[Federal Register Volume 83, Number 75 (Wednesday, April 18, 2018)]
[Rules and Regulations]
[Pages 17226-17278]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-07741]



[[Page 17225]]

Vol. 83

Wednesday,

No. 75

April 18, 2018

Part II





Environmental Protection Agency





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40 CFR Part 50





Review of the Primary National Ambient Air Quality Standards for Oxides 
of Nitrogen; Final Rule

  Federal Register / Vol. 83 , No. 75 / Wednesday, April 18, 2018 / 
Rules and Regulations  

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 50

[EPA-HQ-OAR-2013-0146; FRL-9976-78-OAR]
RIN 2060-AR57


Review of the Primary National Ambient Air Quality Standards for 
Oxides of Nitrogen

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final action.

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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 oxides of nitrogen, as measured by nitrogen dioxide 
(NO2), the EPA is retaining the current standards, without 
revision.

DATES: This final action is effective on May 18, 2018.

ADDRESSES: The EPA has established a docket for this action under 
Docket ID No. EPA-HQ-OAR-2013-0146. Incorporated into this docket is a 
separate docket established for the Integrated Science Assessment for 
this review (Docket ID No. EPA-HQ-ORD-2013-0232). All documents in 
these dockets are listed on the www.regulations.gov website. 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 will be publicly available only in hard copy form. It 
may be viewed, with prior arrangement, at the EPA Docket Center. 
Publicly available docket materials are available either electronically 
in www.regulations.gov or in hard copy at the Air and Radiation Docket 
Information Center, EPA/DC, WJC West Building, Room 3334, 1301 
Constitution Ave. NW, Washington, DC. The Public Reading Room is open 
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Public Reading Room is (202) 
566-1744 and the telephone number for the Air and Radiation Docket 
Information Center is (202) 566-1742.

FOR FURTHER INFORMATION CONTACT: Ms. Breanna Alman, Health and 
Environmental Impacts Division, Office of Air Quality Planning and 
Standards, U.S. Environmental Protection Agency, Mail Code C504-06, 
Research Triangle Park, NC 27711; telephone: (919) 541-2351; fax: (919) 
541-0237; email: [email protected].

Availability of Information Related to This Action

    A number of the documents that are relevant to this decision are 
available through the EPA's website 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 inspection and copying in the EPA 
docket identified above.

SUPPLEMENTARY INFORMATION: 

Table of Contents

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
    D. Summary of Proposed Decisions
    E. Organization and Approach to Final Decisions
II. Rationale for Decision on the Primary Standards
    A. Introduction
    1. Characterization of NO2 Air Quality
    2. Overview of the Health Effects Evidence
    3. Overview of Risk and Exposure Assessment Information
    B. Conclusions on the Primary Standards
    1. Basis for the Proposed Decision
    2. The CASAC Advice in This Review
    3. Comments on the Proposed Decision
    4. Administrator's Conclusions
    C. Decision on the Primary 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. Executive Order 13771: Reducing Regulation and Controlling 
Regulatory Costs
    C. Paperwork Reduction Act (PRA)
    D. Regulatory Flexibility Act (RFA)
    E. Unfunded Mandates Reform Act (UMRA)
    F. Executive Order 13132: Federalism
    G. Executive Order 13175: Consultation and Coordination With 
Indian Tribal Governments
    H. Executive Order 13045: Protection of Children From 
Environmental Health and Safety Risks
    I. Executive Order 13211: Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution or Use
    J. National Technology Transfer and Advancement Act (NTTAA)
    K. Executive Order 12898: Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations
    L. Determination Under Section 307(d)
    M. Congressional Review Act (CRA)
References

Executive Summary

    This document describes the completion of the EPA's current review 
of the primary NAAQS for oxides of nitrogen, of which nitrogen dioxide 
(NO2) is the component of greatest concern for health and is 
the indicator for the primary NAAQS. This review of the standards and 
the air quality criteria (the scientific information upon which the 
standards are based) is required by the Clean Air Act (CAA) on a 
periodic basis. In conducting this review, the EPA has carefully 
evaluated the currently available scientific literature on the health 
effects of NO2, focusing particularly on the information 
newly available since the conclusion of the last review. This section 
briefly summarizes background information about this action and the 
Administrator's decision to retain the current primary NO2 
standards. A full discussion of these topics is provided later in this 
document.

Summary of Background Information

    There are currently two primary standards for oxides of nitrogen: A 
1-hour standard established in 2010 at a level of 100 parts per billion 
(ppb) 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 
based on annual average NO2 concentrations.
    Sections 108 and 109 of the 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

[[Page 17227]]

completing this review is established by a federal court order, which 
requires signature of a notice setting forth the EPA's final decision 
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 welfare effects 
associated with NOX and SOX and the ecological 
welfare effects associated with PM. (U.S. EPA, 2017b).

Summary of Decision

    In this action, the EPA is retaining the current primary 
NO2 standards, without revision. This 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 2016 NOX 
Integrated Science Assessment (ISA); analyses and considerations in the 
Policy Assessment (PA); the advice and recommendations of the Clean Air 
Scientific Advisory Committee (CASAC); and public comments.
    Based on these considerations, the Administrator reaches the 
conclusion that the current body of scientific evidence and the results 
of quantitative analyses supports his judgment that the current 1-hour 
and annual primary NO2 standards, together, are requisite to 
protect public health with an adequate margin of safety, and do not 
call into question any of the elements of those standards. These 
conclusions are consistent with the CASAC recommendations. In its 
advice to the Administrator, the CASAC ``recommend[ed] 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 EPA is retaining the current 1-hour and annual 
NO2 primary standards, without revision.
    As in the last review, the strongest evidence continues to come 
from studies examining respiratory effects following short-term 
NO2 exposures.\1\ In particular, the 2016 NOX 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, p. 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. Additional supporting evidence comes from epidemiologic studies 
reporting associations between short-term NO2 exposures and 
an array of respiratory outcomes related to asthma exacerbation (e.g., 
asthma-related hospital admissions and emergency department (ED) visits 
in children and adults).
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    \1\ The 2016 NOX ISA defines short-term exposures as 
those with durations of minutes up to 1 month, with most studies 
examining effects related to exposures in the range of 1 hour to 1 
week (U.S. EPA, 2016a, p. 1-15).
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    In addition to the effects of short-term exposures, the 2016 
NOX 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. Additional support 
comes from experimental studies supporting the biological plausibility 
of a potential mode of action by which NO2 exposures could 
cause asthma development.
    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, that evidence, together with analyses of 
the potential for NO2 exposures, does 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. Analyses based on information 
from these studies indicate that the current standards provide 
protection against the potential for NO2 exposures that 
could increase AR in people with asthma. In addition, while 
epidemiologic studies report relatively precise associations with 
serious NO2-related health outcomes (i.e., ED 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.
    After considering the current body of scientific evidence, the 
results of quantitative analyses, the CASAC advice, and public 
comments, the Administrator concludes that the current 1-hour and 
annual NO2 primary standards, together, are requisite to 
protect public health with an adequate margin of safety. Therefore, in 
this review, the EPA is retaining the current 1-hour and annual 
NO2 primary standards, without revision.

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

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``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, [is] requisite to protect the public health.'' \2\ 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.'' \3\
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    \2\ 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).
    \3\ 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 
(D.C. Cir. 1980); American Petroleum Institute v. Costle, 665 F.2d 
1176, 1186 (D.C. Cir. 1981); 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 
Association, 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,\4\ 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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    \4\ As used here and similarly throughout this document, 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 lifestage.
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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).\5\
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    \5\ Lists of the 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 the EPA has 
established them. Under section 110 of the Act, 42 U.S.C. 7410, and 
related provisions, states are to submit, for the EPA's 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 the 
EPA, also administer the Prevention of Significant Deterioration 
permitting 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 for the NO2 NAAQS (see 77 FR 
9532 (February 17, 2012)). In addition, there are currently no monitors 
where there are design values (DVs) \6\ above either the 1-hour or 
annual standard (U.S. EPA, 2017a, Figure 2-5), with the maximum DVs in 
2015 being 30 ppb (annual) and 72 ppb (hourly) (U.S. EPA, 2017a 
Section, 2.3.1).
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    \6\ 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. 
The requirements for calculating DVs for the primary NO2 
NAAQS from valid monitoring data are further specified in Appendix S 
to Part 50.
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    While NOX \7\ 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.\8\ The EPA anticipates that NOX

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emissions will continue to decrease over the next 20 years. For 
example, 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 non-road diesel engines, locomotives, and certain marine engines 
are becoming effective throughout the next decade. In future decades, 
these vehicles and engines meeting more stringent NOX 
standards will become an increasingly large fraction of in-use mobile 
sources, leading to large NOX emission reductions.\9\
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    \7\ In this context, NOX refers to the sum of NO and 
NO2, as is common within air pollution research and 
control communities. However, in the larger context of this NAAQS 
review, the terms ``oxides of nitrogen'' and ``nitrogen oxides'' 
generally refer more broadly to gaseous oxides of nitrogen, which 
include NO2 and NO, as well as their gaseous reaction 
products.
    \8\ Highway vehicles include all on-road vehicles, including 
light duty as well as heavy duty vehicles, both gasoline- and 
diesel-powered, and on-highway motorcycles. Off-highway engines, 
vehicles and equipment include aircraft, marine vessels, 
locomotives, off-highway motorcycles, recreational vehicles and 
other non-road products (e.g., lawnmowers, portable generators, 
chainsaws, forklifts). Fuel combustion sources includes electric 
power generating units (EGUs), which derive their power generation 
from all types of fuels.
    \9\ 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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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). 
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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    \10\ In 1971, primary and secondary NO2 NAAQS were 
set at levels of 100 micrograms per cubic meter ([mu]g/m\3\), which 
equals 0.053 parts per million (ppm) or 53 ppb.
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    Industry groups filed petitions for judicial review of the 2010 
rule in the U.S. Court of Appeals for the District of Columbia Circuit. 
API v. EPA, 684 F.3d 1342 (D.C. Cir. 2012). The court upheld the 2010 
rule, denying the petitions' challenges to the adoption of the 1-hour 
NO2 NAAQS and dismissing, for lack of jurisdiction, the 
challenges to statements regarding permitting in the preamble of the 
2010 rule. Id. at 1354.
    Subsequent to the 2010 rulemaking, the Agency revised the deadlines 
by which the near-road monitors were to be operational in order to 
implement a phased deployment approach (78 FR 16184, March 14, 2013), 
with a majority of the network becoming operational by 2015. In 2016, 
after analyzing available monitoring data, the Agency revised the size 
requirements of the near-road network, reducing the network to only 
operate in Core Based Statistical Areas (CBSAs) with populations of 1 
million or more (81 FR 96381, December 30, 2016).
    In February 2012, the EPA announced the initiation of the current 
periodic review of the air quality criteria for oxides of nitrogen and 
of the primary NO2 NAAQS and issued a call for information 
in the Federal Register (77 FR 7149, February 10, 2012). A wide range 
of external experts as well as the 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 NOX ISA and subsequently 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 
NOX 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 NOX 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 recommendations on the 
second draft ISA and the draft REA planning document 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 the CASAC 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 
recommendations, based on its review of the draft PA, were provided in 
a letter to the EPA Administrator dated March 7, 2017 (Diez Roux and 
Sheppard, 2017). The EPA staff took into account these recommendations, 
as well as public comments provided on the draft PA, when developing 
the final PA, which was released in April 2017.\11\
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    \11\ This document may be found at: https://www.epa.gov/naaqs/policy-assessment-review-primary-national-ambient-air-quality-standards-oxides-nitrogen.

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[[Page 17230]]

    On July 14, 2017, the proposed decision to retain the 
NO2 NAAQS was signed, and it was published in the Federal 
Register on July 26 (82 FR 34792). The 60-day comment period ended on 
September 25, 2017, and comments were received from various government, 
industry, and environmental groups, as well as members of the general 
public.
    In addition, in July 2016, a lawsuit was filed against the EPA that 
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 the EPA should withhold consent.\12\ The 
parties to the 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.
---------------------------------------------------------------------------

    \12\ One comment was received from the American Petroleum 
Institute (API) and one was received from an anonymous commenter. 
These comments are available in the docket for the proposed consent 
decree (EPA-HQ-OGC-2016-0719).
---------------------------------------------------------------------------

    Consistent with the review completed in 2010, this review is 
focused on health effects associated with gaseous oxides of nitrogen 
\13\ 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).\14\ The EPA is separately reviewing 
the welfare effects associated with NOX and SOX 
and the ecological welfare effects associated with PM. (U.S. EPA, 
2017a).\15\
---------------------------------------------------------------------------

    \13\ These gaseous oxides of nitrogen can also be referred to as 
``nitrogen oxides'' and include a broad category of gaseous oxides 
of nitrogen (i.e., oxidized nitrogen compounds), including 
NO2, NO, and their various reaction products.
    \14\ Additional information on the PM NAAQS is available at: 
https://www.epa.gov/naaqs/particulate-matter-pm-air-quality-standards.
    \15\ 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.
---------------------------------------------------------------------------

D. Summary of Proposed Decisions

    For reasons discussed in the proposal and summarized in section 
II.B.1 below, the Administrator proposed to retain the current primary 
standards for NO2, without revision.

E. Organization and Approach to Final Decisions

    This action presents the Administrator's final decision in the 
current review of the primary NO2 standards. The final 
decision addressing the primary NO2 standards is based on a 
thorough review in the 2016 NOX ISA of scientific 
information on known and potential human health effects associated with 
exposure to NO2 associated with levels typically found in 
the ambient air. This final decision also takes into account the 
following: (1) Staff assessments in the PA of the most policy-relevant 
information in the ISA, as well as quantitative exposure and risk 
information; (2) the CASAC advice and recommendations, as reflected in 
its letters to the Administrator and its discussions of drafts of the 
ISA and PA at public meetings; (3) public comments received during the 
development of these documents, both in connection with the CASAC 
meetings and separately; and (4) public comments received on the 
proposal. The primary NO2 standards are addressed in section 
II below. Section III addresses statutory and executive order reviews.

II. Rationale for Decision on the Primary Standards

    This section presents the rationale for the Administrator's 
decision to retain the existing primary NO2 standards. This 
rationale is based on a thorough review in the 2016 NOX ISA 
of the latest scientific information, generally published through 
August 2014, on human health effects associated with NO2 and 
pertaining to the presence of NO2 in the ambient air. This 
decision also takes into account: (1) The PA's staff assessments of the 
most policy-relevant information in the ISA and staff analyses of air 
quality, human exposure and health risks, upon which staff conclusions 
regarding appropriate considerations in this review are based; (2) the 
CASAC advice and recommendations, as reflected in discussions of drafts 
of the ISA and PA at public meetings, in separate written comments, and 
in the CASAC letters to the Administrator; (3) public comments received 
during the development of these documents, either in connection with 
the CASAC meetings or separately; and (4) public comments received on 
the proposal. Section II.A provides background on the general approach 
for review of the primary NO2 standards and brief summaries 
of key aspects of the currently available air quality information, as 
well as health effects and exposure/risk information. Section II.B 
presents the Administrator's conclusions on the adequacy of the current 
primary NO2 standards, drawing on consideration of this 
information, advice from the CASAC, and comments from the public. 
Section II.C summarizes the Administrator's decision on the primary 
NO2 standards.

A. Introduction

    The Administrator's approach to reviewing the current primary 
NO2 standards is based, most fundamentally, on using the 
EPA's assessment of the current scientific evidence and associated 
quantitative analyses to inform his judgment regarding primary 
NO2 standards that protect public health with an adequate 
margin of safety. 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 final decision draws 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 approach to informing these judgments is based on the 
recognition that the available health effects evidence generally 
reflects a continuum, consisting of levels at which scientists 
generally agree that health effects are likely to occur, through lower 
levels at which the likelihood and magnitude of the response become 
increasingly uncertain. This approach is consistent with the 
requirements of the NAAQS provisions of the Act and with how the EPA 
and the courts have historically interpreted the Act. These provisions 
require the Administrator to establish primary standards that, in the 
judgment of the Administrator, are requisite to protect public health 
with an adequate margin of safety. In so doing, 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

[[Page 17231]]

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.
    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 in this review 
that builds upon the general approach used in the last review and 
reflects the broader body of evidence and information now available. 
The Administrator's decisions in the prior review were based on an 
integration of information on health effects associated with exposure 
to NO2 with information on the public health significance of 
key health effects, as well as on policy judgments as to when the 
standard is requisite to protect public health with an adequate margin 
of safety and advice from the CASAC and public comments. These 
considerations were informed by air quality and related analyses and 
quantitative exposure and risk information. Similarly, in this review, 
as described in the PA, the proposal, and elsewhere in this document, 
we draw on the current evidence and quantitative assessments of 
exposure pertaining to the public health risk of NO2 in 
ambient air. In considering the scientific and technical information 
here, as in the PA, we consider both the information available at the 
time of the last review and information newly available since the last 
review, including most particularly that which has been critically 
analyzed and characterized in the current ISA. In considering the 
entire body of evidence presented in the current ISA, as in the PA and 
as in the last review, we focus particularly on those health endpoints 
for which the ISA finds associations with NO2 to be causal 
or likely causal. The evidence-based discussions presented below draw 
upon evidence from both controlled human exposure studies and 
epidemiologic studies. Sections II.A.1 through II.A.3 below provide an 
overview of the current NO2 air quality, health effects, and 
quantitative exposure and risk information with a focus on the specific 
policy-relevant questions identified for these categories of 
information in the PA (U.S. EPA, 2017a, Chapter 3).
1. 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 2016 NOX ISA (U.S. EPA, 2016a, Chapter 2).\16\ It 
presents a summary of NO2 atmospheric chemistry (section 
II.A.1.a), trends in ambient NO2 concentrations (section 
II.A.1.b), ambient NO2 concentrations measured at monitors 
near roads (section II.A.1.c), the relationships between hourly and 
annual ambient NO2 concentrations (section II.A.1.d), and 
background concentrations of NO2 (section II.A.1.e).
---------------------------------------------------------------------------

    \16\ The focus is on NO2 in this document, 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 2016 
NOX ISA (U.S. EPA, 2016a, Chapter 2).
---------------------------------------------------------------------------

a. Atmospheric Chemistry
    Ambient concentrations of NO2 are influenced by both 
direct NO2 emissions and by emissions of 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.17 18
---------------------------------------------------------------------------

    \17\ This follows usages in 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.
    \18\ 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.\19\
---------------------------------------------------------------------------

    \19\ 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.
---------------------------------------------------------------------------

b. 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, 2017a, Section 2.3.4).\20\ 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, 2017a, Section 2.1.2, 
Figure 2-3).
---------------------------------------------------------------------------

    \20\ Background concentrations of a pollutant can be defined in 
various ways, depending on context and circumstances. Background 
concentrations of NO2 are discussed in the 2016 
NOX ISA (U.S. EPA, 2016a, Section 2.5.6) and the PA (U.S. 
EPA, 2017a, 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

[[Page 17232]]

concentrations (U.S. EPA, 2017a, Figure 2-5).\21\ The annual and hourly 
DVs trended upward in less than 4% of the sites.\22\ 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).
---------------------------------------------------------------------------

    \21\ Based on an analysis of data from sampling sites with 
sufficient data to produce at least five valid DVs.
    \22\ It is not clear what specific sources may be responsible 
for the upward trends in ambient NO2 concentrations at 
these sites. (See U.S. EPA, 2017a, Section 2.1.2).
---------------------------------------------------------------------------

c. 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 
farther 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 \23\ 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 1-hour 
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).\24\
---------------------------------------------------------------------------

    \23\ Prior to the 2010 rulemaking, monitors were ``not sited to 
measure peak roadway-associated NO2 concentrations . . . 
.'' (75 FR 6479).
    \24\ 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.
---------------------------------------------------------------------------

d. 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). Since the 1980s, the median annual 
NO2 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; data from the new near-road 
monitoring network were not included the analysis of the relationship 
between hourly and annual NO2 concentrations due to the 
limited amount of data available.\25\ 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 
indicates that 1-hour DVs at or below 100 ppb generally correspond to 
annual DVs below 35 ppb, with many monitors recording annual 
concentrations around 30 ppb. (U.S. EPA, 2017a, p. 2-21, Figure 2-11). 
Based on this, an area 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 re-evaluate the 
relationship between 1-hour and annual standards as more data become 
available from recently deployed near-road monitors.
---------------------------------------------------------------------------

    \25\ Area-wide sites are intended to characterize ambient 
NO2 concentrations at the neighborhood and larger spatial 
scales.
---------------------------------------------------------------------------

2. Overview of the Health Effects Evidence
    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 2016 NOX 
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 2016 
NOX 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 \26\ or lifestages (U.S. EPA, 
2016a, 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. With regard to characterization of the health effects 
evidence, the 2016 NOX 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, 2016a, Preamble, Table II).\27\ As 
discussed further below, in evaluating the public health protection 
provided by the current standards, the EPA's focus is on health effects 
determined to have a ``causal'' or a ``likely to be causal'' 
relationship with NO2 exposures. 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 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

[[Page 17233]]

variety of factors such as age, genetic background, nutritional status, 
immune competence, and social factors (U.S. EPA, 2017a, Preamble, 
Section 5.b). Thus, exposure to NO2 is likely one of several 
contributors to the health effects evaluated in the ISA.
---------------------------------------------------------------------------

    \26\ 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.
    \27\ 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 2016 NOX 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 2016 NOX 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 2016 NOX ISA judges there is ``adequate'' evidence (U.S. 
EPA, 2016a, Table 7-27).
    The sections below summarize the evidence for effects related to 
short-term NO2 exposures (e.g., minutes up to 1 month) and 
the evidence for effects related to long-term NO2 exposures 
(e.g., months to years).\28\ The final section discusses the potential 
public health implications of NO2 exposures, based on the 
evidence for populations and lifestages at increased risk of 
NO2-related effects. The focus of these sections is on 
health effects that the 2016 NOX ISA has determined to have 
a ``causal'' or ``likely to be causal'' relationship with 
NO2. Health effects whose causal determinations have changed 
since the last review are also briefly addressed. More information on 
health effects for which causal determinations are suggestive of, but 
not sufficient to infer a causal relationship or inadequate to infer a 
causal relationship (i.e., health effects for which the evidence is 
weaker) may be found in section II.C of the proposal (87 FR 34792, July 
26, 2017).
---------------------------------------------------------------------------

    \28\ Short-term exposures are defined as those with durations of 
minutes up to 1 month, with most studies examining effects related 
to exposures in the range of 1 hour to 1 week (2016 NOX 
ISA, p. 1-15).
---------------------------------------------------------------------------

a. Health Effects With Short-Term Exposure to NO2
    This section discusses the evidence for health effects following 
short-term NO2 exposures. Section II.B.2.a.i 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 2016 NOX ISA. Section II.B.2.a.ii discusses the 
NO2 concentrations at which health effects have been 
demonstrated to occur, based on the considerations and analyses 
included in the PA. Section II.B.2.a.iii discusses NO2 
concentrations in controlled human exposure studies, while section 
II.B.2.a.iv. discusses NO2 concentrations in locations of 
epidemiologic studies.
i. 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 NOX 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 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 NOX ISA noted 
an overarching uncertainty in determining the extent to which 
NO2 is independently associated with effects or whether 
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 that was critically 
evaluated in the 2016 NOX 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).\29\ Chapter 5 of the 2016 NOX ISA presents a 
detailed assessment of the evidence for health effects associated with 
short-term NO2 exposures (U.S. EPA, 2016a). In considering 
the available evidence and the causal determinations presented in the 
2016 NOX ISA, consistent with the PA (U.S. EPA, 2017a), this 
action focuses on respiratory effects described below. Cardiovascular 
effects and mortality are also briefly addressed.
---------------------------------------------------------------------------

    \29\ A list of causal determinations from the 2016 
NOX 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).
---------------------------------------------------------------------------

Respiratory Effects
    The 2016 NOX 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 2016 NOX 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 NOX 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 NOX 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 2016 
NOX 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).\30\
---------------------------------------------------------------------------

    \30\ 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 2016 
NOX ISA comes from a meta-analysis of controlled human 
exposure studies that evaluate the potential for increased AR \31\ 
following 20-minute to 1-hour NO2 exposures (Brown, 
2015).\32\ While

[[Page 17234]]

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.\33\ AR has been the key respiratory outcome from 
controlled human exposures in the previous and the current review of 
the primary NO2 NAAQS. The 2016 NOX 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,\34\ most of which were available 
in the last review (U.S. EPA, 2017a, Tables 3-2 and 3-3). More 
specifically, the meta-analysis identified the fraction of individuals 
having an increase in AR following NO2 exposure, compared to 
the fraction having a decrease, across studies.\35\ 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.\36\
---------------------------------------------------------------------------

    \31\ The 2016 NOX ISA states that AR is ``inherent 
responsiveness of the airways to challenge by bronchoconstricting 
agents'' (U.S. EPA, 2016a, p. 5-9). 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.
    \32\ These studies evaluate the effect of inhaled NO2 
on the inherent responsiveness of the airways to challenge by 
bronchoconstricting agents.
    \33\ A meta-analysis synthesizes data from multiple studies 
using statistical analyses.
    \34\ 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, with the majority 
of study participants having a mild form of asthma. (Brown, 2015).
    \35\ More information on the distribution of study subjects 
across NO2 concentrations can be found below (section 
II.A.2.ii). Information on the fraction of individuals who 
experienced an increase versus a decrease stratified by 
concentration can also be found in that section.
    \36\ ``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 asthma. 
These controlled human exposure studies, the meta-analysis, and 
uncertainties in this body of evidence are discussed in greater detail 
below.
    The 2016 NOX 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 2016 NOX ISA 
considered a halving of the provocative dose (PD) to indicate responses 
that may be clinically relevant.37 38 With regard to this 
approach, the 2016 NOX 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).
---------------------------------------------------------------------------

    \37\ 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).
    \38\ The 2016 NOX 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 AR 
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 2016 NOX ISA to represent an increase in AR that 
indicates a clinically relevant response.
---------------------------------------------------------------------------

    Studies considered for inclusion into the meta-analyses by Brown 
(2015) were identified from the meta-analysis by Goodman et al. (2009), 
the 2016 NOX ISA, and a literature search for controlled 
human exposure studies of individuals with asthma exposed to 
NO2 that were published since the 2008 NOX ISA. 
In one analysis, Brown (2015) showed 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) in 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 the analysis of PD is limited to a 
subset of the studies in which non-specific AR was assessed in 
individuals following resting exposures to NO2 and air.\39\ 
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.
---------------------------------------------------------------------------

    \39\ 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 2016 
NOX 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 2016 NOX ISA also describes 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 2016 
NOX 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

[[Page 17235]]

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 2016 
NOX 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 2016 NOX 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 rarely studied, but NO2 
associations with asthma exacerbation tend to persist in the few 
available copollutant models. The 2016 NOX ISA recognizes, 
however, that copollutant models have inherent limitations and cannot 
conclusively rule out confounding (U.S. EPA, 2015a, Preamble, Section 
4.b).
    The 2016 NOX 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 2016 NOX 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 2016 NOX 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 2016 NOX 
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 fundamental understanding of the 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).
Cardiovascular Effects
    The evidence for a causal relationship between cardiovascular 
health effects and short-term NO2 exposures in the 2016 
NOX ISA was judged ``suggestive of, but not sufficient to 
infer, a causal relationship'' (U.S. EPA, 2016a, Section 5.3.11), which 
reflects a conclusion that the evidence for a causal relationship is 
stronger in the last review, when the conclusion was that the evidence 
was ``inadequate to infer the presence or absence of a causal 
relationship.'' The 2016 determination was primarily supported by 
consistent epidemiologic evidence from multiple new studies indicating 
associations between NO2 concentrations and myocardial 
infarction. More information on these health effects may be found in 
section II.C.1.a.ii of the proposal (87 FR 34792, July 26, 2017).
Mortality
    The 2016 NOX ISA concludes that the evidence for a 
causal relationship between 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). More 
information on these health effects may be found in section 
II.C.1.a.iii of the proposal (87 FR 34792, July 26, 2017).
ii. 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 type of effect for which there is the 
strongest evidence supporting a causal relationship, as discussed in 
the section 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 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 that meet existing 
standards. These considerations are discussed below for controlled 
human exposure studies and epidemiologic studies.
iii. 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

[[Page 17236]]

oxidative stress, respiratory symptoms, and lung function decrements. 
Generally, when considering respiratory effects from controlled human 
exposure studies in healthy adults without asthma, the 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).\40\ There is a substantial body of evidence 
demonstrating increased AR in healthy adults with exposures in the 
range of 1,500-3,000 ppb.
---------------------------------------------------------------------------

    \40\ 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 2016 NOX 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 in these studies make it difficult to interpret 
the likelihood that these effects could potentially occur following 
NO2 exposures at or below the level of the current 
standards.\41\
---------------------------------------------------------------------------

    \41\ Despite the difficulty in interpreting the likelihood that 
these effects would occur at concentrations closer to the current 
standards, as described later (section II.A.3) the current standards 
are expected to protect against exposures at the exposure 
concentrations used in these studies.
---------------------------------------------------------------------------

    Thus, in considering the exposure concentrations evaluated in 
controlled human exposure studies, the PA focuses on the body of 
evidence for NO2-induced increases in 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, having the advantage of being based on the 
same exposure conditions. The meta-analysis by Brown (2015) can also 
provide insight into the extent to which observed changes are due to 
NO2 exposures, with the additional benefit of aiding in the 
identification of trends in individual-level responses across studies 
and the advantage of increased power to detect effects, even in the 
absence of statistically significant effects in individual studies, 
although each study in the meta-analysis may not be based on the exact 
same exposure conditions.\42\
---------------------------------------------------------------------------

    \42\ Tables 3-2 and 3-3 in the NO2 PA (adapted from 
the 2016 NOX 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 PD: The 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
    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. In 
considering such studies, 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 at this 
concentration. 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 its results were not statistically 
significant (n = 4, Orehek et al., 1976). Thus, as noted above, 
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 considering studies in individuals with asthma conducted with 
exercise and at lower concentrations, 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).\43\
---------------------------------------------------------------------------

    \43\ 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 statistically significant results. Only one 
of four studies with exercising exposures of 400 or 600 ppb reported 
statistically significant increases in AR.
---------------------------------------------------------------------------

Consideration of Results From the Brown (2015) Meta-Analysis
    As discussed above, the 2016 NOX ISA assessment of the 
evidence for AR

[[Page 17237]]

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 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 
exposure to filtered air.\44\ 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 2016 
NOX 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)), which informed the 
2016 NOX ISA's emphasis on studies of resting exposures and 
non-specific challenge agents. Overall, the Brown 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).\45\
---------------------------------------------------------------------------

    \44\ More specifically, the Brown (2015) meta-analysis combined 
information from the studies presented in Tables 3-2 and 3-3 of the 
PA. It 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.
    \45\ 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, the PA first 
considers results across all exposure conditions combined (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 significantly different from 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 (i.e., 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 non-specific 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.\46\ For non-specific challenge agents, the 
differences between the fraction 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 exposure concentrations evaluated (p < 0.001).
---------------------------------------------------------------------------

    \46\ 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%, particularly when looking at the allergen challenge group, 
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 non-specific 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. In contrast, for 
exposures during exercise, most study subjects did not experience 
NO2-induced increases in specific AR.\47\ Overall, results 
across studies are less consistent for increases in specific AR 
following NO2 exposures.
---------------------------------------------------------------------------

    \47\ 48% 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 asthma could experience more serious 
effects and/or effects following exposures to lower NO2 
concentrations.\48\ 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.
---------------------------------------------------------------------------

    \48\ Brown (2015) notes, however, that disease status varied in 
the studies included in the meta-analysis, 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 600 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, and can be used to inform the characterization of the 
magnitude of the effects; however, the lack of an apparent dose-
response relationship does not necessarily

[[Page 17238]]

indicate that there is no relationship between the exposure and effect, 
particularly in these analyses based largely on between-subject 
comparisons (i.e., as opposed to comparisons within the same subject 
exposed to multiple concentrations). As discussed in the 2016 
NOX ISA, there are a number of methodological differences 
across studies that could contribute to between-subject differences and 
that could obscure or complicate a dose-response relationship between 
NO2 and AR (U.S. EPA, 2016a, section 5.2.2.1).\49\ 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 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 and reduces the ability to fully characterize 
the health risks associated with these exposures, it does not indicate 
the lack of an NO2 effect.
---------------------------------------------------------------------------

    \49\ For instance, Brown (2015) notes that the few studies 
evaluating effects at multiple NO2 concentrations and at 
resting exposures may indicate some support for a dose-response 
relationship, as they show increasing AR with increasing exposure 
concentrations.
---------------------------------------------------------------------------

    An additional uncertainty in interpreting these studies within the 
context of considering the adequacy of the protection provided by the 
current primary 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 2016 
NOX 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.\50\
---------------------------------------------------------------------------

    \50\ 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.A.3 
below.
---------------------------------------------------------------------------

    Five studies provided data for each individual's PD. 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 PD (indicating increased AR) while 8% showed a 
doubling of the PD (indicating decreased AR). The relative 
distributions of the PDs 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 subset of studies. 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 an apparent 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. The PA placed weight on that lack of consistency, when 
considered in light of the lack of an apparent dose-response 
relationship between NO2 and increased AR, as well as the 
uncertainty in the adversity of the reported effect.
iv. 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 2016 NOX 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 standards, the PA emphasizes those studies conducted in the 
U.S. and Canada.\51\ For short-term exposures to NO2, the PA 
emphasizes studies reporting associations with effects judged in the 
2016 NOX 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 where there is the most 
confidence for NO2-associated health effects and the range 
of concentrations over which confidence in such effects is appreciably

[[Page 17239]]

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?
---------------------------------------------------------------------------

    \51\ 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 
are 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 2016 
NOX 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 effects 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.
    The emphasis that the proposal and this final action place on 
studies to inform the question above is discussed in more detail in the 
proposal for this action (82 FR 34792, July 26, 2017, section II.F.4). 
Briefly, 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 (CI)) health effect 
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).\52\ 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.\53\ These concentrations approximate the DVs that are 
used when determining whether an area meets the 1-hour primary 
NO2 NAAQS.\54\ 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.
---------------------------------------------------------------------------

    \52\ 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).
    \53\ All study locations had maximum annual DVs below 53 ppb 
(U.S. EPA, 2017a, Appendix A).
    \54\ As described in section I.B., 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 DV 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.\55\ 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 about whether an area would have met the current 1-hour 
standard during the study period can be reached based on study areas 
with DV estimates that are at or just below 100 ppb.\56\
---------------------------------------------------------------------------

    \55\ 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.A.1.d).
    \56\ 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 2016 NOX 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 multicity studies tend to have 
greater power to detect associations. The one multicity 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).\57\ Associations in these studies

[[Page 17240]]

were generally not statistically significant, were less precise (i.e., 
wider 95% CI), 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 primary 
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.
---------------------------------------------------------------------------

    \57\ 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 the 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).\58\ Of the studies 
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-
related hospital admissions and 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, 
section 3.5).
---------------------------------------------------------------------------

    \58\ In this case, differential exposure measurement error 
occurs when exposure measurement error varies by pollutant (e.g., 
within a model exposure to PM2.5 may be estimated with 
higher accuracy than exposure to SO2).
---------------------------------------------------------------------------

    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 (Peel 
et al., 2005; Strickland et al., 2010), 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 lack precision and are not 
statistically significant, 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.
b. Health Effects With Long-Term Exposure to NO2
    This section discusses the evidence for health effects associated 
with long-term NO2 exposures. Section II.A.2.b.i 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 2016 NOX ISA. Sections II.A.2.b.ii and 
II.A.2.b.iii discuss the NO2 concentrations at which health 
effects have been demonstrated to occur based on the considerations and 
analyses included in the PA.
i. 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 effects 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 2016 NOX 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. Cardiovascular effects and 
diabetes, reproductive and developmental effects, premature mortality, 
and cancer are also briefly addressed.
Respiratory Effects
    The 2016 NOX 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.\59\ 
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

[[Page 17241]]

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

    \59\ Asthma development is also referred to as ``asthma 
incidence'' in this document 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 causal relationship'' in the 
current review represents a change from 2008 NOX 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, 2016a, 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 2016 
NOX 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 models 
with good NO2 prediction in some studies.
    While the causal determination has been strengthened in this 
review, important uncertainties remain. For example, the 2016 
NOX 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 2016 NOX 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 2016 NOX 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 2016 NOX 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) \60\ 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).
---------------------------------------------------------------------------

    \60\ 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 
(forced expiratory volume in 1 second) -0.98 (-1.70, -0.26), (FVC) -
2.14 (-4.20, -0.04), (peak expiratory flowF) -1.04 (-1.94, -0.13).
---------------------------------------------------------------------------

    While this uncertainty continues to apply to the epidemiologic 
evidence for asthma incidence in children, the 2016 NOX ISA 
explains 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 2016 NOX 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 
provides 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.
    To summarize, the 2016 NOX 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

[[Page 17242]]

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, 
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.
Cardiovascular Effects and Diabetes
    In the previous review, the 2008 NOX 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 2016 NOX ISA 
judged the evidence to be ``suggestive, but not sufficient to infer'' a 
causal relationship (U.S. EPA, 2016a, Section 6.3). More information on 
these health effects may be found in section II.C.2.a.ii of the 
proposal (87 FR 34792, July 26, 2017).
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 NOX 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 2016 NOX 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 2016 
NOX 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. More information on these health effects 
may be found in section II.C.2.a.iii of the proposal (87 FR 34792, July 
26, 2017).
Total Mortality
    In the 2008 NOX ISA, a limited number of epidemiologic 
studies assessed the relationship between long-term exposure to 
NO2 and mortality in adults. The 2008 NOX 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 2016 NOX 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). More 
information on these health effects may be found in section II.C.2.a.iv 
of the proposal (87 FR 34792, July 26, 2017).
Cancer
    The evidence evaluated in the 2008 NOX 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 
conclusion drawn from the integration of evidence is ``suggestive of, 
but not sufficient to infer, a causal relationship'' (U.S. EPA, 2016a, 
Section 6.6.9). More information on cancer outcomes may be found in 
section II.C.2.a.v of the proposal (87 FR 34792, July 26, 2017).
ii. 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, the EPA considers 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 type of effect for which there is 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 concentrations examined in experimental 
studies. These considerations are discussed below for epidemiologic 
studies and experimental studies.
Ambient NO2 Concentrations in Locations of Epidemiologic 
Studies
    As discussed above for short-term exposures (Section II.A.2.a), 
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 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 2016

[[Page 17243]]

NOX ISA (U.S. EPA, 2016a, p. 6-7). 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 2016 NOX ISA as providing key supporting evidence for 
the causal determination.\61\ However, the PA also considers what the 
additional three U.S. and Canadian studies not identified as key 
studies in the 2016 NOX ISA can indicate about the adequacy 
of the current standards, while noting the increased uncertainty in 
these studies related to exposure measurement and copollutant 
confounding (Table 6-5 of the 2016 NOX ISA).
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    \61\ 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 2016 NOX ISA 
identifies three as key studies supporting the causal determination 
(Carlsten et al., 2011; Clougherty et al., 2007; Jerrett et al., 
2008).
---------------------------------------------------------------------------

    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 reflects 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.A.2.a), 
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 
2016 NOX ISA's integrated mode of action information 
describing the biological plausibility for development of asthma 
(section II.B.1, below). In particular, studies demonstrate the 
potential for repeated short-term NO2 exposures to induce 
pulmonary inflammation and development of allergic responses. The 2016 
NOX 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. 6-66 and p. 6-64). More specifically, the 2016 NOX 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.\62\
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    \62\ 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.A.1 above, and in the CASAC 
letter to the Administrator on the draft PA (Diez Roux and Sheppard, 
2017). Thus, as in the recent review of the O3 NAAQS (80 
FR 65292, October 26, 2015), it is appropriate here 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.\63\ \64\
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    \63\ 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).
    \64\ 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 (section II.A.1, 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.A.c, 
above). In addition, mobile source NOX emissions were 
substantially higher during the majority of study periods (1986-2006) 
than they are today (section II.A.b, above), 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.\65\
---------------------------------------------------------------------------

    \65\ As noted above for studies of short-term NO2 
exposures (II.A.2.a), 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 2016 NOX 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

[[Page 17244]]

Angeles estimated DVs) 53 ppb.\66\ These seven communities also had 1-
hour estimated DVs (maximum 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 et al., 2007) \67\ or above 
(Carlsten et al., 2011) 100 ppb.
---------------------------------------------------------------------------

    \66\ 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, DV estimates for the 
Los Angeles and Riverside CBSAs were used to represent multiple 
study communities.
    \67\ 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 during the study period.
---------------------------------------------------------------------------

    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 2016 NOX ISA (Clark et 
al., 2010; McConnell et al., 2010; Nishimura et al., 2013). The 
multicity 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, these studies do not 
report such associations at ambient NO2 concentrations that 
would have clearly met both of 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, 2017a, 
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; and (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 DVs 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 (i.e., asthma 
development) are occurring below the levels of the current primary 
NO2 standards is limited.
iii. 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.\68\ 
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 2016 
NOX ISA indicates that 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, these experimental studies, by themselves, do not provide 
insight into the occurrence of adverse health effects following 
exposures below the levels of the existing primary NO2 
standards.\69\
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    \68\ While there are not controlled human exposure studies for 
long-term exposures, the 2016 NOX 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 (U.S. EPA 
2016a, chapter 6; U.S. EPA, 2017a, section 3).
    \69\ In addition, the 2016 NOX 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.A.2 above.

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[[Page 17245]]

Overall Conclusions for Long Term Exposures
    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.A.2.d, 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.
c. 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 
NOX ISA 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 NOX 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 NOX 
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 NOX ISA again notes that 
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, Section 
7.5.6),\70\ there is widespread potential for elevated ambient 
NO2 exposures. For example, Rowangould (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.
---------------------------------------------------------------------------

    \70\ The 2016 NOX 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 (U.S. EPA, 2017a, Section 3.4) draws from the 2016 
NOX ISA's assessment of the evidence (U.S. EPA, 2016a, 
Chapter 7). The 2016 NOX 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 2016 NOX 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 
2016 NOX ISA then uses a systematic approach for classifying 
the evidence for each potential at-risk factor (U.S. EPA, 2015a, 
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., the recently 
completed review for ozone, 80 FR 65292, October 26, 2015), the PA 
focuses the consideration of potential at-risk populations on those 
factors for which the 2016 NOX ISA determines there is 
``adequate'' evidence (U.S. EPA, 2016a, Table 7-27). For 
NO2, the at-risk populations identified include people with 
asthma, children and older adults (U.S. EPA, 2016a, Table 7-27), and 
this information is 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 conclusions 
regarding the populations at increased risk of NO2-related 
effects 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? (U.S. EPA, 2017a, p. 3-
40).
    In addressing this question, the PA considers the evidence in the 
2016 NOX ISA for effects in people with asthma, children, 
and older adults (U.S. EPA, 2016a, Chapter 7, Table 7-27), 
respectively, as described below.
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)

[[Page 17246]]

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). 
The Brown (2015) meta-analysis 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 differences in time spent outdoors to suggest differences in 
NO2 exposure. However, the Folinsbee et al. (1992) meta-
analysis of information from controlled human exposure studies, which 
supported the 2016 NOX ISA's determination of a causal 
relationship between short-term exposures and respiratory effects, 
clearly demonstrates that adults with asthma are at increased risk for 
NO2-related respiratory health effects compared to healthy 
adults. Thus, consistent with observations made in the 2008 
NOX ISA (U.S. EPA, 2008a), in the current review the 2016 
NOX 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).
Children
    According to the 2010 census, 24% of the U.S. population is less 
than 18 years of age, with 6.5% less than 6 years of age (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). 
Higher activity along with higher ventilation rates relative to lung 
volume and higher propensity for oronasal breathing could potentially 
result in greater NO2 penetration to the lower respiratory 
tracts of children; however, this effect has not been examined for 
NO2 (U.S. EPA, section 4.2.2.3). 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 NO2-
associated health effects with both short- and long-term 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 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 2016 
NOX 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).
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 NOX 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 2016 NOX 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).
PA Conclusions on At-Risk Populations
    As described in the PA, and consistent with the last review, the 
2016 NOX 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% all children, 13% all 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.
3. Overview of Risk and Exposure Assessment Information
    Beyond the consideration of the scientific evidence, discussed 
above in Section II.A.2, the EPA also considers the extent to which new 
or updated quantitative analyses of 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, 2015b) and in the PA 
(U.S. EPA, 2017a), 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. In

[[Page 17247]]

developing the final PA, staff also considered 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 on respiratory health effects associated with 
short and long-term exposure to NO2 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 on short-term 
NO2 exposures in its review of the REA Planning document, 
and for long-term exposures they agreed but encouraged the EPA to 
consider the feasibility of such an assessment for long-term exposures 
(Diez Roux and Frey, 2015b, p. 5). In its review of the draft PA the 
CASAC agreed with the EPA's conclusions on the feasibility of an 
epidemiologic risk assessment based on evidence of long-term 
NO2 exposures (Diez Roux and Sheppard, 2016, p. 2).\71\
---------------------------------------------------------------------------

    \71\ After considering the factors discussed above, we conclude 
that a quantitative risk assessment based on epidemiologic studies 
of long-term NO2 exposures is not warranted in this 
review because of a lack of U.S. epidemiologic studies identified by 
the 2016 NOX ISA as being key studies, lack of baseline 
incidence rates for the health effects of interest, uncertainty 
regarding the shape of the concentration-response function, and a 
lack of studies that have controlled for potential confounders, 
making it difficult to determine the true magnitude of effect (U.S. 
EPA, 2017a, sections 4.4.2.2 and 4.4.2.3).
---------------------------------------------------------------------------

a. 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 new 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,\72\ CBSAs with the highest NO2 design values, and 
CBSAs with a relatively large number of NO2 monitors overall 
(i.e., providing improved spatial characterization).\73\
---------------------------------------------------------------------------

    \72\ As discussed above, near-road monitors are required within 
50 m of major roads in large urban areas that met certain criteria 
for population size or traffic volume. 40 CFR part 58, appendix E, 
Sec. 6.4(a). 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).
    \73\ 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.\74\ Upward adjustment was 
required because all locations in the U.S. meet the current 
NO2 NAAQS.
---------------------------------------------------------------------------

    \74\ 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 100 to 
300 ppb, based largely on studies of non-specific AR in study 
participants exposed to NO2 at rest.\75\ \76\ 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, the risks of these exposures cannot be fully 
characterized based on existing studies and caution is appropriate when 
interpreting the potential public health implications of 1-hour 
NO2 concentrations at or around 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.A.2 above and U.S. EPA, 2017a, Section 
4.2.1).
---------------------------------------------------------------------------

    \75\ Benchmarks from the upper end of this range are supported 
by the results of individual studies, the majority of which 
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.
    \76\ While benchmarks between 100 to 200 ppb were considered, 
analyses were only conducted on concentrations between 100 to 200 
ppb as 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.
---------------------------------------------------------------------------

b. Results of Updated Analyses
    In considering the results of these updated analyses, the EPA 
focuses on the number of days per year that 1-hour NO2 
concentrations at or above the respective benchmarks 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 (U.S. 
EPA, 2017a, Section 4.2.1.2). 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

[[Page 17248]]

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).
c. 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, 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.
i. 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.A.2), 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 individual studies 
show more consistent results above 250 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,\77\ there remains uncertainty in the 
degree to which the effects identified in individual studies within the 
Brown (2015) meta-analysis would be of public health concern, 
specifically at lower concentrations (e.g., 100 ppb). In particular, 
the uncertainties regarding the potential for adverse effects following 
NO2 exposures at lower concentrations when looking across 
individual studies 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,\78\ these uncertainties have the potential to 
be of particular importance for interpreting the public health 
implications of ambient NO2 concentrations at or around the 
100 ppb benchmark.\79\
---------------------------------------------------------------------------

    \77\ 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.''
    \78\ As discussed previously, while the meta-analysis indicates 
that a statistically significant majority of study volunteers 
experienced increased non-specific AR following exposures to 100 ppb 
NO2, results were only 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.
    \79\ 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.A.2), 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 was 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 
experienced a halving of the PD of challenge agent following 
NO2 exposures. This magnitude of change has been recognized 
by the ATS and the ERS 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 subset of volunteers for which non-specific AR 
was reported following exposures to NO2 and air at rest, and 
the interpretation of these results for any specific exposure 
concentration within the range of 100 to 530 ppb is uncertain (see 
section II.A.2, above).
ii. 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 approach 
to adjusting ambient NO2 concentrations was supported by the 
CASAC, who found the approach both suitable and appropriate (Diez Roux 
and Frey, 2015b, p.1). This approach is meant to illustrate a 
hypothetical scenario and does not represent expectations regarding 
future air quality trends. There are, however, some uncertainties in 
this approach. 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.\80\ In 
locations where near-road monitors

[[Page 17249]]

measure the highest NO2 DVs, reliance on those near-road 
monitors to identify air quality adjustment factors would likely 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.
---------------------------------------------------------------------------

    \80\ However, 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).
---------------------------------------------------------------------------

iii. 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 on and 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.
    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, and Los 
Angeles in the EPA's database of metadata for near-road monitors).\81\ 
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, is 
likely to effectively capture the types of locations around roads where 
the highest NO2 concentrations can occur.\82\
---------------------------------------------------------------------------

    \81\ This database is found at http://www3.epa.gov/ttn/amtic/nearroad.html.
    \82\ In the current review, 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). 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 2016 NOX 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 2016 NOX 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 power generation facilities (EGUs) and airports, the two 
types of non-roadway sources that are associated with the highest 
NOX emissions in the U.S (U.S. EPA, 2017a, Appendix B, 
Section B2.3.2).
    While it is difficult to isolate non-road impacts from certain non-
road sources like ports and airports, looking at monitors that are 
influenced by non-road emissions can help characterize the potential 
for such exposures. As discussed below, several study areas have non-
near-road NO2 monitors sited to better characterize the 
impacts of such sources.
    As described in the PA (U.S. EPA, 2017a, Section 4.1.2.3), table 2-
12 in the 2016 NOX 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, and very close to a major rail yard (i.e., 
Bedford Park Rail Yard) and to a four-lane arterial road (US 12 and US 
45) (U.S. EPA, 2016a, Section 2.5.3.2). 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. In addition, 
one of the highest 1-hour daily maximum NO2 concentrations 
recorded in recent years (136 ppb) was observed at a Denver, CO, site 
that is not part of the near-road monitoring network. 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 commercial heating and 
other activities, as well as local traffic (U.S. EPA, 2016a, Section 
2.5.3.2).
d. Conclusions
    As discussed above and in the REA Planning document (U.S. EPA, 
2015b, 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 I.B, recent NO2 concentrations 
measured in all U.S.

[[Page 17250]]

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 all years, 
including worst-case years and 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).\83\
---------------------------------------------------------------------------

    \83\ 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.\84\ These results are similar to 
the results presented in the REA from the last review (U.S. EPA, 2008b, 
tables 7-23 through 7-25), 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, though there is some 
uncertainty as to whether these results fully characterize on and near-
road exposures, in part because most near-road monitors do not yet have 
three years of data. (U.S. EPA, 2017a, Appendix B, Section B5.9, Table 
B5-66).\85\
---------------------------------------------------------------------------

    \84\ The 98th percentile generally corresponds to the 7th or 8th 
highest 1-hour concentration in a year.
    \85\ 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 B5-66).
---------------------------------------------------------------------------

    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 adversity of the 
reported NO2-induced increases in AR following exposures to 
100 ppb NO2. However, by 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 potentially adverse 
NO2-attributable effects is more consistent, as well as 
against exposures to NO2 concentrations at 100 ppb, for 
which the evidence of potentially adverse NO2-attributable 
effects is less consistent, but where the meta-analysis indicates that 
a marginally significant majority of study participants experienced an 
increase in AR following exposures (Brown, 2015).
    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 level for the 1-
hour standard (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), as the REA analyses already estimate no days with 
1-hour NO2 concentrations at or above the 200 ppb benchmark 
in areas just meeting the current 1-hour standard. Thus, the PA 
concludes that these analyses comparing ambient NO2 
concentrations to health-based benchmarks do not provide support for 
considering potential alternative standards that provide a different 
degree of public health protection. Additionally, in its review of the 
PA, 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).

B. Conclusions on the Primary Standards

    In drawing conclusions on the adequacy of the current primary 
NO2 standards, in view of the advances in scientific 
knowledge and additional information now available, the Administrator 
considers the evidence base, information, and policy judgments that 
were the foundation of the last review and reflects upon the body of 
evidence and information newly available in this review. In so doing, 
the Administrator has taken into account both evidence-based and 
exposure- and risk-based considerations, advice from the CASAC, and 
public comment. Evidence-based considerations draw upon the EPA's 
assessment and integrated synthesis of the scientific evidence from 
epidemiological studies and controlled human exposure studies 
evaluating health effects related to exposures to NO2 as 
presented in the ISA, with a focus on policy-relevant considerations as 
discussed in the PA. The exposure- and risk-based considerations draw 
from the results of the quantitative analyses presented in the 2008 REA 
and the additional updated analyses presented in the PA (as summarized 
in section II.D of the proposal and section II.A.3 above) and 
consideration of these results in the PA. As described in section 
II.A.2 of the proposal, consideration of the evidence and exposure/risk 
information in the PA and by the Administrator is framed by 
consideration of a series of key policy-relevant questions. Section 
II.B.1 below summarizes the rationale for the Administrator's proposed 
decision, drawing from section II.E.4 of the proposal. Advice received 
from the CASAC in this review is briefly summarized in section II.B.2 
below. A fuller presentation of PA considerations and conclusions, and 
advice from the CASAC, which were all taken into account by the 
Administrator, is provided in sections II.E.1 through II.E.3 of the 
proposal. Public comments on the proposed decision are addressed in 
section II.B.3 below. The Administrator's conclusions in this review 
regarding the current primary standards are described in section II.B.4 
below.
1. Basis for the Proposed Decision
    At the time of the proposal, the Administrator carefully considered 
the

[[Page 17251]]

assessment of the current evidence and the conclusions reached in the 
2016 NOX ISA; the currently available exposure/risk 
information, including associated limitations and uncertainties; 
considerations and staff conclusions and associated rationales 
presented in the PA; the advice and recommendations from the CASAC; and 
public comments that had been offered up to that point. In reaching his 
proposed conclusion on the primary standard, the Administrator took 
note of evidence-based considerations (as summarized in section 
II.B.1.a below) and exposure- and risk-based considerations (as 
summarized in section II.B.1.b below).
a. Evidence-Based Considerations
    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 was the nature of the 
health effects attributable to NO2 exposures, drawing upon 
the integrated synthesis of the health evidence in the 2016 
NOX ISA and the evaluations in the PA (Chapter 3). The 
following questions guided this consideration: (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 were addressed in 
the proposal for both short-term and long-term NO2 
exposures, with a focus on health endpoints for which the 2016 
NOX ISA concludes that the evidence indicates there is a 
``causal'' or ``likely to be a causal'' relationship.
    With regard to short-term NO2 exposures, the proposal 
noted that, as in the last review, the strongest evidence continues to 
come from studies examining respiratory effects. In particular, the 
2016 NOX 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. The proposal further noted that 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 2016 
NOX 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.\86\
---------------------------------------------------------------------------

    \86\ This is particularly true at low concentrations (i.e., 100 
ppb).
---------------------------------------------------------------------------

    Supporting evidence for a range of NO2-associated 
respiratory effects also comes from epidemiologic studies. In this 
regard, the proposal placed particular focus on studies that have 
examined NO2 associations with asthma-related hospital 
admissions or ED visits, outcomes which are clearly adverse. 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 
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), as well as regarding the potential for exposure measurement 
error and the extent to which near-road NO2 concentrations 
are reflected in the available air quality data.
    Thus, while some new evidence is available in this review, the 
proposal noted that that new evidence did not substantially alter the 
understanding of the respiratory effects that occur following short-
term NO2 exposures. This evidence is summarized in Section 
II.C.1 of the proposal, as well as in Section II.A.2 above, and is 
discussed in detail in the 2016 NOX ISA (U.S. EPA, 2016a, 
section 5.2.2).
    With regard to long-term NO2 exposures, the 2016 
NOX 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. Uncertainties in interpreting associations with 
asthma development include 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. 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 of the proposal, as well as in Section 
II.A.2 above, and is discussed in detail in the 2016 NOX ISA 
(U.S. EPA, 2016a, section 6.2.2).
    Given the evaluation of the evidence in the 2016 NOX 
ISA, and the 2016 NOX ISA's causal determinations, the EPA's 
further consideration of the evidence in the proposal focused 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 considered 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

[[Page 17252]]

current primary NO2 standards? In addressing this question, 
the sections below summarize the proposal's consideration of the 
evidence in the context of the indicator, averaging times, levels, and 
forms of the current standards.
i. 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 (U.S. EPA, 
2016a, Chapter 2), 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, 
the CASAC agreed with this conclusion (Diez Roux and Sheppard, 2017). 
In light of these considerations, EPA proposed to retain the indicator 
for the current standards.
ii. Averaging Time
    The current primary NO2 standards are based on 1-hour 
and annual averaging times. The proposal explained that, 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 the CASAC 
advice in the last review 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).
    The proposal explained that, 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 2016 NOX ISA continue to provide evidence that 
NO2 exposures from less than one hour up to three hours can 
result in 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 2016 NOX 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 2016 NOX 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). As 
in the last review, the 2016 NOX 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 2016 NOX 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). Thus, 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). In light of these 
considerations, EPA proposed to retain the averaging time for the 
current 1-hour standard.
    With regard to protecting against long-term exposures, the proposal 
explained that 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, section 7).
    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 2016

[[Page 17253]]

NOX 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, 
pp. 6-64 and 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, the CASAC 
supported this approach of 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, the 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). In light of these considerations, EPA proposed to retain 
the averaging time for the current annual standard.
iii. 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 considered 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 proposal's consideration of these issues is 
discussed below for short-term and long-term NO2 exposures.
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).\87\ In evaluating the 
NO2 exposure concentrations at which increased AR has been 
observed, the proposal considered both the group mean results reported 
in individual studies and the results from a recent meta-analysis 
evaluating individual-level data (Brown, 2015; U.S. EPA, 2016a, Section 
5.2.2.1).\88\
---------------------------------------------------------------------------

    \87\ As discussed in Section II.C of the proposal and Section 
II.A.2 above, experimental studies have not reported other 
respiratory effects following short-term exposures to NO2 
concentrations at or near those found in the ambient air.
    \88\ As noted earlier in this section, 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, 
allowing us to evaluate the strength of the NO2 and AR 
relationship across different concentrations of NO2 in 
each study, and these studies have the advantage of being based on 
the same exposure conditions. The meta-analysis by Brown (2015) can 
also provide insight into the extent to which observed changes are 
due to NO2 exposures, but has the additional benefit of 
aiding in the identification of 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, though each study in the meta-analysis may not 
be based on the exact same exposure conditions.
---------------------------------------------------------------------------

    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.\89\ As discussed in more detail 
in Section II.C.1 of the proposal, and in Section II.A.2 above, 
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 
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.
---------------------------------------------------------------------------

    \89\ 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 and summarized in the proposal, provided 
information about the ambient NO2 concentrations in 
locations where such studies have examined associations with asthma-
related hospital admissions or ED visits (short-term) or with asthma 
incidence (long-term). In particular, these studies informed 
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 epidemiologic 
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 proposal noted 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

[[Page 17254]]

the one study location with a maximum DV of 100 ppb (Atlanta) would 
have violated the existing 1-hour standard during study periods.\90\ 
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 
proposal also considered 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 ED visits in locations likely to have violated the 
current 1-hour NO2 standard, the proposal placed weight on 
the PA's conclusion 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).
---------------------------------------------------------------------------

    \90\ 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 the 1-
hour standard, the proposal noted 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.\91\ In addition, the proposal 
noted that a 98th percentile form is consistent with the EPA'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.\92\ In light of these considerations, EPA proposed to 
retain the level and form for the current 1-hour standard.
---------------------------------------------------------------------------

    \91\ 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).
    \92\ The 98th percentile typically corresponds to about the 7th 
or 8th highest daily maximum 1-hour NO2 concentration in 
a year.
---------------------------------------------------------------------------

Long-Term
    With regard to health effects related to long-term NO2 
exposures, the proposal first considered 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 (75 FR 6474, February 9, 2010).
    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 
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. 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 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 remains 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 proposal recognized the above uncertainties, it 
considered 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 proposal considered the degree to which the evidence indicates 
adverse respiratory effects associated with long-term NO2 
exposures in locations that would have met the current NAAQS. As 
summarized in Section II.C.2 of the proposal, and in Section II.A.2 
above, the causal determination for long-term exposures is supported 
both by studies of long-term NO2 exposures and by studies 
indicating a potential role in asthma development for repeated short-
term exposures to high NO2 concentrations.\93\
---------------------------------------------------------------------------

    \93\ There remains some uncertainty as to whether the health 
effects associated with long term exposure to NO2 are due 
to repeated higher short term exposures, a longer, cumulative 
exposure, or some mixture of both.
---------------------------------------------------------------------------

    As such, when considering the ambient NO2 concentrations 
present during study periods, the proposal considered these 
concentrations within

[[Page 17255]]

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.\94\ The 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.
---------------------------------------------------------------------------

    \94\ As noted in the PA, near-road monitors were not included in 
this analysis due to the limited amount of data available (U.S. EPA, 
2017a, Figure 2-11).
---------------------------------------------------------------------------

    As discussed in Section II.C.1 of the proposal, and in Section 
II.A.2 above, 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) (U.S. EPA, 
2016a, section 2.5.3.1, e.g., Tables 2-6 and 2-8, Figures 2-16 and 2-
17).
    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 proposal 
placed weight on the PA's conclusion 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 proposal noted the PA's evaluation 
indicating 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. In light of these 
considerations, EPA proposed to retain the level and form for the 
current annual standard.
b. Exposure- and Risk-Based Considerations
    Exposure- and risk-based considerations were also important to the 
proposed decision and its rationale, like the consideration of the 
health evidence discussed in section II.B.1.a above. As described in 
greater detail in Section II.A.3 above, and in the REA Planning 
document (U.S. EPA, 2015b, 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. These analyses were 
presented in the PA. The staff further concluded in the PA 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 proposal began by noting the PA's focus 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.A.3 above, and in section II.D.1 of the 
proposal, 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 updated analyses in the PA consider 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-specific AR in people with asthma 
exposed to NO2 at rest. As discussed in more detail in 
section II.D of the proposal, 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.\95\
---------------------------------------------------------------------------

    \95\ 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 around benchmarks, 
there are multiple uncertainties, as discussed in section II.C.I of the 
proposal and section II.A.3 above. As discussed in more detail in those 
sections, these uncertainties include the lack of an apparent a dose-
response relationship between NO2 and AR in people with 
asthma, and uncertainty in the potential adversity of the reported 
NO2-induced increases in AR.
    As discussed in section II.D.2 of the proposal, and in section 
II.A.3 above, 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 \96\ indicate 
virtually no potential for 1-hour exposures to NO2 
concentrations at or above 200 ppb (or 300 ppb) and almost none for 
exposures

[[Page 17256]]

at or above 150 ppb.\97\ 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.
---------------------------------------------------------------------------

    \96\ 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 (U.S. 
EPA, 2017a, Section 4.2.1).
    \97\ Comparisons of NO2 air quality to health-based 
benchmarks that estimated occurrences of NO2 
concentrations exceeding the 150 and 200 ppb health-based benchmarks 
are found in Figure 4-1 of the PA (U.S. EPA, 2017a).
---------------------------------------------------------------------------

    Section II.D.2 of the proposal noted that 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 the risk of such effects occurring (i.e., at or 
near 100 ppb). Given the results of these analyses, and the 
uncertainties inherent in their interpretation, the proposal placed 
weight on the PA's conclusion 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.
2. The CASAC Advice in This Review
    In the current review of the primary NO2 standards the 
CASAC has provided advice and recommendations based on its review of 
drafts of the 2016 NOX ISA (Frey, 2014a; 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 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 2016 NOX 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 
2016 NOX 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.\98\ 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).
---------------------------------------------------------------------------

    \98\ 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 agreed with 
its conclusion that the available evidence, taken together, does not 
support the need for increased protection against short- or long-term 
NO2 exposures, beyond that provided by the existing 
standards, 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). Further, 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 further 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 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 ``a 
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).

[[Page 17257]]

     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, 2017, p. 8). However, the CASAC recognized that these studies 
``are also subject to uncertainty, including possible confounding with 
other traffic-related pollutants'' (Diez Roux and Sheppard, 2017, p. 
8). The 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, the CASAC recognized the causal associations between long-
term exposures, or repeated short-term exposures, and asthma 
development (Diez Roux and Sheppard, 2017, p. 7) and the 
appropriateness of considering the protection provided by the current 
suite of standards together (Diez Roux and Sheppard, 2017, p. 9). 
Therefore, the CASAC advice on the annual standard takes into account 
the degree of protection provided by that 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, the 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, the 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, the 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, the 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).
3. Comments on the Proposed Decision
    This section presents the responses of the EPA to the public 
comments received on the 2017 NO2 NAAQS proposal (82 FR 
34792, July 26, 2017). All significant issues raised in timely public 
comments have been addressed in this document, as the EPA is not 
preparing a separate Response to Comments document. We have 
additionally considered comments submitted after the close of the 
public comment period, to the extent practicable.
    Overall, the EPA received 17 sets of comments, with the majority 
expressing support for the Administrator's proposed decision to retain 
the current primary standards, without revision. Comments supporting 
the Administrator's proposed decision were received from various 
industry groups,\99\ individuals, and state environmental or health 
agencies.\100\ These commenters generally note their agreement with the 
Administrator's rationale provided in the proposal and many note the 
CASAC concurrence with the EPA that the current evidence does not 
support revision to the standards. Some of the commenters also agree 
with the EPA and the CASAC statements that the information in this 
review has not substantially altered our previous understanding of the 
concentrations at which effects can occur, and that the scientific 
evidence does not support standards more protective than the current 1-
hour and annual standards.
---------------------------------------------------------------------------

    \99\ Comments were received from the following industry groups: 
The NAAQS Implementation Coalition, the Utility Air Regulatory 
Group, Edison Electric Institute, Interstate National Gas 
Associations of America, Cleco Power, the American Fuel and 
Petrochemical Manufacturers, the American Petroleum Institute, The 
Tri-state Generation and Transmission Association, and the Class of 
'85 Regulatory Response Group.
    \100\ Comments were received from the following state 
environmental or health agencies: Texas Commission on Environmental 
Quality (TCEQ) and Arkansas Department of Environmental Quality 
(ADEQ).
---------------------------------------------------------------------------

    Several groups, including some that support the Administrator's 
proposed decision to retain the current standards, provided additional 
comments, including on the EPA's causal determinations in the 2016 
NOX ISA, the margin of safety provided by the current 
standards, and the potential for the scientific information to support 
alternative standards that are less stringent than the current 
standards. In addition, one organization (The American Lung 
Association) argues for more stringent primary NO2 
standards, noting the strong evidence for respiratory effects following 
both short- and long-term NO2 exposures.
    The following sections discuss the public comments on the proposal 
and the EPA's responses to those comments. Section II.B.3.a discusses 
comments on the EPA's assessment of the scientific evidence. Section 
II.B.3.b discusses comments on the degree of protection provided by the 
current standards and on the potential for the available scientific 
information to support standards that are less stringent than the 
current standards. Section II.B.3.c discusses comments recommending 
that the EPA revise the current standards to be more stringent. Section 
II.B.3.d briefly explains the EPA's approach to comments related to 
implementation of the NAAQS, which are outside the scope of this 
action.
a. Comments on the Assessment of the Scientific Evidence
    There were several comments submitted related to the EPA's 
assessment of the scientific evidence. Some commenters agree with the 
causal framework used in the 2016 NOX ISA and with the ISA's 
conclusions regarding the strength of the evidence for various health 
outcomes and for at-risk populations. Other commenters, while agreeing 
with the overall proposed decision to retain the existing primary 
standards, assert that the ISA framework for causal determinations does 
not result in a systematic, balanced, and rigorous evaluation of the 
evidence. As discussed below, these commenters generally claim that the 
2016 NOX ISA does not adequately address uncertainties and 
biases in the evidence and recommend that the EPA should strengthen its 
causal framework.
    Some comments received on the proposed decision express an overall

[[Page 17258]]

objection to ISA conclusions that the evidence linking NO2 
exposures with a variety of health effects has become stronger in this 
review. A subset of these comments further imply that the 2016 
NOX ISA's conclusions on the strength of evidence, and the 
corresponding discussions in the PA, are not entirely consistent with 
the uncertainties noted by the Administrator throughout the discussion 
of his proposed decision on the primary NO2 standards.
    In responding to these comments, the EPA notes that the ISA's 
causal framework has been implemented and refined over multiple NAAQS 
reviews, drawing from extensive interactions with the CASAC and from 
the public input received as part of the CASAC review process. Based on 
application of that framework in the current review, the 2016 
NOX ISA has made causal determinations for a variety of 
health outcomes. The ISA provides a careful and detailed rationale for 
all of its causal determinations, explicitly characterizing the key 
evidence, the reason for the change from the 2008 NOX ISA 
(if a change occurred), and the uncertainties remaining in the body of 
evidence (see, e.g., U.S. EPA, 2016a, Table 1-1). In most cases where 
the causal determination has changed since the 2008 NOX ISA, 
the change has been due to the availability, in the current review, of 
additional studies that reduce uncertainty or bias in the evidence 
(U.S. EPA, 2016a, Table 1-1).\101\ The causal determinations in the 
NOX ISA underwent extensive CASAC review, which included 
multiple opportunities for public input. The EPA considered the CASAC 
advice and the public input in making final causal determinations. The 
CASAC concurred with the 2016 NOX ISA's causal 
determinations and explained the reasons for its concurrence (Diez Roux 
and Frey, 2015a, p.1; Diez Roux and Sheppard, 2017, p. 7).
---------------------------------------------------------------------------

    \101\ The exception to this is the 2016 NOX ISA 
determination that a causal relationship exists between short-term 
NO2 exposure and respiratory effects. This conclusion is 
strengthened from the ``likely to be causal'' relationship 
determined in the 2008 NOX ISA for Oxides of Nitrogen. 
Rather than new evidence, the 2016 NOX ISA notes that 
integrated experimental and epidemiologic evidence for asthma 
exacerbation, with due weight to controlled human exposure studies, 
supports a causal relationship between short-term NO2 
exposure and respiratory effects. Specifically, the 2016 
NOX ISA explains that the conclusion is strengthened from 
the previously determined ``likely to be causal'' relationship 
because the combined controlled human exposure and epidemiologic 
evidence can be linked in a coherent and biologically plausible 
pathway to explain how NO2 exposure can trigger an asthma 
exacerbation. (U.S. EPA, 2016a, pp. 1-17 to 1-19).
---------------------------------------------------------------------------

    For example, in concluding 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), 
the ISA cites ``epidemiologic evidence for NO2-associated 
asthma exacerbation and biological plausibility from NO2-
induced increases in [AR] and allergic inflammation in adults with 
asthma'' (U.S. EPA, 2016a, p. 5-247). In agreement with this causal 
determination, the CASAC states the following (Diez Roux and Sheppard, 
2017, p. 7):

    The CASAC concurs with the finding that short-term exposures to 
NO2 are causal for respiratory effects based on evidence 
for asthma exacerbation. The strongest evidence is for an increase 
in airway responsiveness based on controlled human exposure studies, 
with supporting evidence from epidemiologic studies.

    In addition, in concluding that ``[t]here is likely to be a causal 
relationship between long-term NO2 exposure and respiratory 
effects based on evidence for the development of asthma'' (U.S. EPA, 
2016a, p. 1-20), the ISA notes that ``[r]ecent epidemiologic studies 
consistently indicate increases in asthma incidence in children 
particularly in association with NO2 exposures estimated at 
or near children's homes or schools'' and that experimental evidence 
``provides biological plausibility by characterizing a potential mode 
of action by which long-term NO2 exposure may lead to asthma 
development'' (U.S. EPA, 2016a, p. 6-67). In agreement with this causal 
determination, the CASAC states 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 co-pollutants on 
the association between NO2 and asthma incidence.

    Thus, based on the evidence considered in the 2016 NOX 
ISA, and consistent with the CASAC advice, we disagree with comments 
that the strengthening of the causal determinations in the 2016 
NOX ISA is not justified.
    The EPA further disagrees with comments claiming that, in his 
consideration of the levels of the primary standards, the 
Administrator's discussion of uncertainties and limitations in the 
scientific evidence is inconsistent with the conclusions of the 2016 
NOX ISA that the evidence for several health endpoints is 
stronger now than in the last review. As an initial matter, we note 
that the issues faced by the EPA in drawing causal determinations in 
the 2016 NOX ISA differ from EPA's considerations in 
evaluating the public health protection provided by the standards. In 
drawing the causal determinations, the ISA focuses on the degree to 
which the available evidence indicates that NO2 exposures 
can cause specific health effects. These causal determinations reflect 
the ISA's assessment of studies spanning a relatively wide range of 
exposure concentrations, encompassing the full body of evidence 
relevant for the review. In contrast, in the proposal and in this final 
action, the EPA is additionally tasked with determining what the 
evidence can tell us about the adequacy of the public health protection 
provided by a particular standard or standards. This step typically 
involves focusing on the subset of studies that, together with risk and 
exposure information, can best inform the EPA's consideration of the 
public health impacts associated with particular air quality 
concentrations. Consideration of uncertainties is important for both 
tasks, but the nature of those uncertainties, and exactly how the 
various uncertainties factor into each aspect of the review, may 
differ. For example, strengthening of a causal determination in the ISA 
may be based on studies that clarify a proposed mode of action linking 
exposures with an observed effect, despite being conducted at exposure 
concentrations that would not be allowed by the current standards. Such 
studies may reduce uncertainties in a way that supports strengthening a 
causal determination, but not revising the standard. Thus, the 
Administrator's consideration of uncertainties in the evidence when 
reaching conclusions on the standards is not inconsistent with the ISA 
conclusions that the evidence supports strengthening some causal 
determinations in this review.
    We further note that, in reaching his proposed and final decisions, 
the Administrator's consideration of the evidence, including its 
limitations and uncertainties, draws directly from the 2016 
NOX ISA's assessment of that evidence and from the PA's 
considerations and conclusions related to the adequacy of the public 
health protection provided by the current standards. Both the ISA and 
PA include extensive discussion and consideration of the scientific 
evidence and its uncertainties. As noted above, Table 1-1 in the ISA 
summarizes the key evidence for various NO2-related health

[[Page 17259]]

outcomes, including the remaining uncertainties inherent in that 
evidence. In addition, drawing from the ISA, the PA includes extensive 
consideration of uncertainties and limitations in the evidence as they 
relate to conclusions on the adequacy of the public health protection 
provided by the current primary NO2 NAAQS (U.S. EPA, 2017a, 
sections 3.2.2.1, 3.2.2.2, 3.3.2.1). Contrary to the comments noted 
above, the Administrator's proposed and final decisions draw from the 
characterization in those documents of uncertainties and limitations in 
the evidence (e.g., sections II.A.2, II.A.3, II.B.4 of this final 
action). The Administrator's proposed and final decisions to retain the 
current primary NO2 standards are consistent with the PA's 
conclusions (U.S. EPA, 2017a, section 5.4). Moreover, these decisions 
are consistent with recommendations of the CASAC to retain the current 
standards (Diez Roux and Sheppard, 2017).
    Some comments further criticize the Agency's characterization of 
the evidence by asserting that the EPA places too much emphasis on 
epidemiologic studies that are methodologically flawed and insufficient 
for determining a standard. While we agree that there are uncertainties 
inherent in epidemiologic studies, these uncertainties, which have been 
extensively considered as part of the assessment of the evidence in the 
ISA and the evaluation of policy options in the PA, as well as in the 
proposal and this final action (e.g., summarized in sections II.A.2 and 
II.B.1 above), do not make the epidemiologic evidence insufficient for 
informing decisions on the primary NO2 standards. Rather, 
conclusions in this review draw from the consideration of scientific 
evidence from a range of disciplines, each with its own strengths and 
limitations.\102\ In particular, the 2016 NOX ISA's causal 
determinations are based on the integration of evidence across 
controlled human exposure, epidemiologic, and animal toxicological 
studies. The focus of the ISA's integration is on evaluating the 
consistency and inconsistency in the pattern of effects across studies 
and endpoints as well as the strengths and limitations of the evidence 
across the various disciplines (U.S. EPA, 2016a, p. 1). For each study, 
the 2016 NOX ISA systematically evaluates study design, 
populations evaluated, approach to exposure assessment/assignment, 
approach to outcome assessment, potential for confounding, and 
statistical methodology (U.S. EPA, 2016a, Table A-1). As described 
below, and more fully in the ISA (see e.g., U.S. EPA, 2016a, Table 1-
1), uncertainties and limitations in the evidence, including in the 
evidence from epidemiologic studies, are explicitly considered in the 
ISA's causal determinations and can affect how various aspects of the 
evidence are weighed in making those determinations.
---------------------------------------------------------------------------

    \102\ In fact, relative to other types of evidence, strengths of 
epidemiologic studies can include providing information on the most 
serious pollutant-associated effects in human populations, including 
populations with pre-existing conditions, or at particular life 
stages, that put them at increased risk of such effects.
---------------------------------------------------------------------------

    For example, while the ISA concludes that epidemiologic studies do 
indicate the occurrence of NO2-associated asthma 
exacerbation, it further concludes that ``epidemiologic evidence on its 
own does not rule out the influence of other traffic-related 
pollutants'' (U.S. EPA, 2016a, p. 1-18). The ISA further concludes that 
``[t]he key evidence that NO2 exposure can independently 
exacerbate asthma are the findings from previous controlled human 
exposure studies for increases in airway responsiveness in adults with 
asthma'' (U.S. EPA, 2016a, p. 1-18). Thus, based in part on 
uncertainties in the available epidemiologic evidence, the ISA's 
conclusion that ``[a] causal relationship exists between short-term 
NO2 exposure and respiratory effects'' (U.S. EPA, 2016a, p. 
1-17) places the greatest emphasis on information from controlled human 
exposure studies (e.g., U.S. EPA, 2016a, p. 5-247). As noted above, the 
CASAC endorsed this emphasis, stating 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). In fact, the CASAC recommended 
that the controlled human exposure studies, alone, are sufficient to 
justify the causal determination for short term NO2 
exposures and respiratory effects (Diez Roux and Frey, 2015a, cover 
letter at p. 2).\103\ Consistent with this, information from controlled 
human exposure studies is emphasized in the PA's conclusions on the 
public health protection provided by the current standards against 
short-term NO2 exposures (U.S. EPA, 2017a, sections 3.2 and 
5.4) and in the Administrator's conclusion to retain those standards in 
this final decision (section II.B.4, below).
---------------------------------------------------------------------------

    \103\ Specifically, the CASAC recommended that ``the evidence 
supporting changes to the causal determination status for oxides of 
nitrogen for associations with short-term exposures be based 
primarily on the findings from the controlled human exposure 
studies, as they alone are sufficient to justify the change'' (Diez 
Roux and Frey, 2015a, cover letter at p.2).
---------------------------------------------------------------------------

    In addition, the 2016 NOX ISA's conclusion on long-term 
NO2 exposure and respiratory effects recognizes uncertainty 
in epidemiologic studies due to potential confounding by other traffic-
related pollutants. The ISA specifically concludes that uncertainty 
remains ``in identifying an independent effect of NO2 
exposure from traffic-related copollutants because evidence from 
experimental studies for effects related to asthma development is 
limited, and epidemiologic analysis of confounding is lacking'' (U.S. 
EPA, 2016a, p. 1-32).\104\ However, in making its overall determination 
that ``there is likely to be a causal relationship between long-term 
NO2 exposure and respiratory effects'' the ISA also notes 
that support for biological plausibility comes from experimental 
studies in animals (e.g., U.S. EPA, 2016a, Table 1-1). While 
recognizing remaining uncertainties in the evidence, the CASAC agreed 
with this ISA causal determination, observing that ``[t]he strongest 
evidence is for asthma incidence in children in epidemiologic studies, 
with supporting evidence from experimental animal studies'' (Diez Roux 
and Sheppard, 2017, p. 7).
---------------------------------------------------------------------------

    \104\ Such uncertainties also informed the PA's conclusions on 
the public health protection provided by the current standards (U.S. 
EPA, 2017a, section 5.4).
---------------------------------------------------------------------------

    Thus, the 2016 NOX ISA's conclusions reflect the 
consideration of information from all lines of evidence, not only 
epidemiologic studies, including appropriate consideration of the 
uncertainties and limitations in that evidence. The CASAC reviewed and 
endorsed the 2016 NOX ISA's approach to assessing the 
evidence, including uncertainties and limitations in that evidence, and 
its key conclusions based on the application of that approach (e.g., 
Diez Roux and Frey, 2015a; Diez Roux and Sheppard, 2017, p. 7). 
Additionally, the ISA's careful consideration of scientific evidence 
from multiple disciplines, and the uncertainties and limitations in 
that evidence, including in epidemiologic studies, informed the PA's 
conclusions on the public health protection provided by the current 
standards and the Administrator's decision to retain those standards, 
without revision, in this review. Thus, the EPA does not agree with 
comments that undue emphasis was placed on epidemiologic studies.
    Several comments further contend that the 2016 NOX ISA 
overstates the consistency of results across

[[Page 17260]]

epidemiologic studies and that it does not adequately capture 
uncertainties in the epidemiologic evidence. The EPA disagrees with 
these comments. As noted above, the 2016 NOX ISA 
appropriately characterizes the uncertainties and limitations in the 
epidemiologic evidence, including uncertainties resulting from 
inconsistent results across studies (e.g., U.S. EPA, 2016a, Tables 5-39 
and 6-5). For endpoints where the epidemiologic evidence is not 
consistent, the 2016 NOX ISA discusses the inconsistencies. 
For example, the ISA states that ``[e]pidemiologic evidence for 
NO2-related decreases in lung function in populations with 
asthma is inconsistent as a whole'' (U.S. EPA, 2016a, p. 5-241). In 
contrast, the ISA appropriately characterizes the consistent results of 
epidemiologic studies that evaluate asthma-related outcomes. In 
particular, the 2016 NOX ISA notes that ``[r]ecent studies 
that examined the association between short-term NO2 
exposure and asthma hospital admissions and ED visits consistently 
report positive associations and support the results of U.S. and 
Canadian studies evaluated in the 2008 ISA for Oxides of Nitrogen.'' 
(U.S. EPA, 2016a, p. 5-91). Figures 5-16 and 5-17 in the 2016 
NOX ISA illustrate the consistent, positive associations 
reported in studies that have evaluated the potential for confounding 
of the NO2 association by co-occurring pollutants, a key 
potential uncertainty in NO2 epidemiologic studies (U.S. 
EPA, 2016a, pp. 5-248 to 5-249). Based on its assessment of such 
studies of short-term NO2 exposure and asthma-related 
effects, the 2016 NOX ISA concludes that ``the pattern of 
association observed for NO2 supports the consistency of 
evidence and does not indicate a high probability of associations found 
by chance alone'' (U.S. EPA, 2016a, p. 5-241).
    Some comments criticizing the 2016 NOX ISA's 
characterization of consistency of results across epidemiologic 
studies, and the ISA's consideration of uncertainties in those studies, 
focus specifically on studies of long-term NO2 exposures. 
Such comments claim that the EPA overstates the consistency of the 
epidemiologic evidence, particularly given the potential for 
copollutant confounding and exposure measurement error in studies of 
long-term NO2 exposures. As discussed below, the EPA 
disagrees with these comments.
    Figure 6-1 in the 2016 NOX ISA illustrates the 
consistently positive associations between long-term exposures and 
asthma incidence in children. Based on such studies, the ISA concludes 
the following (U.S. EPA, 2016a, p. 6-63):

    Multiple longitudinal studies demonstrate associations between 
higher ambient NO2 concentrations measured in the first 
year of life, in the year of diagnosis, or over a lifetime and 
asthma incidence in children. Results are consistent across 
locations based on various study designs and cohorts.

    In reaching this conclusion, the 2016 NOX ISA also 
thoroughly discusses the uncertainties and limitations in these 
studies, including uncertainties and limitations stemming from the 
potential for copollutant confounding and exposure measurement error 
(U.S. EPA, 2016a, section 6.2.2.1). For example, with respect to 
studies of long-term exposures, the ISA notes that ``[e]pidemiologic 
studies of asthma development in children have not clearly 
characterized potential confounding by PM2.5 or traffic-
related pollutants'' (U.S. EPA, 2016a, p. 6-64). Drawing from this 
discussion in the ISA, the potential for such confounding is a key 
consideration in the PA's conclusions on the adequacy of the public 
health protection provided by the current primary NO2 NAAQS 
(U.S., EPA, 2017, section 5.4). The Administrator has further 
considered such uncertainty in reaching his proposed and final 
decisions in this review (82 FR 34792, July 26, 2017, section II.F.4; 
and see section II.B.4 below). The 2016 NOX ISA also 
characterizes the potential for exposure measurement error in these 
studies and uncertainties related to reliability of asthma diagnosis 
and age of children and temporality between diagnosis and exposures 
(U.S. EPA, 2016a, section 6.2). Based on the broader body of evidence 
(i.e., including controlled human exposure and animal toxicological 
studies), the 2016 NOX ISA concludes that uncertainty in the 
epidemiologic evidence base ``is partly reduced by the biological 
plausibility provided by findings from experimental studies'' (U.S. 
EPA, 2016a, p. 6-64). When taken together, the 2016 NOX ISA 
concludes that the evidence supports a relationship between long-term 
NO2 exposure and respiratory effects that is ``likely to be 
causal,'' and the CASAC supported this conclusion in its review of 
drafts of the 2016 NOX ISA and the PA (Diez Roux and Frey, 
2015a; Diez Roux and Sheppard, 2017, p. 7).
    Some comments additionally contend that the ISA provides a skewed 
and unbalanced picture of the scientific record by failing to discuss 
null associations in epidemiologic studies and by focusing on results 
at the lag that had the most positive and statistically significant 
association. These comments assert that the ISA ignores temporal 
differences in the lag at which the strongest association was found.
    With regard to reporting null associations, the EPA agrees that the 
assessment of the scientific evidence should consider all relevant, 
well-conducted studies that meet the ISA's criteria for inclusion, 
regardless of whether results are positive, null, or negative. 
Accordingly, the EPA employs a comprehensive approach to ensure that 
all of the relevant literature is identified for consideration and 
evaluation in the ISA (U.S. EPA, 2015a, Figure III, p. 6). As an 
initial step in the development of the 2016 NOX ISA, a call 
for information was published in the Federal Register (77 FR 7149, 
February 2, 2012). This call for information invited members of the 
public to provide information relevant to the assessment, including the 
identification of publications that evaluate potential relationships 
between pollutant exposures and health effects or data from the fields 
of atmospheric or exposure science. Subsequent to this call for 
information, the EPA conducted a comprehensive literature search and an 
evaluation and integration of evidence from the identified studies. As 
part of this process, the EPA evaluated study quality according to 
predefined criteria that are consistent with widely established methods 
in the field (U.S. EPA, 2016a, Table A-1, p. A2). This evaluation and 
assessment of the evidence, which included studies that reported null 
or negative results, was presented in two drafts of the ISA, each of 
which was reviewed by the CASAC at a public meeting where there were 
opportunities for members of the public to provide comments. As 
discussed above, in its advice to the Administrator, the CASAC 
concurred with key conclusions in the ISA regarding the strength of the 
evidence linking NO2 exposures with various health outcomes 
(Diez Roux and Frey, 2015a, cover letter at p. 1; Diez Roux and 
Sheppard, 2017, p. 7).
    In addition, we note that there is ample discussion throughout the 
ISA of null and negative results when they are reported in the studies, 
including epidemiologic studies (e.g., U.S. EPA, 2016a, Figures 5-7 and 
6-1, and accompanying text).\105\ Summary tables

[[Page 17261]]

of key evidence in the ISA for each causal determination discuss 
outcomes for which negative or inconsistent results are observed (see 
Table ES-1 of the 2016 NOX ISA for a comprehensive list of 
summary tables included in the ISA). Additionally, the EPA notes that 
while these comments criticized the EPA's assessment of the evidence, 
they did not identify well-conducted studies, regardless of association 
observed, or lack thereof, that were not included in the 2016 
NOX ISA. Thus, given the extensive public process that the 
EPA has used to identify and assess the relevant scientific evidence, 
including multiple opportunities for CASAC to provide advice and for 
members of the public to provide input, together with the ISA's 
discussion of all relevant, well-conducted studies, regardless of 
results, we do not agree with comments claiming that the ISA provides 
an unbalanced picture of the scientific record by failing to account 
for studies reporting null or negative associations.
---------------------------------------------------------------------------

    \105\ The 2016 NOX ISA also recognizes the potential 
for publication bias, stating that ``[p]ublication bias is another 
source of uncertainty that can impact the magnitude of estimated 
health or welfare effects. It is well understood that studies 
reporting non-null findings are more likely to be published than 
reports of null findings'' (U.S. EPA, 2016a p. li).
---------------------------------------------------------------------------

    Additionally, the EPA does not agree with comments criticizing the 
2016 NOX ISA's approach to identifying the most appropriate 
lags in epidemiologic studies of short-term NO2 exposures. 
We note that lag structure can vary within the population according to 
differences among individuals in time-activity patterns, pre-existing 
disease, or other factors that influence exposure and responses to 
exposure. The ISA specifically notes that ``[t]he lag structure for 
associations with NO2 exposure may vary among health effects 
depending on differences in the time course by which underlying 
biological processes occur'' (U.S. EPA, 2016a, p. 1-39). In addition, 
differences in associations among exposure lags may be influenced by 
``differences in the extent to which single-day and multiday average 
ambient NO2 concentrations represent people's actual 
exposures'' (U.S. EPA, 2016a, p. 1-39).
    In assessing the support for specific lags in epidemiologic studies 
of short-term NO2 exposures and asthma-related effects, the 
ISA notes support for same-day exposures and for exposures averaged 
over multiple days (U.S. EPA, 2016a, section 1.6.2). The ISA further 
notes support for these lags from experimental studies (U.S. EPA, 
2016a, section 1.6.2). Specifically, controlled human exposure studies 
found airway responsiveness in adults with asthma to increase 
immediately after, or 20 minutes to 4 hours after, a single 
NO2 exposure and over 4 days of repeated exposure (U.S. EPA, 
2016a, section 5.2.2.1). In experimental studies, NO2 
exposure enhanced allergic inflammation 30 minutes up to 19 hours after 
a single- or 2-day exposure in humans and 7 days after exposure in rats 
(U.S. EPA, 2016a, section 5.2.2.5). Thus, based on its assessment of 
the evidence, the ISA concludes that ``findings from experimental 
studies provide biological plausibility for the asthma-related effects 
observed in epidemiologic studies in association with 2- or 5-hour 
exposures, same-day NO2 exposures, as well as exposures 
averaged over multiple days'' (U.S. EPA, 2016a, p. 1-40). Accordingly, 
when assessing epidemiologic studies of short-term NO2 
exposures, the ISA focuses on the lags that are best supported in the 
evidence, with a recognition that the most appropriate lag can vary 
according to the specific endpoint evaluated, time-activity patterns of 
members of the study population, the prevalence of pre-existing disease 
in the study population, and other factors that influence pollutant 
exposures or the responses to those exposures.
    Some comments recommend that the EPA conduct quantitative analyses 
of uncertainty whenever possible. As discussed above and elsewhere in 
this document (e.g., sections II.A.2, II.A.3, II.B.1, II.B.4), the EPA 
has thoroughly considered uncertainties in the evidence and in 
available quantitative analyses throughout this review of the primary 
NO2 NAAQS. Uncertainties have been evaluated through a 
combination of qualitative and quantitative approaches, with the 
specific approach depending on the uncertainty being evaluated and the 
data available for its evaluation. For example, the 2016 NOX 
ISA's conclusions are based on an evaluation of the strengths and 
weaknesses in the overall collection of studies across disciplines. The 
ISA's approach to evaluating the evidence and drawing causal 
determinations generally involves qualitative consideration of 
uncertainties in the various lines of evidence (U.S EPA, 2016a, 
preamble). As noted above, this framework has been implemented and 
refined over multiple NAAQS reviews, drawing from extensive 
interactions with the CASAC and from the public input received as part 
of the CASAC review process. The CASAC has reviewed the causal 
determinations in the NOX ISA, including the ISA's 
consideration of uncertainties in the evidence, and has concurred with 
those determinations (Diez Roux and Frey, 2015a, cover letter at p.1; 
Diez Roux and Sheppard, 2017, p. 7).
    With regard to analyses comparing NO2 air quality and 
health-based benchmarks, the PA includes both quantitative and 
qualitative evaluation of uncertainties. For example, quantitative 
sensitivity analyses were used to evaluate the degree to which study 
areas adequately reflect influential factors that could contribute to 
variability in NO2 concentrations and potential exposures 
(U.S. EPA, 2017a, Appendix B, section 2.3.2) and to examine the 
potential impacts of NO2 exposures on or near roadways (U.S. 
EPA, 2017a, Appendix B, section 2.4.2). In addition, the PA includes 
extensive qualitative discussion of uncertainties in air quality-
benchmark comparisons, and the implications of these uncertainties for 
the interpretation of analysis results (U.S. EPA, 2017a, section 
4.2.1.3). This includes consideration of uncertainties in evidence 
underlying the health-based benchmarks, in the approach to adjusting 
ambient NO2 concentrations to simulate just meeting the 
current standard, and in the degree to which monitored NO2 
concentrations reflect the highest potential NO2 exposures. 
Thus, as part of this review, the EPA has thoroughly considered 
uncertainties in the evidence and in available quantitative analyses, 
with the specific approach depending on the uncertainty being evaluated 
and the data available for its evaluation.
b. Comments Relating to Consideration of Less Stringent Standards
    Though most commenters express support for the proposed decision to 
retain the current primary NO2 standards, some of these 
commenters additionally encourage the identification and consideration 
of less stringent standards. Such comments are often based on 
criticisms of the EPA's approach to assessing the scientific evidence, 
as discussed in section II.B.3.a above, with some comments contending 
that the proposal understates the margin of safety provided by the 
current 1-hour and annual standards. Some comments further conclude 
that limitations and uncertainties in the body of scientific evidence 
support the possibility that the current standards are more protective 
than is requisite, claiming that, in its consideration of the adequacy 
of the protection provided by the current standards, the EPA failed to 
consider whether the NO2 NAAQS should be made less 
stringent. One comment additionally asserts that the failure to 
identify alternative, less stringent standards is arbitrary and 
capricious, stating that the EPA has not adequately examined whether 
the uncertainties in the evidence call into question the proposed 
decision to retain the current standards or whether the standard 
level(s) should be less stringent. This

[[Page 17262]]

comment contends that the EPA must examine the possibility that the 
current standards may be too stringent and that, without such an 
examination, there is not adequate foundation in the record to support 
the proposed decision to retain those standards.
    The Administrator has carefully considered whether standards less 
stringent than the current standards would be sufficient to protect 
public health with an adequate margin of safety and, thus, whether 
retaining the current standards would not be requisite (see discussion 
in proposal at 82 FR 34792, July 26, 2017, section II.F.4, and below). 
This consideration is informed by the thorough discussions of the 
uncertainties in the scientific evidence in the 2016 NOX 
ISA, the PA, and elsewhere in this document (U.S. EPA, 2016a, table 1-
1; U.S. EPA, 2017a, section 3; and section II.A.3, above). The 
Administrator is not required to identify or evaluate specific 
alternative standards in order to make a determination than an existing 
standard or suite of standards provide the requisite protection. To the 
contrary, where the record supports a judgment that the current 
standards are requisite to protect public health with an adequate 
margin of safety, and that more or less stringent standards would not 
be requisite, the EPA may conclude, as it has here, that detailed 
evaluation of specific alternative standards is not warranted.\106\
---------------------------------------------------------------------------

    \106\ For example, in the final decision in the recently 
completed review of the National Ambient Air Quality Standards for 
Lead (81 FR 71906, October 18, 2016), the standards were retained 
without consideration of potential alternative levels.
---------------------------------------------------------------------------

    Further, we disagree with the suggestion that, by focusing on 
whether the current standards adequately protect public health, the EPA 
has failed to consider the possibility that those standards should be 
revised to be less stringent in order to provide the requisite level of 
protection. Comments making this claim mistakenly presume that, in 
considering the adequacy the current primary NO2 NAAQS and 
the public health protection they provided, the EPA has not considered 
whether the current standards should be revised to be less stringent. 
In fact, the EPA's consideration of the adequacy of the current 
standards and the public health protection they provide is intended to 
inform, and therefore substantively overlaps with, the Administrator's 
consideration of whether more or less stringent standards would, in his 
judgment, be requisite under the Clean Air Act. Accordingly, in 
considering the adequacy of the current standards to satisfy the CAA's 
requirements, the EPA also evaluates whether identification of 
potential alternative standards, either more or less stringent, is 
warranted. As described below, several considerations support the EPA 
conclusion in this review that standards less stringent than the 
current standards would not be requisite.
    First, compared to the current standards, less stringent standards 
would be more likely to allow NO2 exposures that could 
exacerbate respiratory effects in people with asthma. The current 
NO2 standards are 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., 250 ppb 
and above). In addition, the current standards provide a margin of 
safety, in part by limiting the potential for exposures to 1-hour 
NO2 concentrations at or above 100 ppb, an exposure 
concentration with the potential to exacerbate asthma symptoms but for 
which the evidence indicates uncertainty in the risk of such effects 
occurring (U.S. EPA, 2017a, sections 5.2, 5.4). Although limitations in 
this evidence take on increased importance when considering the 
potential public health implications of such exposures to 100 ppb, as 
discussed in greater detail below (e.g, sections II.B.3.c and II.B.4), 
the CAA requires that a primary NAAQS protect the public health even 
where, as here, the risks from the pollutant cannot be quantified or 
``precisely identified as to nature or degree.'' API v. EPA, 684 F.3d 
at 1350 (internal citation omitted). Further, in setting a standard 
with an adequate margin of safety, the EPA is to ``err on the side of 
caution.'' Id. at 1352. Thus, EPA places weight on the consideration 
that less stringent standards would be expected to be less effective 
than the current standards at protecting against these short-term 
exposures to NO2 concentrations at or above health-based 
benchmarks.
    Second, less stringent standards would be more likely to allow the 
ambient NO2 concentrations that have been reported in 
epidemiologic studies to be associated with clearly adverse effects. 
For example, such standards would be more likely to allow the short-
term ambient NO2 concentrations that have been shown in 
epidemiologic studies conducted in the U.S. or Canada to be associated 
with asthma-related hospitalizations. In addition, recognizing that the 
current 1-hour standard contributes substantially to protection against 
long-term NO2 exposures, less stringent standards would also 
be more likely to allow the long-term ambient concentrations that have 
been reported in epidemiologic studies to be associated with asthma 
development in children. While the EPA recognizes the limitations and 
uncertainties in these studies, they provide evidence for associations 
with asthma-related effects in locations likely to have violated the 
current standards (U.S. EPA, 2017a, sections 3.2.2.2 and 3.3.2.1). 
Therefore, the EPA also places weight on the consideration that, 
compared to the current standards, less stringent standards would allow 
greater risk of the serious health effects reported in these studies.
    Finally, the CASAC advice also supports the EPA conclusion that a 
detailed evaluation of less stringent potential alternative standards 
is not warranted in the current review. Specifically, the CASAC advised 
that the current primary NO2 standards, but not less 
stringent standards, provide protection against adverse effects 
associated with both short- and long-term NO2 exposures. 
Based on its consideration of the evidence, the CASAC concluded 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 p. 9) 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, for the 
reasons discussed above, we disagree with comments advocating for a 
detailed evaluation of potential alternative standards that would be 
less stringent than the current standards and with comments contending 
that EPA has not considered whether the current standards are too 
stringent and, thus, should not be retained.
    Comments advocating for the identification of less stringent 
standards often focus on specific uncertainties in the available health 
evidence, claiming that, because of these uncertainties, the margin of 
safety provided by the current primary NO2 standards is 
larger than acknowledged in the proposal. For example, some comments 
question the EPA's interpretation of controlled human exposure studies 
examining AR, claiming that these studies do not demonstrate adverse 
effects at exposure concentrations below 300 ppb. Such comments contend 
that the EPA should clearly articulate the limitations in controlled 
human exposure studies of AR following NO2 exposures, and in 
the Brown (2015) meta-analysis of individual-level data from these 
studies.
    The EPA agrees that there are uncertainties in the evidence from

[[Page 17263]]

controlled human exposure studies of NO2-induced changes in 
AR. These uncertainties have been discussed and considered extensively 
throughout this review, including in the 2016 NOX ISA and 
the PA (U.S. EPA, 2016a; U.S. EPA, 2017a), and in the Administrator's 
consideration of the evidence in both the proposal (82 FR 34792, July 
26, 2017, section II.F.4) and this final action (section II.B.4, 
below). Specifically, important limitations in the evidence for 
increased AR following NO2 exposures include the lack of an 
apparent dose-response relationship, which limits our ability to fully 
characterize the health risks associated with these exposures, and 
uncertainty in the adversity of the reported increases in AR (e.g., see 
U.S. EPA, 2017a, section 3.2.2.1, and section II.A.2.a.iii above). 
While we agree that it is appropriate to consider these uncertainties 
in reaching decisions on the primary NO2 NAAQS, as described 
below, we disagree that such uncertainties indicate that the reported 
effects do not have the potential to be adverse to public health.
    In particular, as discussed in the ISA, increases in AR are 
considered to be a hallmark of asthma and can lead to poorer control of 
symptoms in people with the disease. Drawing on guidelines from the ATS 
and the ERS, analyses discussed in the 2016 NOX ISA indicate 
that the increases in AR reported following exposures to NO2 
concentrations from 100 to 530 ppb have the potential to be clinically 
relevant in some people with asthma (82 FR 34804, July 26, 2017; U.S., 
EPA, 2016a section 5.2.2.1). While there are no universally agreed upon 
criteria for determining whether such increases should be considered 
adverse, they represent respiratory effects that could be of particular 
concern for people with more severe cases of asthma than have typically 
been evaluated in the available studies of NO2 exposures. 
These studies have generally evaluated people with mild asthma, while 
people with moderate or severe asthma could be more susceptible to 
NO2-induced increases in AR, and thus more likely to exhibit 
adverse responses following NO2 exposures (Brown, 
2015).\107\ Therefore, the uncertainty over the adversity of the 
response reported in controlled human exposure studies and the Brown 
(2015) meta-analysis does not mean that the NO2-induced 
increase in AR is not adverse to any population. Rather, the evidence 
indicates a risk of adversity for some people, especially for those 
with more than mild asthma, though this risk cannot be fully 
characterized based on existing studies. When considered at a 
population level, these risks are amplified and take on public health 
significance.
---------------------------------------------------------------------------

    \107\ Furthermore, the potential for such effects in other at-
risk populations that have generally not been evaluated in 
NO2 controlled human exposure studies (i.e., children and 
older adults) cannot be well-characterized based on the available 
studies.
---------------------------------------------------------------------------

    In light of these observations, we disagree with the assertion that 
controlled human exposure studies do not demonstrate effects that could 
be adverse to public health following exposures to NO2 
concentrations below 300 ppb and with comments that the proposal 
overstates the margin of safety provided by the current standards. 
Rather, while acknowledging uncertainties in the evidence, and that the 
risk cannot be fully characterized based on existing studies, the EPA 
remains concerned about the potential for adverse respiratory effects 
following exposures to such NO2 concentrations, particularly 
in people with more severe cases of asthma than have generally been 
evaluated in the available studies of NO2 exposures. 
Further, given the large percentage of people with asthma that 
experienced an NO2-induced increase in AR in these studies, 
including at exposures at and below 300 ppb,\108\ and the large size of 
the asthmatic population in the United States, the EPA concludes that 
it is appropriate to place weight on NO2-induced increases 
in AR in considering the potential for adverse public health effects 
following NO2 exposures.
---------------------------------------------------------------------------

    \108\ For example, as discussed elsewhere in this document 
(e.g., section II.A.2 above), the Brown (2015) meta-analysis 
reported that following resting NO2 exposure in the range 
of 200 ppb to 300 ppb, increased non-specific AR was reported in 78% 
of study participants.
---------------------------------------------------------------------------

    Additionally, some comments support placing more emphasis on a 
meta-analysis of information from controlled human exposure studies by 
Goodman et al. (2009). These comments assert that Goodman et al. 
concluded that exposures to NO2 concentrations up to 600 ppb 
are not associated with clinically relevant effects.
    The particular basis for these comments appears to be the 
conclusions reached by Goodman et al. (2009) that there is no dose-
response relationship between NO2 exposures and increased 
AR, and that the magnitude of any NO2 effect on airway 
responsiveness is too small to be considered adverse. While the EPA 
acknowledges the lack of an apparent dose-response relationship between 
NO2 exposures and increased AR, potentially due to 
differences in study protocols in the NO2-airway response 
literature (U.S. EPA, 2016a, section 5.2.2.1), the EPA disagrees with 
the approach taken in the Goodman study to use existing data to attempt 
to evaluate whether a dose-response relationship exists. Specifically, 
the EPA notes that while Goodman et al., (2009) did not observe a dose-
response relationship, this could be due to a variety of factors 
inherent to the study design rather than a true absence of a dose-
response relationship.\109\ Examples of such differences between 
studies include the NO2 exposure method (i.e., mouthpiece 
versus chamber), subject activity level (i.e., rest versus exercise) 
during NO2 exposure, choice of airway challenge agent, and 
physiological endpoint used to quantify airway responses.
---------------------------------------------------------------------------

    \109\CF. API v. EPA, 684 F.3d at 1350 (nothing in the context of 
the last NO2 NAAQSreview that ``the [Goodman] study did 
not establish there was `no dose-response relationship'''). In a 
decision upholding the 2010 primary NO2 NAAQS , the court 
held that EPA was ``justified in revising the NAAQS considering the 
evidence of a statistically significant relationship between 
relevant health conditions and NO2 exposure at various 
concentrations, even if the agency did not know the precise dose-
response relationship between V and airway responsiveness, among 
other health effects.'' Id. at 1351.
---------------------------------------------------------------------------

    As a result of these differences in study protocols, the 2016 
NOX ISA judged it appropriate to assess only the fraction of 
study participants who experienced increased or decreased airway 
responsiveness following NO2 exposures. The CASAC endorsed 
this approach of comparing the fractions of study participants, which 
was adopted in the meta-analysis by Brown (2015) and was the focus of 
discussion in the 2016 NOX ISA (U.S. EPA, 2016a, section 
5.2.2.1). When commenting on Brown (2015) in the draft ISA, the CASAC 
noted that it was ``impressed with the meta-analysis of controlled 
human exposure studies'' and found that ``this analysis facilitates the 
inferences that can be drawn from the studies contained in the 
analysis'' (Diez Roux and Frey, 2015a, p. 2 of cover letter, p. 7 of 
consensus comments).
    When the fraction of study participants who experienced increased 
or decreased airway responsiveness was analyzed, both Brown (2015) and 
Goodman et al. (2009) reported that exposures to NO2 
concentrations at and above 100 ppb increased airway responsiveness in 
the majority of people with asthma. Specifically, Table 4 of the 
Goodman et al. (2009) study reports that 64% (95% CI: 58%, 71%) of 
resting asthmatics exposed to NO2 experienced an increase in 
airway responsiveness. Furthermore, Figure 2a of the Goodman et al. 
(2009) study reports that for exposures less than 200 ppb, 61%

[[Page 17264]]

experienced an increase in AR (95% CI: 52%, 70%), while for exposures 
of 200 to 300 ppb, 66% experienced an increase (95% CI: 59%, 74%). 
These findings are consistent with those reported by Brown (2015) and 
discussed in the 2016 NOX ISA (U.S. EPA, 2016a, section 
5.2.2.1).
    Thus, both Goodman et al. (2009) and Brown (2015) report that the 
majority of study subjects experienced increased AR following resting 
NO2 exposures. As discussed further above, increases in AR 
can lead to poorer control of symptoms in people with asthma and 
analyses in the 2016 NOX ISA indicate that the increases in 
AR reported following resting exposures to NO2 
concentrations from 100 to 530 ppb have the potential to be clinically 
relevant in some people with asthma. In addition, people with more 
severe cases of asthma than have typically been evaluated in the 
available studies of NO2 exposures could be more likely to 
exhibit adverse responses following such exposures. Therefore, while we 
agree with comments that it is appropriate to consider the meta-
analysis by Goodman et al. (2009), in addition to that by Brown (2015), 
we do not agree that such consideration supports the conclusion that 
exposures to NO2 concentrations up to 600 ppb are not 
associated with clinically relevant effects.
    Some comments assert that the EPA should place more emphasis on 
controlled human exposure studies that employ allergen challenge, 
rather than those that use non-specific challenge agents, because the 
commenters view such studies as more relevant to real world exposures. 
These comments claim that the lack of effects in studies that used 
allergen challenge increases the uncertainty that NO2 in 
ambient air causes effects of concern.
    As an initial matter, we note that the ATS and the ERS recognize 
increased AR following exposure to non-specific challenge agents (e.g., 
methacholine) as a primary feature in the clinical definition and 
characterization of asthma severity (U.S. EPA, 2016a, section 5.2.2.1; 
Reddel et al., 2009). Thus, we do not agree with the implication of 
these comments that non-specific challenge agents are inherently less 
relevant to the evaluation of NO2-induced changes in AR.
    We further disagree that people would not have real world exposures 
to all of the non-specific challenge agents used in controlled human 
exposure studies. Specifically, both cold dry air and SO2, 
which have been evaluated in studies of non-specific AR following 
NO2 exposures, are nonspecific stimuli that people may 
encounter in the environment.\110\ Thus, when viewed from a public 
health perspective, a member of the public has the potential to be 
exposed to a non-specific challenge agent just as they have the 
potential to be exposed to an allergen to which they have been 
sensitized.
---------------------------------------------------------------------------

    \110\ Of the studies included in the meta-analysis by Brown 
(2015), SO2 was used as a challenge agent in a study of 
resting exposures to 250 ppb NO2 (Table 1 of Brown, 2015) 
and cold dry air was used in several studies of NO2 
exposures during exercise (Table 2 of Brown, 2015).
---------------------------------------------------------------------------

    In addition, while we agree with the potential public health 
significance of increased AR to allergen challenges (e.g., see U.S. EPA 
2016a, pp. 5-24 and 5-25), relatively little individual-level data on 
changes in AR following NO2 exposures was available from 
studies using specific allergen challenges (i.e., about 30% of the AR 
data). With regard to the allergen challenge studies that were 
available, the 2016 NOX ISA (U.S. EPA 2016a, p. 5-25) 
additionally notes that, ``. . . the response to an allergen is not 
only a function of the concentration of inhaled allergen, but also the 
degree of sensitization as measured by the level of allergen-specific 
IgE and responsiveness to nonspecific agents,'' making it difficult to 
predict the level of responsiveness to an allergen. The relatively 
small amount of individual-level data from allergen challenge studies, 
together with the greater difficulty in predicting allergen 
responsiveness, limits the degree to which these studies, by 
themselves, can inform conclusions on the potential public health 
implications of NO2 exposures. Given this, in addition to 
considering results of individual studies, we consider the data from 
studies of allergen challenge, together with data from studies of non-
specific challenge, as part of the meta-analysis by Brown (2015). When 
data from studies of non-specific challenge were combined with data 
from studies of allergen challenge, Brown (2015) reported that the 
majority of study participants experienced increased AR following 
resting exposures from 100 to 200 ppb, 200 to 300 ppb, and above 300 
ppb (Table 5 in Brown, 2015). Thus, based on the larger body of 
information available, including information from studies that 
evaluated AR following allergen challenge, NO2 exposures at 
and above 100 ppb have the potential to increase AR in people with 
asthma.
    Some comments additionally point out the inconsistent results 
reported in controlled human exposure studies conducted in people who 
are exercising, claiming that such inconsistency calls into question 
the plausibility of a causal association between NO2 and 
increased AR. With regard to these comments, the EPA agrees that 
individual studies conducted with exercise have not consistently 
reported NO2-induced increases in AR. However, the EPA does 
not agree with commenters' conclusion that these inconsistencies call 
into question the causal association between NO2 and 
increased AR.
    As noted above, the 2016 NOX ISA has extensively 
considered all available studies that have evaluated the potential for 
NO2 to increase AR in people with asthma. This includes 
studies conducted with participants at rest as well as studies with 
participants engaged in exercise (U.S. EPA, 2016a, section 5.2). As 
discussed in the ISA (U.S. EPA, 2016a, p. 5-23), the presence of a 
response in study participants at rest, but not while engaged in 
exercise, is not enough, in itself, to dismiss the causal association 
between NO2 and airway responsiveness. This issue is 
discussed in detail in the Brown (2015) meta-analysis, and in other 
publications on NO2 by Folinsbee (1992) and Bylin (1993), 
which were considered in the ISA. As discussed in those publications, 
the act of exercising may create a refractory period which may lead to 
diminished airway responsiveness to a challenge. Therefore, observing a 
response in participants at rest, but not exercising, does not indicate 
that there is no causal relationship between NO2 exposures 
and increased airway responsiveness. The CASAC was aware of this 
difference in results across study protocols, but still agreed with 
EPA's determination that there was a causal relationship between 
NO2 exposures and increased airway responsiveness, 
concluding that the Brown (2015) meta-analysis ``provides confirmation 
of causality for short-term effects'' (Diez Roux and Frey, 2015a, p. 
6).
    Some comments supporting the consideration of less stringent 
standards additionally focus on the epidemiologic evidence. 
Specifically, some industry groups comment that the EPA overstates the 
consistency of the epidemiologic evidence, particularly given the 
potential for co-pollutant confounding and exposure measurement error 
in studies of long-term NO2 exposures, and given the results 
of a U.S. multicity study that reported no association between short-
term NO2 exposures and ED visits (Stieb et al., 2009).
    As discussed in greater detail above (Section II.B.3.a), we do not 
agree with comments criticizing the 2016 NOX ISA's 
assessment of the epidemiologic evidence, including comments 
criticizing the ISA's characterization of the consistency of results 
across studies or comments criticizing the assessment

[[Page 17265]]

of uncertainties in those studies. Contrary to these comments, the ISA 
thoroughly considers uncertainties and limitations in the evidence, 
including the potential for co-pollutant confounding and exposure 
measurement error in epidemiologic studies (see e.g., U.S. EPA, 2016a, 
sections 5.2.9.4 and 6.2.2.1). The PA additionally considers such 
uncertainties, and their implications for conclusions on the degree of 
public health protection provided by the current primary NO2 
standards (U.S. EPA, 2017a, sections 3.2.2.2, 3.3.2.1, 5.4).
    With regard to comments on the study by Stieb et al. (2009) in 
particular, commenters correctly point out that this study reported no 
association between short-term NO2 and ED visits. This lack 
of a positive association was discussed in the 2016 NOX ISA 
(U.S. EPA, 2016a, p. 5-84). However, the ISA's conclusion regarding the 
overall consistency of the broader body of available epidemiologic 
studies is based on the generally positive health effect associations 
reported in studies conducted across the U.S., Canada, Europe, and Asia 
(e.g., U.S. EPA, 2016a, Figure 5-7). The relatively small number of 
studies in this group that did not report such positive associations, 
including the study by Stieb et al. (2009), were appropriately 
considered in reaching this broader ISA conclusion and do not call it 
into question. The lack of a positive association in the study by Stieb 
et al. (2009) was also specifically discussed in the PA (U.S. EPA, 
2017a, p. 5-8), which noted that ``the only recent multicity study 
evaluated (Stieb et al., 2009) . . . did not report a positive 
association between NO2 and ED visits'' (U.S. EPA, 2017a, p. 
5-8). This observation, together with information from other key 
epidemiologic studies conducted in the U.S. or Canada,\111\ informed 
the PA's conclusion that ``available U.S. and Canadian epidemiologic 
studies of hospital admissions and ED visits do not indicate the 
occurrence of NO2-associated effects in locations and time 
periods with NO2 concentrations that would clearly have met 
the current 1-hour NO2 standard'' (U.S. EPA, 2017a, p. 5-9). 
Thus, the lack of a positive association with ED visits in the study by 
Stieb et al. (2009) was discussed in the ISA and informed the PA's 
conclusions on the adequacy of the public health protection provided by 
the current primary NO2 NAAQS. Accordingly, we disagree with 
the comments arguing, based on Stieb et al. (2009) or on uncertainties 
and limitations in the epidemiologic evidence, as described more fully 
above (II.B.3.a), that EPA has overstated the consistency of the 
epidemiologic evidence.
---------------------------------------------------------------------------

    \111\ In considering the public health protection provided by 
the current standards, the PA focused on key studies assessed in the 
ISA that were conducted in the U.S. or Canada. Such studies are 
likely to reflect air quality and exposure patterns that are 
generally more 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 (U.S. 
EPA, 2017a, p. 3-20).
---------------------------------------------------------------------------

    Some comments additionally note that current ambient NO2 
concentrations are low, particularly compared to concentrations that 
would be of concern based on the health evidence, and are showing a 
downward trend. These comments contend that current monitoring, 
including available near-road monitoring, shows that NO2 
concentrations remain well below the levels of current standards, 
calling into question the EPA's analysis comparing NO2 air 
quality with health-based benchmarks and its resulting impact on the 
Administrator's determinations in the proposed decision. They further 
assert that the lack of real-world exposures above benchmarks, together 
with the downward trend in NO2 concentrations, contradicts 
EPA's rationale that the level of the current NAAQS must be maintained 
to protect against exposures at 100 ppb or 250 ppb. Based on current 
ambient NO2 concentrations, these commenters argue that the 
EPA should consider how the monitoring data, including from near-road 
monitors, impacts its assessment of exposures and should also examine 
whether alternative, less stringent standards are appropriate.
    Insofar as these comments are premised on the notion that exposure- 
and risk-related considerations in the NAAQS reviews should rely only 
on actual air quality, we disagree. We recognize that available 
monitoring data indicates that recent ambient NO2 
concentrations are below the NO2 exposure concentrations 
shown in controlled human exposure studies to increase AR. For example, 
the PA notes that analyses based on recent NO2 air quality 
``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)'' (U.S. EPA, 2017a, p. 4-19). However, the 
observation that recent NO2 air quality concentrations, 
including from the near-road monitors, are lower than the exposure 
concentrations shown to cause effects does not, in and of itself, 
answer the question whether the current standards are more protective 
than necessary or whether the EPA should consider less stringent 
standards. Rather, it is important to consider the potential 
NO2 exposures that would be permissible under the current 
standards to inform these questions.
    In order to accomplish this, the PA further considers the potential 
for exposures to NO2 concentrations at or above health-based 
benchmarks based on analyses where air quality has been adjusted 
upwards to simulate areas that would ``just meet'' the current primary 
NO2 NAAQS. These analyses provide information on the public 
health protection associated with allowable NO2 air quality 
under the current standards and, therefore, are clearly useful for 
informing a decision on the issue before the EPA. See American 
Petroleum Institute v. EPA, 684 F.3d at 1353 (upholding EPA's approach 
``comparing the benefits of the one-hour standard against not only a 
scenario based upon existing air quality but also upon an alternate 
scenario in which areas just meet the [existing standard].''); American 
Trucking Associations v. EPA, 283 F.3d 355, 370-71 (D.C. Cir. 2002) 
(existence of evidence showing adverse effects occurring at levels 
allowed by the current standards justifies finding that it is 
appropriate to revise the existing NAAQS). This is a reasonable 
approach to informing judgments regarding the current standards, and it 
is consistent with section 109 of the CAA, which requires the EPA to 
review whether the current primary standards--not current air quality--
are requisite to protect public health with an adequate margin of 
safety. CAA section 109(b)(1) and 109(d)(1); see also NEDA/CAP v. EPA, 
686 F.3d 803, 813 (D.C. Cir. 2012) (rejecting the notion that it would 
be inappropriate for EPA to revise a NAAQS if current air quality does 
not warrant revision, stating ``[n]othing in the CAA requires EPA to 
give the current air quality such a controlling role in setting 
NAAQS''). Furthermore, although NO2 air quality has been 
improving and is expected to continue improving, there are inherent 
uncertainties in predicting future air quality. Accordingly, it is 
reasonable to consider the NO2 exposures that could occur 
under a pattern of air quality that just meets the current standards. 
API v. EPA, 684 F.3d at 1352.
    In addition, the CASAC agreed with considering analyses based on 
adjusted air quality, stating that ``[t]he EPA has made a reasonable 
choice in looking both at the number of [benchmark] exceedances of the 
unadjusted data as well as the level of exceedance of the

[[Page 17266]]

adjusted data'' (Diez Roux and Sheppard, 2017, p. 5). Therefore, for 
all of the reasons described above, relatively low recent ambient 
NO2 concentrations, including those at near-road monitors, 
do not call into question analyses comparing NO2 air quality 
to health-based benchmarks or the role those analyses play in the 
Administrator's decision to retain the existing standards.
c. Comments Supporting More Stringent Standards
    One commenter argues that the current NAAQS do not protect public 
health with an adequate margin of safety, and that the standards should 
be revised to be more stringent. Specifically, these comments recommend 
that the level of the 1-hour NO2 standard be set at 50 ppb, 
with a 99th percentile form, and that the level of the annual standard 
should be set at 30 ppb. These comments, and the EPA's responses, are 
discussed below. \112\
---------------------------------------------------------------------------

    \112\ These comments also refer, for the full discussion, to an 
attached comment letter submitted during the 2010 review of the 
primary NO2 NAAQS. This reference suggests that the 
commenter believed the comments submitted as part of the 2010 review 
are still relevant in the current review, given that the 2016 
NOX ISA focused much of its assessment on studies that 
were also included in the 2008 NOX ISA. We note that, to 
the extent a separate response to those comments is required, we 
have already responded to the prior comments in the 2010 final 
decision on the primary NO2 NAAQS (75 FR 6474, February 
9, 2010; U.S. EPA, 2010).
---------------------------------------------------------------------------

    Comments asserting that the current 1-hour standard does not 
protect public health or provide any margin of safety cite the meta-
analysis by Brown (2015) to support this position, arguing that this 
meta-analysis clearly shows that the majority of individuals with 
asthma were adversely affected by a concentration of NO2 
that would meet the current 1-hour standard. To support this point, 
these comments state that Brown (2015) reported increased AR following 
1-hour exposures to 100 ppb NO2, and they point to several 
uncertainties in the individual studies (i.e., that no studies examined 
1-hour concentrations below 100 ppb, that study subjects generally had 
mild asthma rather than more severe cases of disease, and that the 
studies do not provide information about potential effects of such 
exposures on children and seniors, two groups EPA recognizes as being 
particularly at risk). These comments disagree with the weight that EPA 
placed on the lack of consistency in the individual controlled human 
exposures studies at lower concentrations, contending that the Brown 
meta-analysis has greater statistical power than the individual 
studies. These comments further disagree with EPA's citation of 
uncertainties related to lack of exposures below 100 ppb as a rationale 
for retaining the current level of the 1-hour standard, contending that 
the CAA's requirement for an adequate margin of safety is intended to 
protect the population when information is limited.
    As discussed above (Sections II.A.2, II.B.1), while the Brown meta-
analysis shows that most study participants (i.e., generally adults 
with mild asthma) experienced increased AR following resting 
NO2 exposures from 100 to 530 ppb,\113\ there are important 
limitations in the underlying studies, particularly in studies that 
evaluated NO2 exposure concentrations at or near 100 ppb. Of 
the five studies included in the meta-analysis that evaluated resting 
exposures to 100 ppb NO2, a statistically significant 
increase in AR following exposure to NO2 was only observed 
in one (U.S. EPA, 2017a, section 3.2.2.1). Of the four studies that did 
not report statistically significant increases in AR following 
exposures to 100 ppb NO2, three reported trends towards 
decreased AR (U.S. EPA, 2017a, section 3.2.2.1). Thus, individual 
controlled human exposure studies have generally not reported 
statistically significant increases in AR following resting exposures 
to NO2 concentrations at 100 ppb (U.S. EPA, 2017a, section 
3.2.2.1), indicating a greater uncertainty in the risk of such effects 
at 100 ppb.\114\ When considering this general lack of consistent, 
statistically significant results across these five individual studies, 
limitations in the broader body of evidence from controlled human 
exposure studies (i.e., uncertainty in adversity of reported responses 
and the lack of an apparent dose-response relationship), which are 
discussed above and have been considered throughout this review (e.g., 
U.S. EPA, 2017a, section 3.2.2.1), take on increased importance when 
considering the risk of adverse effects and the potential public health 
implications of exposures to 100 ppb NO2.
---------------------------------------------------------------------------

    \113\ As discussed above, the most consistent evidence for 
NO2-induced increases in AR comes from studies of resting 
exposures.
    \114\ In addition, studies that evaluated resting exposures to 
140 ppb and 200 ppb NO2 did not generally report 
statistically significant increases in AR. 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, 
though this evidence suggests a trend toward increased AR following 
NO2 exposures from 140 to 200 ppb (U.S. EPA, 2017a, 
section 3.2.2.1).
---------------------------------------------------------------------------

    In light of the above information from the Brown (2015) meta-
analysis and from the individual studies included in that meta-
analysis, the Administrator's judgment in the proposal was that while 
it is appropriate to consider the degree of protection provided by the 
current 1-hour standard against exposures to NO2 
concentrations as low as 100 ppb,\115\ emphasis should be placed on 
protecting against the potential for exposures to higher NO2 
concentrations, where individual studies generally report statistically 
significant increases in AR (i.e., at or above 250 ppb, as discussed in 
U.S. EPA, 2017a, section 3.2.2.1). The more consistent results across 
studies at such higher exposure concentrations indicate greater concern 
for the risk of an NO2-induced effect.
---------------------------------------------------------------------------

    \115\ Uncertainties in this evidence are of even greater concern 
for NO2 exposure concentrations below 100 ppb, for which 
there are no data available in these studies. On this point, the 
CASAC noted that ``the lack of a clear dose-response model based on 
available data is another source of uncertainty that makes it 
difficult to extrapolate a dose-response relationship at levels 
lower than those measured in the controlled human studies.'' (Diez 
Roux and Sheppard, 2017, pp. 7-8).
---------------------------------------------------------------------------

    To this end, based on the results of the NO2-air quality 
benchmark comparisons reported in the PA (U.S. EPA, 2017a, section 
4.2.1), the current 1-hour standard is estimated to allow virtually no 
potential for 1-hour exposures to NO2 concentrations at or 
above 200 ppb, even under worst-case conditions across a variety of 
study areas with among the highest NOX emissions in the 
United States. 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 1-hour standard limits, 
but does not eliminate, 1-hour exposures to NO2 
concentrations at or above 100 ppb (U.S. EPA, 2017a, section 4.2.1), an 
exposure concentration where uncertainties in the evidence take on 
increased importance. Despite the importance of uncertainties in the 
evidence for increased AR following exposures to NO2 
concentrations at or near 100 ppb, as summarized above, a focus on 
limiting such exposures gives weight to the results of Brown (2015) at 
100 ppb and to the possibility that other at-risk groups (e.g., people 
with more severe asthma, children, older adults) could experience more 
serious effects than reported in available studies. As such, the 
current 1-hour standard provides a margin of safety by virtually 
eliminating the potential for 1-hour exposures to NO2 
concentrations that have been consistently shown to increase AR in 
people with asthma and by limiting exposures to NO2 
concentrations that have the potential to exacerbate asthma

[[Page 17267]]

symptoms, but for which the evidence indicates greater uncertainty in 
the risk of such effects.
    While the EPA recognizes, as discussed in section I.A. above, that 
CAA section 109's requirement for a primary NAAQS to provide an 
adequate margin of safety is intended to address uncertainties 
associated with inconclusive scientific and technical information, it 
also notes that the CAA does not require a primary NAAQS to be 
established at a zero-risk level, or to protect the most sensitive 
individual, but rather at a level that avoids unacceptable risks to 
public health. See Lead Industries Association v. EPA, 647 F.2d at 
1154, 1156 n.51. This approach to considering the degree of protection 
provided by the current NAAQS is consistent with the governing case 
law. The EPA further notes that under CAA section 109, a primary 
standard must be ``requisite''--i.e., neither more nor less stringent 
than necessary--to protect public health with an adequate margin of 
safety. See Whitman v. American Trucking Associations, 531 U.S. at 465-
472, 475-76. Additionally, the selection of any particular approach to 
providing an adequate margin of safety is a policy choice left to the 
Administrator's judgment. See Lead Industries Association v. EPA, 647 
F.2d at 1161-62. As discussed above, the EPA's approach to the margin 
of safety in this review reasonably considers both the potential for 
adverse public health effects following exposures to 100 ppb 
NO2 and the uncertainties in the public health implications 
of such exposures. Thus, the EPA's approach here comports with CAA 
section 109 and the case law described in section I.A above.
    The EPA's approach to considering the degree of protection provided 
by the current NO2 NAAQS is also consistent with advice from 
the CASAC, which recognized that ``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). The CASAC additionally concluded 
that ``there is not a scientific basis for a standard lower than the 
current 1-hour standard'' (Diez Roux and Sheppard, 2017 p. 9). Thus, 
for the reasons discussed above, the EPA disagrees with comments 
claiming that the Brown (2015) meta-analysis indicates adverse effects 
at NO2 concentrations meeting the current 1-hour standard 
and with comments claiming that the Brown (2015) meta-analysis shows 
that the 1-hour standard provides no margin of safety.
    Comments advocating for a more stringent 1-hour standard further 
state that the current 98th percentile form allows too many days with 
NO2 concentrations above 100 ppb, undermining protection for 
people with asthma, including children. These comments contend that the 
EPA's rationale that the 98th percentile provides more stability than 
the 99th percentile has no substantive evidence behind it.
    In reviewing the NAAQS, the Administrator's foremost consideration 
is the adequacy of the public health protection provided by the 
combination of all of the elements of the standard, including the form. 
In particular, the EPA notes that the benchmark analysis presented in 
the PA, which informed the Administrator's proposed decision, evaluates 
the potential for NO2 exposures with air quality just 
meeting the current 1-hour standard, including the 98th percentile 
form, and that analysis found that there were no exceedances of 200 
ppb, and very few exceedances of 100 ppb (1 to 10 annually, on 
average). Thus, as described in more detail above, even under worst-
case conditions across a variety of study areas with among the highest 
NOX emissions in the U.S., the current 1-hour standard, with 
its 98th percentile form, virtually eliminates the potential for 
exposures to the NO2 concentrations that have been shown 
most consistently to increase AR in people with asthma and to which the 
Administrator gives most weight, and greatly limits the potential for 
exposures to lower NO2 concentrations with the potential to 
exacerbate symptoms in some people with asthma, but for which 
uncertainties in the evidence take on increased importance.
    In addition, the CASAC advice provides further support for the 98th 
percentile form. The CASAC accepted the protection provided by the 
current 98th percentile form, together with the other elements of the 
1-hour standard, in recommending retention of the current standard 
without revision. In doing so, it provided the following advice (Diez 
Roux and Sheppard, 2017, p. 9):

    For the 1-hour current standard, the form is based on the 98th 
percentile of daily maximum 1-hour concentrations, which corresponds 
to the 7th or 8th highest daily maximum 1-hour concentration in a 
year. This form limits but does not eliminate exposures at or above 
100 ppb NO2. A 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.

    Thus, in providing its advice to retain the existing 1-hour 
standard, without revision, the CASAC clearly considered the 
implications of the 98th percentile form of that standard.
    With regard to stability, the proposal explained that greater 
regulatory stability was one consideration supporting the selection of 
a 98th percentile form in the last review. In that review, the EPA 
established the 98th percentile form, noting ``the limited available 
information on the variability in peak NO2 concentrations 
near important sources of NO2 such as major roadways'' and 
``the recommendation from the CASAC that the potential for instability 
in the 99th percentile concentration is cause for supporting a 98th 
percentile form'' (75 FR 6493, February 9, 2010).\116\ However, in the 
proposal and in this final action, the Administrator's judgments focus 
primarily on his consideration of the public health protection provided 
by the current standards: A 1-hour standard with a level of 100 ppb and 
a 98th percentile form, and an annual average standard with a level of 
53 ppb. The degree of public health protection provided by the current 
standards is a function of the combination of all elements of these 
standards (i.e., indicator, averaging times, forms, levels). Thus, 
while judgments on stability can be a legitimate consideration, his 
decision to retain the current primary NO2 NAAQS in this 
review (see below) reflects his judgments regarding public health 
protection provided by these standards. Given this, the EPA disagrees 
with comments contending that the form of the 1-hour standard should be 
revised to the 99th percentile.\117\
---------------------------------------------------------------------------

    \116\ 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).
    \117\ These comments also note that EPA established a 99th 
percentile form when it revised the SO2 primary NAAQS in 
2010. The fact that EPA concluded that the 99th percentile was 
appropriate for one NAAQS, based on the combined elements of that 
revised standard and the evidence and information in the supporting 
record, does not mean that such a form should be used for a 
different NAAQS for a different pollutant. Rather, in reviewing each 
NAAQS, EPA makes a determination specific to the pollutant and 
standard in question, in the course of which it evaluates the public 
health protection it provides based on the combination of all the 
elements of the standard and based on the evidence and information 
in the record for that review.
---------------------------------------------------------------------------

    Comments advocating for more stringent standards also assert that 
the EPA should adopt an annual standard

[[Page 17268]]

level of 30 ppb. These comments note the strengthened evidence linking 
long-term NO2 exposures with various health effects, 
particularly asthma development, arguing that it expands the range of 
potential effects and at-risk populations. They further note the 
recognition by the EPA and the CASAC, based on its review of analyses 
in the PA, that the current 1-hour standard and annual standard 
together are estimated to maintain annual NO2 concentrations 
well below 53 ppb. These comments assert that both the EPA and the 
CASAC recognized that the annual standard was not sufficiently 
protective and, based on the degree of control associated with the 1-
hour standard, in effect used 30 ppb as the effective standard for 
annual exposure. These comments thus conclude that EPA should lower the 
level of the annual standard level to 30 ppb.
    We agree with comments that the evidence supporting associations 
between long-term NO2 exposures and a variety of effects, 
particularly the development of asthma in children, has become stronger 
in this review.\118\ While this evidence supports associations with a 
clearly adverse health outcome, given uncertainties in key studies and 
the protection provided by the 1-hour standard against long-term 
NO2 exposures, we disagree with comments that this 
strengthened evidence supports a revised annual standard with a level 
of 30 ppb. Our consideration of these factors is described below.
---------------------------------------------------------------------------

    \118\ The ISA additionally concludes that, compared to the last 
review, stronger evidence is available in this review linking 
various non-respiratory effects with long-term NO2 
exposures (see, e.g., U.S. EPA, 2016a, section 1.5.2). These include 
cardiovascular effects and diabetes, mortality, birth outcomes, and 
cancer. However, compared to the evidence linking NO2 
exposures with the development of asthma, there is greater 
uncertainty in the evidence for these non-respiratory effects. 
Therefore, in considering the public health protection provided by 
the current standards, the focus in this review is on respiratory 
effects (e.g., see U.S. EPA, 2017a, section 5.1). More specifically, 
as noted in the PA ``we consider the full body of health evidence, 
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 [i.e., 
respiratory effects]'' (U.S. EPA, 2017a, p. 3-2).
---------------------------------------------------------------------------

    As discussed in the proposal (82 FR 34792, July 26, 2017, section 
II.F.4), and in the Administrator's final decision below, uncertainties 
in studies of long-term NO2 exposures, and in the 
NO2 air quality present in the locations of those studies, 
limit their utility in identifying a specific revised annual standard 
that would provide the requisite protection. Important uncertainties in 
key U.S. and Canadian epidemiologic studies of long-term NO2 
exposures include the potential for confounding by highly correlated 
co-occurring pollutants and for exposure measurement error (see, e.g., 
sections II.A.2, II.B.1, II.B.4 of this document).
    With regard to potential confounding by co-occurring pollutants, 
the 2016 NOX ISA concludes 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 2016 NOX 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 copollutant models to address copollutant confounding, making 
it difficult to evaluate the independent effect of NO2'' 
(U.S. EPA, 2016a, p. 6-64).
    With regard to exposure measurement error, while some studies used 
well-validated estimates of NO2 exposure (U.S. EPA, 2016a, 
section 6.2.2.1), most of the key epidemiologic studies conducted in 
the U.S. or Canada, which are the studies relevant for informing 
decisions on the standard, employed exposure models ``with unknown 
validation'' or used ``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'' (U.S. EPA, 
2017a, p. 3-35). Thus, it is unclear the extent to which most of the 
key studies conducted in the U.S. or Canada provide reliable estimates 
of asthma incidence for particular NO2 concentrations that 
could be used in identifying a specific revised annual standard that 
would provide the requisite protection.
    In addition, as discussed in detail in the PA, while epidemiologic 
studies conducted in the U.S. or Canada provide evidence for 
associations with asthma-related effects in locations likely to have 
violated the current standards, they do not indicate associations of 
asthma incidence with exposures to long-term NO2 in 
locations that would have clearly met the current standards (U.S. EPA, 
2017a, section 5.1). 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. 
Had such monitors been in place, NO2 design values in these 
study areas may have been higher than indicated by the monitors that 
were in operation during study periods.
    Thus, uncertainties in studies of long-term NO2 
exposures, together with uncertainties in the NO2 air 
quality present in the study locations, limit the degree to which these 
studies can inform the identification of a specific revised annual 
standard that would provide the requisite protection. Taken together, 
these uncertainties limit what studies of long-term NO2 and 
asthma development can tell us with regard to the adequacy of the 
public health protection provided by the current NO2 
standards.
    Beyond the uncertainties discussed above, the EPA further 
recognizes that, as noted in comments, the current 1-hour standard is 
expected to provide substantial protection against long-term 
NO2 exposures. Support for considering protection provided 
by the 1-hour standard against long-term NO2 exposures comes 
from the ISA's integrated mode of action information describing the 
biological plausibility for development of asthma. 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, pp. 6-66 and 
6-64).\119\ Given this, we note that meeting the 1-hour standard with 
its level of 100 ppb is expected to maintain annual average 
NO2 concentrations well below the 53 ppb level of the 
current annual standard. With regard to this protection, the CASAC 
notes that the PA's analyses of historical data indicate that 
``attainment of the 1-hour standard corresponds with annual design 
value averages of 30 ppb NO2'' (Diez Roux and Sheppard, 
2017). While the CASAC did not endorse the degree of public health 
protection provided by the annual standard alone (Diez Roux and 
Sheppard, 2017, p. 9), based on these air quality relationships it 
concluded 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). Thus, to the degree the evidence 
supports additional protection against long-term NO2

[[Page 17269]]

exposures, beyond that provided by the current annual standard alone, 
the 1-hour standard is expected to result in substantial additional 
protection against such exposures.
---------------------------------------------------------------------------

    \119\ The ISA additionally recognizes that because the 
experimental evidence is limited, there remains some uncertainty as 
to whether long-term NO2 exposures have an independent 
effect on asthma development or whether these health effects are due 
to repeated short-term exposures, or a mixture of long-term and 
short-term exposures (see U.S. EPA, 2016a, p. 6-67).
---------------------------------------------------------------------------

    Based on the above information, when taken together, the EPA 
disagrees with comments that the level of the annual standard should be 
revised to 30 ppb. In particular, based on the uncertainties in the 
available key studies of NO2 and asthma incidence conducted 
in the U.S. or Canada, uncertainty in the NO2 concentrations 
present in locations of these key studies, and the substantial 
protection against long-term NO2 exposures that is provided 
by the current 1-hour standard, we conclude that the evidence does not 
support a revised annual standard with a level of 30 ppb.
d. Other Comments
    In addition to the comments presented above, the EPA received 
several comments related to implementation of the NO2 NAAQS, 
including various comments on AERMOD and its use in permitting, as well 
as on the historical difficulty of facilities demonstrating compliance 
with the 1-hour NO2 standard in permitting. As described in 
section I.A above, this action is being taken pursuant to CAA section 
109(d)(1) and relevant case law. Consistent with this case law, the EPA 
has not considered costs, including the costs or economic impacts 
related to permitting or other implementation concerns, in this action. 
Under CAA section 109(d)(1) the EPA has the obligation to periodically 
review the air quality criteria and the existing primary NAAQS and make 
such revisions as may be appropriate. Thus, the scope of this action is 
to evaluate whether the existing NO2 primary standards are 
requisite to protect public health with an adequate margin of safety, 
not to address concerns related to implementation of the existing 
standards. State and federal NO2 control programs such as 
those discussed in section I.B may provide an opportunity for 
permitting and other implementation concerns to be addressed.
4. Administrator's Conclusions
    Having carefully considered the public comments, as discussed 
above, and 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 concludes that the current primary 
NO2 standards are requisite to protect the public health, 
with an adequate margin of safety, and should be retained. The 
Administrator's conclusions are based on a careful consideration of the 
full body of information available in this review, giving weight to the 
assessment of the available policy-relevant scientific evidence and the 
conclusions contained in the 2016 NOX ISA; the PA's 
consideration of this evidence and of analyses comparing NO2 
air quality with health-based benchmarks; the PA's conclusions 
regarding the public health protection provided by the current primary 
NO2 NAAQS and the rationale supporting those conclusions; 
the advice and recommendations from the CASAC; the scientific and 
policy judgments and conclusions discussed in the proposal; and public 
comments on the proposed action. The basis for the Administrator's 
conclusions on the current primary NO2 standards is 
discussed further 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 described in 
detail in the 2016 NOX ISA (U.S. EPA, 2016a, chapter 5 and 
chapter 6) and summarized in the PA (U.S. EPA, 2017a, chapter 3). 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 (section II.A.2), the 
Administrator notes that most of the controlled human exposure studies 
assessed in the 2016 NOX 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 between short-term 
NO2 exposures and 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, the results of these 
newer studies are generally consistent with the epidemiologic studies 
that were available in the last review.
    With regard to respiratory effects of 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 as surrogates for exposures to the broader mixture 
of traffic-related pollutants (U.S. EPA, 2016a, table 1-1 and section 
6.2.2). Supporting evidence also includes studies indicating a 
potential role for repeated short-term NO2 exposures in the 
development of asthma (U.S. EPA, 2016a, pp. 6-64 and 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 2016 
NOX 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) (U.S. EPA, 2016a, table 1-1). As detailed 
in the 2016 NOX 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, table 1-1 and section 6.2.2). Thus, as described 
above (section II.B.1), and consistent with CASAC advice (Diez Roux and 
Sheppard, 2017), the Administrator places the greatest emphasis on the 
evidence for respiratory effects attributable to either short- or long-
term NO2 exposures, which the ISA has determined 
demonstrates a ``causal'' and a ``likely to be causal'' relationship 
with NO2 exposures, respectively.
    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 NOX 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 places 
greatest weight on 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

[[Page 17270]]

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 2016 NOX ISA, to 
directly inform his consideration of the adequacy of the public health 
protection provided by the current primary NO2 standards. 
Adopting the approach taken in the PA, which has been reviewed by the 
CASAC (Diez Roux and Sheppard, 2017, pp. 6 to 9), 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 ED visits, and asthma development in 
children. He particularly emphasizes the results of controlled human 
exposure studies, which were identified in the 2016 NOX 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 advised 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, p. 7).
    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 (Brown, 2015) and on the consistency of 
findings across individual studies. As discussed in sections II.A.2 and 
II.B.1 above, and consistent with the evidence in the last review, the 
Brown (2015) meta-analysis indicates that statistically significant 
majorities 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. In some affected 
individuals, the magnitudes of these increases were large enough to 
have potential clinical relevance (sections II.A.2.a.i and II.B.3, 
above).\120\ 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 (section II.A.2.a).\121\
---------------------------------------------------------------------------

    \120\ As discussed in section II.A.2.a.i of this final action, 
the consideration of clinical relevance by Brown (2015) is based on 
the fraction of exposed individuals who experienced a halving of the 
PD of challenge agent following NO2 exposures. This 
magnitude of change has been recognized by the ATS and the ERS 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.
    \121\ In addition, studies that evaluated resting exposures to 
140 ppb and 200 ppb NO2 did not report statistically 
significant increases in AR, though group mean responses in these 
studies suggest a trend towards such an increase.
---------------------------------------------------------------------------

    Uncertainties in this evidence, discussed in sections II.A.2.a, 
II.A.3, and II.B.1 above, include the lack of an apparent dose-response 
relationship between NO2 exposures and increased AR, which 
limits the degree to which the health risks of these exposures can be 
fully characterized, and uncertainty regarding the potential adversity 
of the reported responses. These uncertainties take on increased 
importance when considering the potential public health implications of 
exposures to lower NO2 concentrations (i.e., at and near 100 
ppb), where individual studies generally do not report NO2-
induced increases in AR.
    While the Administrator recognizes uncertainty in the extent to 
which NO2-induced increases in AR may be adverse, he also 
notes the risk that such increases could be adverse for some people 
with asthma, particularly those with more severe asthma than have 
typically been evaluated in available studies. He further notes that 
this risk cannot be fully characterized based on existing studies. 
However, given that the majority of people with asthma experienced an 
NO2-induced increase in AR in the controlled human exposure 
studies included in the Brown (2015) meta-analysis,\122\ and given the 
large size of the asthmatic population in the United States, the 
Administrator recognizes the potential for effects that are adverse to 
public health following the types of NO2 exposures evaluated 
in the studies analyzed by Brown (2015). Thus, while the Administrator 
is not able to definitively determine whether the increased AR reported 
in these studies would be adverse for a given individual, he concludes 
that, from a public health perspective, it is appropriate to provide 
protection from the risk of adversity associated with such increases. 
As noted above, this is especially true for people with more severe 
asthma and for other at-risk populations that have generally not been 
evaluated in available controlled human exposure studies of 
NO2 and AR (i.e., children and older adults).
---------------------------------------------------------------------------

    \122\ As described above (II.A.2, II.B.1, II.B.3), this is the 
case for individuals exposed while at rest.
---------------------------------------------------------------------------

    Based on information from controlled human exposure studies, which 
is discussed in more detail in sections II.A.2, II.B.1, and II.B.3 of 
this final action, the Administrator is most concerned about the 
potential for people with asthma to experience adverse respiratory 
effects following exposures to NO2 concentrations at or 
above 250 ppb. As noted above, 250 ppb is an exposure concentration 
where the potential for NO2-induced respiratory effects is 
supported both by results of the meta-analysis and by consistent 
results reported across individual studies. Therefore, in reaching 
decisions on the primary NO2 NAAQS, the Administrator 
emphasizes the importance of protecting against such exposures.
    Because results are less consistent across individual studies that 
evaluated lower exposure concentrations, the Administrator places 
greater weight on the uncertainties in the evidence as he considers the 
potential public health implications of such exposures. However, the 
Administrator also recognizes the potential for adverse 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. Available studies have generally 
evaluated people with mild asthma, while people with moderate or severe 
asthma could be more susceptible to NO2-induced increases in 
AR, and thus more likely to exhibit adverse responses following 
NO2 exposures (Brown, 2015). As discussed above, such 
effects have the potential to be adverse to public health, in light of 
the large size of the asthmatic population in the United States. 
Further, as noted above, the Administrator also recognizes the

[[Page 17271]]

potential for such effects in other at-risk populations that have 
generally not been evaluated in NO2 controlled human 
exposure studies (i.e., children and older adults). Thus, when the 
evidence and uncertainties are taken together, the Administrator judges 
that, from a public health perspective, while it is appropriate to 
emphasize the degree of protection against the potential for exposures 
at or above 250 ppb, it is also appropriate to consider the degree of 
protection provided against potential exposures to NO2 
concentrations as low as 100 ppb.
    In further considering the potential public health implications of 
the 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 (U.S. EPA, 2017a, 
section 4.2 and section 5.2), 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. presently 
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).
    To inform his consideration of the public health protection 
associated with allowable NO2 air quality under the current 
standards, the Administrator takes note of the analyses in the PA 
examining the potential for exposures to NO2 concentrations 
at or above health-based benchmarks when air quality has been adjusted 
upwards to simulate areas that would ``just meet'' the current primary 
NO2 NAAQS. Drawing on the discussion of these analyses in 
the PA (U.S. EPA, 2017a, section 5.2), the Administrator 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 \123\). 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 (i.e., about one to 10 days per 
year, on average) (U.S. EPA, 2017a, section 4.2.1). As discussed above, 
100 ppb represents an exposure concentration with the potential to 
exacerbate asthma-related respiratory effects in some people, but for 
which uncertainties in the evidence take on increased importance.
---------------------------------------------------------------------------

    \123\ As discussed above, analyses in the PA estimate no 
occurrences of 1-hour NO2 concentrations at or above 200 
ppb.
---------------------------------------------------------------------------

    Based on his consideration of these results, the Administrator 
concludes that evidence from controlled human exposure studies, 
together with analyses comparing ambient NO2 concentrations 
to health-based benchmarks, supports his overall judgment that the 
current primary NO2 NAAQS are requisite to protect public 
health with an adequate margin of safety. In particular, as discussed 
above, he is most concerned about exposures to NO2 
concentrations at and above 250 ppb, where the potential for 
NO2-induced respiratory effects is supported both by results 
of the meta-analysis and by consistent results reported across 
individual studies. With regard to this, the Administrator notes that 
NO2 air quality that just meets the current standards is 
estimated to allow no potential for exposures to such 1-hour 
NO2 concentrations. The Administrator also recognizes the 
potential for effects that are adverse to public health with exposures 
to lower NO2 concentrations, including as low as 100 ppb, 
although he places greater weight on the uncertainties in the evidence 
at these lower exposure concentrations. In light of these 
uncertainties, the Administrator judges it appropriate to limit, but 
not to eliminate, the potential for 1-hour exposures to NO2 
concentrations as low as 100 ppb. With regard to this, he notes that 
the current standard is estimated to restrict the potential for 
exposures to 1-hour NO2 concentrations at or above 100 ppb 
to a limited number of days per year.
    Thus, given that the current standards are estimated to allow no 
exposures to 1-hour NO2 concentrations at or above 250 ppb, 
and only limited potential for such exposures to concentrations as low 
as 100 ppb, the Administrator concludes that the scientific evidence, 
together with the information from analyses comparing NO2 
air quality with health-based benchmarks, supports his judgment that 
that the current 1-hour and annual NO2 primary standards, 
together, are requisite to protect public health with an adequate 
margin of safety. In reaching this conclusion, the Administrator finds 
that retaining the 1-hour NO2 standard with the level of 100 
ppb reflects a cautious approach, which is warranted given the CAA's 
requirement to for an adequate margin of safety. However, uncertainties 
in the evidence, especially those relating to the adversity of the 
effect and its likelihood to occur at exposures at or below 100 ppb, 
support the Administrator's conclusion that it is not necessary to 
eliminate the potential for exposures to 100 ppb NO2.
    The Administrator also considers what the available epidemiologic 
studies indicate with regard to the adequacy of the public health 
protection provided by the current NO2 standards, noting 
that these studies often examine more serious health effects than the 
controlled human exposure studies. In particular, he considers analyses 
of NO2 air quality in the locations, and during the time 
periods, of available U.S. or Canadian epidemiologic studies of asthma-
related hospital admissions or ED visits. Although the NO2 
epidemiologic evidence is subject to greater uncertainty than the 
controlled human exposure studies of NO2-induced changes in 
AR, as discussed in section II.B.1 above, 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, as 
discussed in greater detail in section II.B.1 above, the Administrator 
notes that epidemiologic studies provide evidence for asthma-related ED 
visits and hospital admissions with exposure to NO2 in 
locations likely to have violated the current standards over at least 
parts of study periods. In contrast, 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 the 
locations of these epidemiologic studies are based on an

[[Page 17272]]

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 evidence for 
associations with asthma-related effects in locations likely to have 
violated the current standards, supporting the decision to not set less 
stringent standards (see section II.B.3, above), they do not provide 
support for such associations in locations that would have clearly met 
those standards. As a result, these studies additionally support the 
decision to not set more stringent 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. While recognizing important uncertainties 
related to potential copollutant confounding and exposure measurement 
error (e.g., see U.S. EPA, 2017a, section 3.3.2.1), the Administrator 
considers what these studies could indicate with regard to the public 
health protection provided by the current standards. As discussed in 
section II.A.2 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 (U.S. 
EPA, 2017a, figure 2-11), when considering these studies of asthma 
development, the Administrator considers the protection provided by the 
combination of both the annual and 1-hour standards.
    In doing so, he notes that key epidemiologic studies conducted in 
the U.S. or 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, but that those studies do not indicate such 
associations in locations that would have clearly met the current 
annual and 1-hour standards (U.S. EPA, 2017a, section 5.1). As 
discussed above for epidemiologic studies of short-term NO2 
exposures, 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 the 
Administrator recognizes the public health significance of asthma 
development in children, he concludes that the available evidence 
supports his decision to not revise the current standards to be more 
stringent. In addition, while there are important uncertainties in 
these studies of long-term NO2 exposures, the Administrator 
also concludes that, in light of the requirement for an adequate margin 
of safety, reported associations in locations likely to have violated 
the current standards support his decision to not revise the current 
standards to be less stringent.
    Based on the above considerations, with their attendant 
uncertainties and limitations, and with consideration of advice from 
CASAC and public comment, the Administrator concludes that the current 
body of scientific evidence, in combination with the results of the 
quantitative analyses comparing NO2 air quality with health-
based benchmarks, supports his judgment that the current 1-hour and 
annual NO2 primary standards, together, are requisite to 
protect public health with an adequate margin of safety, and does not 
call into question any of the four basic elements of those standards 
(i.e., indicator, averaging time, level, and form). The Administrator 
considers these four elements collectively in evaluating the public 
health protection afforded by the current primary NO2 
standards, as discussed above (section II.B.1.a). Based on this 
consideration, and consistent with the CASAC advice (see, e.g., Diez 
Roux and Sheppard, 2017, pp. 6-9), the Administrator judges that each 
of the elements of the current standards should be retained. In 
particular, taking note of the more detailed discussions elsewhere in 
this document and in the proposal, he judges the following:
     NO2 continues to be the appropriate indicator 
for both the current annual and 1-hour standards, and no alternative to 
NO2 has been advanced as a more appropriate surrogate for 
ambient oxides of nitrogen (section II.B.1.a.i above; 82 FR 34792, July 
26, 2017, section II.F.1.a).
     The 1-hour and annual averaging times of the current 
standards, together, can provide protection against short- and long-
term NO2 exposures and should be retained (section 
II.B.1.a.ii above; 82 FR 34792, July 26, 2017, section II.F.1.b).
     The levels and the forms of the current short-term and 
long-term standards should be retained (sections II.B.1.a.iii and 
II.B.3 above; 82 FR 34792, July 26, 2017, section II.F.1.c).
    In considering the requirement for an adequate margin of safety, 
the Administrator notes that the determination of what constitutes an 
adequate margin of safety is expressly left to the judgment of the EPA 
Administrator. See Lead Industries Association v. EPA, 647 F.2d at 
1161-62; Mississippi, 744 F.3d at 1353. He further notes that in 
evaluating how particular standards address the requirement to provide 
an adequate margin of safety, it is appropriate to consider such 
factors as the nature and severity of the health effects, the size of 
sensitive population(s) at risk, and the kind and degree of the 
uncertainties present. Consistent with past practice and long-standing 
judicial precedent, and as described in this section, the Administrator 
takes the need for an adequate margin of safety into account as an 
integral part of his decision-making on a standard. See, e.g., NRDC v. 
EPA, 902 F. 2d 962, 973-74 (D.C. Cir. 1990).
    In reaching the conclusion that the current primary NO2 
standards, together, are requisite to protect public health with an 
adequate margin of safety, the Administrator notes the following with 
regard to effects attributable to short-term NO2 exposures:
     Meeting the current 1-hour NO2 standard is 
expected to allow virtually no potential for exposures to 
NO2 concentrations that have been shown most consistently to 
increase AR in people with asthma (i.e., at or above 250 ppb), even 
under worst-case conditions across a variety of study areas with among 
the highest NOX emissions in the U.S. Based on analyses of 
air quality adjusted upwards to just meet the current 1-hour standard, 
such NO2 concentrations were not estimated to occur, even at 
monitoring sites adjacent to some of the most heavily trafficked 
roadways (U.S. EPA, 2017a, section 4.2.1).
     Meeting the current 1-hour standard limits the potential 
for exposures to 1-hour concentrations at or above 100 ppb. Thus, the 
current standard protects against NO2 exposures with the 
potential to exacerbate symptoms in some people with asthma, but for 
which uncertainties in the evidence take on increased importance (U.S. 
EPA, 2017a, section 4.2.1).

[[Page 17273]]

     Meeting the current 1-hour standard is expected to 
maintain ambient NO2 concentrations below those likely to 
have been present in locations where key epidemiologic studies 
conducted in the U.S. or Canada have reported relatively precise and 
statistically significant associations between short-term 
NO2 and asthma-related hospitalizations (U.S. EPA, 2017a, 
section 3.2.2.2).
    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 in section 
II.B.1 above, meeting the current annual and 1-hour standards is 
expected to maintain ambient NO2 concentrations below those 
likely to have been present in locations where key U.S. and Canadian 
epidemiologic studies have reported associations between long-term 
NO2 and asthma development (U.S. EPA, 2017a, section 
3.3.2.1). 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 
the 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 (U.S. EPA, 2017a, section 2.3.3).\124\ In this regard, the 
Administrator takes note of the CASAC conclusion that ``attainment of 
the 1-hour standard also implies that the annual DV averages 30 ppb 
NO2'' and its advice that ``[g]iven uncertainties in the 
epidemiologic evidence related to lack of near road monitoring and 
potential confounding of traffic-related co-pollutants, 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). The Administrator observes 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).
---------------------------------------------------------------------------

    \124\ This air quality relationship was discussed in the PA 
(U.S. EPA, 2017a, Figure 2-11), 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).
---------------------------------------------------------------------------

    Based on the conclusions and considerations described above in this 
section, the Administrator concludes that his proposed decision, and 
the supporting rationale, analyses, and scientific assessments, remain 
valid. Accordingly, in this review, he judges that it is appropriate to 
retain the current 1-hour and annual primary NO2 standards, 
without revision. As described in sections II.B.2 and II.B.3 above, the 
Administrator notes that his decision to retain the current primary 
NO2 standards in this review, without revision, is 
consistent with the CASAC advice. In particular, the Administrator 
notes that in its letter on the draft PA, the CASAC stated that it 
``recommends retaining, and not changing the existing suite of 
standards'' (Diez Roux and Sheppard, 2017, cover letter at p. 3). The 
Administrator further observes that in addressing the 1-hour standard 
the CASAC ``advise[d] that the current 1-hour standard is protective of 
adverse effects and that there is not a scientific basis'' for a more 
stringent standard (Diez Roux and Sheppard, 2017, p. 9). With respect 
to the annual standard, the Administrator notes that the CASAC 
specifically focused its conclusions on the degree of protection 
provided by the combination of the 1-hour and annual standards, 
advising that ``the suite of the 1-hour and annual standards is 
protective against adverse effects'' (Diez Roux and Sheppard, 2017, p. 
9). In light of this advice from the CASAC, the Administrator finds it 
appropriate to focus on the degree of public health protection provided 
by the current 1-hour and annual NO2 standards together in 
reaching his decision in this review to retain the current primary 
NO2 NAAQS.
    Inherent in the Administrator's conclusions are public health 
policy judgments based on his consideration of the available scientific 
evidence and analyses. 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 weigh their associated 
uncertainties. Based on these considerations and the judgments 
identified herein, the Administrator concludes 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, children, and older adults.
    In reaching this 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 or to protect the most sensitive 
individual, but rather at a level that avoids unacceptable risks to 
public health. In this context, the Administrator's conclusion is that 
the current 1-hour and annual NO2 standards together provide 
the requisite protection and that more or less stringent standards 
would not be requisite.
    More specifically, given the increased risk of adverse effects 
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 likely to have been present in locations where 
epidemiologic studies have reported associations with asthma-related 
hospitalizations and with asthma development in children. Consistent 
with these observations, the Administrator further notes the CASAC 
conclusion, based on its consideration of the evidence, that ``there 
are notable adverse effects at levels that exceed the current [1-hour] 
standard, but not at the level of the current [1-hour] standard'' (Diez 
Roux and Sheppard, 2017, p. 9) and its recommendation to retain, ``and 
not change, the existing suite of standards'' (i.e., both 1-hour and 
annual) (Diez Roux and Sheppard, 2017, cover letter at p. 3). For these 
reasons, the Administrator concludes 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 requisite to

[[Page 17274]]

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, based on the 
scientific information discussed throughout this document (e.g., 
sections II.A.2, II.A.3, II.B.1, II.B.3), including uncertainties 
inherent in that information, 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, the CASAC 
advised that ``there is not a scientific basis for a standard lower 
than the current 1-hour standard'' (Diez Roux and Sheppard, 2017, p. 
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 
well below the level of the annual standard, and observing that there 
is insufficient scientific evidence to make a scientific judgment that 
adverse effects occur at those lower concentrations (Diez Roux and 
Sheppard, 2017, cover letter p. 3).
    Based on all of the above considerations, and consistent with the 
CASAC advice, the Administrator concludes that it is appropriate to 
retain the current standards, without revision, in this review.

C. Decision on the Primary Standards

    For the reasons discussed above, and taking into account 
information and assessments presented in the ISA and PA, the advice and 
recommendations from CASAC, and consideration of public comments, the 
Administrator concludes that the current primary 1-hour and annual 
NO2 standards together are requisite to protect public 
health with an adequate margin of safety, including the health of at-
risk populations, and is retaining the standards without revision.

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.

A. Executive Order 12866: Regulatory Planning and Review and Executive 
Order 13563: Improving Regulation and Regulatory Review

    This action is not a significant regulatory action and was, 
therefore, not submitted to the Office of Management and Budget (OMB) 
for review.

B. Executive Order 13771: Reducing Regulations and Controlling 
Regulatory Costs

    This action is not an Executive Order 13771 regulatory action 
because this action is not significant under Executive Order 12866.

C. 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 revising or retaining NAAQS under section 109 of the 
CAA. This action retains, without any revisions, the current primary 
NAAQS for oxides of nitrogen.

D. 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 retains, 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, 175 
F.3d at 1044-45 (NAAQS do not have significant impacts upon small 
entities because NAAQS themselves impose no regulations upon small 
entities).

E. 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.

F. 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.

G. Executive Order 13175: Consultation and Coordination With Indian 
Tribal Governments

    This action does not have tribal implications, as specified in 
Executive Order 13175. It does not have a substantial direct effect on 
one or more Indian tribes. This action does not change existing 
regulations; it retains, without revision, the current primary NAAQS 
for oxides of nitrogen. The primary NAAQS protect public health, 
including the health of at-risk or sensitive groups, with an adequate 
margin of safety. Thus, Executive Order 13175 does not apply to this 
action.

H. 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. We 
note, however, that the standards retained with this action provide 
protection for children and other at-risk populations against adverse 
health effects. The health effects evidence and risk assessment 
information for this action, which focuses on children and other at-
risk populations, is summarized in section II.A.2 and II.A.3 above and 
described in the ISA and PA, copies of which are in the public docket 
for this action.

I. Executive Order 13211: Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution or Use

    This action is not subject to Executive Order 13211, because it is 
not a significant regulatory action under Executive Order 12866.

J. National Technology Transfer and Advancement Act (NTTAA)

    This action does not involve technical standards.

K. 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). This action is 
to retain without revision the existing primary NAAQS for oxides of 
nitrogen.
    The NAAQS decisions are based on an explicit and comprehensive 
assessment of the current scientific evidence and associated exposure/
risk

[[Page 17275]]

analyses. More specifically, the EPA expressly considers the available 
information regarding health effects among at-risk populations, 
including that available for low-income populations and minority 
populations, in decisions on the primary (health based) NAAQS. Where 
low-income populations or minority populations are among the at-risk 
populations, the decision on the standard is based on providing 
protection for these and other at-risk populations and lifestages. 
Where such populations are not identified as at-risk populations, NAAQS 
that are established to provide protection to the at-risk populations 
would also be expected to provide protection to all other populations, 
including low-income populations and minority populations.
    As discussed in sections II.A.2 and II.B.1 above, and in sections 
II.F and II.C of the proposal, the EPA expressly considered the 
available information regarding health effects among at-risk 
populations in reaching the decision that the existing primary (health-
based) standards for oxides of nitrogen are requisite. The ISA and PA 
for this review, which include identification of populations at risk 
from NO2 health effects, are available in the docket, EPA-
HQ-OAR-2013-0146. Based on consideration of this information and the 
full evidence base, quantitative exposure/risk analyses, advice from 
the CASAC and consideration of public comments, the Administrator 
concludes that the existing standards protect public health, including 
the health of at-risk or sensitive groups, with an adequate margin of 
safety (as discussed in section II.B.4 above).

L. 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).

M. Congressional Review Act (CRA)

    The EPA will submit a rule report to each House of the Congress and 
to the Comptroller General of the United States. This action is not a 
``major rule'' as defined by 5 U.S.C. 804(2).

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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: April 6, 2018.
E. Scott Pruitt,
Administrator.
[FR Doc. 2018-07741 Filed 4-17-18; 8:45 am]
 BILLING CODE 6560-50-P