risk assessment for carcinogenic and noncarcinogenic effects, and how to consider the effects of physiological changes induced by microgravity that might enhance the susceptibility of astronauts to certain spacecraft contaminants. The executive summary of that report is contained in Appendix A of this volume.
SUMMARY OF REPORT ON GUIDELINES FOR DEVELOPING SMACS
As described in Appendix A, the first step in establishing SMACs for a chemical is to collect and review all relevant information available on a compound. Various types of evidence are assessed in establishing SMAC values for a chemical contaminant. These include information from (1) chemical–physical characterizations, (2) structure-activity relationships, (3) in vitro toxicity studies, (4) animal toxicity studies, (5) human clinical studies, and (6) epidemiological studies. For chemical contaminants, toxicity data from human studies are most applicable and are used when available in preference to data from animal studies and in vitro studies. Toxicity data from inhalation exposures are most useful for setting SMACs for airborne contaminants because inhalation is the most likely route of exposure.
For most chemicals, actual human toxicity data are not available. Therefore, toxicity data from studies conducted in animals are extrapolated to estimate the potential toxicity in humans. Extrapolation requires experienced scientific judgment. The toxicity data from animal species most representative of humans in terms of pharmacodynamic and pharmacokinetic properties are used for determining SMACs. If data are not available on which species best represents humans, the data from the most sensitive animal species are used to set SMACs. Safety or uncertainty factors are commonly used when animal data are used to estimate a safe level for humans. The magnitude of uncertainty factors depends on the quality of the animal data used to determine the no-observed-adverse-effect level (NOAEL). Conversion from animals to humans is done on a body-weight or surface-area basis. When available, pharmacokinetic data on tissue doses are considered for use in species interconversion.
Based on the review of the toxicity data and the use of appropriate safety factors, SMACs for different exposure periods are developed, and a rationale is provided for each recommendation. One- or 24-hr emergency SMACs are derived from acute exposure toxicity studies whenever possible. Development of 1- or 24-hr SMACs usually begins with providing a SMAC for the shortest exposure of 1 hr. Values for 24-hr SMACs might necessitate using
