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chambers by huddling together or covering their noses with their own fur. Losses of particulate aerosols to the interior walls of the chambers are also frequently a problem.

Head-only exposure systems eliminate many of these problems. The disadvantages of these systems are that the animal must be restrained and is stressed or anesthetized, and there is difficulty in forming an adequate seal.

Nose- or mouth-only exposure systems further limit exposure to the oral cavity and the respiratory tract. Masks or the use of catheters in the nose are generally used with larger animals. Lung and partial-lung-only exposure systems such as endotracheal tubes are employed to bypass the upper respiratory tract and to directly expose the lung. Most of these methods require that the animal be anesthetized, which may alter normal respiration. Other disadvantages include disruption of normal airflow by the presence of tubes in the airways and the loss of normal humidification and thermal regulation of the inspired air caused by bypassing the upper respiratory tract.

Intratracheal instillation is an alternative to inhalation for evaluating the effects of individual compounds on the respiratory system. While there are several advantages in employing this bioassay technique, it is also known that the distribution of test material to respiratory tissue may differ from that which would be obtained by actual inhalation exposures. Instillation of an aqueous suspension of radiolabeled particles resulted in a less uniform deposition than inhalation (Brain et al., 1976).

Animal Models in Inhalation Studies

The selection of an appropriate animal model for inhalation studies with potentially toxic agents is compounded by the fact that one of the major functions of the mammalian sensory apparatus is to limit the exposure to toxic agents either by altering breathing or by producing avoidance behavior (Alarie, 1973; Wood, 1978). Also, the selection of animal species and strains for inhalation exposure studies requires thorough evaluation. The use of several (at least three) animal species, several dose levels, and animals that metabolize the suspect toxin in a similar manner to humans is recommended for those studies that attempt to evaluate human hazards (Stuart, 1976). The appropriate animal model should have (1) a similarity to the human respiratory tract with



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