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Male and female albino Wistar rats were exposed to concentrations of 0, 1, 10 or 20 ppm formaldehyde vapour during 6 h/day, 5 days/wk for 13 weeks. Treatment-related changes observed at 20 ppm included in both sexes: stared coats, uncoordinated locomotion and excitation during the first 30 minutes of each exposure, yellowing of the fur, growth retardation, a decreased level of plasma protein, severe and extensive karatinized stratified squamous metaplasia of the nasal respiratory epithelium, and focal degeneration and squamous metaplasia occasionally accompanied by keratinization of the olfactory epithelium; in males only; increased activities of plasma aspartate amino transferase (ASAT), alanine amino transferase (ALAT) and alkaline phosphatase (ALP) and squamous metaplasia of the laryngeal epithelium. Lesions seen at 10 ppm included yellowing of the fur and moderate squamous metaplasia of the nasal respiratory epithelium. The only change observed in three out of twenty 1 ppm exposed animals that might or might not be treatment-related was minimal focal epithelial hyperplasia and squamous metaplasia of the respiratory epithelium lining the nasal septum and maxillary turbinates. No histopathological evidence of hepatotoxicity was detected in any of the formaldehyde-treated groups. An in vivo/in vitro cell proliferation study showed an increase in [3H]-thymidine labeling index of the respiratory epithelium lining the nasoturbinates of rats exposed to 10 or 20 ppm formaldehyde on three successive days, whereas at the 1 ppm level the labeling index was similar to that of controls. It was concluded that under the conditions of the present 13-week inhalation study, formaldehyde at concentrations up to 10 ppm was not hepatotoxic to rats. At the 20 ppm formaldehyde level, a slight effect on the liver of male rats cannot be completely excluded. The study was inconclusive with respect to 1 ppm formaldehyde being a cytotoxic or a no-cytotoxic effect level for the nasal epithelium.

This study gives additional data which indicate that glutathione-mediated metabolism is of minor importance in humans exposed to TRI. In spite of indications to the contrary, significant metabolism of the cysteine conjugate via beta-lyase, which could result in a toxic metabolite, cannot be ruled out completely.

Male Wistar rats were exposed for 4 weeks, 5 days a week, to 0 (controls), 5 or 10 ppm formaldehyde continuously (8 hours a day), or to 10 or 20 ppm formaldehyde interruptedly (eight 30 min exposure periods separated by 30 min non-exposure periods). Histopathology and cell proliferation studies indicated that under the conditions of exposure used, concentration rather than the total dose of formaldehyde determined the severity of the cytotoxic effects on the nasal epithelium.