Fr. Cassee et al., CHANGES IN THE NASAL EPITHELIUM OF RATS EXPOSED BY INHALATION TO MIXTURES OF FORMALDEHYDE, ACETALDEHYDE, AND ACROLEIN, Fundamental and applied toxicology, 29(2), 1996, pp. 208-218
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