TRAVEL, exploration, and study in space are challenging and fascinating scientific objectives for the 21st century. To be successful in those endeavors, the National Aeronautics and Space Administration (NASA) must continue to develop life support and technology programs for more frequent, complex, and longer missions. Because of the closed environment of spacecraft, an important issue is the inevitable accumulation of contaminants in the air and water systems. To prevent adverse health effects and degradation of work performance, it will be necessary to minimize space crews' exposures to those contaminants.
NASA has established exposure guidelines for airborne contaminants, called spacecraft maximum allowable concentrations (SMACs). SMACs are determined using guidelines developed for NASA by the National Research Council (NRC). However, for water contaminants, NASA's requirements have been based on standards from the U.S. Public Health Service and the U.S. Environmental Protection Agency for public drinking water. Those standards were established to protect the general public and are not always appropriate for application to NASA missions, because exposure conditions in space are different from those on Earth.
NASA requested that the NRC develop guidelines for setting exposure guidance levels for spacecraft water contaminants, similar to those
established for airborne contaminants by the NRC in 1992 (Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants). The NRC was asked to consider only chemical contaminants, not microbial agents. The NRC assigned this task to the Committee on Toxicology. The Subcommittee on Spacecraft Water Exposure Guidelines, a multidisciplinary group of experts, was convened to develop the guidelines presented in this report for calculating exposure levels that will prevent adverse health effects and degradation in crew performance. These guidance levels are called spacecraft water exposure guidelines (SWEGs).
SWEGs are to be established for exposures of 1, 10, 100, and 1000 days. The 1-day SWEG is a concentration of a substance in water that is judged to be acceptable for the performance of specific tasks during rare emergency conditions lasting for periods up to 24 hours. The 1-day SWEG is intended to prevent irreversible harm and degradation in crew performance. Temporary discomfort is permissible as long as there is no effect on judgment, performance, or ability to respond to an emergency. Longer-term SWEGs are intended to prevent adverse health effects (either immediate or delayed) and degradation in crew performance that could result from continuous exposure in closed spacecraft for as long as 1000 days. In contrast with the 1-day SWEG, longer-term SWEGs are intended to provide guidance for exposure under what is expected to be normal operating conditions in spacecraft.
The subcommittee used the NRC's 1992 SMAC guidelines as a general model for developing SWEGs. In addition, the subcommittee considered the following: (1) sources of spacecraft water contaminants, (2) methods to rank the contaminants for risk assessment, (3) relevance of available animal toxicity data for predicting toxicity to humans in space, (4) risk assessment methods for deriving exposure guidelines, (5) methods for modifying risk estimates to account for altered physiologic changes and stresses caused by microgravity, and (6) exposure guidelines established by other organizations.
WATER CONTAMINANT SOURCES
To provide a space crew with an adequate water supply, it is necessary to recycle spacecraft wastewater during long space flights. Water
is needed for drinking, hygienic uses, and oxygen generation. Water on long space flights can be recovered onboard from several sources, including humidity condensate, used hygiene water, and urine. Humidity condensate will likely have the greatest contaminant variability because it will include contaminants released into the cabin from by-products of crew metabolism, food preparation, and hygiene activities; from routine operation of the air revitalization system; from off-gassing of materials and hardware; from payload experiments; from routine in-flight use of the crew health care system; and from other sources. Wash water will include detergents and other personal hygiene products. Urine contains electrolytes, small molecular weight proteins, and metabolites of nutrients and drugs. The urine is chemically treated and distilled before recycling, which causes a variety of by-products to be formed. Other sources of chemical contaminants include mechanical leaks, microbial metabolites, payload chemicals, biocidal agents added to the water to retard bacterial growth, fouling of the filtration system, and incomplete processing of the water.
Contaminants in the atmosphere can also end up as toxic substances in the water system. The air and water systems of the International Space Station constitute a single life support system, and the use of condensate from inside the cabin as a source of drinking water could introduce unwanted substances into the water system.
RANKING CONTAMINANTS FOR RISK ASSESSMENT
Ideally, SWEGs should be established for all chemical substances that might be found in spacecraft water. As a practical matter, it would be difficult to develop SWEGs for the more than 400 chemical species that have been identified on space missions in the past. Priorities are needed among the candidate chemicals for risk assessment. Setting priorities for risk assessment is a function separate from conducting the risk assessments themselves. There are three alternative approaches that NASA can use to select candidate chemicals for risk assessment. One involves a subjective selection of chemicals, in which selection parameters may not necessarily be specified. In this approach, NASA would make qualitative judgments about which chemicals to evaluate. The second approach would be to specify a set of parameters that should be considered when making a selection (such as
the magnitude of routine and accidental exposures, short- and long-term effects, and ability to monitor and control exposure). A third approach would expand on the second by quantifying and weighing parameters and using a formula to calculate priorities for different substances. Each approach has benefits and limitations, and a successful system for selecting a substance might involve a combination of them.
DATA FOR ESTABLISHING SWEGs
In developing SWEGs, several types of data should be evaluated, including data on (1) the physical and chemical characteristics of the contaminant, (2) in vitro toxicity studies, (3) toxicokinetic studies, (4) animal toxicity studies conducted over a range of exposure durations, (5) genotoxicity studies, (6) carcinogenicity bioassays, (7) human clinical and epidemiology studies, and (8) mechanistic studies. All observed toxic effects should be considered, including mortality, morbidity, functional impairment, neurotoxicity, immunotoxicity, reproductive toxicity, genotoxicity, and carcinogenicity.
Data from oral exposure studies should be used, particularly drinking water and feed studies, in which the duration of exposure approximates anticipated human exposure times. Gavage studies can also be used, but they should be interpreted carefully because they involve the bolus administration of a substance directly to the stomach within a brief period of time. Such exposure could induce blood concentrations of contaminants and attendant effects that might not be observed if the administration were spread out over several smaller doses, as would be expected with the normal pattern of water consumption. Dermal absorption and inhalation studies should also be evaluated, because exposure from those routes occur when water is used for hygiene purposes.
There are several important determinants for deriving a SWEG, including identifying the most sensitive target organ or body system affected; the nature of the effect on the target tissue; dose-response relationships for the target tissue; the rate of recovery; the nature and severity of the injury; cumulative effects; toxicokinetic data; interactions with other chemicals; and the effects of microgravity.
There are several risk assessment methods that can be used to derive SWEGs. Risk assessments for exposure to noncarcinogenic substances traditionally have been based on the premise that an adverse health effect will not occur below a specific threshold exposure. Given this assumption, an exposure guidance level can be established by dividing the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level (LOAEL) by an appropriate set of uncertainty factors. This method requires making judgements about the critical toxicity end point relevant to a human in space, the appropriate study for selecting a NOAEL or LOAEL, and the magnitudes of the uncertainty factors used in the process.
For carcinogenic effects known to result from direct mutagenic events, no threshold dose would be assumed. However, when carcinogenesis results from nongenotoxic mechanisms, a threshold dose can be considered. Estimation of carcinogenic risk involves fitting mathematical models to experimental data and extrapolating to predict risks at doses that are usually well below the experimental range. The multistage 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 several biologic events (e.g., mutations) that must occur in a specific order. There also is a two-stage model that explicitly provides for tissue growth and cell kinetics.
An alternative to the traditional carcinogenic and noncarcinogenic risk assessment methods is the benchmark-dose (BMD) approach. The BMD is the dose associated with a specified low level of excess health risk, generally in the risk range of 1%-10% (BMD 01 and BMD10), that can be estimated from modeled data with little or no extrapolation outside the experimental dose range. Like the NOAEL and LOAEL, respectively, the BMD01 and BMD10 are starting points for establishing exposure guidelines and should be modified by appropriate exposure conversions and uncertainty factors.
Scientific judgment is often a critical, overriding factor in applying the methods described above. The subcommittee recommends that when sufficient dose-response data are available, the BMD approach
be used to calculate exposure guidelines. However, in the absence of sufficient data, or when special circumstances dictate, the other, more traditional approaches should be used.
SPECIAL CONSIDERATIONS FOR NASA
When deriving SWEGs, either by the traditional or BMD approach, it will be necessary to use exposure conversions and uncertainty factors to adjust for weaknesses or uncertainties about the data. When adequate data are available, exposure conversions that NASA should use include those to adjust for target tissue dose, differences in exposure duration, species differences, and differences in routes of exposure. Uncertainty factors should also be used to extrapolate animal exposure data to humans, when human exposure data are unavailable or inadequate; to extrapolate data from subchronic studies to chronic exposure; to account for using BMD10 instead of BMD01 (or a LOAEL instead of a NOAEL); to account for experimental variation; and to adjust for space-flight factors that could alter the toxicity of water contaminants. The latter factors are used to account for uncertainties associated with microgravity, radiation, and stress. Some of the ways astronauts can be physically, physiologically, and psychologically compromised include decreased muscle mass, decreased bone mass, decreased red blood cell mass, depressed immune systems, altered nutritional requirements, behavioral changes, shift of body fluids, altered blood flow, altered hormonal status, altered enzyme concentrations, increased sensitization to cardiac arrhythmia, and altered drug metabolism. There is generally little information to permit a quantitative conversion that would reflect altered toxicity resulting from spaceflight environmental factors. Thus, space-flight uncertainty factors should be used when available information on a substance indicates that it could compound one or more aspects of an astronaut's condition that might already be compromised in space.
Another commonly used uncertainty factor is one that accounts for variable susceptibilities in the human population. That uncertainty factor is used to protect sensitive members of the general population, including young children, pregnant women, and the immune compromised. Because the astronaut population is typically composed of
healthy nonpregnant adults, the subcommittee believes that an uncertainty factor for intraspecies differences should only be used if there is evidence that some individuals could be especially susceptible to the contaminant.
EXPOSURE GUIDELINES SET BY OTHER ORGANIZATIONS
Several regulatory agencies have established exposure guidance levels for some of the contaminants of concern to NASA. Those guidance levels should be reviewed before SWEGs are established. The purpose of this comparison would not be simply to mimic the regulatory guidelines set elsewhere, but to determine how and why other exposure guidelines might differ from those of NASA and to assess whether those differences are reasonable in light of NASA's special needs.