ABSTRACT

INTRODUCTION Inhalation toxicity testing is becoming increasingly important, among other things because of the increasing number of drugs that are administered through the intranasal route to avoid enzymatic and acid breakdown and first pass metabolism in the gastrointestinal mucosa and the liver. The nature and site of damage to the nasal mucosa are influenced by a series of factors related to the airborne substance (dose, exposure concentration, solubility, polarity, diffusion rate, particle size, shape, and density), the exposure pattern (continuous, interrupted, peak loads), the subject (genetic constitution, anatomy of the respiratory tract, respiration rate, detoxification systems), and coexposures (lifestyle, occupation). A great number of chemicals are capable of inducing upper respiratory tract tumors in rodents. Nasal tumors are encountered most frequently, whereas laryngeal tumors are relatively rare (1-5). A large number of nitrosamines are capable of inducing nasal tumors in rats and hamsters (6-9). Furthermore, tumors of the nose develop in experimental animals after exposure to a variety of industrial chemicals such as ethylene dibromide (10), dimethyl sulfate (11), formaldehyde (12), acetaldehyde (13), bis(chloromethyl) ether (14), hexamethylphosphoramide (15), propylene oxide (16,17), phenylglycidyl ether (18), dimethylcarbamoyl chloride (19), epichlorohydrin (20), and vinyl chloride (21).