CHANGES IN THE NASAL EPITHELIUM OF RATS EXPOSED BY INHALATION TO MIXTURES OF FORMALDEHYDE, ACETALDEHYDE, AND ACROLEIN

Formaldehyde, acetaldehyde, and acrolein are well-known upper respirat ory tract irritants and occur simultaneously as pollutants in many ind oor and outdoor environments. The upper respiratory tract, and especia lly the nose, is the prime target for inhaled aldehydes. To study poss ible additive or interactive effects on the nasal epithelium we carrie d out 1- and 3-day inhalation studies (6 hr/day) with formaldehyde (1. 0, 3.2, and 6.4 ppm), acetaldehyde (750 and 1500 ppm), acrolein (0.25, 0.67, and 1.40 ppm), or mixtures of these aldehydes, using male Wista r rats and exposure concentrations varying from clearly nontoxic to to xic. The (mixtures of) aldehydes were studied for histopathological an d biochemical changes in the respiratory and olfactory epithelium of t he nose. In addition, cell proliferation was determined by incorporati on of bromodeoxyuridine and proliferating cell nuclear antigen express ion. Effects were primarily observed after 3 days of exposure. Histopa thological changes and cell proliferation of the nasal epithelium indu ced by mixtures of the three aldehydes appeared to be more severe and more extensive in both the respiratory and the olfactory part of the n ose than those observed after exposure to the individual aldehydes at comparable exposure levels. As far as nasal histopathological changes and cell proliferation are concerned neither dose addition nor potenti ating interactions occurred at no-toxic-effect levels, except for a po ssible potentiating effect of acetaldehyde at noneffect levels. The re sults did not indicate a major role for aldehyde dehydrogenases in the biotransformation of the aldehydes studied. Activities of glutathione S-transferase and glutathione reductase after 3 days of exposure to a crolein, atone or in combination with formaldehyde and acetaldehyde, w ere depressed whereas the glutathione peroxidase activity was elevated . No decrease of nonprotein sulphydryl levels were observed. These fin dings suggest that, for no-toxic-effect levels, combined exposure to t hese aldehydes with the same target organ (nose) and exerting the same type of adverse effect (nasal cytotoxicity), but partly with differen t target sites (different regions of the nasal mucosa), is not associa ted with a greater hazard than that associated with exposure to the in dividual chemicals. (C) 1996 Society of Toxicology