REVIEW OF THE NAAQS FOR CARBON MONOXIDE:
1983 REASSESSMENT OF SCIENTIFIC AND
TECHNICAL INFORMATION
August 1983
Strategies and Air Standards Division
Office of Air Quality Planning and Standards
U.S. Environmental Protection Agency
Research Triangle ParK , NC 27711
DRAFT
DO NOT QUOTE OR CITE
Th.is document is a preliminary draft. It has not been formally
released by EPA and should not at this stage be construed to
represent Agency policy. It is being circulated for comment
on its technical accuracy and policy implications.
-------
TABLE OF CONTENTS
I. PURPOSE 1
II. BACKGROUND 1
A. Legislative Requirements
B. Original CO Standards and Proposed 2
Revisions of the Standards
C. Developments Subsequent to Proposal 4
III. APPROACH 5
IV. CRITICAL ELEMENTS IN THE PRIMARY STANDARDS REVIEW 7
A. Mechanisms of Toxicity 7
B. Reported Effects, Levels of Effects, 8
and Severity of Effects
1. Cardiovascular Effects 8
2. Neurobehavioral Effects 12
3. Perinatal Effects 13
C. Sensitive Population Groups 14
D. Uncertainty in Estimating COHb Levels 17
E. Exposure Analysis Estimates 21
F. Margin of Safety Considerations 24
V. FACTORS TO BE CONSIDERED IN SELECTING PRIMARY STANDARDS 28
A. Averaging Times 28
B. Form of the Standards 28
C. Levels of the Standards 30
D. Staff Conclusions and Recommendations 32
REFERENCES
-------
,.i
REVIEW OF THE NAAQS FOR CARBON MONOXIDE:
1983 REASSESSMENT OF SCIENTIFIC AND TECHNICAL INFORMATION
I.
PURPOSE
The purpose of this paper is to evaluate the key studies and scientific
information contained in the draft EPA document, "Revised Evaluation of
Heal th Effects Associ ated wi th Carbon Monoxi de Exposure:
An Addendum to
the 1979 EPA Air Quality Criteria Document for Carbon Monoxide,"1 and to
identify the critical elements that the EPA staff believe should be considered
in the review and possible revision of the current primary and secondary
national ambient air quality standards (NAAQS) for carbon monoxide (CO).
The paper also provides staff recommendations on alternative regulatory
approaches.
II.
BACKGROUND
A.
Legislative Requirements
Since 1970 the Clean Air Act has provided authority and guidance
for the listing of certain ambient air pollutants which may endanger public
health or welfare and the setting and revising of NAAQS for those pollutants.
Primary standards must be based on health effects criteria and provide an
adequate margin of safety to ensure protection of public health.
As several
recent judicial decisions have made clear, the economic and technological
feasibility of attaining primary or secondary standards are not to be
c
considered in setting them, although such factors should be considered in
the development of state plans to implement the standards.2,3
The requirement that primary standards provide an adequate margin of
safety was intended' to address uncertai nti es associ ated wi th i nconcl usi ve
scientific and technical information available at the time of standard
setting as well as to provide a reasonable degree of protection against
-------
~
2
hazards that research has not yet identified.2,3 Thus in providing an
adequate margin of safety, the Administrator is regulating not only to
prevent pollution levels that have been demonstrated to be harmful, but
also to prevent pollutant levels for which the risks of harm, even if not
precisely identified as to nature or degree, are considered unacceptable.
In weighing these risks for margin of safety purposes, 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 other
uncertainties that must be addressed.
The selection of any particular
approach to providing an adequate margin of safety is a policy choice left
specifically to the Administrator.2
Secondary standards must be based on the welfare effects criteria and
must protect the public welfare from any known or anticipated adverse
effects associated ~th the presence of the pollutant in the ambient air.
Welfare effects are defined in section 302(h) of the Clean Air Act to
include effects on soil, water, crops, vegetation, man-made materials,
animals, weather, visibility, hazards to transportation, economic values,
personal comfort and well-being, and similar factors.
The Clean Air Act requires periodic review and, if appropriate, revision
of existing criteria and standards.
If, in the Administrator.s judgment,
the Agency.s review and revision of criteria make appropriate the proposal
of new or revised standards, such standards are to be revised and promulgated
in accordance with section 109{b} of the Act.
Alternatively, the Administrator
may find that revision of the standards is not appropriate and conclude the
review by reaffirming them.
B.
Original CO Standards and Proposed Revisions of the Standards
Original CO Standards.
On April 30,1971, the Environmental
Protection Agency promulgated NAAQS for CO under section 109 of the Clean.
-------
3
Ai r Act (36 FR 8186).
Identical primary and secondary standards were set
at levels of 9 ppm, 8-hour average, and 35 ppm, I-hour average, neither to
be exceeded more than once per year.
The scientific and medical bases for
these standards are described in the 1970 document, "Air Quality Criteria
for Carbon Monoxide.1I4 The standards set in 1971 were primarily based on
work by Beard and Wertheim (1967)5 suggesting that low-level CO exposures
resulting in carboxyhemoglobin (COHb) levels of 2 to 3 percent were associated
with impairment of ability to discriminate time intervals, a central nervous
system effect.
Proposed Revisions of the Standards.
In 1979, EPA published a revised
Criteria Document for C06 and a Staff Paper6a in which several key considerations
were identified as major factors in the possible revision of the CO standards.
As discussed in the August 18, 1980 proposal notice (45 FR 55066), the 1979
Criteria Document,6 and the Staff Paper,6a the Beard and Wertheim study5 is no
longer considered a sound scientific basis for the primary CO standards.
However, medical evidence published since 1970 indicated, at the time of
proposal, that aggravation of angina and other cardiovascular diseases may
occur at COHb levels as low as 2.7 to 3.0 percent.
Assessment of this
and other medical evidence led EPA to propose: (1) retaining the 8-hour
primary standard level of 9 ppm, (2) revising the I-hour primary standard
level from 35 ppm to 25 ppm, (3) revoking the existing secondary CO standards
(since no adverse welfare effects have been reported at or near ambient CO
levels), (4) changing the form of the standard from deterministic to statistical
(i .e., EPA proposed to state allowable exceedances as expected values
rather than as explicit values), and (5) adopting a daily interpretation
for exceedances of the CO standards, so that exceedances would be determined
on the basis of the number of days on which the 8- or I-hour average concentrations
were above the standard levels (45 FR 55066).
-------
4
C.
Developments Subsequent to Proposal
On June 18, 1982, EPA announced (47 FR 26407) an additional publi.c
comment period concerning several key issues and technical documents related
to the review of the CO standards.
These issues included:
(1) the role of
the Aronow (1981) study,7 (2) consideration of a multiple exceedance 8-hour
standard, (3) the technical adequacy of the revised draft sensitivity
analysis8 on the Coburn model predictions of COHb levels, and (4) the
technical adequacy of the revised exposure analysis.9
The Clean Air
Scientific Advisory Committee (CASAC) met on July 6, 1982 to provide its
advice on these issues.
CASAC's recommendations arising from that meeting
are summarized in an August 31,1982 letter to the Administrator.l0
The 1980 proposal (45 FR 55066) was based in part on several health
studies conducted by Dr. Wilbert Aronow.11-17
Based largely on evaluation of
these studies in 1979 by EPA staff and CASAC, it was concluded at the time
of proposal that COHb levels of 2.7-3.0 percent represent a he~lth concern
for individuals ~th angina and other types of cardiovascular heart disease.
In March 1983 EPA learned that the Food and Drug Administration (FDA)
had raised serious questions regarding the technical adequacy of several
studies conducted by Dr. Aronow on experimental drugs, leading FDA to
reject use of the Aronow drug studies data.
While there was no direct
evidence that similar problems might exist for'Dr. Aronow's CO studies, EPA
concluded that an independent assessment of these studies was advisable prior
to a final decision on the CO NAAQS.
An expert committee was convened by
EPA and met ~th Dr. Aronow to discuss his studies and to examine the
limited available data and records from his CO studies.
In its report,18
the Committee (chaired by Dr. Steven M. Horvath, Director of the Institute
of Environmental Stress, University of California - Santa Barbara) concluded
-------
5
that EPA should not rely on Dr. Aronow's data due to concerns regarding
various problems asociated with the studies which substantially limit the
validity and usefulness of the studies results.
The Environmental Criteria and Assessment Office (ECAO) has prepared a
draft Addendum1 to the 1979 CO Criteria Document which re-evaluates the
scientific data base concerning health effects associated with exposure to
CO at or near ambient exposure levels, in light of the diminished value .of
the Aronow studies and taking into account any new findings that have become
available beyond those reviewed in the 1979 CO Criteria Document.
III.
APPROACH
The approach used in this paper is to assess and integrate information
derived from the draft Addendum to the 1979 CO Criteria Document and other
staff analyses in the context of those critical elements which the staff
believes should be considered in the review of the primary (health based)
standards.
Only the primary standards are addressed, because, as explained
in the proposal notice (45 FR 55066), no standards appear to be requisite
to protect the public welfare from any known or anticipated adverse effects
from ambient CO exposures.
Particular attention is drawn to those judgments
that must be based on careful interpretation of incomplete or uncertain
evidence.
In such instances, the paper states the staff's evaluation of
the evidence as it relates to a specific judgment, sets forth appropriate
alternatives that should be considered, and recommends a course of action.
Section IV reviews and integrates important scientific and technical
information relevant to review of the primary CO standards.
The essential
elements with regard to the primary standards that are addressed in
Section IV include the following:
-------
6
(1 )
(2 )
(3 )
identification of possible mechanisms of toxicity;
description of effects of concern including reported effect levels;
identification of the most sensitive population groups and
estimates of their size;
(4)
discussion of uncertainties in estimating COHb levels that result
from exposures to CO;
(5 )
estimates of the number of sensitive persons that would reach.
various COHb levels upon attainment of alternative standards; and
(6 )
discussion of margin of safety considerations.
Drawi ng from the di scussi on and i nformati on presented in Secti on IV,
Section V identifies and assesses the factors that should be considered in
selecting among alternative regulatory approaches.
Preliminary staff
recommendations on alternative policy options also are presented.
-------
7
IV.
CRITICAL ELEMENTS IN THE PRIMARY STANDARDS REVIEW
Mechanisms of Toxicity
A.
At the time of proposal of the NAAQS for CO. the primary mechanism
for toxic effects from CO exposure was thought to be hypoxia resulting
from COHb formation.
Several other possible mechanisms of toxicity were
addressed in the 1979 Criteria Document but at the time of publication
were not considered of major importance compared to COHb hypoxia at
ambient CO exposure levels.
Presently, the most important mechanism of CO toxicity at low-level
CO exposures is still thought to be COHb hypoxia.
This mechanism involves
diffusion of exogenous CO through the lungs into the blood ~th resultant
formation of COHb.
CO hypoxia results from preferential binding of CO by
hemoglobin, thus reducing the amount available to bind oxygen (02).
The CO
bound to hemoglobin affects the binding of 02 to the remaining hemoglobin
and, thus, further reduces the 02 delivery to tissues.
Because the
affinity constant for CO is between 200 and 250 times that for 02, blood
levels of 2 to 4.5 percent COHb can result from continued exposure to
concentrations of CO as low as 20 to 150 ppm ~thin two hours for individuals
engaged in moderate activity (ventilation rate = 20 liters per minute).
Models designed to estimate COHb levels arising from CO exposure have
been developed by Coburn et al. (1965).19
Other possible mechanisms of toxicity have been discussed by Coburn
(1979).20
These alternative mechanisms involve binding of CO to such
hemoproteins as cytochrome oxidase, myoglobin, tryptophan deoxygenase,
and tryptophan catalase.
Because the affinity constants for these proteins
are much less than that for hemoglobin, it is unlikely that they playa
major role in CO hypoxia.
However, in tissues with a high 02 gradient
-------
8
between blood and tissue, it is reasonable to assume that the interaction
of CO with these proteins (particularly with myoglobin in heart muscle)
may playa role in CO toxicity.
The conclusion drawn in the draft
Addenduml is that regardless of the mechanism of toxicity, COHb levels
provide a meaningful and useful physiological marker to estimate both
endogenous production of CO and exposure to exogenous sources of CO.
Presently COHb levels provide the best marker available for CO toxicity.
B.
Rep6rted Eff~cts, Levels6f Effect~, and Severity 6f Effects
Table 1 is a summary of key clinical studies reporting human health
effects associ ated wi th 1 ow-l evel exposures to CO.
This table is based
on evidence discussed in the 1979 Criteria Document6 and in the Draft
Addenduml but excludes a series of studies by Dr. Aronow due to problems
which substantially limit the validity and usefulness of the Aronow
studies.18 Table 1 is intended to be used in conjunction with the following
discussion, but each study should be viewed in light of the qualifications,
if any, discussed in the 1979 CO Criteria Document, in the draft Addendum,
and in this staff reassessment.
Cardiovascular Effects
1.
The lowest observed CO exposure levels producing human health effects
have been reported in individuals suffering from chronic angina pectoris.
Angina pectoris, commonly referred to simply as angina, is a symptom of
cardiovascular stress in which mild exercise or excitement can produce
pressure or pain in the chest due to insufficient oxygenation of heart
muscle.
Anderson et al. {l973)21 reported that experimental subjects with angina
exhibit statistically significant reduced time to onset of exercise-induced
-------
TABLE 1.
9
Lowest Observed Effect Levels For Human Health Effects
Associated With Low Level Carbon Monoxide Exposure
Effects
Statistically significant decreased
exercise capacity (i .e.,
~hortened duration of exercise
before onset of pain) in patients
~th angina pectoris and increased
duration of angina attacks
Statistically significant decreased
(-5-7%) work time to exhaustion
in exercising young healthy men
Statistically significant decreased
maximal oxygen consumption and
exercise time during strenuous
exercise in young healthy men
No statistically significant
vigilance decrements after
exposure to CO
Statistically significant
decreased maximal oxygen
consumption during strenuous
exercise in young healthy men
Statistically significant impair-
ment of vigilance tasks in
healthy experimental subjects
Statistically significant diminu-
tion of visual perception, manual
dexterity, ability to learn, or
performance in complex sensorimotor
tasks (such as driving)
COHb concen-
trati on, %a
References
2.9-4.5
Anderson et al.,' 197321
3.3 and
4.3
Horvath et ale ,'197530
5-5.5
Klein et al., 198033
Stewart et al., 197832
Wei ser et al., 198078
Be low
5
Haider et al.~ 197635
Wi nneke, 1973 J6
Christensen et al., 197737
Benignus and Otto~ 197738
Putz et al., 1976J9
Ekblom and Huot, 197229
Pirnay et al. 197176
Vogel and Gleser, 197277
7-20
5-7.6
Horvath et al. , 197144
Groll-Knapp et al., 197245
Fodor and Winnekej 197246
Putz et al., 1976 9
Bender, et al.~ 197147
Schulte, 197340
O'Donnell et al., 197149
McFarland et al.d 194441
McFarland, 19735
Putz et al., 197639
Salvatore, 197451
Wright et al., 197352
Rockwell and Weir, 197553
Rummo and sarlanis~ 197454
Putz et a14j 19794
, Put z, 1979 '
5-17
aThe physiologic norm (i .e., COHb levels resulting from the normal catabolism
of hemoglobin and other heme-containing materials) has been estimated to be
in the range of 0.3 to 0.7 percent (Coburn et al., 1963).28
-------
10
angina after exposure to low levels of CO resulting in mean COHb levels
of 2.9 (range 1.3-3.8 percent) and 4.5 percent (range 2.8-5.4 percent).
In the same study, it was reported that subjects experienced statistically
significant increases in duration of angina attacks during exercise at a
mean COHb level of 4.5 percent.
As discussed in the draft Addendum1, the
Anderson et al. (1973)21 study provides reasonably good evidence for the above
effects occurring in angina patients at mean COHb levels of 2.9 to 4.5
percent.
There remain some concerns about the study findings due to
ambiguities regarding the design and conduct of the study and the small
number of subjects (N=10) examined.
In similar studies Aronow et al. (1973)12 and Aronow (1981)7 report
decreased time to onset of angina for exercising subjects ~th reported
COHb levels in the range of 2 to 3 percent.
In addition, Aronow et al.
(1974)13 reported that subjects ~th peripheral vascular disease had
reduced time to onset of leg pain at similar COHb levels.
As discussed
earlier, however, these results should be considered only in developing
a margin of safety for effects below 3 percent COHb.
Until independent
studies attempting to replicate the Aronow studies have been completed,
more conclusive statements are not possible concerning effects on individuals
~thangina or peripheral vascular disease at COHb levels below 2.9
percent COHb.
In another controlled human experimental study, Davies and Smith
(1980)22 reported possible effects on cardiac function in healthy individuals
exposed continually to 0 ppm CO (0.5 percent COHb), 15 ppm CO (2.4 percent
COHb), or 50 ppm CO (7.1 percent COHb) for 8 days.
P-wave changes taken from
EKG tracings were reported in 3 of 15 subjects at 15 ppm CO, in 6 of 15
at 50 ppm CO, and 0 of 14 at 0 ppm CO.
One subject showed marked $-T
-------
11
segment changes at 15 ppm CO.
It was suggested by the authors that
P-wave changes reported were due to interference by CO of normal atrial
pacemaking or conducting tissue activity.
Although they hypothesize that
CO specifically affects the myocardial tissue as well as reduces blood
oxygenation, the P-wave changes reported in this study have not yet been
identified as adverse.
Increased blood flow was reported by Ayres et ale (1969,1970,
1979).23,24,79 This effect occurs as a compensatory response to CO exposure
and may be related to coronary damage or cerebrovascular effects at very
high blood flow rates due to the added stress on the vascular system.
Community epidemiology studies which may have provided supporting evidence
for these effects, however, have instead provided inconclusive results.
In the Goldsmith and Landau (1968),25 Kurt et ale (1978),26 and Kurt et
ale
(1979)27 studies the relationships between CO exposure and mortality
from myocardial infarction (heart attack), sudden death due to atherosclerotic
heart disease, and cardiorespiratory complaints remain in question.
Maximum aerobic capacity (V02max) and exercise capacity are
indirect measures of cardiovascular capacity which have been reported to
be reduced in several carefully conducted studies involving hormal healthy
adults exposed to CO.
These effects, while not as serious as the possible
impact of CO on angina, are still a matter of some concern since they
have been found to occur in healthy individuals.
A decline in 902max for healthy individuals with COHb levels
",
ranging from 5-20 percent was reported in a series of studies (Ekblom and
Huot, 1972;29 Weiser et al., 1980;78 Stewart et al., 1978;32), reviewed
in the 1979 Criteria Document6.
Horvath et al., (1975)30 found decreases
(p <.10) in 902max when COHb levels were 4.3 percent.
Also COHb levels
-------
12
of 3.3 percent and 4.3 percent reduced work ti me to exhausti on by 4.9 and
7 percent respectively.
Simil ar results were al so found (Stewart et al. ,
1978;79 Klein et al., 198033) following exhaustive treadmill exercise at
5 percent COHb.
The effects of CO on the fibrinolytic system have been reported in
numerous publications and may be related to heart attacks and strokes,
although evidence at this time is very limited.
In a series of studies
Kalmaz et ale (1977;55 1978;56 198057) concluded that prolonged exposure of
rabbits to low levels of CO may change circulating platelet counts and/or
congeni tal pl atel et functi on di so-rders, however, thi s has not been confi rmed
in man.
Accelerated clot lysis time suggestive of enhanced blood fibrinolytic
activity in humans was reported by El-Attar and Sairo (1968),58 while
others reported relationships between CO exposure and increases in fibrinogen
and blood coagulation (Alexieva et al., 1975;59 Panchenko et al., 197760).
Haft (1979)61 reported that smoking increases the activity of platelets and
that cigarette smokers have shortened platelet survival time.
Neither
this study nor others clearly implicate acute CO exposure in observed
alterations in fibrinolytic activity and chronic exposure studies of
humans are too poorly controlled to confirm coagulation system effects.
Thus, this area of cardiovascular effects research needs to be developed
far beyond the present state of knowledge before being acceptable even as
suggestive evidence.
2.
Neurobehavi oral Effects
Central nervous system (CNS) effects have been reported in numerous
studies (Bender et al., 197147; Schulte, 197348; O'Donnell et al., 197149;
McFarland et al., 1944;41 McFarland, 1973;50 Putz et al., 1976;39
-------
13
Salvatore, 1974;51 Wright et al., 1973;52 Rockwell and Weir, 1975;53
Rummo and Sarlanis, 197454) for CO exposures resulting in COHb levels of
5-17 percent.
The range of effects included impaired vigilance, visual
perception, manual dexterity, learning ability, and performance of complex
tasks.
While Beard and Grandstaff (1975)34 have suggested vigilance effects
may occur at levels of COHb as low as 1.8 percent COHb, several other
studies (Haider et al., 197635; Winneke, 197336; Christensen et al., 197737;
Benignus and Otto, 197738; and Putz et al., 197639) have not found any
vigilance decrements below 5 percent COHb.
Measurement methods used
to detect effects may have been too insensitive to detect changes in the
latter vigilance studies, but in the draft Addendum, it was concluded
that, at least under some conditions, small decrements in vigilance occur
at 5 percent COHb.
Benignus et al. (1983)40 concluded that no reliable evidence for time
discrimination decrements caused by exposure to low levels of CO exists.
Concentration-related decrements in dark adaptation at COHb levels as low
as 5 percent were reported by McFarland et al. (1944).41
This effect, however,
is not considered to be adverse at ambient levels of CO exposure.
Studi es by Putz et al. (1976) ,39 Putz et al. (1979)42, and Putz (1979)43
reported that 5 percent COHb produced decrements in compensatory tracking,
a hand-eye coordination task.
These effects are not considered to be of
major concern because nonsmokers rarely attain 5 percent COHb at ambient
CO exposure levels and the effect only was found during high task difficulty.
Perinatal Effects
3.
The 1979 Criteria Document suggests that based on limited animal
toxicology data CO may produce perinatal effects on the fetus or newborn.
-------
14
Long-term exposures to CO may result in a slower elimination of CO by the
fetus and may lead to interference ~th fetal tissue oxygenation during
development.
Because the fetus may be developing at or near critical
tissue oxygenation levels, even exposures to moderate levels of CO may
produce deleterious effects on the fetus (Longo, 1977).62 Although this
has not yet been demonstrated in humans, evidence from smoking mothers is
suggestive of fetal and newborn effects (Peterson, 1981).63
Research on sudden infant death syndrome (5ID5) recently has suggested
a possible link between ambient CO levels and increased incidence of SIDS
(Hoppenbrouwers et al., 1981).64
It has been pointed out by Goldstein
(1982)65 that indoor sources of CO, as well as other poll utants (e.g.,
nitrogen dioxide, lead), may be at least as important as CO in causing
SIDS and that the relationship between SIDS and ambient pollution levels
may be only coincidental.
Because the number of potentially confounding
factors makes finding an association between CO and SID5 extremely difficult,
further confirmation is needed before any causal relationship can be
inferred.
C.
Sensitive Population Groups
This section identifies those groups most likely to be particularly
sensitive to low-level CO exposures based on the health effects evidence
and considerations presented in the draft Addendum1 and Section B of this
paper.
Those groups i ncl ude: (1) i ndi vi dual s ~ th angi na, peri pheral
vascul ar di sease, and other cardi ovascul ar di seases, (2) persons ~ th
chronic respiratory disease (e.g., bronchitis, emphysema, and asthma),
(3) elderly individuals, especially those ~th reduced cardiopulmonary
functions,
(4) fetuses and young infants, (5) individuals suffering from
anemi a and/or those ~ th abnormal hemogl obi n types that affect oxygen
-------
15
carrying capacity or transport in the blood.
In addition, individuals
taking certain medications or drinking alcoholic beverages may be at greater
.
risk for CO-induced effects based on some limited evidence suggesting
interactive effects between CO and some drugs.
Visitors to high altitude
locations are also expected to be more vulnerable to CO health effects due
to reduced levels of oxygen in the air they breathe.
Fi nally, i ndi vi dual s
~th some combination of the diseaase states or conditions listed above
(e.g., individuals ~th angina visiting a high altitude location) may be
particularly sensitive to low-level CO exposures, although there is no
experimental evidence to confirm this hypothesis.
Table 2 briefly summarizes the rationale for the judgments that these
groups are more likely to be affected by low-level CO exposures and presents
population estimates for each group.
For most of the groups listed in Table 2
there is little specific experimental evidence to clearly demonstrate that
they are indeed at increased risk for CO-induced health effects.
However,
it is reasonable to expect that individuals ~th preexisting illnesses or
physiological conditions which limit oxygen absorption into blood or its
transport to body tissues would be more susceptible to the hypoxic (i .e.,
oxygen starvation) effects of CO.
In our judgment, the available health effects evidence still suggests
that persons ~th angina, peripheral vascular disease, and other types of
cardi ovascul ar di sease are the group at greatest ri sk from 1 ow-l evel , ambi ent
exposures to CO.
This judgment is based principally on the Anderson et al.
(1973) study21 which indicates that individuals ~th angina may be affected
at COHb levels in the range 2.9-4.5 percent.
In addition, while there is
less confidence in the dose-response relationship reported in Aronow et al.
(1974),13 this study still suggests that individuals ~th peripheral vascular
disease may be at risk from ambient exposures to CO.
-------
Group
Corona ry Hea rt
Di sease
Angina Pectoris
16
Table 2.
Summary of Potentially Sensitive Population Groupsa
Rationale
Anderson et al. (1973) suggests
reduced time until onset of
exercise-induced angina in
2.9-4.5% COHb range.
Population
Esti mates
7 .0 mi 11 i on (i n 1979)
5.6 million (in 1979)
Percent of
Population
5.0 (of the adult
population)
4.0 (of the adult
population)
Reference
DHEW, 197566
Chronic Obstructive
Pulmonary Diseases
DHEW, 197367
Bronchitis
Emphysema
Asthma
Reduced reserve capacities for
dealing with cardiovascular
stresses and already reduced
oxygen supply in blood likely
to hasten onset of health effects
associ ated wi th CO-i nduced
hypoxi a.
6.5 million (1970)
1.5 mill i on (1970)
6.0 million (1970)
3.3
0.7
3.0
Fetuses and
Young Infants
DHEW, 197868
Several animal studies (Longo,
1977) report deleterious effects
in offspring (e.g., reduced
bi rth wei ght, increased nel'born
mortality, and lower behavioral
activity levels).
3.1 million live
births/year (1975)
Anemia
Pernicious and
Deficiency Anemias
Oxygen carrying capacity of blood
is already reduced increasing
likelihood of CO-induced hypoxia
effects at lower CO exposure
levels than for non-anemic
i ndi vi dual s.
3.0 mi 11 i on (1973)
.15 mill i on (1973 )
1.4
0.07
DHEW, 197769
Peri phera 1
Vascular Disease
DHEW, 197470
Aronowet al. (1974)13 suggests
reduced time until onset of
exercise-induced leg pain after
exposure to CO.
0.7 million (1979)
0.3
El derl y
DOC, 198071
CO exposures may increase
susceptibility of elderly
individuals to other
cardiovascular stresses due
to already reduced reserve
capacities to maintain
adequate oxygen supply to
body ti ssues. .
24.7 million (1980)
> 65 years old
aAll subgroups listed are not necessarily sensitive to CO exposure at low levels.
-------
17
D.
Uncertainty in Estimating COHb Levels
The health effect studies discussed above report the effects observed
at varying COHb levels.
In order to set ambient CO standards based on
these studies, it is necessary to estimate the ambient concentrations of
CO that are likely to result in COHb levels at or near those observed in the
studies.
A model known as the Coburn equation60 has been developed to
estimate COHb levels resulting from CO concentrations as a function of
time and various physiological factors (e.g., blood volume, endogenous CO
production rate).
Table 3 presents baseline estimates (i.e., a typical set
of physiological parameters was used) of COHb levels expected to be reached
by non-smokers exposed to various constant concentrations of CO for either
1 or 8 hours based on the Coburn model.
There are, however, at least two uncertainties involved in estimating
CUHb levels resulting from exposure to CO concentrations.
Fi rst, even
among otherwi se "normal" (non-anemi c) persons wi th cardi ovascul ar heart
disease, there is a distribution for each of the physiological parameters
used in the Coburn model in the population.
These variations are sufficient
to produce noticeable deviations from the COHb levels in Table 3 that were
predicted using the typical set of physiological parameters.
Second,
predictions based on exposure to constant CO concentrations inadequately
represent the responses of individuals exposed to widely fluctuating CO
concentrations that typically occur in ambient exposure situations.
As discussed in the proposal preamble (45 FR 55066), EPA attempted
to represent these uncertainties in a draft Sensitivity Analysis.
This
analysis used the Coburn model to examine the effects of fluctuating CO
concentrations and variations in physiological parameters on COHb estimates.
-------
18
Table 3. Predicted COHb Response to Exposure to Constant CO Concentrations
Percent COHb Based on Coburn Equationa
Exposure Time
1 hour exposure 8 hours exposure
Intermittent Intermittent
CO Rest/Light Moderate Rest/Light Moderate
(ppm) Activity Activity Activity Activity
7.0 0.7 0.7 1.1 1.1
9.0 0.7 0.8 1.4 1.4
12.0 0.8 0.9 1.7 1.8
15.0 0.9 1.1 2.1 2.2
20.0 1.1 1.3 2.7 2.9
25.0 1.2 1.5 3.4 3.6
35.0 1.5 2.0 4.6 4.9
50.0 2.0 2.7 6.4 6.9
a
Assumed parameters: alveolar ventilation rates = 10 liters/min (intermittent
rest/light activity) and 20 liters/min (moderate activity); hemoglobin =
15 g/100 ml (normal male); altitude = sea level; initial COHb level = 0.5 percent;
endogenous CO production rate = 0.007 ml/min; blood volume = 5500 ml, Haldane
constant (measure of affinity of hemoglobin for CO) = 218; lung diffusivity
for CO = 30 ml/min/torr.
-------
19
Since proposal, EPA has revised the Sensitivity Analysis73 to address
concerns raised in several public comments.
Table 4 presents estimates
of the distribution of COHb levels in the sensitive population based on
variations in physiological parameters upon exposure to three different
patterns of CO levels which just meet a given CO standard.
The estimates
given in Table 4 and others contained in the Sensitivity Analysis report73
are based on the assumption that the entire sensitive population is
exposed to CO levels just meeting a given standard.
The impact of fluctuating air quality levels on COHb uptake can be
roughly estimated by comparing the result of a constant 9 ppm exposure
for 8 hours (1.4 percent COHb from Table 3) with a "typical" (50th percentile)
adult exposed to several different air quality patterns that result in
the same maximum 8-hour dose (i .e., 9 ppm, 8-hour average).
The various
patterns examined in the Sensitivity Analysis indicate COHb levels ranging
from 1. 4 to 1. 9 percent (from Table 4) can be reached for the "typi ca 1"
adult exposed to air quality reaching a 9 ppm, 8-hour average.
A similar
compari son of the resul ts for ai r qual i ty wi th a 12 ppm, 8-hour average
peak exposure, indicates that the impact of fluctuating CO levels can
increase the peak COHb value by up to 0.5-0.6 percent COHb.
The Sensitivity Analysis results in Table 4 also illustrate the
effect of using distributions for each physiological parameter rather
than just a representative set of physiological parameters in applying
the Coburn model.
For any given air quality pattern, the effect of the
distribution of physiological parameters is to generate a distribution
that is fairly tight around the 50th percentile individual.
For exampl e,
95 percent of the population is estimated to be within + 0.3 percent COHb
of the medi an adul t val ue after exposure to the mi drange pattern wi th a
peak 9 ppm, 8-hour average.
-------
20
Tab 1 e 4. Percentage of Sensiti ve Persons wi th Carboxyhemogl obi n
Greater than or Equal to Specified Peak Value When Exposed to
Ai r Qual ity Associ ated wi th Alternati ve Ei ght-Hour Dail y
Maximum Carbon Monoxide Standardsa,b,c
Peak
COHb
%
9 ppm, 8-hr
1 Expected Exceedance
Low Midrange High
Pattern. Pattern. Pattern
12 ppm, 8-hr
1 Expected Exceedance
Low Midrange High
Pattern. Pattern Pattern
3.7
3.5
3.3
3.1
2.9
2.7
2.5
2.3
2.1
1.9
1.7
1.5
1.3
1.1
<0.01
0.05
3
39
97
100
<0.01
0.02
0.4
5
35
88
100
100
<0.01
0.02
0.2
2
10
53
98
100
100
100
<0.01
0.01
0.2
4
36
91
100
100
100
<0.01
0.01
0.2
2
12
49
88
99
100
100
100
<0.01
0.01
0.1
0.6
2
9
36
84
100
100
100
100
100
100
aCOHb responses to fluctuating CO concentrations were dynamically evaluated
using the Coburn model prediction of the COHb level resulting from one
houris exposure as the initial COHb level for the next hour. The series of
I-hour CO concentrations used were from 20 sets of actual air quality data.
Each pattern was proportionally rolled back or up so that its peak 8-hour
CO concentration equalled the level of the 8-hour standard. Of the 20
selected patterns, results from 3 patterns are presented here. The low
pattern tends to give the lowest peak COHb levels, the midrange pattern
tends to give a midrange value, and the high pattern tends to give the
highest value. .
bHaldane constant = 218.
Altitude = 0.0 ft.
Alveolar ventilation rate = 10 liters/min.
cThe estimation of distributions for each of the physiological parameters
used in the Coburn model and the Monte Carlo procedure used to generate
these estimates are discussed in Appendix C of the Sensitivity Analysis.73
-------
21
Since proposal, EPA has made considerable improvements in its exposure
analysis methodology which, unlike the Sensitivity Analysis, treats
movement of people and variation of CO concentration levels through time
and space.
EPA staff believes that the revised Exposure Analysis,74 described
below, represents the best available tool for estimating the percentage
of the sensitive population who would reach various CO concentrations
and COHb levels upon attainment of alternative CO standards.
Since the
Exposure Analysis model simulates the exposure of individuals on an
hourly basis and simulates actual air quality patterns, the impact of
fluctuating CO levels is taken into account in the Exposure Analysis
results.
The resul ts of the revi sed Sensi ti vi ty Analysi s are useful,
however, in characterizing the uncertainties resulting from variations in
physiological parameters in the population which at this time are not
fully accounted for in the Exposure Analysis.
Exposure Analysis Estimates
E.
EPA's revised exposure analysis report, "The NAAQS Exposure
Model (NEM) Applied to Carbon Monoxide,"74 contains estimates of the
numbers and percentage of urban Ameri can adul ts wi th cardi ovascul ar heart
disease that would be exposed to various ambient CO levels if alternative
a-hour CO standards were just attained.
In addition, estimates have been
made of the percentage of this sensitive population that would exceed
selected COHb levels each year.
These latter estimates were derived by
applyi ng the Coburn model, whi ch rel ates patterns of CO- exposure to
resultant COHb levels, to the exposure model outputs using a typical
set of physiological parameters for men and for women.
In contrast to the Sensitivity Analysis,73 the Exposure Analysis74
simulates pollutant concentrations and the activities of people with regard
-------
22
to time, place, and exercise level.
In the exposure model, the population
is represented by an exhaustive set of "cohorts" (i .e., age-occupational
groups that tend to "track together" in time and space).
For each hour of
the year each cohort is located in one .of fi ve "mi croenvi ronments." A
microenvironment is a general physical location such as indoors-at-home or
inside a transportation vehicle.
CO levels in each of the microenvironments
are estimated by the use of multiplicative "transformation factors,"
which relate CO levels recorded at the nearest monitor to estimated CO
levels for each microenvironment.
The multiplicative transformation
factors are based on the growing literature on (1) indoor and inside-motor-
vehicle air pollution and (2) statistical analyses of monitoring data
(e.g., how ambient values change with height and distance from a monitor).
A more detailed description of the approach, input data, and assumptions
used to derive exposure estimates appears in the Exposure Analysis report.74
The exposure analysis model described above was applied to four
urban areas:
Chicago, Los Angeles, Philadelphia, and St. Louis.
Exposure
estimates for the sensitive population living in urban areas in the
United States were obtained primarily by associating each urban area in
the United States having a population greater than 200,000 with one of
the four cities mentioned above.
The association was made on the basis
of geographic proximity to one of the base areas, average wind speed, peak
CO concentrations, observed climate, and general character of the area.
Table 5 provides estimates for 1987 of the percentage of the sensitive
population living in urban areas who would exceed various COHb levels
upon attainment of two alternative 8-hour standards.
For example,
less than 0.1 percent of the sensitive population in urban areas
-------
23
Table 5. Cumulative Percent of Sensitive Population in Urban
Areas Whose COHb Levels Would Exceed Specified COHbValues
Upon Attainment of Alternative 8-Hour Standardsa,b,c
8-Hour Standards
9 ppm 12 ppm 15 ppm
1 Expected 1 Expected 1 Expected
. Exceedance . Exceedance. Exceedance
COHb Level
Exceeded (Percent)
3.0 <.01 1.1
2.9 .02 2.5
2.7 0.1 5.9
2.5 0.8 9.7
2.3 <0.1 4.1 14
2.1 0.1 8.6 20
aprojected cardiovascular and peripheral vascular disease population
in all urbanized areas in the United States for 1987 is 5,300,000 adults.
bThese exposure estimates are based on air quality distributions which
have been adjusted to just attain the given standards.
cThese exposure estimates are based on best judgments of microenvironment
transformation factors. Projections for one urban area based on lower
and upper estimates of the microenvironment transformation factors are
provided in the Exposure Analysis report.74
-------
24
is estimated to exceed 2.1 percent COHb due to CO exposures associated
wi th attai nment of a 9 ppm standard wi th 1 expected exceedance allowed
per year and approximately 20 percent of the sensitive population is
estimated to exceed 2.1 percent COHbupon attainment of a 15 ppm standard
with 1 expected exceedance allowed per year.
It should be noted that the
estimates given in Table 5 are based on air quality distributions which
have been adjusted to just attain the given standards.
Several factors make the nationwide exposure ~stimates uncertain.
They
i nc1 ude:
(1) the paucity of information on several of the needed inputs
(e.gq the microenvironment multiplicative transformation factors), (2) the
fact that' nationwide estimates were extrapolated from only four urbanized
areas, and (3) the use of two representative sets of physiological parameters
(one for men and one for women) rather than the distributions of the
physiological parameters in applying the Coburn model to derive COHb
estimates.
The Exposure Analysis report74 describes some limited sensitivity
analysis runs for one urbanized area to give a rough idea of the degree
of uncertainty involved in the analysis. .In addition, the results of the
Coburn Model Sensitivity Ana1ysis,73 discussed previously in Section 0,
suggest that the uncertainty introduced by use of two representative sets
of physiological parameters rather than the distributions of the parameters
is not very large.
F.
Margin of Safety Considerations
In determi ni ng whi ch standards wi 11 provi de an adequate margi n of
safety, the Administrator must consider uncertainties regarding the lowest
levels at which adverse health effects occur, as well as uncertainties
about the 1 eve1 s of COHb that wi 11 resul t from CO exposure at the 1 evel s
associ ated wi th attai nment of a lternati ve standards.
The staff recommends
-------
25
, that the fo11 owi ng factors and sources of uncertai nty be consi dered in
selecting the primary standards:
1.
Human susceptibility to health effects and the levels at which
these effects occur varies considerably among individuals, and EPA cannot
be certain that experimental evidence has accounted for the full range of
susceptibility.
In addition, for ethical reasons, clinical investigators
have generally excluded from their studies individuals who may be especially
sensi ti ve to CO exposure, such as those wi th myocardi a1 i nfarcti on or
multiple disease states (e.g., angina and anemia).
Another factor is that,
apart from the Aronow et a1. studies,7,12,13 there are neither positive nor
negative human exposure studies testing cardiovascular effects at COHb
levels below the 2.9 percent level reported by Anderson et a1.21
2.
Several Aronowet a1. studies7,12,13 report decreased time to
onset of angina and peripheral vascular disease at COHb levels in the range
of 2.0-3.0 percent.
In view of the concerns expressed in the Horvath
Committee report,18 the findings from these Aronow studies are questionable.
Therefore, EPA staff recommends that the Aronow et a1. findings be considered
only as a margin of safety consideration.
The Aronow studies suggest the
possibility of effects at lower levels of CO but the results remain to be
confirmed.
3.
There is some animal study evidence indicating that there may
be detrimental effects on fetal development (e.g., reduced birth weight,
i ncreased ne~orn mortal i ty, and behavi oral effects) associ ated wi th CO
exposure.
Similar types of effects have also been found in studies of the
effects of maternal smoking on human fetuses.
However, it is not possible
at this time to sort out the confounding influence of other components of
-------
26
tobacco smoke in causing the effects observed in the human studies.
While
human exposure-response relationships for fetal effects remain to be
determined, these findings denote a need for caution in evaluating the
margin of safety provided by alternative CO standards.
Other groups that may be affected by ambient CO exposures but for which
there is little or no experimental evidence providing exposure-response
relationships include:
anemic individuals, persons with chronic resptratory
diseases, elderly individuals, visitors to high altitude locations, and
individuals on certain medications.
5.
Uncertainties regarding the uptake of CO, including those related
to the accuracy of the Coburn equation in assessing variations in the
population due to differing physiological parameters and exposure to
varying air quality patterns, should be considered in judging which
standards provide an adequate margin of safety.
6.
There are several factors contributing to uncertainties about the
estimates provided by the Exposure Analysis74 of the expected number of
individuals achieving various COHb levels upon attainment of alternative
standards.
These factors include:
the paucity of information on several
of the needed inputs, the fact that nationwide estimates were extrapolated
from only four urbanized areas, and the use of two representative sets of
physiological parameters (one for men and one for women) rather than the
distributions of physiological parameters in applying the Coburn model to
derive COHb estimates.
The Exposure Analysis report74 describes some
limited sensitivity analysis runs for one urbanized area to give a rough
idea of the degree of uncertainty involved.
7.
Uncertainty regarding adverse health effects that may result from
very short duration, high-level CO exposures (the bolus effect).
However,
-------
27
this factor is probably not a critical consideration because, as discussed
in the proposal notice (45 FR 55077), existing air quality data indicate
that attainment of an 8-hour averaging time standard should limit the
magnitude of short-term peak concentrations.
8.
There is some concern about possible interactions between CO and
other pollutants, although there is little experimental evidence to document
such interactions at this time.
-------
28
v.
FACTORS TO BE CONSIDERED IN SELECTING PRIMARY STANDARDS
This section draws on the previous evaluation of scientific information
and summarizes the principal factors bearing on selection of primary CO
standard levels and on designating appropriate averaging times and forms.
Preliminary staff recommendations for each of these choices also are
presented.
Averagi ng Ti mes
A.
Currently there are primary CO standards for both I-hour and 8-
hour averaging times.
The original 8-hour averaging time was selected
primarily because most individuals achieve equilibrium or near equilibrium
levels of COHb after 8 hours of continuous exposure.
Another reason for
the 8-hour averaging time is that many people are exposed in approximately
8-hour blocks of time (e.g., work, sleep).
The 8-hour averaging time
provides a good indicator for tracking continuous exposures that occur
during any 24-hour period.
The I-hour averaging time provides an
appropriate time frame for evaluating health effects ~rom short-term
exposures.
As discussed in the June 1979 staff paper,6a the 1- and 8-
hour averaging time standards can also provide reasonable protection
agai nst hi gh spikes of 1 ess than I-hour durati on (lithe bol us effect II) in
the urban ambient environment.
The staff recommends both the 1- and 8-
hour averaging times be retained for the primary standards.
B.
Form of the Standards
The current CO standards are stated in a deterministic form,
allowing only one exceedance per year.
The general limitations of the
deterministic form are discussed in Biller and Feagans (1981).75
Recognition of these limitations has ledEPA to promulgate a statistical
form for the ozone standards (44 FR 8202) and to propose a statistical
-------
29
form for the CO standards (45 FR 55066).
The statistical form of the
standard (e.g., stati ng an all owabl e number of exceedances of the standard
level as ari average or expected number per year) offers a more stable
target for control programs and is less sensitive than a deterministic form
to very unusual meteorological conditions.
The emissions reductions to
be achieved in the required control implementation program would be based
on a statistical analysis of the monitoring data over a multi-year period
(e.g., the preceding 3-year period).
EPA has considered the possibi lity of setting a multiple expected
exceedances standard (47 FR 26407).
At a July 6, 1982 public meeting,
the CASAC discussed several advantages and liabilities of setting a
multiple expected exceedances standard for CO.
Based on the discussion
at that meeting, the Chairman of CASAC sent a letter to the Administrator
recommendi ng adopti on of a mul ti pl e expected exceedances standard wi th a
standard level suitably adjusted to provide adequate protection of public
health.10
Subsequent to the CASAC meeting, the Agency received a number of
comments both for and against multiple exceedances standards.
In part i c u 1 a r ,
the State and Territorial Air Pollution Program Administrators (STAPPA)
sent a resolution to EPA expressing the view that a single exceedance CO
standard would be preferable to a multiple exceedance standard because the
former (1) is more directly related to the health effects of concern and
(2) is more clearly understood by the public than a multiple expected
exceedances standard.
The staff recommends that for the CO decision the
standards be stated in terms of a single expected exceedance based on
(1) the comments made by State air pollution control agencies and others
regarding the advantages of a single exceedance standard and (2) the
advantages of a stati sti cal (i .e., expected exceedance) standard di scussed
above.
-------
30
C.
Levels of the Standards
The principal conclusions derived from the scientific evidence
described in Section IV of this paper and in the draft Addendum to the
1979 Criteria Document1 that are relevant to the standard selection process
are summarized below:
(1 )
Cardiovascular effects are judged to be the health effects of
greatest concern that have been associated ~th CO exposure levels observed
in the ambient air.
In particular, there is no change in the staff's judgment
as stated in the 1980 proposal that decreased time to onset of angina and
prolonged duration of angina attacks should be considered adverse health
effects.
The staff concludes from its review of the scientific evidence
that aggravation of angina is likely to occur at COHb levels in the range
2.9-4.5 percent.
This judgment is based principally on the Anderson
et al. (1973)21 study.
The Aronow studies7 ,12,13 report that aggravation
of angina and peripheral vascular disease may occur at levels below 2.9
percent COHb.
However, in view of the concerns expressed by the Horvath
panel18 about the design and conduct of the Aronow studies, further experimental
confirmation is needed on the question of whether these effects occur at
levels below 2.9 percent COHb.
The Aronow studies should be considered
only in developing a margin of safety.
(2 )
Several controlled human exposure studies30,79,33 have reported
effects on maximum aerobic and exercise capacity for healthy vigorously
exercising adults exposed to CO.
The staff's assessment of these studies is
that small (5-7 percent) reducti ons in work time are 1 i kely to occur at
COHb levels in the range 3.3-5.0 percent.
It should be noted, however, that
the effects observed at these levels are not clearly of health significance.
At higher COHb levels (7 percent), one study29 reported a 38 percent decrease
in work time for healthy adults engaged in heavy exercise.
-------
31
At submaximal exercise levels there appear to be little if any effects
on aerobic or work capacity for healthy individuals exposed to COHb levels
up to 15-20 percent.
However, the possibility that individuals with severe
chronic respiratory disease may be affected at COHb levels below 5 percent
has not been investigated.
The possible impairment of work capacity for
i ndi vi dual s wi th chroni crespi ratory di sease shoul d, therefore be i ncl uded
as a margin of safety consideration in selection of the final standards~
(3 )
Additional factors which we believe should be considered in
selecting CO primary standards which provide an adequate margin of safety
include:
(a) there are no valid human controlled experimental studies
reporting no adverse health effects at COHb levels below 2.9 percent for
cardiovascular effects,
(b)
concern about animal study evidence indicating that there
may be detrimental effects on fetal development,
(c)
concern about other potentially sensitive population groups
that have not been adequately tested such as the elderly, anemics, and
visitors to high altitude,
(d)
uncertainties regarding the uptake of CO and the accuracy of
the Coburn equation in assessing uptake under varying conditions,
(e)
uncertainties about the Exposure Analysis74 estimates of the
expected number of individuals achieving various COHb levels upon attainment
of alternative standards,
(f)
uncertainty regarding adverse health effects that may result
from very short duration high-level CO exposures (the bolus effect), and
(g)
concern about possible interactions between CO and other
pollutants.
-------
32
All of the above factors were previously discussed in greater detail in
Section IV-F of this paper.
Staff Conclusions and Recommendations
D.
Based on the assessment of the scientific evidence discussed in the
draft Addendum1 and in previous sections of this paper, the staff remains
concerned that adverse health effects may be experienced by large numbers
of sensitive individuals at COHb levels in the range 2.9 to 4.5 percent.
Unless the primary standards are set to keep most of the sensitive population
somewhat below these levels, we believe that the Agency would not be
exercising the degree of prudence called for by the Clean Air Act requirement
that primary standards be set to provide "an adequate margin of safety."
Based on the revised Exposure Analysis74 estimates summarized in Table 5,
8-hour standards ~th one expected exceedance allowed per year in the range
of 9 to 15 ppm are estimated to keep 99 percent or more of the sensitive
population below 3.0 percent COHb.
Standards ~ thi n thi s range waul d
provide different levels of protection.
For example, a 9 ppm, 8-hour
average standard is estimated to keep more than 99 percent of the sensitive
population below 2.1 percent COHb and a 15 ppm standard would keep almost
99 percent of the sensitive population below 3.0 percent COHb.
In using
the Exposure Analysis estimates to evaluate the protection afforded by
alternative standards, it should be noted that the above exposure estimates
are based on best judgments of certain key inputs to the analysis.
The
uncertainty associated ~th these estimates should, therefore, also be
considered in evaluating alternative standards.
To the extent that the
uncertainty may lead to underestimates of the protection afforded by any
particular standard, selection of a more protective standard is appropriate.
-------
33
In view of the lack of negative controlled human exposure evidence
concerning the impact of COHb levels below 2.9 percent on individuals ~th
cardiovascular disease, the margin of safety considerations discussed in
Section IV-F of this paper, and the precautionary nature of the Clean Air
Act, the staff is concerned that 8-hour standards at the upper end of the
range 9 to 15 ppm would provide little or no margin of safety.
Therefore,
the staff recommends that the Administrator retain or select an 8-hour
standard in the range 9 to 12 ppm.
With regard to the I-hour primary
standard the staff recommends that I-hour standards in the range 25 to 35
ppm be retained or set to provide a comparable level of protection.
-------
REFERENCES
1.
u.S. Environmental Protection Agency, Environmental Criteria Assessment
Offi ceo Revi sed Eval uati on of Heal th Effects Associ ated wi th Carbon
Monoxide Exposure: An Addendum to the 1979 EPA Air Quality Criteria
Document for Carbon Monoxide (Draft). Research Triangle Park, N.C.
August 1983.
2. . Lead 1~d~stri~~'As~0~i~ti6~~ lnc~ v~EPA, 647 F.2d 1130 (D.C. Cir.
T980), cert. denied 101 S. Ct. 621 (f913'O).
3.
American Petroleum I~stitutev. Costle, 665 F.2d 1176 (D.C. Cir. 1981),
cert. denied 102 S. Ct. 1737 (1982).
4.
u.S. Department of Health, Education, and Welfare. Air Quality Criteria
for Carbon Monoxide. AP-62.' March 1970.
5.
Beard, R.P., and G.A. Wertheim.
small doses of carbon monoxide.
1 967 .
Behavi oral i mpai rment associ ated wi th
Am. J. Public Health iZ:2012-2022,
6.
u.S. Environmental Protection Agency, Air Quality Criteria for Carbon
Monoxide. U.S. EPA No. 600/8-79-022. Research Triangle Park, N.C.
October 1979.
6a. U.S. Environmental Protection Agency, Office of Air Quality Planning
and Standards. Preliminary Assessment of Adverse Health Effects from
Carbon Monoxide and Implications for Possible Modifications of the
Standard. Research Triangle Park, N.C. June 1979.
7.
Aronow, W.S. Aggravation of angina pectoris by two percent carboxyhemoglobin.
American Heart Journal 101:154-156, 1981.
u.S. Environmental Protection Agency, Office of Air Quality Planning
and Standards. Sensitivity Analysis on Coburn Model Predictions of
Carboxyhemogl obi n Level s Associ ated wi th Al ternati ve Carbon Monoxi de
Standards (Draft). Research Triangle Park, N.C. February 1, 1982.
8.
9.
Johnson, T. and R.A. Paul. The NAAQS Exposure Model (NEM) Applied to
Carbon Monoxi de (Draft). Prepared by PEDCo Envi ronmental, Inc., for
U.S. EPA, Office of Air Quality Planning and Standards. Durham, N.C.
June 17, 1982.
10. Friedlander, S.K., Chairman, Clean Air Scientific Advisory Committee.
Letter to Ann M. Gorsuch, EPA Administrator. August 31,1982.
11. Aronow, W.S., D.N. Harri s, M.W. Isbell, S.N. Rokaw, and B. Imparato.
Effect of freeway travel on angina pectoris. Ann. Intern. Med. 77:669-
676, 1972.
12. Aronow, W.S., and M.W. Isbell. Carbon monoxide effect on exercise-
induced angina pectoris. Ann. Intern. Med. 79:392-395, 1973.
-------
23.
24.
25.
2
13. Aronow, W.S., E.A. Stemmer, and M.W. Isbell. Effect of carbon monoxide
exposure on intermittent claudication. Circulation 49:415-417,1974.
14. Aronow, W.S., J. Casidy, J.S. Vangrow, H. March, J.C. Kern, J.R.
Goldsmith, M. Khemka, J. Pagano, and M. Vawter. Effect of cigarette
smoking and breathing carbon monoxide on cardiovascular hemodynamics on
anginal patients. Circulation 50:340-347, 1974.
15. Aronow, W.S., and J. Cassidy. Effect of carbon monoxide on maximal
treadmill exercise: A study in normal persons. Ann. Intern. Med.'
83:496-499, 1975.
16. Aronow, W.S., J. Ferlinz, and F. Glauser. Effect of carbon monoxide on
exercise performance in chronic obstructive pulmonary disease. Am. J.
Med. ~:904-908, 1977.
17. Aronow, W.S. Effect of passive smoking on angina pectoris.
Med. 229:21-24, 1978.
N. Eng. J.
18. Horvath, S.M., S.M. Ayres, D.S. Sheps, and J. Ware. [Letter to Or.
Lester D. Grant, including the peer-review committee report on Or.
Aronow's sutdies.] May 25, 1983. Available from: U.S. Environmental
Protection Agency, Central Docket Section, Washington, D.C.; docket no.
OAQPS-79, IV-H-58, 1983.
19.
Coburn, R.F., R.E. Forster, and P.B. Kane. Considerations of the
physiological variables that determine the blood carboxyhemoglobin
concentration in man. J. Clin. Invest. 44:1899-1910, 1965.
20.
Coburn, R.F. Mechanisms of carbon monoxide toxicity.
~: 310-322, 1979.
Prevo Med.
21.
Anderson, E.W., R.J. Andelman, J.M. 'Strauch, N.J. Fortuin, and J.H.
Knelson. Effect of low-level carbon monoxide exposure on onset and
durati on of angi na pectori s: A study on 10 pati ents wi th i schemi c
heart disease. Ann. Intern. Med. zg:46-50, 1973.
Davies, D.M. and D.J. Smith. Electrocardiographic changes in healthy
men during continuous low-level carbon monoxide exposure. Environ.
Res. ~:9-15, 1980.
22.
Ayres, S.M., H.S. Mueller, J.J. Gregory, S. Giannelli, Jr., and J.L.
Penny. Systemic and myocardial hemodynamic responses to relatively
small concentrations of carboxyhemoglobin (COHb). Arch. Environ.
Health 18:699-709, 1969.
Ayres, S.M., S. Giannelli, Jr., and H. Mueller. Myocardial and systemic
responses to carboxyhemoglobin. In: Biological Effects of Carbon
Monoxide, Proceedings of a Conference, New York, Academy of Sciences,
New York, January 12-14, 1970. Ann. NY Acad. Sci. 174:268-293,1970.
Goldsmith, J.R., and S.A. Landau.
Science 162:1352-1359, 1968.
Carbon monoxide and human health.
-------
36.
37.
3
26.
Kurt, T.L., R.P. Mogielnicki, and J.E. Chandler. Association of the
frequency of acute cardi orespi ratory compl ai nts wi th ambi ent 1 evel s of
carbon monoxide. Chest 74:10-14, 1978.
Kurt, T.L., R.P. Mogielnicki, J.E. Chandler, and K. Hirst. Ambient
carbon monoxide levels and acute cardiorespiratory complints: an
exploratory study. Am. J. Public Health 69:360-363, 1979.
27.
28.
Coburn, R.F., W.S. Blakemore, and R.E. Forster. Endogenous carbon
monoxide production in man. J. Clin. Invest. 42:1172-1178, 1963.
29.
Ekblom, B., and R. Huot. Response to submaximal and maximal exercise
at different levels of carboxyhemoglobin. Acta Physiol. Scand. 86:474-
482, 1972.
30.
Horvath, S.M., P.B. Raven, T.E. Dahms, and D.J. Gray. Maximal aerobic
capacity at different levels of carboxyhemoglobin. J. Appl. Physiol.
38:300-303, 1975.
31.
Dahms, T.E., S.M. Horvath, and D.J. Gray. Technique for accurately
producing desired carboxyhemoglobin levels during rest and exercise.
J. Appl. Physiol. 38:366-368,1975.
32.
Stewart, R.D., P.E. Newton, J. Kaufman, H.V. Forster, and J.P. Klein.
Effect of a rapid 4 percent carboxyhemoglobin saturation increase on
maximal treadmill exercise. CRC-APRAC-CAPM-22-75, 1978.
33.
Klein, J.P., H.V. Forster, R.D. Stewart, and A. Wu. Hemoglobin affinity
for oxygen during short-term exhaustive exercise. J. Appl. Physiol.
48:236-242, 1980.
34.
Beard, R.R., and N.W. Grandstaff. Carbon monoxide and human functions.
In: Behavioral Toxicology. B. Weiss and V.G. Laties, eds., Plenum
Press '. New York, 1975. pp. 1-26.
Haider, M., E. Groll-Knapp, H. Hoeller, M. Neuberger, and H. Stidl.
Effects of moderate CO dose on the central nervous system--
el ectrophysi 01 ogi cal and behavi our data and cl i ni cal rel evance. In:
Clinical Implications of Air Pollution Research, Air Pollution MeCffcal
Research Conference, American Medical Association, San Francisco,
California, December 5-6, 1974. A.J. Finkel and W.C. Duel, eds.,
Publishing Sciences Group, Inc., Acton, MA, 1976. pp. 217-232~
35.
Winneke, G. Behavioral effects of methylene chloride and carbon
monoxide as assessed by sensory and psychomotor performance. In:
Behavioral Toxicology. Early Detection of Occupational HazardS:
Proceedings of a Workshop, National Institute for Occupational Safety
and Health and Uni versity of Ci nci nnati , Ci nci nnati , Ohi 0, June 24-29,
1973. C. Xintaras B.L. Johnson, and I. de Groot, eds., HEW Publication
No. (NIOSH) 74-126, U. S. Department of Health, Education and Welfare.
Christensen, C.L., J.A. Gliner, S.M. Horvath, and J.A. Wagner. Effects
of three kinds of hygoxias on vigilance performance. Av. Sp. Env.
Med. 48:491-496, 1977.
-------
47.
48.
49.
50.
4
38.
Benignus, V.A., D.A. Otto, J.D. Prah, and G. Benignus. Lack of effects
of carbon monoxide on human vigilance. Percept. Mot. Skills 45:1007-
1014, 1977. . -
39.
Putz, V.R., B.L. Johnson, and J.V. Setzer. Effects of CO on Vigilance
Performance. Effects of Low Level Carbon Monoxide.on Divided Attention,
Pitch Discrimination, and the Auditory Evoked Potential. DHEW (NIOSH)
Publication No. 77-124, U.S. Department of Health, Education, and
Wel fare, Nati onal Insti tute of Occuapti onal Safety and Heal th,
Ci nci nnati , OH, November, 1976.
40.
Benignus, V.A., K.E. Muller, C.N. Barton, J.D. Prah, and L.L. Benignus.
Neurobehavioral effects of CO exposure in humans. . Protocol 1, Final
report. U.S. Army Medical Research and Development Command, Fort'
Detrick, Frederick, MD. Project Order 1812 January, 1983.
41.
McFarland, R.A., F.J.W. Roughton, M.H. Halperin, and J.I. Niven.
effects of carbon monoxide and altitude on visual thresholds. J.
Aviat. Med. 15:593-602, 1971.
The
42.
Putz, V.R. The effects of carbon monoxide on dual-task performance.
Human Factors 11:13-24, 1979.
Putz, V.R., B.L. Johnson, and J.V. Setzer. A comparative study of the
effects of carbon monoxide and methylene chloride on human performance.
In: Proc. 1st~Ann. NIOSH Sci. Symp. Chicago: Pathotox Pub1ixhing
Co., 1979.
43.
44.
Horvath, S.M., P.B. Raven, T.E. Dahms, and D.J. Gray. Maximal aerobic
capaci ty at di fferent 1 evel s carboxyhemog1 obi n. J. App1. Physi 01 .
38:300-303, 1975.
45.
Groll-Knapp, E., H. Wagner, H. Hauck, and M. Haider. Effects of low
carbon monoxide concentrations on vigilance and computer-analyzed
brain potentials. Staub Reinhalt. Luft )2:64-68, 1972.
Fodor, G.G., and G. Winneke. Effect of low CO concentrations on
resistance to monotony and on psychomotor capacity. Staub Reinha1t.
Luft )2:45-54, 1972.
46.
Bender, W.W. Gothert, G. Malorny, and P. Sebbesse. Effects of low
carbon monoxide concentrations in man. Arch. Toxico1. 21:142-158, 1971.
Schulte, J.H. Effects of mild carbon monoxide intoxication.
Environ. Health 2:524-530, 1973.
O'Donnell, R.D., P. Mikulka, P. Heinig, and J. Theodore. Low level
carbon monoxide exposure and human psychomotor performance. Toxico1.
App1. Pharma-co1. 18:593-602,1971.
Arch. .
McFarland, R.A. Low level exposure to carbon monoxide and driving
performance. Arch. Environ. Health 27:355-359, 1973.
-------
62.
63.
64.
5
51.
Salvatore, S. Performance decrement caused by mild carbon monoxide
levels on two visual functions. J. Safe Res. ~:131-134, 1974.
Wright, G., P. Randell, and R.J. Shephard. Carbon monoxide and driving
skills. Arch. Environ. Health 27:349-354, 1973.
52.
53.
Rockwell, T.J., and F.W. Weir. The Interactive Effects of Carbon Monoxide
and Alcohol on Driving Skills. Ohio State University Research
Foundation, Columbus, OH, January 1975.
Rummo, N., and K. Sarlanis. The effect of carbon monoxide on several
measures of vigilance in a simulated driving task. J. Safe Res. 6:126-
130, 1974.
54.
55.
Kalmaz, E.V., L.W. Carter, C.A. Nau, and J.W. Hampton. Effect of
carbon monoxide exposure on blood. Fibrinolytic activity in rabbits.
Environ. Res. li:194-202, 1977.
Kalmaz, E.V., L.W. Carter, R.L. Coleman, and J.W. Hampton. Enhancement
of Fibrinolysis in rabbits exposed to low and moderate levels of carbon
monoxide inhibited by epsilon amino caproic acid. Thromb. Haemostasis
~: 109-121, 1978.
56.
57.
Kalmaz, E.V., L.W. Canter, and J.W. Hamptom. Effect of long-term low
and moderate levels of carbon monoxide exposure on platelet counts of
rabbits. J. Environ. Pathol. Toxicol. 4:351-8, 1980.
El-Attar, O.A., and D.M. Sairo. Effect of carbon monoxide on the whole
fibrinolytic activity. Ind. Med. Surge 12:774-777,1968.
58.
59.
Alexieva, T., J. Boyadjieva, S. Ivanova, and E. Marinova. Some of the
early criteria in the diagnosis of chronic carbon monoxide poisoning.
Probe Khygiennta 1:73-78, 1975.
Panchenko, LN., I.F. Nalcha, N.I. Dzyuba, and N.P. Luk' Yanova. The
effect of industrial factors in the development of cerebral atherosclerosis
in workers in a methanol plant. Vrach. Delo. 4:109-113, 1977.
60.
61.
Haft, J.I. Role of blood platelets in coronary artery disease.
J. Cardiol. 4j:1197-1206, 1979.
Am.
Longo, L.D. The biological effects of carbon monoxide on the pregnant
woman, fetus, and newborn infant. Am. J. Obstet. Gynecol. 129:69-103,
1977 . -
Peterson, D. The sudden infant death syndrome - reassessment of growth
retardation in relation to maternal smoking and the hypoxia hypothesis.
Am. J. Epid. 113:583-589, 1981.
Hoppenbrouwers, T., M. Calub, K. Arakawa, and J.E. Hodgman. Seasonal
relationship of sudden infant death syndrome and environmental
pollutants. Am. J. Epid. 113:623-635,1981.
-------
75.
76.
77.
6
65.
Goldstein, I. Letter to the editor: Seasonal relationship of sudden
infant death syndrome and environmental pollutants. Am. J. Epid.
116:189-191,1982.
u.S. Department of Health Education, and Welfare (DHEW). Coronary
Heart Diseases in Adults: United States, 1960-1962 DHEW Publication
No. (PHS) 79-1919. Public Health Service. Hyattsville, Maryland. 1975.
66.
67.
U.S. Department of Health Education, and Welfare (DHEW). Prevalence
of Selected Chronic Respiratory Conditions: United States, 1970.
DHEW Publication No. (HRA) 74-1511. Rockville, Maryland. 1973.
U.S. Department of Health Education, and Welfare (DHEW). Vital
Statistics of the United States, 1975, Volume I. DHEW Publication'
No. (PHS) 78-1113. Hyattsvi 11 e, Maryl and. 1978.
68.
69.
U.S. Department of Health Education, and Welfare (DHEW). Prevalence
of Chronic Conditions of the Genitourinary, Nervous, Indocrine,
Metabolic, and Blood and Blood-Forming Systems and other Selected
Chronic Conditions: United States, 1973. DHEW Publication No. (HRA)
77-1536. Rockville, Maryland. 1977.
70.
U.S. Department of Health Education, and Welfare (DHEW).
of Chronic Circulatory Conditions: United States, 1972.
No. (HRA) 75-1521. Rockvi 11 e, Maryl and. 1974.
Prevalence
DHEW Publication
71.
U.S. Department of Commerce.
States, 1980 (101st edition).
Statistical Abstract of the United
Bureau of Census.
72.
Coburn, R.F., R.E. Forster, and P.B. Kane. Considerations of the
physiological variables that determine the blood carboxyhemoglobin
concentration in man. J. Clin. Invest. 44: 1899-1910, 1965.
Biller, W.F. and H.M. Richmond. Sensitivity Analysis on Coburn Model
Predictions of COHb Levels Associated ~th Alternative CO Standards.
Prepared for Office of Air Quality Planning and Standards, U.S. EPA.
Research Triangle Park, N.C. November 1982.
73.
74.
Johnson, T. and R.A. Paul. The NAAQS Exposure Model (NEM) Applied to
Carbon Monoxi de (Draft) Prepared by PEDCo Envi ronmental, Inc. for
Office of Air Quality Planning and Standards, U.S. EPA, Durham, N.C.
August 1983.
Biller, W.F. and T.B. Feagans. Statistical Forms of national ambient
air quality standards. Presented at Environmetrics ..181 Conference.
Alexandria, Virginia. April 8-10, 1981.
Pirnay, F., J. Dujardin, R. Deroanne, and J.M. Petit. Muscular exercise
during intoxication by carbon monoxide J. Appl. Physiol. 31:573-575,1971.
Vogel, J .A. and M.A. Gl eser. Effects of carbon monoxi de on oxygen
transport during exercise. J. Appl. Physiol. .32:234-239,1972.
-------
7
78.
Weiser, P.C., C.G. Morrill, D.W. Dickey, T.L. Kurt, and G.J.A. Cropp.
Effects of low-level carbon monoxide exposure on the adaptation of
healthy young men to aerobic work at an altitude of 1,610 meters. In:
Environmental Stress. Individual Human Adaptations. L.J. Folinsbee:
J.A. Wagner, J.F. Borgia, B.L. Drinkwater, J.A. Gliner, and J.F. Bedi,
eds. , Academi c Press, New York, 1978. pp. 101-110.
79.
Ayres, S.M., R.G. Evans, and M.E. Buehler. The prevalence of
carboxyhemoglobinemia in New Yorkers and its effects on the coronary
and systemic circulation. Prevo Med. ~:323-332, 1979.
------- |