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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1 (1994)

Chapter: Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants

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Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
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Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
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Page 10
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 11
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 12
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 13
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 14
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 15
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 16
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 17
Suggested Citation:"Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants." National Research Council. 1994. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 1. Washington, DC: The National Academies Press. doi: 10.17226/9062.
×
Page 18

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Executive Summary: Spacecraft Maximum Allowable Concentrations for Space Station Contaminants The National Aeronautics and Space Administration (NASA) is pre- paring to launch a manned space station-Space Station Freedom-by the mid-1990's. Because Space Station Freedom will be a closed complex environment, some contamination of its atmosphere is inevitable. Sev- eral hundred chemicals are likely to be found in the closed atmosphere of the space station, most in very low concentrations. Important sources of atmospheric contaminants include metabolic waste products of crew members and off-gassing of cabin materials and equipment. Release of chemicals from experiments performed on board the space station is also a possible source of contamination, and the water reclamation system has the potential to introduce novel compounds into the air. NASA is con- cerned about the health, safety, and functional abilities of crews exposed to these contaminants. This report, prepared by the Committee on Toxicology of the National Research Council's Board on Environmental Studies and Toxicology, is in response to a request from NASA for guidelines to develop spacecraft maximum allowable concentrations (SMACs) for space-station contami- nants. SMACs are used to provide guidance on allowable chemical ex- posures during normal operations and emergency situations. Short-term SMACs refer to concentrations of airborne substances (such as gas, va- por, or aerosol) that will not compromise the performance of specific tasks during emergency conditions lasting up to 24 hr. Exposure to 1- or 24-hr SMACs will not cause serious or permanent effects but may cause 9

10 SMACS FOR SELECTED AIRBORNE CONTAMINANTS reversible effects that do not impair judgment or interfere with proper responses to emergencies such as fires or accidental releases. Long-term SMACs are intended to avoid adverse health effects (either immediate or delayed) and to avoid degradation in crew performance with continuous exposure in a closed space-station environment for as long as 180 days. Chemical accumulation, detoxification, excretion, and repair of toxic insults are thus important in determining 180-day SMACs. ENVIRONMENTAL CONTROL AND LIFE-SUPPORT SYSTEM The environmental control and life-support system (ECLSS) of the space station is designed to control temperature, humidity, and composi- tion of space-station air, including COz removal; recover water; dispose of waste; and detect and suppress fires. Fires are a great potential haz- ard and much attention has been given to suppressing them. A fire sup- pression system is available, but if all else fails, an escape vehicle can be used. A subsystem of the ECLSS, the atmosphere revitalization system, which includes a mass spectrometer called the major constituent ana- lyzer, will analyze cabin air for Oz, Nz, Hz, CO, HzO, and CH4 in all areas of the habitation and laboratory modules. A design criterion for the atmosphere revitalization subsystem is the maintenance of space-station exposure levels below the 180-day SMACs under normal conditions. MODIFICATION OF CONTAMINANT TOXICITY BY ENVIRONMENTAL FACTORS The special conditions of the space environment must be taken into account in defining spacecraft contaminant exposure limits. Deposition of particles is clearly different and lung function and the toxic potential of inhaled particles may be different under microgravity conditions than under full gravity conditions, as on earth. Astronauts will be physically, physiologically, and psychologically compromised for the following reasons: loss of muscle and bone mass, altered immune system, cardiovascular changes, decreased red-blood-

EXECUTIVE SUMMARY 11 cell mass, altered nutritional requirements, behavioral changes from stress, fluid shift in the body, altered hormonal status, and altered drug metabolism. These changes could be important factors in disease sus- ceptibility. The physiological changes noted in spaceflight to date demonstrate that the astronaut is in an altered homeostatic state and thus may be more susceptible to toxic chemicals. How this altered state modifies reactions to chemicals in the space-station environment is not fully known. The physiological changes induced in the space crew are important and their impact must be taken into account in developing SMAC values for vari- ous contaminants. SOURCES AND TYPES OF DATA FOR ESTABLISHMENT OF SMACS The subcommittee recommends the use of data derived from a number of sources in establishing SMAC values. These sources provide infor- mation on a variety of health effects including mortality, morbidity, clin- ical signs and symptoms, pulmonary effects, neurobehavioral effects, immunotoxicity, reproductive and developmental toxicity, pathology, mutagenicity, carcinogenicity, and biochemical and enzyme changes. Chemical-Physical Characteristics of Toxicants The chemical and physical characteristics of a substance provide valu- able information on potential tissue dosimetry of the compound within the body and on its likely toxic effects. Preliminary estimates of the toxic potential of new chemicals also may be derived from known toxicities of structurally similar, well-investigated compounds. However, additional uncertainty (safety) factors must be applied to arrive at safe levels for those congeners that have no dose-response data from intact animals. In Vitro Toxicity Studies Useful information can be obtained from studies conducted to investi-

12 SMACS FOR SELECTED AIRBORNE CONTAMINANTS gate adverse effects of chemicals on cellular or subcellular systems in vitro. Systems in which toxicity data have been collected include isolated organ systems, single-cell systems, and tissue cultures from multicellular organisms maintained under defined conditions or from functional units derived from whole cells. In vitro studies can be used to elucidate the toxic effects of chemicals and to study their mechanism of action. Animal Toxicity Studies The data necessary to evaluate the relationship between exposure to a toxic chemical and its effects on people are frequently not available from human experience; therefore, animal toxicity studies must be relied on to provide information on responses likely to occur in humans. The usefulness of animal data depends in part on the route of exposure and species used. Although inhalation studies are most relevant in assess- ing the toxicity of atmospheric contaminants, data from skin absorption, ingestion, and parenteral studies are also useful. The relevance of animal data to humans may be limited by the absence of information on affected target organs and knowledge of metabolic pathways and pharmacokinet- ics in animals and humans. Clinical and Epidemiological Observations In establishing SMACs for chemicals, dose-response data from human exposure should be used whenever possible. Data from clinical inhala- tion exposures are most useful because inhalation is the most likely route of exposure. Human toxicity data also are available from epidemiologi- cal studies of long-term industrial exposures, from short-term high-level exposures following accidents, or from therapeutic uses of some pharma- ceutical agents. Some of these data provide a basis for estimating a dose-response relationship. Epidemiological studies have contributed to our knowledge of the health effects of many airborne chemical hazards. The limitations of epi- demiology stem from its use of available data. The accuracy of data on health outcomes varies with the source of the information, and records documenting historical exposure levels are often sparse. For example,

EXECUTIVE SUMMARY 13 mortality information derived from death certificates is sometimes inac- curate, and exposure information collected from administrative purposes is limited. Despite these limitations, if the populations studied are large enough and have been exposed to high enough doses over a sufficient period to allow for the expression of disease, epidemiological studies usually provide valuable information on the effects of exposure in hu- mans without resorting to cross-species extrapolation or to exposing hu- mans in an experimental situation to possible injuries from chemical haz- ards. Phannacokinetics and Metabolism Evaluation of the health effects of any chemical in a given environ- ment is greatly facilitated by an understanding of its physiological dispo- sition in the body. Many chemicals require some form of metabolic acti- vation to exert their toxic effects. The formation of reactive metabolites may depend on the level of exposure and the pharmacokinetics of the chemical. Modern pharmacokinetic studies can provide physiologically based models describing disposition of chemicals within organs and tis- sues in the body. The space station is a closed system with limited capac- ity to clear the air of chemical vapors; the crew contributes to the remov- al of the chemicals from the air through sequestration and metabolism. Toxic metabolites may be highly reactive chemically. These metabo- lites are biologically reactive intermediates that may covalently bind to nucleic acids or proteins that in turn, may alter DNA replication or tran- scription. In addition to formation of reactive metabolites, metabolic activity also may lead to formation of species of active oxygen that may damage nucleic acids or proteins or cause lipid peroxidation. The result- ing health effects may range from direct, short-term target-organ toxicity to carcinogenesis. Biological Markers Biological markers are indicators of change within an organism that link exposure to a chemical to subsequent development of adverse health effects. Biological markers within an exposed individual can indicate the

14 SMACS FOR SELECTED AIRBORNE CONTAMINANTS degree of exposure to a pollutant and may provide evidence of the initial structural, functional, or biochemical changes induced by the exposure and, ultimately, the biochemical or physiological changes associated with adverse health effects. Biological markers can be divided into three classes: 1. Biological markers of exposure to pollutants may be thought of as "footprints" that the chemical leaves behind upon interaction with the body. Such markers contain the chemical itself or a metabolic fragment of the chemical and thus are usually chemical-specific. 2. Biological markers of the effects of exposure include the totality of subclinical and clinical signs of chemically induced disease states. The markers of greatest interest are those that are early predictors of serious effects or late-occurring effects. Such markers would be useful in deter- mining what levels of pollutants in the space station can be tolerated without causing irreversible deleterious health effects. 3. Biological markers of increased susceptibility to the effects of ex- posure to pollutants could be used to predict which persons are most likely to be at excess risk as space-station crew members. RISK ASSESSMENT (DEVELOPMENT OF EXPOSURE CRITERIA) The assessment of toxicants that do not induce carcinogenic or muta- genic effects traditionally has been based on the concept that an adverse health effect will not occur below a certain level of exposure, even if exposure continues over a lifetime. Given this assumption, a reference dose intended to avoid toxic effects may be established by dividing the no-observed-adverse-effect level by an appropriate uncertainty factor or set of factors. For carcinogenic effects, especially those known to be due to direct mutagenic events, no threshold dose may exist. However, when carcino- genesis is due to epigenetic or nongenotoxic mechanisms, a threshold dose may be considered. Attempts to estimate carcinogenic risks associ- ated with levels of exposure have involved fitting mathematical models to experimental data and extrapolating from these models to predict risks at doses that are usually well below the experimental range. The multi-

EXECUTIVE SUMMARY 15 stage model of Armitage and Doll is used most frequently for low-dose extrapolation. According to multistage theory, a malignant cancer cell develops from a single stem cell as a result of a number of biological events (e.g., mutations) that must occur in a specific order. Recently, a two-stage model that explicitly provides for tissue growth and cell kinet- ics also has been used in carcinogenic risk assessment. The multistage model, characterized by low-dose linearity, forms the basis for setting SMACs for carcinogens. Low-dose linearity is generally assumed for chemical carcinogens that act through direct interaction with genetic material. ISSUES IN MAKING RECOMMENDATIONS FOR THE ESTABLISHMENT OF SMACS A number of issues need to be considered in developing recommenda- tions for establishing SMACs. These issues include (1) translating animal toxicity data to predict toxicities in humans; (2) determining 30- or 180- day SMACs for carcinogens based on toxicological or epidemiological studies that often involve long-term or lifetime exposure; (3) considering limits set by the Occupational Safety and Health Administration, the American Conference of Governmental Industrial Hygienists, and the National Research Council in developing SMACs; (4) evaluating the tox- icities of mixtures; and (5) modifying risk assessments based on the al- tered environment in the microgravity of space.

Appendix B Reports on Spacecraft Maximum Allowable Concentrations (SMACs) for Selected Airborne Contaminants

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