HISTOPATHOLOGY AND CELL REPLICATION RESPONSES IN THE RESPIRATORY-TRACT OF RATS AND MICE EXPOSED BY INHALATION TO GLUTARALDEHYDE FOR UP TO 13 WEEKS

In addition to being a respiratory tract irritant and cross-linking ag ent, glutaraldehyde has a number of properties in common with the rode nt nasal carcinogen, formaldehyde. The acute and subchronic responses to glutaraldehyde in the respiratory tract of rats and mice were chara cterized using histopathology and epithelial cell labeling index as en d points. Male and female F344 rats and B6C3F1 mice were whole-body ex posed for 1 day, 4 days, 6 weeks, or 13 weeks to 0, 62.5, 125, 250, 50 0, or 1000 ppb glutaraldehyde using a recycling inhalation chamber. Th e respiratory tract, with special reference to the nose, was examined by light microscopy and histoautoradiography. Unit length labeling ind ex (ULLI) was determined by nuclear thymidine labeling for selected si tes, chosen on the basis of histopathology. A small number of animals exposed to 1000 ppb (rats and mice) or 500 ppb (mice) died before the 6-week time point; these deaths were attributed to glutaraldehyde expo sure-associated occlusion of the external nares. Treatment-induced les ions, including epithelial erosions, inflammation, and squamous metapl asia, were confined to the anterior third of the nose and were present in both sexes and species. No histopathological evidence of glutarald ehyde-induced responses was observed in the trachea, central airways, or lungs, while the larynx showed minimal changes. There were clear in creases in ULLI in association with acute and subacute cytotoxic respo nses, with similar concentration-response relationships. Neutrophilic infiltration of the squamous epithelium of the nasal vestibule, presen t in both rats and mice, became progressively more severe with increas ing exposure time and was associated with increased ULLI. The latter r esponses were generally most severe at the higher glutaraldehyde expos ure concentrations, while in female mice they were present at all conc entrations of glutaraldehyde studied. Lesions induced by glutaraldehyd e were more anterior in the nose than those reported for formaldehyde, they differed in character, and no evidence of ''pre-neoplastic'' les ions or karyomegaly, reported for formaldehyde, was observed with glut araldehyde. (C) 1994 Society of Toxicology.