Summary

Human spaceflight is inherently risky, with numerous potential hazards posed at each phase of a mission. Potential health risks during spaceflights include short-term health consequences from being in microgravity, as well as long-term health consequences that arise, or continue, months or years after a flight. Additional health considerations are risks posed by exposure to environmental contaminants onboard spacecraft. Because the International Space Station and spacecraft are closed environments that require recirculation of air and water supplies, some contamination of the air and water will occur. Even with onboard air and water purification systems, chemicals will accumulate in the air and water as they recirculate or are recycled onboard. Therefore, it is necessary for the National Aeronautics and Space Administration (NASA) to identify hazardous contaminants and determine exposure levels that are not expected to pose a health risk to astronauts.

NASA uses spacecraft maximum allowable concentrations (SMACs) and spacecraft water exposure guidelines (SWEGs) to provide guidance on acceptable exposures to air and water contaminants during normal operations and emergency situations. Short-term SMACs and SWEGs are concentrations intended to prevent irreversible harm and degradation in crew performance during rare emergency conditions lasting for periods up to 24 hours. Longer-term SMACs and 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 1,000 days.

The National Academies of Sciences, Engineering, and Medicine have a long history of supporting NASA in the setting of chemical exposure guidelines. Methods for developing SMACs and SWEGs were established in 1992 and 2000, respectively, and exposure guidelines were developed continuously until 2008. In 2015, NASA requested that the Academies resume its assistance to the agency by updating the methods for establishing SMACs and SWEGs. In response to the request, the Academies convened the Committee on Spacecraft Exposure Guidelines, which held two public meetings to get background on the original methods and to gather other relevant information. The committee has focused on identifying refinements that could be made to NASA’s existing procedures that would bring them more in line with advances that have been made in risk assessment. NASA will use the updated methods to reevaluate some of the existing exposure

guidelines and to develop SMACs and SWEGs for new chemicals, and the committee will subsequently review the proposed guidelines to ensure that they are derived in accordance with current risk assessment practices.

REFINING THE PROCESS OF DEVELOPING EXPOSURE GUIDELINES

NASA’s approach to deriving SMACs and SWEGs has followed established risk-assessment practices and will remain largely the same as in the past, but a number of refinements to the process have since been developed to help improve the basis of the exposure guidelines. To establish exposure guidelines, NASA conducts hazard assessments on individual contaminants. The hazard assessment process includes evaluating the scientific literature over a broad range of information, including the physical and chemical characteristics of the contaminant, in vitro toxicity studies, toxicokinetic studies, animal toxicity studies conducted over a range of exposure durations, carcinogenicity bioassays, human clinical and epidemiologic studies, and mechanistic studies. In recent years, other federal agencies have begun implementing procedures for better documenting how they conduct literature-based evaluations, so that other stakeholders and the public can understand and replicate them. The procedures typically include documenting the literature search strategies, specifying the criteria that are used to select studies, and describing how different lines of evidence were integrated to draw conclusions about critical health end points.

Recommendations:

NASA should provide better documentation of its strategy for conducting literature searches and the basis for selecting studies for inclusion in the chemical assessment. For the literature searches, a template should be created to describe the search approach to ensure that relevant information is captured. At a minimum, NASA should specify the databases and sources that were searched, describe the search strategies for each database and source searched, and specify the dates of each search and the publication dates included.

The starting point for calculating SMACs and SWEGs is the dose or exposure concentration associated with a critical effect. Ideally, the point of departure is obtained from human data, but may also be obtained from a well-conducted animal study. When sufficient dose-response data are available, NASA uses quantitative approaches (e.g., benchmark dose modeling) to estimate the dose or concentration associated with a specified response incidence (e.g., 1-10%). Points of departure can also be derived from physiologically based pharmacokinetic models, which can be designed to estimate appropriate dose metrics, such as estimates of human equivalent doses from animal data, to address route-to-route extrapolations,

and to facilitate high-to-low dose extrapolations. In the absence of dose-response data, a no-observed-adverse-effect level or a lowest-observed-adverse-effect level is used. The point of departure is subsequently adjusted by uncertainty factors to account for uncertainties associated with the data.

For noncancer end points, NASA has considered the traditional set of uncertainty factors used in risk assessment, as well as “spaceflight factors” to account for additional uncertainties associated with the physical, physiological, and psychological changes that occur in microgravity. The six spaceflight factors that have been used by NASA are for microgravity effects on bone mineral density, renal stone formation, the cardiovascular system, red-blood-cell formation, immune response, and organoleptic considerations. Such spaceflight factors are applied when the effects of a chemical could be exacerbated by one of these conditions. Data should be used whenever possible to select the magnitude of the uncertainty or spaceflight factor or to eliminate the need for it, including data on similar chemicals, toxicokinetic and toxicodynamic data, or other data that allow quantification of differences or variability.

The committee observed that the direct and indirect effects of microgravity on the liver do not appear to have been routinely considered by NASA in the past. The stresses of spaceflight may affect the normal function of the liver as well as potentially increase its susceptibility to chemical injury, depending on a specific chemical’s mode of toxic action. Thus, it will be prudent to consider a spaceflight factor for hepatic effects in updating or establishing SMACs or SWEGs.

Recommendations:

• NASA should ensure that key decisions made in deriving SMACs and SWEGs are explained and justified. Examples of key decision points are the selection of the point of departure, determining the magnitude of the uncertainty and spaceflight factors, and extrapolation procedures.
• An additional spaceflight factor for susceptibility or exacerbation of effects on liver function should be added to the special spaceflight considerations used in deriving SMACs and SWEGs.
• The values of the uncertainty and spaceflight factors should be selected on the basis of chemical-specific data, to the extent possible. The factors should be considered in context with each other to avoid making duplicative adjustments for the same uncertainty.

SELECTING AND PRIORITIZING CHEMICALS

The options for choosing candidate chemicals for risk assessment remain the same as previously established. One choice is subjective in which selections are made on the basis of informed expert judgment. The second approach provides a slightly more formal approach, in which parameters for making the decision are specified but their weights and interrelationships are not. The third ap-

proach is more formulaic and involves specifying and quantifying the elements that are considered and using a weighting system for ranking contaminants. Overall, the committee found that these and other ranking schemes all involve a mix of data and to some degree expert judgment. The main differences are the specific mix of parameters considered and the extent to which explicit or implicit judgments come together to produce reliable results. The committee concluded that the output of most prioritization schemes is so uncertain that they are only useful in making preliminary screening assessments or classifications and should not be used for sorting contaminants in a specific order.

Recommendation:

The committee endorses NASA’s use of a combination of approaches to select chemicals for risk assessment. The process should be described to support the selection process.