Pathology and cell proliferation induced by intra-nasal instillation of aldehydes in the rat: comparison of glutaraldehyde and formaldehyde.

The relative toxicities of formaldehyde and glutaraldehyde to the rat nasal epithelium were determined following intra-nasal instillation of aqueous solutions of these compounds into one nostril of male Fischer 344 (F-344) rats. Lesions identical in appearance to those resulting from acute inhalation exposure to formaldehyde were induced by both compounds in a concentration-dependent manner. Treatments included India ink or 1 M methylene blue (for instillation deposition studies); sterile saline (vehicle control); 40, 200, 400, and 800 mM formaldehyde; and 10, 20, and 40 mM glutaraldehyde. Dye-treated rats were sacrificed immediately, and nasal passages were examined to determine the localization of instilled materials. Three days after treatment, all other animals received a single ip injection of 5-bromo-2'-deoxyuridine 2 hr prior to sacrifice, and the nasal passages were prepared for histopathology and cell proliferation studies. While sterile saline and 10 mM glutaraldehyde induced no significant epithelial changes, 20 and 40 mM glutaraldehyde induced extensive lesions in the treated side of the nose. Aldehyde-induced lesions included inflammation, epithelial degeneration, respiratory epithelial hypertrophy, and squamous metaplasia in association with marked increases (3-8-fold) in labeling index for both compounds. Formaldehyde induced similar lesions but required concentrations of 200 mM or more to elicit a toxic response. Thus, glutaraldehyde is approximately an order of magnitude more toxic to the nasal epithelium than formaldehyde. These studies also indicate that the nose is very resistant to the aldehydes studied, requiring instillation of millimolar concentrations before toxic responses occurred.