Interactive effects of ozone and formaldehyde on the nasal respiratory lining epithelium in rats.
The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats were exposed by inhalation during 22 h/d for 3 consecutive days to 0.3, 1.0, or 3.0 ppm formaldehyde, or to 0.2, 0.4, or 0.8 ppm ozone, or to mixtures of 0.4 ppm ozone and 0.3, 1.0, or 3.0 ppm formaldehyde, or to 1.0 ppm formaldehyde and 0.2, 0.4, or 0.8 ppm ozone, or they were sham-exposed to clean air. The noses were examined for pathological changes at six standard cross levels by light microscopy and for epithelial cell proliferation by counting [3H-methyl]thymidine-labeled cells at cross levels II and III. Ozone at 0.4 ppm or 0.8 ppm or formaldehyde at 3 ppm enhanced cell proliferation at cross level II at all locations, except for the epithelium of the septum, which was not affected by ozone. At cross level III ozone alone did not induce cell proliferation, but formaldehyde at 0.3 and 1 ppm tended to reduce cell proliferation while at 3 ppm proliferation was slightly stimulated. The combined exposure to 0.4 ppm ozone and 0.3 ppm formaldehyde induced less cell proliferation at cross levels II and III when compared with that of 0.4 ppm ozone alone. Less cell proliferation was also seen at cross level II when animals were exposed to 0.4 or 0.8 ppm ozone in combination with 1 ppm formaldehyde than when exposed to these ozone concentrations alone. A more than additive increase in cell proliferation was found at cross level II after exposure to 0.4 ppm ozone in combination with 3 ppm formaldehyde, and at cross level III in animals exposed to 0.4 ppm ozone and 1 or 3 ppm formaldehyde. Treatment-related histopathological nasal changes, such as disarrangement, loss of cilia, and hyper/metaplasia of the epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde. Simultaneous exposure to both materials did not noticeably affect type, degree, and size of the microscopic nasal lesions.
Reuzel
P G
PG
TNO-CIVO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Wilmer
J W
JW
Woutersen
R A
RA
Zwart
A
A
Rombout
P J
PJ
Feron
V J
VJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005557:Formaldehyde / Q000633:toxicity*; D006965:Hyperplasia; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D005557:Formaldehyde; D010126:Ozone