Formaldehyde is a nasal carcinogen in the rat but the cancer risk this
chemical poses for humans remains to be determined. Formaldehyde indu
ces nonlinear, concentration-dependent increases in nasal epithelial c
ell proliferation and DNA-protein cross-link formation following short
-term exposure. Presented in this review are results from a mechanisti
cally based formaldehyde inhalation study in which an important endpoi
nt was the measurement of cell proliferation indices in target sites f
or nasal tumor induction. Male Fischer 344 rats were exposed to 0, 0.7
, 2, 6, 10, or 15 ppm formaldehyde for up to 2 years (6 hr/day, 5 day/
week). Statistically significant increases in cell proliferation were
confined to the 10 and 15 ppm groups, which remained elevated througho
ut the study. The concentration-dependent increases in cell proliferat
ion correlated strongly with the tumor response curve, supporting the
proposal that sustained increases in cell proliferation are an importa
nt component of formaldehyde carcinogenesis. The nonlinearity observed
in formaldehyde-induced rodent nasal cancer is consistent with a high
-concentration effect of regenerative cell proliferation of the target
organ coupled with the genotoxic effects of formaldehyde. Cell kineti
c data from these studies provide important information that may be ut
ilized in the assessment of risk for humans exposed to formaldehyde.