Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents Appropriate Use of Animal Models (2006) / Chapter Skim
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5 Experimental Design
5 Experimental Design
Pages 33-40
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5 Experimental Design DELIVERY OF DOSE Inhalation In this chapter, we discuss the advantages and disadvantages of existing methods for delivering a dose of an aerosolized bioterrorism agent in animal models. The first method is inhalation delivery, which often entails the whole-body approach.
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34 DEVELOPING COUNTERMEASURES AGAINST AEROSOLIZED AGENTS aerosol dose from their own fur or that of other animals. To reduce variability, the Committee recommends that food should be removed during aerosol exposure.
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EXPERIMENTAL DESIGN 35 significantly increase aerosol delivery to the lungs of rhesus macaques compared to nebulization-only delivery to their mouths (Beck and others 2002)
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Microsprayers are commercially available for mice and larger mammals, including nonhuman primates, and can be introduced into the lungs inside of a bronchoscope, which also aids visualization and targeting. Like intratracheal instillation, the delivered dose can be precisely controlled.
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As the studies used to determine the LD values usually use a relatively limited number of animals (especially in the case of nonhuman primates) , these upper and lower bounds estimated from a probit analysis are very large.
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. At the Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents Workshop, some details were presented on the LD50 that the U.S.
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It should also include the species, stock, and strain of the laboratory animal used. In the case of nonhuman primates, it is necessary to include the source and country of origin of the animals (Flick-Smith and others 2005)
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Most of the preceding discussion has assumed that standard models of exposure are available for aerosolized agents -- i.e., a fixed method for generation of an aerosolized agent and a set route of administration. Validation of such models across species is needed so that one is not comparing intranasal administration in one animal model with aspiration in another.
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