
[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  

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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 chappell.regina@epa.gov. 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 Once submitted, comments cannot be edited or withdrawn.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: alman.breanna@epa.gov.

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

[[Page 34796]]

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.
---------------------------------------------------------------------------

    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\
---------------------------------------------------------------------------

    \11\ This document may be found at: https://www.epa.gov/naaqs/policy-assessment-review-primary-national-ambient-air-quality-standards-oxides-nitrogen.
---------------------------------------------------------------------------

    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\
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

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.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    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).
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

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.
---------------------------------------------------------------------------

    \21\ She also considered public comments received on the 
proposal (75 FR 6490, February, 9, 2010).
---------------------------------------------------------------------------

    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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

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).
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

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).
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

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\
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

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).
---------------------------------------------------------------------------

    \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\
---------------------------------------------------------------------------

    \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\
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    \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
---------------------------------------------------------------------------

    \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\
---------------------------------------------------------------------------

    \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


