National Academies Press: OpenBook
« Previous: 3 Carbon Dioxide
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

4
Carbon Monoxide

This chapter summarizes the relevant epidemiologic and toxicologic studies on carbon monoxide (CO). Selected chemical and physical properties, toxicokinetic and mechanistic data, and inhalation exposure levels from the National Research Council (NRC) and other agencies are also presented. The subcommittee considered all of that information in its evaluation of the Navy’s current and proposed 1-hour (h), 24-h, and 90-day exposure guidance levels for CO. The subcommittee’s recommendations for CO exposure levels are provided at the conclusion of this chapter along with a discussion of the adequacy of the data for defining those levels and the research needed to fill the remaining data gaps.

PHYSICAL AND CHEMICAL PROPERTIES

CO is a colorless, odorless gas (Budavari et al. 1989). Selected physical and chemical properties are summarized in Table 4-1.

OCCURRENCE

CO primarily is produced by partial oxidation of carbon-containing materials (Pierantozzi 1995). In the outdoor environment, major sources of CO are motor vehicles and fires (EPA 2000). In the indoor environment, sources include tobacco smoking, combustion engines, and combustion appliances, such as furnaces and gas stoves. On submarines, the primary sources of CO are tobacco smoking, diesel generators, and high-temperature paints (Crawl 2003). Data collected on nine nuclear-powered ballistic missile submarines indicate an average CO concentration of 5 parts per

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

TABLE 4-1 Physical and Chemical Properties of Carbon Monoxidea

Synonyms

Carbonic oxide, carbon oxide, flue gas

CAS registry number

630-08-0

Molecular formula

CO

Molecular weight

28.01

Boiling point

−191.5°C

Melting point

−205.0°C

Flash point

Explosive limits

12.5% to 74.2% (volume % in air)

Specific gravity

0.968 with respect to air

Vapor pressure

>1 atm at 20°C

Solubility

Sparingly soluble in water; appreciably soluble in ethyl acetate, chloroform, and acetic acid

Conversion factors

1 ppm = 1.15 mg/m3; 1 mg/m3 = 0.87 ppm

aData on vapor pressure are from HSDB (2004); data on explosive limits are from IPCS (2001); all other data are from Budavari et al. (1989).

Abbreviations: atm, atmosphere; mg/m3, milligram per cubic meter; ppm, parts per million; —, not available or not applicable.

million (ppm) and a range of 0-14 ppm, and data collected on 10 nuclear-powered attack submarines indicate an average CO concentration of 3 ppm and a range of 0-14 ppm (Hagar 2003).

SUMMARY OF TOXICITY

The toxicology of CO in humans was reviewed by the World Health Organization (WHO) (1999), the U.S. Environmental Protection Agency (EPA) (2000), and the NRC (2002). Only human and animal data directly relevant to derivation of the EEGL and CEGL values are discussed in this chapter.

CO interferes with the oxygenation of blood and the delivery of oxygen to tissues because it has about 245 times more affinity for hemoglobin than does oxygen (Roughton 1970). The formation of carboxyhemoglobin (COHb) reduces the oxygen-carrying capacity of blood and shifts the oxygen dissociation curve, reducing the release of oxygen to tissues. Hypoxemia and subsequent tissue hypoxia comprise the best understood mechanism of CO toxicity. The cytotoxic effects of CO independent of oxygen are subjects of current research. CO also binds to muscle myoglobin, cytochrome c oxidase, and cytochrome P-450, and many of the adverse effects of CO might be associated with those reactions (WHO 1999;

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

EPA 2000; Raub et al. 2000). Endogenous production of CO accounts for a background COHb level of about 1% (Radford et al. 1981; Doherty 2000). The log-log plot of CO uptake and COHb saturation, as computed from the Coburn-Foster-Kane equation, is shown in Figure 4-1 (Peterson and Stewart 1975).

The brain and cardiovascular system are the primary targets of CO toxicity. The adverse effects of CO exposures range from subtle vascular and neurologic changes to more serious conditions, such as loss of consciousness and death. Even when CO-intoxicated patients receive treatments, more than 10% of survivors might experience permanent brain damage, and in many cases, the onset of adverse effects is delayed as long as 1 week or more. The primary cause of neurologic injury might be hypotension leading to impaired tissue perfusion (Varon et al. 1999). CO intoxication causes hypotension by myocardial depression, peripheral vasodilation, and ventricular dysrhythmia (Varon et al. 1999).

Morbid complications of CO intoxication are greatly affected by a variety of factors related to cardiovascular health, including the degree and duration of hypotension, and the presence of pre-existing cardiac or pulmonary disease, anemia, or cardiac dysfunction (arrhythmias or other conditions) (Ehrich et al. 1944; Stewart et al. 1975). COHb concentrations in smokers average 4% and range from 3% to 8%; heavy smokers could have COHb concentrations as high as 15% (Raub et al. 2000; Omaye 2002). Submariners who smoke theoretically might be subject to additional health risks from environmental exposure given their already elevated COHb levels.

A number of short- and long-term adaptations to compensate for reduced oxygenation of blood and tissues related to CO exposure have been identified. Those changes are found in humans and animals and include increased coronary and brain blood flow in the short-term and increased hematopoiesis over time (WHO 1999). However, cardiovascular disease might reduce or eliminate the body’s ability to compensate for CO-related hypoxemia and tissue hypoxia (WHO 1999).

Effects in Humans

Accidental Exposures

In their review of U.S. mortality records from 1979-1988, Cobb and Etzel (1991) identified 56,133 (0.3%) of the total death records (NCHS

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

FIGURE 4-1 Carbon monoxide concentrations reached in blood (percent saturation at various durations of exposure) in a normal human subject as a function of inspired CO. Abbreviations: PB, barometric pressure; PCO2, average partial pressure of carbon dioxide in lung capillaries; VA, alveolar ventilation rate; Vb, blood volume; M, equilibrium constant; DL, diffusing capacity of the lungs; [COHb]o, control value of carboxyhemoglobin prior to carbon monoxide exposure; VCO, rate of endogenous carbon monoxide production. Source: Peterson and Stewart 1975. Reprinted with permission from the Journal of Applied Physiology; copyright 1975, the American Physiology Society.

2002) that indicated CO toxicity as a contributing cause of death. Acutely fatal CO poisoning is likely due to hypoxia and its adverse effects on the heart, as suggested by the large number of patients who exhibited marked hypotension and lethal arrhythmias prior to CO-induced death.

Sokal and Kralkowska (1985) provided an analysis of 39 patients (18-78 years of age) intoxicated by CO produced from the combustion of household gas or coal-stove gas. Of the 39 patients exposed to CO, 16 showed mild intoxication and 12 showed moderate intoxication exhibiting symptoms, such as headache, vomiting, tachycardia, and breathing problems, after exposures that lasted about 5 h. COHb concentrations averaged

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

27%. Eight patients presented with symptoms of severe intoxication, including loss of consciousness and pathologic neurologic signs, tachycardia, and tachypnea after exposures that lasted about 9 h. COHb concentrations averaged 34%. Four subjects exhibited very severe effects, including central nervous system (CNS) damage, and circulatory and respiratory disturbances after exposures that lasted about 10 h. COHb concentrations averaged 31%. The subcommittee notes the lack of agreement between the total number of patients in the study and the number of patients categorized by clinical degree of intoxication.

Ely et al. (1995) reported adverse effects of CO exposures in employees of a sewing company located in a warehouse where a propane-fueled forklift was in operation. Thirty people were exposed to CO concentrations at up to 386 ppm. The five workers who exhibited the most severe symptoms had an average estimated COHb concentration of 35%. One of those workers had seizures. The majority of people exposed reported CNS, behavioral, gastrointestinal, and cardiovascular abnormalities, including headache (93%), dizziness (63%), nausea (60%), chest pain (57%), difficulty breathing (23%), visual changes (20%), and confusion (17%). Eleven of 25 patients contacted 2 years after exposure reported seeking medical care for persistent symptoms.

Hassan et al. (2003) reported two cases of CO poisoning that resulted in sensorineural hearing loss. The subject of the acute poisoning case, a 30-year-old man, presented with a COHb concentration of 29.9%. That subject showed only partial recovery from hearing loss. A 61-year-old woman reported to have endured chronic CO exposure presented with bilateral hearing loss that improved with time. Overall findings indicate that CO affects high-frequency hearing (1-8 kilohertz).

Experimental Studies

The adverse clinical effects of CO have been evaluated extensively in both healthy and high-risk individuals (WHO 1999; EPA 2000); however, only the studies that are most relevant to the safety of submarine crew members (healthy adult males) are discussed here. Table 4-2 summarizes the relevant experimental studies in humans. Chiodi et al. (1941) conducted controlled exposure studies in which four male subjects were exposed to CO at 1,500-3,500 ppm repeatedly for durations of 70 minutes (min) or longer. The subjects had COHb concentrations at up to 52%. There were no adverse effects on basal oxygen consumption, ventilation, pulse rate, blood pressure, or arterial blood pH in that study. The only adverse effect

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

TABLE 4-2 Human Toxicity Summary

Concentration (ppm)

Exposure Duration

COHb %

Number of Subjects

Effects

Reference

NS

NS

NS

NS

Linear relationship described betweendecline in VO2-max and increasing COHb2

EPA 1979; Horvath 1981

NS

NS

4.5

NS

Decrements in brightness discrimination in trained subjects

MacFarland et al. 1944

NS

NS

6-7

50

Deficit in “careful driving” skills

Wright et al. 1973

NS

NS

8-12

20

No adverse effects on visual discrimination or depth perception

Ramsey 1973

NS

NS

9

18

No decrement in night vision

Luria and McKay 1979

NS

NS

10 and higher

3

Increased reaction time; decreased precisionin maintenance of separation distance between cars; decrease in estimation of time

Ray and Rockwell 1970

700

Time needed to reach target COHb

11 and 17

27

Driving not “seriously” affected; statistically significant increase in roadway viewing time

MacFarland 1973

100

NS

0-20

49

Numbers of errors and completion time increased with increasing COHb concentrations for several but not all tests of cognitive ability beginning at COHb concentrations <5%; no subjective sym ptoms occurred at COHb concentrations <20%

Schulte 1963

NS

NS

40-45

4

Inability to perform tasks requiring minimal exertion

Chiodi et al. 1941

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

NS

5-60 min

15-20

NS

Oxygen uptake in tissues unchanged during submaximal exercise

Chevalier et al. 1966; Pirnay et al. 1971; Vogel et al. 1972

NS

15 min

~5-21

5

Maximal physical performance was reduced with increasing concentrations of COHb

Ekblom and Huot

1972

300

45 min

~5

20

Increased reaction time to visual stimuli; light detection sensitivity and depth perception unaffected

Ramsey 1972

50

1 h

2.1

9

“No untoward subjective symptoms or objective signs of illness”

Stewart et al. 1970

100

1 h

~2.5

10

“No untoward subjective symptoms or objective signs of illness”

Stewart et al. 1970

~10,000 “booster dose,” 225 maintenance

~1 h

~18-20

8

Reduced maximal oxygen uptake; during submaximal exercise, oxygen delivery to tissues is maintained by increased cardiac output but smaller arteriovenous oxygen concentration difference

Vogel and Gleser 1972

50

1.5-2.5 h

~2

3, 5, or 9, depending on the test

Observed impaired vigilance; no effects on response latency, short-term memory, and ability to subtract numbers mentally

Beard and Grandstaff 1975

250

1.5-2.5 h

~7

3, 5, or 9, depending on the test

No effects on vigilance, response latency, short-term memory, and ability to subtract numbers mentally

Beard and Grandstaff 1975

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Concentration (ppm)

Exposure Duration

COHb %

Number of Subjects

Effects

Reference

27-100 to maintain target COHb

2 h

5, 10, 15, and 20

16

Cardiovascular system compensated for reduced oxygen carrying capacity of blood by augmenting heart rate, cardiac contractility, and cardiac output for submaximal upper and lower body exercise; compensatory mechanisms began to fail at moderate exercise and CO exposure

Kizakevich et al. 2000

11,569 initially, 142 maintenance

2.25 h

~ 17

21

Visual function not affected

Hudnell and Benignus 1989

500

2 h-2 h and 20 min

~26 (after 2 h and 20 min)

6

“Increase in heart rate with minimal exertion;” frontal headaches after 1 hr of exposure; minimal exertion intensified headache pain; headache pain peaked 3.5 h post-exposure; changes in visual evoked response at COHb >20%, returned to normal at COHb <15%

Stewart et al. 1970

100

2.5 h

7

NS

Decrements in two learning tasks; no changes in several other measures of intellectual performance

Bender et al. 1971

100

2.5 h

5.7

16

Increased response times noted in the secondary task of a dual-task procedure in which the primary task was tapping a board

Mihevic et al. 1983

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

 

 

 

 

with a stylus, and the secondary task was announcing or subtracting numbers appearing on a display

 

0-1,000; gradually rising concentration reached 1,000 after 2 h and was maintained for 30 min

2 h 30 min

~32 (peak at 2.5 h)

2

Headaches noted during exposure became incapacitating 6 h post-exposure and were not ameliorated with a night’s sleep; clinical chemistries and electrocardiograms remained normal; changes in visual evoked response at COHb >20%, returned to normal at COHb <15%; performance impairment noted for manual coordination and hand reaction time tests

Stewart et al. 1970

2, 50, 100, 200, 500

2.5 h

Up to 20

27 (in groups of 2-8)

No impairment in ability to perform time estimation tests

Stewart et al. 1973

2, 50, 100, 200, 500

2.5 h

Up to 20

27 (3 sessions with 1 subject, 47 sessions with 2-8)

Time estimation ability, manual coordination, inspection, and arithmetic performance not impaired

Stewart et al. 1975

0, 50, 125, 200, 250

3 h

1, 3, 6.6, 10.4, 12.4

10

No symptoms and no effects on time perception and tracking performance; subjects exposed at 200 and 250 ppm were not blinded regarding exposure

Mikulka et al. 1970; O’Donnell et al. 1971

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Concentration (ppm)

Exposure Duration

COHb %

Number of Subjects

Effects

Reference

5, 35, 70

4 h

1, 3, 5

30

Dual-task conditions included hand-controlled tracking with low- and high-frequency conditions and monitoring lights and responding with a button press to indicate brighter lights; differences in tracking performance noted in the 70-ppm group after 3 h of exposure and in the 35- and 70-ppm exposure groups after 4 h in the high-frequency condition; reaction times on the light detection task increased in the 35- and 70- ppm exposure groups in the final hour of exposure

Putz 1979

70

4 h

5

12

Dual-task conditions as in Putz (1979) and auditory vigilance; statistically significant differences in tracking, response time on light monitoring, and auditory vigilance after 1.5-2 h of exposure

Putz et al. 1979

200

4 h

~16 (after 4 h)

11

Three subjects reported “mild sinus” headaches in the 4th h; headaches vanished 30 min to 2 h post-exposure; no impairment of coordination, reaction time, and visual acuity

Stewart et al. 1970

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

0, 50, 100, 175, 250

4 h

NS

18

Ability to estimate the length of an auditory signal, compared with a standard signal, reduced at all CO-exposure concentrations; time to onset of performance deficit decreased with increasing CO exposure

Beard and Wertheim 1967

<2, 50, 100, 200, 500

5 h

Up to 20

27 (in groups of 2-8)

No impairment in ability to perform time estimation tests

Stewart et al. 1973

<2, 50, 100, 200, 500

5 h

Up to 20

27 (3 sessions with 1 subject, 47 sessions with 2-8)

Time estimation ability, manual coordination, inspection, and arithmetic performance not impaired

Stewart et al. 1975

100

8 h

11-13

2

“No impairment”

Stewart et al. 1970

50

24 h

~8

3

“No untoward subjective symptoms or objective signs of illness”

Stewart et al. 1970

50

5 d

7

15

No effects on visual functions

Davies et al. 1981

0, 15, 50

24 h/d, 8 d

0.5, 2.4, 7.1

30

Electrocardiographic P-wave changes in 3 of 15 subjects in 15-ppm group and in 6 of 15 subjects in 50-ppm group

Davies and Smith 1980

Abbreviations: COHb, carboxyhemoglobin; d, day; h, hour; min, minute; NS, not stated; ppm, parts per million; VO2-max, maximal oxygen consumption.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

observed was increased cardiac output (20-50% over baseline) at COHb concentrations greater than 40%.

COHb concentrations at 40% caused drastic reductions in the ability of subjects to perform tasks requiring even minimal strength (Chiodi et al. 1941); however, COHb concentrations at 15-20% did not appear to elicit that effect (Chevalier et al. 1966; Pirnay et al. 1971; Ekblom and Huot 1972; Vogel and Gleser 1972; Vogel et al. 1972; Kizakevich et al. 2000). Some controlled experimental studies have found a linear relationship between COHb concentrations at 5-20% and decrements in human exercise performance, measured as maximal oxygen uptake (EPA 1979, 1984, 1991; Horvath 1981; Shephard 1983, 1984). However, the decrements were not considered clinically significant.

From a pool of 18 healthy men (24-42 years of age), Stewart et al. (1970) exposed groups of 2-11 to CO concentrations ranging from 25 to 1,000 ppm for periods of 30 min to 24 h. The exposures took place in sedentary exposure chambers. The study evaluations included measurements of hand and foot reaction time in a driving simulator, Crawford collar and pin tests, Crawford screw tests, a hand steadiness test, the Flanagan coordination test, a complete audiogram, a resting 12-lead electrocardiogram, and measurements of visual evoked response. CO was well tolerated at concentrations up to 100 ppm (COHb at 12.5%) for up to 8 h, eliciting no subjective signs or visual or performance impairments. During a 4-h exposure at 200 ppm, 3 of 11 subjects developed mild sinus-like symptoms during the last hour of exposure when COHb concentrations were their highest (about 16%). Mild headaches occurred at the end of the first hour of a 2-h exposure at 500 ppm (COHb at 25.5%) and were followed by excruciatingly severe occipitofrontal headaches at 3.5 h post-exposure.

Alterations in visual evoked response and other neurobehavioral end points have been inconsistently reported by investigators. For example, some studies reported no adverse effects on vision, visual evoked response, visual discrimination, depth perception, tracking, or manual coordination in subjects who had COHb concentrations ranging from 3% to 20% (MacFarland et al. 1944; Stewart et al. 1970, 1975; Ramsey 1972, 1973; Putz 1979; Putz et al. 1979; Luria and McKay 1979; Davies et al. 1981; Hudnell and Benignus 1989).

Putz (1979), Putz et al. (1979), and Mihevic et al. (1983) used dual-task procedures to evaluate neurobehavioral performance at COHb concentrations up to 5.7% for exposure durations of 2.5-4 h. The primary manual tasks tested were tracking with a hand control (Putz 1979; Putz et al. 1979), and tapping targets on a board with a stylus (Mihevic et al. 1983). Second-

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

ary tasks were detecting light brightness and responding with a button press (Putz 1979; Putz et al. 1979) and “digit manipulation” that entailed calling out a number on a display or calling out the result of subtracting the number from 100 (Mihevic et al. 1983). In all three studies, the reaction times for the secondary tasks increased after exposure. For example, in Putz (1979) and Putz et al. (1979), reaction times for the highest-exposure condition increased about 70-80 milliseconds. The potential adverse effects described by Putz (1979), Putz et al. (1979), and Mihevic et al. (1983) were considered clinically insignificant.

Beard and Wertheim (1967) reported decrements in time-estimation ability in a study of 18 subjects exposed to CO at 0, 50, 100, 175, and 250 ppm for 4 h. The authors saw a dose-dependent decrease in correct responses. Decrements occurred within 25 min of exposure at 250 ppm, within 30 min of exposure at 175 ppm, within 50 min of exposure at 100 ppm, and within 90 min of exposure at 50 ppm (Beard and Wertheim 1967). COHb concentrations were not reported; however, on the basis of Figure 4-1, 4-h exposures at 50, 100, 175, and 250 ppm would result in COHb concentrations of about 3%, 5%, 8%, and 10%, respectively. In contrast, Mikulka et al. (1970) and O’Donnell et al. (1971) exposed 10 subjects to CO at 0, 50, 125, 200, and 250 ppm for 3 h and found no consistent differences in tracking, time estimation, or the Pensacola Ataxia Battery at any exposure concentration. COHb concentrations averaged 1%, 3%, 6.6%, 10.4%, and 12.4%, respectively. The authors noted that the subjects in the 200- and 250-ppm trials were not blinded regarding exposure (Mikulka et al 1970; O’Donnell et al. 1971). Stewart et al. (1973, 1975) could not replicate the Beard and Wertheim (1967) findings using three different time-estimation tasks, including the one employed by Beard and Wertheim (1967).

Beard and Grandstaff (1975) exposed groups of three, five, or nine subjects to CO concentrations at 0, 50, 175, and 200 ppm for 2 h. COHb concentrations corresponding to the exposures were <2% in the control groups, about 2% at 50 ppm, 5-6% at 175 ppm, and about 7% at 200 ppm. The authors found performance decrements related to CO exposure in the vigilance and perceptual tracking tests, and in a time-estimation task, but not in problem-solving, digit span, and spatial perception tasks. The results of the problem-solving task were confounded by learning. The spatial perception and digit span tasks were not consistently affected by CO. The authors concluded that the interactive nature of the digit span task and the difficulty of the spatial perception task contributed to increased arousal, which mitigated the effects of CO exposure (Beard and Grandstaff 1975).

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Putz et al. (1979) observed performance decrements in auditory vigilance after 1.5-2 h exposure to CO at 70 ppm (COHb at 5%). Christensen et al. (1977) exposed 10 subjects for 2 h under four conditions: no exposure, exposure to low oxygen (17%), exposure to CO at 114 ppm, and exposure to CO at 113 ppm in a low-oxygen environment. The authors noted a vigilance performance deficit under low-oxygen conditions (0.5% COHb), but they noted no differences from controls during the CO or CO in low-oxygen exposures. COHb concentrations during those exposures were 2.5% and 2.6% at 50 min and 4.8% and 5.1% at 120 min, respectively.

CO exposures associated with COHb concentrations as low as 6% and as high as 17% have been found to affect performance on driving measures, such as time required to respond to a velocity change in a lead car, glare recovery, hand steadiness, and roadway viewing time (Ray and Rockwell 1970; MacFarland 1973; Wright et al. 1973). However, no serious decrements in driving ability occurred at COHb concentrations 17% (MacFarland 1973).

CO exposures associated with COHb concentrations at 7% affected subjects’ ability to learn 10 nonsense syllables and decreased subjects’ ability to recite a series of digits in reverse order; however, subjects showed no changes in ability to perform other tasks involving calculations, analogies, shape selection, dot counting, and letter recognition (Bender et al. 1971).

Benignus (1994) conducted a meta-analysis of the neurobehavioral effects of CO exposures that included data from a number of the studies described above (Ramsey 1973; Stewart et al. 1970, 1973; Wright et al. 1973; Christensen et al. 1977; Putz et al. 1979). Data on how CO exposure affected vigilance, reaction time, hand steadiness, visual threshold, time discrimination, and reasoning were included. The resulting dose-response curves indicated that COHb concentrations of 18-25% are required to produce 10% deficits in neurobehavioral functions in healthy, sedentary adults (Benignus 1994).

Davies and Smith (1980) conducted an 18-day experiment in an enclosed environment where 8 days of exposure were preceded by a 5-day control period and followed by a 5-day recovery period. Fifteen naval serviceman were exposed to CO at 15 ppm, another 15 were exposed to CO at 50 ppm, and 14 servicemen served as controls. The mean COHb concentrations in the 15- and 50-ppm exposure groups were 2.4% and 7.1%, respectively. Electrocardiographic P-wave changes greater than 0.1 millivolts (mV) were observed in 3 of the 15 subjects exposed to CO at 15 ppm and in 6 of the 15 subjects exposed to CO at 50 ppm after 2 days of expo-

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

sure. The authors concluded that those changes were the result of a specific toxic effect on conducting tissue (Davies and Smith 1980).

Occupational and Epidemiologic Studies

Seufert and Kiser (1996) investigated the effects of passive smoking on the end-expiratory CO concentrations of the nonsmokers among 126 crewmen aboard a nuclear-powered submarine during a 62-h submergence. Of the men, 40 were smokers, and 86 were nonsmokers. The CO concentration on board increased from 2.6 to 9.2 ppm during the 62-h study period. The average end-expiratory CO concentrations among nonsmokers was 9 ppm at the start of the study and 21 ppm after 62 h of submergence. End-expiratory CO concentrations among smokers averaged 26 ppm at the start of the study and increased an average of 8.4 ppm during submergence. Post-exposure end-expiratory CO concentrations in nonsmokers were similar to the presubmergence levels measured in smokers (Seufert and Kiser 1996).

During 52 days of a submarine tour, Wilson and Schaefer (1979) found increased hematocrit, hemoglobin, and red blood cell counts in smoking and nonsmoking submariners and increased reticulocytes in the smokers. CO concentrations ranged from 15 to 20 ppm, and the average carbon dioxide (CO2) concentration was 9,000 ppm. Those findings could result from the low-oxygen environment as well as the CO concentrations.

No adverse health effects were observed in Holland Tunnel workers exposed to CO at an average concentration of 70 ppm (COHb at 5-10%) for 2-h periods during their 8-h workshifts for about 13 years (Sievers et al. 1942). In a retrospective study of bridge and tunnel officers exposed to CO who had average COHb levels at <5%, a significant increase in mortality from arteriosclerotic heart disease was reported in the tunnel workers (Stern et al. 1988). The authors suggested that their findings might be the result of long-term continuous CO exposures or acute peak exposures or both. However, their data on duration of employment were not related to heart disease mortality and did not support the long-term exposure hypothesis (Stern et al. 1988). Smith and Steichen (1993) reviewed the human and animal literature and concluded that CO is not atherogenic.

Many epidemiologic studies of the general population have shown positive correlations between short-term exposures to ambient air pollutants and increased mortality and exacerbation of pre-existing illness, as assessed by daily counts of deaths or hospital admissions. Studies of particulate matter and mortality are perhaps the most well known and convincing

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

example of this literature. The evidence for ambient CO exposure and health effects is less well established as illustrated below. Air pollution studies are often hampered by biologic, epidemiologic, and statistical uncertainties and data gaps. Selected studies with CO findings, reviewed below, highlight some of the key issues including the confounding effects of other air pollutants and weather, and the lack of information on long-term health effects.

Studies in North America and Europe suggest that there are associations between short- and long-term exposures to CO, hospital admissions in general, and admissions for cardiovascular and respiratory diseases. Morris et al. (1995) reported that for the period 1986-1989, the increases in relative risk (RR) of hospital admissions associated with 10-ppm increases in ambient CO concentrations ranged from 10% in New York City (RR = 1.1) to 37% in Los Angeles (RR = 1.37); other cities like Chicago, Houston, Milwaukee, and Philadelphia showed increases within that range. In a single pollutant model, CO had the greatest effect on RR. Burnett et al. (1997) evaluated the adverse effects of daily measures of ambient air pollution during summertime in Toronto, Canada, on the basis of unscheduled hospital admissions on the same day for cardiac and respiratory diseases. The mean daily 1-h maximum CO concentration was 1.8 ppm. There were no significant correlations between CO exposure concentrations and cardiovascular or respiratory admissions. Poloniecki et al. (1997) reported that ambient CO concentrations in London were positively associated with hospital admissions on the following day for cardiovascular diseases and myocardial infarctions over all seasons when CO was modeled alone. In a multiple-pollutant model with black smoke and ozone, CO was associated with myocardial infarction admissions during the cool months (Poloniecki et al. 1997). Although Burnett et al. (1997) did not find any correlation between CO concentrations and hospital admissions at a mean daily 1-h maximum CO concentration of 1.8 ppm, Poloniecki et al. (1997) found associations at lower CO concentrations. Poloniecki et al. (1997) reported that their 90th-percentile CO concentration was 1.8 ppm. On the basis of the studies by Burnett et al. (1997) and Poloniecki et al. (1997), it appears that ambient CO concentrations have stronger effects on cardiovascular risk during cool months than they do during summertime.

The average daily 1-h maximum CO concentrations in these studies have been as low as 0.2 ppm; however, the CO metrics employed in the studies are difficult to justify because of the variability in endogenous CO production. In addition, it is difficult to mechanistically and pathophysiologically explain associations between low-level CO exposures and the exacerbation of heart disease.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

The air pollution studies were not considered in deriving the EEGLs and CEGL for CO. Outcomes in the general population are not relevant to the healthy submariner population, and the studies lack precise exposure measures.

Effects in Animals

A large number of acute and repeated-dose animal toxicity studies have been conducted and reported. Given the large amount of available human data on the effects of CO exposures, only relevant animal studies are discussed here. Table 4-3 summarizes the studies discussed below.

Acute Toxicity

In unrestrained male Crl:CD rats, the LC50 values (concentrations lethal to 50% of subjects) for the 5-, 15-, 30-, and 60-min exposure periods were 10,151 ppm (95% confidence interval [CI] = 9,580-10,953 ppm), 5,664 ppm (95% CI = 5,218-6,078 ppm), 4,710 ppm (95% CI = 4,278-5,254 ppm), and 3,954 ppm (95% CI = 3,736-4,233 ppm), respectively (E.I. du Pont de Nemours and Co. 1981). COHb concentrations at 60% or higher are lethal in unrestrained rats. Acute effects are more severe in restrained rats (NAC 2004). Thirty-minute LC50 values for Swiss-Webster and ICR mice were 3,570 and 8,000 ppm, respectively (Hilado et al. 1978). In guinea pigs, the LC50 for acute 4-h exposure was 5,718 ppm (95% CI = 4,809-6,799 ppm) (Rose et al. 1970).

In monkeys exposed to CO at 1,000 ppm for several hours, severe intoxication was observed at 25 min of exposure and was followed by observed deficits in behavioral task performance, physical activity, and coordinated movements (Purser and Berrill 1983). The threshold for ventricular fibrillation induced by an electrical shock was reduced in monkeys by exposures to CO at 100 ppm for 6 h (COHb at 9.3%) (DeBias et al. 1976). In dogs, exposures to CO at 100 ppm for 2 h (COHb at 6.3-6.5%) increased the susceptibility to induced ventricular fibrillations (Aronow et al. 1979). COHb concentrations at 13-15% increased the severity and extent of ischemic injury and the magnitude of ST-segment elevation in myocardially infarcted dogs.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

TABLE 4-3 Animal Toxicity Summary

Concentration (ppm)

Exposure Duration

COHb %

Species

Effects

Reference

10,151

5 min

60 or

Crl:CD rats

LC50s for unrestrained rats

E.I. du Pont de

5,664

15 min

higher in

 

 

Nemours and Co.1981

4,710

30 min

rats that

 

 

 

3,954

60 min

died

 

 

 

3,570

30 min

NS

Swiss-Webster

LC50s for Swiss-Webster and ICR mice

Hilado et al. 1978

8,000

30 min

NS

ICR

 

 

1,000

30 min

NS

Male cynomolgus monkeys

Monkeys became less active after 20 min of exposure and appeared severely intoxicated lying or rolling on the floor after 25 min; behavioral task performance was unaffected for the initial 15 min of exposure, slowing at the first signs of intoxication

Purser and Berrill 1983

100

2 h

~6

Dogs

Decreased ventricular fibrillation threshold

Aronow et al.1979

5,718

4 h

NS

Male Hartley strain guinea pigs

LC50

Rose et al. 1970

100

6 h

~9.3

40 monkeys, 9 with myocardial infarction

Voltage necessary to induce fibrillation was highest for normal, control monkeys and lowest for infarcted monkeys breathing CO; CO exposure alone lowered fibrillation thresholds as did myocardial infarction; effects of CO and infarction together were additive

DeBias et al. 1976

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

5,000, 10,000

3 min, 6-12times perday for 3-4 wk

NS

Guinea pigs

After immunization with sheep red blood cells,three of four exposure groups had increased numbers of pulmonary alveolar macrophages, and all had increased polymorphonuclear leukocytes; reduced numbers of plaque-forming cells in spleen and lungs

Snella and Rylander 1979

50

6 wk

NS

15 dogs

Pathologic electrocardiograms in 10 dogs, pathology of heart in 7 dogs, and pathology of brain in 6 dogs

Lindenberg et al. 1962

100

6 wk

NS

Dogs

Pathologic changes in heart and brain

Lindenberg et al.1962

50, 100

6 wk

NS

Dogs

Abnormal electrocardiograms appeared in second week and persisted through study period

Preziosi et al. 1970

100

5.75 h/d, 6d/wk for 11 wk

21

Dogs

Electrocardiograph changes; degenerativechanges in individual muscle fibers

Ehrich et al. 1944

100

5.75 h/d, 6d/ wk for 11 wk

~ 20

Dogs

Gait and posture anomalies were observed, and cerebral cortical damage found at autopsy

Lewey and Drabkin 1944

100

5.75 h/d, 6d/wk for 11 wk

~20

1 dog withligated posterior coronary artery

Severe cerebral damage and myocardial alternations

Lewey and Drabkin 1944

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Concentration (ppm)

Exposure Duration

COHb %

Species

Effects

Reference

50

24 h/d for 3 mon

NS

Dogs

No electrocardiographic or heart rate changes observed

Musselman et al. 1959

100

23 h/d for 14wk

~14

Dogs, normal and with myocardial infarction

Animals remained in good health, no obvious untoward signs could be attributed to exposure

DeBias et al. 1972

100

23 h/d for 24wk

~12

Monkeys, normal and with myocardial infarction

Electrocardiograms of infarcted and noninfarcted animals exposed to CO displayed increased P-wave amplitudes; a greater degree of myocardial ischemia, signified by higher incidence of T-wave inversion, observed in infarcted animals exposed to CO

DeBias et al. 1973

Up to 462

12 h/d for 14 mon

~20

Female monkeys, standard or cholesterol added diet

No myocardial infarctions observed; nodifferences in plasm a cholesterol or aortic or coronary atherosclerosis could be attributed to exposure

Malinow et al. 1976

Abbreviations: COHb, carboxyhemoglobin; d, day; h, hour; LC, concentration lethal to 50% of subjects; m50 in, minute; month, mon; NS, not stated; ppm, parts per million.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Repeated Exposures and Subchronic Toxicity

Several investigators examined the cardiovascular toxicity of sub-chronic and chronic CO exposures in nonrodent models. Pathologic changes in the heart and brain have been noted in animals subchronically exposed to CO concentrations capable of generating COHb concentrations in excess of 20%. Lindenberg et al. (1962) evaluated the effects of CO in eight dogs exposed to CO at 100 ppm. Four dogs were exposed continuously for 24 h per day, 7 days per week for 6 weeks, and another four dogs were exposed intermittently for 6 weeks. All dogs had abnormal electrocardiograms, and some of their hearts showed histologic evidence of muscle degeneration. In that study, Lindenberg et al. (1962) also exposed dogs to CO at a concentration of 50 ppm for 24 h per day, 7 days per week for 6 weeks. The exposures produced COHb concentrations of 2.6-5.5%. CO exposures caused no changes in hemoglobin levels or hematocrit; however, electrocardiographic changes similar to, but less severe than, those observed in the 100-ppm exposure group were noted in the third week of exposure.

Preziosi et al. (1970) reported that dogs exposed both intermittently (6 h per day, 5 days per week) and continuously at 50 and 100 ppm for 6 weeks had abnormal electrocardiograms in the second week of exposure and continuing through the exposure period. Heart and brain pathology were observed in some dogs in all exposure groups. Heart pathology included right and left heart dilation and myocardial thinning, which was accompanied by older scarring in some cases and fatty degeneration of heart muscle in others. Brain findings included mobilization of glial cells and thinning of the white matter in the central semi ovale. Four dogs exposed to CO at 100 ppm for 5.75 h per day, 6 days per week for 11 weeks showed electrocardiographic changes, degenerative changes in heart muscle fibers, and histopathologic damage to the brain (Lewey and Drabkin 1944). Ehrich et al. (1944) exposed four dogs to CO at 100 ppm on the same schedule for 11 weeks. Electrocardiographic changes occurred at variable times during the exposure. Although the gross pathologies of the hearts were normal, marked degenerative changes in individual fibers were observed. Dogs were exposed by Musselman et al. (1959) to CO at 50 ppm for 24 h per day, 7 days per week for 3 months. No changes in electrocardiograms or heart rates were observed.

DeBias et al. (1972) did not observe electrocardiographic or hematologic changes in normal and cardiac-infarcted dogs exposed to CO at 100 ppm (COHb at 14%) for 23 h per day for 14 weeks. DeBias et al. (1973) observed increased P-wave amplitudes in the myocardia of both normal and cardiac-infarcted cynomologus monkeys during exposures to CO at 100

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

ppm for 23 h per day for 24 weeks. T-wave inversions were more common in infarcted animals. Characteristic increases in hematocrit, hemoglobin, and red blood cell counts were observed in both normal and infarcted animals. Four monkeys with P-wave changes were selected for histopathology. Nuclear hyperplasia of the atria was observed in all four, suggesting atrial hypertrophy. No pathologic changes in brain, spleen, muscle, lungs, kidneys, or adrenal glands were found.

Chronic Toxicity

Malinow et al. (1976) found no myocardial infarctions or electro-cardiographic abnormalities in normal or cholesterol-fed cynomologus monkeys exposed to pulses of CO at up to 462 ppm for 30 min per hour, 12 h per day for 14 months.

Reproductive Toxicity in Males

No reports on the potential reproductive toxicity of CO in males were available.

Immunotoxicity

Snella and Rylander (1979) exposed one group of guinea pigs to CO at 5,000 ppm and three groups of guinea pigs to CO at 10,000 ppm for 3 min, 6 or 12 times per day for 3-4 weeks. The animals were injected with sheep red blood cells one week prior to cessation of exposure and sacrifice. All exposed groups showed increased polymorphonuclear leukocytes in pulmonary lavage fluid, and three of the four groups exhibited increased numbers of pulmonary alveolar macrophages. The numbers of plaque-forming cells among spleen and lung cells were reduced compared with controls, but the changes were not statistically significant. This study was included for completeness, but it is not relevant to setting the EEGL and CEGL values because of the high CO concentrations used and the unusual exposure regimen.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Genotoxicity

There are no reports on the genotoxic potential of CO.

Carcinogenicity

There are no reports on the carcinogenic potential of CO.

TOXICOKINETIC AND MECHANISTIC CONSIDERATIONS

The information in this section was obtained from reviews by WHO (1999), EPA (2000), and Raub et al. (2000). CO absorption occurs through the lungs at the respiratory bronchioles and alveolar ducts and sacs. The rate of uptake of CO is largely a function of the rate of COHb formation, and that relationship is linear at lower CO concentrations. CO is transferred from a gas phase to a liquid phase, across the air-blood barrier. CO diffuses across the alveolar-capillary membrane, through plasma, across the red blood cell membranes, and finally into the red blood cell stroma to bind to hemoglobin. Because of the rapid binding of CO with hemoglobin in the red blood cells, there is a high pressure differential between red blood cells and air, favoring rapid diffusion of CO into blood. CO uptake is substantially faster than CO elimination because of the low blood-to-air CO gradient and the tight binding of CO to hemoglobin. CO diffusion capacity increases with physical exercise, and there are significant diurnal variations that result from factors, such as variations in hemoglobin concentrations, blood flow, oxygen consumption, and ventilatory pattern (Forster 1987; Frey et al. 1987).

CO has about 245 times more affinity for hemoglobin than does oxygen. In humans, the vast majority of CO is in the vascular compartment, and about 10-15% of CO is in extravascular tissues. There are considerable amounts of CO bound to myoglobin in cardiac and skeletal muscles. During exercise, CO will diffuse from blood to skeletal muscle because the relative rate of CO binding increases more for myoglobin than for hemoglobin. Brain concentrations of CO are about 30-40 times lower than blood concentrations.

The factors that govern CO uptake also control CO elimination. The elimination half-lives of CO in blood show considerable interhuman and

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

concentration-related variabilities. At 2-20% COHb, the elimination half-life of CO is 3-5 h and is slightly higher at higher COHb concentrations. During sleep, the elimination half-life of CO is increased to about 8 h, and smokers eliminate CO much more slowly than do nonsmokers. Health status has a significant influence on CO elimination. Endogenous production of CO also affects the release of CO.

Formation of COHb reduces the oxygen-carrying capacity of blood and shifts the oxygen dissociation curve, reducing the release of oxygen to tissues. CO hypoxia and intracellular hypoxia caused by smoking and cardiovascular diseases are additive. Pathologic conditions, such as anemia, polycythemia, and coronary artery disease, are known to enhance the adverse hypoxic effects of CO significantly. CO does not accumulate in the body with chronic exposure; however, the anoxia associated with chronic exposure can cause central nervous system damage (Omaye 2002). CO also binds to myoglobin, cytochrome P-450, and other hemoproteins. CO binding to hemoproteins is favored at low intracellular pressure of oxygen, particularly in brain and myocardial tissues. Other potential biochemical mechanisms of action of CO include inhibition of hemoprotein function, free radical production (increase in nitric oxide production), and stimulation of guanylate cyclase. At the physiologic level, the mechanisms involve alterations in blood flow, mitochondrial dysfunction, altered production of high-energy intermediates, and vascular damage (arterial damage, leakage of albumin, and leukocyte sequestration) (WHO 1999; EPA 2000; Raub et al. 2000).

INHALATION EXPOSURE LEVELS FROM THE NRC AND OTHER ORGANIZATIONS

A number of organizations have established or proposed inhalation exposure limits or guidelines for CO. Selected values are summarized in Table 4-4.

SUBCOMMITTEE RECOMMENDATIONS

The subcommittee’s recommendations for EEGL and CEGL values for CO are summarized in Table 4-5. The current and proposed U.S. Navy values are provided for comparison.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

TABLE 4-4 Selected Inhalation Exposure Levels for Carbon Monoxide from NRC and Other Agenciesa

Organization

Type of Level

Exposure Level (ppm)

Reference

Occupational

 

 

 

ACGIH

TLV-TWA

25

ACGIH 2002

NIOSH

REL-Ceiling

200

NIOSH 2004

 

REL-TWA

35

 

OSHA

PEL-TWA

50

29 CFR 1910.1000

Spacecraft

 

 

 

NASA

SMAC

 

NRC 1994

 

1 h

55

 

 

24 h

20

 

 

30 days

10

 

 

180 days

10

 

Submarine

 

 

 

NRC

EEGL

 

NRC 1985

 

1 h

400

 

 

24 h

50

 

 

CEGL

 

NRC 1985

 

90 days

20

 

 

SEAL 1 (10 days)

125

NRC 2002

 

SEAL 2 (24 h)

150

NRC 2002

General Public

 

 

 

NAC

Proposed AEGL-1 (1 h)

NR

66 Fed. Reg. 21940 (2001)

 

Proposed AEGL-2 (1 h)

83

 

 

Proposed AEGL-1 (8 h)

NR

 

 

Proposed AEGL-2 (8 h)

27

 

aThe comparability of EEGLs and CEGLs with occupational and public health standards or guidance levels is discussed in Chapter 1, section “Comparison to Other Regulatory Standards or Guidance Levels.”

Abbreviations: ACGIH, American Conference of Governmental Industrial Hygienists; AEGL, acute exposure guideline level; CEGL, continuous exposure guidance level; EEGL, emergency exposure guidance level; h, hour; NAC, National Advisory Committee; NASA, National Aeronautics and Space Administration; NIOSH, National Institute for Occupational Safety and Health; NR, not recommended; NRC, National Research Council; OSHA, Occupational Safety and Health Administration; PEL, permissable exposure limit; REL, recommended exposure limit; SEAL, submarine escape action level; SMAC, spacecraft maximum allowable concentration; TLV, Threshold Limit Value; TWA, time-weighted average.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

TABLE 4-5 Emergency and Continuous Exposure Guidance Levels for Carbon Monoxide

Exposure Level

U.S. Navy Values (ppm)

NRC Recommended Values (ppm)

Current

Proposed

EEGL

 

 

 

 

 

1 h

400

55

180

 

24 h

50

20

45

CEGL

 

 

 

 

 

90 days

20

10

9

Abbreviations: CEGL, continuous exposure guidance level; EEGL, emergency exposure guidance level; h, hour; NRC, National Research Council; ppm, parts per million.

1-Hour EEGL

In deriving the 1-h EEGL, the subcommittee focused on neuro-behavioral impairments to hand coordination, driving and tracking tasks, and cognitive functions and physical performance deficits resulting from acute CO exposures. Scientific reviews and a statistical meta-analysis of the neurobehavioral effects of CO exposure concluded that even moderate impairments (>10% decrements in performance) are not expected at COHb concentrations below 20% (Benignus 1994; WHO 1999; EPA 2000). Also, Kizakevich et al. (2000) showed that healthy young men can perform submaximal upper and lower body exercise without overt cardiovascular impairment after 1-2 h of CO exposure and at COHb concentrations of up to 20%. Therefore, the subcommittee set the 1-h EEGL with the goal of keeping COHb concentrations below the 20% COHb threshold.

Recognizing possible differences between COHb concentrations in smokers and nonsmokers, the subcommittee started with a CO concentration of 200 ppm, which would result in COHb concentrations of about 5% on the basis of Figure 4-1. Adjusting for the low-oxygen atmosphere (see Box 4-1), the subcommittee calculated a 1-h EEGL of 180 ppm. That guidance level should be protective against severe headaches according to the research of Stewart et al. (1970) and be tolerated by both smokers and nonsmokers without critical neurobehavioral performance impairments. However, the subcommittee notes that heavy smokers with a baseline COHb of 15% could attain a COHb of 20% in 1 h (Raub et al. 2000). No additional uncertainty factors were applied, because the value is based on a large body of human research, and the subcommittee considers a 1-h

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

exposure at 180 ppm to be a no-observed-adverse-effect level (NOAEL).

The subcommittee acknowledges that the experimental human literature on the acute effects of CO exposures includes a number of studies that report subtle deficits in visual detection thresholds and impaired performance on vigilance, time-estimation, and driving performance tasks at low COHb concentrations (MacFarland et al. 1944; Beard and Wertheim 1967; MacFarland 1973; Wright et al. 1973; Beard and Grandstaff 1975; Putz et al. 1979). However, Beard and Grandstaff (1975) and other authors also reported that higher cognitive functions typically were unaffected (Schulte 1963; Bender et al. 1971). Attempts to replicate the findings of MacFarland et al. (1944) and Beard and Wertheim (1967) were unsuccessful (Mikulka et al. 1970; Stewart et al. 1970, 1973, 1975; O’Donnell et al. 1971). Furthermore, the magnitudes of the changes reported in those neurobehavioral studies were considered to be mild to moderate. For example, the subcommittee concluded that decrements in crew members’ ability to detect subtle changes in the brightness of lights would not impair the crew’s performance of essential tasks. In addition, the test conditions used to evaluate vigilance did not reflect emergency conditions aboard submarines. Other performance-related findings, such as the deficits in driving skills demonstrated by MacFarland (1973) and Wright et al. (1973), were not of sufficient magnitude to be of concern in deriving the 1-h EEGL.

24-Hour EEGL

The effects of concern for setting the 24-h EEGL were cardiovascular effects and impaired neurobehavioral performance. The subcommittee identified a NOAEL of 50 ppm on the basis of a lack of neurobehavioral findings in the 24-h exposure study by Stewart et al. (1970) and a minimal lowest-observed-adverse-effect level (LOAEL) of 50 ppm on the basis of the electrocardiographic (P-wave) changes observed after 2 days of exposure in the Davies and Smith (1980) study. By applying an adjustment factor for the low-oxygen environment, the subcommittee calculated a 24-h EEGL of 45 ppm. The subcommittee does not expect that a 24-h exposure at 45 ppm would result in lasting cardiovascular effects, and therefore, no LOAEL-to-NOAEL uncertainty factor was applied. No uncertainty factors were applied because the key studies employed healthy male subjects.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

90-Day CEGL

The cardiovascular effects of CO exposures are of primary concern in setting the 90-day CEGL. There are no experimental human studies of appropriate duration. The one long-term observational study (Wilson and Schaefer 1979) did not evaluate cardiovascular effects, and environmental conditions on board submarines have changed since that study was conducted. Therefore, the subcommittee selected the DeBias et al. (1973) study of normal and cardiac-infarcted cynomolgus monkeys exposed to CO at 100 ppm for 23 h per day for 24 weeks as the starting point for the derivation of the CEGL. The infarcted monkeys exposed to CO exhibited a higher incidence of electrocardiographic T-wave inversions, and both the normal and infarcted monkeys exposed to CO at 100 ppm developed increased P-wave amplitudes, making the 100-ppm concentration a minimal LOAEL. By adjusting the LOAEL for the low-oxygen atmosphere, the subcommittee arrived at a value of 90 ppm.

An intraspecies uncertainty factor of 3 was applied on the basis of the work by Davies and Smith (1980) in which 3 of 15 healthy subjects exhibited electrocardiographic P-wave changes after 2 days of exposure to CO at 15 ppm. A LOAEL-to-NOAEL uncertainty factor of 3 brought the total uncertainty factor to 10. The subcommittee therefore recommends a 90-day CEGL of 9 ppm.

DATA ADEQUACY AND RESEARCH NEEDS

Although the literature on the effects of CO exposures in humans and animals is extensive, a number of data gaps remain. The conflicting results of studies on the neurobehavioral and cardiovascular effects of low-level CO exposures are of concern for submariners. There is little experimental or epidemiologic information available on the potential for increased health risks in smokers exposed to CO. Subchronic and chronic low-level exposure studies and long-term follow-up studies in submariners, including those who smoke, are needed to reduce uncertainty in the derivation of the 90-day CEGL.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

BOX 4-1

Adjustment for the Low-Oxygen Atmosphere

The subcommittee used the Haldane equation to determine the adjustment for low-oxygen atmospheres applied to the EEGLs and the CEGL for CO. The Haldane equation relates the partial pressure of carbon monoxide (PCO) in air, the partial pressure of oxygen in air (PO2), and the concentrations of COHb and oxyhemoglobin (O2Hb) in blood (Douglas et al. 1912). The Haldane constant, M, is equal to about 200 (Douglas et al. 1912).


Haldane Equation:

COHb is inversely related to PO2. In a lower-oxygen atmosphere, less CO would be required to reach a certain COHb level.


The average PO2 in the submarine atmosphere is 148-149 millimeters of mercury (mmHg) (Hagar 2003), or about 90% that of the outside atmosphere at sea level. Under those conditions, it would take about 10% less CO to reach a certain COHb concentration over a defined exposure period. Therefore, the subcommittee applied a factor of 0.9 to the starting CO concentrations identified in the experimental literature when deriving the EEGL and CEGL values. Adjustments to the EEGL and CEGL values may be required when oxygen concentrations are outside the range cited above.

REFERENCES

ACGIH (American Conference of Governmental Industrial Hygienists). 1996. Carbon monoxide. In Documentation of the Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs), Supplements to the Sixth Edition. American Conference of Governmental Industrial Hygienists, Cincinnati, OH.

ACGIH (American Conference of Governmental Industrial Hygienists). 2002. Carbon Monoxide. Pp. 20 in Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs) for 2002. American Conference of Governmental Industrial Hygienists, Cincinnati, OH.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Aronow, W.S., E.A. Stemmer, and S. Zweig. 1979. Carbon monoxide and ventricular fibrillation threshold in normal dogs. Arch. Environ. Health 34(3):184-186.

Beard, R.R., and N.W. Grandstaff. 1975. Carbon monoxide and human functions. Pp. 1-27 in Behavioral Toxicology, B. Weiss and V.G. Laties, eds. New York: Plenum Press.

Beard, R.R., and G.A. Wertheim. 1967. Behavioral impairment associated with small doses of carbon monoxide. Am. J. Public Health 57(11):2012-2022.

Bender, W., M. Gothert, G. Malorny, and P. Sebbesse. 1971. Effects of low carbon monoxide concentration in man [in German]. Arch. Toxicol. 27(2):142-158 (as cited in NRC 1985).

Benignus, V.A. 1994. Behavioral effects of carbon monoxide: Meta analysis and extrapolations. J. Appl. Physiol. 76(3):1310-1316.

Budavari, S., M.J. O’Neil, A. Smith, and P.E. Heckelman, eds. 1989. Carbon monoxide. Pp. 275 in The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biological, 11th Ed. Rahway, NJ: Merck and Co.

Burnett, R.T., S. Cakmak, J.R. Brook, and D. Krewski. 1997. The role of particle size and chemistry in the association between summertime ambient air pollution and hospitalization for cardiorespiratory diseases. Environ. Health Perspect. 105(6):614-620.

Chevalier, R.B., R.A. Krumholz, and J.C. Ross. 1966. Reaction of nonsmokers to carbon monoxide inhalation: Cardiopulmonary responses at rest and during exercise. J. Am. Med. Assoc. 198(10):1061-1064 (as cited in NRC 1985).

Chiodi, H., D.B. Dill, F. Consolazio, and S.M. Horvath. 1941. Respiratory and circulatory responses to acute carbon monoxide poisoning. Am. J. Physiol. 134:683-693.

Christensen, C.L., J.A. Gliner, S.M. Horvath, and J.A. Wagner. 1977. Effects of three kinds of hypoxias on vigilance performance. Aviat. Space Environ. Med. 48(6):491-496.

Cobb, N., and R.A. Etzel. 1991. Unintentional carbon monoxide-related deaths in the United States, 1979 through 1988. J. Am. Med. Assoc. 266(5):659-663.

Crawl, J.R. 2003. Review/Updating of Limits for Submarine Air Contaminants. Presentation at the First Meeting on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, January 23, 2003, Washington, DC.

Davies, D.M., and D.J. Smith. 1980. Electrocardiographic changes in healthy men during continuous low-level carbon monoxide exposure. Environ. Res. 21(1):197-206.

Davies, D.M., E.J. Jolly, R.J. Pethybridge, and W.P. Colquhoun. 1981. The effects of continuous exposure to carbon monoxide on auditory vigilance in man. Int. Arch. Occup. Environ. Health 48(1):25-34.

DeBias, D.A., N.C. Birkhead, C.M. Banerjee, L.A. Kazal, R.R. Holburn, C.H Greene, W.V. Harrer, L.M. Rosenfeld, H. Menduke, N. Williams, and M.H. Friedman. 1972. The effects of chronic exposure to carbon monoxide on the

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

cardiovascular and hematologic systems in dogs with experimental myocardial infarction. Int. Arch. Arbeitsmed. 29(3):253-267.

DeBias, D.A., C.M. Banerjee, N.C. Birkhead, W.V. Harrer, and L. Kazal. 1973. Carbon monoxide inhalation effects following myocardial infarction in monkeys. Arch. Environ. Health 27(3):161-167.

DeBias, D.A., C.M. Banerjee, N.C. Birkhead, C.H Greene, D. Scott, and W.V. Harrer. 1976. Effects of carbon monoxide inhalation on ventricular fibrillation. Arch. Environ. Health 31(1):38-42.

Doherty, S. 2000. History, pathophysiology, clinical presentation and role of hyperbaric oxygen in acute carbon monoxide poisoning. Emerg. Med. 12(1):5 5-61.

Douglas, C.G., J.S. Haldane, and J.B.S. Haldane. 1912. The laws of combination of haemoglobin with carbon monoxide and oxygen. J. Physiol. 44:275-304 (as cited in WHO 1999).

Ehrich, W.E., S. Bellet, and F.H. Lewey. 1944. Cardiac changes from carbon monoxide poisoning. Am. J. Med. Sci. 208:511-523.

E.I. du Pont de Nemours and Co. 1981. Inhalation toxicity of Common Combustion Gases. Haskell Laboratory Report No. 238-81. Haskell Laboratory, Newark, DE (as cited in NAC 2004).

Ekblom, B., and R. Huot. 1972. Response to submaximal and maximal exercise at different levels of carboxyhemoglobin. Acta. Physiol. Scand. 86(4):474-482.

Ely, E.W., B. Moorehead, and E.F. Haponik. 1995. Warehouse workers’ headache: Emergency evaluation and management of 30 patients with carbon monoxide poisoning. Am. J. Med. 98(2):145-155.

EPA (U.S. Environmental Protection Agency). 1979. Air Quality Criteria for Carbon Monoxide. EPA- 600/8-79-022. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC (as cited in WHO 1999).

EPA (U.S. Environmental Protection Agency). 1984. Revised Evaluation of Health Effects Associated with Carbon Monoxide Exposure: An Addendum to the 1979 EPA Air Quality Criteria Document for Carbon Monoxide. EPA-600/8-83-003F. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC (as cited in EPA 2000).

EPA (U.S. Environmental Protection Agency). 1991. Air Quality Criteria for Carbon Monoxide. EPA-600/8-90/045F. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC (as cited in EPA 2000).

EPA (U.S. Environmental Protection Agency). 2000. Air Quality Criteria for Carbon Monoxide. EPA-600/P-99/001F. National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Frey, T.M., R.O. Crapo, R.L. Jensen, and C.G. Elliot. 1987. Diurnal variation of the diffusing capacity of the lung: Is it real? Am. Rev. Respir. Dis. 136(6):1381-1384 (as cited in EPA 2000).

Forster, R.E. 1987. Diffusion of gases across the alveolar membrane. Pp. 71-88 in Handbook of Physiology: A Critical, Comprehensive Presentation of Physiological Knowledge and Concepts. Section 3: The Respiratory System. Vol. IV. Gas Exchange, A.P. Fishman, L.E. Farhi, S.M. Tenney, and S.R. Geiger, eds. Bethesda, MD: American Physiological Society (as cited in EPA 2000).

Hagar, R. 2003. Submarine Atmosphere Control and Monitoring Brief for the COT Committee. Presentation at the First Meeting on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, January 23, 2003, Washington, DC.

Hassan, M.S., J. Ray, and F. Wilson. 2003. Carbon monoxide poisoning and sensorineural hearing loss. J. Laryngol. Otol. 117(2):134-137.

Hilado, C.J., H.J. Cumming, A.M. Machado, C.J. Casey, and A. Furst. 1978. Effect of individual gaseous toxicants on mice. Proc. West. Pharmacol. Soc. 21:159-160 (as cited in NAC 2004).

Horvath, S.M. 1981. Impact of air quality in exercise performance. Exerc. Sport Sci. Rev. 9:265-296 (as cited in WHO 1999).

Hudnell, H.K., and V.A. Benignus. 1989. Carbon monoxide exposure and human visual detection thresholds. Neurotoxicol. Teratol. 11(4):363-371.

HSDB (Hazardous Substances Data Bank). 2004. Carbon Monoxide. TOXNET, Specialized Information Services, U.S. Library of Medicine, Bethesda, MD. [Online]. Available: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB [accessed April 6, 2004].

IPCS (International Programme on Chemical Safety). 2001. Carbon Monoxide. International Chemical Safety Cards ICSC: 0023. Chemical Safety Information from Intergovernmental Organizations, World Health Organization, United Nations Environment Programme, and International Labour Organization. [Online]. Available: http://www.inchem.org/documents/icsc/icsc/eics0023.htm [accessed April 6, 2004].

Kizakevich, P.N., M.L. McCartney, M.J. Hazucha, L.H. Sleet, W.J. Jochem, A C. Hackney, and K. Bolick. 2000. Noninvasive ambulatory assessment of cardiac function in health men exposed to carbon monoxide during upper and lower body exercise. Eur. J. Appl. Physiol. 83(1):7-16.

Lewey, F.H., and D.L. Drabkin. 1944. Experimental chronic carbon monoxide poisoning in dogs. Am. J. Med. Sci. 208:502-511.

Lindenberg, R., D. Levy, T. Preziosi, and M. Christensen. 1962. An Experimental Investigation in Animals of the Functional and Morphological Changes from Single and Repeated Exposures to Carbon Monoxide. Paper presented at the American Industrial Hygiene Association Meeting, Washington, DC (as cited in NIOSH 1972).

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Luria, S.M., and C.L. McKay. 1979. Effects of low levels of carbon monoxide on visions of smokers and nonsmokers. Arch. Environ. Health 34(1):38-44.

Malinow, M.R., P. McLaughlin, D.S. Dhindsa, J. Metcalfe, A.J. Ochsner III, J. Hill, and P. McNulty. 1976. Failure of carbon monoxide to induce myocardial infarction in cholesterol-fed cynomolgus monkeys (Macaca fascicularis). Cardiovasc. Res. 10(1):101-108.

MacFarland, R.A., F.J.W. Roughton, M.H. Halperin, and J.I. Niven. 1944. The effects of carbon monoxide and altitude on visual thresholds. J. Aviat. Med. 15:381-394 (as cited in NRC 1985).

MacFarland, R. 1973. Low-level exposure to carbon monoxide and driving performance. Arch. Environ. Health 27:355-359 (as cited in NRC 1985).

Mihevic, P.M., J.A. Gliner, and S.M. Horvath. 1983. Carbon monoxide exposure and information processing during perceptual-motor performance. Int. Arch. Occup. Environ. Health 51(4):355-363.

Mikulka, P., R. O’Donnell, P. Heinig, and J. Theodore. 1970. The effect of carbon monoxide on human performance. Ann. N.Y. Acad. Sci. 174(1):409-420.

Morris, R.D., E.N. Naumova, and R.L. Munasinghe. 1995. Ambient air pollution and hospitalization for congestive heart failure among elderly people in seven large US cities. Am. J. Public Health 85(10):1361-1365.

Musselman, N.P., W.A. Groff, P.P. Yevich, F.T. Wilinski, M.H. Weeks, and F.W. Oberst. 1959. Continuous exposure of laboratory animals to low concentration of carbon monoxide. Aerosp. Med. 30:524-529 (as cited in NRC 1994).

NAC (National Advisory Committee). 2004. Interim Acute Exposure Guideline Levels (AEGLs) for Carbon Monoxide, Draft 1: 01/2004. National Advisory Committee/AEGL, U.S. Environmental Protection Agency, Washington, DC.

NCHS (National Center for Health Statistics). 2002. Section 1. General Mortality. Pp. 1., Table 1-1 in Vital Statistics of the United States, 1993, Vol. 2. Mortality, Part A. National Center for Health Statistics, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Hyattsville, MD. [Online]. Available: http://www.cdc.gov/nchs/data/vsus/mort93_2a.pdf [accessed April 5, 2004].

NIOSH (National Institute for Occupational Safety and Health). 1972. Occupational Exposure to Carbon Monoxide, Criteria for a Recommended Standard. DHEW (NIOSH) 73-11000. National Institute for Occupational Safety and Health, Health Services and Mental Health Administration, U.S. Department of Health, Education, and Welfare, Cincinnati, OH.

NIOSH (National Institute for Occupational Safety and Health). 2004. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) 2004-103. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Cincinnati, OH.

NRC (National Research Council). 1985. Carbon monoxide. Pp. 17-38 in Emergency and Continuous Exposure Guidance Levels for Selected Airborne Contaminants, Vol. 4. Washington, DC: National Academy Press.

NRC (National Research Council). 1994. Carbon monoxide. Pp. 61-90 in Space-

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

craft Maximum Allowable Concentrations for Selected Airborne Contaminants, Vol. 1. Washington, DC: National Academy Press.

NRC (National Research Council). 2002. Carbon monoxide. Pp. 69-96 in Review of Submarine Escape Action Levels for Selected Chemicals. Washington, DC: National Academy Press.

O’Donnell, R.D., R. Mikulka, P. Heinig, and J. Theodore. 1971. Low level carbon monoxide exposure and human psychomotor performance. Toxicol. Appl. Pharmacol. 18(3):593-602.

Omaye, S.T. 2002. Metabolic modulation of carbon monoxide toxicity. Toxicology 180(2):139-150.

Peterson, J.E., and R.D. Stewart. 1975. Predicting the carboxyhemoglobin levels resulting from carbon monoxide exposures. J. Appl. Physiol. 39(4):633-638.

Pierantozzi, R. 1995. Carbon Monoxide. Pp. 97-122 in Kirk-Othmer Encyclopedia of Chemical Technology, 4th Ed., Vol. 5. Carbon and Graphite Fibers to C1-Chlorocarbons, 4th Ed., J.I. Kroschwitz, and M. Howe-Grant, eds. New York: John Wiley and Sons.

Pirnay, F., J. Dujardin, R. Deroanne, and J.M. Petit. 1971. Muscular exercise during intoxication by carbon monoxide. J. Appl. Physiol. 31:573-575 (as cited in NRC 1985).

Poloniecki, J.D., R.W. Atkinson, A.P. de Leon, and H.R. Anderson. 1997. Daily time series for cardiovascular hospital admission and previous day's air pollution in London, UK. Occup. Environ. Med. 54(8):535-540.

Preziosi, T.J, R. Lindenberg, D. Levy, and M. Christenson. 1970. An experimental investigation in animals of the functional and morphologic effects of single and repeated exposures to high and low concentrations of carbon monoxide. Ann. N.Y. Acad. Sci. 174(1):369-384.

Purser, D.A., and K.R. Berrill. 1983. Effects of carbon monoxide on behavior in monkeys in relation to human fire hazard. Arch. Environ. Health 38(5):308-315 (as cited in NAC 2004).

Putz, V.R. 1979. The effects of carbon monoxide on dual-task performance. Hum. Factors 21(1):13-24.

Putz, V.R., B.L. Johnson, and J.V. Setzer. 1979. A comparative study of the effects of carbon monoxide and methylene chloride on human performance. J. Environ. Pathol. Toxicol. 2(5):97-112.

Radford, E., T. Drizd, and R. Murphy. 1981. Blood Carbon Monoxide Levels in Persons 3-74 Years of Age in the United States, 1976-1980. Advance Data Report No. 76. National Center for Health Statistics, Hyattsville, MD (as cited in NRC 1985).

Ramsey, J.M. 1972. Carbon monoxide, tissue hypoxia, and sensory and psychomotor response in hypoxaemic subjects. Clin. Sci. 42(5):619-625.

Ramsey, J.M. 1973. Effects of single exposures of carbon monoxide on sensory and psychomotor performance. Am. Ind. Hyg. Assoc. J. 34(5):212-216.

Raub, J.A., M. Mathieu-Nolf, N.B. Hampson, and S.R. Thom. 2000. Carbon monoxide poisoning—a public health perspective. Toxicology 145(1):1-14.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Ray, A.M., and T.H. Rockwell. 1970. An exploratory study of automobile driving performance under the influence of low levels of carboxyhemoglobin. Ann. N.Y. Acad. Sci. 174(1):396-408.

Rose, C.S., R.A. Jones, L.J. Jenkins, and J. Siegel. 1970. The acute hyperbaric toxicity of carbon monoxide. Toxicol. Appl. Pharmacol. 17(3):752-760 (as cited in NAC 2004).

Roughton, F.J.W. 1970. The equilibrium of carbon monoxide with human hemoglobin in whole blood. Ann. N.Y. Acad. Sci. 174(1):177-188 (as cited in WHO 1999).

Schulte, J.H. 1963. Effects of mild carbon monoxide intoxication. Arch. Environ. Health 38:524-530.

Seufert, K.T., and W.R. Kiser. 1996. End-expiratory carbon monoxide levels as an estimate of passive smoking exposure aboard a nuclear-powered submarine. South. Med. J. 89(12):1181-1183. [Online]. Available: http://www. sma.org/mj/96dec9.htm [accessed February 9, 2004].

Shephard, R.J. 1983. Carbon monoxide: The silent killer. American Lecture Series No. 1059. Springfield, IL: C.C. Thomas (as cited in EPA 2000).

Shephard, R.J. 1984. Athletic performance and urban air pollution. Can. Med. Assoc. J. 131(2):105-109 (as cited in EPA 2000).

Sievers, R.F., T.I. Edwards, and A.L. Murray. 1942. A Medical Study of Men Exposed to Measured Amounts of Carbon Monoxide in the Holland Tunnel for 13 Years. Public Health Bulletin No. 278. Washington, DC: U.S. Government Printing Office (as cited in ACGIH 1996).

Smith, C.J., and T.J. Steichen. 1993. The atherogenic potential of carbon monoxide. Atherosclerosis 99(2):137-149.

Snella, M.C., and R. Rylander. 1979. Alteration in local and systemic immune capacity after exposure to burst of CO. Environ. Res. 20(1):74-79.

Sokal, J.A., and E. Kralkowska. 1985. The relationship between exposure duration, carboxyhemoglobin, blood glucose, pyruvate and lactate and the severity of intoxication in 39 cases of acute carbon monoxide poisoning in man. Arch. Toxicol. 57(3):196-199.

Stern, F.B., W.E. Halperin, R.W. Hornung, V.L. Ringenburg, and C.S. McCammon. 1988. Heart disease mortality among bridge and tunnel officers exposed to carbon monoxide. Am. J. Epidemiol. 128(6):1276-1288.

Stewart, R.D., J.E. Peterson, E.D. Baretta, R.T. Bachand, M.J. Hosko, and A.A. Herrmann. 1970. Experimental human exposure to carbon monoxide. Arch. Environ. Health 21(2):154-164.

Stewart, R.D., P.E. Newton, M.J. Hosko, and J.E. Peterson. 1973. Effect of carbon monoxide on time perception. Arch. Environ. Health. 27(3):155-160.

Stewart, R.D., P.E. Newton, M.J. Hosko, J.E. Peterson, and J.W. Mellender. 1975. The effect of carbon monoxide on time perception, manual coordination, inspection, and arithmetic. Pp. 29-60 in Behavioral Toxicology, B. Weiss and V.G. Laties, eds. New York: Plenum Press.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×

Varon, J., P.E. Marik, R.E. Fromm, Jr., and A. Gueler. 1999. Carbon monoxide poisoning: A review for clinicians. J. Emerg. Med. 17(1):87-93.

Vogel, J.A., and M.A. Gleser. 1972. Effect of carbon monoxide on oxygen transport during exercise. J. Appl. Physiol. 32(2):234-239.

Vogel, J.A., M.A. Gleser, R.C. Wheeler, and B.K. Whitten. 1972. Carbon monoxide and physical work capacity. Arch. Environ. Health 24(3):198-203 (as cited in NRC 1985).

WHO (World Health Organization). 1999. Carbon Monoxide, 2nd Ed. Environmental Health Criteria 213. Geneva: World Health Organization. [Online]. Available: http://www.inchem.org/documents/ehc/ehc/ehc213.htm [accessed January 8, 2004].

Wilson, A.J., and K.E. Schaefer. 1979. Effect of prolonged exposure to elevated carbon monoxide and carbon dioxide levels on red blood cell parameters during submarine patrols. Undersea Biomed. Res. 6(Suppl.): S49-S56.

Wright, G., P. Randell, and R.J. Shepard. 1973. Carbon monoxide and driving skills. Arch. Environ. Health 27(6):349-354.

Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 67
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 68
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 69
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 70
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 71
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 72
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 73
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 74
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 75
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 76
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 77
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 78
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 79
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 80
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 81
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 82
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 83
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 84
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 85
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 86
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 87
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 88
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 89
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 90
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 91
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 92
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 93
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 94
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 95
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 96
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 97
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 98
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 99
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 100
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 101
Suggested Citation:"4 Carbon Monoxide." National Research Council. 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/11170.
×
Page 102
Next: 5 Formaldehyde »
Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1 Get This Book
×
Buy Paperback | $87.00 Buy Ebook | $69.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

U.S. Navy personnel who work on submarines are in an enclosed and isolated environment for days or weeks at a time when at sea. Unlike a typical work environment, they are potentially exposed to air contaminants 24 hours a day. To protect workers from potential adverse health effects due to those conditions, the U.S. Navy has established exposure guidance levels for a number of contaminants. The Navy asked a subcommittee of the National Research Council (NRC) to review, and develop when necessary, exposure guidance levels for 10 contaminants.

Overall, the subcommittee found the values proposed by the Navy to be suitable for protecting human health. For a few chemicals, the committee proposed levels that were lower than those proposed by the Navy. In conducting its evaluation, the subcommittee found that there is little exposure data available on the submarine environment and echoed a previous recommendation from an earlier NRC report to conduct monitoring that would provide a complete analysis of submarine air and data on exposure of personnel to contaminants.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!