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ToxSci Advance Access published online on June 16, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh198
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received March 17, 2004
Accepted June 3, 2004

Respiratory Toxicology

Uptake of Inspired Propylene Oxide in the Upper Respiratory Tract of the F344 Rat

John B. Morris 1*, Marcy I. Banton 2, Lynn H. Pottenger 3

1 Department of Pharmaceutical Sciences, School of Pharmacy, 372 Fairfield Rd., Box U-2092, University of Connecticut Storrs, CT 06269-2092
2 Lyondell Chemical Company, Houston, TX 77010
3 Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674

* To whom correspondence should be addressed. E-mail: morris{at}uconnvm.uconn.edu.


  Abstract

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 sulfhdryls (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 minute 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 hour 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 hour 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.


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