7
Carbon Dioxide

John T. James, Ph.D., D.A.B.T.

Toxicology Group

Habitability and Environmental Factors Division

Johnson Space Center

National Aeronautics and Space Administration

Houston, Texas

OCCURRENCE AND USE

Carbon dioxide is the major expired by-product of human metabolism; if not effectively controlled, it can rapidly accumulate to dangerous concentrations in spacecraft atmospheres. On earth, the outdoor CO2 concentration is typically about 0.03%, and average indoor air contains CO2 in the range of 0.08% to 0.1% (IEQ 2006). In nominal spacecraft operations, the CO2 concentration is typically about 0.5%, but the concentration approached 2% during the troubled Apollo 13 mission (Michel et al. 1975). Carbon dioxide can also enter the atmosphere of a space habitat from accidental combustion of materials, from operation of payloads that use CO2 as an intravehicular propellant, and from use of the fire extinguisher, which, on the U.S. segment of the International Space Station (ISS), is CO2.

SUMMARY OF ORIGINAL APPROACH

The original spacecraft maximum allowable concentrations (SMACs) for CO2 were set by Wong (1996) and the National Research Council (NRC) SMACs Subcommittee, with substantial input and cooperation from National Aeronautics and Space Administration (NASA) environmental control engineers and the ISS Program Office. The following end points were evaluated: neurological (visual impairment, tremor, central nervous system [CNS] depression), headache, dyspnea and intercostal pain, increases in airway resistance, intolerance to hyperventilation, exercise impairment, and testicular injury. For all end points except testicular injury, the data came from human studies; testicular injury data came from exposed guinea pigs and rats. The “small n factor” was often used to compensate for the fact that many results were from human studies



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7 Carbon Dioxide John T. James, Ph.D., D.A.B.T. Toxicology Group Habitability and Environmental Factors Division Johnson Space Center National Aeronautics and Space Administration Houston, Texas OCCURRENCE AND USE Carbon dioxide is the major expired by-product of human metabolism; if not effectively controlled, it can rapidly accumulate to dangerous concentrations in spacecraft atmospheres. On earth, the outdoor CO2 concentration is typically about 0.03%, and average indoor air contains CO2 in the range of 0.08% to 0.1% (IEQ 2006). In nominal spacecraft operations, the CO2 concentration is typically about 0.5%, but the concentration approached 2% during the troubled Apollo 13 mission (Michel et al. 1975). Carbon dioxide can also enter the atmosphere of a space habitat from accidental combustion of materials, from operation of pay- loads that use CO2 as an intravehicular propellant, and from use of the fire extin- guisher, which, on the U.S. segment of the International Space Station (ISS), is CO2. SUMMARY OF ORIGINAL APPROACH The original spacecraft maximum allowable concentrations (SMACs) for CO2 were set by Wong (1996) and the National Research Council (NRC) SMACs Subcommittee, with substantial input and cooperation from National Aeronautics and Space Administration (NASA) environmental control engineers and the ISS Program Office. The following end points were evaluated: neuro- logical (visual impairment, tremor, central nervous system [CNS] depression), headache, dyspnea and intercostal pain, increases in airway resistance, intoler- ance to hyperventilation, exercise impairment, and testicular injury. For all end points except testicular injury, the data came from human studies; testicular in- jury data came from exposed guinea pigs and rats. The “small n factor” was of- ten used to compensate for the fact that many results were from human studies 112

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113 Carbon Dioxide in which a no-effect level was identified for the specific end point, but there was not an effect (or low) response level. Under these conditions, the no-observed- adverse-effect level (NOAEL) was multiplied by the factor √(n)/10, where n was the number of subjects in the study. The original summary table is presented in Appendix A. The end points were considered as described in the following sec- tions (Wong 1996). Neurological This end point was evaluated from the observation that 3% CO2 was a NOAEL for CNS effects in two studies; one was a 5-d exposure involving 7 subjects and the other was a 2-wk exposure involving 12 subjects (Glatte et al. 1967; Storm and Giannetta 1974). The calculation was as follows: AC (CNS) = 3% (NOAEL) × √(19)/10 (small n factor) = 1.3% where AC is acceptable concentration. This AC was applied to all exposure times because CNS effects would not be acceptable even for brief periods; however, there is no basis for supposing that prolonged exposures would result in an accumulation of CO2 that could have CNS effects. Headaches Evidence was presented that CO2-induced headaches are transient and that they were rare in a 30-d study of six humans exposed to 2% CO2 and exercising periodically during their exposure (Radziszewski et al. 1988). On the basis of this observation, 2% was assigned as a NOAEL for CO2-induced headaches (Wong 1996). Dyspnea and Intercostal Pain Wong used two studies to determine the AC for this adverse effect. Menn et al. (1970) found that exposure to 2.8% CO2 for 0.5 h did not elicit intercostal pain or dyspnea in eight subjects. Likewise, Sinclair et al. (1971) found none of his four subjects experienced dyspnea or intercostal pain when exposed to 2.8% CO2 for 1 h or 15-20 d. From these data, Wong derived a short-term AC to pro- tect against this end point. He did not use the small n factor, because some risk of minor effects is tolerated for short-term exposures. The 1- and 24-h ACs to protect against dyspnea and intercostal pain were as follows: 1- and 24-h AC (dyspnea, intercostal pain) = 2.8%.

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114 SMACs for Selected Airborne Contaminants For the longer-term SMACs, these effects would not be tolerated, so the small n factor was used with data from Sinclair et al. (1971) (n = 4) and Radziszewski et al. (1988) (n = 6) as follows: 7-, 30-, and 180-d AC (dyspnea, intercostal pain) = 2.8% (NOAEL) × √(10)/10 (small n factor) = 0.9 % Hyperventilation and Exercise Ability For short durations (1 or 24 h), hyperventilation was viewed as a physio- logical adaptation and SMACs were not set for contingencies for this effect. For long-term exposures, hyperventilation would not be acceptable, so Wong used the results of three studies to set this limit (Sinclair et al. 1969; Guillerm and Radziszewski 1979; Radziszewski et al. 1988). He noted that one can conclude from those three studies (n=14) that prolonged exposure to 2% CO2 does not cause noticeable hyperventilation. The calculation was as follows: 7-, 30-, and 180-d AC (hyperventilation) = 2% (NOAEL) × √(14)/10 (small n factor) = 0.7% For long-term exposures, Wong also considered whether the crew’s ability to exercise would be impaired. Looking at three studies (Glatte et al. 1967; Sinclair et al. 1971; Radziszewski et al. 1988) with a total of 16 subjects, Wong (1996) concluded that prolonged exposures to 2% CO2 did not limit the ability to exer- cise. The calculation was as follows: 7-, 30-, 180-d AC (exercise ability) = 2% (NOAEL) × √(16)/10 (small n factor) = 0.8% Increases in Airway Resistance On the basis of a report by Glatte et al. (1967) using seven subjects, Wong (1996) deduced that an exposure to 3% CO2 for 5 d was a NOAEL for increased airway resistance. This level was not adjusted for the small n factor in setting ACs for 1- and 24-h exposures, because the safety factor is not needed for con- tingency situations. Thus, 1- and 24-h AC (incr. airway resistance) = 3% Wong (1996) pointed out that the increased resistance is thought to be due to direct, local hypercapnia effects on the larynx; hence, severity would not be ex- pected to increase with time of exposure. The long-term ACs to prevent in- creased airway resistance were calculated by using the small n factor as follows:

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115 Carbon Dioxide 7-, 30-, and 180-d AC (incr. airway resistance) = 3% (NOAEL) × √(7)/10 (small n factor) = 0.8% Testicular Effects One of the more challenging findings Wong (1996) encountered was the report that rats exposed to CO2 concentrations as low as 2.5% showed sloughing of mature spermatids and Sertoli cells after only 4 h of exposure (Vandemark et al. 1972). Since the changes in the testis were reversible 36 h after an 8-h expo- sure, this observation was not used to set a short-term AC for testicular effects. To set the long-term standard in humans, Wong noted that a study in which guinea pigs and rats were exposed to 3% CO2 for 42 d turned up no evi- dence of testicular effects in either species (Schaefer et al. 1971). The NRC SMAC Subcommittee advised that the toxicity is due to acidosis, and therefore the sensitivities of rodent and human testes to this effect should not differ. Thus, 7-, 30-, and 180-d AC (testicular effects) = 3% (NOAEL in rodents) CHANGES IN FUNDAMENTAL NRC- RECOMMENDED APPROACHES The primary new tool for interpreting toxicity data is the benchmark dose modeling provided by the U.S. Environmental Protection Agency. This tool is regarded as an improvement over the NOAEL and lowest-observed-adverse- effect level (LOAEL) approach because it uses the entire dose-response curve to predict behavior of the dose-response relationship at concentrations below the lowest tested dose. RELEVANT DATA SINCE 1995 Relevant data have emerged since the original SMAC was written in 1995. Two human studies were published shortly after that date, but they have serious limitations for risk assessment. Sun et al. (1996) exposed three subjects to 2.5% CO2 for about ½ h (the time is unclear) and found that their depth perception (stereoacuity) decreased. In a related experiment, Yang et al. (1997) found that the ability of the three subjects to detect motion decreased with exposure to 2.5% CO2. Both effects disappeared once the CO2 exposure ended. These are interesting findings, but they are not suitable for human risk assessment because of the small value of n and because the relevance to crew performance during a contingency is unclear. The original acceptable concentration for preventing visual impairment was 1.3 %, which seems consistent with these reports (Wong 1996). Certainly, if CO2 impairs visual ability in operationally significant ways, that must be considered in setting limits. Further experiments are required to determine the significance of these preliminary findings.

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116 SMACs for Selected Airborne Contaminants In a study of four human subjects (males in their 20s), exposures to 0.7% and 1.2% CO2 for 20 d were found to increase the velocity of cerebral blood flow for the first 1-3 days of exposure; however, the flow gradually returned to preexposure values over the next 20 d (Sliwka et al. 1998). Only the subjects exposed to the higher concentration of CO2 reported headaches, and that oc- curred only during the first days of exposure before adaptation. The authors concluded that autoregulation of cerebral vascular blood flow was preserved during chronic (20-d) exposure to these low levels of CO2. In what appears to be a companion paper to the one of Sliwka et al. (1998)., Manzey and Lorenz (1998) investigated the mental performance of four subjects continuously exposed to 0.7% and 1.2% CO2 in a confined space for 26 d. They used four standardized performance tests: grammatical reasoning, mem- ory search, unstable tracking, and dual task (doing unstable tracking and mem- ory search together). Subjects were tested three times before CO2 was intro- duced, 12 times during the exposures, and once after the exposures ended. They concluded that concentrations up to 0.7% in the ambient atmosphere do not cause any detrimental effects on human subjective mood or performance. A slight decrement was noted in the tracking task during exposures to 1.2% CO2, but, in the judgment of the investigators, the magnitude of the effect was much smaller than those caused by other space flight stressors. These findings are con- sistent with the SMACs set by Wong (1996). Evidence from Russian Mir Space Station had suggested that sleep quality changed in space, so this was investigated in a manner similar to the two inves- tigations described above (Gundel et al. 1998). Four males exposed to 0.7% or 1.2% CO2 were evaluated with “sleep polygraphs,” which involved monitoring seven channels that included electroencephalogram and electrocardiogram pa- rameters. The authors found that neither level of CO2 altered sleep quality over the 26 d of the test. Horn et al. (2003) reported on the incidence of minor health complaints in 122 submarine crew members exposed to an average CO2 concentration of 0.49% during a 101-d mission. The only minor health problem that might rea- sonably be associated with CO2 exposure is trouble sleeping and no apparent change was noted when the premission, first-half mission, and last-half mission were compared (not a statistically based conclusion). There was no control group, and the end points were poorly defined, so the results of this study add little to our understanding of the potential long-term effects of exposure to CO2. There are a few studies of 5-7 d duration that evaluate crew survival during dis- abled-submarine tests. Typically, these studies focus on gross parameters of survival as opposed to detailed visual, memory, and neuromuscular testing, and they involve extreme cold along with high concentrations of CO2. These studies were judged not to be useful for setting SMACs for CO2 exposure. The NRC (2007) set exposure limits for Navy submarine operations based largely on the SMAC document (Wong 1996). The only new studies identified in that report were those described above (Sun et al. 1996; Yang et al. 1997).

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117 Carbon Dioxide NEW RISK ASSESSMENT APPROACHES Table 7-1 summarizes the opportunities that may exist to apply new risk assessment tools to the key studies supporting the original SMAC document. RATIONALE FOR REVISIONS TO PREVIOUS SMACS A large body of information exists on the physiological effects of excess CO2 inhalation in human volunteers and in submariners chronically exposed to concentrations often exceeding 1%. No single study or small subset of studies gives definitive guidance for each potential adverse effect of long-term exposure to CO2. Wong (1996) pieced together a rational picture of the potential adverse effects of exposure to CO2 and derived a defensible set of SMACs, with which the NRC SMAC Subcommittee agreed. None of the studies meet current-day standards and many were never published in the peer-reviewed literature. Since Wong’s effort, there have been no new studies to suggest that the original long-term SMACs need to be revised. On the basis of the visual-effects data of Sun et al. (1996) and Yang et al. (1997), the NRC Continuous Exposure Guid- ance Level (CEGL) Submarine Subcommittee (2007) determined a 90-d CEGL as follows: 90-d CEGL =2.5% (LOAEL, visual effects) × 1/3 (limited data factor) = 0.8% The factor of 3 was applied for “limited data.” Indeed, the two studies on which this is based involved only three subjects given acute exposures of uncer- tain duration. RATIONALE FOR THE 1,000-DAY SMAC No studies are available that qualify as authentic chronic studies. The longest human exposures to elevated concentrations of CO2 have occurred on submarines, and they seldom lasted longer than 100 d. Physiologically, the SMAC set for 180 d of exposure elicits a mild, subclinical adaptation to CO2, and there is no reason to suppose such an adaptation could not persist for 1,000 d. However, three factors present unique problems for chronic exposures to CO2 in space: (1) crews on exploration missions will receive sustained exposure to elevated CO2 levels and will not have the option to “fly up” more CO2 scrub- bing capability if the CO2 levels become intolerable, (2) the repair and rescue options for missions in deep space are much more limited than low-earth-orbit missions, and (3) anecdotal data from ISS crews suggest that a few individuals may have a risk of mild headaches at concentrations near or above 0.6% CO2 (Carr 2006). The 1,000-d SMAC is set conservatively at 0.5% to compensate for

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118 SMACs for Selected Airborne Contaminants TABLE 7-1 Applicability of a Benchmark Dose Modeling Approach Applicability of the Study Description BMD Approach Glatte et al. Humans exposed to 3% (n = 7) or 4% (n = 4) Unsuited for BMD (1967) CO2 for 5 d. Findings were not reported as dose- due to lack of dose- response data. For example, at 3% subjects could response data and exercise for 1 h, but at 4% they struggled to do small n value. 10 min. No psychomotor changes were found. Blood pH changes were compensated. Menn et al. Humans (n = 7-8) exercised for 30 min, exposed Data unsuited for (1970) to 1%, 2%, 2.8%, and 4% CO2. The highest two BMD because any levels caused dyspnea and intercostal pain, and apparent adverse the highest level caused headache. The only effects were not given quantitative data were physiology data, not in quantitative dose- toxicity data. response terms. Radziszewki Human experiments in days (and %) as follows: No suitable toxicity et al. (1988) 1 d (4.3%), 9 d (3.8%), 8 d (2.9%), 30 d (1.9%, data. 1%, and 0.5%); n = 5 or 6. A number of physiological changes and exercise limitations were noted at the higher concentrations, but they were not indicative of adverse effects, nor were they quantitatively expressed. Schaefer et The data consist of transient adaptations, Only a small portion al. (1971) changes in organ weights, changes in enzymes, of the data appear to and descriptive histological effects in rats and be quantitative, and guinea pigs exposed to concentrations from 1% they do not yield a to 30% CO2 for various times. The emphasis was dose-response on exposures to 3% or 15% CO2. Large relationship. differences were noted in the susceptibility of rats and guinea pigs. Sinclair et From 4 to 8 subjects were exposed to 1% to 4% Data in original report al. (1969) CO2 and exercised for 30 min. Subjects (n = 3 or are illegible and 4 ) were exposed for 5 or 11 d to 4% CO2; blood provide no basis for a and cerebrospinal fluid CO2, bicarbonate, pH, dose-response curve. and ventilation parameters were measured. Nine preventricular complexes were noted in the group that exercised. Sinclair et Four subjects exposed to 2.8% CO2 for 1 h or No adverse effects al. (1971) 15-20 d. CO2 retention increased during work. were identified, one The level was well tolerated at rest and with exposure level. exercise. Some physiological changes. Storm and Four groups (n = 6) were exposed to air or 4% No adverse effects on Giannetta CO2 for 2 wk in an active or a bed-rested state. parameters measured. (1974) They showed no decrement in psychomotor performance. Abbreviation: BMD, benchmark dose modeling.

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119 Carbon Dioxide these realities and to force a somewhat more robust air revitalization design that provides a larger safety margin during exploration-class missions. RATIONALE FOR AN INCREASE IN THE 1-HOUR SMAC The original SMAC for 1 h was based on extrapolation of observed NOAELs in 19 subjects exposed to 3 % CO2 for 5 to 14 d (Wong 1996). In our view, that approach is too conservative for a 1-h emergency exposure. The ag- gregate of data in human studies suggests that, during a 1-h exposure to 2% CO2, physiological adaptation, mild headache, and hyperventilation may occur, but performance decrements will be insignificant. The short-term SMACs are set for emergencies, and some risk of mild effects on the crew is acceptable. According to current flight rules, the flight surgeon would not allow the crew to exercise if the CO2 level were anywhere near 2%. Also, we expect that the crew will have adapted somewhat to relatively high CO2 (about 0.5%) levels during the space flight, so a “sudden” increase above the running levels would be better tolerated than if no preexposure had occurred. Mild headache and hyperventila- tion would be easily tolerated for 1 h, thus the 1-h SMAC is increased to 2%. COMPARISON OF SMACS WITH OTHER AIR QUALITY LIMITS The 1-h SMAC is close to the Navy CEGL, but the 24-h SMAC is about half the 24-h CEGL. This seems reasonable because the space crew is likely to have fewer resources to deal with an emergency situation if CO2 becomes ele- vated above nominal. For example, the space crew might have to repair the CO2 scrubber (a so- phisticated task requiring at least several hours), whereas the submarine crew should be able to engage additional scrubbers as needed to stabilize the level of CO2. Table 7-2 compares SMACs with other air quality limits. The long-term SMACs (0.7%) are between the Navy CEGL (0.8%) and the industrial-worker exposure limits (0.5%). This is reasonable; industrial workers may need a lower limit because they never get a chance to physiologically adapt to workplace CO2 exposures, whereas physiological adaptation occurs in long-term continuous exposures and astronauts are unaffected by CO2 exposures confined to less than 0.7%. The rationale for a lower 1,000-d SMAC of 0.5% has already been stated. RECOMMENDATIONS FOR ADDITIONAL RESEARCH The most useful practical experiment would be to repeat the work of Sun et al. (1996) and Yang et al. (1997) in which they found evidence of visual dis- turbances. Before such an experiment begins, the user community must agree on how much of a “visual” deficit can be accepted given the methods available to

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120 SMACs for Selected Airborne Contaminants TABLE 7-2 Comparison of Exposure Standards Source (Year Set) Time Limit (%) Reference NRC NRC 2007 EEGL 1h 2.5 EEGL 24 h 2.5 CEGL 90 d 0.8 OSHA NIOSH 2005 PEL Working lifetime 0.5 NIOSH NIOSH 2005 REL Working lifetime 0.5 IDLH Brief 4.0 ACGIH ACGIH 2004 TLV Working lifetime 0.5 STEL 15 min 3.0 2.0a Updated in current NASA 1h document SMAC 1.3 Wong 1996 24 h 0.7 Wong 1996 7-180 d 0.5b Updated in current 1,000 d document a New value replaces 1.3%; mild headache and hyperventilation acceptable for 1 h. b New value based on avoiding any risk of mild headache; no previous value set. Abbreviations: ACGIH, American Conference of Governmental Industrial Hygienists; CEGL, continuous exposure guidance level; EEGL, emergency exposure guidance level; IDLH, immediately dangerous to life and health; NIOSH, National Institute for Occupa- tional Safety and Health; NRC, National Research Council; OSHA, Occupational Safety and Health Administration; PEL, permissible exposure limit; REL, recommended expo- sure limit; SMAC, Spacecraft Maximum Allowable Concentration; STEL, short -term exposure limit; TLV, threshold limit value. measure such a deficit. The experiment must be done with several visual end points and with at least 10 subjects, and it must use at least three exposures. In addition, it would be useful to develop a dose-response curve for the testicular lesions Vandemark et al. (1972) reported, because their findings appear to be inconsistent with those of other studies. The mechanism(s) of these effects needs to be understood in order to determine whether the effects are due to acidosis. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 2004. Threshold Limit Values. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. Carr, C. 2006. NASA White Paper. Houston, TX: National Aeronautics and Space Ad- ministration.

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121 Carbon Dioxide Glatte, H., B.O. Hartman, and B.E. Welch. 1967. Nonpathologic hypercapnia in man. Pp. 110-129 in Lectures in Aerospace Medicine. Report SAM-TR-68-116. Brooks Air Force Base, TX: USAF Aerospace Medical Division, USAF School of Medicine. Guillerm, R., and E. Radziszewski. 1979. Effects on man of 30-day exposure to PICO2 of 14 torr (2%): Application to exposure limits. Undersea Biomed. Res. (Suppl. 6): S91-S114. Gundel, A., R.A. Parisi, R. Strobel, and M.R. Weihrauch. 1998. Characterization of sleep under ambient CO2 levels of 0.7 % and 1.2%. Aviat. Space Environ. Med. 69(5):491-495. Horn, W.G., T.L. Thomas, K. Marino, and T.I. Hooper. 2003. Health experience of 122 submarine crewmembers during a 101-day submergence. Aviat. Space Environ. Med. 74(8):858-862. IEQ. 2006. Carbon Dioxide. Fact Sheets. IEQ Corporation [online]. Available: http://www.ieqcorp.com/carbon_dioxide.htm [accessed May 14, 2007]. Manzey, D., and B. Lorenz. 1998. Effects of chronically elevated CO2 on mental per- formance during 26 days of confinement. Aviat. Space Environ. Med. 69(5):506- 514. Menn, S.J., R.D. Sinclair, and B.E. Welch. 1970. Effect of inspired PCO2 up to 30 mmHg on response of normal man to exercise. J. Appl. Physiol. 28(5):663-671. Michel, E.L., J.M. Waligora, D.J. Horrigan, and W.H. Schumate. 1975. Environmental factors. Section 2, Chapter 5 in Biomedical Results of Apollo, R.S. Johnston, L.F. Dietlein, and C.A. Berry, eds. NASA-SP 368. Washington, DC: National Aeronau- tics and Space Administration. NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to Chemical Hazards: Carbon dioxide. NIOSH Publication No. 2005-149. National Institute for Occupational Safety and Health [online]. Available: http://www.cdc.gov/niosh/npg/npgd0103.html [accessed March 27, 2007]. NRC (National Research Council). 2007. Carbon dioxide. Pp. 46-66 in Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, Vol. 1. Washington, DC: The National Academies Press. Radziszewski, E., L. Giacomoni, and R. Guillerm. 1988. Physiological effects in man as a result of long duration confinement in an atmosphere enriched with carbon diox- ide. Pp. 19-23 in Proceedings of the Colloquium on Space and Sea, November 24- 27, 1987, Marseille, France, T.D. Guyenne, ed [in French]. Paris: European Space Agency. [Translated to English by N. Timacheff]. Schaefer, K.E., H. Niemoeller, A. Messier, E. Heyder, and J. Spencer. 1971. Chronic CO2 Toxicity: Species Differences in Physiological and Histopathological Effects. Re- port 656. Groton, CT: Naval Submarine Medical Research Laboratory. 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 Con- tamination in Confined Spaces, Sept. 16-18, Wright-Patterson Air Force Base, Dayton, Ohio, R.D. O'Donnell, H.A. Leon, A. Azar, C.H. Wang, R.L. Patrick, W. Mautner, M.E. Umstead, and ML. Taylor, eds. Air Force Aerospace Medical Re- search Lab Wright-Patterson AFB, OH. 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, NY: Academic Press. Sliwka, U., J.A. Kransney, S.G. Simon, P. Schmidt, and J. North. 1998. Effects of sus- tained low-level elevations of carbon dioxide on cerebral blood flow and autoregu-

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122 SMACs for Selected Airborne Contaminants lation of the intracerebral arteries in humans. Aviat. Space Environ. Med. 69(3):299-306. Storm, W.F., and C.L. Giannetta. 1974. Effects of hypercapnia and bedrest on psychomo- tor performance. Aerospace Med. 45(4):431-433. Sun, M., C. Sun, and Y. Yang. 1996. Effect of low-concentration CO2 on stereoacuity and energy expenditure. Aviat. Space Environ. Med. 67(1):34-39. 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(3):457-459. Wong, K.L. 1996. Carbon dioxide. Pp. 105-187 in Spacecraft Maximum Allowable Con- centrations for Selected Airborne Contaminants, Vol. 2. Washington, DC: National Academy Press. Yang, Y., C. Sun, and M. Sun. 1997. The effect of moderately increased CO2 concentra- tion on perception of coherent motion. Aviat. Space Environ. Med. 68(3):187-191.

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APPENDIX A Table 7-3 summarizes the original SMACs set by Wong (1996). The current SMACs established by this committee are summarized in Table 7-2. TABLE 7-3 End Points and Acceptable Concentrations (Wong 1996) Uncertainty Factors Acceptable Concentrations End Point Exposure Data Species and Reference Species Small n 1h 24 h 7d 30 d 180 d Visual impairment, NOAEL at 3%, Human (n = 7, 12) — 10/(19)½ 1.3 1.3 1.3 1.3 1.3 tremor, CNS 24 h/d, 5 d or (Glatte et al. 1967; Storm depression 2 wk and Giannetta 1974) Headache NOAEL at 2%, Human (n = 6) — — 2 2 2 2 2 24 h/d, 30 d (Radziszewski et al. 1988; Guillerm and Radziszewski 1979) Dyspnea, NOAEL at Human (n = 8, 4) — — 2.8 2.8 — — — intercostal pain 2.8%, 0.5 or 1 h (Menn et al. 1970; Sinclair et al. 1971) NOAEL at Human (n = 4, 6) — 10/(10)½ — — 0.9 0.9 0.9 2.8%, 15 or (Sinclair et al. 1971; 20 d Radziszewski et al. 1988) Airway resistance NOAEL at 3%, Human (n = 7) — — 3 3 — — — increases 24 h/d, 5 d (Glatte et al. 1967) NOAEL at 3%, Human (n = 7) — 10/(10)½ — — 0.8 0.8 0.8 24 h/d, 5 d (Glatte et al. 1967) (Continued) 123

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TABLE 7-3 Continued 124 Uncertainty Factors Acceptable Concentrations End Point Exposure Data Species and Reference Species Small n 1h 24 h 7d 30 d 180 d Hyperventilation Tolerability NOAEL at 2%, Human (n = 4, 4, 6) — 10/(14)½ — — 0.7 0.7 0.7 24 h/d, 11 or 30 (Sinclair et al. 1969; d Radziszewski et al. 1988; Guillerm and Radziszewski 1979) Exercise impairment NOAEL at 2%, Human (n = 6, 4, 6) — 10/(16)½ — — 0.8 0.8 0.8 24 h/d, 5, 15, or (Glatte et al. 1967; Sinclair 30 d et al. 1971; Radziszewski et al. 1988) Testicular injury NOAEL at 3%, Rat and guinea pig 1 — — — 3 3 3 24 h/d, 42 d (Schaefer et al. 1971) SMAC 1996 1.3 1.3 0.7 0.7 0.7 Source: Wong 1996.