Development of a Mouse Whole-Body Exposure System from a Directed-Flow, Rat Nose-Only System

Abstract

In many inhalation exposure experiments, such as pharmacokinetic studies in unrestrained pregnant animals, it is desirable to expose unrestrained animals and to remove animals from the exposure system at intermediate time points. A two-tiered, 32-port, directed-flow, nose-only exposure system was modified with extended 0.635-mm stainless steel inlet tubes to create a whole-body, modified nose-only (WB-MNO) exposure system. Individual pregnant CD-1 mice held within a rat nose-only tube were exposed to a well-mixed methanol (MeOH) atmosphere. The volume of an individual mouse (∼30 ml) constituted approximately 5% of the 600-ml tube volume. Maternal MeOH pharmacokinetics were obtained on gestational day 8 following 6-h WB-MNO MeOH exposures at either 10,000 or 15,000 ppm. Results from these WB-MNO exposures were compared with a 6-h, 15,000 ppm MeOH exposure using a Hinners-type 1-m³ whole-body inhalation chamber (WB-H). The WB-MNO exposure atmosphere was produced using a wick generator heated to 29-35°C and a fluid-metering pump. The vapor was mixed with the total air supply (12-15 Umin). Atmospheric MeOH concentrations (mean ± SEM) achieved were 10,224 ± 35 and 15,210 ± 39 ppm for the WB-MNO and 14,980 ± 70 ppm for the WB-H exposures. End-of-exposure maternal plasma MeOH concentrations were 65 ± 25 (10,000 ppm, WB-MNO), 223 ± 23 (15,000 ppm, WB-MNO), and 194 ± 13 mM (15,000 ppm, WB-H). These findings suggest that the WB-MNO system results in maternal MeOH pharmacokinetics that are similar to those observed using more conventional WB-H exposure systems. The WB-MNO should lend itself to numerous additional applications for pharmacokinetic and toxicity studies.