[Federal Register Volume 76, Number 29 (Friday, February 11, 2011)]
[Proposed Rules]
[Pages 8158-8220]
[FR Doc No: 2011-2404]

Vol. 76

Friday,

No. 29

February 11, 2011

Part VI

Environmental Protection Agency

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40 CFR Parts 50, 53 and 58

National Ambient Air Quality Standards for Carbon Monoxide; Proposed
Rule

Federal Register / Vol. 76, No. 29 / Friday, February 11, 2011 /
Proposed Rules

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 50, 53 and 58

[EPA-HQ-OAR-2008-0015; FRL-9261-4; 2060-AI43]

National Ambient Air Quality Standards for Carbon Monoxide

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: Based on its review of the air quality criteria and the
national ambient air quality standards (NAAQS) for carbon monoxide
(CO), EPA is proposing to retain the current standards. EPA is also
proposing changes to the ambient air monitoring requirements for CO
including those related to network design.

DATES: Comments must be received on or before April 12, 2011.
    Public Hearings: If, by February 18, 2011, EPA receives a request
from a member of the public to speak at a public hearing concerning the
proposed regulation, we will hold a public hearing on February 28, 2011
in Arlington, Virginia.

ADDRESSES: Submit your comments, identified by Docket ID No. EPA-HQ-
OAR-2008-0015 by one of the following methods:
     http://www.regulations.gov: Follow the on-line
instructions for submitting comments.
     E-mail<EMAIL_ADDRESS>     Fax:<PHONE_NUMBER>.
     Mail: Docket No. EPA-HQ-OAR-2008-0015, Environmental
Protection Agency, Mail code 6102T, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. Please include a total of two copies.
     Hand Delivery: Docket No. EPA-HQ-OAR-2008-0015,
Environmental Protection Agency, EPA West, Room 3334, 1301 Constitution
Ave., NW., Washington, DC. Such deliveries are only accepted during the
Docket's normal hours of operation, and special arrangements should be
made for deliveries of boxed information.
    Instructions: Direct your comments to Docket ID No. EPA-HQ-OAR-
2008-0015. EPA's policy is that all comments received will be included
in the public docket without change and may be made available online at
http://www.regulations.gov, including any personal information
provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through http://www.regulations.gov or e-mail. The http://www.regulations.gov Web site
is an ``anonymous access'' system, which means EPA will not know your
identity or contact information unless you provide it in the body of
your comment. If you send an e-mail comment directly to EPA without
going through www.regulations.gov your e-mail address will be
automatically captured and included as part of the comment that is
placed in the public docket and made available on the Internet. If you
submit an electronic comment, EPA recommends that you include your name
and other contact information in the body of your comment and with any
disk or CD-ROM you submit. If EPA cannot read your comment due to
technical difficulties and cannot contact you for clarification, EPA
may not be able to consider your comment. Electronic files should avoid
the use of special characters, any form of encryption, and be free of
any defects or viruses. For additional information about EPA's public
docket visit the EPA Docket Center homepage at http://www.epa.gov/epahome/dockets.htm.
    Public Hearing. If a public hearing is held, it will be held at the
U.S. Environmental Protection Agency Conference Center, First Floor
Conference Center South, One Potomac Yard, 2777 S. Crystal Drive,
Arlington, VA 22202. All visitors will need to go through security and
present a valid photo identification, such as a driver's license. To
request a public hearing or information pertaining to a public hearing,
contact Ms. Jan King, Health and Environmental Impacts Division, Office
of Air Quality Planning and Standards (C504-02), Environmental
Protection Agency, Research Triangle Park, North Carolina 27711;
telephone number (919) 541- 5665; fax number<PHONE_NUMBER>; e-mail
address<EMAIL_ADDRESS>See the SUPPLEMENTARY INFORMATION for
further information about a possible public hearing.
    Docket: All documents in the docket are listed in the http://www.regulations.gov index. 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, will be publicly available only in hard copy.
Publicly available docket materials are available either electronically
in http://www.regulations.gov or in hard copy at the Air and Radiation
Docket and Information Center, EPA/DC, EPA West, 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 and
Information Center is<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Dr. Deirdre Murphy, 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:<PHONE_NUMBER>; fax: 919-
541-0237; e-mail<EMAIL_ADDRESS>For further information
specifically with regard to section IV of this notice, contact Mr.
Nealson Watkins, Air Quality Analysis Division, Office of Air Quality
Planning and Standards, U.S. Environmental Protection Agency, Mail code
C304-06, Research Triangle Park, NC 27711; telephone:<PHONE_NUMBER>;
fax:<PHONE_NUMBER>; e-mail<EMAIL_ADDRESS>To request a public
hearing or information pertaining to a public hearing, contact Ms. Jan
King, Health and Environmental Impacts Division, Office of Air Quality
Planning and Standards (C504-02), Environmental Protection Agency,
Research Triangle Park, North Carolina 27711; telephone number (919)
541- 5665; fax number<PHONE_NUMBER>; e-mail address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

General Information

What should I consider as I prepare my comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through
http://www.regulations.gov or e-mail. Clearly mark the part or all of
the information that you claim to be CBI. For CBI information in a disk
or CD ROM that you mail to EPA, mark the outside of the disk or CD ROM
as CBI and then identify electronically within the disk or CD ROM the
specific information that is claimed as CBI. In addition to one
complete version of the comment that includes information claimed as
CBI, a copy of the comment that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2.
    2. Tips for Preparing Your Comments. When submitting comments,
remember to:

     Identify the rulemaking by docket number and other
identifying information (subject heading, Federal Register date and
page number).
     Follow directions--the agency may ask you to respond to
specific questions or organize comments by referencing a Code of
Federal Regulations (CFR) part or section number.
     Explain why you agree or disagree, suggest alternatives,
and substitute language for your requested changes.
     Describe any assumptions and provide any technical
information and/or data that you used.
     Provide specific examples to illustrate your concerns, and
suggest alternatives.
     Explain your views as clearly as possible, avoiding the
use of profanity or personal threats.
     Make sure to submit your comments by the comment period
deadline identified.

Availability of Related Information

    A number of the documents that are relevant to this rulemaking are
available through EPA's Office of Air Quality Planning and Standards
(OAQPS) Technology Transfer Network (TTN) Web site at http://www.epa.gov/ttn/naaqs/standards/co/s_co_index.html. These documents
include the Plan for Review of the National Ambient Air Quality
Standards for Carbon Monoxide (Integrated Review Plan or IRP, USEPA,
2008), available at http://www.epa.gov/ttn/naaqs/standards/co/s_co_cr_pd.html, the Integrated Science Assessment for Carbon Monoxide
(USEPA, 2010a), available at http://www.epa.gov/ttn/naaqs/standards/co/s_co_cr_isa.html, the Quantitative Risk and Exposure Assessment for
Carbon Monoxide--Amended (USEPA, 2010b), available at http://www.epa.gov/ttn/naaqs/standards/co/s_co_cr_rea.html, and the Policy
Assessment for the Review of the Carbon Monoxide National Ambient Air
Quality Standards (USEPA, 2010c), available at http://www.epa.gov/ttn/naaqs/standards/co/s_co_cr_pa.html. These and other related
documents are also available for inspection and copying in the EPA
docket identified above.

How can I find information about a possible public hearing?

    To request a public hearing or information pertaining to a public
hearing on this document, contact Ms. Jan King, Health and
Environmental Impacts Division, Office of Air Quality Planning and
Standards (C504-02), Environmental Protection Agency, Research Triangle
Park, North Carolina 27711; telephone number (919) 541- 5665; fax
number<PHONE_NUMBER>; e-mail address<EMAIL_ADDRESS>If a request
for a public hearing is received by February 18, 2011, information
about the hearing will be posted prior to the hearing on EPA's Web site
for carbon monoxide regulatory actions at http://www.epa.gov/airquality/urbanair/co/.

Table of Contents

    The following topics are discussed in this preamble:
I. Background
    A. Legislative Requirements
    B. Related Carbon Monoxide Control Programs
    C. Review of the Air Quality Criteria and Standards for Carbon
Monoxide
II. Rationale for Proposed Decisions on the Primary Standards
    A. Air Quality Information
    1. Anthropogenic Sources and Emissions of Carbon Monoxide
    2. Ambient Concentrations
    B. Health Effects Information
    1. Carboxyhemoglobin as Biomarker and Mechanism of Toxicity
    2. Nature of Effects
    3. At-Risk Populations
    4. Potential Impacts on Public Health
    C. Human Exposure and Dose Assessment
    1. Summary of Design Aspects
    2. Key Limitations and Uncertainties
    D. Conclusions on Adequacy of the Current Standards
    1. Approach
    2. Evidence-Based and Exposure/Dose-Based Considerations in the
Policy Assessment
    3. CASAC Advice
    4. Administrator's Proposed Conclusions Concerning Adequacy
    E. Summary of Proposed Decisions on Primary Standards
III. Consideration of a Secondary Standard
    A. Background and Considerations in Previous Reviews
    B. Evidence-Based Considerations in the Policy Assessment
    C. CASAC Advice
    D. Administrator's Proposed Conclusions Concerning a Secondary
Standard
IV. Proposed Amendments to Ambient Monitoring Requirements
    A. Monitoring Methods
    1. Proposed Changes to Part 50, Appendix C
    2. Proposed Changes to Part 53
    3. Implications for Air Monitoring Networks
    B. Network Design
    1. Background
    2. On-Road Mobile Sources
    3. Near-Road Environment
    4. Urban Downtown Areas and Urban Street Canyons
    5. Meteorological and Topographical Influences
    6. Proposed Changes
    7. Microscale Carbon Monoxide Monitor Siting Criteria
V. Statutory and Executive Order Reviews
    A. Executive Order 12866: Regulatory Planning and Review
    B. Paperwork Reduction Act
    C. Regulatory Flexibility Act
    D. Unfunded Mandates Reform Act
    E. Executive Order 13132: Federalism
    F. Executive Order 13175: Consultation and Coordination with
Indian Tribal Governments
    G. Executive Order 13045: Protection of Children from
Environmental Health and Safety Risks
    H. Executive Order 13211: Actions that Significantly Affect
Energy Supply, Distribution or Use
    I. National Technology Transfer and Advancement Act
    J. Executive Order 12898: Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations References

I. Background

A. Legislative Requirements

    Two sections of the Clean Air Act (CAA) govern the establishment
and revision of the NAAQS. Section 108 (42 U.S.C. 7408) directs the
Administrator to identify and list ``air pollutant[s]'' that in her
``judgment, cause or contribute to air pollution which may reasonably
be anticipated to endanger public health or welfare'' and satisfy two
other criteria, including ``whose presence * * * in the ambient air
results from numerous or diverse mobile or stationary sources'' and to
issue air quality criteria for those that are listed. 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 * * * .''
    Section 109 (42 U.S.C. 7409) directs the Administrator to propose
and promulgate ``primary'' and ``secondary'' NAAQS for pollutants for
which air quality criteria are issued. Section 109(b)(1) defines a
primary standard as one ``the attainment and maintenance of which in
the judgment of the Administrator, based on such criteria and allowing
an adequate margin of safety, are requisite to protect the public
health.'' \1\ A secondary standard, as defined in section 109(b)(2),
must ``specify a level of air quality the attainment and maintenance of
which, in the judgment of the Administrator, based on such criteria, is
requisite to protect the public welfare from any known or anticipated
adverse effects

associated with the presence of such air pollutant in the ambient
air.'' \2\
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    \1\ The legislative history of section 109 indicates that a
primary standard is to be set at ``the maximum permissible ambient
air level * * * which will protect the health of any [sensitive]
group of the population,'' and that for this purpose ``reference
should be made to a representative sample of persons comprising the
sensitive group rather than to a single person in such a group'' [S.
Rep. No. 91-1196, 91st Cong., 2d Sess. 10 (1970)].
    \2\ Welfare effects as defined in section 302(h) (42 U.S.C.
7602(h)) 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 include 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. Lead Industries Association v. EPA, 647 F.2d 1130, 1154 (DC
Cir 1980), cert. denied, 449 U.S. 1042 (1980); American Petroleum
Institute v. Costle, 665 F.2d 1176, 1186 (DC Cir. 1981), cert. denied,
455 U.S. 1034 (1982). 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 include 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 pollution 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 or at background concentration
levels, see Lead Industries Association v. EPA, 647 F.2d at 1156 n. 51,
but rather at a level that reduces risk sufficiently so as to protect
public health with an adequate margin of safety.
    In addressing the requirement for an adequate margin of safety, EPA
considers such factors as the nature and severity of the health effects
involved, the size of the population(s) at risk, 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. Lead
Industries Association v. EPA, 647 F.2d at 1161-62; Whitman v. American
Trucking Associations, 531 U.S. 457, 495 (2001).
    In setting standards that are ``requisite'' to protect public
health and welfare, as provided in section 109(b), EPA's task is to
establish standards that are neither more nor less stringent than
necessary for these purposes. Whitman v. American Trucking
Associations, 531 U.S. 457, 473. In establishing ``requisite'' primary
and secondary standards, EPA may not consider the costs of implementing
the standards. Id. at 471.
    Section 109(d)(1) of the CAA requires that ``[n]ot 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. * *
*'' This independent review function is performed by the Clean Air
Scientific Advisory Committee (CASAC).

B. Related Carbon Monoxide Control Programs

    States are primarily responsible for ensuring attainment and
maintenance of ambient air quality standards once EPA has established
them. Under section 110 of the Act, and related provisions, States are
to submit, for EPA approval, State implementation plans (SIPs) that
provide for the attainment and maintenance of such standards through
control programs directed to sources of the pollutants involved. The
States, in conjunction with EPA, also administer the prevention of
significant deterioration program. See CAA sections 160-169. In
addition, Federal programs provide for nationwide reductions in
emissions of these and other air pollutants through the Federal motor
vehicle and motor vehicle fuel control program under title II of the
Act, (CAA sections 202-250) which involves controls for emissions from
moving sources and controls for the fuels used by these sources; new
source performance standards under section 111; and title IV of the Act
(CAA sections 402-416), which specifically provides for major
reductions in CO emissions.

C. Review of the Air Quality Criteria and Standards for Carbon Monoxide

    EPA initially established NAAQS for CO on April 30, 1971. The
primary standards were established to protect against the occurrence of
carboxyhemoglobin levels in human blood associated with health effects
of concern. The standards were set at 9 parts per million (ppm), as an
8-hour average and 35 ppm, as a 1-hour average, neither to be exceeded
more than once per year (36 FR 8186). In the 1971 decision, the
Administrator judged that attainment of these standards would provide
the requisite protection of public health with an adequate margin of
safety and would also provide requisite protection against known and
anticipated adverse effects on public welfare, and accordingly set the
secondary (welfare-based) standards identical to the primary (health-
based) standards.
    In 1985, EPA concluded its first periodic review of the criteria
and standards for CO (50 FR 37484). In that review, EPA updated the
scientific criteria upon which the initial CO standards were based
through the publication of the 1979 Air Quality Criteria Document for
Carbon Monoxide (AQCD; USEPA, 1979a) and prepared a Staff Paper (USEPA,
1979b), which, along with the 1979 AQCD, served as the basis for the
development of the notice of proposed rulemaking which was published on
August 18, 1980 (45 FR 55066). Delays due to uncertainties regarding
the scientific basis for the final decision resulted in EPA's
announcing a second public comment period (47 FR 26407). Following
substantial reexamination of the scientific data, EPA prepared an
Addendum to the 1979 AQCD (USEPA, 1984a) and an updated Staff Paper
(USEPA, 1984b). Following review by CASAC (Lippmann, 1984), EPA
announced its decision not to revise the existing primary standard and
to revoke the secondary standard for CO on September 13, 1985, due to a
lack of evidence of effects on public welfare at ambient concentrations
(50 FR 37484).
    On August 1, 1994, EPA concluded its second periodic review of the
criteria and standards for CO by deciding that revisions to the CO
NAAQS were not warranted at that time (59 FR 38906). This decision
reflected EPA's review of relevant scientific information assembled
since the last review, as contained in the 1991 AQCD (USEPA, 1991) and
the 1992 Staff Paper (USEPA, 1992). Thus, the primary standards were
retained at 9 ppm with an 8-hour averaging time, and 35 ppm with a 1-
hour averaging time, neither to be exceeded more than once per year (59
FR 38906).
    EPA initiated the next periodic review in 1997 and the final 2000
AQCD (U.S. EPA, 2000) was released in August 2000. After release of the
AQCD, Congress requested that the National Research Council (NRC)
review the

impact of meteorology and topography on ambient CO concentrations in
high altitude and extreme cold regions of the U.S. The NRC convened the
Committee on Carbon Monoxide Episodes in Meteorological and
Topographical Problem Areas, which focused on Fairbanks, Alaska as a
case-study.
    A final report, ``Managing Carbon Monoxide Pollution in
Meteorological and Topographical Problem Areas,'' was published in 2003
(NRC, 2003) and offered a wide range of recommendations regarding
management of CO air pollution, cold start emissions standards,
oxygenated fuels, and CO monitoring. Following completion of the NRC
report, EPA did not conduct rulemaking to complete the review.
    On September 13, 2007, EPA issued a call for information from the
public (72 FR 52369) requesting the submission of recent scientific
information on specified topics. A workshop was held on January 28-29,
2008 (73 FR 2490) to discuss policy-relevant scientific and technical
information to inform EPA's planning for the CO NAAQS review. Following
the workshop, a draft Integrated Review Plan (IRP) (USEPA, 2008a) was
made available in March 2008 for public comment and was discussed by
the CASAC via a publicly accessible teleconference consultation on
April 8, 2008 (73 FR 12998; Henderson, 2008). EPA made the final IRP
available in August 2008 (USEPA, 2008b).
    In preparing the Integrated Science Assessment for Carbon Monoxide
(ISA or Integrated Science Assessment), EPA held an authors'
teleconference in November 2008 with invited scientific experts to
discuss preliminary draft materials prepared as part of the ongoing
development of the CO ISA and its supplementary annexes. The first
draft ISA (USEPA, 2009a) was made available for public review on March
12, 2009 (74 FR 10734) and reviewed by CASAC at a meeting held on May
12-13, 2009 (74 FR 15265). A second draft ISA (USEPA, 2009b) was
released for CASAC and public review on September 23, 2009 (74 FR
48536), and it was reviewed by CASAC at a meeting held on November 16-
17, 2009 (74 FR 54042). The final ISA was released in January 2010
(USEPA, 2010a).
    In May 2009, OAQPS released a draft planning document, the draft
Scope and Methods Plan (USEPA, 2009c), for consultation with CASAC and
public review at the CASAC meeting held on May 12-13, 2009. Taking into
consideration comments on the draft Plan from CASAC (Brain, 2009) and
the public, OAQPS staff developed and released for CASAC review and
public comment a first draft Risk and Exposure Assessment (REA) (USEPA,
2009d), which was reviewed at the CASAC meeting held on November 16-17,
2009. Subsequent to that meeting and taking into consideration comments
from CASAC (Brain and Samet, 2010a) and public comments on the first
draft REA, a second draft REA (USEPA, 2010d) was released for CASAC
review and public comment in February 2010, and reviewed at a CASAC
meeting held on March 22-23, 2010. Drawing from information in the
final CO ISA and the second draft REA, EPA released a draft Policy
Assessment (PA) (USEPA, 2010e) in early March, 2010 for CASAC review
and public comment at the same meeting. Taking into consideration
comments on the second draft REA and the draft PA from CASAC (Brain and
Samet, 2010b, 2010c) and the public, staff completed the quantitative
assessments which are presented in the final REA (USEPA, 2010b). Staff
additionally took into consideration those comments and the final REA
analyses in completing the final Policy Assessment (USEPA, 2010c) which
was released in October, 2010.
    The schedule for completion of this review is governed by a court
order resolving a lawsuit filed in March 2003 by a group of plaintiffs
who alleged that EPA had failed to perform its mandatory duty, under
section 109(d)(1), to complete a review of the CO NAAQS within the
period provided by statute. The court order that governs this review,
entered by the court on November 14, 2008 and amended on August 30,
2010, provides that EPA will sign, for publication, notices of proposed
and final rulemaking concerning its review of the CO NAAQS no later
than January 28, 2011 and August 12, 2011, respectively.
    This action presents the Administrator's proposed decisions on the
current CO standards. Throughout this preamble a number of conclusions,
findings, and determinations proposed by the Administrator are noted.
Although they identify the reasoning that supports this proposal, they
are not intended to be final or conclusive in nature. The EPA invites
general, specific, and technical comments on all issues involved with
this proposal, including all such proposed judgments, conclusions,
findings, and determinations.

II. Rationale for Proposed Decisions on the Primary Standards

    This section presents the rationale for the Administrator's
proposed decision to retain the existing CO primary standards.\3\ As
discussed more fully below, this rationale is based on a thorough
review, in the Integrated Science Assessment, of the latest scientific
information, published through mid-2009, on human health effects
associated with the presence of CO in the ambient air. This proposal
also takes into account: (1) Staff assessments of the most policy-
relevant information in the ISA and staff analyses of air quality,
human exposure and health risks presented in the REA and the Policy
Assessment, upon which staff conclusions regarding appropriate
considerations in this review are based; (2) CASAC advice and
recommendations, as reflected in discussions of drafts of the ISA, REA
and PA at public meetings, in separate written comments, and in CASAC's
letters to the Administrator; and (3) public comments received during
the development of these documents, either in connection with CASAC
meetings or separately.
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    \3\ As explained below in section IV.A, EPA is proposing to
repromulgate the Federal reference method for CO, as set forth in
Appendix C of 40 CFR part 50. Consistent with EPA's proposed
decision to retain the standards, the recodification clarifies and
updates the text of the FRM, but does not make substantive changes
to it.
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    In presenting the rationale and its foundations, this section
begins with a summary of current air quality information in section
II.A. Section II.B summarizes the body of evidence supporting this
rationale, including key health endpoints associated with exposure to
ambient CO. This rationale also draws upon the results of the
quantitative exposure and risk assessments, discussed below in section
II.C. Evidence- and exposure/dose-based considerations that form the
basis for the Administrator's proposed decisions on the adequacy of the
current standard are discussed in section II.D.2.a and II.D.2.b,
respectively. CASAC advice is summarized in section II.D.3. The
Administrator's proposed conclusions are presented in section II.D.4.

A. Air Quality Information

    This section provides a general overview of the current air quality
conditions to provide context for this consideration of the current
standards for carbon monoxide. A more comprehensive discussion of air
quality information is provided in the ISA (ISA, sections 3.2 and 3.4)
and summarized in the Policy Assessment, and a more detailed discussion
of aspects particularly relevant to the exposure assessment is provided
in the REA (REA, chapter 3).

1. Anthropogenic Sources and Emissions of Carbon Monoxide
    Carbon monoxide in ambient air is formed primarily by the
incomplete combustion of carbon-containing fuels and by photochemical
reactions in the atmosphere. As a result of the combustion conditions,
CO emissions from large fossil-fueled power plants are typically very
low because optimized fuel consumption conditions make boiler
combustion highly efficient. In contrast, internal combustion engines
used in many mobile sources have widely varying operating conditions.
Therefore, higher and more varying CO formation results from the
operation of these mobile sources (ISA, section 3.2). As with previous
reviews of the CO NAAQS, mobile sources continue to be a significant
source sector for CO in ambient air, as indicated by national emissions
estimates from on-road vehicles, which accounted for approximately half
of the total CO emissions by individual source sectors in 2002 (ISA,
Figure 3-1).\4\ National-scale anthropogenic CO emissions have
decreased by approximately 45% between 1990 and 2005, with nearly all
of this national-scale reduction coming from reductions in on-road
vehicle emissions (ISA, Figure 3-2; PA, Figure 1-1; 2005 NEI \5\). The
role of mobile source emissions is evident in the spatial and temporal
patterns of ambient CO concentrations, which are heavily influenced by
the patterns associated with mobile source emissions (ISA, chapter 3).
In some metropolitan areas of the U.S., due to their greater motor
vehicle density relative to rural areas, on-road mobile source
contribution to all ambient CO emissions was estimated to be as high as
approximately 75%, based on the 2002 National Emissions Inventory (ISA,
p. 3-2). However, the mobile source contribution can vary widely in
specific areas. As an example, 2002 NEI estimates of on-road mobile
source emissions in urban Denver County, Colorado are about 74% of
total CO emissions and emissions from all mobile sources (on-road and
non-road combined) are estimated to contribute about 98% (ISA, section
3.2.1). In contrast, 2002 NEI estimates of on-road CO emissions were
just 20% of the total for rural Garfield County, Colorado\6\ (ISA,
chapter 3, Figure 3-6).
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    \4\ EPA compiles CO emissions estimates for the U.S. in the
National Emissions Inventory (NEI). Estimates come from various
sources and different data sources use different data collection
methods, most of which are based on engineering calculations and
estimates rather than measurements. Although these estimates are
generated using well-established approaches, uncertainties are
inherent in the emission factors and models used to represent
sources for which emissions have not been directly measured.
Uncertainties vary by source category, season and region (ISA,
section 3.2.1). At the time of the ISA development, the 2002 NEI was
providing the most recent publicly available CO emissions estimates
for the U.S. that meet EPA's data quality assurance objectives. Such
estimates are now available from the 2005 NEI.
    \5\ The emissions trends information in this statement is drawn
from recently available 2005 National Emissions Inventory estimates
(http://www.epa.gov/ttn/chief/net/2005inventory.html, Tier
Summaries) and 1990 and other estimates, available at http://www.epa.gov/ttn/chief/net/critsummary.html Figure 3-2 from the ISA
provides estimates through 2002.
    \6\ The 2002 National Emissions Inventory estimate for on-road
emissions in Garfield County is 20,000 tons, and the total emissions
from all sources is estimated to be 98,831 (99K) tons. Thus, in this
example the on-road vehicles accounts for 20.2% of the total
emissions (ISA, section 3, figure 3-6). In contrast, the 2002 Denver
County on-road emissions account for 74% of the total for the county
which is estimated at approximately 180,000 tons.
---------------------------------------------------------------------------

2. Ambient Concentrations
    As described in section II.A.1 above, mobile source emissions are
major contributors to CO emissions in urban areas, with corresponding
influence on ambient CO concentrations and associated concentration
gradients, with highest ambient concentrations occurring on or nearest
roadways, particularly highly travelled roadways, and lowest
concentrations in more distant locations (ISA, section <IP_ADDRESS>; REA,
section 3.1.3). For example, as described in the ISA CO concentrations
measured within 20 meters of an interstate highway can range from 2 to
10 times greater than CO concentrations measured as far as 300 meters
from a major road, possibly influenced by wind direction and on-road
vehicle density (ISA, section <IP_ADDRESS>, Figures 3-29 and 3-30; Zhu et
al., 2002; Baldauf et al., 2008a,b). Additionally, the role of motor
vehicles in influencing ambient concentrations contributes to the
occurrence of diurnal variation in concentrations reflecting rush hour
patterns (ISA, <IP_ADDRESS>; REA, p. 3-8). The influence of motor vehicle
emissions on ambient concentrations contributes to the important role
of in-vehicle microenvironments in influencing short-term ambient CO
exposures, as described in more detail in the REA and summarized in
sections II.C.1 and II.D.2 below.
    In 2009, approximately 350 ambient monitoring stations across the
U.S. reported continuous hourly averages of CO concentrations to EPA's
Air Quality System.\7\ For the most recent period for which air quality
status relative to the CO NAAQS has been analyzed (2009), all areas of
the U.S. meet both CO NAAQS.\8\ As of September 27, 2010, there are no
areas designated as nonattainment for the CO NAAQS (75 FR 59090). Since
2005, one area (Jefferson County, Alabama) has failed to meet the 8-
hour standard during some periods. Large CO emissions sources in this
area are associated with an integrated iron and steel facility. As
described in section 1.3.3 of the Policy Assessment, 2009
concentrations of CO at most currently operating monitors are well
below the current standards, with just a few locations having
concentrations near the controlling 8-hour standard of 9 ppm as a
second maximum 8-hour average.\9\ Of the counties with monitoring sites
in 2009, sites in 3 counties reported second maximum 8-hour average
concentrations at or above 6.4 ppm (PA, Figure 1-2).
---------------------------------------------------------------------------

    \7\ http://www.epa.gov/ttn/airs/airsaqs/.
    \8\ The air quality status in areas monitored relative to the CO
NAAQS is provided at http://www.epa.gov/air/airtrends/values.html.
    \9\ As the form of the CO 8-hour standard is not-to-be-exceeded
more than once per year, the second highest 8-hour average in a year
is the design value for this standard. Based on the current rounding
convention, the standard is met if the CO concentrations over a year
result in a design value at or below 9.4 ppm. Additional information
is available at http://www.epa.gov/airtrends/values.html.
---------------------------------------------------------------------------

    The current levels of ambient CO across the U.S. reflect the steady
declines in ambient concentrations that have occurred over the past
several years. Both the second highest 1-hour and 8-hour concentrations
have significantly declined since the last review. At the set of sites
across the U.S. that have been continuously monitored since 1990 the
average second highest 8-hour and 1-hour concentrations have declined
by nearly 70% (PA, section 1.3.3).

B. Health Effects Information

1. Carboxyhemoglobin as Biomarker and Mechanism of Toxicity
    As discussed in the Integrated Science Assessment, in this review,
as in the past (e.g., USEPA, 2000; USEPA, 1991), the best characterized
mechanism of action of CO is tissue hypoxia caused by binding of CO to
hemoglobin to form carboxyhemoglobin (COHb). Accordingly, COHb level in
blood continues to be well recognized as an important internal dose
metric and the one most commonly used in evaluating CO exposure and the
potential for health effects (ISA, p. 2-4, sections 4.1, 4.2, 5.1.1;
1991 AQCD, 2000 AQCD, 2010 ISA).
    Increasing levels of COHb with subsequent decrease in oxygen
availability for organs and tissues are of

concern in people with pre-existing heart disease who have compromised
compensatory mechanisms (e.g., lack of capacity to increase blood flow
in response to increased CO). The integrative review of health effects
of CO indicates that ``the clearest evidence indicates that individuals
with [coronary artery disease] are most susceptible to an increase in
CO-induced health effects'' (ISA, section 5.7.8) and the evidence
continues to support levels of COHb in the blood as the most useful
indicator of CO exposure that is related to the health effects of CO of
major concern.
    Carboxyhemoglobin occurs in the blood due to endogenous CO
production from biochemical reactions associated with normal breakdown
of heme proteins, as well as in response to inhaled (exogenous) CO
exposures (ISA, section 4.5). The production of endogenous CO and
levels of endogenous COHb vary with several physiological
characteristics (e.g., slower COHb elimination with increasing age), as
well as some disease states, which can lead to higher endogenous levels
in some individuals (ISA, section 4.5). The amount of COHb formed in
response to exogenous CO is dependent on the CO concentration and
duration of exposure, exercise (which increases the amount of air
removed and replaced per unit of time for gas exchange), the pulmonary
diffusing capacity for CO, ambient pressure, health status, and the
specific metabolism of the exposed individual (ISA, chapter 4; 2000
AQCD, chapter 5). The formation of COHb is a reversible process, but
the high affinity of CO for hemoglobin, which affects the elimination
half-time for COHb, can lead to increased COHb levels in some
circumstances.
    As discussed in the REA, exposure to CO in ambient air can occur
outdoors as well as through infiltration of ambient air into indoor
locations (REA, section 2.3). Additionally, indoor sources such as gas
stoves and tobacco smoke can, where present, be important contributors
to total CO exposure and can result in much greater CO exposures and
associated COHb levels than those associated with ambient sources (ISA,
section <IP_ADDRESS>).\10\ For example, indoor source-related exposures,
such as faulty furnaces or other combustion appliances, have been
estimated in the past to lead to COHb levels on the order of twice as
high as those short-term exposures to ambient CO considered more likely
to be encountered by the general public (2000 AQCD, p. 7-4). Further,
some assessments performed for previous reviews have included modeling
simulations both without and with indoor sources (gas stoves and
tobacco smoke) to provide context for the assessment of ambient CO
exposure and dose (e.g., U.S. EPA, 1992; Johnson et al., 2000), and
these assessments have found that nonambient sources have a
substantially greater impact on the highest total exposures experienced
by the simulated population than do ambient sources (Johnson et al.,
2000; REA, sections 1.2 and 6.3).\11\. However, the focus of this REA,
conducted to inform the current review of the CO NAAQS, is on sources
of ambient CO. While recognizing this information regarding the
potential for indoor sources, where present, to play a role in CO
exposures and COHb levels, the exposure modeling in the current review
(described in section II.C below) did not include indoor CO sources in
order to focus on the impact of ambient CO sources on population COHb
levels.
---------------------------------------------------------------------------

    \10\ A significant source of nonambient CO long recognized as
contributing to elevated COHb levels is tobacco smoking (e.g., ISA,
Figure 4-12). Further, baseline COHb levels in active smokers have
been estimated to range from 3 to 8% for one- to two-pack-per-day
smokers. As a result of their higher baseline COHb levels, smokers
may exhale more CO into the air than they inhale from the ambient
environment when not smoking. Tobacco smoking can also contribute to
increased CO exposures and associated COHb levels in nonsmokers
(2000 AQCD, p. 7-4).
    \11\ As has been recognized in previous CO NAAQS reviews, such
sources cannot be effectively mitigated by setting more stringent
ambient air quality standards (59 FR 38914).
---------------------------------------------------------------------------

    Apart from the impaired oxygen delivery to tissues related to COHb
formation, the evidence also indicates alternative mechanisms of CO-
induced effects independent of limited oxygen availability (2000 AQCD,
section 5.9; ISA, section 5.1.3). These mechanisms are primarily
associated with CO's ability to bind heme-containing proteins other
than hemoglobin and myoglobin, and involve a wide range of molecular
targets and CO concentrations, as described in the 2000 AQCD (USEPA,
2000, section 5.6) and in the ISA (ISA, section 5.1.3). Older
toxicological studies demonstrated that exposure to high concentrations
of CO resulted in altered functions of heme proteins other than
myoglobin and hemoglobin, potentially interfering with basic cell and
molecular processes and leading to dysfunction and/or disease. More
recent toxicological in vitro and in vivo studies have provided
evidence of alteration of nitric oxide signaling, inhibition of
cytochrome C oxidase, heme loss from protein, disruption of iron
homeostasis and alteration of cellular reduction-oxidation status (ISA,
section <IP_ADDRESS>). The ISA notes that these mechanisms may be
interrelated. The evidence for these alternative mechanisms and the
role they may play in CO-induced health effects at concentrations
relevant to the current NAAQS is not clear.
    As noted in the ISA, ``CO may be responsible for a continuum of
effects from cell signaling to adaptive responses to cellular injury,
depending on intracellular concentrations of CO, heme proteins and
molecules which modulate CO binding to heme proteins'' (ISA, section
<IP_ADDRESS>). However, as noted in the Policy Assessment, new research
based on this evidence for pathways other than those related to
impaired oxygen delivery to tissues is needed to further understand
these pathways and their linkage to CO-induced effects in susceptible
populations. Thus, the evidence indicates that COHb continues to be the
most useful and well-supported indicator of CO exposures and the best
biomarker to characterize the potential for health effects associated
with exposures to ambient CO at this time (PA, section 2.2.1).
2. Nature of Effects
    As observed in the Policy Assessment, the long-standing body of
evidence that has established many aspects of the biological effects of
CO continues to contribute to our understanding of the health effects
of ambient CO (PA, section 2.2.1). Binding to heme proteins and the
alteration of their function is the common mechanism underlying
biological responses to CO. Upon inhalation, CO diffuses through the
respiratory zone (alveoli) to the blood where it binds to hemoglobin,
forming COHb. Accordingly, inhaled CO elicits various health effects
through binding to, and associated alteration of the function of, a
number of heme-containing molecules, mainly hemoglobin (see e.g., ISA,
section 4.1). The best characterized health effect associated with CO
levels of concern is hypoxia (reduced oxygen availability) induced by
increased COHb levels in blood and decreased oxygen availability to
critical tissues and organs, specifically the heart (ISA, section
5.1.2). Consistent with this, medical conditions that affect the
biological mechanisms to compensate for this effect (e.g., vasodilation
and increased coronary blood flow with increased oxygen delivery to the
myocardium) can contribute to a reduced amount of oxygen available to
key body tissues, potentially affecting organ system

function and limiting exercise capacity (2000 AQCD, section 7.1).\12\
---------------------------------------------------------------------------

    \12\ For example, people with peripheral vascular diseases and
heart disease patients often have markedly reduced circulatory
capacity and reduced ability to compensate for increased circulatory
demands during exercise and other stress (2000 AQCD, p. 7-7).
---------------------------------------------------------------------------

    The body of health effects evidence for CO has grown considerably
since the review completed in 1994 with the addition of numerous
epidemiological and toxicological studies (ISA; 2000 AQCD). This
evidence provides additional detail and support to our prior
understanding of CO effects and population susceptibility. Most
notably, the current evidence includes much expanded epidemiological
evidence that is consistent with previous conclusions regarding
cardiovascular disease-related susceptibility (ISA, section 5.7; 2000
AQCD, section 7.7). In this review, the clearest evidence for ambient
CO-related effects is available for cardiovascular effects. Using an
established framework to characterize the evidence as to likelihood of
causal relationships between exposure to ambient CO and specific health
effects (ISA, chapter 1) the ISA states that ``Given the consistent and
coherent evidence from epidemiologic and human clinical studies, along
with biological plausibility provided by CO's role in limiting oxygen
availability, it is concluded that a causal relationship is likely to
exist between relevant \13\ short-term CO exposures and cardiovascular
morbidity'' (ISA, p. 2-6, section 2.5.1). Additionally, as mentioned
above, the ISA judges the evidence to be suggestive of causal
relationships between relevant short- and long-term CO exposures and
CNS effects, birth outcomes and developmental effects following long-
term exposure, respiratory morbidity following short-term exposure, and
mortality following short-term exposure (ISA, section 2.5, Table 2-1).
---------------------------------------------------------------------------

    \13\ Relevant CO exposures are defined in the ISA as ``generally
within one or two orders of magnitude of ambient CO concentrations''
(ISA, section 2.5).
---------------------------------------------------------------------------

    Similar to the previous review, results from controlled human
exposure studies of individuals with coronary artery disease (CAD) \14\
(Adams et al., 1988; Allred et al., 1989a, 1989b, 1991; Anderson et
al., 1973; Kleinman et al., 1989, 1998; Sheps et al., 1987 \15\) are
the ``most compelling evidence of CO-induced effects on the
cardiovascular system'' (ISA, section 5.2). Additionally, the use of an
internal dose metric, COHb, adds to the strength of the findings in
these controlled exposure studies. As a group, these studies
demonstrate the role of short-term CO exposures in increasing the
susceptibility of people with CAD to incidents of exercise-associated
myocardial ischemia. Toxicological studies described in the current
review provide evidence of CO effects on the cardiovascular system,
including electrocardiographic effects of 1-hour exposures to 35 ppm CO
in a rat strain developed as an animal model of cardiac susceptibility
(ISA, section <IP_ADDRESS>).
---------------------------------------------------------------------------

    \14\ Coronary artery disease (CAD), often also called coronary
heart disease or ischemic heart disease is a category of
cardiovascular disease associated with narrowed heart arteries.
Individuals with this disease may have myocardial ischemia, which
occurs when the heart muscle receives insufficient oxygen delivered
by the blood. Exercise-induced angina pectoris (chest pain) occurs
in many of them. Among all patients with diagnosed CAD, the
predominant type of ischemia, as identified by ST segment
depression, is asymptomatic (i.e., silent). Patients who experience
angina typically have additional ischemic episodes that are
asymptomatic (2000 AQCD, section <IP_ADDRESS>). In addition to such
chronic conditions, CAD can lead to sudden episodes, such as
myocardial infarction (ISA, p. 5-24).
    \15\ Statistical analyses of the data from Sheps et al., (1987)
by Bissette et al (1986) indicate a significant decrease in time to
onset of angina at 4.1% COHb if subjects that did not experience
exercise-induced angina during air exposure are also included in the
analyses.
---------------------------------------------------------------------------

    Among the controlled human exposure studies, the ISA places
principal emphasis on the study of CAD patients by Allred et al.
(1989a, 1989b, 1991) \16\ (which was also considered in the previous
review) for the following reasons: (1) Dose-response relationships were
observed; (2) effects were observed at the lowest COHb levels tested
(mean of 2-2.4% COHb \17\ following experimental CO exposure), with no
evidence of a threshold; (3) objective measures of myocardial ischemia
(ST-segment depression) \18\ were assessed, as well as the subjective
measure of decreased time to induction of angina; (4) measurements were
taken both by CO-oximetry (CO-Ox) and by gas chromatography (GC), which
provides a more accurate measurement of COHb blood levels \19\; (5) a
large number of study subjects were used; (6) a strict protocol for
selection of study subjects was employed to include only CAD patients
with reproducible exercise-induced angina; and (7) the study was
conducted at multiple laboratories around the U.S. This study evaluated
changes in time to exercise-induced onset of markers of myocardial
ischemia resulting from two short (approximately 1-hour) CO exposures
targeted to result in mean study subject COHb levels of 2% and 4%,
respectively (ISA, section 5.2.4). In this study, subjects (n=63) on
three separate occasions underwent an initial graded exercise treadmill
test, followed by 50 to 70-minute exposures under resting conditions to
room air CO concentrations or CO concentrations targeted for each
subject to achieve blood COHb levels of 2% and 4%. The exposures were
to average CO concentrations of 0.7 ppm (room air concentration range
0-2 ppm), 117 ppm (range 42-202 ppm) and 253 ppm (range 143-357 ppm).
After the 50- to 70-minute exposures, subjects underwent a second
graded exercise treadmill test, and the percent change in time to onset
of angina and time to ST endpoint between the first and second exercise
tests was determined. For the two CO exposures, the average post-
exposure COHb concentrations were reported as 2.4% and 4.7%, and the
subsequent post-exercise average COHb concentrations were reported as
2.0% and 3.9%.\20\
---------------------------------------------------------------------------

    \16\ Other controlled human exposure studies of CAD patients
(listed in Table 2-2 of the PA, and discussed in more detail in the
1991 and 2000 AQCDs) similarly provide evidence of reduced time to
exercise-induced angina associated with elevated COHb resulting from
controlled short-duration exposure to increased concentrations of
CO.
    \17\ These levels and other COHb levels described for this study
below are based on GC analysis unless otherwise specified. Matched
measurements available for CO-oximetry (CO-Ox) and gas
chromatography (GC) in this study indicate CO-Ox measurements of
2.65% (post-exercise mean) and 3.21% (post-exposure mean)
corresponding to the GC measurement levels of 2.00% (post-exercise
mean) to 2.38% (post-exposure mean) for the lower exposure level
assessed in this study (Allred et al., 1991).
    \18\ The ST-segment is a portion of the electrocardiogram,
depression of which is an indication of insufficient oxygen supply
to the heart muscle tissue (myocardial ischemia). Myocardial
ischemia can result in chest pain (angina pectoris) or such
characteristic changes in ECGs or both. In individuals with coronary
artery disease, it tends to occur at specific levels of exercise.
The duration of exercise required to demonstrate chest pain and/or a
1-mm change in the ST segment of the ECG were key measurements in
the multicenter study by Allred et al (1989a, 1989b, 1991).
    \19\ As stated in the ISA, the gas chromatographic technique for
measuring COHb levels ``is known to be more accurate than
spectrophotometric measurements, particularly for samples containing
COHb concentrations < 5%'' (ISA, p. 5-41). CO-oximetry is a
spectrophotometric method commonly used to rapidly provide
approximate concentrations of COHb during controlled exposures (ISA,
p. 5-41). At the low concentrations of COHb (<5%) more relevant to
ambient CO exposures, co-oximeters are reported to overestimate COHb
levels compared to GC measurements, while at higher concentrations,
this method is reported to produce underestimates (ISA, p.4-18).
    \20\ While the COHb blood level for each subject during the
exercise tests was intermediate between the post-exposure and
subsequent post-exercise measurements (e.g., mean 2.4-2.0% and 4.7-
3.9%), the study authors noted that the measurements at the end of
the exercise test represented the COHb concentrations at the
approximate time of onset of myocardial ischemia as indicated by
angina and ST segment changes. The corresponding ranges of CO-Ox
measurements for the two exposures were 2.7-3.2% and 4.7-5.6%. In
this document, we refer to the GC-measured mean of 2.0% or 2.0-2.4%
for the COHb levels resulting from the lower experimental CO
exposure.

---------------------------------------------------------------------------

    Across all subjects, the mean time to angina onset for control
(``room'' air) exposures was approximately 8.5 minutes, and the mean
time to ST endpoint was approximately 9.5 minutes (Allred et al.,
1989b). Relative to room-air exposure that resulted in a mean COHb
level of 0.6% (post-exercise), exposure to CO resulting in post-
exercise mean COHb concentrations of 2.0% and 3.9% were observed to
decrease the exercise time required to induce ST-segment depression by
5.1% (p=0.01) and 12.1% (p<0.001), respectively. These changes were
well correlated with the onset of exercise-induced angina, the time to
which was shortened by 4.2% (p=0.027) and 7.1% (p=0.002), respectively,
for the two experimental CO exposures (Allred et al., 1989a, 1989b,
1991).\21\ As at the time of the last review, while ST-segment
depression is recognized as an indicator of myocardial ischemia, the
exact physiological significance of the observed changes among those
with CAD is unclear (ISA, p. 5-48).
---------------------------------------------------------------------------

    \21\ Another indicator measured in the study was the combination
of heart rate and systolic blood pressure which provides a clinical
index of the work of the heart and myocardial oxygen consumption,
since heart rate and blood pressure are major determinants of
myocardial oxygen consumption (Allred et al., 1991). A decrease in
oxygen to the myocardium would be expected to be paralleled by
ischemia at lower heart rate and systolic blood pressure. This heart
rate-systolic blood pressure indicator at the time to ST-endpoint
was decreased by 4.4% at the 3.9% COHb dose level and by a
nonstatistically-significant, smaller amount at the 2.0% COHb dose
level.
---------------------------------------------------------------------------

    No controlled human exposure studies have been specifically
designed to evaluate the effect of controlled short-term exposures to
CO resulting in COHb levels lower than a study mean of 2% (ISA, section
5.2.6). However, an important finding of the multi-laboratory study was
the dose-response relationship observed between COHb and the markers of
myocardial ischemia, with effects observed at the lowest increases in
COHb tested, without evidence of a measurable threshold effect. As
reported by the authors, the results comparing ``the effects of
increasing COHb from baseline levels (0.6%) to 2 and 3.9% COHb showed
that each produced further changes in objective ECG measures of
ischemia'' implying that ``small increments in COHb could adversely
affect myocardial function and produce ischemia'' (Allred et al.,
1989b, 1991).
    The epidemiological evidence has expanded considerably since the
last review including numerous additional studies that are coherent
with the evidence on markers of myocardial ischemia from controlled
human exposure studies of CAD patients (ISA, section 2.7). The most
recent set of epidemiological studies in the U.S. have evaluated the
associations between ambient concentrations of multiple pollutants
(i.e. fine particles or PM2.5, nitrogen dioxide, sulfur
dioxide, ozone, and CO) at fixed-site ambient monitors and increases in
emergency department visits and hospital admissions for specific
cardiovascular health outcomes including ischemic heart disease (IHD),
myocardial infarction (MI), congestive heart failure (CHF), and
cardiovascular diseases (CVD) as a whole (Bell et al., 2009; Koken et
al., 2003; Linn et al., 2000; Mann et al., 2002; Metzger et al., 2004;
Symons et al., 2006; Tolbert et al., 2007; Wellenius et al., 2005).
Findings of positive associations for these outcomes with metrics of
ambient CO concentrations are coherent with the evidence from
controlled human exposure studies of myocardial ischemia-related
effects resulting from elevated CO exposures (ISA, section 2.5.1; ISA,
Figure 2-1). In these studies, the ambient CO concentration averaging
time for which health outcomes were analyzed varied from 1 hour to 24
hours, with the air quality metrics based on either a selected central-
site monitor for the area or an average for multiple monitors in the
area of interest. The study areas for which positive associations of
these metrics were reported with IHD, MI and CVD outcomes include: the
Atlanta, Georgia metropolitan statistical area; the greater Los
Angeles, California area; and a group of 126 urban counties. Together
the individual study periods spanned the years from 1988 through 2005.
The risk estimates from these studies indicate statistically
significant positive associations were observed with ambient CO
concentrations based on air quality for the day of hospital admission
or based on the average of the selected ambient CO concentration metric
across that day and 2 or 3 days previous (ISA, Figures 5-2 and 5-5).
Many of the studies for these outcomes include same day or next day lag
periods, which, as noted in the ISA ``are consistent with the proposed
mechanism and biological plausibility of these CVD outcomes'' (ISA, p.
5-40).\22\
---------------------------------------------------------------------------

    \22\ Of the studies for which risk estimates are based on multi-
day averages (the Atlanta studies and the California study by Mann
et al., 2002), the California study by Mann et al., (2002) also
observed a significant positive association with same day CO
concentration.
---------------------------------------------------------------------------

    Additionally, there are U.S. studies reporting associations with
hospital admissions for CHF, a condition that affects an individual's
ability to compensate for reduced oxygen availability. These include
one in southern California which reported a significant association for
ambient CO with hospital admissions for CHF (Linn et al., 2000), as
well as studies in Allegheny County (Pittsburgh) for 1987-1999 study
period (Wellenius et al., 2005), and Denver for the months of July-
August during 1993-1997 (Koken et al., 2003; ISA, pp. 5-31 to 5-33).
Risk estimates for all three of these studies are based on the 24-hour
CO concentration, with the California and Allegheny County studies'
association with same-day air quality, while the association shown for
the Denver study was with ambient CO concentration three days prior to
health outcome (PA, Table 2-1).
    As noted by the ISA, ``[s]tudies of hospital admissions and ED
visits for IHD provide the strongest [epidemiological] evidence of
ambient CO being associated with adverse CVD outcomes'' (ISA, p. 5-40,
section 5.2.3). With regard to studies for other measures of
cardiovascular morbidity, the ISA notes that ``[t]hough not as
consistent as the IHD effects, the effects for all CVD hospital
admissions (which include IHD admissions) and CHF hospital admissions
also provide evidence for an association of cardiovascular outcomes and
ambient CO concentrations'' (ISA, section 5.2.3). While noting the
difficulty in determining the extent to which CO is independently
associated with CVD outcomes in this group of studies as compared to CO
as a marker for the effects of another traffic-related pollutant or mix
of pollutants, the ISA concludes that the epidemiological evidence,
particularly when considering the copollutant analyses, provides
support to the clinical evidence for a direct effect of short-term
ambient CO exposure on CVD morbidity (ISA, pp. 5-40 to 5-41).
    As discussed in detail in the ISA, additional epidemiological
studies have evaluated associations of ambient CO with other
cardiovascular effects since the last review. For example, preliminary
evidence of a link between exposure to CO and alteration of blood
markers of coagulation and inflammation in individuals with CAD or CVD
has been provided by a few well conducted and informative studies (ISA,
Table 5-6; Delfino et al., 2008; Liao et al., 2005). As noted by the
ISA, however, further studies are warranted to investigate the role of
these markers in prothrombotic events and their possible contribution
to the pathophysiology of CO-induced aggravation of ischemic heart
disease

(ISA, section <IP_ADDRESS>). Other epidemiological studies (including field
and panel studies) also provide some evidence of a link between CO
exposure and heart rate and heart rate variability (ISA, section
<IP_ADDRESS>). With regard to the two of three studies reporting a positive
association with heart rate, the ISA concluded that ``further research
is warranted'' to corroborate the results, while the larger number of
studies for heart rate variability parameters is characterized as
having mixed associations (ISA, p. 5-15). Additionally, of the two
studies of electrocardiogram changes indicative of ischemic events
(ISA, section <IP_ADDRESS>), one found no association and, in the other
study, the association with CO did not remain statistically significant
in multipollutant models, unlike the association with black carbon in
that study (ISA, p. 5-16). A limited number of epidemiological studies
(Bell et al., 2009; Linn et al., 2000) have investigated hospital
admissions for stroke (including both hemorrhagic and ischemic forms)
and generally report small or no associations with ambient CO
concentrations (ISA, section <IP_ADDRESS>, Table 5-8 and Figure 5-3).
    At the time of the last review, there was evidence for effects
other than cardiovascular morbidity, including neurological,
respiratory and developmental effects. Evidence for these effects
includes the following.
     With regard to neurological effects, acute exposures to CO
have long been known to induce CNS effects such as those observed with
CO poisoning, although limited and equivocal evidence available at the
time of the last review included indications of some neurobehavioral
effects to result from CO exposures resulting in a range of 5-20% COHb
(2000 AQCD, section 6.3.2). No additional clinical or epidemiological
studies are now available that investigated such effects of CO at
ambient levels (ISA, section 5.3).
     With regard to potential effects of CO on birth outcomes
and developmental effects, the potential vulnerability of the fetus and
very young infant to CO was recognized during the 1994 review and in
the 2000 AQCD. The CO-specific evidence available, however, included
limited epidemiological analyses focused primarily on very high CO
exposures associated with maternal smoking, and animal studies
involving very high CO exposures (USEPA, 1992; 2000 AQCD). The 2000
AQCD concluded that typical ambient CO levels were unlikely to cause
increased fetal risk (2000 AQCD, p. 6-44). The current review includes
additional epidemiological and animal toxicological studies. The
currently available evidence includes limited but suggestive
epidemiologic evidence for a CO-induced effect on preterm-birth, birth
defects, decrease in birth weight, other measures of fetal growth, and
infant mortality (ISA, section 5.4.3). The available animal
toxicological studies provide some support and coherence for these
birth and developmental outcomes at higher than ambient exposures,\23\
although a clear understanding of the mechanisms underlying potential
reproductive and developmental effects is still lacking (ISA, section
2.5.3).
---------------------------------------------------------------------------

    \23\ The lowest exposures eliciting an effect in the animal
studies were exposures of 22 hours per day over about 14 prenatal
days at a concentration of 12 ppm (ISA, Table 5-17).
---------------------------------------------------------------------------

     With regard to respiratory effects, the 2000 AQCD
concluded it unlikely that CO has direct effects on lung tissue, except
at extremely high concentrations (2000 AQCD, p. 6-45). There is
currently limited, suggestive evidence of an association between short-
term exposure to CO and respiratory-related outcomes. Only preliminary
evidence is available, however, regarding a mechanism that could
provide plausibility for CO-induced effects (ISA, section <IP_ADDRESS>).
    Thus, while there is some additional evidence on neurological,
respiratory and developmental effects, it remains limited.
    In summary, rather than altering conclusions from the previous
review, the current evidence provides continued support and some
additional strength to the previous conclusions regarding the health
effects associated with exposure to CO and continues to indicate
cardiovascular effects, particularly effects related to the role of CO
in limiting oxygen availability, as those of greatest concern at low
exposures.
3. At-Risk Populations
    In identifying population groups or life stages at greatest risk
for health risk from a specific pollutant, the terms susceptibility,
vulnerability, sensitivity, and at-risk are commonly employed. The
definition for these terms sometimes varies, but in most instances
``susceptibility'' refers to biological or intrinsic factors (e.g.,
lifestage, gender) while ``vulnerability'' refers to nonbiological or
extrinsic factors (e.g., visiting a high-altitude location, medication
use). Additionally, in some cases, the terms ``at-risk'' and sensitive
have been used to encompass both of these concepts. At times, however,
factors of ``susceptibility'' and ``vulnerability'' are intertwined and
are difficult to distinguish. In the ISA for this review, the term
susceptibility has been used broadly to recognize populations that have
a greater likelihood of experiencing effects related to ambient CO
exposure, such that use of the term susceptible populations in the ISA
is defined as follows (ISA, section 5.7, p. 5-115):

    Populations that have a greater likelihood of experiencing
health effects related to exposure to an air pollutant (e.g., CO)
due to a variety of factors including, but not limited to: genetic
or developmental factors, race, gender, lifestage, lifestyle (e.g.,
smoking status and nutrition) or preexisting disease, as well as
population-level factors that can increase an individual's exposure
to an air pollutant (e.g., CO) such as socioeconomic status [SES],
which encompasses reduced access to health care, low educational
attainment, residential location, and other factors.

    Thus, susceptible populations are at greater risk of CO effects and
are also referred to as at-risk in the corresponding discussion in the
REA and Policy Assessment and the summary below.
    The current evidence, while much expanded in a number of ways,
continues to support the conclusions from the previous review regarding
susceptible populations for exposure to ambient CO. In the AQCD for the
review completed in 1994 and in the 2000 AQCD, the evidence best
supported the identification of patients with CAD as a population at
increased risk from low levels of CO (USEPA, 1992; 2000 AQCD). Other
groups were also recognized as potentially susceptible in the 2000 AQCD
based on consideration of the clinical evidence and theoretical work,
as well as laboratory animal research (2000 AQCD, p. 7-6). These
include fetuses and young infants; pregnant women; the elderly,
especially those with compromised cardiovascular function; people with
conditions affecting oxygen absorption, blood flow, oxygen carrying
capacity or transport; people using drugs with central nervous system
depressant properties or exposed to chemical substances that increase
endogenous formation of CO; and people who have not adapted to high
altitude and are exposed to a combination of high altitude and CO. For
these potentially susceptible groups, little empirical evidence was
available by which to specify health effects associated with ambient or
near-ambient CO exposures (2000 AQCD, p. 7-6).
    As summarized in the Policy Assessment, based on the evidence from
controlled human exposure studies also considered in the last review,
and the

now much-expanded epidemiological evidence base which is coherent with
the evidence from these studies, the population with pre-existing
cardiovascular disease associated with limitation in oxygen
availability continues to be the best characterized population at risk
of adverse CO-induced effects, with CAD recognized as ``the most
important susceptibility characteristic for increased risk due to CO
exposure'' (ISA, section 2.6.1). An important factor determining the
increased susceptibility of this population is their inability to
compensate for the reduction in oxygen levels due to an already
compromised cardiovascular system. Individuals with a healthy
cardiovascular system (i.e., with healthy coronary arteries) have
operative physiologic compensatory mechanisms (e.g., increased blood
flow and oxygen extraction) for CO-induced hypoxia and are unlikely to
be at increased risk of CO-induced effects (ISA, p. 2-10).\24\ In
addition, the high oxygen consumption of the heart, together with the
inability to compensate for the hypoxic effects of CO, make the cardiac
muscle of a person suffering with CAD a critical target for the hypoxic
effects of CO.
---------------------------------------------------------------------------

    \24\ The other well-studied individuals at the time of the last
review were healthy male adults that experienced decreased exercise
duration at similar COHb levels during short term maximal exercise.
This population was of lesser concern since it represented a smaller
sensitive group, and potentially limited to individuals that would
engage in vigorous exercise such as competing athletes (1991 AQCD,
section 10.3.2).
---------------------------------------------------------------------------

    In the Integrated Science Assessment for the current review,
recognition of susceptibility of the population with pre-existing
cardiovascular disease, such as CAD, is supported by the expanded
epidemiological database, which includes a number of studies reporting
significant increases in hospital admissions for IHD, angina and MI in
relation to CO exposures (ISA, section 2.7). Further support is
provided by epidemiologic studies (Mann et al., 2002; and Peel et al.,
2007) of increased hospital admissions and emergency department visits
for IHD among individuals with secondary diagnoses for other
cardiovascular outcomes including arrhythmia and congestive heart
failure (ISA, section 5.7), and toxicological studies reporting altered
cardiac outcomes in animal models of cardiovascular disease (ISA,
section <IP_ADDRESS>).
    Cardiovascular disease comprises many types of medical disorders,
including heart disease, cerebrovascular disease (e.g., stroke),
hypertension (high blood pressure), and peripheral vascular diseases.
Heart disease, in turn, comprises several types of disorders, including
ischemic heart disease (CHD or CAD, myocardial infarction, angina),
congestive heart failure, and disturbances in cardiac rhythm (2000
AQCD, section <IP_ADDRESS>). Types of cardiovascular disease other than
those discussed above may also contribute to increased susceptibility
to the adverse effects of low levels of CO (ISA, section <IP_ADDRESS>). For
example, some evidence with regard to other types of cardiovascular
disease such as congestive heart failure, arrhythmia, and non-specific
cardiovascular disease, although more limited for peripheral vascular
and cerebrovascular disease, indicates that ``the continuous nature of
the progression of CAD and its close relationship with other forms of
cardiovascular disease suggest that a larger population than just those
individuals with a prior diagnosis of CAD may be susceptible to health
effects from CO exposure'' (ISA, p. 5-117).
    Although there were little experimental data available at the time
of the last review to adequately characterize specific health effects
of CO at ambient levels for other potentially at-risk populations,
several other populations were identified as being potentially more at
risk of CO-induced effects due to a number of factors. These factors
include pre-existing diseases that could inherently decrease oxygen
availability to tissues, lifestage vulnerabilities (e.g., fetuses,
young infants or newborns, the elderly), gender, lifestyle, medications
or alterations in the physical environment (e.g., increased altitude).
This is consistent with the ISA conclusions in the current review which
recognize other populations that may be potentially susceptible to the
effects of CO as including: Those with other pre-existing diseases that
may have already limited oxygen availability or increased COHb
production or levels, such as people with obstructive lung diseases,
diabetes and anemia; older adults; fetuses during critical phases of
development and young infants or newborns; those who spend a
substantial time on or near heavily traveled roadways; visitors to
high-altitude locations; and people ingesting medications and other
substances that enhance endogenous or metabolic CO formation (ISA,
section 2.6.1). In recognizing the potential susceptibility of these
populations, the Policy Assessment also noted the lack of information
on specific COHb levels that may be associated with health effects in
these other groups and the nature of those effects, as well as a way to
relate the specific evidence available for the CAD population to these
other populations (PA, section 2.2.1).
    The current evidence continues to support the identification of
people with cardiovascular disease as having susceptibility to CO-
induced health effects (ISA, 2-12), with those having CAD as the
population with the best characterized susceptibility to CO-induced
health effects (ISA, sections <IP_ADDRESS> and 5.7.8).\25\ An important
susceptibility consideration for this population is the inability to
compensate for CO-induced hypoxia since individuals with CAD have an
already compromised cardiovascular system. Included in this susceptible
population are those with angina pectoris (cardiac chest pain), those
who have experienced a heart attack, and those with silent ischemia or
undiagnosed IHD (AHA, 2003). People with other cardiovascular diseases,
particularly heart diseases, are also at risk of CO-induced health
effects. We also recognize other populations potentially susceptible to
CO-induced effects, most particularly those with other pre-existing
diseases that cause limited oxygen availability, increased COHb levels,
or increased endogenous CO production, such as people with obstructive
lung diseases, diabetes and anemia; however, information characterizing
susceptibility for this population is limited.
---------------------------------------------------------------------------

    \25\ As recognized in the ISA, ``Although the weight of evidence
varies depending on the factor being evaluated, the clearest
evidence indicates that individuals with CAD are most susceptible to
an increase in CO-induced health effects'' (ISA, p. 2-12).
---------------------------------------------------------------------------

4. Potential Impacts on Public Health
    In light of the evidence described above with regard to factors
contributing to greater susceptibility to health effects of ambient CO,
this section, drawing from the Integrated Science Assessment and
discussion in the Policy Assessment, discusses the health significance
of the effects occurring with the lowest relevant (short-term)
exposures to ambient CO and the size of the at-risk populations in the
U.S. These considerations are important elements in the
characterization of potential public health impacts associated with
exposure to ambient CO.
    We first consider the effects identified by the evidence at the
lowest studied short-term exposures. As discussed in section II.B.2
above, the study by Allred et al., (1989a, 1989b, 1991) indicates that
increases in blood COHb in response to 1-hour CO exposures

produce evidence of myocardial ischemia in CAD patients with
reproducible exercise-induced angina. At a study group average COHb
level of 2-2.4%, the statistically significant reduction in the time to
exercise-induced markers of myocardial ischemia in CAD patients was 4-
5% on average (approximately 30 seconds), with larger reductions
observed at the higher studied COHb level. In discussing public health
implications of the observed responses, the study authors noted that
the responses observed at the studied COHb levels were similar to those
considered clinically significant when evaluating medications to treat
angina from coronary artery disease (Allred et al., 1989a, 1991). The
independent review panel for the study further noted that frequent
encounters in ``everyday life'' with increased COHb levels on the order
of those tested in the study might be expected to limit activity and
affect quality of life (Allred et al., 1989b, pp. 38, 92-94; 1991 AQCD,
p. 10-35).
    In the review completed in 1994, the body of evidence that
demonstrated cardiovascular effects in CAD patients exposed to CO was
given primary consideration, with the Administrator judging that
``cardiovascular effects, as measured by decreased time to onset of
angina pain and by decreased time to onset of significant ST-segment
depression, are the health effects of greatest concern, which clearly
have been associated with CO exposures at levels observed in the
ambient air'' (59 FR 38913). Additionally, as discussed in section
II.B.2 above, a dose-response relationship has been documented for COHb
resulting from brief, elevated CO exposures in persons with pre-
existing CAD, with no evidence of threshold (59 FR 38910; ISA, section
5.2.4; Allred et al., 1989a, 1989b, 1991).
    In the 1994 review decision (as discussed in section II.D.1.a
below), less significance was ascribed to the effects at the lower COHb
level assessed in the Allred et al., study (1989a, 1989b, 1991), which
were described to be of less certain clinical importance, than effects
reported from short-term CO exposure studies that assessed higher COHb
levels (59 FR 38913-38914). In the current review of the evidence, the
ISA describes the physiological significance of the changes at the
lowest tested dose level (e.g., 2% COHb from Allred et al., 1989b) as
unclear, additionally noting that variability in severity of disease
among individuals with CAD is likely to influence the critical level of
COHb which leads to adverse cardiovascular effects (ISA, p. 2-6).
    In considering potential public health impacts of CO in ambient
air, we also consider the size of the at-risk populations. The
population with CAD is well recognized as susceptible to increased risk
of CO-induced health effects (ISA, sections <IP_ADDRESS> and 5.7.8). The
2007 estimate from the National Health Interview Survey (NHIS)
performed by the U.S. Centers for Disease Control of the size of the
U.S. population with coronary heart disease, angina pectoris (cardiac
chest pain) or who have experienced a heart attack (ISA, Table 5-26) is
13.7 million people (ISA, pp. 5-117). Further, there are estimated to
be three to four million additional people with silent ischemia or
undiagnosed IHD (AHA, 2003). In combination, this represents a large
population that is more susceptible to ambient CO exposure when
compared to the general population (ISA, section 5.7).
    In addition to the population with diagnosed and undiagnosed CAD,
the ISA notes the size of the larger population of people with all
types of heart disease (HD), which may also be at increased risk of CO-
induced health effects (ISA, section 2.6.1). Within this broader group,
implications of CO exposures are more significant for those persons for
whom their disease state affects their ability to compensate for the
hypoxia-related effects of CO (ISA, section 4.4.4). The NHIS estimates
for 2007 indicate there is a total of approximately 25 million people
with heart disease of any type (ISA, Table 5-26).
    Other populations potentially susceptible to the effects of CO
include people with chronic obstructive pulmonary disease, diabetes and
anemia, as well as older adults and fetuses during critical phases of
development (as discussed in section II.B.3 above). In considering
potential impacts on such populations, we recognize that the evidence
is limited or lacking with regard to effects of CO at ambient levels,
and associated exposures and COHb levels, while providing no indication
of susceptibility to ambient CO greater than that of CHD and HD
populations.

C. Human Exposure and Dose Assessment

    Our consideration of the scientific evidence in the current review,
as at the time of the last review (summarized in section II.D.1 below),
is informed by results from a quantitative analysis of estimated
population exposure and resultant COHb levels. This analysis provides
estimates of the percentages of simulated at-risk populations expected
to experience daily maximum COHb levels at or above a range of
benchmark levels under varying air quality scenarios (e.g., just
meeting the current or alternative standards). The benchmark COHb
levels were identified based on consideration of the evidence discussed
in section II.B above. The following subsections summarize the design
and methods of the quantitative assessment (section II.C.1) and the
important uncertainties associated with these analyses (section
II.C.2). The results of the analyses, as they relate to considerations
of the adequacy of the current standards, are discussed in section
II.D.2 below.
1. Summary of Design Aspects
    In this section, we provide a summary of key aspects of the
assessment conducted for this review, including the study areas and air
quality scenarios investigated, modeling tools used, at-risk
populations simulated, and COHb benchmark levels of interest. The
assessment is described in detail in the REA and summarized in the PA
(section 2.2.2).
    The assessment estimated CO exposure and associated COHb levels in
simulated at-risk populations in two urban study areas in Denver and
Los Angeles, in which current ambient CO concentrations are below the
current standards. We selected these areas because: (1) Areas of both
cities have been included in prior CO NAAQS exposure assessments and
thus serve as an important connection with past assessments; (2)
historically, they have generally had the highest ambient CO
concentrations among urban areas in the U.S.; and (3) Denver is at high
altitude and represents an important risk scenario due to the potential
increased susceptibility to CO exposure associated with high altitudes.
In addition, of 10 urban areas across the continental U.S. selected for
detailed air quality analysis in the ISA and having ambient monitors
meeting a 75% completeness criterion, the two study area locations were
ranked first (Los Angeles) and second (Denver) regarding the percentage
of elderly population within 5, 10, and 15 km of monitor locations, and
ranked first (Los Angeles) and fifth (Denver) regarding number of 1-
and 8-hour daily maximum CO concentration measurements (ISA, section
<IP_ADDRESS>).
    Estimates were developed for exposures to ambient CO associated
with current ``as is'' conditions (2006 air quality) and also for
higher ambient CO concentrations associated with air quality conditions
simulated to just

meet the current 8-hour standard,\26\ as well as for air quality
conditions simulated to just meet several alternative standards.
Although we consider it unlikely that air concentrations in many urban
areas across the U.S. that are currently well below the current
standards would increase to just meet the 8-hour standard, we recognize
the potential for CO concentrations in some areas currently below the
standard to increase to just meet the standard. We additionally
recognize that this simulation can provide useful information in
evaluating the current standard. Accordingly, we simulated conditions
of increased CO concentrations that just meet the current 8-hour
standard in the two study areas. In so doing, we recognize the
uncertainty associated with simulating this hypothetical profile of
higher CO concentrations that just meet the current 8-hour standard. We
note, however, that an analysis of the ratios of 1-hour to 8-hour
design value metrics based on 2009 ambient CO concentrations in U.S.
locations indicates that the relationships between design values for
the two study areas under the air quality conditions simulated to just
meet the current 8-hour standard fall well within the 2009 national
distribution of such ratios (Policy Assessment, section 2.2.2).\27\
---------------------------------------------------------------------------

    \26\ As noted elsewhere, the 8-hour standard is the controlling
standard for ambient CO concentrations.
    \27\ More specifically, the ratio of the 1-hour design value to
the 8-hour design value for the Los Angeles study area corresponds
to approximately the 25th percentile of U.S. counties in 2009 and
the ratio for the Denver study area corresponds to approximately the
75th percentile of U.S. counties in 2009. Under ``as is'' conditions
the ratios for these two study areas correspond to approximately the
40th percentile of the 2009 national distribution (Policy
Assessment, section 2.2.2).
---------------------------------------------------------------------------

    The exposure and dose modeling for the assessment, presented in
detail in the REA, relied on version 4.3 of EPA's Air Pollutant
Exposure model (APEX4.3), which estimates human exposure using a
stochastic, event-based microenvironmental approach (REA, chapter 4).
This model has a history of application, evaluation, and progressive
model development in estimating human exposure and dose for several
NAAQS reviews, including CO, ozone (O3), nitrogen dioxide
(NO2), and sulfur dioxide (SO2). As described in
section II.D.1 below, the review of the CO standards completed in 1994
relied on population exposure and dose estimates generated from the
probabilistic NAAQS exposure model (pNEM), a model that, among other
differences from the current modeling approach with APEX4.3, employed a
cohort-based approach (Johnson et al., 1992; U.S. EPA,
1992).28 29 Each of the model developments since the use of
pNEM in that review have been designed to allow APEX to better
represent human behavior, human physiology, and microenvironmental
concentrations and to more accurately estimate variability in CO
exposures and COHb levels (REA, chapter 4).\30\
---------------------------------------------------------------------------

    \28\ When using the cohort approach, each cohort is assumed to
contain persons with identical exposures during the specified
exposure period. Thus, variability in exposure will be attributed to
differences in how the cohorts are defined, not necessarily
reflecting differences in how individuals might be exposed in a
population. In the assessment for the review completed in 1994, a
total of 420 cohorts were used to estimate population exposure based
on selected demographic information (11 groups using age, gender,
work status), residential location, work location, and presence of
indoor gas stoves (Johnson, et al., 1992; USEPA, 1992).
    \29\ The use of pNEM in the prior review also (1) relied on a
limited set of activity pattern data (approximately 3,600 person-
days), (2) used four broadly defined categories to estimate
breathing rates, and (3) implemented a geodesic distance range
methodology to approximate workplace commutes (Johnson et al., 1992;
U.S. EPA, 1992). Each of these approaches used by pNEM, while
appropriate given the data available at that time, would tend to
limit the ability to accurately model expected variability in the
population exposure and dose distributions.
    \30\ APEX4.3 includes new algorithms to (1) simulate
longitudinal activity sequences and exposure profiles for
individuals, (2) estimate activity-specific minute-by-minute oxygen
consumption and breathing rates, (3) address spatial variability in
home and work-tract ambient concentrations for commuters, and (4)
estimate event-based microenvironmental concentrations (PA, section
2.2.2).
---------------------------------------------------------------------------

    As used in the current assessment, APEX probabilistically generates
a sample of hypothetical individuals from an actual population database
and simulates each individual's movements through time and space (e.g.,
indoors at home, inside vehicles) to estimate his or her exposure to
ambient CO (REA, chapter 4). The individual's movements are simulated
based on data available from recent activity pattern surveys (CHAD \31\
now has about 34,000 person-days of data) and the most recent U.S.
census data on population demographics and home-to-workplace commutes.
Based on exposure concentrations, minute-by-minute activity levels, and
physiological characteristics of the simulated individuals (see REA,
chapters 4 and 5), APEX estimates the level of COHb in the blood for
each individual at the end of each hour based on a nonlinear solution
to the Coburn-Forster-Kane equation (REA, section 4.4.7). These results
across each simulated individual were then summarized in the REA and
discussed in the Policy Assessment in terms of the percent of the
simulated at-risk populations expected to experience one or more
occurrences of daily maximum end-of-hour COHb levels of interest.
---------------------------------------------------------------------------

    \31\ CHAD is EPA's Comprehensive Human Activity Database which
provides input data for APEX model simulations (REA, sections 4.3
and 4.4).
---------------------------------------------------------------------------

    As discussed in section II.B above, people with cardiovascular
disease are the population of primary focus in this review, and more
specifically, as described in the ISA, coronary artery disease, also
known as coronary heart disease, is the ``most important susceptibility
characteristic for increased risk due to CO exposure'' (ISA, p. 2-11).
Controlled human exposure studies have provided quantitative COHb dose-
response information for this specific population with regard to
effects on markers of myocardial ischemia. Accordingly, based on the
current evidence with regard to quantitative information of COHb levels
and association with specific health effects, the at-risk populations
simulated in the quantitative assessment were (1) adults with CHD (also
known as ischemic heart disease [IHD] or CAD), both diagnosed and
undiagnosed, and (2) adults with any heart diseases, including
undiagnosed ischemia.\32\ Evidence characterizing the nature of
specific health effects of CO in other populations is limited and does
not include specific COHb levels related to health effects in those
groups. As a result, the quantitative assessment does not develop
separate quantitative dose estimates for populations other than those
with CHD or HD.
---------------------------------------------------------------------------

    \32\ As described in section 1.2 above, this is the same
population group that was the focus of the CO NAAQS exposure/dose
assessments conducted previously (e.g., USEPA, 1992; Johnson et al.,
2000).
---------------------------------------------------------------------------

    In representing the two at-risk populations and their activity
patterns, individuals were simulated based on age and gender
distributions for CHD and HD populations. These distributions were
developed by augmenting the prevalence estimates provided by the
National Health Interview Survey for adults with CAD and adults with
heart diseases of any type (HD) with estimates of undiagnosed ischemia
(as described in section 5.5.1 of the REA). The undiagnosed ischemia
estimates were developed based on two assumptions: (1) There are 3.5
million persons in U.S. with undiagnosed IHD (AHA, 2003) and (2)
persons with undiagnosed IHD are distributed within the population in
the same manner as persons with diagnosed IHD (REA, section 5.5.1).
    APEX simulations performed for this review focused on exposures to
ambient

CO occurring in eight microenvironments,\33\ absent any contribution to
microenvironment concentrations from indoor (nonambient) CO sources. As
noted in section II.B.1 above, however, where present, indoor sources,
including gas stoves, attached garages and tobacco smoke, can also be
important contributors to total CO exposure (ISA, sections 3.6.1 and
3.6.5). Previous assessments, that have included modeling simulations
both with and without certain indoor sources, indicated that the impact
of such sources can be substantial with regard to the portion of the
at-risk population experiencing higher exposures and COHb levels
(Johnson et al., 2000). While we are limited with regard to information
regarding CO emissions from indoor sources today and how they may
differ from the time of the 2000 assessment, we note that ambient
contributions have notably declined, and indoor source contributions
from some sources may also have declined. Thus, as indicated in the
Policy Assessment, we have no firm basis to conclude a different role
for indoor sources today with regard to contribution to population CO
exposure and COHb levels.
---------------------------------------------------------------------------

    \33\ The 8 microenvironments modeled in the REA comprised a
range of indoor and outdoor locations including residences as well
as motor vehicle-related locations such as inside vehicles, and
public parking and fueling facilities, where the highest exposures
were estimated (REA, sections 5.9 and 6.1).
---------------------------------------------------------------------------

    The REA developed COHb estimates for the simulated at-risk
populations with attention to both COHb in absolute terms and in terms
of the contribution to absolute levels associated with ambient CO
exposures. Absolute COHb refers to the REA estimates of COHb levels
resulting from endogenously produced CO and exposure to ambient CO (in
the absence of any nonambient sources). The additional REA estimates of
ambient CO exposure contribution to COHb levels were calculated by
subtracting COHb estimates obtained in the absence of CO exposure--
i.e., that due to endogenous CO production alone (see REA, Appendix
B.6)--from the corresponding end-of-hour absolute COHb estimates for
each simulated individual. Thus, the REA reports estimates of the
maximum end-of-hour ambient contributions across the simulated year, in
addition to the maximum absolute end-of hour COHb levels.
    As discussed in the Policy Assessment (section 2.2.2), the absence
of indoor (nonambient) sources in the REA simulations is expected to
result in simulated individuals with somewhat higher estimates of the
contribution of short-duration increases in ambient CO exposure to COHb
levels (ambient contribution) than would be expected for individuals in
situations where the presence of nonambient sources contributes to
higher baseline COHb levels (i.e., COHb prior to a short-duration
exposure event). The amount by which the ambient contribution estimates
might differ is influenced by the magnitude of nonambient-source
exposures and associated baseline COHb levels. One reason for this is
that in the presence of indoor sources, baseline COHb levels will be
higher for a given population group than COHb levels for that group
arising solely from endogenous CO in the absence of any exposure, which
is the ``baseline'' for the REA estimates of ambient contribution to
COHb (REA, appendix B.6).\34\ As CO uptake depends in part on the
amount of CO already present in the blood (and the blood-air CO
concentration gradient), in general, a higher baseline COHb, with all
other variables unchanged, will lead to relatively lesser uptake of CO
from short-duration exposures (ISA, section 4.3; AQCD, section 5.2).
Additionally, as is indicated by the REA estimates, the attainment of a
particular dose level is driven largely by short-term (and often high
concentration) exposure events. This is because of the relatively rapid
uptake of CO into a person's blood, as demonstrated by the pattern in
the REA time-series of ambient concentrations, microenvironmental
exposures, and COHb levels (REA, Appendix B, Figure B-2). For example
the time lag for response of an individual's COHb levels to variable
ambient CO (and hence exposure) concentrations may be only a few hours
(e.g., REA, Figure B-2).
---------------------------------------------------------------------------

    \34\ As they result only from endogenous CO formation, the REA
``baseline'' COHb levels would also be expected to be, and generally
are, lower than the initial, pre-exposure, COHb levels of subjects
in the controlled exposure studies. REA estimates of endogenously
formed COHb averaged about 0.3% across the simulated populations,
with slightly higher levels in the higher altitude Denver study area
(REA, pp. B-21 to B-22). Levels in the Denver study population
ranged from 0.1 to 1.1% COHb, with an average of 0.31%, while levels
for Los Angeles ranged from 0.1 to 0.7% with an average of 0.27%
COHb. Initial, pre-exposure COHb levels in the subjects of the
Allred et al. study (1989b), which reflect the subjects pre-study
exposure history as well as endogenous CO formation, ranged from 0.2
to 1.1%, averaging about 0.6% COHb.
---------------------------------------------------------------------------

    In considering the REA dose estimates in the Policy Assessment, as
described in section II.D.2 below, staff considered estimates of the
portion of the simulated at-risk populations estimated to experience
daily maximum end-of-hour absolute COHb levels above identified
benchmark levels (at least once and on multiple occasions), as well as
estimates of the percentage of population person-days (the only metric
available from the modeling for the 1994 review), and also population
estimates of daily maximum ambient contribution to end-of-hour COHb
levels. In identifying COHb benchmark levels of interest, primary
attention was given to the multi-laboratory study in which COHb was
analyzed by the more accurate GC method (Allred et al., 1989a, 1989b,
1991) discussed in section II.B.2 above. The REA identified a series of
benchmark levels for considering estimates of absolute COHb: 1.5%,
2.0%, 2.5% and 3% COHb (REA, section 2.6). This range includes the
range of COHb levels identified as levels of concern in the review
completed in 1994 (2.0 to 2.9%) and the level given particular focus
(2.1%) at that time, as described in section 2.1.1 above (USEPA, 1992;
59 FR 48914). Selection of this range of benchmark levels is based on
consideration of the evidence from controlled human exposure studies of
subjects with CAD (discussed in section 2.2.1 above), with the lower
end of the range extending below the lowest mean COHb level resulting
from controlled exposure to CO in the clinical evidence (e.g., 2.0%
post-exercise in Allred et al., 1989b). The extension of this range
reflects a number of considerations, including: (1) Comments from the
CASAC CO panel on the draft Scope and Methods Plan (Brain, 2009); (2)
consideration of the uncertainties regarding the actual COHb levels
experienced in the controlled human exposure studies; (3) that these
studies did not include individuals with most severe cardiovascular
disease;\35\ (4) the lack of studies that have evaluated effects of
experimentally controlled short-term CO exposures resulting in mean
COHb levels below 2.0-2.4%; and (5) the lack of evidence of a threshold
at the increased COHb levels evaluated. We note that CASAC comments on
the first draft REA recommended the addition of a benchmark at 1.0%
COHb and results are presented for this COHb level in the REA. Given
that this level overlaps with the upper part of the range of endogenous
levels in healthy individuals as characterized in the ISA (ISA, p. 2-
6), and is within the upper

part of the range of baseline COHb levels in the study by Allred et al
(1989b, Appendix B), however, we considered that it may not be
appropriate to place weight on it as a benchmark level and accordingly
have not focused on interpreting absolute COHb estimates at and below
this level in the discussion below. Additionally we note the REA
estimates indicating that, in the absence of CO exposure, approximately
0.5% to 2% of the simulated at-risk populations in the two study areas
were estimated to experience a single daily maximum end-of-hour COHb
level, arising solely from endogenous CO production, at or above 1%
(REA, Appendix B, Figure B-3).
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    \35\ Although the CAD patients evaluated in the controlled human
exposure study by Allred et al. (1989a, 1989b, 1991) are not
necessarily representative of the most sensitive population, the
level of disease in these individuals ranged from moderate to
severe, with the majority either having a history of myocardial
infarction or having >=70% occlusion of one or more of the coronary
arteries (ISA, p. 5-43).
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    The Policy Assessment also considered the evidence from controlled
human exposure studies in interpreting the REA estimates of maximum
ambient exposure contributions to end-of-hour COHb levels (described in
sections 4.4.7 and 5.10.3 of the REA). As discussed above, the study by
Allred et al (1989a, 1989b, 1991) observed reduced time to exercise-
induced angina and ST-segment change in groups of subjects with pre-
existing CAD for which controlled CO exposures increased their COHb
levels by on average 1.4-1.8% and 3.2-4.0% COHb from initial COHb
levels of on average 0.6% COHb (ISA, section 5.2.4; Allred et al.,
1989a, 1989b, 1991). The study reported a dose-response relationship in
terms of time reduction per 1% increase in COHb concentration based on
analysis of the full data set across both exposure groups. For purposes
of the discussion in this document, we have presented the percentage of
the simulated at-risk populations estimated to experience maximum
ambient contribution to end-of-hour COHb levels above and below a range
of levels extending from 1.4 to 2.0%. As noted above, the Policy
Assessment recognized distinctions between the REA ``baseline''
(arising from prior ambient exposure and endogenous CO production) and
the pre-exposure COHb levels in the controlled human exposure study
(arising from ambient and nonambient exposure history, as well as from
endogenous CO production), and also noted the impact of ``baseline''
COHb levels on COHb levels occurring in response to short ambient CO
exposure events such as those simulated in the REA as discussed above.
2. Key Limitations and Uncertainties
    Numerous improvements have been made over the last decade that have
reduced the uncertainties associated with the models used to estimate
COHb levels resulting from ambient CO exposures under different air
quality conditions, including those associated with just meeting the
current CO NAAQS (REA, section 4.3). This progression in exposure model
development has led to the model currently used by the Agency
(APEX4.3), which has an enhanced capacity to estimate population CO
exposures and more accurately predicts COHb levels in persons exposed
to CO. Our application of APEX4.3 in this review, using updated data
and new algorithms to estimate exposures and doses experienced by
individuals, better represents the variability in population exposure
and COHb dose levels than the model version used in previous CO
assessments.\36\ However, while APEX 4.3 is greatly improved when
compared with previously used exposure models, its application is still
limited with regard to data to inform our understanding of spatial
relationships in ambient CO concentrations and within microenvironments
of particular interest. Further information regarding model
improvements and remaining exposure modeling uncertainties are
summarized in section 2.2.2 of the Policy Assessment and described in
detail in chapter 7 of the REA.
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    \36\ APEX4.3 provides estimates for percent of population
projected to experience a single or multiple occurrences of a daily
maximum COHb level above the various benchmark levels, as well as
percent of person-days.
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    The uncertainties associated with the quantitative estimates of
exposure and dose were considered using a generally qualitative
approach intended to identify and compare the relative impact that
important sources of uncertainty may have on the estimated potential
health effect endpoints (i.e., estimates of the maximum end-of-hour
COHb levels in the simulated at-risk population). The approach used was
developed using World Health Organization (WHO) guidelines on
conducting a qualitative uncertainty characterization (WHO, 2008) and
was also applied in the most recent NO2 (USEPA, 2008c) and
SO2 NAAQS reviews (USEPA, 2009e). A qualitative approach was
employed given the extremely limited data available to inform
probabilistic uncertainty analyses. The qualitative approach used
varies from that of WHO (2008) in that a greater focus of the
characterization performed was placed on evaluating the direction and
the magnitude of the uncertainty; that is, qualitatively rating how the
source of uncertainty, in the presence of alternative information, may
affect the estimated exposures and health risk results. Additionally,
consistent with the WHO (2008) guidance, the REA discusses the
uncertainty in the knowledge base (e.g., the accuracy of the data used,
acknowledgement of data gaps) and decisions made where possible (e.g.,
selection of particular model forms), though qualitative ratings were
assigned only to uncertainty regarding the knowledge base.
    Sixteen separate sources of uncertainty associated with four main
components of the assessment were identified. By comparing judgments
made regarding the magnitude and direction of influence that the
identified sources have on estimated exposure concentrations and dose
levels and the existing uncertainties in the knowledge base, seven
sources of uncertainty (i.e., the spatial and temporal representation
of ambient monitoring data, historical data used in representing
alternative air quality scenarios, activity pattern database,
longitudinal profile algorithm, microenvironmental algorithm and input
data, and physiological factors) were identified as the most important
areas of uncertainty in this assessment (PA, section 2.2.2). Taking
into consideration improvements in the model algorithms and data since
the last review, and having identified and characterized these
uncertainties here, the Policy Assessment concludes that the estimates
associated with the current analysis, at a minimum, better reflect the
full distribution of exposures and dose as compared to results from the
1992 analysis. As noted in the Policy Assessment, however, potentially
greater uncertainty remains in our characterization of the upper and
lower percentiles of the distribution of population exposures and COHb
dose levels relative to that of other portions of the respective
distribution. When considering the overall quality of the current
exposure modeling approach, the algorithms, and input data used,
alongside the identified limitations and uncertainties, the REA and
Policy Assessment conclude that the quantitative assessment provides
reasonable estimates of CO exposure and COHb dose for the simulated
population the assessment is intended to represent (i.e., the
population residing within the urban core of each study area).
    The Policy Assessment additionally notes the impact on the REA dose
estimates for ambient CO contribution to COHb of the lack of nonambient
sources in the model simulations. This aspect of the assessment design
may contribute to higher estimates of the contribution of short-
duration ambient CO exposures to total COHb than would

result from simulations that include the range of commonly encountered
CO sources beyond just those contributing to ambient air CO
concentrations. Although the specific quantitative impact of this on
estimates of population percentages discussed in this document is
unknown, consideration of COHb estimates from the 2000 assessment
indicates a potential for the inclusion of nonambient sources to
appreciably affect absolute COHb (REA, section 6.3) and accordingly
implies the potential, where present, for an impact on overall ambient
contribution to a person's COHb level.

D. Conclusions on Adequacy of the Current Standards

    The initial issue to be addressed in the current review of the
primary CO standards is whether, in view of the advances in scientific
knowledge and additional information now available, the existing
standards should be retained or revised. In evaluating whether it is
appropriate to retain or revise the current standards, the
Administrator builds upon the last review and reflects the broader body
of evidence and information now available. The Administrator has taken
into account both evidence-based and quantitative exposure- and risk-
based considerations in developing conclusions on the adequacy of the
current primary CO standards. Evidence-based considerations include the
assessment of evidence from controlled human exposure, toxicological
and epidemiological studies evaluating short- or long-term exposures to
CO, with supporting evidence related to dosimetry and potential mode of
action, as well as the integration of evidence across each of these
disciplines, and with a focus on policy-relevant considerations as
discussed in the PA. The exposure/dose-based considerations draw from
the results of the quantitative analyses presented in the REA and
summarized in section II.C above, and consideration of those results in
the PA. More specifically, estimates of the magnitude of ambient CO-
related exposures and associated COHb levels associated with just
meeting the current primary CO NAAQS have been considered. Together the
evidence-based and risk-based considerations have informed the
Administrator's proposed conclusions related to the adequacy of the
current CO standards in light of the currently available scientific
evidence.
1. Approach
    In considering the evidence and quantitative exposure and dose
estimates with regard to judgments on the adequacy afforded by the
current standards, we note that the final decision is largely a public
health policy judgment. A final decision must draw upon scientific
information and analyses about health effects 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. Our approach to informing these judgments, discussed more
fully below, is based on the recognition that the available health
effects evidence generally reflects a continuum, consisting of ambient
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 EPA and the courts have historically interpreted the Act.
These provisions require the Administrator to establish primary
standards that, in the Administrator's judgment, 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 level, but rather
at a level that avoids unacceptable risks to public health, including
the health of sensitive groups.\37\
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    \37\ The sensitive population groups identified in a NAAQS
review may (or may not) be comprised of low income or minority
groups. Where low income/minority groups are among the sensitive
groups, the rulemaking decision will be based on providing
protection for these and other sensitive population groups. To the
extent that low income/minority groups are not among the sensitive
groups, a decision based on providing protection of the sensitive
groups would be expected to provide protection for the low income/
minority groups (as well as any other less sensitive population
groups).
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    The following subsections include background information on the
approach used in the previous review of the CO standards (section
II.D.1.a) and also a description of the approach for the current review
(section II.D.1.b).
a. Previous Reviews
    The current primary standards for CO are set at 9 parts per million
(ppm) as an 8-hour average and 35 ppm as a 1-hour average, neither to
be exceeded more than once per year. These standards were initially set
in 1971 to protect against the occurrence of carboxyhemoglobin (COHb)
levels that may be associated with effects of concern (36 FR 8186).
Reviews of these standards in the 1980s and early 1990s identified
additional evidence regarding ambient CO, CO exposures, COHb levels,
and associated health effects (USEPA, 1984a, 1984b; USEPA, 1991; USEPA,
1992; McClellan, 1991, 1992). Assessment of the evidence in those
reviews, completed in 1985 and 1994, led the EPA to retain the existing
primary standards without revision (50 FR 37484, 59 FR 38906).
    The 1994 decision to retain the primary standards without revision
was based on the evidence published through 1990 and reviewed in the
1991 AQCD (USEPA, 1991), the 1992 Staff Paper assessment of the policy-
relevant information contained in the AQCD and the quantitative
exposure assessment (USEPA, 1992), and the advice and recommendations
of CASAC (McClellan 1991, 1992). At that time, as at the time of the
first NAAQS review (50 FR 37484), COHb levels in blood were recognized
as providing the most useful estimate of exogenous CO exposures and
serving as the best biomarker of CO toxicity for ambient-level
exposures to CO (59 FR 38909). Consequently, COHb levels were used as
the indicator of health effects in the identification of health effect
levels of concern for CO (59 FR 38909).
    In reviewing the standards in 1994 the Administrator first
recognized the need to determine the COHb levels of concern ``taking
into account a large and diverse health effects database.'' The more
uncertain and less quantifiable evidence was taken into account to
identify the lower end of this range to provide an adequate margin of
safety for effects of clear concern. To consider ambient CO
concentrations likely to result in COHb levels of concern, a model
solution to the Coburn-Forster-Kane (CFK) differential equation was
employed in the analysis of CO exposures expected to occur under air
quality scenarios related to just meeting the current 8-hour CO NAAQS,
the controlling standard (USEPA, 1992).\38\ Key considerations in this
approach are described below.
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    \38\ Air quality analyses of CO levels in the U.S. consistently
demonstrate that meeting the 8-hour standard results in 1-hour
maximum concentrations well below the corresponding 1-hour standard.
---------------------------------------------------------------------------

    The assessment of the science that was presented in the 1991 AQCD
(USEPA, 1991) indicated that CO is associated with effects in the
cardiovascular system, central nervous system (CNS), and the developing
fetus. Additionally, factors recognized as having the potential to
alter the effects

of CO included exposures to other pollutants, some drugs and some
environmental factors, such as altitude. Cardiovascular effects of CO,
as measured by decreased time to onset of angina and to onset of
significant electrocardiogram (ECG) ST-segment depression were judged
by the Administrator to be ``the health effects of greater concern,
which clearly had been associated with CO exposures at levels observed
in ambient air'' (59 FR 38913).
    Based on the consistent findings of response in patients with
coronary artery disease across the controlled human exposure evidence
(Adams et al., 1988; Allred et al., 1989a, 1989b, 1991; Anderson et
al., 1973; Kleinman et al., 1989, 1998; Sheps et al., 1987 \39\) and
discussions of adverse health consequences in the 1991 AQCD and the
1992 Staff Paper,\40\ at the CASAC meetings and in the July 1991 CASAC
letter, the Administrator concluded that ``CO exposures resulting in
COHb levels of 2.9-3.0 percent (CO-Ox) or higher in persons with heart
disease have the potential to increase the risk of decreased time to
onset of angina pain and ST-segment depression'' (59 FR 38913). While
EPA and CASAC recognized the existence of a range of views among health
professionals on the clinical significance of these responses, CASAC
noted that the dominant view was that they should be considered
``adverse or harbinger of adverse effect'' (McClellan, 1991) and EPA
recognized that it was ``important that standards be set to
appropriately reduce the risk of ambient exposures which produce COHb
levels that could induce such potentially adverse effects'' (59 FR
38913).
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    \39\ See footnote 15 above.
    \40\ Based on consideration of the key studies, including those
two that investigated more than a single target COHb level,
discussions in the 1991 AQCD and with CASAC, the 1992 Staff Paper
recommended that ``2.9-3.0% COHb (CO-Ox), representing an increase
above initial COHb of 1.5 to 2.2% COHb, be considered a level of
potential adversity for individuals at risk'' (59 FR 38911; USEPA,
1992; USEPA, 1991, pp. 1-11 to 1-12; Allred et al., 1989a, 1989b,
1991; Anderson et al., 1973).
---------------------------------------------------------------------------

    In further considering additional results from the controlled human
exposure evidence, such as the results from Allred et al. (1989a,
1989b) at 2.0% COHb (using GC measurement) induced by short
(approximately 1-hour) CO exposure, as well as other aspects of the
available evidence and uncertainties regarding modeling estimates of
COHb formation and human exposure to COHb levels in the population
associated with attainment of a given CO NAAQS, the Administrator
recognized the need to extend the range of COHb levels for
consideration in evaluating whether the current CO standards provide an
adequate margin of safety to those falling between 2.0 to 2.9% COHb (59
FR 38913). Factors considered in recognizing this margin of safety
included the following (59 FR 38913).
     Uncertainty regarding the clinical importance of
cardiovascular effects associated with exposures to CO that resulted in
COHb levels of 2 to 3 percent. Although recognizing the possibility
that there is no threshold for these effects even at lower COHb levels,
the clinical importance of cardiovascular effects associated with short
(approximately 1-hour) exposures to CO resulting in COHb levels as low
as 2.0% COHb by GC (Allred et al., 1989a,b) was described as ``less
certain'' than effects noted for exposures contributing to higher COHb
(CO-Ox) levels (59 FR 38913).
     Findings of short-term reduction in maximal work capacity
measured in trained athletes exposed to CO at levels resulting in COHb
levels of 2.3 to 7 percent.
     The potential that the most sensitive individuals have not
been studied, the limited information regarding the effects of ambient
CO in the developing fetus, and concern about visitors to high
altitudes, individuals with anemia or respiratory disease, or the
elderly.
     Potential for short term peak CO exposures to be
responsible for impairments (impairment of visual perception,
sensorimotor performance, vigilance or other CNS effects) which could
be a matter of concern for complex activities such as driving a car,
although these effects had not been demonstrated to be caused by CO
concentrations in ambient air.
     Concern based on limited evidence for individuals exposed
to CO concurrently with drugs (e.g., alcohol), during heat stress, or
co-exposure to other pollutants.
     Uncertainties, described as ``large,'' that remained
regarding modeling COHb formation and estimating human exposure to CO
which could lead to overestimation of COHb levels in the population
associated with attainment of a given CO NAAQS.
     Uncertainty associated with COHb measurements made using
CO-Ox which may not reflect COHb levels in angina patients studied,
thereby creating uncertainty in establishing a lowest effects level for
CO.
    Based on these considerations of the evidence, the Administrator
identified a range of COHb levels for considering margin of safety,
extending from 2.9% COHb (representing an increase of 1.5% above
baseline when using CO-Ox measurements) at the upper end down to 2% at
the lower end (59 FR 38913), and also concluded that ``evaluation of
the adequacy of the current standard should focus on reducing the
number of individuals with cardiovascular disease from being exposed to
CO levels in the ambient air that would result in COHb levels of 2.1
percent'' (59 FR 38914). She additionally concluded that standards that
``protect against COHb levels at the lower end of the range should
provide an adequate margin of safety against effects of uncertain
occurrence, as well as those of clear concern that have been associated
with COHb levels in the upper-end of the range'' (59 FR 38914).
    To estimate CO exposures and resulting COHb levels that might be
expected under air quality conditions that just met the current
standards, an analysis of exposure and associated internal dose in
terms of COHb levels in the population of interest in the city of
Denver, Colorado was performed (59 FR 38906; USEPA, 1992). That
analysis indicated that if the 9 ppm 8-hour standard were just met, the
proportion of the nonsmoking population with cardiovascular disease
experiencing a daily maximum 8-hour exposure at or above 9 ppm for 8
hours decreased by an order of magnitude or more as compared to the
proportion under then-existing CO levels, down to less than 0.1 percent
of the total person-days in that population. Further, upon meeting the
8-hour standard, EPA estimated that less than 0.1% of the nonsmoking
cardiovascular-disease population would experience a COHb level greater
than or equal to 2.1% and a smaller percentage of the at-risk
population was estimated to exceed higher COHb levels (59 FR