Development of a Nose-only Inhalation Toxicity Test Chamber That Provides Four Exposure Concentrations of Nano-sized Particles

Summary

A nose-only inhalation toxicity chamber capable of testing inhalation toxicity at four different exposure concentrations was designed and validated for flow field uniformity and cross-contamination between the exposure ports for each concentration. Here, we present a protocol to confirm that the designed chamber is effective for inhalation toxicity testing.

Abstract

Using a numerical analysis based on computerized fluid dynamics, a nose-only inhalation toxicity chamber with four different exposure concentrations is designed and validated for flow field uniformity and cross-contamination among the exposure ports for each concentration. The designed flow field values are compared with the measured values from exposure ports located horizontally and vertically. For this purpose, nanoscale sodium chloride particles are generated as test particles and introduced to the inhalation chamber to evaluate the cross-contamination and concentration maintenance among the chambers, for each concentration group. The results indicate that the designed multiconcentration inhalation chamber can be used in animal inhalation toxicity testing without cross-contamination among concentration groups. Moreover, the designed multiconcentration inhalation toxicity chamber can also be converted to a single-concentration inhalation chamber. Further testing with gas, organic vapor, or non-nanoscale particles will ensure the use of the chamber in the inhalation testing of other test articles.

Introduction

Inhalation toxicity testing is the most reliable method for assessing the risks of chemical agents, particles, fibers, and nanomaterials^1,2,3. Thus, most regulatory agencies require the submission of inhalation toxicity testing data when the exposure to chemicals, particles, fibers, and nanomaterials is via inhalation^4,5,6,7,8. Currently, there are two types of inhalation toxicity systems: whole-body and nose-only ....

Protocol

1. Numerical analysis methods

1. Perform the analysis of the flow field inside the chamber according to the geometrical shape, as described in Figure 1 and Table 1¹⁴.
   NOTE: A numerical analysis of the flow field according to the geometric shape predicts the flow of the aerosol and evaluates it as a testable device.
2. Design the chamber with 4 stages x 12 columns, 48 ports in total, where the core is divided into an inner and outer tower, as described in Figure 1B.
   NOTE: Each stage has 12 exposure ports for placing the experimental animals....

Results

Experimental set-up

Figure 1 shows a schematic diagram of a nose-only inhalation chamber system, including a particle generator with an MFC, nose-only chamber, and particle measurement instrument for monitoring the air quality, controller, and exhaust module, based on section 2 of the protocol.

Numerical analysis design

Discussion

Inhalation toxicity testing is currently the best method for evaluating aerosolized materials (particles and fibers), vapors, and gases inhaled by the human respiratory system^14,15. There are two inhalation exposure methods: whole-body and nose-only. However, a nose-only system minimizes exposure by noninhalation routes, such as skin and eyes, and allows testing with minimal quantities of the test article, making it the preferred exposure method recommended by th.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
FLUENT V.17.2	ANSYS		Software
mass flow meter (MFM)	TSI	4043
SMPS (scanning mobility particle sizer)	Grimm	SMPS+C
5-Jet atomizer	HCTM	5JA-1000
Mass flow controller (MFC)	Horiba	S48-32