© 1994 Oxford University Press
research-article |
Histopathology and Cell Replication Responses in the Respiratory Tract of Rats and Mice Exposed by Inhalation to Glutaraldehyde for up to 13 Weeks
* CIIT, P.O. Box 12137. Research Triangle Park. North Carolina 27709
Battelle Pacific Northwest Laboratories P.O. Box 999, MSIN K4-10, Richland, Washington 99352
Chemical Pathology Branch, National Toxicology Program NIEHS, P.O Box 12233, Research Triangle Park, North Carolina 27709
Received November 1, 1993; accepted March 31, 1994
In addition to being a respiratory tract irritant and cross-linking agent, glutaraldehyde has a number of properties in common with the rodent nasal carcinogen, formaldehyde. The acute and subchronic responses to glutaraldehyde in the respiratory tract of rats and mice were characterized using histopathology and epithelial cell labeling index as end points. Male and female F344 rats and B6C3F1 mice were whole-body exposed for 1 day, 4 days, 6 weeks, or 13 weeks to 0, 62.5, 125, 250, 500, or 1000 ppb glutaraldehyde using a recycling inhalation chamber. The respiratory tract, with special reference to the nose, was examined by light microscopy and histoautoradiography. Unit length labeling index (ULLI) was determined by nuclear thymidine labeling for selected sites, 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 exposure-associated occlusion of the external nares. Treatment-induced lesions, including epithelial erosions, inflammation, and squamous metaplasia, were confined to the anterior third of the nose and were present in both sexes and species. No histopathological evidence of glutaraldehyde-induced responses was observed in the trachea, central airways, or lungs, while the larynx showed minimal changes. There were clear increases in ULLI in association with acute and subacute cytotoxic responses, with similar concentration-response relationships. Neutrophilic infiltration of the squamous epithelium of the nasal vestibule, present in both rats and mice, became progressively more severe with increasing exposure time and was associated with increased ULLI. The latter responses were generally most severe at the higher glutaraldehyde exposure concentrations, while in female mice they were present at all concentrations of glutaraldehyde studied. Lesions induced by glutaraldehyde were more anterior in the nose than those reported for formaldehyde, they differed in character, and no evidence of "pre-neoplastic" lesions or karyomegaly, reported for formaldehyde, was observed with glutaraldehyde.