Evaluation of a small whole-body exposure chamber for mice


Authored by  W Teck Tan, S Krishnan, B Phillips, A Kuczaj, J Hoeng, P Vanscheeuwijck

Introduction
Inhalation chambers designed for small exposure groups are useful for the screening and efficacy testing of prototype Reduced-Risk Products or new drugs due to their limited availability and potentially high cost. A SCIREQ InExpose™ whole-body exposure chamber for mice was modified to enable characterization of the test atmosphere within the chamber during exposure, to improve animal loading/unloading procedures, and for mechanical integration with existing systems within our facility. Whole-body exposure mode is a preferred way for inhalation exposure of mice in models which may be sensitive to restraint-based stress effects. The small whole-body exposure chamber (sWBEC) has 16 positions; 15 are used for exposure, and one is used for sample collection to enable characterization of the test atmosphere. This sWBEC has a volume of ~5 L and therefore requires a low amount of the test item to be delivered to the chamber while respecting the minimum air change rate recommended in the Organisation for Economic Co-operation and Development test guidelines.

Methods and Results
Tests were performed to determine the spatial and temporal homogeneity of the aerosol distribution within the sWBEC using an aerosol generated by nebulizing a liquid solution of nicotine (Nic) dissolved in propylene glycol (PG), vegetable glycerine (VG), and phosphatebuffered saline (PBS). The mass median aerodynamic diameter and geometric standard deviation of the aerosol ranged from 1.0–1.5 µm and 1.3–1.8, respectively. Spatial homogeneity was quantified by determining the amount of mass deposited passively onto filter pads placed at various positions within the sWBEC. Passive deposition, as opposed to the active drawing of aerosol out of the chamber, was preferred to avoid altering the flow patterns within the sWBEC. The spatial variation resulted in coefficients of variation (CV) of 14%. Temporal homogeneity was quantified by drawing aerosol from within the sWBEC to determine the concentration of nicotine at five time points distributed over a six-hour period. Passive deposition was not applied here, as the concentration of nicotine in the sWBEC cannot be quantified based on the amount deposited passively on the filter pad. The time to reach 95% of the equilibrium nicotine concentration (t95) was estimated to be ~82 minutes (Figure 1) using the equation described in Pauluhn et al., 2007. Upon reaching saturation, the repeated aerosol samples demonstrated good temporal homogeneity (CV = 2.4%).

Conclusions
Our evaluation of the sWBEC demonstrated that the aerosol distribution within the sWBEC is comparable to that of exposure chambers evaluated by other investigators (O’Shaughnessy et al., 2003; Cheng & Moss 1995). The t95 for nicotine is a parameter that has not been reported prior to this. The presented results solidify the understanding of the system functioning and may serve as a basis for comparing the aerosol dynamics between other exposure chambers.

Tan_Evaluation of a small whole-body exposure chamber for mice_EAC 2019