Methods for Developing Spacecraft Water Exposure Guidelines (2000) / Chapter Skim
Currently Skimming:
3 Sources and Types of Data for Establishing Spacecraft Water Exposure Guidelines
3 Sources and Types of Data for Establishing Spacecraft Water Exposure Guidelines
Pages 57-74
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 57... ...
Guidelinesfor Developing Spacecraft Maximum Allowable Concentrahonsfor Space Station Contaminants (SMACs) , but with important differences.
|
From page 58... ...
Several types of information are evaluated to develop risk-based SWEGs for water, including data on the physical and chemical properties of the substance; human clinical and epidemiologic studies; animal toxicity data from studies, In which exposure ranges from acute to chronic, to identify toxic and carcinogenic end points; in vitro toxicity studies; and mechanistic studies. Data from oral exposure studies are the most relevant for deriving SWEGs, but dermal absorption and inhalation studies should also be evaluated because exposure from those routes occurs when there are volatile constituents in the water or when water is used for hygiene purposes.
|
From page 59... ...
HUMAN STUDIES Human toxicity data frequently are obtained from epidemiologic studies of low-level, long-term environmental and industrial exposures as wed as short-term exposures, usually to large quantities of toxicants after accidents. These data sometimes provide a basis for estimating a dose-response relationship.
|
From page 60... ...
However, exposure-response data for humans often are not available, and extrapolation from animal data is necessary. The most useful animal studies are those in which the exposure occurs by relevant routes of administration (oral for drinking-water contaminants; dermal absorption and inhalation for contaminants found in water used for purposes of hygiene)
|
From page 61... ...
The relative absorption from water and food must be considered in evaluating animal studies and in estimating human exposure to contaminants in drinking water and water-reconstituted food. Subchronic studies that assess regular treatment with the chemical over 90 days (typically)
|
From page 62... ...
Ideally, toxic effects should be related to several factors, including total dose, number of treatments with the test substance, and frequency of administration. Toxic effects for a specific substance might be different in animals exposed to the contaminant by repeated exposure to low doses over an extended period than they will be in animals exposed to a single, high dose.
|
From page 63... ...
IN VITRO TOXICITY STUDIES Important information can be obtained from studies that investigate adverse effects of chemicals on cellular or subceBular systems in vitro. Systems in which toxicity data have been collected include isolated organ systems (e.g., isolated perfused livers and lungs)
|
From page 64... ...
Extrapolation from industrial thresholds and other related exposure standards for such determinations is limited by the use of tests based on gross toxic effects under conditions of discontinuous exposure that seldom consider the more subtle effects revealed by performance unpairment. Moreover, data on the effects of water contaminants on human performance are rarely available, and the interactive influences of stressful, physically demanding spaceflight environments are undetermined.
|
From page 65... ...
The results of these studies also suggest that taste aversion procedures might provide a novel and selective paradigm for assessing the interactive effects of water contaminants and purification agents. The effectiveness of animal tests for predicting the human response to metal chelators, for example, has been demonstrated in reported studies with BAL (British antilewisite or 2,3-~mercaptopropanol)
|
From page 66... ...
, and there are several publications that provide guidance on evaluating and interpreting reproductive toxicity end points for human health risk assessment (e.g., ILS] 1999; NRC in press)
|
From page 67... ...
The altered gene products primarily involved in carc~nogenesis are generally the proteins that control cell division, growth, and movement, thereby promoting clonal expansion and metastasis. Some of them are transcription factors, tumor suppressors, mitotic check point controllers, chromosome structure stabilizers, DNA damage recogni
|
From page 68... ...
Detection of low levels of mutagenicity combined with positive biomarker data (Perera 1997) provides strong evidence for mutagenic potency.
|
From page 69... ...
Experiments in mechanistic toxicology might include, but not be limited to, studies of routes of administration, absorption, metabolism, excretion, tissue distribution, formation of biologic reactive intermediates, covalent binding to specific macromolecules, physiolog~caDy based pharmacokinetic models, and polymorphisms. The recent development of investigative tools In molecular biology has opened new ways to evaluate mechanisms of toxicity.
|
From page 70... ...
As relevant human data are accumulated they should be incorporated into the SWEGs process. SUMMARY In developing SWEGs, several types of data should be evaluated, including the physical and chemical characteristics of the contaminant, human clinical and epidemiologic studies, in vitro toxicity studies,
|
From page 71... ...
For completeness, developmental effects should be considered in the analyses, even though pregnant astronauts are barred from space flight. Data from oral exposure studies should be used, particularly drinking water and feed studies, in which the duration of exposure approximates human exposure times.
|
From page 72... ...
Gau.1980. Flavor aversions rapidly produced by inorganic lead and triethyl tin.
|
From page 73... ...
.1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants.
|
From page 74... ...
1984. Conditioned taste aversion in the adult rat induced by dietary ingestion of cadmium or cobalt.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.