[Federal Register Volume 59, Number 146 (Monday, August 1, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-18659]


[[Page Unknown]]

[Federal Register: August 1, 1994]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 50

[AD-FDL-4735-5]

 

National Ambient Air Quality Standards for Carbon Monoxide--Final 
Decision

AGENCY: U.S. Environmental Protection Agency (U.S. EPA).

ACTION: Final decision.

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SUMMARY: Identical primary (health-based) and secondary (welfare-based) 
national ambient air quality standards (NAAQS) for carbon monoxide (CO) 
were promulgated in 1971 at 9 parts per million (ppm), 8-hour average, 
and 35 ppm, 1-hour average, neither to be exceeded more than one time 
per year. In 1985, the EPA announced the decision not to revise the 
primary CO NAAQS and at the same time to revoke the secondary CO NAAQS. 
In accordance with sections 108 and 109 of the Clean Air Act (Act), the 
EPA has reviewed and revised the criteria upon which the existing NAAQS 
for CO are based. Based on that review, this document announces the 
EPA's final decision under section 109(d)(1) that revisions of the 
NAAQS for CO are not appropriate at this time.

ADDRESSES: A docket containing information relating to the EPA's review 
of the CO NAAQS (Docket No. A-93-05) is available for public inspection 
in the Air and Radiation Docket and Information Center of the U.S. 
Environmental Protection Agency, South Conference Center, Room 4, 401 M 
Street, SW., Washington, DC. The docket may be inspected between 8 a.m. 
and 4 p.m. on weekdays, and a reasonable fee may be charged for 
copying. The information in the docket constitutes the complete basis 
for the decision announced in this notice. For availability of related 
information, see SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Dr. David J. McKee, Air Quality 
Management Division (MD-12), U.S. Environmental Protection Agency, 
Research Triangle Park, NC 27711, telephone (919) 541-5288.

SUPPLEMENTARY INFORMATION:

Availability of Related Information

    Certain documents are available from: U.S. Department of Commerce, 
National Technical Information Service, 5285 Port Royal Road, 
Springfield, Virginia 22161. Available documents include: the revised 
criteria document, ``Air Quality Criteria for Carbon Monoxide'' (EPA/
600/8-90-045F; NTIS # PB 93-167492, $77.00 paper copy and $27.00 
microfiche), and the 1992 staff paper, ``Review of the National Ambient 
Air Quality Standards for Carbon Monoxide: Assessment of Scientific and 
Technical Information-OAQPS Staff Paper'' (EPA-452/R-92-004, August 
1992; NTIS No. PB 93-157717, $19.50 paper copy and $9.00 microfiche). 
(Add $3.00 handling charge per order.) Other documents generated in 
connection with review of this standard (e.g., exposure analysis) are 
available in the EPA Docket No. A-93-05.
    The contents of this document are listed in the following outline:

I. Background
    A. Legislative Requirements Affecting This Decision
    1. Primary and Secondary Standards
    2. Related Control Requirements
    B. Existing Primary Standards for Carbon Monoxide
    C. Review of Air Quality Criteria and Standards for Carbon 
Monoxide; Development of the Staff Paper
    D. Decision Docket
II. Scientific Basis for This Regulatory Decision
    A. Measuring and Assessing Carboxyhemoglobin Levels
    B. Health Effects Associated With Carbon Monoxide
    1. Mechanisms of Toxicity
    2. Cardiovascular Effects
    3. Effects on Exercise Capacity and Oxygen Uptake
    4. Central Nervous System Effects
    5. Developmental Toxicity Effects
    6. Environmental Factors, Drugs, and Other Pollutants
    C. Populations Potentially at Risk
III. Rationale for This Decision
    A. Carboxyhemoglobin Levels of Concern
    B. Margin of Safety
    C. Relationship Between CO Exposure and COHb Levels
    D. Estimating Population Exposure
    E. Decision on the Primary Standards
IV. Final Decision Not to Revise the Standards
V. Regulatory Impacts
    A. Regulatory Impact Analysis
    B. Impact on Small Entities
VI. Other Reviews
References

I. Background

A. Legislative Requirements Affecting This Decision

1. Primary and Secondary Standards
    Two sections of the Act govern the establishment and revision of 
NAAQS. Section 108 (42 U.S.C. 7408) directs the Administrator to 
identify pollutants which may reasonably be anticipated to endanger 
public health and welfare and to issue air quality criteria for them. 
These air quality criteria are 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 
identified under section 108. Section 109(b)(1) defines a primary 
standard as one the attainment and maintenance of which, in the 
judgment of the Administrator, based on the criteria and allowing an 
adequate ``margin of safety,'' [is] requisite to protect the public 
health. 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 [the] criteria, is 
requisite to protect the public welfare from any known or anticipated 
adverse effects associated with the presence of [the] pollutant in the 
ambient air. 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, manmade 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.
    The U.S. Court of Appeals for the District of Columbia Circuit has 
held that the requirement for an adequate ``margin of safety'' for 
primary standards 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 
(D.C. Cir. 1980), cert. denied, 101 S. Ct. 621 (1980); American 
Petroleum Institute v. Costle, 665 F.2d 1176, 1177 (D.C. Cir. 1981), 
cert. denied, 102 S. Ct. 1737 (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, by selecting primary standards that provide 
an adequate ``margin of safety,'' the Administrator is seeking not only 
to prevent pollution levels that have been demonstrated to be harmful 
but also to prevent lower pollutant levels that she finds may pose an 
unacceptable risk of harm, even if the risk is not precisely identified 
as to nature or degree.
    In selecting a ``margin of safety,'' the EPA considers such factors 
as the nature and severity of the health effects involved, the size of 
the sensitive population(s) at risk, and the kind and degree of the 
uncertainties that must be addressed. Given that the ``margin of 
safety'' requirement by definition only comes into play where no 
conclusive showing of adverse effects exists, such factors, which 
involve unknown or only partially quantified risks, have their inherent 
limits as guides to action. The selection of any particular approach to 
provide an adequate ``margin of safety'' is a policy choice left 
specifically to the Administrator's judgment. [Lead Industries 
Association v. EPA, supra, 647 F.2d at 1161-62].
    Section 109(d)(1) of the Act requires that not later than December 
31, 1980, and at 5-year intervals thereafter, the Administrator shall 
complete a thorough review of the criteria published under section 108 
and the NAAQS and shall make such revisions in such criteria and 
standards as may be appropriate. Section 109(d)(2) (A) and (B) requires 
that a scientific review committee be appointed and provides that the 
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 revisions of existing criteria and standards 
as may be appropriate. If the EPA decides to revise an existing 
standard, the rulemaking procedures of section 307(d) apply.1
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    \1\The EPA has also chosen to follow rulemaking procedures in 
several NAAQS reviews that did not involve revision of existing 
standards. However, the EPA interprets section 307(d) as not 
requiring such procedures where the Administrator decides to retain 
an existing standard without change; i.e., to maintain the status 
quo. Although such a decision is subject to judicial review as a 
final action under section 307(b), neither the Act nor its 
legislative history evidences any intent to require rulemaking where 
the Administrator has not concluded that revision of an existing 
NAAQS is appropriate. The Agency's conclusion that rulemaking 
procedures are not required to retain an existing NAAQS without 
revision is not affected by the Court's brief reference to the use 
of rulemaking procedures in Environmental Defense Fund v. Thomas, 
870 F.2d 892, 900 (2d Cir.), cert. denied, 110 S.Ct. 537 (1989). As 
a practical matter, even without the use of rulemaking procedures, 
the process by which the EPA reviews existing criteria and standards 
involves substantial opportunities for public and expert comment on 
both its assessment of relevant scientific and technical data and 
its proposed use of the data for decision making purposes.
---------------------------------------------------------------------------

    The process by which the EPA has reviewed the existing air quality 
criteria and standards for CO under section 109(d) is described in a 
later section of this notice.
2. Related Control Requirements
    States are primarily responsible for ensuring attainment and 
maintenance of ambient air quality standards once the EPA has 
established them. Under title I of the Act (42 U.S.C. 7410), States are 
to submit, for EPA approval, State implementation plans (SIP's) that 
provide for the attainment and maintenance of such standards through 
control programs directed to sources of the pollutants involved. The 
States, in conjunction with the EPA, also administer the prevention of 
significant deterioration program (42 U.S.C. 7470-7479) and the 
visibility protection program (42 U.S.C. 7491-7492) for these and other 
air pollutants. In addition, Federal programs provide for nationwide 
reductions in emissions of air pollutants through the Federal motor 
vehicle control program under title II of the Act (42 U.S.C. 7521-
7574), which involves controls for automobile, truck, bus, motorcycle, 
and aircraft emissions; the new source performance standards under 
section 111 (42 U.S.C. 7411); and the national emission standards for 
hazardous air pollutants under section 112 (42 U.S.C. 7412).

B. Existing Primary Standards for Carbon Monoxide

    On April 30, 1971, the EPA promulgated NAAQS for CO under section 
109 of the Act (36 FR 8186). Identical primary and secondary NAAQS were 
set at 9 ppm as an 8-hour average and 35 ppm as a 1-hour average, 
neither to be exceeded more than once per year. Scientific and 
technical bases for these NAAQS are provided in the document, ``Air 
Quality Criteria for Carbon Monoxide'' (U.S. Dept. of Health, Education 
and Welfare, 1970). The NAAQS promulgated in 1971 were based largely 
upon research by Beard and Wertheim (1967) who reported that CO 
exposures which produced carboxyhemoglobin (COHb) levels of 2 to 3 
percent were associated with central nervous system (CNS) effects such 
as impaired ability to discriminate time intervals.
    A revised Air Quality Criteria for Carbon Monoxide (U.S. EPA, 
1979a), prepared by the Environmental Criteria and Assessment Office 
(ECAO), and a Staff Paper (U.S. EPA, 1979b), prepared by the Office of 
Air Quality Planning and Standards (OAQPS), identified several major 
factors pertinent to subsequent action taken on the NAAQS for CO. The 
Clean Air Scientific Advisory Committee (CASAC) met on June 14-15, 1979 
to review drafts of these documents and provide advice on the CO 
standards. As discussed in a notice of proposed rulemaking (45 FR 
55066) published on August 18, 1980, although the Beard and Wertheim 
(1967) study no longer could serve as a basis for the CO NAAQS, other 
studies available in 1980 provided alternative evidence of decreased 
time to onset of angina attack at COHb levels as low as 2.7 to 3.0 
percent. This as well as other scientific evidence served as the basis 
for the EPA to propose: (1) Retaining the 8-hour primary standard level 
of 9 ppm, (2) revising the 1-hour primary standard level from 35 ppm to 
25 ppm, (3) revoking the existing secondary CO NAAQS due to a lack of 
evidence of adverse welfare effects at or near ambient CO levels, (4) 
changing the form of the standard from deterministic to statistical by 
stating allowable exceedances as expected values rather than as 
explicit values, and (5) adopting a daily interpretation for 
exceedances of the CO NAAQS so exceedances would be determined on the 
basis of days on which the 8- or 1-hour average concentrations were 
above the standard levels.
    On June 18, 1982, the EPA announced (47 FR 26407) that a second 
public comment period was necessary to open discussion on several 
important issues and additional analyses. These issues included: (1) 
The role of the Aronow (1981) study in assessing CO effects; (2) 
consideration of a multiple exceedance 8-hour standard for CO; (3) 
technical adequacy of the revised draft sensitivity analysis (Biller 
and Richmond, 1982) on the Coburn, Forster, and Kane model predictions 
of COHb levels; and (4) technical adequacy of the revised exposure 
analysis (Johnson and Paul, 1983). The CASAC met on July 6, 1982 to 
discuss these issues and provide advice, a summary of which was sent to 
the Administrator on August 31, 1982 (Friedlander, 1982).
    The 1980 proposal (45 FR 55066) was based in large part on studies 
by Dr. Wilbert Aronow (Aronow, 1978; Aronow, et al., 1972, 1973, 1974a, 
1974b, 1977; Aronow and Isbell, 1973; Aronow and Cassidy, 1975), which 
provided the CASAC and the EPA staff with a basis for concluding that 
COHb levels of 2.7-3.0 percent posed a health risk of concern in 
individuals with angina and other types of cardiovascular disease. A 
subsequent disclosure in March 1983 by the Food and Drug Administration 
(FDA) concerning work conducted for the FDA by Dr. Aronow caused the 
EPA to question the scientific credibility of Dr. Aronow's research on 
CO. As a result, the EPA decided it would be prudent to conduct an 
independent review of his CO research prior to making a decision on the 
CO standards. A committee of experts was convened and chaired by Dr. 
Steven Horvath (University of California, Santa Barbara). Following 
meetings with Dr. Aronow and examination of limited data and records 
available from his CO studies, the committee concluded in its report 
(Horvath et al., 1983) that the EPA should not rely on Dr. Aronow's 
studies for a decision on levels of the CO NAAQS due to problems 
regarding data collection/analysis.
    As a result of this finding, the ECAO prepared a draft Addendum to 
the 1979 Air Quality Criteria for Carbon Monoxide. Concurrently, the 
OAQPS prepared a draft Review of the NAAQS for Carbon Monoxide: 
Reassessment of Scientific and Technical Information. These documents 
were prepared to reevaluate the scientific and technical evidence on 
health effects of CO at or near ambient levels in consideration of the 
reduced usefulness of the Aronow studies. Both documents were reviewed 
by the CASAC at a public meeting on September 25, 1983. The CASAC sent 
a closure letter to the Administrator on May 17, 1984, which concluded 
that the draft Addendum and the draft Staff Paper Reassessment 
represented scientifically-balanced and defensible summaries of health 
effects literature for CO. On August 9, 1984, the EPA announced (49 FR 
31923) availability of the final Addendum (1984b) and final Staff 
Reassessment (1984a), both of which had been revised to reflect the 
CASAC's and public comments. In the same notice, the EPA reviewed the 
basis for the 1980 proposal to revise the CO standards and solicited 
additional public comment. In a subsequent Federal Register notice (50 
FR 37484) published on September 13, 1985, the EPA announced its final 
decision not to revise the existing primary standards and to revoke the 
secondary standards for CO. In doing so, the Administrator determined 
that the existing 1-hour and 8-hour primary NAAQS provided adequate 
protection from exposure to ambient CO.

C. Review of Air Quality Criteria and Standards for Carbon Monoxide; 
Development of the Staff Paper

    On July 22, 1987, the ECAO published in the Federal Register (52 FR 
27580) a call for information to assist in the development of a draft 
revised Air Quality Criteria for Carbon Monoxide (Criteria Document). 
Notice of availability of the external review draft Criteria Document 
was published in the Federal Register (55 FR 14858) on April 19, 1990. 
This draft Criteria Document included discussion of several new studies 
of effects of CO on angina patients, which had been initiated in light 
of the controversy discussed above. The CASAC reviewed the draft 
Criteria Document at a public meeting held on April 30, 1991. The EPA 
placed a transcript of the CASAC meeting in the docket (ECAO-CD-86-
073). The EPA carefully considered comments received from the public 
and the CASAC members in preparing the final Criteria Document (U.S. 
EPA, 1991). On July 17, 1991, the CASAC sent to the Administrator a 
``closure letter'' (McClellan, 1991) outlining key issues and 
recommendations and indicating that the document provides a 
scientifically-balanced and defensible summary of current knowledge of 
the effects of this pollutant and provides an adequate basis for the 
EPA to make a decision as to the appropriate primary NAAQS for CO.
    Immediately following the CASAC meeting of April 30, 1991, the 
OAQPS began development of the revised draft Staff Paper. This document 
was released for public review in February 1992. The CASAC held a 
public meeting on March 5, 1992 to review the draft revised Staff 
Paper. A copy of the transcript of this meeting has been placed in the 
docket (A-93-05). Major issues discussed at the meeting included: 
interpretation of new scientific information, the definition of adverse 
health effects associated with CO exposure, populations at risk, COHb 
levels of concern, and estimates of population exposure. In response to 
comments made by the public and the CASAC members, minor revisions to 
the Staff Paper were made and briefly reviewed at a public meeting of 
the CASAC held on April 28, 1992 prior to preparation of the final 
Staff Paper (U.S. EPA, 1992). The CASAC came to closure on its review 
of the Staff Paper in a letter to the Administrator dated August 11, 
1992. In that ``closure letter'' (McClellan, 1992) the CASAC states 
that ``this document is consistent with all aspects of the scientific 
evidence presented in the criteria document for carbon monoxide. It has 
organized the relevant information in a logical fashion and the 
Committee believes that it provides a scientifically adequate basis for 
regulatory decisions on carbon monoxide. The staff paper concludes, and 
the CASAC concurs, that a standard of the present form and with a 
numerical value similar to that of the present standard would be 
supported by the present scientific data on health effects of exposure 
to carbon monoxide.''

D. Decision Docket

    On February 2, 1993, the EPA created a docket (Docket No. A-93-05) 
for this decision. The docket incorporated by reference a separate 
docket established in 1986 for criteria document revision (Docket No. 
ECAO-CD-86-073).

II. Scientific Basis for This Regulatory Decision

A. Measuring and Assessing COHb Levels

    As concluded in the Staff Paper (U.S. EPA, 1992, p. 10), blood COHb 
level is not only the best indicator of CO exposure but also has been 
related to health effects of major concern for CO. In most CO health 
effects studies, the co-oximeter (CO-Ox) has been used to measure COHb 
at levels in the range of 0 to 5 percent COHb; however, concerns have 
been raised regarding accuracy of the CO-Ox.
    While CO-Ox measurements are very precise (i.e., replicable), 
research has shown that the accuracy (i.e., ability to detect the 
actual level) of these optical instruments is not always sufficient to 
use alone at levels  5 percent COHb (Allred et al., 1989a,b, 
1991). As indicated in the Criteria Document (U.S. EPA, 1991, pp. 8-72 
to 8-73), the results from linear regression analyses of comparisons 
between CO-Ox instruments and various reference instruments [involving 
gas chromatography (GC)] show a fairly linear slope and a wide range of 
intercept values, thus suggesting good precision but poor accuracy for 
the CO-Ox. In the only health effects study that used both CO-Ox and GC 
methods to measure COHb levels in subjects with heart disease, 
researchers found that the spread of COHb values was much greater for 
the CO-Ox values than for the GC values (Allred et al., 1989a,b, 1991).
    In order for optical instruments such as CO-Ox to be used to 
measure COHb levels accurately at low levels, they must be calibrated 
routinely with an alternative method (U.S. EPA, 1991, p. 8-64). When 
properly calibrated, CO-Ox instruments provide useful information on 
mean COHb values; however, variation in individual oxyhemoglobin 
(O2Hb) levels appears to influence COHb readings (Allred et al., 
1989a,b) and, as noted above, CO-Ox instruments also give a broader 
range of COHb values when compared to GC measurements on the same 
samples (Allred et al., 1989a,b, 1991). Although the CASAC identified 
the GC as the method of choice (McClellan, 1992), the fact that most of 
the health effects literature for CO relies on CO-Ox measurements led 
to the decision that CO-Ox data would be used in establishing levels of 
concern.

B. Health Effects Associated With Carbon Monoxide

    Health effects associated with exposure to CO include 
cardiovascular system effects, CNS effects, and developmental toxicity 
effects, as well as effects of combined exposure to CO and other 
pollutants, drugs, and environmental factors. Cardiovascular effects of 
CO are directly related to a reduced oxygen (O2) content of the 
blood caused by combination of CO with hemoglobin (Hb) to form COHb and 
resulting in tissue hypoxia. Most healthy individuals have mechanisms 
(e.g., increased blood flow, blood vessel dilation) which compensate 
for this reduction in tissue O2 levels, although the effect of 
reduced maximal exercise capacity has been reported in healthy persons 
even at low COHb levels. Compensatory mechanisms are less effective in 
elderly people, pregnant women, small children, and in certain people 
with anemia or pulmonary and cardiovascular diseases, thereby 
increasing their susceptibility to potential adverse effects of CO 
during exercise. Research studies considered most significant to the 
establishment of NAAQS for CO are summarized in Table 1 and are 
discussed below.
1. Mechanisms of Toxicity
     The mechanism of toxicity principally associated with health 
effects of greatest concern from CO exposure is hypoxia induced by 
elevated COHb levels. The primary exchange route for CO to human 
tissues is through the lungs. Although CO is a naturally occurring 
chemical in blood being produced endogenously by normal catabolic 
processes, blood COHb levels do not often exceed 0.5 to 0.7 percent in 
normal individuals unless exogenous CO is breathed. Some individuals 
with high endogenous CO production can have COHb levels of 1.0 to 1.5 
percent (e.g., anemics). Exogenous CO diffuses through the respiratory 
zone (alveoli) to the blood where it binds to Hb to form COHb. The 
chemical affinity of CO for Hb is 218 to 250 times greater than that of 
O2 (Roughton, 1970; Wyman et al., 1982; Rodkey et al., 1969). This 
preferential binding of CO to Hb limits the availability of Hb for 
O2 transport to tissues throughout the body. As COHb levels 
increase, the dissociation curve for normal human blood is shifted to 
the left resulting in more reduced delivery of O2 to tissues and a 
greater of CO-induced hypoxia. It is this reduced O2 delivery to 
heart muscle tissue which is of great concern for individuals with 
ischemic heart disease because their already compromised condition puts 
them at increased risk.

Table 1.--Key Health Studies for Establishing NAAQS for Carbon Monoxide 
------------------------------------------------------------------------
   COHb                                                                 
 concent.        Health effects                  Referencesb            
 percenta                                                               
------------------------------------------------------------------------
2.3-7.0...  Decreased short-term      Drinkwater et al. (1974), Ekblom  
             maximal exercise          and Huot (1972), Horvath et al.  
             duration in young         (1975), Raven et al. (1974a,b),  
             healthy men.              Weiser et al. (1978).            
2.9-5.9...  Decreased exercise        Adams et al. (1988), Allred et al.
             duration due to           (1989a,b; 1991), Anderson et al. 
             increased chest pain      (1973), Kleinman et al. (1989),  
             (angina) in patients      Sheps et al. (1987).             
             with ischemic heart                                        
             disease.                                                   
5.0-20.0..  Decreased maximal oxygen  Ekblom and Huot (1972), Klein et  
             consumption with short-   al. (1980), Pirnay et al. (1971),
             term strenuous exercise   Stewart et al. (1978), Vogel and 
             in young healthy men.     Gleser (1972), Weiser et al.     
                                       (1978).                          
5.0-20.0..  Equivocal effects on      Benignus et al. (1977, 1987,      
             visual perception,        1990a,b), Bunnell and Horvath    
             audition, motor and       (1988), Christensen et al.       
             sensorimotor              (1977), Gliner et al. (1983),    
             performance, vigilance,   Harbin et al. (1988), Hudnell and
             and other measures of     Benignus (1989), McFarland (1970,
             neurobehavioral           1973), McFarland et al. (1944),  
             performance.              Mihevic et al. (1983), O'Donnell 
                                       et al. (1971), Putz et al. (1976)
                                       Putz (1979), Roche et al. (1981),
                                       Rummo and Sarlanis (1974),       
                                       Seppannen et al. (1977), Von Post-
                                       Lingen (1964), Winneke (1974).   
------------------------------------------------------------------------
aBlood COHb levels determined by optical methods.                       
bReferences also found in U.S. EPA (1991) and U.S. EPA (1992).          

    Although several other mechanisms of toxicity are discussed in the 
Criteria Document (U.S. EPA, 1991), these are not considered to be as 
well understood as COHb hypoxia. Intracellular effects of CO (U.S. EPA, 
1991, pp. 9-22 to 9-31) have been associated with CO toxicity. 
Preferential binding of CO to myoglobin, cytochrome P-450, and 
cytochrome c oxidase has been studied and could lead to impairment of 
intracellular oxygen transport to mitochondria. However, mechanisms of 
toxicity associated with CO-induced inhibition of these hemoproteins at 
relevant CO levels are not well understood at this time and will 
require further research.
    Based on the review and conclusions drawn in the Criteria Document 
(U.S. EPA, 1991), COHb levels provide the most useful estimate of 
exogenous CO exposures and serve as the best biomarker of CO toxicity 
for ambient-level exposures to CO. Thus, COHb levels are used as the 
indicator of health effects and to identify the lowest effects level 
for CO.
2. Cardiovascular Effects
    The best documented cardiovascular effects of CO in patients with 
chronic heart disease are decreased time to onset of chest pain and ST-
segment depression during exercise stress. The commonly accepted 
criterion of exercise-induced myocardial ischemia is 1 mm or greater 
ST-segment depression. The ST segment is a portion of the 
electrocardiogram (ECG), depression of which is an indication of 
insufficient O2 supply to heart muscle tissue.
    Five key studies on cardiovascular effects of CO (Allred et al., 
1989a,b, 1991; Kleinman et al., 1989; Adams et al., 1988; Sheps et al., 
1987; Anderson et al., 1973) have provided evidence of the potential 
for CO to enhance development of exercise-induced myocardial ischemia 
in patients who suffer from angina pectoris. (Angina pectoris is a 
spasmodic, strangling sensation or heavy chest pain, often radiating to 
the arms, especially the left, most often due to lack of O2 to the 
heart muscle and precipitated by effort or excitement.) An early study 
by Anderson et al. (1973) reported decreased time to onset of angina 
pain for COHb levels as low as 2.9 (CO-Ox), representing a 1.6 percent 
increase in average COHb levels over baseline. Details of this study 
were reported at length in the Addendum (U.S. EPA, 1984b).
    More recent controlled exposure studies of angina patients have 
provided substantial new evidence of decreased time to early onset of 
chest pain. (See discussion in U.S. EPA, 1991, pp. 10-21 to 10-35). A 
study which provides strong evidence of the health effects of CO is the 
multicenter study of Allred et al. (1989a,b, 1991). There are several 
reasons why this particular study is important to the CO NAAQS review: 
(1) Dose-response relationships are shown, (2) information on ST-
segment depression of subjects is available, (3) COHb measurements were 
taken using both GC and CO-Ox, (4) a large number of subjects was used, 
and (5) it was conducted at multiple laboratories around the U.S. This 
study involved 63 males (41-75 years of age) with coronary artery 
disease living in three different U.S. cities. The objective was to 
assess the impact of exposure to CO on time to onset of significant 
ischemia during a standard treadmill test. Unusual care was taken to 
establish presence of coronary artery disease in all subjects prior to 
testing. The protocol for the study was quite similar to that used in 
the Aronow studies, i.e., two exercise tests were performed on the same 
day separated by a recovery period and a double-blind exposure period. 
Subjects were exposed to either clean air, 117 ppm CO, or 253 ppm CO 
for 50 to 70 minutes while performing symptom-limited exercise on a 
treadmill. Time to onset of angina and time to ST-segment depression 
were determined for each test following exposure to both CO levels and 
compared to clean air (<2 ppm CO) exposure. After exposure to 117 ppm 
and 253 ppm CO, COHb levels measured before the exercise stress test 
were 2.4 and 4.7 percent COHb (GC) and 3.2 and 5.6 percent COHb (CO-
Ox), respectively. After the stress test COHb levels were 2.0 and 3.9 
percent (GC) and 2.7 and 4.7 percent (CO-Ox). Using the objective 
measure of time to ST-segment depression, CO exposure which produced 
3.2 percent COHb (CO-Ox, pretest) resulted in a 5.1 percent (p=0.01) 
decrease in time to the ST criterion, and 5.6 percent COHb (CO-Ox, 
pretest) decreased time to the ST criterion by 12.1 percent (p<0.001) 
relative to clean air exposure. Combining slopes for the 62 individuals 
yielded a significant (p<0.005) regression which indicates that there 
was a 3.9 percent decrease in time to ST criterion for every 1 percent 
increase in COHb. Time to onset of angina also was reduced in the same 
subjects, and regression analysis yielded a significant relationship 
(p<0.025). Both endpoints (time to angina and time to ST change) were 
highly correlated.
    In another study (Sheps et al., 1987), 30 nonsmokers with ischemic 
heart disease (ages 38-75) were exercised during exposure to 100 ppm CO 
or air using a 3-day, randomized double blind protocol. Following CO 
exposure, average COHb levels were 4.1 percent (CO-Ox), representing a 
2.2 percent COHb increase from the initial COHb level. In comparing 
results of air-exposed subjects to CO-exposed subjects as a group, no 
statistically significant differences were reported in time to onset of 
angina, maximal exercise time, maximal ST-segment depression, or time 
to significant ST-segment depression. Although the authors concluded 
that 4.1 percent COHb did not produce clinically significant effects in 
the paired subject group, 3 of 30 patients did experience angina on CO-
exposure days but not on air-exposure days. Further analysis of the 30 
person data base from Sheps et al. (1987) of time to onset of angina 
that included these three patients indicated a statistically-
significant decrease for CO exposure compared to air exposure (Bissette 
et al., 1986). The same group of researchers (Adams et al., 1988) 
exposed 30 subjects with obstructive coronary artery disease to either 
air or sufficient CO to reach COHb levels of 5.9 percent (CO-Ox), 
representing an average increase of 4.2 percent COHb above initial COHb 
levels. As in the earlier study, several patients experienced angina on 
the CO-exposure day and not on the air-exposure day but never the 
reverse. Results of this study provide statistically significant 
evidence that exposure to CO induces earlier onset of angina and 
ventricular dysfunction as well as poorer exercise performance in 
patients with ischemic heart disease. Although the Sheps et al. (1987) 
and Adams et al. (1988) studies did not observe statistically-
significant changes in time to onset of angina using conventional 
statistical procedures, results of these studies are not incompatible 
with the rest of the studies reporting an effect of CO (U.S. EPA, 1991, 
p. 10-32).
    A separate study of effects of CO exposure was conducted with 26 
nonsmoking male, angina patients (Kleinman and Whittenberger, 1985; 
Kleinman et al., 1989). One hour of exposure to 100 ppm CO raised COHb 
levels to 3.0 percent (CO-Ox), representing an average increase of 1.5 
percent COHb over initial COHb level. For the group, CO exposure 
resulted in a decrease in time to onset of angina by 6.9 percent 
compared to clean air exposure (Kleinman and Whittenberger, 1985). This 
was a statistically-significant difference (p=0.03). Reanalysis, 
necessitated by dropping two subjects due to inconsistent medical 
records, resulted in an average decrease of 5.9 percent (p=0.046) in 
time to onset of angina for CO exposure compared to air exposure 
(Kleinman et al., 1989). For the eight patients who exhibited 
depression in the ST segment of ECG traces during exercise, there was a 
decrease of 10 percent (p<0.036) in time to onset of angina and a 
decrease of 19 percent (p<0.044) in time to onset of ST-segment 
depression.
    Allred et al. (1989b, 1991) discuss possible reasons for some 
differences in results of the above-cited studies. These studies have 
different designs, types of exercise tests, inclusion criteria (e.g., 
patient populations), exposure conditions, and measurement methods for 
COHb. Of the studies, only two (Allred et al., 1989a,b, 1991; Anderson 
et al., 1973) investigate more than a single target level of COHb, and 
of those two, only Allred et al. (1989a,b, 1991) demonstrate a dose-
response effect of COHb on time to onset of angina. Different 
measurement methodologies for COHb also may account for some of the 
discrepancies between studies. As discussed in Section V.C.1. of the 
Staff Paper (U.S. EPA, 1992) and in the Criteria Document (U.S. EPA, 
1991, pp. 8-70 to 8-74), only Allred et al. (1989a,b, 1991) used both 
the GC and CO-Ox to measure COHb and found the spread of COHb values to 
be much greater for the CO-Ox than for the GC. Another difference in 
the studies was that Allred et al. (1989a,b, 1991) used more rigorous 
subject entry criteria. All subjects were male, were required to have 
stable exertional angina and reproducible exercise-induced ST-segment 
depression and angina, and were required to have either a previous 
myocardial infarction, angiographic disease or a positive thallium 
test.
    The major conclusion which can be drawn regarding most of the 
studies discussed above is that all show a decrease in time to onset of 
angina at postexposure COHb levels ranging from 2.9 to 5.9 percent (CO-
Ox). This represents incremental increases of 1.5 to 4.4 percent COHb 
from preexposure baseline levels. Therefore, there are clearly 
demonstrable effects of low-level CO exposure in patients with ischemic 
heart disease (U.S. EPA, 1991, pp. 10-34 to 10-35). Across-study 
comparison is depicted in the Criteria Document (U.S. EPA, 1991, p. 10-
33), presented as an adaptation from Allred et al. (1989b, 1991), and 
suggests reasonably good consistency. For purposes of comparison, only 
optical methods (CO-Ox) were used to avoid confusion.
    The adverse nature of the effects described in the five key studies 
is uncertain due to the range of professional judgments on the clinical 
significance of small performance decrements produced by exercise and 
CO exposure. Although some physicians may not be greatly concerned 
about decrements in performance occurring around 3.0 percent COHb (CO-
Ox), consistency across studies of response for both decrease in time 
to onset of angina and ST-segment depression suggest that the effect 
does occur and may limit the activity of persons with ischemic heart 
disease. Bassan (1990) indicates that 58 percent of cardiologists 
believe that recurrent exercise-induced angina attacks are associated 
with substantial risk of precipitating myocardial infarction, fatal 
arrhythmia, or slight but cumulative myocardial damage (U.S. EPA, 1991, 
p. 10-35). Based on discussions in the Criteria Document (U.S. EPA, 
1991) and at the April 30, 1991 and March 5, 1992 CASAC meetings, staff 
recommended in the Staff Paper (U.S. EPA, 1992, p. 22) that 2.9 to 3.0 
percent COHb (CO-Ox), representing an increase above initial COHb of 
1.5 to 2.2 percent COHb, be considered a level of potential adversity 
for individuals at risk.
3. Effects on Exercise Capacity and Oxygen Uptake
    Maximal oxygen uptake and maximal exercise capacity are direct 
measures of cardiovascular capacity and can provide insight into the 
impact of CO on the cardiovascular systems of healthy individuals. 
Although decreases in these attributes may not be very serious in 
healthy persons for CO exposures typically found in the ambient air, 
they can be indicative of the extent to which an individual's ability 
to function normally may be affected while engaging in activities which 
require high levels of sustained exercise.
    Numerous researchers have studied the effects of CO on oxygen 
uptake and exercise performance in healthy individuals. Several 
investigators (Klein et al., 1980; Stewart et al., 1978; Weiser et al., 
1978; Ekblom and Huot, 1972; Vogel and Gleser, 1972; Pirnay et al., 
1971) found statistically-significant decreases (3 to 23 percent) in 
maximal oxygen uptake under conditions of short-term maximal exercise 
at COHb levels ranging from 5 to 20 percent (CO-Ox). Horvath et al. 
(1975) found that the lowest level at which COHb marginally influenced 
maximal oxygen uptake (p<0.10) was about 4.3 percent (CO-Ox); COHb 
levels of 3.3 percent and 4.3 percent (CO-Ox) reduced work time to 
exhaustion by 4.9 percent and 7 percent, respectively. Similar results 
were found following exhaustive treadmill exercise at 5 percent COHb 
(CO-Ox) (Stewart et al., 1978; Klein et al., 1980). Short-term maximal 
exercise duration has been shown to be reduced by 3 to 38 percent at 
COHb levels ranging from 2.3 to 7 percent (CO-Ox) (Horvath et al., 
1975; Drinkwater et al., 1974; Raven et al., 1974a,b; Weiser et al., 
1978; Ekblom and Huot, 1972). Since CO has not been shown to impair 
submaximal work capacity, changes in short-term maximal exercise should 
be of concern mainly for competing athletes (U.S. EPA, 1991, p. 10-73).
4. Central Nervous System Effects
    A variety of CNS effects has been found to be associated with CO 
exposures which result in COHb levels of 5 to 20 percent (CO-Ox). These 
effects include changes in visual perception, hearing, motor 
performance, sensorimotor performance, vigilance, and other measures of 
neurobehavioral performance.
    Of the behaviors studied, the most sensitive to disruption by COHb 
are those that require sustained attention or sustained performance. 
For example, the group of studies on motor and sensorimotor 
performance, which have used a variety of measures (e.g., fine motor 
skills, reaction time, and tracking), offer the most consistent 
evidence for effects occurring at COHb levels as low as 5 percent. 
Although Winneke (1974) found some effects on steadiness and precision 
at 10 percent COHb (CO-Ox), several other investigators (Mihevic et 
al., 1983; O'Donnell, 1971; Seppanen et al., 1977) reported no CO 
effect at COHb levels ranging from 5.5 to 12.7 percent (CO-Ox). 
Reaction time was unaffected by COHb levels of 7 and 10 percent (CO-Ox) 
(Rummo and Sarlanis, 1974; Winneke, 1974), and the pervasive finding is 
that COHb elevation does not affect reaction time for COHb levels as 
high as 20 percent (CO-Ox) (U.S. EPA, 1991, p. 10-118). Compensatory 
tracking was not significantly affected by COHb levels of 5.8 percent 
(CO-Ox) (Gliner et al., 1983) or by levels of 12 to 13 percent (CO-Ox) 
(O'Donnell et al., 1971); however, tracking tasks were significantly 
affected by COHb levels of 5 percent (CO-Ox) (Putz et al., 1976; Putz, 
1979). Results of the Putz et al. (1976) study were confirmed by 
Benignus et al. (1987) but not by Benignus et al. (1990a) when 
attempting to demonstrate a dose-effect relationship using the same 
experimental design. Benignus et al. (1990b) discusses possible reasons 
for high variability between studies, and the Criteria Document (U.S. 
EPA, 1991, p. 10-121) concludes that COHb elevation produces small 
decrements in tracking that are sometimes statistically significant. 
Numerous other studies (Benignus et al., 1977; Bunnell and Horvath, 
1988; Christensen et al., 1977; Harbin et al., 1988; Hudnell and 
Benignus, 1989; McFarland, 1970, 1973; McFarland et al., 1944; Roche et 
al., 1981; von Post-Lingen, 1964) provide additional support for 
neurobehavioral effects associated with COHb levels above 5 percent.
    Even though new information regarding neurobehavioral effects of 
COHb levels in the range of 5-20 percent (CO-Ox) has been published 
during the past decade, conditions under which these effects occur are 
poorly understood (U.S. EPA, 1991, p. 10-143). Because neurobehavioral 
effects have not yet been demonstrated at COHb levels below 5 percent 
(CO-Ox), the Staff Paper (U.S. EPA, 1992, p. 24) recommended focussing 
on the cardiovascular effects which have been reported at lower COHb 
levels. Standards which protect sensitive populations from adverse 
cardiovascular effects also should provide adequate protection against 
adverse neurobehavioral effects of CO occurring in the exposed 
population.
5. Developmental Toxicity Effects
    Developmental toxicity covers a variety of effects in the 
developing organism including fetal death, structural abnormalities, 
altered growth and functional deficits. The fetus may be particularly 
vulnerable to the toxic effects of CO exposure because fetal 
development often occurs at or near critical tissue oxygenation levels 
(Longo, 1977). The COHb levels tend to be naturally elevated in the 
fetus due to differences in uptake and elimination of CO from fetal 
hemoglobin.
    Human data on developmental toxicity of CO are very limited for 
obvious ethical reasons. Maternal smoking, however, has been associated 
with a number of adverse health effects, many of which can be 
attributed to very high CO exposures (500-1000 ppm) from cigarette 
smoke. These effects include spontaneous abortion and subsequent fetal 
death due to depressed birth weight, increased number of hospital 
admissions during the first 5 years of life, and poorer than predicted 
school performance during the first 11 years of life. These and other 
effects of smoking are reviewed in a report to the U.S. Surgeon General 
(National Institute of Child Health and Human Development, 1979). Data 
(Hoppenbrouwers et al., 1981) supporting a link between environmental 
CO exposure and sudden infant death syndrome (SIDS) are suggestive, but 
further study is needed before any causal relationship can be inferred.
    Finally, animal studies have provided evidence of fetal mortality, 
teratogenicity, reduced body weight, morphological changes, altered 
cardiovascular development, and neurochemical changes. However, these 
studies are often conducted at CO levels much greater than those found 
in the ambient air, and extrapolation to human health effects at 
ambient CO exposures remains very difficult.
6. Environmental Factors, Drugs, and Other Pollutants
    Several additional factors have been investigated for potential 
interactions with CO that may alter health effects. Among the more 
important are altitude, drugs, coexposure to other pollutants, and heat 
stress. Altitude is a matter of concern because of the large 
populations exposed to CO while living in cities above 1500 meters. 
While there are some data to support the possibility that effects of 
inhaling CO and effects of high altitude may be additive (Cooper et 
al., 1985; McDonagh et al., 1986), several studies even at 2,000 m to 
4,500 m show little or no additivity (McGrath, 1988; Horvath, 1988; 
Horvath and Bedi, 1989). Most other studies have been conducted at CO 
levels which are too high to be of regulatory use.
    There is evidence that interactions of drug effects with CO 
toxicity can occur in both directions, i.e., CO toxicity may be 
enhanced by drug use, and toxic or other effects of drugs may be 
altered by CO exposure. A recent study (Knisely et al., 1989) reported 
a large interaction of CO exposure and alcohol in mice, demonstrating 
that alcohol doubled the acute toxicity of CO. In the same study, CO 
exposure in combination with administration of barbiturates and other 
psychoactive drugs produced additive but not synergistic effects. 
Combined exposures of CO and other pollutants have been investigated 
primarily using animal subjects with only a few human studies being 
published. No interaction was observed in humans for CO in combination 
with common ambient air pollutants such as nitrogen dioxide, ozone, and 
peroxyacetyl nitrate (Raven et al., 1974a,b; Drinkwater et al., 1974; 
Gliner et al., 1975), although a greater decrement in exercise 
performance was reported in these studies when heat stress was combined 
with 50 ppm CO.
    The Staff Paper (U.S. EPA, 1992, p. 26) recommended that 
information on CO in combination with other pollutant exposures and 
environmental stresses be treated as a margin of safety consideration.

C. Populations Potentially at Risk

    In the Administrator's judgment, the available health effects data 
identify individuals with angina (e.g., history of heart disease) as 
the group at greatest risk from low-level, ambient air exposures to CO. 
Based on 1989 data of the American Heart Association (AHA, 1989) and 
1990 information from the Department of Health and Human Services 
(DHHS, 1990), individuals with both diagnosed and undiagnosed ischemic 
heart disease total approximately 10 to 11 million or about 4.5 percent 
of the U.S. population. As discussed earlier, concern for these 
individuals is due to the fact that their condition is due to an 
insufficient supply of oxygen to cardiac tissue. Further reduction in 
oxygen reserve capacity by exposure to CO increases the probability of 
adverse health effects occurring.
    Several other groups have been identified in the Criteria Document 
(U.S. EPA, 1991) and Staff Paper (U.S. EPA, 1992) as being potentially 
at risk of being sensitive to CO exposure. These groups include: (1) 
Persons with cerebrovascular disease, (2) those individuals with anemia 
or chronic obstructive lung disease, and (3) fetuses and young infants. 
In addition, visitors to high altitude locations may be more 
susceptible due to lower oxygen content in the air, and those persons 
using drugs or alcohol may be at greater risk due to the interactive 
health effects of CO with these substances. For a complete list of 
probable risk groups, see the Criteria Document (U.S. EPA, 1991, p. 12-
1).
    For many of the groups identified above, there is little or no 
experimental evidence to demonstrate that they are at increased risk of 
CO-induced health effects. However, it is reasonable to expect that 
individuals with preexisting illness (e.g., congestive heart failure, 
peripheral vascular or cerebrovascular disease, sickle-cell anemia, 
hematological disease, chronic obstructive lung disease) which limit 
oxygen absorption or oxygen transport to body tissues would be somewhat 
more susceptible to hypoxic (i.e., oxygen starvation) effects of CO 
(pp. 12-1 and 12-2, U.S. EPA, 1991). Since no human experimental 
evidence exists which identifies CO effects levels for these other 
groups, the Administrator is considering the possible effects of CO on 
these groups only in the determination of what constitutes an adequate 
margin of safety.

III. Rationale for This Decision

    This decision completes the EPA's review of health effects of CO 
assembled over a 5-year period and contained in the Criteria Document 
(U.S. EPA, 1991).2 This review includes the evaluation of key 
studies published through 1990 incorporated in the Criteria Document 
(U.S. EPA, 1991), the Staff Paper (U.S. EPA, 1992) assessment of most 
relevant information contained in the Criteria Document (U.S. EPA, 
1991), and the advice and recommendations of the CASAC as presented 
both in the discussion of these documents at public meetings and in the 
CASAC's 1991 (McClellan, 1991) and 1992 (McClellan, 1992) ``closure 
letters.''
---------------------------------------------------------------------------

    \2\ As previously noted, the EPA believes that section 307(d) 
does not require rulemaking procedures where the Administrator 
concludes that revision of an existing NAAQS is not appropriate.
---------------------------------------------------------------------------

A. Carboxyhemoglobin Levels of Concern

    In selecting the appropriate level(s) and averaging time(s) for the 
primary NAAQS for CO, the Administrator must first determine the COHb 
levels of concern taking into account a large and diverse health 
effects data base. The scientific quality and strength of health data 
are assessed in the Criteria Document (U.S. EPA, 1991) and in the Staff 
Paper (U.S. EPA, 1992). Based on these assessments, judgments are made 
here to identify those studies that are most useful in establishing a 
range of COHb levels to be considered in standard setting. In addition, 
the more uncertain or less quantifiable evidence is reviewed to 
determine the lower end of the range that would provide an adequate 
margin of safety from effects of clear concern. Those judgments 
relevant to the establishment of an appropriate range of COHb levels 
are summarized in the discussion below.
    The Administrator judges that cardiovascular effects, as measured 
by decreased time to onset of angina pain and by decreased time to 
onset of significant ECG 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. Decrease in time to 
onset of exercise-induced angina pain is well documented in studies of 
angina patients whose postexposure COHb levels have been raised to 2.9-
5.9 percent (CO-Ox), which represents incremental increases of 1.5 to 
4.4 percent COHb from baseline levels (Allred et al., 1989a,b, 1991; 
Kleinman et al., 1989; Adams et al., 1988; Sheps et al., 1987; Anderson 
et al., 1973). Time to onset of significant ECG ST-segment change, 
which is indicative of myocardial ischemia in patients with documented 
coronary artery disease and a more objective indicator of ischemia than 
angina pain, provides supportive evidence of health effects occurring 
as low as 2.9-3.0 percent COHb (CO-Ox). In light of the above data and 
discussions of adverse health consequences in the Criteria Document 
(U.S. EPA, 1991, p. 10-35) and Staff Paper (U.S. EPA, 1992, p. 29), at 
the April 30, 1991 and March 5, 1992 CASAC meetings, and in the July 
17, 1991 letter to the Administrator from the CASAC Chairman 
(McClellan, 1991), the Administrator concludes 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. As 
stated by McClellan (1991), ``Among health professionals there is a 
range of views as to the clinical significance of these changes with 
the dominant view being that the changes should be considered as 
adverse or a harbinger of adverse effects.'' It is important that 
standards be set to appropriately reduce the risk of ambient exposures 
which produce COHb levels that could induce such potentially adverse 
effects.
    Clinical importance of cardiovascular effects associated with 
exposures to CO resulting in COHb levels of 2 to 3 percent remains less 
certain. One recent study (Allred et al., 1989a,b) provides evidence of 
a 5.1 percent decrease in time to ST-segment depression at 2.0 percent 
COHb when using the GC to measure COHb levels. Although it is possible 
that there is no threshold for these effects even at lower COHb levels, 
the health significance of such small changes in ST-segment depression 
appears to be relatively trivial. The Administrator, therefore, 
concludes that results suggesting cardiovascular effects in angina 
patients when COHb levels are between 2.0 and 2.9 percent only be 
considered in evaluating whether the current CO standards provide an 
adequate margin of safety.

B. Margin of Safety

    There are several factors which the Administrator believes should 
be considered in evaluating the adequacy of the current CO NAAQS: (a) 
short-term reduction in maximal work capacity has been measured in 
trained athletes exposed to CO sufficient to produce COHb levels as low 
as 2.3 to 7 percent; (b) the wide range of human susceptibility to CO 
exposures and ethical considerations in selecting subjects for 
experimental purposes together suggest that the most sensitive 
individuals have not been studied; (c) animal studies of developmental 
toxicity and human studies of the effects of maternal smoking provide 
evidence that exposure to high concentrations of CO can be detrimental 
to fetal development, although very little is known about the effects 
of ambient CO exposures on the developing fetus; (d) though little is 
known about effects of CO on potentially sensitive populations other 
than those with ischemic heart disease, there is reason for concern 
about visitors to high altitudes, individuals with anemia or 
respiratory disease, and the elderly; (e) impairment of visual 
perception, sensorimotor performance, vigilance or other CNS effects 
has not been demonstrated to be caused by CO concentrations commonly 
found in the ambient air; however, short-term peak CO exposures may be 
responsible for impairments which could be a matter of concern for 
complex activities such as driving a car; (f) limited evidence suggests 
concern for individuals exposed to CO concurrently with drug use (e.g., 
alcohol) during heat stress, or coexposure to other pollutants; (g) 
large uncertainties remain regarding modelling COHb formation and 
estimating human exposure to CO which could lead to overestimation or 
underestimation of COHb levels in the population associated with 
attainment of a given CO NAAQS; and (h) COHb measurements made using 
the CO-Ox may not reflect COHb levels in angina patients studied, 
thereby creating uncertainty in establishing a lowest effects level for 
CO.
    In summary, the Administrator concludes that the lowest COHb level 
at which adverse effects have been demonstrated in persons with angina 
is around 2.9-3.0 percent, representing an increase of 1.5 percent 
above baseline when using the CO-Ox to measure COHb. These data serve 
to establish the upper end of the range of COHb levels of concern. 
Taking into account uncertainties in the data, the less significant 
health endpoints, and less quantifiable data on other potentially 
sensitive groups, staff recommends that the lower end of the range be 
established at 2.0 percent COHb. Below this level, the potential for 
public health risk appears to be small. The Administrator, therefore, 
concludes that results suggesting cardiovascular effects in angina 
patients when COHb levels are between 2.0 and 2.9 percent only be 
considered in evaluating whether the current CO standards provide an 
adequate margin of safety.

C. Relationship Between CO Exposure and COHb Levels

    In order to set ambient CO standards based on an assessment of 
health effects at various COHb levels, it is necessary to estimate the 
ambient CO concentrations that are likely to result in COHb levels of 
concern. The Criteria Document (U.S. EPA, 1991, p. 9-21) concludes that 
the best all around model for predicting COHb levels is the Coburn, 
Forster, Kane (CFK) differential equation (Coburn et al., 1965). The 
CFK model estimates COHb levels resulting from exposure to CO 
concentrations as a function of time and various physiological and 
environmental factors (e.g., blood volume, endogenous CO production 
rate, ventilation rate, altitude).
    Over the last 20 years, modelers have developed and evaluated both 
linear and nonlinear solutions to the CFK model. The linear CFK model 
assumes that O2Hb is constant and does not vary with COHb level. 
The nonlinear CFK model incorporates the interdependence between 
O2Hb and COHb. At COHb levels below 6 percent, both approaches 
give estimates that are within 0.5 percent COHb (Smith, 1990). While 
the linear CFK model is easier to solve and gives approximately the 
same COHb estimate in the range of interest (i.e., 1 to 5 percent 
COHb), the nonlinear solution tends to be more accurate physiologically 
(U.S. EPA, 1992, p. 12). With the assumption of a linear relationship 
between O2Hb and COHb, there is an analytical solution to the nonlinear 
CFK equation (Muller and Barton, 1987).
    The Staff Paper (U.S. EPA, 1992, p. 13) provides baseline estimates 
(i.e., typical physiological parameters are used) of COHb levels 
expected to be reached by nonsmokers exposed to various constant 
concentrations of CO for either 1 or 8 hours based on the CFK model. 
(Smokers are not included because they have voluntarily exposed 
themselves to high CO levels.) There are, however, two major 
uncertainties involved in estimating COHb levels resulting from 
exposure to CO concentrations. First, among the population with 
cardiovascular disease, or any other group of interest, there is a 
distribution for each of the physiological parameters used in the CFK 
model. Past work (Biller and Richmond, 1982) has shown that these 
variations are sufficient to produce noticeable deviations from the 
COHb levels. Second, predictions based on exposure to constant CO 
concentrations can underestimate or overestimate response of 
individuals exposed to widely fluctuating CO levels that typically 
occur in the ambient environment (Biller and Richmond, 1992).

D. Estimating Population Exposure

    The Agency's review includes an analysis of CO exposures expected 
to be experienced by residents of Denver, Colorado, under air quality 
scenarios related to the current situation when the 8-hour CO NAAQS is 
just attained. (The 8-hour CO NAAQS is modeled because it is the 
``controlling standard'' in Denver and in every other U.S. 
nonattainment area for CO.) The analysis includes passive smoking and 
gas stove CO emissions as indoor sources of CO pollution. However, it 
does not include other less-common CO sources (e.g., wood stoves, 
fireplaces, and faulty furnaces). Although these sources of exposure 
may be of concern for such high risk groups as individuals with 
cardiovascular disease, pregnant women, and their unborn children, the 
contribution of indoor sources cannot be effectively mitigated by 
ambient air quality standards. The exposure analysis is abstracted in 
the Staff Paper (U.S. EPA, 1992) and reported in more complete form in 
Johnson et al. (1992).
    The analysis indicates that if the current 8-hour standard is 
attained, the proportion of the nonsmoking population with 
cardiovascular disease experiencing exposures at or above 35 ppm for 1 
hour and 9 ppm for 8 hours decreases by an order of magnitude or more, 
down to less than 1 percent of the total person-days in that 
population. Likewise, attaining the current 8-hour standard reduces the 
proportion of the nonsmoking cardiovascular-disease population person 
days at or above COHb levels of concern by an order of magnitude or 
more. At the 8-hour standard, the EPA estimates that fewer than 0.1 
percent of the nonsmoking cardiovascular-disease population would 
experience a COHb level  2.1 percent (U.S. EPA, 1992, p. 
40). A smaller population is estimated to exceed higher COHb 
percentages.

E. Decision on the Primary Standards

    Based on this assessment, and considering the 1985 review of 
similar CO effects and effects levels, the Administrator concludes that 
the evaluation of adequacy of the current CO standards 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 or greater. 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.
    Based on the exposure analysis results described above, the 
Administrator concludes that relatively few people of the 
cardiovascular sensitive population group analyzed will experience COHb 
levels  2.1 percent when exposed to CO levels in the absence 
of indoor sources when the current ambient standards are attained. The 
analysis also indicates, however, that certain indoor sources (e.g., 
passive smoking, gas stove usage) contribute to total CO exposure. In 
addition, other indoor CO sources such as wood stoves and fireplaces 
also contribute to total CO exposure, but they were not explicitly 
modeled. Although these sources of exposure may be of concern for such 
high risk groups as individuals with cardiovascular disease, pregnant 
women, and their unborn children, the contribution of indoor sources 
cannot be effectively mitigated by ambient air quality standards.
    When the EPA promulgated CO primary NAAQS on April 30, 1971 (36 FR 
8186), two averaging times--1-hr and 8-hr--were selected. The 8-hr 
standard was chosen because most individuals, even at rest, appear to 
approach equilibrium levels of COHb after 8 hours of exposure. In 
addition the 8-hr period approximates blocks of time for which people 
are often exposed in a particular location or activity (e.g., sleeping, 
working) and provides a good indicator for tracking continuous 
exposures that occur during any 24-hr period. The 1-hr standard was 
chosen because a 1-hr averaging period provides a better indicator of 
short-term health effects of CO. The 1-hr standard provides reasonable 
protection from effects which might be encountered from very short 
duration peak (bolus) exposures in the urban environment. Review of 
current scientific information in the Criteria Document (U.S. EPA, 
1991) indicates that these reasons for choosing averaging times for the 
CO standards remain valid and there are no compelling arguments for 
selecting new or different averaging times. The Administrator also 
considered and concurs with the staff recommendations contained in the 
Staff Paper (U.S. EPA, 1992) that both averaging times be retained for 
primary CO standards.
    For the above reasons, the Administrator determines under section 
109(d)(1) that revisions of the current 1-hr (35 ppm) and 8-hr (9 ppm) 
primary standards for CO are not appropriate at this time. As discussed 
more fully above, this determination is based on and completes the 
EPA's review of the health effects information contained in the final 
Criteria Document (U.S. EPA, 1991), the assessment in the final Staff 
Paper (U.S. EPA, 1992), and comments made by the CASAC (McClellan, 
1991, 1992).

IV. Final Decision Not To Revise the Standards

    The EPA has completed its review and revision of the air quality 
criteria document concerning the national primary and secondary air 
quality standards for CO and has made a final decision pursuant to CAA 
section 109(d)(1) that no revision of the standards for CO is 
appropriate. This decision is a final Agency action based on a 
determination of nationwide scope and effect. It is, therefore, subject 
to judicial review under CAA section 307(b) exclusively in the U.S. 
Court of Appeals for the District of Columbia Circuit. Any petition for 
judicial review of this final action must be filed within sixty days 
after August 1, 1994.

V. Regulatory Impacts

A. Regulatory Impact Analysis

    Under Executive Order 12866 [58 FR 51,735 (October 4, 1993)], the 
Agency must determine whether the regulatory action is ``significant'' 
and, therefore, subject to Office of Management and Budget (OMB) review 
and the requirements of the Executive Order. The Order defines 
``significant regulatory action'' as one that is likely to result in a 
rule that may:
    (1) have an annual effect on the economy of $100 million or more or 
adversely affect in a material way the economy, a sector of the 
economy, productivity, competition, jobs, the environment, public 
health or safety, or State, local, or tribal governments or 
communities;
    (2) create a serious inconsistency or otherwise interfere with an 
action taken or planned by another Agency;
    (3) materially alter the budgetary impact of entitlements, grants, 
user fees, or loan programs or the rights and obligations or recipients 
thereof; or
    (4) raise novel legal or policy issues arising out of legal 
mandates, the President's priorities, or the principles set forth in 
the Executive Order.''
    Pursuant to the terms of Executive Order 12866, the OMB has 
notified the EPA that this action is a ``significant regulatory 
action'' within the meaning of the Executive Order. For this reason, 
this action was submitted to the OMB for review. Changes made in 
response to the OMB suggestions or recommendations will be documented 
in the public record.

B. Impact on Small Entities

    Under the Regulatory Flexibility Act (RFA), 5 U.S.C. 601 et seq., 
the EPA must prepare initial and final regulatory flexibility analyses 
assessing the impact of certain decisions on small entities. These 
requirements are inapplicable to rules or other actions for which the 
EPA is not required by the Administrative Procedure Act (APA), 5 U.S.C. 
551 et seq., or other law to publish a notice of proposed rulemaking 
[(5 U.S.C. 603(a), 604(a)]. Under section 307(d) of the Act, as the EPA 
interprets it, neither the APA nor the Act requires rulemaking 
procedures where the Agency decides to retain existing NAAQS without 
change. Accordingly, the EPA has determined that the impact assessment 
requirements of the RFA are inapplicable to this final decision.

VI. Other Reviews

    This decision was submitted to the OMB for review. Comments from 
the OMB and the EPA's responses to these comments are available for 
public inspection at the EPA's Air and Radiation Docket Information 
Center (Docket No. A-93-05), South Conference Center, Room 4, Waterside 
Mall, 401 M Street, S.W., Washington, DC.

List of Subjects in 40 CFR Part 50

    Environmental protection, Air pollution control, Carbon monoxide, 
Ozone, Sulfur oxides, Particulate matter, Nitrogen dioxide, Lead.

    Dated: July 15, 1994.
Carol M. Browner,
Administrator.

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[FR Doc. 94-18659 Filed 7-29-94; 8:45 am]
BILLING CODE 6560-50-P