CHLOROFORM-INDUCED OLFACTORY MUCOSAL DEGENERATION AND OSSEOUS ETHMOIDHYPERPLASIA ARE NOT ASSOCIATED WITH OLFACTORY DEFICITS IN FISCHER-344RATS

Adult female F-344 rats were trained (avoidance rate > 70%) over four days with a coupled tone-(n = 10 rats/dose) or 2 ppm acetaldehyde-cued (n = 6 rats/dose) foot shock paradigm. Rats were gavaged with chlorof orm dissolved in corn oil for 5 days/week for 3 week at 0 or 400 (tone -cued) or 0, 34, 100, or 400 (odor-cued) mg/kg body weight/day. Tone-c ued response was reevaluated 6, 16, and 38 days after the first chloro form dose (day 1). Olfaction was assessed on days 6-7, 20-21, and 41-4 2 using 2 or 0.0002 ppm acetaldehyde. Nasal histopathology (n = 4-5 ra ts/dose) was assessed on days 6, 20, and 42. Significantly decreased b ody weights were observed following a single 100 or 400 mg/kg chlorofo rm dose. Body weights in the 400 mg/kg/day chloroform group remained d epressed for 17 days. Histopathology revealed degenerative changes in olfactory mucosa and underlying ethmoid turbinate bones that were esse ntially identical in nature and severity, including dose-response and progression, to those reported previously for chloroform gavage (Larso n et al., Food Chem. Toxicol., 1995;33:443-456). At all dose level and sacrifice timepoints, however, regions of morphologically normal olfa ctory mucosa were present; especially in dorsal medial and ventral lat eral regions of the nose. Neither odor-nor tone-cued avoidance behavio rs were affected, indicating that even fairly severe and extensive chl oroform-induced olfactory mucosal degeneration is not associated with a detectable olfactory deficit in rats. (C) 1997 Elsevier Science Irel and Ltd.