ToxSci Advance Access originally published online on June 16, 2004
Toxicological Sciences 2004 81(1):216-224; doi:10.1093/toxsci/kfh198
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Toxicological Sciences vol. 81 no. 1 © Society of Toxicology 2004; all rights reserved.
Uptake of Inspired Propylene Oxide in the Upper Respiratory Tract of the F344 Rat
* Department of Pharmaceutical Sciences, School of Pharmacy, 372 Fairfield Rd., Box U-2092, University of Connecticut, Storrs, Connecticut 06269-2092; Lyondell Chemical Company, Houston, Texas 77010; and Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674
Received March 17, 2004; accepted June 3, 2004
Propylene oxide (1,2-epoxypropane) is a nasal toxicant and weak site-of-contact carcinogen in the rodent. The current study was aimed at providing quantitative information on upper respiratory tract (URT) dosimetry of this vapor. Since depletion of nasal non-protein sulfhydryls (NPSH) may be important in the toxicity of this vapor and may serve as a biomarker for delivery of propylene oxide to nasal tissues, measurements of respiratory and olfactory NPSH content after propylene oxide exposure were also made. Towards these ends, uptake of this vapor was measured in the surgically isolated URT of the F344 rat at constant velocity inspiratory flow rates of 50 or 200 ml/min throughout a 60-min exposure. Immediately after exposure, nasal respiratory and olfactory tissues were removed and analyzed for NPSH content. Propylene oxide was scrubbed from the airstream with moderate efficiency in the isolated URT. Similar uptake efficiencies were observed at inspired concentrations of 25, 50, 100, and 300 ppm, averaging 25 and 11% at flow rates of 50 and 200 ml/min, respectively. After 1-h exposure to concentrations of 100 ppm or more, statistically significant depletion of nasal respiratory mucosal NPSH was observed. Nasal respiratory mucosal NPSH levels averaged approximately 90, 70, 50, 40, and 15% of control levels after 1-h exposure to 25, 50, 100, 300, or 500 ppm propylene oxide. Olfactory mucosal NPSH levels also generally decreased at 300 or 500 ppm propylene oxide, but did not demonstrate statistically significant, consistent changes after propylene oxide exposure.
Key Words: propylene oxide; upper respiratory tract; F344 rat; nasal non-protein sulfhydryls.
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