National Ambient Air Quality Standards for Carbon MonoxideFinal Decision

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.

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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

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COHb

concent. Health effects Referencesb

percenta

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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).

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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 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.''

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\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.

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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]

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