Subchronic (13-week) inhalation toxicity study of formaldehyde in male rats: 8-hour intermittent versus 8-hour continuous exposures

Male Wistar rats were exposed for 13 weeks, 5 days a week to 0 (controls), 1 or 2 ppm formaldehyde continuously (8 h a day), or to 2 or 4 ppm formaldehyde interruptedly (eight 30-min exposure periods separated by 30-min non-exposure periods a day). Histopathological changes were only found in the nose of animals (interruptedly) exposed to 4 ppm formaldehyde and comprised an increased degree and incidence of disarrangement and squamous metaplasia accompanied by basal cell hyperplasia and occasionally by keratinization of the respiratory epithelium. Two ppm formaldehyde was the non-toxic effect level. Cell proliferation studies demonstrated a slightly higher cell turnover of the nasal respiratory epithelium exposed (interruptedly) to 4 ppm formaldehyde than in controls. It was concluded that under the conditions of repeated exposure to marginally cytotoxic concentrations during a period of 13 weeks the exposure concentration rather than the total 'dose' (= concentration x exposure time) determined the severity of the cytotoxic effects of formaldehyde on the nasal epithelium.