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--> B3 Carbon Dioxide King Lit Wong, Ph.D. Johnson Space Center Toxicology Group Biomedical Operations and Research Branch Houston, Texas Physical and Chemical Properties Carbon dioxide is an odorless and colorless gas (Sax, 1984). Synonym: Carbonic anhydride Formula: CO2 CAS number: 124389 Molecular weight: 44 Boiling point: Not applicable Melting point: Sublime at-78°C Vapor pressure: Not applicable Conversion factors at 25°C, 1 atm: 1 ppm = 1.80 mg/m3 1 mg/m3 = 0.56 ppm Occurrence and Use CO2 normally exists in the atmosphere at 0.03% (Morey and Shattuck, 1989). In a Danish study, the maximal CO2 concentrations inside 14 town-hall buildings (6 had natural and 8 had mechanical ventilation) were measured to be 0.05-0.13% (Skov et al., 1987). Wang (1975) reported that the CO2 concentration inside a university auditorium built up to about 0.06-0.09% during a lecture. CO2 is not used in space shuttles, but it will be used as a fire extinguishant in the space station.
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--> Metabolism is a source of CO2 in spacecraft, and thermodegradation of organic materials is a potential source of CO2 (Coleman et al., 1968; Terrill et al., 1978; Wooley et al., 1979). Humans produce CO2 via oxidative metabolism of carbohydrates, fatty acids, and amino acids; the production rate is dependent on the caloric expenditure of the individual (Baggott, 1982; Diamondstone, 1982; LeBaron, 1982; Olson, 1982). A young adult male produces about 22,000 me of CO2 per day (Baggott, 1982). For a 70-kg adult doing light work in spaceflight, the amount of CO2 exhaled was estimated to be 500 L/d (Clamann, 1959). The amount of CO2 exhaled by a group of normal male subjects, aged 18-45, inside a steel chamber was measured at 469 L/d per person (Consolazio et al., 1947). During a 7-d shuttle mission with seven crew members, the mean CO2 concentration in the cabin was about 2 mm Hg, which was equivalent to 0.26% in an atmosphere of 760 mm Hg, with a 5-h peak of 9 mm Hg or 1.2% (NASA, 1984). Pharmacokinetics and Metabolism When inhaled, CO2 freely penetrates cellular membranes (Baggott, 1982). The diffusion rate of CO2 through the alveolar membrane into blood is about 20 times that of O2 (West, 1979). CO2 is carried in blood in three forms, the bicarbonate being the major form. Ninety percent of the CO2 in blood reacts with water, under the catalysis of carbonic anhydrous inside the erythrocytes, to form carbonic acid, which in turn is ionized to bicarbonate (Baggott, 1982). This reaction also takes place in serum in the absence of carbonic anhydrous, but it proceeds much more slowly than with catalysis (Baggott, 1982). The other two forms of CO2 transport in blood are relatively minor. About 5% of the CO2 in blood is dissolved in serum and cytoplasm (Baggott, 1982). The solubility of CO2 in water is approximately 20 times that of O2, so that CO2 dissolved in plasma is a more important form of transport in blood than dissolved O2 (West, 1979). CO2 is present in blood in the third form as carbamino compounds, which are formed from the reaction of CO2 with uncharged amino groups in hemoglobin (Baggott, 1982). The carbamino form accounts for about 5 % of the CO2 in blood (Baggott, 1982).
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--> Normally, CO2 is eliminated from the body via exhalation. A healthy man exhales CO2 at about 220 mL/min at rest and 1,650 mL/min during moderate exercise (Cotes, 1979, pp. 266, 276, 384). The CO2-bicarbonate system functions as the major buffering system in blood (Baggott, 1982). In acidosis, an individual is exposed to a high concentration of CO2. Hyperventilation increases the CO2 exhalation, which raises the pH in blood (Baggott, 1982). In alkalosis, the individual will hypoventilate to reduce CO2 exhalation and the kidney will excrete bicarbonate ions into the urine, both of which lower the pH in blood (Baggott, 1982). Toxicity Summary Acute and Short-Term Toxicity Miscellaneous Signs and Symptoms Both hearing and vision can be impaired by CO2. A 6-min exposure to 6.1-6.3% CO2 resulted in a 3-8% decrease in hearing threshold in six human subjects (Gellhorn and Spiesman, 1935). For CO2 exposures of six human subjects lasting 5-22 min, 3-4% CO2 was the threshold for causing slight hearing impairment and 2.5% was the no-observed-adverse-effect level (NOAEL) (Gellhorn and Spiesman, 1934, 1935). Because the amount of hearing impairment produced by about 6% CO2 is very small and because the SMACs are expected to be much lower than 6%, hearing impairment is not considered in setting the SMACs for CO2. Acute exposures to 6% CO2 affected vision by reducing visual intensity discrimination in 1-2 min (Gellhorn, 1936) and by causing visual disturbances in several hours in an unspecified number of men (Schulte, 1964). CO2 exposures can cause other symptoms, such as tremor, discomfort, dyspnea, headache, and intercostal pain. Tremor was produced in human subjects exposed to 6% CO2 for several hours (number of subjects unknown) (Schulte, 1964) or 7-14% CO2 for 10-20 min (12 subjects) (Sechzer et al., 1960). Exposures of six volunteers to 6% CO2 for 20.5-22 min led to discomfort (Gellhorn and Spiesman, 1935).
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--> Dyspnea Available data indicate that acute exposures to CO2 at concentrations higher than 3% definitely could produce dyspnea. For instance, White et al. (1952) found that, in a 16-min exposure to 6% CO2 in O2, 19 of 24 volunteers had slight or moderate dyspnea, and the dyspneic sensation was severe in the remaining five subjects. A 17-32 min exposure of 16 human subjects to 4-5 % CO2 (Schneider and Truesdale, 1922) or a 2.5-10 min exposure to 7.6% CO2 (Dripps and Comroe, 1947) resulted in dyspnea. There were conflicting data on whether 2.8-3% CO2 would cause dyspnea. On one hand, Menn et al. (1970) found that, in a 30-min exposure to 2.8% CO2, dyspnea was detected in three of eight human subjects during maximal exercise, but not during half-maximal or two-thirds-maximal exercises. On the other hand, Sinclair et al. (1971) showed that a 1-h or 15- to 20-d exposure of four volunteers to 2.8% CO2 failed to produce any dyspnea during steady strenuous exercise. However, Schulte (1964) reported that an exposure to CO2 at concentrations as low as 2% for several hours resulted in dyspnea on exertion in an unknown number of human subjects. In the study conducted by Menn et al., 1.1% CO2 failed to cause dyspnea in eight subjects even during maximal exercise in 30 min. There were also conflicting data on CO2's dyspneic effect in resting subjects. Brown (1930a) showed that 3.2% CO2 or 2.5-2.8% CO2 did not produce dyspnea in five resting human subjects. In contrast, Schulte (1964) reported that an exposure to 3% CO2 for several hours resulted in dyspnea even at rest, without specifying the number of human subjects on which he based his conclusion. The bulk of the data indicate that the NOAEL for CO2 exposures based on dyspnea appears to be 2.8% because astronauts will engage in moderate, but not maximal, exercise. Headaches In addition to dyspnea, acute CO2 exposures could produce headaches. Without specifying the size of population he based his conclusion on, Schulte (1964) reported that human subjects exposed to 2% or 3% CO2 for several hours developed headaches on mild exertion; the
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--> headache was more severe at 3% CO2 than 2%. Sinclair et al. (1971) showed that a 1-h exposure of four human subjects to 2.8% CO2 resulted in occasional mild headaches during strenuous steady-state exercise. Menn et al. (1970) found that mild-to-moderate frontal headaches developed in six of eight human subjects exposed to 3.9% CO2 for 30 min while doing two-thirds-maximal exercise. A similar exposure to 1.1% or 2.8% CO2 failed to cause headaches (Menn et al., 1970). Therefore, there is conflicting evidence whether 2.8% CO2 produces headaches during exertion. In a comparison of the data on exercising subjects (Schulte, 1964; Menn et al., 1970; Sinclair et al., 1971) and on subjects at rest (Schneider and Truesdale, 1922; Brackett et al., 1965), CO2 appears to cause more headaches at a lower concentration during exercise than at rest. White et al. (1952) showed that, soon after a 16-min exposure of 24 subjects to 6% CO2, one developed a severe headache and nine developed mild headaches of very short durations. In a study of five or six resting human subjects conducted by Brown (1930a), an exposure to 3.2% CO2 in 13.4% O2 for several hours produced headache and giddiness, but an exposure to 2.5-2.8% CO2 in 14.6-15% O2 was devoid of any symptoms. Schneider and Truesdale (1922) showed that, in 16 resting volunteers exposed to 1-8% CO2 for 17-32 min, headaches developed only at a CO2 concentration of 5 % or more and the headache could be intense. In a study by Brackett et al. (1965), 7% CO2 caused mild headache in approximately seven resting volunteers in 40-90 min. CO2 exposures do not cause headaches immediately. Menn et al. (1970) reported that headaches mostly developed near the end of a 30-min exposure to 3.9% CO2 while the subjects were performing two-thirds-maximal exercise. Glatte et al. (1967a) found that, in a 5-d exposure to 3% CO2, mild-to-moderate throbbing frontal headaches were detected in four of seven human subjects in the first day. A similar response was found in human subjects exposed to 4% CO2 (Glatte et al., 1967b; Menn et al., 1968). The headaches usually began in the first few hours of exposure. The headaches produced by CO2 are not long lasting. In a 30-min exposure to 3.9% CO2, the headaches disappeared an hour after the exposure (Menn et al., 1970). In human subjects exposed to 3% or 4% CO2 for 5 d, they recovered from the headaches in 3 d (Glatte et al., 1967b; Menn et al., 1968). Menn et al. (1970) postulated that the
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--> headaches are caused by CO2-induced dilation of cerebral blood vessels (Patterson et al., 1955). The disappearance of the headaches soon after an acute exposure or disappearing beginning on the third day of a 5-d exposure suggests, as another possibility, that the headaches are due to CO2-induced acidosis. As discussed above, it is not certain whether 2.8% CO2 could cause headaches. Similarly, there is conflicting evidence on 2% CO2. Without specifying the size of the study population, Schulte (1964) reported that headaches were detected in human subjects exposed to 2% CO2 for several hours on mild exertion. In contrast, Radziszewski et al. (1988) showed that a 30-d exposure of six human subjects to 2% CO2 rarely produced headaches, even when they exercised. Intercostal Pain Acute CO2 exposures can produce intercostal pain. Menn et al. (1970) reported that a 30-min exposure to 2.8% CO2 caused intercostal muscle pain during maximal exercise in two of eight human subjects. They did not report any intercostal pain in the subjects during two-thirds- or half-maximal exercise. However, Sinclair et al. (1971) showed that a 1-h exposure to 2.8% CO2 failed to produce intercostal muscle pain in four volunteers during steady strenuous exercise. It is possible that the test subjects in Sinclair's study did not exercise maximally during the exposure to 2.8% CO2, so that they did not experience the intercostal pain that was reported by those in Menn's study. Menn et al. failed to detect intercostal muscle pain in eight human subjects exposed to 1.1% CO2 for 30 min even during maximal exercise. Because astronauts will not be exercising maximally in the spacecraft, 2.8% is chosen as the NOAEL for intercostal muscle pain resulting from acute CO2 exposures. Acid-Base Balance An exposure to CO2 at concentrations much higher than the normal value of 0.03% increases the pCO2 in blood (Mines, 1981). The increased pCO2 in blood lowers the blood pH, although the lowering is
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--> reduced somewhat by the bicarbonate and protein buffers in blood (Mines, 1981). Acidosis is known to occur in humans after a 1-h exposure to 2.8% CO2 (Sinclair et al., 1971). Both the CO2 absorption and acidosis happen very rapidly. During a 1-h exposure of volunteers to 7% CO2, the arterial pCO2 and HCO3 concentrations were raised, while the arterial plasma pH dropped from 7.40 to 7.30 as early as 10 min into the exposure (Brackett et al., 1965). These arterial parameters remained at a plateau from min 10-60 during the CO2 exposure. The decreases in arterial plasma pH in humans resulting from acute CO2 exposures are tabulated as follows. TABLE 3-1 Arterial pH Decreases After Acute CO2 Exposures Concentration, % Exposure Duration Arterial pH Drop Reference 1.5 1 d 0.05 Schaefer, 1963b 2 2 h 0 Guillerm and Radziszewski, 1979 2 2-3 d 0.01 Guillerm and Radziszewski, 1979 2.8 1 d 0.02 Glatte et al., 1967a 3.0 6-24 h 0.025 Sinclair et al., 1969 7 10-60 min 0.10 Brackett et al., 1965 10 10-60 min 0.22 Brackett et al., 1965 Electrolyte Levels Messier et al. (1976) reported some electrolyte changes in 7-15 human subjects in 57-d submarine patrols, the atmosphere of which was maintained at 0.8-1.2% CO2, 19-21% O2, and CO at <25 ppm. On the first day of a patrol, the plasma levels of calcium decreased, with no change in plasma phosphorus levels, but the erythrocyte level of calcium increased. Respiratory System The most obvious effect of CO2 exposures is increased alveolar ventilation, which is not a toxic effect per se, but it and other physiological
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--> changes inducible by CO2 will be described in the Toxicity Summary. If O2 is maintained at a constant concentration, alveolar ventilation of humans varies linearly with the CO2 concentration at ventilation up to about 60 L/min (Cotes, 1979, pp. 149, 258, 363). The amounts of ventilatory increase during an acute exposure of normal human subjects to CO2 at various concentrations are summarized in Table 3-2. The hyperventilatory response is due mainly to a tidal volume increase, although the respiratory rate was found to increase in one study but not in another (Schaefer, 1963b; Glatte et al., 1967a; Guillerm and Radziszewski, 1979). The hyperventilatory response to inhaled CO2 is triggered by CO2's effect on chemoreceptors in the brain and the carotid chemoreceptors (Cotes, 1979, pp. 149, 258, 363; Phillipson et al., 1981). When the CO2 exposure terminates, residual hyperventilation helps to lower the pCO2 in blood, and thus the hyperventilation plays a role in restoring the normal blood pH. Three studies show that human subjects acclimate somewhat to the hyperventilatory effect of CO2 (Chapin et al., 1955; Schaefer, 1958; Radziszewski et al., 1988). The alveolar ventilation at rest was 15.1 L/min shortly after an exposure to 3% CO2 began, but it was lowered to 12.9 L/min near the end of the 78-h exposure (Chapin et al., 1955). Schaefer (1958) also reported acclimation to CO2's ventilatory effect. He presented evidence that diving instructors, who had held their breaths daily for long durations under water (resulting in CO2 accumulation in their bodies), showed a smaller hyperventilatory response toward acute CO2 challenges than other volunteers who were not accustomed to CO2 retention. Some of the data from Radziszewski et al. (1988), summarized in Table 3-2 showed that the hyperventilatory response to CO2 was diminished about one fifth at 24 h compared with 2 h in a continuous CO2 exposure. Some evidence indicates that CO2 can stimulate or depress ventilation depending on the concentration. As mentioned above, CO2 stimulates respiration at a concentration as low as 1%. CO2 at concentrations higher than 8% has been reported to depress respiration in humans (Cotes, 1979, pp. 149, 258, 363). However, a 3.8-min exposure of human subjects to 10.4% CO2 is known to stimulate respiration (Dripps and Comroe, 1947). So the exact CO2 concentration required to consistently depress respiration is unknown and it might be much higher than 8%.
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--> TABLE 3-2 Hyperventilatory Responses to Acute CO2 Exposures Concentration, %. Exposure No. Increase in Minimum Volume, % Duration (mean ± SD) Reference 0.5-0.6 5 10 min 14 ± 4 Campbell et al., 1913 0.5 6 24 h —a Radziszewski et al., 1988 1 16 17-32 min 32 Schneider and Truesdale, 1922 1 6 24 h 19 Radziszewski et al., 1988 2 16 17-32 min 80 Schneider and Truesdale, 1922 2 6 2 h 60 Radziszewski et al., 1988 2 6 24 h 45 Radziszewski et al., 1988 2.1-2.5 3 10 min 63 ±13 Campbell et al., 1913 2.2 3 10 min 36 ±21 Eldridge and Davis, 1959 2.5 3 10-20 min 30 ± 9 Brown et al., 1948 2.5 9 ≈20 min 33 ± 21 Tashkin and Simmons, 1972 3 16 17-32 min 148 Schneider and Truesdale, 1922 3 5 2 h 70 Radziszewski et al., 1988 3 5 24 h 50 Radziszewski et al., 1988 3.8 5 2 h 160 Radziszewski et al., 1988 3.8 5 24 h 130 Radziszewski et al., 1988 4 16 17-32 min 208 Schneider and Truesdale, 1922 4.2 3 10 min 184 ± 110 Eldridge and Davis, 1959 4.3 5 2 h 240 Radziszewski et al., 1988 4.3 5 24 h 180 Radziszewski et al., 1988 5 3 10-20 min 130 ± 30 Brown et al., 1948 5 9 ≈20 min 91 ± 60 Tashkin and Simmons, 1972 5 16 17-32 min 309 Schneider and Truesdale, 1922 5.7-6.1 5 10 min 413 ± 57 Campbell et al., 1913 5.9 7 5 min 184 Brown, 1930a 6 3 20.5-22 min 203 Brown, 1930a 6 23 16 min 200 White et al., 1952 6 16 17-32 min 419 Schneider and Truesdale, 1922 7 16 17-32 min 512 Schneider and Truesdale, 1922 7.5 3 10-20 min 474 ± 242 Brown et al., 1948 7.5 9 ≈20 min 269 ± 123 Tashkin and Simmons, 1972 8 16 17-32 min 640 Schneider and Truesdale, 1922 8.8 5 7-10 min 228 Brown, 1930a 10 9 ≈20 min 456 ± 189 Tashkin and Simmons, 1972 12.4 7 0.75-2 min 153 Brown, 1930a a Statistically not significant.
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--> Exposures to CO2 are also known to affect lung functions. CO2 inhalation for 2 h at 5% or 7.5% decreased specific airway conductance in volunteers, but 2.5% CO2 did not change the conductance (Tashkin and Simmons, 1972). A 120% increase in the total lung resistance was detected in human subjects who inhaled 8% CO2 in 19% O2 for 3-6 min (Nadel and Widdicombe, 1962). There are no data on the structural effect of CO2 on the lungs of human beings. However, Schaefer and his colleagues reported that acute exposures to CO2 injured the lungs of guinea pigs (Niemoeller and Schaefer, 1962; Schaefer et al., 1964a). In some of the guinea pigs exposed to 15% CO2 in 21% O2, Schaefer's group detected subpleural atelectasis, an increase of lamellar bodies in alveolar lining cells, congestion, edema, and hemorrhage in the lungs in 1 or 6 h (Schaefer et al., 1964a). When the exposure was extended to 1 or 2 d, they reported that hyaline membranes were seen in the lungs, in addition to the pulmonary injuries seen at 1 and 6 h. As the exposure was further extended to 7 or 14 d, they described a decline in incidences of atelectasis, edema, hemorrhages, and hyaline membranes in the lung. In that 1964 study, Schaefer's group looked at a total of six time points, with 4-14 guinea pigs exposed to CO2 per time point. However, they used only 13 guinea pigs as controls, and they did not specify how many control guinea pigs were sacrificed per time point. That means, on the average, only two control guinea pigs were sacrificed at each time point and that is grossly inadequate. In another study, Niemoeller and Schaefer (1962) reported that CO2 exposures at 1.5 % or 3 % could produce similar lung injuries as 15% CO2. In this study, the same problem existed. They used only four control guinea pigs in the 1.5%-CO2 experiment in which a group of exposed guinea pigs was examined at four time points. Similarly, in the 3%-CO2 experiment, they used seven guinea pigs to control for examinations of exposed guinea pigs at five time points. Consequently, their findings that CO2 exposures produced lung injuries in guinea pigs might not be reliable. Therefore, their findings in the lungs of guinea pigs (Niemoeller and Schaefer, 1962; Schaefer et al., 1964a) are disregarded in setting SMACs. Cardiovascular System CO2 exposures are known to affect the heart and the circulatory sys-
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--> tem. A 17-32-min exposure of humans to 1% or 2% CO2 is known to cause slight increases of systolic and diastolic pressure (Schneider and Truesdale, 1922). In another human study, a 15-30-min exposure to 5% or 7% CO2 caused increases in blood pressure and cerebral blood flow and a decrease in cerebrovascular resistance (Kety and Schmidt, 1948). In the same study, no change in cardiac output was detected, but in another study, a 4-25-min exposure of volunteers to 7.5% CO 2 increased the cardiac output and blood pressure (Grollman, 1930). In addition to changing the cardiac output, CO2 can increase the heart rate. A 10-15-min exposure to 5.4% CO2 or a 4-25-min exposure to 7.5% CO2 increased the pulse rate in humans (Grollman, 1930; Schaefer, 1958). Acute CO2 exposures can result in some EKG changes. Nodal and atrial premature systoles, premature ventricular contractions, inversion of P waves, low P waves, and increased T-wave voltage were observed in psychiatric patients exposed to 30% CO2 in 70% O2 for 38 s (MacDonald and Simonson, 1953). Similarly, McArdle (1959) exposed psychiatric patients to 30% CO2 in 70% O2 for 10-15 breaths, and he detected acidosis, marked increases in systolic and diastolic pressures, atrial extrasystoles, atrial tachycardia (but no ventricular extrasystole), increased P-wave voltage, low or inverted P waves, spiked T waves with a broad base, increased T-wave voltage, slight increases in PR intervals and QRS intervals, and a marked increase in the QT interval, which was the most consistent finding. The fact that it took only 35-45 breaths of the mixture of 30% CO2 in 70% O2 to produce narcosis in these patients suggests that the CO2 concentration used was very high. In CO2 exposures at lower concentrations, lower incidences of abnormal cardiac rhythm result. For instance, in human subjects breathing 7-14% CO2, balance O2, for 10-20 min at rest, premature nodal contraction was detected in only 2 of 27 subjects (versus 0 of 27 before the exposure) and premature ventricular contraction was found in only 3 of 27 subjects (versus 1 of 27 before the exposure) (Sechzer et al., 1960). At even lower CO2 concentrations, only minor EKG changes were produced without any abnormal rhythm. In human subjects, a 6-8 min exposure to 6% CO2 depressed the amplitude of the QRS complex and T wave, but there were no T-wave inversions or changes in the S-T segment (Okajima and Simonson, 1962). These EKG changes were more severe in men of about 60 years of age than in men in their twenties. In volunteers doing moderate or maximal exercise while exposed
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--> Undersea Biomed. Res. (Submarine Suppl.):S91-S114. Haldane, J., and J.L. Smith. 1892. The physiological effects of air vitiated by respiration. J. Pathol. Bacteriol. 1:168-186. Haring, O.M. 1960. Cardiac malformations in rats induced by exposure of the mother to carbon dioxide during pregnancy. Circ. Res. 8:1218-1227. Hartzell, G., and W.G. Switzer. 1985. On the toxicities of atmospheres containing both carbon monoxide and carbon dioxide. J. Fire Sci. 3:307-309. Hofbauer, J., K. Hobarth, and O. Zechner. 1990. The significance of citrate excretion and calcium/citrate quotients in urine in patients with calcium calculi. Z. Urol. Nephrol. 83:597-602. Hopson, G.D., J.W. Littles, and W.C. Patterson. 1974. MSFC Skylab Thermal and Environmental Control System Mission Evaluation. Rep. No. NASA TM X-64822. National Aeronautics and Space Administration, Washington, D.C. Huntoon, C.L., P.C. Johnson, and N.M. Cintron. 1989. Hematology, immunology, endocrinology, and biochemistry. Pp. 222-239 in Space Physiology and Medicine, A.E. Nicogossian, ed. Philadelphia: Lea & Febiger. Isom, G.E., and R.M. Elshowihy. 1982. Naloxone-induced enhancement of carbon dioxide stimulated respiration. Life Sci. 31:113-118. Jackson, J.K., J.R. Wamsley, M.S. Bonura, and J.S. Seeman. 1972. Pp. 34, 48-50 in Program Operational Summary: Operational 90 Day Manned Test of a Regenerative Life Support. Rep. No. NASA CR-1835. National Aeronautics and Space Administration, Washington, D.C. Johnston, R.F. 1959. The syndrome of carbon dioxide intoxication: Its etiology, diagnosis, and treatment. Univ. Mich. Med. Bull. 25: 280-292. Kety, S.S., and C.F. Schmidt. 1948. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J. Clin. Invest. 27:484-492. Kryger, M.H. 1981. Respiratory failure 2: Carbon dioxide. Pp. 205-219 in Pathophysiology of Respiration, M.H. Kryger, ed. New York: John Wiley & Sons. Lai, Y.-L., Y. Tsuya, and J. Hildebrandt. 1978. Ventilatory responses to acute CO2 exposure in the rat. J. Appl. Physiol. 45:611-618.
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--> Lambertsen, C.J. 1971. Therapeutic gases: Oxygen, carbon dioxide, and helium. Ch. 55 in Drill's Pharmacology in Medicine, J.R. DiPalma, ed. New York: McGraw-Hill. Leach, C.S., and P.C. Rambaut. 1977. Biochemical responses of the Skylab crewmen: An overview. In Biomedical Results from Skylab, R.S. Johnston and L.F. Dietlein, eds. National Aeronautics and Space Administration, Washington, D.C. LeBaron, F.N. 1982. Lipid metabolism I. P. 473 in Textbook of Biochemistry with Clinical Correlations, T.M. Devlin, ed. New York: John Wiley & Sons. Levin, B.C., M. Paabo, J.L. Gurman, S.E. Harris, and E. Braun. 1987. Toxicological interactions between carbon monoxide and carbon dioxide. Toxicology 47:135-164. Levin, B.C., M. Paabo, L. Highbarger, and N. Eller. 1989. Synergistic Effects of Nitrogen Dioxide and Carbon Dioxide Following Acute Inhalation Exposures in Rats. Society of the Plastics Industry, Inc. Available from the National Technical Information Services, Springfield, Va., Doc. No. PB89-214779. Luft, U.C., S. Finkelstein, and J.C. Elliott. 1974. Respiratory gas exchange, acid-base balance, and electrolytes during and after maximal work breathing 15 mm Hg PICO2. Pp. 282-293 in Topics in Environmental Physiology and Medicine: Carbon Dioxide and Metabolic Regulations, G. Nahas and K.E. Schaefer, eds. New York: Springer-Verlag. MacDonald, F.M., and E. Simonson. 1953. Human electrocardiogram during and after inhalation of thirty percent carbon dioxide. J. Appl. Physiol. 6:304-310. McArdle, L. 1959. Electrocardiographic studies during the inhalation of 30 per cent carbon dioxide in man. Br. J. Anaesth. 31:142-151. McCarthy, D.S. 1981. Airflow obstruction. P. 16 in Pathophysiology of Respiration, M.H. Kryger, ed. New York: John Wiley & Sons. Massie, B.M., and M. Sokolow. 1990. Heart and great vessels. Pp. 267-271 in Current Medical Diagnosis and Treatment in 1990, S.A. Schroeder, M.A. Krupp, L.M. Tierney, Jr., and S.J. McPhee, eds. Norwalk, Conn.: Appleton and Lange. Meessen, H. 1948. Chronic carbon dioxide poisoning experimental studies. Arch. Pathol. 45:36-40. Menn, S.J., R.D. Sinclair, and B.E. Welch. 1968. Response of Normal Man to Graded Exercise in Progressive Elevations of CO2. Rep.
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--> No. SAM-TR-68-116. Aerospace Medical Division, USAF School of Aerospace Medicine, Brooks Air Force Base, San Antonio, Tex. Menn, S.J., R.D. Sinclair, and B.E. Welch. 1970. Effect of inspired pCO2 up to 30 mm Hg on response of normal man to exercise. J. Appl. Physiol. 28:663-61. Messier, A.A., and K.E. Schaefer. 1971. The effect of chronic hypercapnia on oxygen affinity and 2,3-diphosphoglycerate. Resp. Physiol. 12:291-296. Messier, A.A., E. Heyder, and K.E. Schaefer. 1971. Effect of 90-Day Exposure to 1% CO2 on Acid-Base Status of Blood. Rep. No. 655. U.S. Naval Submarine Medical Center, Submarine Base, Groton, Conn. Messier, A.A., E. Heyder, W.R. Braithwaite, C. McCluggage, A. Peck, and K.E. Schaefer. 1976. Calcium, magnesium, and phosphorus metabolism, and parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on submarines. Undersea Biomed. Res. 6(Suppl.):S57-S70. Mines, A.H. 1981. Pp. 91-99 in Respiratory Physiology. New York: Raven Press. Mitsuda, H., S. Ueno, H. Mizuno, H. Fujikawa, K. Konaka, and C. Fukada. 1982. Effects of various molecular oxygen levels in mixed gas on acute respiratory insufficiency induced with carbon dioxide inhalation in rats. Kankyo Kagaku Sogo Kenkyusho Nenpo 2:35-46. Morey, P.R. and D.E. Shattuck. 1989. Role of ventilation in the causation of building-associated illness. Occup. Med. State of the Art Rev. 4:625-642. Morey-Holton, E.R., H.K. Schnoes, H.F. DeLuca, M.E. Phelps, R.F. Klein, R.H. Nissenson, and C.D. Arnaud. 1988. Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2. Aviat. Space Environ. Med. 59:1038-1041. Mukherjee, D.P., and S.P. Singh. 1967. Effect of increased carbon dioxide in inspired air on the morphology of spermatozoa and fertility of mice. J. Reprod. Fert. 13:165-167. Nadel, J.A. and J.G. Widdicombe. 1962. Effect of changes in blood as tensions and carotid sinus pressure on tracheal volume and total lung resistance to airflow. J. Physiol. 163:13-33. NASA. 1984. PPCO2 history for STS 51-D. P. 4.3.7-7 in Shuttle Operations Data Book. Doc. No. JSC 08934. NASA, Johnson Space Center, Houston, Tex.
OCR for page 181
--> NASA. 1988. PPCO2 Constraint. Flight Rule No. 13-8. NASA, Johnson Space Center, Houston, Tex. Naval Submarine Medical Research Laboratory. 1982. Position Paper: The Toxic Effects of Chronic Exposures to Low Levels of Carbon Dioxide. Rep. No. 973. Naval Submarine Medical Center, Naval Submarine Base, Groton, Conn. Niemoeller, H., and K.E. Schaefer. 1962. Development of hyaline membranes and atelectasis in experimental chronic respiratory acidosis. Proc. Soc. Exp. Biol. Med. 110:804-808. Notter, R.H., and J.N. Finkelstein. 1984. Pulmonary surfactant: An interdisciplinary approach. J. Appl. Physiol. 57:1613-1624. NRC. 1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants. Washington, D.C.: National Academy Press. Okajima, M., and E. Simonson. 1962. Effect of breathing six percent carbon dioxide on ECG changes in young and older healthy men. J. Gerontol. 17:286-288. Olson, M.S. 1982. Bioenergetics and oxidative metabolism. P. 279 in Textbook of Biochemistry with Clinical Correlations, T.M. Devlin, ed. New York: John Wiley & Sons. Pak, C.Y.C., C. Skurla, and J.A. Harvey. 1985. Graphic display of urinary risk factors for renal stone formation. J. Urol. 134:867-870. Pak, C.Y.C., K. Hill, N.M. Cintron, and C. Huntoon. 1989. Assessing applicants to the NASA flight program for their renal stone-forming potential. Aviat. Space Environ. Med. 60:157-161. Patterson, J.L., H. Heyman, L.L. Battery, and R.W. Ferguson. 1955 Threshold of response of the cerebral vessels of man to increases in blood carbon dioxide. J. Clin. Invest. 34:1857-1864. Peck, A.S. 1971. The Time Course of Acid-Base Balance While on FBM Patrol. Rep. No. 675. Naval Submarine Medical Center, Naval Submarine Base, Groton, Conn. Pepelko, W.E. 1970. Effects of hypoxia and hypercapnia, singly and combined, on growing rats. J. Appl. Physiol. 28:646-651. Phillipson, E.A., G. Bowes, E.R. Townsend, J. Duffin, and J.D. Cooper. 1981. Carotid chemoreceptors in ventilatory responses to changes in venous CO2 load. J. Appl. Physiol. 51:1398-1403. Pingree, B.J.W. 1977. Acid-base and respiratory changes after prolonged exposure to 1% carbon dioxide. Clin. Sci. Mol. Med. 52:67-74.
OCR for page 182
--> Radziszewski, E., R. Guillerm, R. Badre, and C. Abran. 1976. Cinetique de la compensation de l'acidose respiratoire induite par l'hypercapnie chronique experimentale chez l'homme. Bull. Eur. Physiopathol . Resp. 12:-100. Radziszewski, E., L. Giacomoni, and R. Guillerm. 1988. Effets physiologiques chez l'homme du confinement de longue duree en atmosphere enrichie en dioxyde de carbone. Pp. 19-23 in Proceedings of the Colloquium on Space and Sea. European Space Agency, Brussels, Belgium. Redding, R.A., T. Arai, W.H.J. Douglas, H. Tsurutani, and J. Oven. 1975. Early changes in lungs of rats exposed to 70% O2. J. Appl. Physiol. 38:136-142. Riley, R.L., and B. Barnea-Bromberger. 1976. Acid-Base Changes in Blood of Brewery Workers Exposed to CO2. An unpublished report cited by NIOSH in Criteria for a Recommended Standard. Occupational Exposure to Carbon Dioxide, Rep. No. NIOSH-76-194. National Institute for Occupational Safety and Health, Cincinnati, Ohio. Rodkey, F.L., and H.A. Collison. 1979. Effects of oxygen and carbon dioxide on carbon monoxide toxicity. J. Combust. Toxicol. 6: 208-212. Sax, I. 1984. P. 640 in Dangerous Properties of Industrial Materials. New York: Van Nostrand Reinhold. Schaefer, K.E. 1949a. [Influence exerted on the psyche and the excitatory processes in the peripheral nervous system under long-term effects of 3% CO2.] Pfluegers Arch. Gesamte. Physiol. Menschen Tiere 251:716-725. Schaefer, K.E. 1949b. [Respiratory and acid-base balance during prolonged exposure to a 3% CO2 atmosphere.] Pfluefers Arch. Gesamte. Physiol. Menschen. Tiere. 251:689-715. Schaefer, K.E. 1958. Effects of Carbon Dioxide as Related to Submarines and Diving Physiology. Memo. Rep. No. 58-11. Naval Medical Research Laboratory, New London, Conn. Schaefer, K.E. 1959. Experiences with submarine atmospheres. J. Aviat. Med. 30:350-359. Schaefer, K.E. 1961a. Blood pH and pCO2 homeostasis in chronic respiratory acidosis related to the use of amine and other buffers. Ann. N.Y. Acad. Sci. 92:401-413.
OCR for page 183
--> Schaefer, K.E. 1961b. A concept of triple tolerance limits based on chronic carbon dioxide toxicity studies. Aerospace Med. 32:197-204. Schaefer, K.E. 1963a. The effects of CO2 and electrolyte shifts on the central nervous system. Pp. 101-123 in Selective Vulnerability of the Brain in Hypoxemia, J.P. Schade, ed. Oxford, U.K.: Blackwell Scientific Publications. Schaefer, K.E. 1963b. Respiratory adaptation to chronic hypercapnia. Ann. N.Y. Acad. Sci. 109:772-782. Schaefer, K.E. 1963c. Acclimatization to low concentration of carbon dioxide. Ind. Med. Surg. 32:11-13. Schaefer, K.E. 1979. Physiological stresses related to hypercapnia during patrols on submarines. Undersea Biomed. Res. 6(Suppl.): S15-S47. Schaefer, K.E., B.J. Hastings, C.R. Carey, and G. Nichols, Jr. 1963a. Respiratory acclimatization to carbon dioxide. J. Appl. Physiol. 18: 1071-1078. Schaefer, K.E., G. Nichols, Jr., and C.R. Carey. 1963b. Calcium phosphorus metabolism in man during acclimatization to carbon dioxide. J. Appl. Physiol. 18:1079-1084. Schaefer, K.E., M.E. Avery, and K. Bensch. 1964a. Time course of changes in surface tension and morphology of alveolar epithelial cells in CO2-induced hyaline membrane disease. J. Clin. Invest. 43:2080-2093. Schaefer, K.E., G. Nichols, Jr., and C.R. Carey, 1964b. Acid-base balance and blood and urine electrolytes of man during acclimatization to CO2. J. Appl. Physiol. 19:48-58. Schaefer, K.E., N. McCabe and J. Withers. 1968. Stress response in chronic hypercapnia. Am. J. Physiol. 214:543-548. Schaefer, K.E., H. Niemoeller, A. Messier, E. Heyder, and J. Spencer. 1971. Chronic CO2 Toxicity: Species Difference in Physiological and Histopathological Effects. Rep. No. 656. Naval Submarine Medical Research Laboratory, Groton, Conn. Schaefer, K.E., S.M. Pasquale, A.A. Messier, and H. Niemoeller. 1979a. CO2-induced kidney calcification. Undersea Biomed. Res. (Submarine Suppl.):S143-S153. Schaefer, K.E., W.H.J. Douglas, A.A. Messier, M.L. Shea, and P.A.
OCR for page 184
--> Gohman. 1979b. Effect of prolonged exposure to 0.5% CO2 on kidney calcification and ultrastructure of lungs. Undersea Biomed. Res. (Submarine Suppl.):S155-S161. Schaefer, K.E., S. Pasquale, A.A. Messier, and M. Shea. 1980. Phasic changes in bone CO2 fractions, calcium, and phosphorus during chronic hypercapnia. J. Appl. Physiol. 48:802-811. Schwille, P.O., and U. Herrmann. 1992. Environmental factors in the pathophysiology of recurrent idiopathic calcium urolithiasis (RCU), with emphasis on nutrition. Urol. Res. 20:72-83. Schneider, E.C., and D. Truesdale. 1922. The effects on the circulation and respiration of an increase in the carbon dioxide content of the blood in man. Am. J. Physiol. 63:155-175. Schulte, J.H. 1964. Sealed environments in relation to health and disease. Arch. Environ. Health 8:438-452. Sechzer, P.H., L.D. Egbert, H.W. Linde, D.Y. Cooper, R.D. Dripps, and H.L. Price. 1960. Effect of CO2 inhalation on arterial pressure, ECG and plasma catecholamines and 17-OH corticosteroids in normal man. J. Appl. Physiol. 15:454-458. Shih, K.C. 1987. P. C-34 in SL-2 Subsystem and Verification Flight Instrumentation Data. Doc. No. TM-SEAD-87004. MacDonald Douglas Huntsville, Huntsville, Ala. Sinclair, R.D., J.M. Clark, and B.E. Welch. 1969. Carbon dioxide tolerance levels for space cabins. Proceedings of the Fifth Annual Conference on Atmospheric Contamination in Confined Spaces, Sept. 16-18, Wright-Patterson Air Force Base, Dayton, Ohio. Sinclair, R.D., J.M. Clark, and B.E. Welch. 1971. Comparison of physiological responses of normal man to exercise in air and in acute and chronic hypercapnia. Pp. 409-417 in Underwater Physiology, C.J. Lambertsen, ed. New York: Academic Press. Skov, P., O. Valbjorn, and the Danish Climate Study Group (DISG) 1987. The ''sick'' building syndrome in the office environment: The Danish town hall study. Environ. Int. 13:339-349. Stein, S.N., H.E. Lee, J.H. Annegers, S.A. Kaplan, and D.G. McQuarrie. 1959. The effects of prolonged inhalation of hypernormal amounts of carbon dioxide. I. Physiological effects of 3 percent CO2 for 93 days upon monkeys. Pp. 527-536 in Research Report NM 24 01 00.01.01, Vol. 17. Naval Medical Research Institute, Bethesda, Md.
OCR for page 185
--> Strachova, Z., and F. Plum. 1973. Reproducibility of the rebreathing carbon dioxide response test using an improved method. Am. Rev. Resp. Dis. 107:864-869. Storm, W.F., and C.L. Giannetta. 1974. Effects of hypercapnia and bedrest on psychomotor performance. Aerosp. Med. 45:431-433. Sullivan, T.Y., and P.-L. Yu. 1983. Airway anesthesia effects on hypercapnic breathing pattern in humans. J. Appl. Physiol. 55:368-376. Tansey, W.A., J.M. Wilson, and K.E. Schaefer. 1979. Analysis of health data from 10 years of Polaris submarine patrols. Undersea Biomed. Res. 6(Suppl.):S217-S246. Tashkin, D.P., and D.H. Simmons. 1972. Effect of carbon dioxide breathing on specific airway conductance in normal and asthmatic subjects. Am. Rev. Resp. Dis. 106:729-739. Tenney, S.M. 1954. Ventilatory response to carbon dioxide in pulmonary emphysema. J. Appl. Physiol. 6:477-484. Terrill, J.B., R.R. Montgomery, and C.F. Reinhardt. 1978. Toxic gases from fires. Science 200:1343-1347. Thomas, J.A. 1991. Toxic responses of the reproductive system. Pp. 484-520 in Cassarett and Doull's Toxicology: The Basic Science of Poisons, M.O. Amdur, J. Doull, and C.D. Klaassen, eds. New York: Pergammon Press. Thun, M.J., and S. Schober. 1991. Urolithiasis in Tennessee: An occupational window into a regional problem. Am. J. Public Health 81:587-591. Trinchieri, A., A. Mandressi, P. Luongo, G. Longo, and E. Pisani. 1991. The influence of diet on urinary risk factors for stones in healthy subjects and idiopathic renal calcium stone formers. Br. J. Urol. 67:230-236. U.S. Navy. 1988. Nuclear Powered Submarine Atmosphere Control Manual. S9510-AB-ATM-010/(U). Department of the Navy, Washington, D.C. van Aswegen, C.H., P. Hurter, C.A. van der Merwe, and D.J. du Plessis. 1989. The relationship between total urinary testosterone and renal calculi. Urol. Res. 17:181-183. Vandemark, N.L., B.D. Schanbacher, and W.R. Gomes. 1972. Alterations in testes of rats exposed to elevated atmospheric carbon dioxide. J. Reprod. Fertil. 28:457-459.
OCR for page 186
--> Vogel, J.M. 1975. Effect of spaceflight on bone mineral. Acta Astronautica 2:129-140. Wamsley, J.R., E.W. Youngling, and W.F. Behm. 1969. High fidelity simulations in the evaluation of environmental stress: Acute CO2 exposure. Aerospace Med. 40:1336-1340. Wang, T.C. 1975. A study of bioeffluents in a college classroom. ASHRAE Transact. 81:32-33. Wasserstein, A.G., P.D. Stolley, K.A. Soper, S. Goldfarb, G. Maislin, and Z. Agus. 1987. Case-control study of risk factors for idiopathic calcium nephrolithiasis. Miner. Electrolyte Metab. 13:85-95. Weitzman, D.O., and J.A.S. Kinney. 1969. Effect on Vision of Repeated Exposure to Carbon Dioxide. Rep. No. 566. Naval Submarine Medical Center, Naval Submarine Base, Groton, Conn. West, J.B. 1979. Pp. 23, 74 in Respiratory Physiology: The Essentials. Baltimore: Williams & Wilkins. Whedon, G.D., L. Lutwak, P.C. Rambaut, M.W. Whittle, M.C. Smith, J. Reid, C. Leach, C.R. Stadler, and D.D. Sanford. 1977. Mineral and nitrogen metabolic studies, Experiment M071. Pp. 164-174 in Biomedical Results from Skylab, R.S. Johnston and L.F. Dietlein, eds. National Aeronautics and Space Administration, Washington, D.C. Whedon, G.D. 1984. Disuse osteoporosis: Physiological aspects. Calcif. Tissue Int. 36:S146-S150. White, C.S., J.H. Humm, E.D. Armstrong, and N.P.V. Lundgren. 1952. Human tolerance to acute exposure to carbon dioxide. Pp. 439-455 in Rep. No. 1: Six Per Cent Carbon Dioxide in Air and in Oxygen. Aviation Med. (Oct.). 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, J.R., and J.A. Clements. 1987. Metabolism and turnover of lung surfactant. Am. Rev. Resp. Dis. 135:426-444. Wooley, W.D., S.A. Ames, and P.J. Fardell. 1979. Chemical aspects of combustion toxicology of fires. Fire Materials 3:110-120. Yonezawa, A. 1968. [Influence of carbon dioxide inhalation on renal circulation and electrolyte metabolism.] Jpn. Cir. J. 32:1119-1120. Zharov, S.G., Y.A. Il'in, Y.A. Kovalenko, I.R. Kalinichenko, L.I.
OCR for page 187
--> Karpova, N.S. Mikerova, M.M. Osipova, and Y.Y. Simonov. 1963. Effect on man of prolonged exposure to atmosphere with a high CO2 content. Pp. 155-158 in Proceedings of the International Congress of Aviation and Space Medicine. International Congress of Aviation and Space Medicine, Rome. Zink, P., and G. Reinhardt. 1975. Carbon dioxide poisoning after prolonged exposure. Beitr. Gerichtl. Med. 33:211-213.
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