SIGNIFICANT HAR^, LEVELS FOR CARBON MONOXIDE
DRAF
U.S. ENVIRONMENTAL DROTECTION AGENCY
JULY 1380
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SIGNIFICANT HARM LEVELS FOR CARBON MONOXIDE
"Significant harm levels" for criteria pollutants are those ambient
concentrations of the pollutants associated with specific adverse health
effects which create "an imminent and substantial endangerment to the health
of persons."
As stated in the Federal Register, Vol. 40, No. 162, p. 36333, August 20,
1975:
Life threatening or permanently disabling exposures are clearly
serious threats to health. Reversible but acutely incapacitating
health effects also would be sufficiently disturbing to the
general public to require remedial action. It is our opinion
that both of these do, in fact, constitute "significant harm."
In 1971, the following "significant harm level" was established for
carbon monoxide (CO):
50 ppm 8-hr average
75 ppm 4-hr average
125 ppm 1-hr average
The purpose of this paper is to identify adverse health effects, which
have been documented in scientific journals, associated with exposure of
humans to levels of CO which may cause significant harm.
Health Effects of Carbon Monoxide
Health effects of CO are presently thought to be caused primarily by a
reduction in the ability of the blood to transport oxygen (02) and a consequent
interference with biochemical utilization of 02 in tissues. The toxicity of
CO is due to strong coordination bonds formed between CO and the iron atoms in
hemoglobin (Hb). Carbon monoxide and Hb interact in the blood to form carboxy-
hemoglobin (COHb).
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The attraction between CO and Hb is more than 200 times stronger than the
"attraction between Q~ and Hb and effectively eliminates the binding site from
the normal transport of O^. Myoglobin also exhibits a very strong affinity
for CO; however, muscle impairment has not yet been clearly demonstrated.
All humans have some level of CO in their circulatory systems. The
normal catabolism of Hb results in endogenous levels of between 0.3 to 0.7
2
percent COHb. Levels above this can normally be assumed to result from
exogenous sources. It is important to note that high variability in COHb
concentrations is commonly found between individuals both for endogenous COHb
production and for COHb concentrations resulting from exposure to similar
ambient CO levels. This is demonstrated by the effect of exercise on COHb
levels as shown in Table 1.
Health effects which have been attributed to CO exposure at or near
significant harm levels include: (1) aggravation of angina pectoris,
intermittent claudication, and peripheral arteriosclerosis; (2) decreased
exercise capacity in normal persons and in patients with chronic obstructive
pulmonary disease, angina pectoris, intermittent claudication and peripheral
arteriosclerosis; (3) changes in heart functioning and possible impairment;
(4) reduced birth weight; and (5) impairment of vigilance, visual perception,
manual dexterity, ability to learn, and performance on complex sensorimotor
tasks, such as driving. The above health effects are summarized in Table 2
along with references and the ranges of specific levels of CO exposure
associated with the health effects.
Presently, the scientific community recognizes two general classifications
of health effects associated with CO exposure. These are cardiovascular effects
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TABLE 1. PERCENT COHb AS A FUNCTION OF CO EXPOSURE
PERCENT COHb BASED ON COBURN EQUATION3
CO
(ppm)
5.0
9.0
15.0
20.0
25.0
35.0
50.0
Resting
0.6
0.7
1.0
1.1
1.3
1.6
2.2
1
Moderate
Exercise
0.6
0.8
1.1
1.4
1.6
2.1
2.9
Exposure Time (Hours)
2 4
Resting
0.
0.
1.
1.
1.
2.
3.
7
9
3
6
9
5
5
Moderate
Exercise
0.7
1.0
1.5
2.0
2.4
3.2
4.5
Resting
0.8
1.2
1.8
2.3
2.8
3.8
5.2
Moderate
Exercise
0.8
1.3
2.0
2.6
3.2
4.5
6.3
Resting
0.
1.
2.
2.
3.
4.
7.
9
4
2
9
6
9
0
8
Moderate
Exercise
0.9
1.5
2.4
3.1
3.8
5.3
7.6
% COHb at
Equilibrium
Based on
Haldane
Equation
0.9
1.6
-
3.5
-
-
8.2
Assumed conditions: Alveolar ventilation rates: resting = 10 L/min,
moderate exercise = 20 L/min (equivalent to 3
mph walk on level ground or light industry or housework);
hemoglobin - 15 g/100 mL (normal); altitude = sea level;
endogenous COHb level =0.5 percent.
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TABLE 2. ESTIMATED HEALTH EFFECTS LEVELS FOR CARBON MONOXIDE EXPOSURE
Effects
COHb concen- .
tration, percent5
References
Passive smoking aggravates 1.8-2.3
angina pectoris
Decreased exercise capacity 2.5-3.0
in patients with angina pec-
toris, intermittent claudica-
tion, or peripheral arterio-
sclerosis
Impairment of vigilance tasks 3.0-7.6
in healthy experimental subjects
Decreased exercise performance 3.0-4.9
in normal persons and in
patients with chronic obstructive
pulmonary disease
Increased angina attacks for
freeway travel
Changes in heart functioning
and possible impairment
Linear relationship between COHb
and decreasing maximal oxygen
consumption during strenuous
exercise in young healthy men
Statistically significant diminu- 5-17
tion of visual perception, manual
dexterity, ability to learn, or
performance in complex sensorimotor
tasks (such as driving)
3.8-8.0
3.9-5.0
5-20
Aronow, 1978
Anderson et al., 1973
Aronow and Isbell, 1973
Aronow et al., 1974
Aronow and Rokaw, 1971
Horvath et al. , 1971
Groll-Knapp et al., 1972
Fodor and Winneke, 1972
Aronow and Cassidy, 1975
Aronow et al., 1977
Aronow et al., 1972
Aronow et al., 1974
Ayres et al., 1969
Ayres et al., 1970
Ekblom and Huot, 1972
Horvath, 1975
Dahms et al., 1975
Seppanen, 1977
Bender, et al., 1971
Schulte, 1973
O'Donnell et al., 1971
McFarland, 1973
Putz et al., 1976
Salvatore, 1974
Wright et al., 1973
Rockwell and Weir, 1975
Rummo and Sarlanis, 1974
The physiologic norm (i.e., COHb Levels resulting from the normal metabolic
breakdown of hemoglobin and other heme-containing materials) has been
estimated to be in the range of 0.3 to 0.7 percent.
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and central nervous system effects. There has been evidence presented that CO
toxicity may be, at least in part, due to non-hypoxic inhibition of oxidase
enzymes; however, this has not yet been clearly demonstrated or accepted by
the scientific community.
•Cardiovascular Effects
4
Cardiovascular failure is the leading cause of death in the United States.
What portion of these deaths can be directly or indirectly attributed to CO
exposure remains uncertain. It has been stated that a large segment of the
population over forty, possibly as large as one-half, may have sufficiently
defective cardiovasculatures to be susceptible to adverse health effects
associated with CO concentrations commonly found in urban air.
It is well documented that persons suffering from angina pectoris will
experience early onset of pain from angina attacks after an 8-hr equivalent
6-9
exposure to CO concentrations of 15 to 18 ppm (2.5 percent COHb) and exercise.
This effect is thought to be the result of an oxygen debt caused by a defective
cardiovasculature in conjunction with a reduced blood 02 supply. This blood
OP supply, which is inversely related to CO exposure, will continue to decrease
as CO concentrations increase.
Studies conducted at ambient CO concentrations sufficient to achieve COHb
levels of 5-10 percent have shown changes in myocardial metabolism and possible
impairment. ' As a result of studies in which 26 men between the ages of
41 and 60 were exposed to 100 ppm of CO for four hours, it was suggested "that
exposure to low,levels of CO may worsen myocardial ischemia, impair myocardial
function and enhance development of arrhythmias during exercise in a large
segment of the population " Other results suggest that COHb concentrations
of 5 percent interfere with oxygen delivery to the myocardium. Carbon
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monoxide not only hastens development of atherosclerosis but has a sufficiently
damaging effect on myocardial tissue to worsen the effects of coronary occlu-
sions.18'19
At significant harm levels for CO, it could be expected that persons who
otherwise might have been considered normal could begin to experience adverse
health effects caused by CO exposure. Those individuals who have a pre-exist-
ing oxygen debt (e.g., anemics, asthmatics, angina patients, fetuses) will
very likely find their conditions exacerbated at these CO levels. Although
the extent to which any individual is affected depends upon the physiology,
exercise and exposure patterns of that person, it can be stated that an 8-hr
exposure to 50 ppm CO (7-8 percent COHb) would create adverse cardiovascular
effects in a large segment of the U. S. population.
Central Nervous System
Health effects associated with.the central nervous system (CNS) do not
begin to consistently appear in most individuals until equivalent 8-hr expo-
sures of 35-40 ppm CO (5 percent COHb) are experienced. Early studies suggesting
effects at levels as low as 2.5 to 3 percent COHb have not been replicated and
are not presently considered to reflect the level of effect for the CNS in
20 21
normal individuals. '
Many studies have documented an impairment of vigilance in healthy experi-
22 23 24
mental subjects. ' ' In one study, the impairment was due to exposure of
subjects to levels of CO (average 26 ppm and peak 111 ppm) found while driving
2?
in urban traffic. It was suggested that persons who sustain increases in
COHb saturation of more than about 2 percent to 3 percent may become less
effective in coping effectively with unexpected events and more likely to
perform routine tasks in an inefficient manner.
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Significant decrements were found in several measures of vigilance in a
simulated driving task following exposure of subjects to levels of CO sufficient
25
to produce 6 to 8 percent COHb. Even at levels as low as 3.4 percent COHb,
26
it was shown that the ability to drive safely may be impaired.
Numerous other studies suggest a significant diminution of visual perception,
manual dexterity, and ability to learn after CO exposures resulting in 5
07-33
percent to 10 percent COHb. The implications of such effects should be
evident.
The long-term exposure impacts have not yet been well characterized for
the CNS. Studies have not been performed and published for persons with
impaired cerebrovasculatures. However, the reduction in vigilance and manual
dexterity associated with significant harm levels of CO may result in an
increase in automobile accidents and in job-related or household accidents.
The reduction in ability to learn may begin to play an important role in
hindering the learning process of school children exposed to significant harm
levels of CO.
Conclusions
The present significant harm standards appear to adequately protect
normal individuals in the United States. However, there may be groups
constituting a significant portion of the population of the United States
with extensive cardiovascular or cerebrovascular damage. Individuals in these
groups may show adverse health effects below significant harm levels.
In comments by the Senate Committee on Public Works, the Committee stated
that "emergency authority is necessary to provide for immediate, effective
action whenever air pollution agents reach levels of concentration that are
associated with: (1) the production of significant health effects,
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(2) incapacitating body damage, or (3) irreversible body damage in any
significant portion of the general populations. The term "significant portion
[was] not intended to exclude sensitive elements of society such as asthmatics,
but only those groups of particularly susceptible persons for whom other
precautionary measures should be taken. Secondly, the emergency situation
34
exists whenever there is any perceptible increase in the mortality rate."
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REFERENCES
1. 1970 Clean Air Act, Section 303.
2. Coburn, R. F., R. E. Forster, and P. B. Kane. Considerations of the
physiological and variables that determine the blood carboxyhemoglobin
concentration in man. J. Clin. Invest. 44:1899-1910, 1965.
3. Goldbaum, L. R., T. Orellano, and E. Oergal. Mechanism of the toxic
action of carbon monoxide. Ann. Clin. Lab. Sci. 6:372-376, 1976.
4. National Center for Disease Control, U.S. Environmental Health Services
Division. Occupational exposure to CO in selected rural work environments.
Atlanta, GA, 1973.
5. Transcript of CASAC CO Subcommittee meeting January 30-31, 1979. (Office
of General Counsel and ECAO)
6. Aronow, W. S. Effect of passive smoking on angina pectoris. N. Engl. J.
Med. 299:21-24, 1978.
7. Aronow, W. S., and S. N. Rokaw. Carboxyhemoglobin caused by smoking
non-nicotine cigarettes: effects in Angina Pectoris. Circulation
44:782-788, 1971.
8. 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
duration of angina pectoris: A study on 10 patients with ischemic heart
disease. Ann. Intern. Med. 79:46-50, 1973.
9. Aronow, W. S., C. N. Harris, M. W. Isbell, S. N. Rokaw, and B. Imparato.
Effect of freeway travel on angina pectoris. Ann. Intern. Med. 77:669-676,
1972.
10. Aronow, W. S., J. Cassidy, 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.
11. Aronow, W. S., E. A. Stemmer, and M. W. Isbell. Effect of carbon monoxide
exposure on intermittent claudication. Circulation 49:415-417, 1974.
12. Aronow, W. S., and M. W. Isbell. Carbon monoxide effect on exercise-induced
angina pectoris. Ann. Intern. Med. 79:392-395, 1973.
13. 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.
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14. Aronow, W. S. , J. Ferlinz, and F. Glauser. Effect of carbon monoxide on
exercise performance in chronic obstructive pulmonary disease. Am. J.
Med. 53:904-908, 1977.
15. Ayres, S. M., H. S. Mueller, J. J. Gregory, S. Giannelli, Jr., and J. L. Penny.
Systemic and myocardial hemodynamic responses to relatively small concentra-
tions of carboxyhemoglobin (COHb). Arch. Environ. Health 18:699-709,
1969.
16. Knelson, J. H. Discussion of the Carbon Monoxide Standards for the
Federal German Republic: lr\: Carbon Monoxide - Origin, Measurement, and
Air Quality Criteria. VOI Berichte No. 180, 1972, pp. 120-124, Pro-
ceedings of the Colloquium Held in Dusseldorf October 28-29, 1971.
Reprinted from Staub Reinhalt. Luft 32(4), April 1972.
17. Ayres, S. M., S. Giannelli, Jr., H. Mueller. Myocardial and systemic
responses to carboxyhemoglobin. Ln: Biological effects of carbon
monoxide, R. F. Coburn, ed. Ann. N.Y. Acad. Sci. 174(Art. l):268-293,
October 5, 1970.
18. Astrup, P. Some physiological and pathological effects of moderate
carbon monoxide exposure. Br. Med. J. 4:447-452, 1972.
19. Astrup, P. Carbon monoxide, smoking and cardiovascular disease.
Circulation 48:1167-1168, 1973.
20. Beard, R. R., and G. A. Wertheim. Behavioral impairment associated with
small doses of carbon monoxide. Am. J. Public Health 57:2012-2022, 1967.
21. 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.
22. Horvath, S. M., T. E. Dahms, and J. F. O'Hanlon. Carbon monoxide and
human vigilance. A deleterious effect of present urban concentrations.
Arch. Environ. Health 23:343-347, 1971.
23. 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 32:64-68, 1972.
24. Fodor, G. G., and G. Winneke. Effect of low CO concentrations on
resistance to monotony and on psychomotor capacity. Staub Reinhalt. Luft
32:46-54, 1972.
25. Rummo, N., and K. Sarlanis. The effect of carbon monoxide on several
measures of vigilance in a simulated driving task. J. Saf. Res. 6:126-130,
1974.
26. Wright, G., P. Randell, and R. J. Shephard. Carbon monoxide and driving
skills. Arch. Environ. Health 27:349-354, 1973.
27. Bender, W., M. Gothert, G. Malorny, and P. Sebbesse. Effects of low
carbon monoxide concentrations in man. Arch. Toxicol. £7:142-158, 1971.
10
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28. Schulte, J. H. Effects of mild carbon monoxide intoxication. Arch.
Environ. Health 7:524-530, 1973.
29. O'Donnell, R. D., P. Chikos, and J. Theodore. Effect of carbon monoxide
exposure on human sleep and psychomotor performance. J. Appl. Physio!.
31:513-518, 1971.
30. McFarland, R. A., W. H. Forbes, H. J. Stoudt, J. D. Dougherty, T. J. Crowley,
R. C. Moore, and T. J. Nalwalk. A Study of the Effects of Low Levels of
Carbon Monoxide upon Humans Performing Driving Tasks. Final Report.
Harvard University, Guggenheim Center for Aerospace Health and Safety,
Boston, MA, May 1973.
31. 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 Welfare,
National Institute of Occupational Safety and Health, Cincinnati, OH,
November, 1976.
32. Salvatore, S. Performance decrement caused by mild carbon monoxide
levels on two visual functions. J. Saf. Res. 6:131-134, 1974.
33. 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.
34. Library of Congress, Committee on Public Works, U.S. Senate. A Legislative
History of the Clean Air Amendments of 1970, Committee Print Serial No.
93-18, January 1974.
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