This article reviews the available data on the carcinogenicity of
formaldehyde from experimental and epidemiologic studies and makes recommendations for further research. Two definitive chronic inhalation bioassays on rodents have demonstrated that
formaldehyde produces
nasal cancer in rats and mice at 14 ppm and in rats at 6 ppm, which is within the domain of present permissible human exposure (8-hr time-weighted average of 3 ppm, a 5 ppm ceiling, and
a 10 ppm short-term exposure limit). Biochemical and physiologic studies in rats have shown that inhaled
formaldehyde can depress respiration, inhibit mucociliary clearance, stimulate cell proliferation, and crosslink
DNA and
protein in the nasal mucosa. No deaths from
nasal cancer have been reported in epidemiologic studies of cohorts exposed to
formaldehyde, but three case-control studies suggest the possibility of increased risk. Although excesses of
lung cancer deaths have been observed in some studies at industrial plants with
formaldehyde exposure, uncertainties in interpretation limit the evaluation of these findings. Excess
cancers of the brain and of lymphatic and hematopoietic tissues have been reported in certain studies of industrial groups and in most studies of
formaldehyde-exposed professionals, but whether these excesses are related to
formaldehyde exposure is not known. Several properties of
formaldehyde pose unique problems for future research: the mechanisms responsible for its nonlinear response; its probable mechanism of carcinogenic action as a cross-linking agent; its formation in tissues as a normal metabolite; its possible action as a promoter and/or a cocarcinogen; and the importance of
glutathione as a host defense at low exposure.