Deposition of acetone vapor in the upper respiratory tract of the B6C3F1 mouse.
Deposition of inspired acetone vapor in the surgically isolated upper respiratory tract (URT) of the anesthetized B6C3F1 mouse was measured under unidirectional constant velocity flow conditions for comparison with our previous studies on the rat, hamster and guinea-pig. Acetone metabolism in mouse nasal mucosal homogenates was examined in vitro. Acetone was metabolized by nasal homogenates via an NADPH-dependent pathway with a Vmax of 12 micrograms/min/whole nose and an apparent Km of 72 micrograms/ml. The enzyme responsible was not identified; however, metabolism was inhibited by pyrazole but not inhibited by metyrapone or incubation under nitrogen. URT deposition efficiency was measured at flow rates of 21, 33 or 70 ml/min and averaged 25, 20 and 14%, respectively; the efficiencies at each flow rate were significantly different (P less than 0.01). Deposition was measured at inspired concentrations ranging from 1,500-20,000 micrograms/liter. Deposition efficiencies were similar at all concentrations; the lack of saturation suggests this vapor was not metabolized when inspired. Kinetic analysis of the deposition data revealed that metabolism rates of inspired acetone were only a small fraction of that measured in vitro, suggesting that in vitro data could not be directly extrapolated to the in vivo setting. Deposition efficiency of acetone in the URT of the mouse was similar to that previously observed in the URT of the F344 rat, but was less efficient than that in the Sprague-Dawley rat and more efficient than that in the hamster or guinea-pig.
Morris
J B
JB
School of Pharmacy, University of Connecticut, Storrs 06269.
D000096:Acetone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009296:Nasal Cavity / Q000378:metabolism* / Q000502:physiology; D009297:Nasal Mucosa / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012119:Respiration / Q000502:physiology
D000096:Acetone