exceed those measured by monitors in the
current network, the potential for NO2 exposures at or above
benchmarks could be underestimated. In the last review, this
uncertainty was determined to be particularly important for potential
exposures around roads. The 2008 REA estimated that the large majority
of modeled exposures to ambient NO2 concentrations at or
above benchmarks occurred on or near roads (U.S. EPA, 2008b, Figures 8-
17 and 8-18). When characterizing ambient NO2
concentrations, the 2008 REA attempted to address this uncertainty by
estimating the elevated NO2 concentrations that can occur on
or near the road. These estimates were generated by applying
literature-derived adjustment factors to NO2 concentrations
at monitoring sites located away from the road.\88\
---------------------------------------------------------------------------
\88\ Sensitivity analyses included in Appendix B of the PA use
updated data from the scientific literature (Richmond-Bryant et al.,
2016) to estimate ``on-road'' NO2 concentrations based on
monitored concentrations around a roadway in Las Vegas (Appendix B,
Section B2.4.2). However, there remains considerable uncertainty in
the relationship between on-road and near-road NO2
concentrations, and in the degree to which they may differ.
Therefore, in evaluating the potential for roadway-associated
NO2 exposures, the PA focuses on the concentrations at
locations of near-road monitors (U.S. EPA, 2017a, Chapter 4).
---------------------------------------------------------------------------
In the current review, given that the 23 selected study areas have
among the highest NOX emissions in the U.S., and given the
siting characteristics of existing NO2 monitors, this
uncertainty likely has only a limited impact on the results of the air
quality-benchmark comparisons. In particular, as described above,
mobile sources tend to dominate NOX emissions within most
CBSAs, and the 23 study areas evaluated have among the highest mobile
source NOX emissions in the U.S. (U.S. EPA, 2017a, Appendix
B, Section B2.3.2). Most study areas have near-road NO2
monitors in operation, which are required within 50 m of the most
heavily trafficked roadways in large urban areas. The majority of these
near-road monitors are sited within 30 m of the road, and several are
sited within 10 m (see Atlanta, Cincinnati, Denver, Detroit, Los
Angeles in EPA's database of metadata for near-road monitors \89\).
Thus, as explained in the PA, even though the location of highest
NO2 concentrations around roads can vary (U.S. EPA, 2017a,
Section 2.1), the near-road NO2 monitoring network, with
monitors sited from 2 to 50 m away from heavily trafficked roads, are
likely to effectively capture the types of locations around roads where
the highest NO2 concentrations can occur.\90\
---------------------------------------------------------------------------
\89\ This database is found at http://www3.epa.gov/ttn/amtic/nearroad.html.
\90\ However, it remains possible that some areas (e.g., street
canyons in urban environments) could have higher ambient
NO2 concentrations than indicated by near-road monitors.
Sensitivity analyses estimating the potential for on-road
NO2 exposures are described in Appendix B of the PA (U.S.
EPA, 2017a).
---------------------------------------------------------------------------
This conclusion is consistent with the ISA's analysis of available
data from near-road NO2 monitors, which indicates that near-
road monitors with target roads having the highest traffic counts also
had among the highest 98th percentiles of 1-hour daily maximum
NO2 concentrations (U.S. EPA, 2016a, Section 2.5.3.2). The
ISA concludes that ``[o]verall, the very highest 98th percentile 1-hour
maximum concentrations were generally observed at the monitors adjacent
to roads with the highest traffic counts'' (U.S. EPA, 2016a, p. 2-66).
It is also important to consider the degree to which air quality-
benchmark comparisons appropriately characterize the potential for
NO2 exposures near non-roadway sources of NOX
emissions. As noted in the PA, the 23 selected study areas include
CBSAs with large non-roadway sources of NOX emissions. This
includes study areas with among the highest NOX emissions
from electric
[[Page 34820]]
power generation facilities (EGUs) and airports, the two types of non-
roadway sources that emit the most NOX in the U.S. (U.S.
EPA, 2017a, Appendix B, Section B2.3.2). As discussed below, several
study areas have non-near-road NO2 monitors sited to
determine the impacts of such sources.
Table 2-12 in the ISA (U.S. EPA, 2016a) summarizes NO2
concentrations at selected monitoring sites that are likely to be
influenced by non-road sources, including ports, airports, border
crossings, petroleum refining, or oil and gas drilling. For example,
the Los Angeles, CA CBSA includes one of the busiest ports and one of
the busiest airports in the U.S. Out of 18 monitors in the Los Angeles
CBSA, three of the five highest 98th percentile 1-hour maximum
concentrations were observed at the near-road site, the site nearest
the port, and the site adjacent to the airport (U.S. EPA, 2016a,
section 2.5.3.2). In the Chicago, IL CBSA, the highest hourly
NO2 concentration measured in 2014 (105 ppb) occurred at the
Schiller Park, IL monitoring site, located adjacent to O'Hare
International airport, a four-lane arterial (U.S. 12 and U.S. 45), and
very close to a major rail yard (i.e., Bedford Park Rail Yard) (U.S.
EPA, 2016a, Section 2.5.3.2).\91\ In addition, one of the highest 1-
hour daily maximum NO2 concentrations recorded in recent
years (136 ppb) was observed at a Denver, CO non-near-road site. This
concentration was observed at a monitor located one block from high-
rise buildings that form the edge of the high-density central business
district. This monitor is likely influenced by local traffic, as well
as by commercial heating and other activities (U.S. EPA, 2016a, Section
2.5.3.2).\92\ Thus, beyond the NO2 near-road monitors, some
NO2 monitors in study areas are also sited to capture high
ambient NO2 concentrations around important non-roadway
sources of NOX emissions.
---------------------------------------------------------------------------
\91\ Sections B5.1 and B5.2 of Appendix B in the PA (U.S. EPA,
2017a) provide data on the large sources of NOX emissions
in study areas.
\92\ Recent traffic counts on the nearest streets were 44,850
(in 2014) and 23,389 (in 2013) vehicles per day, respectively.
Traffic counts on other streets within one block of this monitor
were 22,000, 13,000, 5,000, and 2,490 vehicles per day. Together,
this adds up to more than 100,000 vehicles per day on streets within
one block of this non-near-road monitor (U.S. EPA, 2016A, Section
2.5.3.2).
---------------------------------------------------------------------------
4. Conclusions
As discussed above and in the REA Planning document (U.S. EPA,
2015, Section 2.1.1), an important uncertainty identified in the 2008
REA was the characterization of 1-hour NO2 concentrations
around major roadways. In the current review, data from recently
deployed near-road NO2 monitors improves understanding of
such ambient NO2 concentrations.
As discussed in Section II.B.2, recent NO2
concentrations measured in all U.S. locations meet the existing primary
NO2 NAAQS. Based on these recent (i.e., unadjusted) ambient
measurements, analyses estimate almost no potential for 1-hour
exposures to NO2 concentrations at or above benchmarks, even
at the lowest benchmark examined (i.e., 100 ppb).
Analyses of air quality adjusted upwards to just meet the current
1-hour standard estimate no days with 1-hour NO2
concentrations at or above the 200 ppb benchmark, and virtually none
for exposures at or above 150 ppb. This is the case for both average
and worst-case years, including in study areas with near-road monitors
sited within a few meters of heavily trafficked roads. With respect to
the lowest benchmark evaluated, analyses estimate that the current 1-
hour standard allows the potential for exposures to 1-hour
NO2 concentrations at or above 100 ppb on some days (e.g.,
in most study areas, about one to 10 days per year, on average).\93\
---------------------------------------------------------------------------
\93\ Because the results show almost no days with 1-hour ambient
NO2 concentrations above 150 ppb, the results for the 100
ppb benchmark are due primarily to 1-hour NO2
concentrations that are closer to 100 ppb than 200 ppb.
---------------------------------------------------------------------------
These results are consistent with expectations, given that the
current 1-hour standard, with its 98th percentile form, is anticipated
to limit, but not eliminate, exposures to 1-hour NO2
concentrations at or above 100 ppb.\94\ These results are similar to
the results presented in the REA from the last review, based on
NO2 concentrations at the locations of area-wide ambient
monitors (U.S. EPA, 2017a, Appendix B, Section B5.9, Table B5-66). In
contrast, compared to the on/near road simulations in the last review,
these results indicate substantially less potential for 1-hour
exposures to NO2 concentrations at or above these benchmarks
(U.S. EPA, 2017a, Appendix B, Section B5.9, Table B5-66).\95\
---------------------------------------------------------------------------
\94\ The 98th percentile generally corresponds to the 7th or 8th
highest 1-hour concentration in a year.
\95\ On-/near-road simulations in the last review estimated that
a 1-hour NO2 standard with a 98th percentile form and a
100 ppb level could allow about 20 to 70 days per year with 1-hour
NO2 concentrations at or above the 200 ppb benchmark and
about 50 to 150 days per year with 1-hour concentrations at or above
the 100 ppb benchmark (U.S. EPA, 2017a, Appendix B, Table B5-56).
---------------------------------------------------------------------------
When these results and associated uncertainties are taken together,
the current 1-hour NO2 standard is expected to allow
virtually no potential for exposures to the NO2
concentrations that have been shown most consistently to increase AR in
people with asthma (i.e., above 200 ppb), even under worst-case
conditions across a variety of study areas with among the highest
NOX emissions in the U.S. Such NO2 concentrations
were not estimated to occur, even at monitoring sites adjacent to some
of the most heavily trafficked roadways. In addition, the current
standard is expected to limit, though not eliminate, exposures to 1-
hour concentrations at or above 100 ppb. Though the current standard is
estimated to allow 1-hour NO2 concentrations at or above 100
ppb on some days, there is uncertainty regarding the potential public
health implications of exposures to 100 ppb NO2. However, in
limiting exposures to NO2 concentrations at or above 100
ppb, the current standard provides protection against exposures to
higher NO2 concentrations, for which the evidence of adverse
NO2-attributable effects is more certain, as well as against
exposures to NO2 concentrations at 100 ppb, for which the
evidence of adverse NO2-attributable effects is less
certain.
Given the results of these analyses, and the uncertainties inherent
in their interpretation, the PA concludes that there is little
potential for exposures to ambient NO2 concentrations that
would be of clear public health concern in locations meeting the
current 1-hour standard. Additionally, while a lower standard level
(i.e., lower than 100 ppb) would be expected to further limit the
potential for exposures to 100 ppb NO2, the public health
implications of such reductions are unclear, particularly given that no
additional protection would be expected against exposures to
NO2 concentrations at or above the higher benchmarks (i.e.,
200 ppb and above). Thus, the PA concludes that these analyses
comparing ambient NO2 concentrations to health-based
benchmarks do not provide support for considering potential alternative
standards to increase public health protection, beyond the protection
provided by the current standards.
E. Summary of CASAC Advice
In the current review of the primary NO2 standards the
CASAC has provided advice and recommendations based on its review of
drafts of the ISA (Diez Roux and Frey, 2015a), of the REA Planning
document (Diez Roux and Frey, 2015b), and of the draft PA (Diez Roux
and Sheppard, 2017). This section summarizes key CASAC advice regarding
the strength of the evidence for respiratory effects, the quantitative
analyses conducted and presented in
[[Page 34821]]
the PA, and the adequacy of the current primary NO2
standards to protect the public health.
Briefly, with regard to the strength of the evidence for
respiratory effects, the CASAC agreed with the ISA conclusions. In
particular, the CASAC concurred ``with the finding that short-term
exposures to NO2 are causal for respiratory effects based on
evidence for asthma exacerbation'' (Diez Roux and Sheppard 2017, p. 7).
It further noted that ``[t]he strongest evidence is for an increase in
airway responsiveness based on controlled human exposure studies, with
supporting evidence from epidemiologic studies'' (Diez Roux and
Sheppard 2017, p. 7). The CASAC also agreed with the ISA conclusions on
long-term exposures and respiratory effects, specifically stating the
following (Diez Roux and Sheppard 2017, p. 7):
Long-term exposures to NO2 are likely to be causal
for respiratory effects, based on asthma development. The strongest
evidence is for asthma incidence in children in epidemiologic
studies, with supporting evidence from experimental animal studies.
Current scientific evidence for respiratory effects related to long-
term exposures is stronger since the last review, although
uncertainties remain related to the influence of copollutants on the
association between NO2 and asthma incidence.
With regard to support for the updated quantitative analyses
conducted in the current review, the CASAC agreed with the conclusions
in the PA.\96\ In particular, the CASAC noted that it was ``satisfied
with the short-term exposure health-based benchmark analysis presented
in the Draft PA and agree[d] with the decision to not conduct any new
model-based or epidemiologic-based analyses'' (Diez Roux and Sheppard,
2017, p. 5). The CASAC further supported ``the decision not to conduct
any new or updated quantitative risk analyses related to long-term
exposure to NO2'' noting ``that existing uncertainties in
the epidemiologic literature limit the ability to properly estimate and
interpret population risk associated with NO2, specifically
within a formal risk assessment framework'' (Diez Roux and Sheppard,
2017, p. 5).
---------------------------------------------------------------------------
\96\ The PA conclusions build upon the preliminary conclusions
presented in the REA Planning document, which was also reviewed by
the CASAC (Diez Roux and Frey, 2015b).
---------------------------------------------------------------------------
In addition, in its review of the draft PA, the CASAC concurred
with staff's overall preliminary conclusions that it is appropriate to
consider retaining the current primary NO2 standards without
revision, stating that, ``the CASAC recommends retaining, and not
changing the existing suite of standards'' (Diez Roux and Sheppard,
2017). The CASAC's advice on the current standards is discussed in more
detail below (Section II.F.3).
F. Proposed Conclusions on the Adequacy of the Current Primary NO2
Standards
In evaluating whether, in view of the advances in scientific
knowledge and additional information now available, it is appropriate
to retain or revise the current primary NO2 standards, the
Administrator builds upon the last review and reflects upon the body of
evidence and information now available. The Administrator has taken
into account evidence-based and quantitative exposure- and risk-based
considerations, as well as advice from the CASAC, and his own public
health policy judgements in developing proposed conclusions on the
adequacy of the current primary NO2 standards. Evidence-
based considerations draw upon the ISA's assessment and integrated
synthesis of the scientific evidence from epidemiologic studies,
controlled human exposure studies, and experimental animal studies
evaluating health effects related to exposures to NO2, with
a focus on policy-relevant considerations. The exposure-/risk-based
considerations draw from the comparisons of NO2 air quality
with health-based benchmarks presented in the PA. Together with careful
consideration of advice from CASAC, these evidence-based and exposure-/
risk-based considerations have informed the Administrator's proposed
conclusions related to the adequacy of the current NO2
standards.
The following sections summarize these evidence-based (Section
II.F.1) and exposure-/risk-based (Section II.F.2) considerations and
the advice received from CASAC (Section II.F.3). Section II.F.4
presents the Administrator's proposed conclusions regarding the
adequacy of the current primary NO2 standards.
1. Evidence-Based Considerations
As discussed in Section II.C, in considering the evidence available
in the current review with regard to adequacy of the current 1-hour and
annual NO2 standards, the first topic of consideration is
the nature of the health effects attributable to NO2
exposures, drawing upon the integrated synthesis of the health evidence
in the ISA and the evaluations in the PA (Sections II.C.1 and II.C.2).
The following questions guide those considerations: (1) To what extent
does the currently available scientific evidence alter or strengthen
conclusions from the last review regarding health effects attributable
to ambient NO2 exposures? (2) Are previously identified
uncertainties reduced or do important uncertainties remain? (3) Have
new uncertainties been identified? These questions are addressed for
both short-term and long-term NO2 exposures, with a focus on
health endpoints for which the ISA concludes that the evidence
indicates there is a ``causal'' or ``likely to be a causal''
relationship.
With regard to short-term NO2 exposures, as in the last
review, the strongest evidence continues to come from studies examining
respiratory effects. In particular, the ISA concludes that evidence
indicates a ``causal'' relationship between short-term NO2
exposure and respiratory effects, based on evidence related to asthma
exacerbation. While this conclusion reflects a strengthening of the
causal determination, compared to the last review, this strengthening
is based largely on a more specific integration of the evidence related
to asthma exacerbations rather than on the availability of new,
stronger evidence. Additional evidence has become available since the
last review, as summarized below; however, this evidence has not
fundamentally altered the understanding of the relationship between
short-term NO2 exposures and respiratory effects.
The strongest evidence supporting this ISA causal determination
comes from controlled human exposure studies demonstrating
NO2-induced increases in AR in individuals with asthma. A
meta-analysis of data from these studies indicates the majority of
exposed individuals, generally with mild asthma, experienced increased
AR following exposures to NO2 concentrations as low as 100
ppb, while individual studies most consistently report such increases
following exposures to NO2 concentrations at or above 250
ppb. Most of the controlled human exposure studies assessed in the ISA
were available in the last review, particularly studies of non-specific
AR. As in the last review, there remains uncertainty due to the lack of
an apparent dose-response relationship between NO2 exposures
and AR and uncertainty in the potential adversity of NO2-
induced increases in AR.
Supporting evidence for a range of NO2-associated
respiratory effects also comes from epidemiologic studies. While some
recent epidemiologic studies provide new evidence based on improved
exposure characterizations and copollutant modeling, these studies are
consistent with the evidence from the last review and do not
[[Page 34822]]
fundamentally alter the understanding of the respiratory effects
associated with ambient NO2 exposures. Due to limitations in
the available epidemiologic methods, uncertainty remains in the current
review regarding the extent to which findings for NO2 are
confounded by traffic-related copollutants (e.g., PM2.5, EC/
BC, CO).
Thus, while some new evidence is available in this review, that new
evidence has not substantially altered the understanding of the
respiratory effects that occur following short-term NO2
exposures. This evidence is summarized in Section II.C.1 above, and is
discussed in detail in the ISA (U.S. EPA, 2016a, section 5.2.2).
With regard to long-term NO2 exposures, the ISA
concludes that there is ``likely to be a causal relationship'' between
long-term NO2 exposure and respiratory effects, based
largely on the evidence for asthma development in children. New
epidemiologic studies of asthma development have increasingly utilized
improved exposure assessment methods (i.e., measured or modeled
concentrations at or near children's homes and followed for many
years), which partly reduces uncertainties from the last review related
to exposure measurement error. Explicit integration of evidence for
individual outcome categories (e.g., asthma incidence, respiratory
infection) provides an improved characterization of biological
plausibility and mode of action. This improved characterization
includes the assessment of new evidence supporting a potential role for
repeated short-term NO2 exposures in the development of
asthma. High correlations between long-term average ambient
concentrations of NO2 and long-term concentrations of other
traffic-related pollutants, together with the general lack of
epidemiologic studies evaluating copollutant models that include
traffic-related pollutants, remains a concern in interpreting
associations with asthma development. Specifically, the extent to which
NO2 may be serving primarily as a surrogate for the broader
traffic-related pollutant mix remains unclear. Thus, while the evidence
for respiratory effects related to long-term NO2 exposures
has become stronger since the last review, there remain important
uncertainties to consider in evaluating this evidence within the
context of the adequacy of the current standards. This evidence is
summarized in Section II.C.2 above, and is discussed in detail in the
ISA (U.S. EPA, 2016a, section 6.2.2).
Given the evaluation of the evidence in the ISA, and the ISA's
causal determinations, the EPA's further consideration of the evidence
focuses on studies of asthma exacerbation (short-term exposures) and
asthma development (long-term exposures), and on what these bodies of
evidence indicate with regard to the basic elements of the current
primary NO2 standards. In particular, the EPA considers the
following question: To what extent does the available evidence for
respiratory effects attributable to either short- or long-term
NO2 exposures support or call into question the basic
elements of the current primary NO2 standards? In addressing
this question, the sections below summarize the PA's consideration of
the evidence in the context of the indicator, averaging times, levels,
and forms of the current standards.
a. Indicator
The indicator for both the current annual and 1-hour NAAQS for
oxides of nitrogen is NO2. While the presence of gaseous
species other than NO2 has long been recognized (discussed
in Section II.B.1, above), no alternative to NO2 has been
advanced as being a more appropriate surrogate for ambient gaseous
oxides of nitrogen. Both previous and recent controlled human exposure
studies and animal toxicology studies provide specific evidence for
health effects following exposure to NO2. Similarly, the
large majority of epidemiologic studies report health effect
associations with NO2, as opposed to other gaseous oxides of
nitrogen. In addition, because emissions that lead to the formation of
NO2 generally also lead to the formation of other
NOX oxidation products, measures leading to reductions in
population exposures to NO2 can generally be expected to
lead to reductions in population exposures to other gaseous oxides of
nitrogen. Therefore, an NO2 standard can also be expected to
provide some degree of protection against potential health effects that
may be independently associated with other gaseous oxides of nitrogen
even though such effects are not discernable from currently available
studies. Given these considerations, the PA reached the conclusion that
it is appropriate in the current review to consider retaining the
NO2 indicator for standards meant to protect against
exposures to gaseous oxides of nitrogen. In its review of the draft PA,
CASAC agreed with this conclusion (Diez Roux and Sheppard, 2017).
b. Averaging Time
The current primary NO2 standards are based on 1-hour
and annual averaging times. Together, these standards can provide
protection against short- and long-term NO2 exposures.
In establishing the 1-hour standard in the last review, the
Administrator considered evidence from both experimental and
epidemiologic studies. She noted that controlled human exposure studies
and animal toxicological studies provided evidence that NO2
exposures from less than one hour up to three hours can result in
respiratory effects such as increased AR and inflammation. These
included five controlled human exposure studies that evaluated the
potential for increased AR following 1-hour exposures to 100 ppb
NO2 in people with asthma. In addition, epidemiologic
studies had reported health effect associations with both 1-hour and
24-hour NO2 concentrations, without indicating that either
of these averaging periods was more closely linked with reported
effects. Thus, the available experimental evidence provided support for
considering an averaging time of shorter duration than 24 hours while
the epidemiologic evidence provided support for considering both 1-hour
and 24-hour averaging times. Given this evidence, the Administrator
concluded that, at a minimum, a primary concern with regard to
averaging time was the level of protection provided against 1-hour
NO2 exposures. Based on available analyses of NO2
air quality, she further concluded that a standard with a 1-hour
averaging time could also be effective at protecting against effects
associated with 24-hour NO2 exposures (75 FR 6502, February
9, 2010).
Based on the considerations summarized above, the Administrator
judged in the last review that it was appropriate to set a new
NO2 standard with a 1-hour averaging time. She concluded
that such a standard would be expected to effectively limit short-term
(e.g., 1- to 24-hours) NO2 exposures that had been linked to
adverse respiratory effects. She also retained the existing annual
standard to continue to provide protection against effects potentially
associated with long-term exposures to oxides of nitrogen (75 FR 6502,
February 9, 2010). These decisions were consistent with CASAC advice to
establish a short-term primary standard for oxides of nitrogen based on
using 1-hour maximum NO2 concentrations and to retain the
current annual standard (Samet, 2008, p. 2; Samet, 2009, p. 2).
As in the last review, support for a standard with a 1-hour
averaging time comes from both the experimental and epidemiologic
evidence. Controlled human exposure studies evaluated in the ISA
continue to provide evidence that NO2 exposures from less
than 1-hour up to three hours can result in
[[Page 34823]]
increased AR in individuals with asthma (U.S. EPA, 2016a, Tables 5-1
and 5-2). These controlled human exposure studies provide key evidence
supporting the ISA's determination that ``[a] causal relationship
exists between short-term NO2 exposure and respiratory
effects based on evidence for asthma exacerbation'' (U.S. EPA, 2016a,
p. 1-17). In addition, the epidemiologic literature assessed in the ISA
provides support for short-term averaging times ranging from 1-hour up
to 24-hours (e.g., U.S. EPA, 2016a Figures 5-3, 5-4 and Table 5-12).
Consistent with the evidence in the last review, the ISA concludes that
there is no indication of a stronger association for any particular
short-term duration of NO2 exposure (U.S. EPA, 2016a,
section 1.6.1). Thus, a 1-hour averaging time reasonably reflects the
exposure durations used in the controlled human exposure studies that
provide the strongest support for the ISA's determination of a causal
relationship. In addition, a standard with a 1-hour averaging time is
expected to provide protection against the range of short-term exposure
durations that have been associated with respiratory effects in
epidemiologic studies (i.e., 1-hour to 24-hours). In the PA, staff
reached the conclusion that when taken together, the combined evidence
from experimental and epidemiologic studies continues to support an
NO2 standard with a 1-hour averaging time to protect against
health effects related to short-term NO2 exposures. In its
review of the draft PA, the CASAC found that there continued to be
scientific support for the 1-hour averaging time (Diez Roux and
Sheppard, 2017, p. 7).
With regard to protecting against long-term exposures, the evidence
supports considering the overall protection provided by the combination
of the annual and 1-hour standards. The current annual standard was
originally promulgated in 1971 (36 FR 8186, April 30, 1971), based on
epidemiologic studies reporting associations between respiratory
disease and long-term exposure to NO2. The annual standard
was retained in subsequent reviews, in part to provide a margin of
safety against the serious effects reported in animal studies using
long-term exposures to high NO2 concentrations (e.g., above
8,000 ppb) (U.S. EPA, 1995).
As described above, evidence newly available in the current review
demonstrates associations between long-term NO2 exposures
and asthma development in children, based on NO2
concentrations averaged over year of birth, year of diagnosis, or
entire lifetime. Supporting evidence indicates that repeated short-term
NO2 exposures could contribute to this asthma development.
In particular, the ISA states that ``findings for short-term
NO2 exposure support an effect on asthma development by
describing a potential role for repeated exposures to lead to recurrent
inflammation and allergic responses,'' which are ``identified as key
early events in the proposed mode of action for asthma development''
(U.S. EPA, 2016a, p. 6-64 and p. 6-65). Taken together, the evidence
supports the potential for recurrent short-term NO2
exposures to contribute to the asthma development that has been
reported in epidemiologic studies to be associated with long-term
exposures. For these reasons, the PA reached the conclusion that, in
establishing standards to protect against adverse health effects
related to long-term NO2 exposures, the evidence supports
the consideration of both 1-hour and annual averaging times. In its
review of the draft PA, CASAC supported this approach to considering
the protection provided against long-term NO2 exposures by
considering the combination of the annual and 1-hour NO2
standards. With reference to the current annual standard, CASAC
specifically noted that ``it is the suite of the current 1-hour and
annual standards, together, that provide protection against adverse
effects'' (Diez Roux and Sheppard, 2017, p. 9).
c. Level and Form
In evaluating the extent to which evidence supports or calls into
question the levels or forms of the current NO2 standards,
the EPA considers the following question: To what extent does the
evidence indicate adverse respiratory effects attributable to short- or
long-term NO2 exposures lower than previously identified or
below the existing standards? In addressing this question, it is useful
to consider the range of NO2 exposure concentrations that
have been evaluated in experimental studies (controlled human exposure
and animal toxicology) and the ambient NO2 concentrations in
locations where epidemiologic studies have reported associations with
adverse outcomes. The PA's consideration of these issues is discussed
below for short-term (II.F.1.c.i) and long-term (II.F.1.c.ii)
NO2 exposures.
i. Short-Term
Controlled human exposure studies demonstrate the potential for
increased AR in some people with asthma following 30-minute to 1-hour
exposures to NO2 concentrations near those in the ambient
air (U.S. EPA, 2017a, Section 3.2.2).\97\ In evaluating the
NO2 exposure concentrations at which increased AR has been
observed, both the group mean results reported in individual studies
and the results from a recent meta-analysis evaluating individual-level
data are considered (Brown, 2015; U.S. EPA, 2016a, Section 5.2.2.1).
Group mean responses in individual studies, and the variability in
those responses, can provide insight into the extent to which observed
changes in AR are due to NO2 exposures, rather than to
chance alone, and have the advantage of being based on the same
exposure conditions. The meta-analysis can aid in identifying trends in
individual-level responses across studies and can have the advantage of
increased power to detect effects, even in the absence of statistically
significant effects in individual studies.
---------------------------------------------------------------------------
\97\ As discussed in Section II.C, experimental studies have not
reported other respiratory effects following short-term exposures to
NO2 concentrations at or near those found in the ambient
air.
---------------------------------------------------------------------------
When individual-level data were combined in a meta-analysis, Brown
(2015) reported that statistically significant majorities of study
participants experienced increased AR following resting exposures to
NO2 concentrations from 100 to 530 ppb. In some affected
individuals, the magnitudes of these increases were large enough to
have potential clinical relevance. Following exposures to 100 ppb
NO2 specifically, the lowest exposure concentration
evaluated, a marginally statistically significant majority of study
participants experienced increased AR.\98\ As discussed in more detail
in Section II.C.1, individual studies consistently report statistically
significant NO2-induced increases in AR following resting
exposures to NO2 concentrations at or above 250 ppb, but
have generally not reported statistically significant increases in AR
following resting exposures to NO2 concentrations from 100
to 200 ppb. Limitations in this evidence include the lack of an
apparent dose-response relationship between NO2 and AR and
remaining uncertainty in the adversity of the reported increases in AR.
These uncertainties become increasingly important at the lower
NO2
[[Page 34824]]
exposure concentrations (i.e., at or near 100 ppb), as the evidence for
NO2-induced increases in AR becomes less consistent across
studies at these lower concentrations.
---------------------------------------------------------------------------
\98\ Brown (2015) reported a p-value of 0.08 when data were
combined from studies of specific and non-specific AR. When the
analysis was restricted only to non-specific AR following exposures
to 100 ppb NO2, the percentage who experienced increased
AR was larger and statistically significant. In contrast, when the
analysis was restricted only to specific AR following exposures to
100 ppb NO2, the majority of study participants did not
experience increased AR (U.S. EPA, 2016a; Brown 2015).
---------------------------------------------------------------------------
The epidemiologic evidence from U.S. and Canadian studies, as
considered in the PA, provides information about the ambient
NO2 concentrations in locations where such studies have
examined associations with asthma-related hospital admissions or
emergency department visits (short-term) or with asthma incidence
(long-term). In particular, these studies inform consideration of the
extent to which NO2-health effect associations are
consistent, precise, statistically significant, and present for
distributions of ambient NO2 concentrations that likely
would have met the current standards. To the extent NO2-
health effect associations are reported in study areas that would
likely have met the current standards, the evidence would support the
potential for the current standards to allow the NO2-
associated effects indicated by those studies. In the absence of
studies reporting associations in locations meeting the current
NO2 standards, there would be greater uncertainty regarding
the potential for reported effects to be caused by NO2
exposures that occur with air quality meeting those standards. There
are also important uncertainties in the evidence which warrant
consideration, including the potential for copollutant confounding and
exposure measurement error, and the extent to which near-road
NO2 concentrations are reflected in the available air
quality data.
With regard to epidemiologic studies of short-term NO2
exposures conducted in the U.S. or Canada, the PA notes the following.
First, the only recent multicity study evaluated (Stieb et al., 2009),
which had maximum 1-hour DVs ranging from 67 to 242 ppb, did not report
a positive association between NO2 and ED visits. In
addition, of the single-city studies (U.S. EPA, 2017a, Figure 3-1) that
reported positive and relatively precise associations between
NO2 and asthma hospital admissions and ED visits, most
locations had NO2 concentrations likely to have violated the
current 1-hour NO2 standard over at least part of the study
period. Specifically, most of these locations had maximum estimated DVs
at or above 100 ppb and, had near-road NO2 monitors been in
place during study periods, DVs would likely have been higher. Thus, it
is likely that even the one study location with a maximum DV of 100 ppb
(Atlanta) would have violated the existing 1-hour standard during study
periods.\99\ For the study locations with maximum DVs below 100 ppb,
mixed results have been reported, with associations that are generally
statistically non-significant and imprecise. As with the studies
reporting more precise associations, near-road monitors were not in
place during these study periods. If they had been, 1-hour DVs could
have been above 100 ppb. In drawing conclusions based on this
epidemiologic evidence, the PA also considers the potential for
copollutant confounding as ambient NO2 concentrations are
often highly correlated with other pollutants. This can complicate
attempts to distinguish between independent effects of NO2
and effects of the broader pollutant mixture. While this has been
addressed to some extent in available studies, uncertainty remains for
the most relevant copollutants (i.e., those related to traffic such as
PM2.5, EC/BC, and CO). Taken together, while available U.S.
and Canadian epidemiologic studies report NO2-associated
hospital admissions and emergency department visits in locations likely
to have violated the current 1-hour NO2 standard, the PA
concludes that these studies do not indicate the occurrence of such
NO2-associated effects in locations and time periods with
NO2 concentrations that would clearly have met the current
1-hour NO2 standard (i.e., with its level of 100 ppb and
98th percentile form).
---------------------------------------------------------------------------
\99\ Based on recent air quality information for Atlanta, 98th
percentiles of daily maximum 1-hour NO2 concentrations
are higher at near-road monitors than non-near-road monitors (U.S.
EPA, 2017a, Figures 2-9 and 2-10). These differences could have been
even more pronounced during study periods, when NOX
emissions from traffic sources were higher (U.S. EPA, 2017a, Section
2.1.2).
---------------------------------------------------------------------------
In giving further consideration specifically to the form of 1-hour
standard, the PA notes that the available evidence and information in
this review is consistent with that informing consideration of form in
the last review. The last review focused on the upper percentiles of
the distribution of NO2 concentrations based, in part, on
evidence for health effects associated with short-term NO2
exposures from experimental studies which provided information on
specific exposure concentrations that were linked to respiratory
effects (75 FR 6475, February 9, 2010). In that review, the EPA
specified a 98th percentile form, rather than a 99th percentile, for
the new 1-hour standard. In combination with the 1-hour averaging time
and 100 ppb level, a 98th percentile form was judged to provide
appropriate public health protection. In addition, compared to the 99th
percentile, a 98th percentile form was expected to provide greater
regulatory stability.\100\ In addition, a 98th percentile form is
consistent with the PA's consideration of uncertainties in the health
effects that have the potential to occur at 100 ppb. Specifically, when
combined with the 1-hour averaging time and the level of 100 ppb, the
98th percentile form limits, but does not eliminate, the potential for
exposures to 100 ppb NO2.\101\
---------------------------------------------------------------------------
\100\ As noted in the last review, a less stable form could
result in more frequent year-to-year shifts between meeting and
violating the standard, potentially disrupting ongoing air quality
planning without achieving public health goals (75 FR 6493, February
9, 2010).
\101\ The 98th percentile corresponds to about the 7th or 8th
highest daily maximum 1-hour NO2 concentration in a year.
---------------------------------------------------------------------------
ii. Long-Term
With regard to health effects related to long-term NO2
exposures, the PA first considers the basis for the current annual
standard. It was originally set to protect against NO2-
associated respiratory disease in children reported in some
epidemiologic studies (36 FR 8186, April 30, 1973). In subsequent
reviews, the EPA has retained the annual standard, judging that it
provides protection with an adequate margin of safety against the
effects that have been reported in animal studies following long-term
exposures to NO2 concentrations well-above those found in
the ambient air (e.g., above 8,000 ppb for the development of lesions
similar to those found in humans with emphysema) (60 FR 52879, October
11, 1995). In the 2010 review, the EPA noted that, though some evidence
supported the need to limit long-term exposures to NO2, the
evidence for adverse health effects attributable to long-term
NO2 exposures did not support changing the level of the
annual standard.
In the current review, the strengthened ``likely to be causal''
relationship between long-term NO2 exposures and respiratory
effects is supported by epidemiologic studies of asthma development and
related effects demonstrated in animal toxicological studies. While
these studies strengthen the evidence for effects of long-term
exposures, compared to the last review, they are subject to important
uncertainties, including the potential for confounding by traffic-
related copollutants. The potential for such confounding is
particularly important to consider when interpreting epidemiologic
studies of long-term NO2 exposures given (1) the relatively
high correlations observed between measured
[[Page 34825]]
and modeled long-term ambient concentrations of NO2 and
long-term concentrations of other roadway-associated pollutants; (2)
the general lack of information from copollutant models on the
potential for NO2 associations that are independent of other
traffic-related pollutants or mixtures; and (3) the general lack of
supporting information from experimental studies that evaluate long-
term exposures to NO2 concentrations near those in the
ambient air. Thus, it is unclear the degree to which the observed
effects in these studies are independently related to exposure to
ambient concentrations of NO2. The epidemiologic evidence
from some U.S. and Canadian studies is also subject to uncertainty with
regard to the extent to which the studies accurately characterized
exposures of the study populations, further limiting what these studies
can tell us regarding the adequacy of the current primary
NO2 standards.
While the PA recognizes the above uncertainties, it considers what
studies of long-term NO2 and asthma development indicate
with regard to the adequacy of the current primary NO2
standards. As discussed above for short-term exposures, the PA
considers the degree to which the evidence indicates adverse
respiratory effects associated with long-term NO2 exposures
in locations that would have met the NAAQS. As summarized in Section
II.C.2, the causal determination for long-term exposures is supported
both by studies of long-term NO2 exposures and studies
indicating a potential role in asthma development for repeated short-
term exposures to high NO2 concentrations.
As such, when considering the ambient NO2 concentrations
present during study periods, the PA considers these concentrations
within the context of both the 1-hour and annual NO2
standards. Analyses of historical data indicate that 1-hour DVs at or
below 100 ppb generally correspond to annual DVs below 35 ppb.\102\
CASAC noted this relationship, stating that ``attainment of the 1-hour
standard corresponds with annual design value averages of 30 ppb
NO2'' (Diez Roux and Sheppard, 2017). Thus, meeting the 1-
hour standard with its level of 100 ppb would be expected to maintain
annual average NO2 concentrations below the 53 ppb level of
the current annual standard.
---------------------------------------------------------------------------
\102\ As noted in the PA, near-road monitors were not included
in this analysis due to the limited amount of data available.
---------------------------------------------------------------------------
As discussed in Section II.C.1, while annual estimated DVs in study
locations were often below 53 ppb, maximum 1-hour estimated DVs in most
locations were near or above 100 ppb. Because these study-specific
estimated DVs are based on the area-wide NO2 monitors in
place during study periods, they do not reflect the NO2
concentrations near the largest roadways, which are expected to be
higher in most urban areas. Had near-road monitors been in place during
study periods, estimated NO2 DVs based on near-road
concentrations likely would have been higher in many locations, and
would have been more likely to exceed the level of the annual and/or 1-
hour standard(s).
Given the paucity of epidemiologic studies conducted in areas that
were close to or below the current standards, and considering that no
near road monitors were in place during the study periods, the PA
concludes that the epidemiologic evidence does not provide support for
NO2-attributable asthma development in children in locations
with NO2 concentrations that would have clearly met the
current annual and 1-hour NO2 standards. The strongest
epidemiologic evidence informing the level at which effects may occur
comes from U.S. and Canadian epidemiologic studies that are subject to
critical uncertainties related to copollutant confounding and exposure
assessment. Furthermore, the PA's evaluation indicates that most of the
locations included in epidemiologic studies of long-term NO2
exposure and asthma incidence would likely have violated either one or
both of the current NO2 standards, over at least parts of
the study periods.
iii. PA Conclusions
Taking note of the conclusions in the PA, and based on the
information discussed above, the EPA revisits the question posed above:
To what extent does the evidence indicate adverse respiratory effects
attributable to short- or long-term NO2 exposures lower than
previously identified or below the existing standards?
In addressing this question, the PA notes that (1) experimental
studies do not indicate adverse respiratory effects attributable to
either short- or long-term NO2 exposures lower than
previously identified and that (2) epidemiologic studies do not provide
support for associations between adverse effects and ambient
NO2 concentrations that would have clearly met the current
standards. Taken together, the PA concludes that the available evidence
does not support the need for increased protection against short- or
long-term NO2 exposures, beyond that provided by the
existing standards. In its review of the draft PA, the CASAC agreed
with this conclusion, stating that ``[t]he CASAC concurs with the EPA
that the current scientific literature does not support a revision to
the primary NAAQS for nitrogen dioxide'' (Diez Roux and Sheppard, 2017,
p. 9). Therefore, the PA did not identify potential alternative
standard levels or forms for consideration.
2. Exposure- and Risk-Based Considerations
As described in greater detail in Section II.D above, and in the
REA Planning document (U.S. EPA, 2015, Section 2.1.1) and the PA (U.S.
EPA, 2017a, Chapter 4), the EPA conducted updated analyses comparing
ambient NO2 concentrations (i.e., as surrogates of potential
exposures) to health-based benchmarks, with a particular focus on study
areas where near-road monitors have been deployed. In the PA, staff
concluded that updated quantitative risk assessments were not supported
in the current review, based on uncertainties in the available evidence
and the likelihood that such analyses would be subject to the same
uncertainties identified in the risk estimates in the prior review
(U.S. EPA, 2017a, Chapter 4). The CASAC stated that it was ``satisfied
with the short-term exposure health-based benchmark analysis presented
in the draft PA'' and that it ``support[ed] the decision not to conduct
any new or updated quantitative risk analyses related to long-term
exposure to NO2'' (Diez Roux and Sheppard, 2017).
When considering analyses comparing NO2 air quality with
health-based benchmarks, the PA focuses on the following specific
questions: (1) To what extent are ambient NO2 concentrations
that may be of public health concern estimated to occur in locations
meeting the current NO2 standards? (2) What are the
important uncertainties associated with those estimates?
As discussed in Section II.D, benchmarks are based on information
from controlled human exposure studies of NO2 exposures and
AR. In identifying specific NO2 benchmarks, and considering
the weight to place on each, the PA considers both the group mean
results reported in individual studies and the results of a meta-
analysis that combined data from multiple studies (Brown, 2015; U.S.
EPA, 2016a, Section 5.2.2.1), as described above.
When taken together, the results of individual controlled human
exposure studies and of the meta-analysis by Brown (2015) support
consideration of NO2 benchmarks between 100 and 300 ppb,
based largely on studies of non-
[[Page 34826]]
specific AR in people with asthma exposed at rest. As discussed in more
detail in II.D, benchmarks from the upper end of this range are
supported by the results of individual studies, the majority of which
reported statistically significant increases in AR following
NO2 exposures at or above 250 ppb, and by the results of the
meta-analysis by Brown (2015). Benchmarks from the lower end of this
range, including 100 ppb, are supported by the results of the meta-
analysis, even though individual studies do not consistently report
statistically significant NO2-induced increases in AR at
these lower concentrations. In particular, while the meta-analysis
indicates that the majority of study participants with asthma
experienced an increase in AR following exposures to 100 ppb
NO2 (Brown, 2015), individual studies have not generally
reported statistically significant increases in AR following resting
exposures to 100 ppb NO2.\103\
---------------------------------------------------------------------------
\103\ Meta-analysis results for exposures to 100 ppb
NO2 were statistically significant when analyses were
restricted to non-specific AR, but not when analyses were restricted
to specific AR (Brown, 2015).
---------------------------------------------------------------------------
In further considering the potential public health implications of
exposures to NO2 concentrations at or above benchmarks,
there are multiple uncertainties, as discussed in Section II.C.I. As
discussed in more detail in that section, there is no indication of a
dose-response relationship between NO2 and AR in people with
asthma, and there is uncertainty in the clinical relevance and
potential adversity of the reported NO2-induced increases in
AR.
As discussed in Section II.D, analyses of unadjusted air quality,
which meets the current standards in all locations, indicate almost no
potential for 1-hour exposures to NO2 concentrations at or
above any of the benchmarks examined, including 100 ppb. Analyses of
air quality adjusted upwards to just meet the current 1-hour standard
\104\ indicate virtually no potential for 1-hour exposures to
NO2 concentrations at or above 200 ppb (or 300 ppb), and
almost none for exposures at or above 150 ppb. This is the case for
both estimates averaged over multiple years and estimates in worst-case
years, including at near-road monitoring sites within a few meters of
heavily trafficked roads. With respect to the lowest benchmark
evaluated, analyses estimate that there is potential for exposures to
1-hour NO2 concentrations at or above 100 ppb on some days
(e.g., about one to 10 days per year, on average, at near-road
monitoring sites). As described above, this result is consistent with
expectations, given that the current 1-hour standard, with its 98th
percentile form, is expected to limit, but not eliminate, the
occurrence of 1-hour NO2 concentrations of 100 ppb.
---------------------------------------------------------------------------
\104\ In all study areas, ambient NO2 concentrations
required smaller upward adjustments to just meet the 1-hour standard
than to just meet the annual standard. Therefore, as noted above and
in the PA (U.S. EPA, 2017a, Section 4.2.1), when adjusting air
quality to just meet the current NO2 NAAQS, the
adjustment needed to just meet the 1-hour standard was applied.
---------------------------------------------------------------------------
These analyses indicate that the current 1-hour NO2
standard is expected to allow virtually no potential for exposures to
the NO2 concentrations that have been shown most
consistently to increase AR in people with asthma, even under worst-
case conditions across a variety of study areas with among the highest
NOX emissions in the U.S. Such NO2 concentrations
are not estimated to occur, even at monitoring sites adjacent to some
of the most heavily trafficked roadways. In addition, the current 1-
hour standard provides protection against NO2 exposures that
have the potential to exacerbate asthma symptoms, but for which the
evidence indicates greater uncertainty in both the occurrence of such
exacerbations and in their severity, should they occur (i.e., at or
near 100 ppb). Given the results of these analyses, and the
uncertainties inherent in their interpretation, the PA concludes that
there is little potential for exposures to ambient NO2
concentrations that would be of public health concern in locations
meeting the current 1-hour standard.
3. CASAC Advice
As discussed above (Section II.E), in the current review of the
primary standards for NO2, the CASAC has provided advice and
recommendations based on its review of drafts of the ISA, of the REA
Planning document, and of the draft PA. The CASAC's advice on the
adequacy of the current primary NO2 standards was provided
as part of its review of the draft PA (Diez Roux and Sheppard, 2017).
Overall, the CASAC concurred with the draft PA's preliminary conclusion
that it is appropriate to consider retaining the current primary
NO2 standards without revision, stating that, ``the CASAC
recommends retaining, and not changing the existing suite of
standards'' (Diez Roux and Sheppard, 2017). The CASAC provided the
following advice with respect to the individual elements of the
standards:
Indicator and averaging time: The CASAC stated ``there is
strong evidence for the selection of NO2 as the indicator of
oxides of nitrogen'' and ``for the selection of 1-hour and annual
averaging times'' (Diez Roux and Sheppard, 2017 p. 9). With regard with
to averaging time in particular, the CASAC stated that ``[c]ontrolled
human and animal studies provide scientific support for a 1-hour
averaging time as being representative of an exposure duration that can
lead to adverse effects'' (Diez Roux and Sheppard, 2017, p. 7). The
CASAC further concluded that ``[e]pidemiologic studies provide support
for the annual averaging time, representative of likely to be causal
associations between long-term exposures, or repeated short-term
exposures, and asthma development'' (Diez Roux and Sheppard, 2017, p.
7).
Level of the 1-hour standard: The CASAC stated ``there are
notable adverse effects at levels that exceed the current standard, but
not at the level of the current standard. Thus, the CASAC advises that
the current 1-hour standard is protective of adverse effects and that
there is not a scientific basis for a standard lower than the current
1-hour standard'' (Diez Roux, and Sheppard 2017, p. 9).
Form of the 1-hour standard: The CASAC also ``recommends
retaining the current form'' for the 1-hour standard (Diez Roux and
Sheppard 2017). Recognizing that the form allowed for some 1-hour
concentrations that exceeded 100 ppb, the CASAC explained that the
``scientific rationale for this form is there is uncertainty regarding
the severity of adverse effects at a level of 100 ppb NO2,
and thus some potential for maximum daily levels to exceed this
benchmark with limited frequency may nonetheless be protective of
public health'' (Diez Roux and Sheppard, 2017, p. 10). It further noted
that the choice of form reflected the Administrator's policy judgment.
(Diez Roux and Sheppard, 2017, p. 10).
Level of the annual standard: In providing advice on the
level of the annual standard, the CASAC commented that the long-term
epidemiologic studies ``imply the possibility of adverse effects at
levels below that of the current annual standard'' (Diez Roux and
Sheppard, p. 8). However, CASAC recognized that these studies ``are
also subject to uncertainty, including possible confounding with other
traffic-related pollutants'' (Diez Roux and Sheppard, p. 8). CASAC also
commented that these epidemiologic studies may have uncertainty related
to exposure error and pointed out that estimated DVs in study areas do
not account for near-road monitoring. Furthermore, CASAC recognized the
causal associations between long-term exposures, or repeated short-term
exposures, and asthma development (Diez Roux and
[[Page 34827]]
Sheppard, p. 7) and the appropriateness of considering the protection
provided by the current suite of standards together (Diez Roux and
Sheppard, p. 9). Therefore, the CASAC's advice on the annual standard
takes into account the degree of protection provided by this standard,
in combination with the current 1-hour standard. In particular, the
CASAC recognized that meeting the 1-hour NO2 standard can
limit long-term NO2 concentrations to below the level of the
annual standard, observing that ``an hourly DV of 100 ppb
NO2 is associated with DV values that average approximately
30 ppb NO2'' and that ``there is insufficient evidence to
make a scientific judgment that adverse effects occur at annual DVs
less than 30 ppb NO2'' (Diez Roux and Sheppard, 2017, p. 9).
Thus, in providing support for retaining the existing annual standard,
the CASAC specifically noted that ``the current suite of standards is
more protective of annual exposures compared to the annual standard by
itself'' and that ``it is the suite of the current 1-hour and annual
standards, together, that provide protection against adverse effects''
(Diez Roux and Sheppard, 2017, p. 9). Therefore, the CASAC ``recommends
retaining the existing suite of standards'' (Diez Roux and Sheppard,
2017, p. 9), including the current annual standard.
In addition, CASAC also provided advice on areas for additional
research based on key areas of uncertainty that came up during the
review cycle (Diez Roux and Sheppard, 2017, p. 10-12). As part of this
advice, CASAC stated that ``[t]here is an ongoing need for research in
multipollutant exposure and epidemiology to attempt to distinguish the
contribution to NO2 exposure to human health risk'' (Diez
Roux and Sheppard, 2017, p. 10). More specifically, CASAC pointed to
the importance of further understanding the effects of co-pollutant
exposures and the variability in ambient NO2 concentrations,
particularly considering ``locations of peak exposure occurrences
(e.g., on road in vehicles, roadside for active commuters, in street
canyons, near other non-road facilities such as rail yards or
industrial facilities)'' (Diez Roux and Sheppard, 2017, p. 11). In
particular, CASAC recognized the importance of the new near-road
monitoring data in reducing those uncertainties, stating that ``[t]he
amount of data from near-road monitoring will increase between now and
the next review cycle and should be analyzed and evaluated'' (Diez Roux
and Sheppard, 2017, p. 11).
4. Administrator's Proposed Conclusions Regarding the Adequacy of the
Current Primary NO2 Standards
Taking into consideration the large body of evidence concerning
NO2-related health effects and available estimates of the
potential for NO2 exposures, including the uncertainties and
limitations inherent in the evidence and those estimates, the
Administrator proposes to conclude that the current primary
NO2 standards provide the requisite protection of public
health, with an adequate margin of safety, and should be retained
without revision in this review. The Administrator's proposed
conclusions are informed by a careful consideration of the full body of
information available in this review, giving particular weight to the
assessment of the scientific evidence in the ISA; analyses in the PA
comparing NO2 air quality with health-based benchmarks; the
PA's consideration of the evidence and analyses; and the advice and
recommendations from the CASAC. The basis for the Administrator's
proposed conclusions on the current primary NO2 standards is
discussed below.
As an initial matter, the Administrator takes note of the well-
established body of scientific evidence supporting the occurrence of
respiratory effects following NO2 exposures. As in the last
review, the clearest evidence indicates the occurrence of respiratory
effects following short-term NO2 exposures. The strongest
support for this relationship comes from controlled human exposure
studies demonstrating NO2-induced increases in AR in
individuals with asthma. As discussed above, the Administrator notes
that most of the controlled human exposure studies assessed in the ISA
were available in the last review, with the addition in this review of
an updated meta-analysis that synthesizes data from these studies. He
also notes that these studies provided an important part of the body of
evidence supporting the decision in the last review to establish the 1-
hour NO2 standard with its level of 100 ppb. Beyond the
controlled human exposure studies, additional supporting evidence comes
from epidemiologic studies reporting associations with a range of
asthma-related respiratory effects, including effects serious enough to
result in emergency room visits or hospital admissions. While there is
some new evidence in the current review from such epidemiologic studies
of short-term NO2 exposures, the results of these newer
studies are generally consistent with the epidemiologic studies that
were available in the last review.
With regard to long-term NO2 exposures, the
Administrator notes that the evidence supporting associations with
asthma development in children has become stronger since the last
review, though uncertainties remain regarding the degree to which
estimates of long-term NO2 concentrations in these studies
are serving primarily as surrogates for exposures to the broader
mixture of traffic-related pollutants. Supporting evidence also
includes studies indicating a potential role for repeated short-term
NO2 exposures in the development of asthma (U.S. EPA, 2016a,
p. 6-64 and p. 6-65).
In addition, the Administrator acknowledges that the evidence for
some non-respiratory effects has strengthened since the last review. In
particular, based on the assessment of the evidence in the ISA, he
notes the stronger evidence for NO2-associated
cardiovascular effects (short- and long-term exposures), premature
mortality (long-term exposures), and certain reproductive effects
(long-term exposures). As detailed in the ISA, while this evidence has
generally become stronger since the last review, it remains subject to
greater uncertainty than the evidence of asthma-related respiratory
effects (U.S. EPA, 2016a).
The Administrator's evaluation of the public health protection
provided against ambient NO2 exposures also involves
consideration of populations and lifestages that may be at greater risk
of experiencing NO2-attributable health effects. In the
current review, the Administrator's consideration of potential at-risk
populations draws from the 2016 ISA's assessment of the evidence (U.S.
EPA, 2016a, Chapter 7). Based on the ISA's systematic approach to
evaluating factors that may increase risks in a particular population
or during a particular lifestage, the Administrator is most concerned
about the potential effects of NO2 exposures in people with
asthma, children, and older adults (U.S. EPA, 2016a, Table 7-27).
Support for potentially higher risks in these populations is based
primarily on evidence for asthma exacerbation or asthma development.
Evidence for other health effects is subject to greater uncertainty
(U.S. EPA, 2017a, Section 3.4).
The Administrator further uses the scientific evidence outlined
above, and described in detail in the ISA (U.S. EPA, 2016a), to
directly inform his consideration of the adequacy of the public health
protection provided by the current primary NO2 standards.
Consistent with the approach in the PA
[[Page 34828]]
(U.S. EPA, 2017a), and with CASAC advice (Diez Roux and Sheppard,
2017), the Administrator specifically considers the evidence within the
context of the degree of public health protection provided by the
current 1-hour and annual standards together, including the combination
of all elements of these standards (i.e., indicator, averaging times,
forms, levels).
In doing so, the Administrator focuses on the results of controlled
human exposure studies of AR in people with asthma and on the results
of U.S. and Canadian epidemiologic studies of asthma-related hospital
admissions, asthma-related emergency department visits, and asthma
development in children. He particularly emphasizes the results of
controlled human exposure studies, which were identified in the ISA as
providing ``[t]he key evidence that NO2 exposure can
independently exacerbate asthma'' (U.S. EPA, 2016a, p. 1-18). The
Administrator's decision to focus on these studies is in agreement with
the CASAC, which stated that, of the evidence for asthma exacerbation,
``[t]he strongest evidence is for an increase in AR based on controlled
human exposure studies, with supporting evidence from epidemiologic
studies'' (Diez Roux and Sheppard, 2017).
In considering the controlled human exposure studies of AR, the
Administrator focuses both on the results of an updated meta-analysis
of data from these studies and on the consistency of findings across
individual studies. As discussed above, and consistent with the
evidence in the last review, the meta-analysis indicates that the
majority of study volunteers, generally with mild asthma, experienced
increased AR following 30-minute to 1-hour resting exposures to
NO2 concentrations from 100 to 530 ppb. Based on these
results, the Administrator notes the potential for people with asthma
to experience NO2-induced respiratory effects following
exposures in this range, and that people with more severe asthma could
experience more serious effects. The Administrator further notes that
individual studies consistently report statistically significant
increases in AR following exposures to NO2 concentrations at
or above 250 ppb, with less consistent results across studies conducted
at lower exposure concentrations, particularly 100 ppb (II.C.1).
Uncertainties in this evidence, discussed in sections II.C.1, II.D.3,
and II.F.2 above, include the lack of an apparent dose-response
relationship and uncertainty in the potential adversity of responses.
When the information discussed above is taken together, the
Administrator judges it appropriate to consider the degree of
protection provided against exposures to NO2 concentrations
at and above 100 ppb, though his concern is greater for exposures to
higher concentrations. In particular, based on the results of the meta-
analysis and on the consistent results across individual studies, the
Administrator is most concerned about the potential for people with
asthma to experience adverse respiratory effects following
NO2 exposures at or above 250 ppb. Because results are less
consistent across individual studies that evaluated lower exposure
concentrations, the Administrator becomes increasingly concerned about
uncertainties in the evidence as he considers the potential
implications of such exposures. While taking these uncertainties into
consideration, the Administrator remains concerned about the potential
for respiratory effects following exposures to NO2
concentrations as low as 100 ppb, particularly in people with more
severe cases of asthma than have generally been evaluated in the
available NO2 controlled human exposure studies. Thus, when
the evidence and uncertainties are taken together, the Administrator
judges that it is appropriate to consider the degree of protection
provided against potential exposures to NO2 concentrations
at or above 100 ppb, with the most emphasis on the potential for
exposures at or above 250 ppb.
In further considering the potential public health implications of
controlled human exposure studies, the Administrator looks to the
results of quantitative comparisons between NO2 air quality
and health-based benchmarks. As discussed in the PA, these comparisons
can help to place the results of the controlled human exposure studies,
which provide the basis for the benchmark concentrations, into a
broader public health context. In considering the results of the
analyses comparing NO2 air quality to specific health-based
benchmarks, the Administrator first recognizes that all areas of the
U.S. meet the current primary NO2 standards. When based on
recent unadjusted NO2 air quality, these analyses estimate
almost no days with the potential for 1-hour exposures to
NO2 concentrations at or above health-based benchmarks,
including the lowest benchmark examined (i.e., 100 ppb).
The Administrator additionally recognizes that, even when ambient
NO2 concentrations are adjusted upward to just meet the
existing 1-hour standard, the analyses estimate no days with the
potential for exposures to the NO2 concentrations that have
been shown most consistently to increase AR in people with asthma
(i.e., above 250 ppb). Such NO2 concentrations were not
estimated to occur, even under worst-case conditions across a variety
of study areas with among the highest NOX emissions in the
U.S., and at monitoring sites adjacent to some of the most heavily
trafficked roadways in the U.S. In addition, analyses with adjusted air
quality indicate a limited number of days with the potential for
exposures to 1-hour NO2 concentrations at or above 100 ppb,
an exposure concentration with the potential to exacerbate asthma-
related respiratory effects, but for which uncertainties in the
evidence become increasingly important.
Based on the information above, the Administrator reaches the
proposed conclusion that evidence from controlled human exposure
studies of AR, together with analyses comparing ambient NO2
concentrations to health-based benchmarks, supports the degree of the
public health protection provided by the current primary NO2
NAAQS. In particular, he is concerned about exposures to NO2
concentrations at and above 250 ppb, where the potential for
NO2-induced respiratory effects is supported by results of
the meta-analysis and by consistent results reported across individual
studies. With regard to this, the Administrator notes that meeting the
current standards is estimated to allow no potential for exposures to
1-hour NO2 concentrations at or above 250 ppb. The
Administrator is also concerned about exposures to lower NO2
concentrations, including concentrations as low as 100 ppb though, as
described above, he becomes increasingly concerned about the
uncertainties in the evidence at such low exposure concentrations. In
considering the degree of protection provided against exposures to 100
ppb NO2, in light of uncertainties, the Administrator judges
it appropriate to limit such exposures, but not necessarily to
eliminate them. With regard to this, he notes that the current standard
is estimated to allow limited potential for exposures to NO2
concentrations at or above 100 ppb. Thus, given the substantial
protection provided against exposures to NO2 concentrations
at and above 250 ppb, and the protection provided against exposures to
concentrations as low as 100 ppb, the Administrator reaches the
proposed conclusion that the evidence, when considered in light of its
uncertainties, supports the degree of
[[Page 34829]]
public health protection provided by the current primary NO2
NAAQS.
Although the NO2 epidemiologic evidence is subject to
greater uncertainty than the controlled human exposure studies of
NO2-induced changes in AR, the Administrator also considers
what the available epidemiologic studies indicate with regard to the
adequacy of the public health protection provided by the current
standards. In particular, he considers analyses of NO2 air
quality in the locations, and during the time periods, of available
U.S. and Canadian epidemiologic studies. These analyses can provide
insights into the extent to which NO2-health effect
associations are present for distributions of ambient NO2
concentrations that would be allowed by the current standards. The
presence of such associations would support the potential for the
current standards to allow the NO2-associated effects
indicated by epidemiologic studies. To the degree studies have not
reported associations in locations meeting the current NO2
standards, there is greater uncertainty regarding the potential for
reported effects to occur following the NO2 exposures that
are associated with air quality meeting those standards.
With regard to studies of short-term NO2 exposures, the
Administrator notes that epidemiologic studies provide consistent
evidence for asthma-related emergency department visits and hospital
admissions with exposure to NO2 in locations likely to have
violated the current standards over at least parts of study periods
(based on the presence of relatively precise and generally
statistically significant associations across several studies). These
studies have not consistently shown such NO2-associated
outcomes in areas that would have clearly met the current standards. In
this regard, the Administrator recognizes that the NO2
concentrations identified in these epidemiologic studies are based on
an NO2 monitoring network that, during study periods, did
not include monitors meeting the current near-road monitoring
requirements. This is particularly important given that NO2
concentrations near the most heavily-trafficked roadways were likely to
have been higher than those reflected by the NO2
concentrations measured at monitors in operation during study years. As
such, the estimated DVs associated with the areas at the times of the
studies could have been higher had a near-road monitoring network been
in place. Thus, while these epidemiologic studies provide consistent
evidence for associations with asthma-related effects, the
Administrator notes that studies conducted in the U.S. and Canada do
not provide support for associations with asthma-related hospital
admissions or emergency department visits in locations that would have
clearly met the current standards.
With regard to studies of long-term NO2 exposures, the
Administrator notes that the preponderance of evidence for respiratory
health effects comes from epidemiologic studies evaluating asthma
development in children. As discussed above, these studies report
associations with long-term average NO2 concentrations,
while the broader body of evidence indicates the potential for repeated
short-term NO2 exposures to contribute to the development of
asthma. Because of this, and because air quality analyses indicate that
meeting the current 1-hour standard can also limit annual
NO2 concentrations, when considering these studies of asthma
development, the Administrator considers the protection provided by the
combination of both the annual and 1-hour standards. While available
epidemiologic studies conducted in the U.S. and Canada consistently
report associations between long-term NO2 exposures and
asthma development in children in locations likely to have violated the
current standards over at least parts of study periods, those studies
do not indicate such associations in locations that would have clearly
met the current annual and 1-hour standards. This is particularly the
case given that NO2 concentrations near the most heavily-
trafficked roadways are not likely reflected by monitors in operation
during study years. Thus, while recognizing the public health
significance of asthma development in children, and recognizing that
NO2 concentrations violating the current standards have been
associated with asthma development, the Administrator places weight on
the PA's conclusion that the evidence does not provide support for
NO2-attributable asthma development in children in locations
with NO2 concentrations that would have clearly met both the
annual and 1-hour standards.
Taking all of these considerations into account, the Administrator
reaches the proposed conclusion that the current body of scientific
evidence, in combination with the results of quantitative analyses
comparing NO2 air quality with health-based benchmarks,
supports the degree of public health protection provided by the current
1-hour and annual primary NO2 standards and does not call
into question any of the elements of those standards. He further
reaches the proposed conclusion that the current 1-hour and annual
NO2 primary standards, together, are requisite to protect
public health with an adequate margin of safety.
In particular, with regard to short-term exposures and the current
1-hour standard, the Administrator takes note of the well-established
body of scientific evidence supporting the occurrence of respiratory
effects following short-term NO2 exposures. In reaching the
proposed conclusion that the current standards provide requisite
protection against these effects, the Administrator notes:
Meeting the current 1-hour NO2 standard
provides a substantial margin of safety against exposures to
NO2 concentrations that have been shown most consistently
to increase AR in people with asthma, even under worst-case
conditions across a variety of study areas with among the highest
NOX emissions in the U.S. Such NO2
concentrations were not estimated to occur, even at monitoring sites
adjacent to some of the most heavily trafficked roadways.
Meeting the current 1-hour standard limits the
potential for exposures to 1-hour concentrations at or above 100
ppb. Thus, the current standard provides protection against
NO2 exposures with the potential to exacerbate symptoms
in some people with asthma, but for which uncertainties in the
evidence become increasingly important.
Meeting the current 1-hour standard is expected to
maintain ambient NO2 concentrations below those present
in locations where key U.S. and Canadian epidemiologic studies
reported precise and statistically significant associations between
short-term NO2 and asthma-related hospitalizations.
In addition, with regard to long-term NO2 exposures, the
Administrator notes that the evidence supporting associations with
asthma development in children has become stronger since the last
review, though important uncertainties remain. As discussed above,
meeting the current annual and 1-hour standards is expected to maintain
ambient NO2 concentrations below those present in locations
where key U.S. and Canadian epidemiologic studies reported such
associations between long-term NO2 and asthma development.
In considering the protection provided against exposures that could
contribute to asthma development, the Administrator recognizes the air
quality relationship between the current 1-hour standard and annual
standard, and that analyses of historical ambient NO2
concentrations suggest that meeting the 1-hour standard with its level
of 100 ppb would be expected to maintain annual average NO2
concentrations well-below the 53 ppb level of the annual standard, and
generally below 35
[[Page 34830]]
ppb.\105\ The Administrator judges that, as additional years of data
become available from the recently deployed near-road NO2
monitors, it will be important to evaluate the degree to which this
relationship is also observed in the near-road environment, and the
degree to which the annual standard provides additional protection,
beyond that provided by the 1-hour standard. Such an evaluation could
inform future reviews of the primary NO2 NAAQS, consistent
with the CASAC advice that ``in the next review cycle for oxides of
nitrogen . . . EPA should review the annual standard to determine if
there is need for revision or revocation'' (Diez Roux and Sheppard,
2017, p. 9).
---------------------------------------------------------------------------
\105\ This air quality relationship was discussed in the PA
where it was noted that the analysis did not include data from near-
road monitors due to the limited amount of data available for the
years analyzed (1980-2015).
---------------------------------------------------------------------------
Therefore, in this review, the Administrator proposes to retain the
current primary NO2 standards, without revision. As
described in section II.F.3 above, the Administrator notes that his
proposed decision to retain the current primary NO2
standards in this review is consistent with CASAC advice provided as
part of its review of the draft PA. In particular, the Administrator
notes that ``the CASAC recommends retaining, and not changing the
existing suite of standards'' (Diez Roux and Sheppard, 2017). CASAC
specifically focused its conclusions on the degree of protection
provided by the combination of the 1-hour and annual standards against
short- and long-term NO2 exposures. In particularly, the
CASAC stated that ``it is the suite of the current 1-hour and annual
standards, together, that provide protection against adverse effects''
(Diez Roux and Sheppard, 2017, p. 9).
Inherent in the Administrator's proposed conclusions are public
health policy judgments on the public health implications of the
available scientific evidence and analyses, including how to weigh
associated uncertainties. These public health policy judgments include
judgments related to the appropriate degree of public health protection
that should be afforded against risk of respiratory morbidity in at-
risk populations, such as the potential for worsened respiratory
effects in people with asthma, as well judgments related to the
appropriate weight to be given to various aspects of the evidence and
quantitative analyses, including how to consider their associated
uncertainties. Based on these considerations and the judgments
identified here, the Administrator reaches the proposed conclusion that
the current standards provide the requisite protection of public health
with an adequate margin of safety, including protection of at-risk
populations, such as people with asthma.
In reaching this proposed conclusion, the Administrator recognizes
that in establishing primary standards under the Act that are requisite
to protect public health with an adequate margin of safety, he is
seeking to establish standards that are neither more nor less stringent
than necessary for this purpose. The Act does not require that primary
standards be set at a zero-risk level, but rather at a level that
avoids unacceptable risks to public health. In this context, the
Administrator's proposed conclusion is that the current standards
provide the requisite protection and that more or less stringent
standards would not be requisite.
More specifically, given the adverse effects reported to be
associated with NO2 concentrations above the current
standards, the Administrator does not believe standards less stringent
than the current standards would be sufficient to protect public health
with an adequate margin of safety. In this regard, he particularly
notes that, compared to the current standards, less stringent standards
would be more likely to allow (1) NO2 exposures that could
exacerbate respiratory effects in people with asthma, particularly
those with more severe asthma and (2) ambient NO2
concentrations that have been reported in epidemiologic studies to be
associated with asthma-related hospitalizations and with asthma
development in children. Consistent with these observations, the
Administrator further notes CASAC's conclusion, based on its
consideration of the evidence, that ``there are notable adverse effects
at levels that exceed the current standard, but not at the level of the
current standard'' (Diez Roux and Sheppard, 2017 pg. 9). Therefore, the
Administrator reaches the proposed conclusion that standards less
stringent than the current 1-hour and annual standards (e.g., with
levels higher than 100 ppb and 53 ppb, respectively) would not be
sufficient to protect public health with an adequate margin of safety.
The Administrator additionally recognizes that the uncertainties
and limitations associated with the many aspects of the estimated
relationships between respiratory morbidity and NO2
exposures are amplified with consideration of progressively lower
ambient NO2 concentrations. In his view, and consistent with
the conclusions in the PA, there is appreciable uncertainty in the
extent to which reductions in asthma exacerbations or asthma
development would result from revising the primary NO2 NAAQS
to be more stringent than the current standards. Therefore, the
Administrator also does not believe standards more stringent than the
current standards would be appropriate. With regard to this, CASAC
advised that ``there is not a scientific basis for a standard lower
than the current 1-hour standard'' (Diez Roux and Sheppard, 2017 pg.
9). The CASAC also did not advise setting the level of the annual
standard lower than the current level of 53 ppb, noting that the 1-hour
standard can generally maintain long-term NO2 concentrations
below the level of the annual standard (Diez Roux and Sheppard, 2017).
Based on all of the above considerations, and consistent with CASAC
advice, the Administrator reaches the proposed conclusion that it is
appropriate to retain the current standards, without revision, in this
review. He further proposes that the available evidence and information
do not warrant the identification of potential alternative standards
that provide a different degree of public health protection. In
reaching these proposed conclusions, the Administrator recognizes that
different public health policy judgments could lead to different
conclusions regarding the extent to which the current standards protect
the public health. Such judgments include those related to the
appropriate degree of public health protection that should be afforded
as well as the appropriate weight to be given to various aspects of the
evidence and information, including how to consider uncertainties.
Therefore, the Administrator solicits comment on his proposed
conclusions regarding the public health protection provided by the
current primary NO2 standards and on his proposal to retain
those standards, without revision, in this review. He invites comment
on all aspects of these proposed conclusions and their underlying
rationales, including on his proposal that the current standards are
requisite, i.e., neither more nor less stringent than necessary, to
protect the public health with an adequate margin of safety and on the
evidence-based and exposure-/risk-based considerations supporting that
proposal.
III. Statutory and Executive Order Reviews
Additional information about these statutes and Executive Orders
can be found at http://www2.epa.gov/laws-regulations/laws-and-executive-orders.
[[Page 34831]]
A. Executive Order 12866: Regulatory Planning and Review and Executive
Order 13563: Improving Regulation and Regulatory Review
The Office of Management and Budget (OMB) determined that this
action is a significant regulatory action. Accordingly, it was
submitted to OMB for review. Any changes made in response to OMB
recommendations have been documented in the docket. Because this rule
does not propose to change the existing NAAQS for NO2, it
does not impose costs or benefits relative to the baseline of
continuing with the current NAAQS in effect. EPA has thus not prepared
a Regulatory Impact Analysis for this rule.
B. Paperwork Reduction Act (PRA)
This action does not impose an information collection burden under
the PRA. There are no information collection requirements directly
associated with a decision to retain a NAAQS without any revision under
section 109 of the CAA and this action proposes to retain the current
primary NO2 NAAQS without any revisions.
C. Regulatory Flexibility Act (RFA)
I certify that this action will not have a significant economic
impact on a substantial number of small entities under the RFA. This
action will not impose any requirements on small entities. Rather, this
action proposes to retain, without revision, existing national
standards for allowable concentrations of NO2 in ambient air
as required by section 109 of the CAA. See also American Trucking
Associations v. EPA. 175 F.3d at 1044-45 (NAAQS do not have significant
impacts upon small entities because NAAQS themselves impose no
regulations upon small entities).
D. Unfunded Mandates Reform Act (UMRA)
This action does not contain any unfunded mandate as described in
the UMRA, 2 U.S.C. 1531-1538 and does not significantly or uniquely
affect small governments. This action imposes no enforceable duty on
any state, local or tribal governments or the private sector.
E. Executive Order 13132: Federalism
This action does not have federalism implications. It will not have
substantial direct effects on the states, on the relationship between
the national government and the states, or on the distribution of power
and responsibilities among the various levels of government.
F. Executive Order 13175: Consultation and Coordination With Indian
Tribal Governments
This action does not have tribal implications, as specified in
Executive Order 13175. This action does not change existing
regulations. It does not have a substantial direct effect on one or
more Indian Tribes, since Tribes are not obligated to adopt or
implement any NAAQS. The Tribal Authority Rule gives Tribes the
opportunity to develop and implement CAA programs such as the primary
NO2 NAAQS, but it leaves to the discretion of the Tribe
whether to develop these programs and which programs, or appropriate
elements of a program, they will adopt. Thus, Executive Order 13175
does not apply to this action.
G. Executive Order 13045: Protection of Children From Environmental
Health and Safety Risks
This action is not subject to Executive Order 13045 because it is
not economically significant as defined in Executive Order 12866. The
health effects evidence and risk assessment information for this
action, which focuses on children, people with asthma, and older
adults, in addressing the at-risk populations, is summarized in section
II.C.3 above and described in the ISA and PA, copies of which are in
the public docket for this action.
H. Executive Order 13211: Actions That Significantly Affect Energy
Supply, Distribution or Use
This action is not a ``significant energy action'' because it is
not likely to have a significant adverse effect on the supply,
distribution, or use of energy. The purpose of this notice is to
propose to retain the current primary NO2 NAAQS. This
proposal does not change existing requirements. Thus, the EPA concludes
that this proposal does not constitute a significant energy action as
defined in Executive Order 13211.
I. National Technology Transfer and Advancement Act (NTTAA)
This action does not involve technical standards.
J. Executive Order 12898: Federal Actions To Address Environmental
Justice in Minority Populations and Low-Income Populations
The EPA believes that this action does not have disproportionately
high and adverse human health or environmental effects on minority,
low-income populations and/or indigenous peoples, as specified in
Executive Order 12898 (59 FR 7629, February 16, 1994). The
documentation for this decision is contained in Section II. The action
proposed in this notice is to retain without revision the existing
primary NAAQS for oxides of nitrogen based on the Administrator's
conclusion that the existing standards protect public health, including
the health of sensitive groups, with an adequate margin of safety. The
EPA expressly considered the available information regarding health
effects among at-risk populations in reaching the proposed decision
that the existing standards are requisite.
K. Determination Under Section 307(d)
Section 307(d)(1)(V) of the CAA provides that the provisions of
section 307(d) apply to ``such other actions as the Administrator may
determine.'' Pursuant to section 307(d)(1)(V), the Administrator
determines that this action is subject to the provisions of section
307(d).
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List of Subjects in 40 CFR Part 50
Environmental protection, Air pollution control, Carbon monoxide,
Lead, Nitrogen dioxide, Ozone, Particulate matter, Sulfur oxides.
Dated: July 14, 2017.
E. Scott Pruitt,
Administrator.
[FR Doc. 2017-15591 Filed 7-25-17; 8:45 am]
BILLING CODE 6560-50-P