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Cytotoxic and adaptive effects in rat nasal epithelium after 3-day and 13-week exposure to low concentrations of formaldehyde vapour

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Author: Zwart, A. · Woutersen, R.A. · Wilmer, J.W.G.M. · Spit, B.J. · Feron, V.J.
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:Toxicology, 1, 51, 87-99
Identifier: 230510
Keywords: formaldehyde · animal experiment · cytotoxicity · histology · inhalation · nonhuman · nose mucosa · priority journal · rat · Adaptation, Physiological · Animal · Cell Division · Epithelium · Female · Formaldehyde · Male · Microscopy, Electron · Mucociliary Clearance · Nose · Rats · Rats, Inbred Strains · Support, Non-U.S. Gov't · Volatilization


To study in detail possible effects of low concentrations of formaldehyde on the nasal epithelium, Wistar rats were exposed to 0, 0.3, 1 and 3 ppm formaldehyde vapour for 6 h/day, 5 days/week during 3 days or 13 weeks, using in vivo [3H]thymidine labeling for cell proliferation studies, and light and electron microscopy for detecting morphological effects. Compound related histopathological nasal changes varying from epithelial disarrangement to epithelial hyperplasia and squamous metaplasia were found in the 3 ppm group, and were restricted to a small area of the anterior part of the nose which is normally covered with respiratory epithelium. These changes were confirmed by electron microscopy and were not observed in the other groups. Increased cell turnover in the same anterior location confirmed high mitotic activity in the 3 ppm group after 3 days and 13 weeks of exposure. At a slightly more posterior level in the nose a transient response in cell turnover was observed. After 3 days of exposure a nearly log-linear relationship was found between cell turnover and exposure concentration reaching a 10-fold increase in the 3 ppm group, and suggesting challenge of the mucociliary and/or regenerative defence systems not only at 3 ppm but also at 0.3 and 1 ppm. After 13 weeks of exposure mean turnover rates in all exposed groups were markedly lower than after 3 days, and the mean rates of the formaldehyde-exposed groups tended to be below that of controls. The variation in turnover rate after 13 weeks had increased in a concentration related way, suggesting individual variation in adaptation. The most likely adaptive mechanism at this more posterior level of the nose seemed to be the mucociliary defence apparatus. Chemicals/CAS: formaldehyde, 50-00-0; Formaldehyde, 50-00-0