Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants (1992) / Chapter Skim
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'ESTABLISHMENT OF SPACECRAFT MAXIMUM ALLOWABLE CONCENTRATIONS'
'ESTABLISHMENT OF SPACECRAFT MAXIMUM ALLOWABLE CONCENTRATIONS'
Pages 59-96
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From page 59... ...
Exposure at the 1- and 24-hr SMACs might produce such effects as increased respiratory rate from increased carbon dioxide, headache or mild central nervous system effects from carbon monoxide, and respiratory tract or eye irritation from ammonia or sulfur dioxide. The 1- and 24-hr SMACs are exposure levels that should not cause serious or permanent effects.
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From page 60... ...
Chemical-Physical Characteristics of Toxicant The chemical and physical characteristics of a chemical provide valuable information on the dosimetry of the compound within the body and on the likely toxic effects. For example, size and water solubility of inhaled particles strongly influence where the material deposits in the respiratory tract.
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From page 61... ...
Animal Toxicity Studies The data necessary to evaluate the relationship between exposure to a pollutant and its effects on a population are frequently not available from human experience. For many air pollutants, studies in animals have provided the only useful data.
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From page 62... ...
Thus, animals flown in the space shuttle or the space station are likely to be more appropriate surrogates for humans. For example, rats flown aboard Cosmos 1887 showed altered hepatic function.
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Epidemiological Observations Human toxicity data frequently are obtained from epidemiological studies of long-term industrial exposures as well as short-term exposures usually to high levels of toxicants following accidents. These data sometimes provide a basis for estimating a dose-response relationship.
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From page 64... ...
toxicity end points. Dosimetry Deposition of Particles, Gases, and Vapors in the Respiratory Tract Under Microgravity Conditions Aerosols deposit in the respiratory tract of people primarily by the processes of sedimentation, impaction, interception, and diffusion.
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From page 65... ...
Thus, the deposition of small particles, gases, and vapors in the respiratory tract will not be significantly affected by microgravity conditions. As the particle size increases (1-5 nm range)
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From page 66... ...
The space station is a closed system with limited capacity to clear the air of chemical vapors, while the crew contributes to the removal of some chemicals through sequestration and metabolism. Thus, physiologically based pharmacokinetic models of the disposition of inhaled materials should be useful in helping to assess the risk of disease from airborne toxicants in the space station.
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From page 67... ...
Biological markers are indicators of change within an organism that link an exposure to polluted air to subsequent development of an adverse health effect. It is convenient to divide biological markers into three groups: (1)
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From page 68... ...
The biological markers of greatest interest are those that are early predictors of late-occurring effects. Such markers would be invaluable in assessing what levels of pollutants can be tolerated in the space station without causing irreversible deleterious health effects.
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From page 69... ...
Toxicity End Points: Humans and Animals Mortality Short-term exposure to a pollutant at high concentrations may result in death, which may be immediate or delayed. Mortality is a widely used and important index in animal experiments and is also most useful in epidemiological studies as an index of serious health effects.
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From page 70... ...
Chemicals passing through the hepatic circulation may be acted upon to yield detoxification products or may be activated metabolically to become more toxic chemical entities. Metabolic activation of many chemicals leads to liver damage.
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From page 71... ...
Reproductive and Developmental Effects The reproductive and developmental effects of exposure to spacecraft toxicants could be either overt or subtle, and the full complement of potential reproductive effects that could occur in the space station is not known. Adverse effects on factors such as reproductive capacity or behavior in offspring of returned astronauts could escape detection easily against the background of human variation.
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From page 72... ...
The agents that merit special attention are those that interfere with reproduction or development at exposure levels too low to be considered acutely toxic. The concept of target-organ toxicity can be used to focus attention on those chemicals whose most vulnerable target is reproductive function or in utero development.
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From page 73... ...
to establish SMACs is inappropriate particularly if the industrial standards are based on gross toxic effects of the compounds and involve discontinuous exposures. Subtle effects, such as performance impairment, seldomly have been considered in establishing industrial TLVs.
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From page 74... ...
Chemical contaminants in the air of the space station should be assessed by accepted methods for their tumor-promotion potential. In general, promotion appears to be a dose-dependent phenomenon.
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Data from short-term mutagen assays can be helpful in establishing permissible emergency peak concentrations as well as maximum allowable concentrations during long-term exposure.
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From page 76... ...
. Mutations in either male or female germ cells may lead to reproductive and developmental toxicity (Kay and Mattison, 1985; Goldsmith et al., 1984)
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From page 77... ...
Animal models have been extremely valuable in identifying immunotoxic agents and in developing immune profiles, identifying mechanisms of action, and alerting humans to potential health risks associated with exposure to specific xenobiotics, either consumed as drugs or through environmental exposure. Many immunoassays have been validated in animals to detect drug and chemical-induced immunomodulation.
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From page 78... ...
RISK ASSESSMENT Noncarcinogenic Effects Toxicological risk assessment for agents without the capacity to induce carcinogenic or mutagenic effects has traditionally 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. The existence of a so-called "threshold" dose is supported by the fact that the toxicity of many agents is manifest only after the depletion of a known physiological reserve.
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From page 79... ...
First, the committee proposed that NOEL be expressed in milligrams per kilogram of body weight rather than milligrams per kilogram of diet to adjust for dietary consumption patterns. Second, the committee suggested reducing the traditional 100-fold safety factor to only 10-fold in the presence of doseresponse data derived from human studies.
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From page 80... ...
For noncarcinogenic effects, the RfC approach should be the primary method used for setting SMACs. Uncertainty (safety)
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From page 81... ...
This model provides a good description of many forms of human cancer that allow for two to six stages in the carcinogenic process. Assuming that the rates of transition between stages in the multistage model are linearly related to dose, the dose-response curve for the multistage model is linear at low doses.
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From page 82... ...
. The value qf represents an upper bound on the slope of the dose-response curve in the low-dose region and on the excess risk above background associated with a unit measure of dose (such as 1 mg/kg of body weight per day)
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From page 83... ...
Conversely, when a late stage is dosedependent, late-life exposures pose a higher risk. In the context of the classical multistage model, the potential increased excess risk from
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From page 84... ...
(1990) noted that if upper confidence limits on individual estimates of carcinogenic risk of the same order of magnitude simply are summed as an approximation to an upper confidence limit on the total excess risk of a mixture, the upper bound will be conservative.
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From page 85... ...
. The use of a general power function of body weight for species conversion includes bodyweight conversion as a special case with a power of unity.
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From page 86... ...
toxicity studies are available. Higher uncertainty factors also may be used because of the altered physiological status of astronauts in the space shuttle or space station.
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From page 87... ...
Suppose that data from a long-term animal bioassay or human epidemiological study have been used to arrive at an average daily lifetime exposure level, d, of a particular chemical, corresponding to a particular lifetime excess carcinogenic risk. As reported by COT, a lifetime risk level of 10"4 has been used by the U.S.
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From page 88... ...
, that would yield the same total exposure as the average daily lifetime exposure level d, and then apply an adjustment factor, /, based on the multistage model. This approach has been followed by COT (NRC, 1986b)
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From page 89... ...
(5) It must be remembered that extrapolation from a daily lifetime exposure level and conversion to an instantaneous exposure level using Eq.
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From page 90... ...
The continuous exposure guidance levels (CEGLs) recommended by COT for submarines are ceiling concentrations designed to avoid adverse health effects, either immediate or delayed, of more prolonged exposures and to avoid degradation in crew performance that might endanger the objectives of a particular mission as a consequence of continuous exposure for up to 90 days.
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From page 91... ...
. All the documents used to establish previous industrial or public exposure limits for airborne materials should be reviewed for pertinent information before establishing SMACs.
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From page 92... ...
The panoply of all physiological changes considered important demonstrates that the individual astronaut is in an altered homeostatic state. How this altered state modifies reactions to chemicals in the space station environment requires additional information.
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From page 93... ...
The lifetime excess risk of cancer resulting from exposure to a chemical contaminant in space for periods up to 180 days should not exceed 10~4 or other levels acceptable to NASA. The lifetime risk associated with such short-term exposures may be estimated on the basis of a time-weighted average lifetime dose in Eq.
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From page 94... ...
Therefore, it is important to take into account the physiological changes induced in the space crew and the impact of these changes on SMAC values for various contaminants. GENERAL APPROACH TO ESTABLISHING SMACs The first step in producing a document describing the SMAC for a chemical is to collect and review all relevant information available on the compound.
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From page 95... ...
, developmental, carcinogenic, neurotoxic, respiratory, and other organ-related effects -- are evaluated, the most important or most sensitive effects receiving the major attention. For the many compounds, such as upper respiratory tract irritants, for which there are reliable human data and a high degree of confidence that effects from a single exposure will be reversible, then NASA may establish exposure limits directly from the available data.
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From page 96... ...
When data from chronic studies are available, they are used to derive 180-day SMACs, applying safety factors as needed. With carcinogenic chemicals, an estimate of risk is provided for the recommended SMACs.
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