NASAL TOXICITY OF CHLOROFORM IN MALE F344 RATS AND FEMALE B6C3F(1) MICE FOLLOWING A 1-WEEK INHALATION EXPOSURE

Chloroform is an important environmental water and air pollutant. Inha lation exposure of female B6C3F(1) mice and F-344 rats for 6 hr/day fo r 7 consecutive days to 0, 1, 3, 10, 30, 100, or 300 ppm of chloroform resulted in concentration-dependent lesions in the nasal passages. Ch loroform-induced changes included increased epithelial mucosubstances in the respiratory epithelium of the nasopharyngeal meatus, primarily in the rats. A complex set of responses was seen in specific regions o f the ethmoid turbinates, predominantly in the rats. These lesions in the ethmoid region, which involved all of the endo- and ectoturbinates , were most severe peripherally and generally spared the tissue adjace nt to the medial airways. These changes were characterized by atrophy of Bowman's glands, increased numbers of vimentin-positive cells in th e periosteum, new bone formation, and increased numbers of periosteal cells in S phase as determined by bromodeoxyuridine incorporation. Add itional changes were site-specific loss of mucosubstances and loss of immunocytochemical staining of acini and ducts of Bowman's glands for P450-2E1 and pancytokeratin, and loss of P450-2E1 immunostaining of th e olfactory epithelium. The only change noted in the mice was increase d cell proliferation without the osseous hyperplasia. The no-observed- effect level for these responses ranged from 3 to 100 ppm, with histol ogical changes and induced cell proliferation being the most sensitive parameters. It is proposed that the osseous changes induced by chloro form exposure may be secondary to primary degeneration of adjacent Bow man's glands. The relevance of these changes to human health risks inc lude potential damage to the sense of smell, but such effects would no t be expected at the low levels of chloroform commonly encountered in the environment. (C) 1994 Academic Press, Inc.