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Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein

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Author: Cassee, F.R. · Groten, J.P. · Feron, V.J.
Institution: TNO Voeding
Source:Fundamental and Applied Toxicology, 2, 29, 208-218
Identifier: 233260
doi: doi:10.1006/faat.1996.0024
Keywords: Biology · acetaldehyde · acrolein · aldehyde dehydrogenase · formaldehyde · glutathione peroxidase · glutathione reductase · glutathione transferase · animal experiment · animal model · animal tissue · article · cell proliferation · chemical interaction · controlled study · histopathology · inhalation · male · nonhuman · nose mucosa · olfactory epithelium · rat · respiratory epithelium · upper respiratory tract · Acetaldehyde · Acrolein · Administration, Inhalation · Air Pollutants · Aldehyde Dehydrogenase · Animals · Antigens, Nuclear · Autopsy · Biological Markers · Biotransformation · Bromodeoxyuridine · Cell Division · Dose-Response Relationship, Drug · Epithelial Cells · Epithelium · Formaldehyde · Gene Expression Regulation · Male · Nasal Mucosa · Nuclear Proteins · Rats · Rats, Wistar · Staining and Labeling


Formaldehyde, acetaldehyde, and acrolein are well-known upper respiratory tract irritants and occur simultaneously as pollutants in many indoor and outdoor environments. The upper respiratory tract, and especially the nose, is the prime target for inhaled aldehydes. To study possible additive or interactive effects on the nasal epithelium we carried 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 Wistar rats and exposure concentrations varying from clearly nontoxic to toxic. The (mixtures of) aldehydes were studied for histopathological and biochemical changes in the respiratory and olfactory epithelium of the nose. In addition, cell proliferation was determined by incorporation of bromodeoxyuridine and proliferating cell nuclear antigen expression. Effects were primarily observed after 3 days of exposure. Histopathological changes and cell proliferation of the nasal epithelium induced by mixtures of the three aldehydes appeared to be more severe and more extensive in both the respiratory and the olfactory part of the nose 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 potentiating interactions occurred at no-toxic-effect levels, except for a possible potentiating effect of acetaldehyde at noneffect levels. The results 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 acrolein, alone or in combination with formaldehyde and acetaldehyde, were depressed whereas the glutathione peroxidase activity was elevated. No decrease of nonprotein sulphydryl levels were observed. These findings suggest that, for no-toxic-effect levels, combined exposure to these aldehydes with the same target organ (nose) and exerting the same type of adverse effect (nasal cytotoxicity), but partly with different target sites (different regions of the nasal mucosa), is not associated with a greater hazard than that associated with exposure to the individual chemicals.