Development and characterization of an oro-nasal inhalation plethysmography mask exposure system

Abstract

An oro-nasal inhalation plethysmography mask exposure system (ONIPMES) was developed to challenge nonhuman primates and rabbits with biological agents while determining real-time respiratory parameters. The system included novel challenge plethysmography and sample collection masks that delivered aerosol directly to the breathing zone of the animals and to the sample collection probes. Challenge plethysmography masks were fitted with a differential pressure transducer that interfaced with a signal amplifier and computer software to quantify respiratory tidal volume, frequency, and minute volume. Challenge plethysmography masks were calibrated and verified with certified registered gas-tight syringes. Accuracy was determined from simultaneous comparison tests between the challenge plethysmography mask and head-out plethysmographs using live animals. For cynomolgus macaques, the mean differences in tidal volume, frequency, and minute volume were 4.20 ± 0.872 mL, 3.50 ± 3.15 breaths per minute (bpm), and 99.3 ± 91.7 mL/min. For New Zealand white rabbits, the mean differences in tidal volume, frequency, and minute volume were 1.13 ± 0.551 mL, 1.07 ± 0.404 bpm, and 209.3 ± 97.37 mL/min. Standardized tests were used to characterize the inhalation exposure system. The fractional leak rate was 4.17 × 10−5 min−1. The theoretical T99 was 1.694 min and the observed T99 was 0.588 min. Mask to mask spatial variation was 0.9%. The particle size distribution (PSD), mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD) of a 25 mg/mL saline solution was 1.2 ± 0.01 µm and 1.9 ± 0.20. The ONIPMES minimizes dermal and ocular contamination and multiple species may be used.