Cover Image

PAPERBACK
$45.52



View/Hide Left Panel

SPACECRAFT WATER EXPOSURE GUIDELINES FOR SELECTED CONTAMINANTS


VOLUME 3



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 1
SPACECRAFT WATER EXPOSURE GUIDELINES FOR SELECTED CONTAMINANTS VOLUME 3

OCR for page 1

OCR for page 1
Introduction Construction of the International Space Station (ISS)—a multinational ef- fort—began in 1999. In its present configuration, the ISS is expected to carry a crew of three to six astronauts for up to 180 days (d). Because the space station is a closed and complex environment, some contamination of its internal atmos- phere and water system is unavoidable. Several hundred chemical contaminants are likely to be found in the closed-loop atmosphere and recycled water of the ISS. To protect space crews from contaminants in potable and hygiene water, the National Aeronautics and Space Administration (NASA) requested that the National Research Council (NRC) provide guidance on how to develop water exposure guidelines and subsequently review NASA’s development of the expo- sure guidelines for specific chemicals. The exposure guidelines are to be similar to those the NRC established for airborne contaminants (NRC 1992, 1994, 1996a,b, 2000a). The NRC was asked to consider only chemical contaminants and not microbial agents. The NRC convened the Committee on Spacecraft Ex- posure Guidelines to address this task. The Committee published its first report, Methods for Developing Spacecraft Water Exposure Guidelines, in 2000. A sec- ond report, Spacecraft Water Exposure Guidelines for Selected Contaminants, Volume 1 (2004a), used these guidelines to set exposure levels for nine chemi- cals: chloroform, dichloromethane, di-n-butyl phthalate, di(2-ethylhexyl)phtha- late, 2-mercaptobenzothiazole, nickel, phenol, N-phenyl-beta-naphthylamine, and silver. Spacecraft Water Exposure Guidelines for Selected Contaminants, Volume 2 (2007a), presented SWEGs for acetone, alkylamines, ammonia, bar- ium, cadmium, caprolactam, formaldehyde, formate, manganese, total organic carbon, and zinc. This report presents spacecraft water exposure guidelines (SWEGs) for antimony, benzene, ethylene glycol, methanol, methyl ethyl ke- tone, and propylene glycol. SWEGs are to be established for exposures of 1, 10, 100, and 1,000 d. The 1-d SWEG is the concentration of a substance in water that is judged to be ac- ceptable for the performance of specific tasks during rare emergency conditions lasting for up to 24 h. The 1-d SWEG is intended to prevent irreversible harm and degradation in crew performance. Temporary discomfort is permissible pro- 3

OCR for page 1
4 Spacecraft Water Exposure Guidelines vided judgment, performance, and ability to respond to an emergency are not affected. Longer-term SWEGs are intended to prevent adverse health effects (immediate or delayed) and degradation in crew performance that could result from continuous exposure in closed spacecraft for as long as 1,000 d. In contrast to the 1-d SWEG, longer-term SWEGs are intended to provide guidance for exposure under the expected normal operating conditions in spacecraft. WATER CONTAMINANTS Water used in NASA’s space missions must be carried from Earth or gen- erated by fuel cells. The water is used for drinking, food reconstitution, oral hy- giene, other hygienic uses (hand washing, showers, urine flushing), and oxygen generation. Because of plans for longer spaceflights and habitation of the ISS, water reclamation, treatment, and recycling are required. Water for long space- flights can be reclaimed from several onboard sources, including humidity con- densate from the cabin, hygiene water (shower and wash water), and urine. Each of those sources has a variety of contaminants. Humidity condensate will have contaminants released into the cabin from crew activities (for example, 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, and from routine in-flight use of the crew health care system. Wash water will in- clude detergents and other personal hygiene products. Urine contains electro- lytes, small-molecular-weight proteins, and metabolites of nutrients and drugs. It is chemically treated and distilled before recycling, which causes a variety of by-products to be formed. Other sources of chemical contaminants include me- chanical leaks, microbial metabolites, payload chemicals, biocidal agents added to the water to retard bacterial growth (such as silver and iodine), fouling of the filtration system, and incomplete processing of the water. It is also possible that contaminants in the spacecraft atmosphere will end up as toxic substances in the water system. The air and water systems of the ISS constitute a single life-support system, and the use of condensate from inside the cabin as a source of drinking water could introduce some unwanted substances into the water system. SUMMARY OF THE REPORT ON METHODS FOR DEVELOPING SWEGs Data In developing SWEGs, several types of data should be evaluated, includ- ing data on (1) the physical and chemical characteristics of the contaminant, (2) in vitro toxicity studies, (3) toxicokinetic studies, (4) mechanistic studies, (5)

OCR for page 1
5 Introduction animal toxicity studies conducted over a range of exposure durations, (6) genotoxicity studies, (7) carcinogenicity bioassays, (8) human clinical and epi- demiology studies. All observed toxic effects should be considered, including mortality, morbidity, functional impairment, specific organ system toxicities (such as renal, hepatic, and endocrine), neurotoxicity, immunotoxicity, repro- ductive toxicity, genotoxicity, and carcinogenicity. Taste and odor thresholds are also relevant end points for setting SWEGs. Data from oral exposure studies should be used—particularly drinking wa- ter and feed studies in which the duration of exposure approximates anticipated human exposure times. Gavage studies can also be used, but they should be in- terpreted carefully because they involve the bolus administration of a substance directly to the stomach within a brief period. Such exposure could result in 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 ab- sorption and inhalation studies should also be evaluated, because exposure from those routes occurs 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 micro- gravity. Risk Assessment Several risk assessment methods can be used to derive SWEGs. Risk as- sessments for exposure to noncarcinogenic substances traditionally have been based on the premise that an adverse health effect will not occur below a spe- cific 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 uncer- tainty factors. This method requires making judgments 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. Estimating car- cinogenic risk involves fitting mathematical models to experimental data and extrapolating to predict risks at doses that are usually well below the experimen- tal range. A linearized form of the multistage model has historically been used 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 (for

OCR for page 1
6 Spacecraft Water Exposure Guidelines example, mutations) that must occur in a specific order. Other models, such as two-stage clonal expansion models, have been used in cancer risk assessment. EPA’s Guidelines for Carcinogen Risk Assessment (EPA 2005) also introduce modifications to the assessment process. An alternative to the traditional NOAEL and LOAEL risk assessment methods that are used to set carcinogenic and noncarcinogenic concentrations 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% to 10% (BMDL01 and BMDL10), that can be estimated from modeled data with little or no extrapolation outside the experimental dose range. The BMDL01 and BMDL10 are defined as the statistical lower confidence limits of doses that cor- respond to excess risks of 1% and 10% above background concentrations, re- spectively, and these are often used as a point of departure for estimating doses thought to be of negligible risks. Use of the lower confidence limit provides a suitable method to account for sampling variability. However, the use of a cen- tral estimate of the BMD, with incorporation of an additional uncertainty factor to account for experimental variation, may be more appropriate for certain kinds of data. Like the NOAEL and LOAEL, the BMDL01 and BMDL10 are points of departure for establishing exposure guidelines and should be modified by appro- priate exposure conversions and uncertainty factors. Scientific judgment is often a critical, overriding factor in applying the methods described above. It is recommended 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 circum- stances dictate, the other, more traditional approaches should be used. Special Considerations for NASA When deriving SWEGs, by either the NOAEL/LOAEL or the BMD ap- proach, it is 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.1 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 BMDL10 instead of BMDL01 (or a LOAEL in- stead of a NOAEL); to account for experimental variation; and to adjust for spaceflight factors that could alter the toxicity of water contaminants. The latter 1 Two liters per day was used as the default for drinking water consumption, although this quantity may not be applicable in all situations.

OCR for page 1
7 Introduction factors are used to account for uncertainties associated with microgravity, radia- tion, 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 sensiti- zation to cardiac arrhythmias, 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, spaceflight un- certainty factors should be used when available information on a substance indi- cates 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 vari- able 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 popula- tion typically consists of healthy nonpregnant adults, the committee believes that an uncertainty factor for intraspecies differences should be used only if there is evidence that some individuals could be especially susceptible to a contaminant. These differences could be observed among astronauts who possess genetic polymorphisms for well-established genes. 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. REVIEW OF SWEG REPORTS NASA is responsible for selecting the water contaminants for which SWEGs will be established and for developing documentation on how SWEG values were determined. As described above, the procedure for developing SWEGs involves identifying toxicity effects relevant to astronauts and calculat- ing exposure concentrations on the basis of those end points. The lowest expo- sure concentration is selected as the SWEG, because the lowest value would be expected to protect astronauts from manifesting other effects as well. To ensure that the SWEGs are developed in accordance with the NRC guidelines (2000b), NASA requested that the NRC committee independently

OCR for page 1
8 Spacecraft Water Exposure Guidelines review NASA’s draft SWEGs documents. NASA’s draft documents summarize data relevant to assessing risk from exposure to individual contaminants in water only; they are not comprehensive reviews of the available literature on specific contaminants. Furthermore, although the committee is mindful that contami- nants will be present as mixtures in drinking water and the potential exists for interactions, it was asked to consider each chemical on an individual basis. The committee reviews NASA’s SWEG documents and provides comments and recommendations in a series of interim reports (see NRC 1999, 2000c,d,e, 2001, 2002, 2003, 2004b,c, 2005a,b, 2006a,b, 2007b,c, 2008). The committee reviews NASA’s documents as many times as necessary until it is satisfied that the SWEGs are scientifically justified. Because of the enormous amount of data presented in the SWEG reports, the NRC committee cannot verify all the data NASA used. The NRC committee relies on NASA for the accuracy and completeness of the toxicity data cited in the SWEG reports. This report is the third volume in the series Spacecraft Water Exposure Guidelines for Selected Chemicals. SWEG reports for antimony, benzene, ethyl- ene glycol, methanol, methyl ethyl ketone, and propylene glycol are included in the appendix of this report. The committee concludes that the SWEGs developed in those documents are scientifically valid values based on the data NASA re- viewed and are consistent with the NRC (2000b) guideline report. SWEG re- ports for additional chemicals will be presented in later volumes. REFERENCES EPA (U.S. Environmental Protection Agency). 2005. Guidelines for Carcinogen Risk Assessment. EPA/630/P-03/001F. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC. March 2005 [online]. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=116283 [accessed August 1, 2008]. NRC (National Research Council). 1992. Guidelines for Developing Spacecraft Maxi- mum Allowable Concentrations for Space Station Contaminants. Washington, DC: National Academy Press. NRC (National Research Council). 1994. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Volume 1. Washington, DC: National Academy Press. NRC (National Research Council). 1996a. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Volume 2. Washington, DC: National Academy Press. NRC (National Research Council). 1996b. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Volume 3. Washington, DC: National Academy Press. NRC (National Research Council). 1999. Letter Report 1 on Spacecraft Water Exposure Guidelines. Washington, DC: National Academy Press.

OCR for page 1
9 Introduction NRC (National Research Council). 2000a. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Volume 4. Washington, DC: National Academy Press. NRC (National Research Council). 2000b. Methods for Developing Spacecraft Water Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2000c. Letter Report 2 on Spacecraft Water Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2000d. Interim Report 3 on Spacecraft Water Expo- sure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2000e. Interim Report 4 on Spacecraft Water Expo- sure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2001. Interim Report 5 on Spacecraft Water Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2002. Interim Report 6 on Spacecraft Water Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2003. Interim Report 7 on Spacecraft Water Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2004a. Spacecraft Water Exposure Guidelines for Selected Contaminants. Volume 1. Washington, DC: National Academy Press. NRC (National Research Council). 2004b. Interim Report 8 on Spacecraft Water Expo- sure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2004c. Interim Report 9 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2005a. Interim Report 10 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2005b. Interim Report 11 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2006a. Interim Report 12 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2006b. Interim Report 13 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2007a. Spacecraft Water Exposure Guidelines for Selected Contaminants. Volume 2. Washington, DC: National Academy Press. NRC (National Research Council). 2007b. Interim Report 14 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2007c. Interim Report 15 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press. NRC (National Research Council). 2008. Interim Report 16 on Spacecraft Exposure Guidelines. Washington, DC: National Academy Press.

OCR for page 1