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The development and evaluation of a new aerosol irritant assay with minimal animal stress. Karwowski, Andrzej Stanislaw

Abstract

Current methods evaluate pulmonary irritants by placing experimental animals in closed chambers and exposing them to fixed concentrations of irritants for fixed periods of time. This unfortunately results in significant amounts of physical and psychological distress for the animals since they are trapped in the noxious environment without any possibility of escape. The objective of this project was to develop a new assay to evaluate pulmonary irritants in mice, while minimising the stress experienced by the animals. Thus, this assay was based on the principle of avoidance. The Minimal Animal Stress Irritant Assay Chamber (MASIAC) consists of two symmetrical chambers separated by a central disc with an opening, through which the mice can move freely. An irritant aerosol is introduced into one chamber and a control (non-irritating) aerosol into the other. If the animals feel any irritation or discomfort because of the irritant aerosol, they have the opportunity to escape the environment as soon as they detect it. The MASIAC was evaluated and the results indicate that it is an effective, reproducible and sensitive assay. Analysing the EC50s of 112 mice, they were found to be logio-normally distributed, with a mean of -1.57 and standard deviation of 0.48. The irritation that the MASIAC detects is not limited to any particular type of irritant, because it has the potential to detect any form of discomfort that the mice perceive. Since a group of mice were tested at the same time, the influence of the group on the responses of the mice was investigated. It was found that the mice tended to avoid clustering together. When multiple experiments were performed on the same group of animals, it was found that the mice were either sensitised to the irritant, or they learned to avoid it. There are a number of possible avenues for future research for the MASIAC, including environmental pollution, human asthma, and as a quantifiable model of learning.

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