In September 2006, overheating of the oxygen generator in the Russian segment of the International Space Station resulted in high concentrations of several aromatic compounds. Samples taken several hours after the incident showed a concentration of benzene in the U.S. segment of 0.5 mg/m3.

TOXIC MECHANISM OF ACTION

Acute benzene toxicity causes gastrointestinal problems and neurotoxicity (HSDB 2005). Chronic benzene toxicity can lead to hematotoxicity. In the body, benzene is metabolized by a hepatic enzyme (CYP2E1) to benzene oxide, which spontaneously forms phenol. Phenol is further metabolized to hydroquinone by the same hepatic enzyme. Hydroquinone and related hydroxy metabolites are converted to benzoquinones by myeloperoxidase in the bone marrow. Benzoquinones are hematotoxic, genotoxic compounds that can be transformed to less toxic hydroxyl metabolites by NAD(P)H: quinone oxidoreductase 1 (Rothman et al. 1997).

SUMMARY OF ORIGINAL APPROACH

James and Kaplan (1996), along with the National Research Council (NRC) Subcommittee on Toxicology, analyzed the acute and chronic toxicity of benzene by assessing available research. They set SMACs based on four categories of benzene toxic effects; nervous system effects, hematologic effects, immunologic effects, and risk of leukemia. The lowest values were selected as the final SMACs, all of which were set to protect the immune system, with the exception of the 180-d SMAC, which was also set to be protective against leukemia. Their analysis of toxic effects followed the guidelines provided to NASA by the NRC Committee on Toxicology, with a few notable exceptions (NRC 1992).

Deviations from defaults require an explanation. Some key deviations from past practices include the following: (1) using a species factor of 3 instead of 10 for effects caused by metabolites of benzene, (2) applying a spaceflight factor to an immunotoxicant because of the immune-modulating effects of spaceflight, (3) applying a radiation uncertainty factor because of benzene’s leukemogenic properties and the relatively high radiation exposure of astronauts, and (4) deviating their analysis from the NRC-recommended linearized multistage model because of uncertainty about the human epidemiology database and variations in low-dose extrapolation methods used by investigators (James and Kaplan 1996). Explanations are provided for specific acceptable concentrations (ACs) below.

1- and 24-h SMACs, 1996

The 1- and 24-h SMACs were set at 10 and 3 parts per million (ppm), re-



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