One-year inhalation toxicity study of formaldehyde in male rats with a damaged or undamaged nasal mucosa

To study the effect of bilateral intranasal electrocoagulation damage on the susceptibility of rats to formaldehyde vapour, male Wistar rats with a damaged or undamaged nasal mucosa were exposed to atmospheres containing 0, 0.1, 1 or 10 ppm formaldehyde vapour during 6 h/day, 5 days/wk for 13 or 52 weeks. Electrocoagulation damage was induced in the anterior third part of the nose. The repair process followed the pattern of wound healing. Loss of turbinates and perforation of the septum were common irreversible findings. After 13 weeks basal cell hyperplasia and squamous metaplasia of the respiratory epithelium, and rhinitis were still visible. After 52 weeks effects attributable to electrocoagulation were slight basal cell hyperplasia and some rhinitis. Major formaldehyde‐related adverse effects in the 10 ppm group not subjected to electrocoagulation included growth retardation, reduced urine production, and rhinitis accompanied by squamous metaplasia of the nasal respiratory epithelium. No adverse effects were seen at 0.1 or 1 ppm in rats with an intact nasal mucosa. The principal untoward effects of formaldehyde in electrocoagulation‐treated rats seen after 13 and/or 52 weeks comprised increase in basal cell hyperplasia, squamous metaplasia of the nasal respiratory epithelium, damage to the olfactory epithelium at 10 ppm, and focal squamous metaplasia of nasal respiratory epithelium at 0.1 and 1 ppm. Major conclusions were: (a) the rat nose damaged by electrocoagulation is more susceptible to the cytotoxic action of formaldehyde than the undamaged nose, (b) 10 ppm formaldehyde has no adverse effect on organs remote to the site of entry in rats with an undamaged nose, and (c) 1 ppm formaldehyde did not visibly affect the intact nasal epithelium.