characteristics of an ideal animal model have been summarized (Table 1). The use of small animals wherever possible is both economically beneficial and fosters use of the lowest possible phylogenetic species. Exposure of the model should resemble as closely as possible that of the human, to enable distribution of the chemical xenobiotic to appropriate target organs. Lastly, endpoints of toxicity must be carefully selected to resemble, or have relevance to, those observed in humans. Endpoints should occur with low spontaneous incidence.

TABLE 1

 

Features of an Ideal Animal Model for Environmental Disease

Use of a small animal species

Exposure through a natural route

Similarity in site of lesion development in humans

Similarity in cell type affected

Low incidence of toxicity end point occurrence in controls

Similar biological handling of toxicant (absorption, metabolism, storage, excretion) to humans

Modified from ref. 8.

Attention to design in development of an animal model for pulmonary sensitivity (10) has allowed its use in study of several environmentally related lung disorders. The basic features allowing for exposures and monitoring of responses are presented in Figure 1 and listed in Table 2. Guinea pigs are used since they are readily accessible, small rodents known to demonstrate strong allergic anaphylactic lung responses. Exposure is by inhalation of airborne atmospheres of chemical xenobiotics. Chemical atmospheres are generated in the mixing chamber. The concentration of xenobiotic, as well as the size of aerosol particles is established from samples taken at the ports in the mixing chamber. The desired chemical concentrations are achieved by adjusting the generator feed and airflow exhaust from this chamber.

Animals are exposed to this atmosphere by connecting individual plethysmographs to the mixing chamber using polytetrafluoroethylene (PTFE) tubing. The system is designed to accommodate 4 plethysmographs simultaneously.

Although exposure is predominantly via the inhalation route, dermal contact with the xenobiotic also occurs. Further, through grooming maneuvers and operation of the respiratory escalator, ingestion of the xenobiotic also occurs. Additionally, deliberate exposure through the ingestion route can be provided in this model by incorporating xenobiotics into the food supply placed within, each plethysmograph.

During exposure, animals are neither sedated nor restrained within plethysmographs. The benefit derived from this design is the maintenance of a normal body position and therefore an appropriate breathing pattern of animals. This results in the deposition of inhaled particles in the appropriate regions of the respiratory tract and thereby allows



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