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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



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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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;

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants         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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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).

OCR for page 67
Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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-

OCR for page 67
Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.

OCR for page 67
Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.

OCR for page 67
Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants 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.