Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure

Groups of approximately 120 male and 120 female Fischer 344 rats and C57BL/6 X C3H F1 mice were exposed by inhalation to 0, 2.0, 5.6, and 14.3 ppm of formaldehyde gas 6 hr/day, 5 days/week, for 24 months. This exposure period was followed by up to 6 months of nonexposure. Interim sacrifices were conducted at 6, 12, 18, 24, 27, and 30 months. Significant formaldehyde-induced lesions were restricted to the nasal cavity and proximal trachea. The distribution and severity of these lesions were concentration dependent. Rhinitis, epithelial dysplasia, and squamous metaplasia occurred in all exposure groups of rats and in the intermediate and high exposure groups of mice. There was regression of rhinitis, dysplasia, and metaplasia at 27 months (3 months postexposure) in the 14.3- and 5.6-ppm groups of mice and in the 2.0- and 5.6-ppm groups of rats. Squamous cell carcinomas were observed in the nasal cavities of 103 rats (52 females and 51 males) and 2 male mice exposed to 14.3 ppm and in 2 rats (one male and one female) exposed to 5.6 ppm of formaldehyde gas. Formaldehyde inhalation was also weakly associated with an increase in the frequency of polypoid adenomas in the nasal cavity of male rats.