OBJECTIVE

With NASA’s current focus on exploration missions beyond low Earth orbit to the Moon and Mars, there is a need to derive an acceptable concentration (AC) of xylene in spacecraft atmospheres for 1,000 d, which has not previously been derived. Typical spacecraft concentrations have been 0.48 ppm, and it is not known what the concentrations will be for the newer spacecraft being designed for Mars and Moon missions (NASA, personal communication, May 19, 2008). Spacecraft maximum allowable concentrations (SMACs) for xylene were originally developed and published in Volume 3 of this series, Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, for exposure durations of 1 h, 24 h, 7 d, 30 d, and 180 d (Garcia 1996). This document reviews all available subchronic and chronic duration xylene exposure studies and derives exposure limits acceptable for exposures up to 1,000-d (1,000-d AC). At the same time, NASA will evaluate the need to update the previously published SMACs for up to 180 d based on toxicologic studies published since the last evaluation. NASA will also consider whether the previously used data are suitable for processing by current risk assessment methodologies (such as benchmark dose computations) recommended by the National Research Council (NRC) Committee on Spacecraft Exposure Guidelines.

PHARMACOKINETICS AND METABOLISM

A detailed summary of the pharmacokinetics and metabolism of xylene was presented in the 1996 SMAC document (Garcia 1996). A brief summary is presented here. It has been reported that humans absorb about 60% of the xylene from inhalation exposures over concentrations ranging from 46 to 200 ppm, and the percent retained is independent of the duration of exposure time from 15 min to 8 h in a single day, or after 5 d of 6-h/d exposure. The percent retention varies only slightly among individuals and among the three isomers of xylene (Sedivec and Flek 1976, Riihimäki et al. 1979). Postexposure, 4% to 6% of the amount retained is expired as unchanged xylene. In humans exposed to 100 ppm, the half-lives for elimination of xylene were 0.8 h for the initial phase, 7.7 h for the intermediate phase, and 17.7 h for the slowest phase (Sedivec and Flek 1976).

Monitoring of urine from humans exposed to xylene both experimentally and in the workplace indicates that almost all the absorbed xylene undergoes oxidation of the methyl group by the microsomal mixed function oxidases to yield methylhippuric acid (MHA), which is excreted in the urine (Ogata et al. 1970, Sedivec and Flek 1976, Senczuk and Orlowski 1978, Ogata and Fujii 1979, Riihimäki et al. 1979). Metabolism of xylene does not appear to saturate even at 200 ppm of exposure (Riihimäki et al. 1979). Urinary excretion of MHA correlates well with xylene uptake, so that one can use it to estimate exposure. Physiologically based pharmacokinetic (PBPK) models indicate that the elimination of MHA is linear up to an exposure concentration of 500 ppm (Kaneko et



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