Nasal NPSH depletion and propylene oxide uptake in the upper respiratory tract of the mouse.
Propylene oxide is a nasal toxicant and weak site-of-contact carcinogen in the mouse and rat. To aid in inhalation risk assessment of this vapor and to provide data for comparison to the rat, the current study was aimed at providing quantitative information on upper respiratory tract (URT) dosimetry of this vapor in the mouse. Toward this end, uptake efficiencies of propylene oxide were measured in the surgically isolated URT of the male B6C3F1 mouse under constant velocity inspiratory flow conditions at flow rates of 12 and 50 ml/min and exposure concentrations of 25, 50, 100, 300, or 500 ppm. URT uptake efficiencies were measured continuously during 1 h exposure; mice were terminated immediately after exposure and nasal respiratory and olfactory mucosal nonprotein sulfhydryl (NPSH) levels were determined. Propylene oxide was scrubbed with moderate efficiency in the URT, with uptake efficiencies of < or = 33 and < or = 16% at the low and high inspiratory flow rates, respectively. Uptake efficiencies were slightly (approximately 5%) higher at low (25 or 50 ppm) than high (300 or 500 ppm) exposure concentrations, suggesting that a saturable uptake pathway may exist. Nasal tissue NPSH levels were significantly depleted at exposure concentrations of 300 and 500 ppm but not at concentrations of 100 ppm or lower. Similar levels of NPSH depletion were observed in both nasal respiratory and olfactory mucosa. These data from mouse show some key differences when compared with those reported for the rat.
Morris
John B
JB
Toxicology Program, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N. Eagleville Road, Storrs, CT 06269-3092, USA. john.morris@uconn.edu
Pottenger
Lynn H
LH
D000818:Animals; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019570:Inhalation Exposure; D008297:Male; D051379:Mice; D009297:Nasal Mucosa / Q000378:metabolism*; D012137:Respiratory System / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D004852:Epoxy Compounds; D013438:Sulfhydryl Compounds; C009068:propylene oxide