Olfactory and hepatic changes following inhalation of 3-trifluoromethyl pyridine in rats.
Rats exposed by inhalation to 3-trifluoromethylpyridine (3-FMP) for 10, 30 or 90 days showed an unusual response in the nasal passages. Focal histological change including reduction in the number of cell layers, disorganisation, vacuolation and minimal necrosis was confined to the olfactory epithelium. Axon bundles and the olfactory bulb were unaffected but there was loss of PAS staining affinity in Bowman's glands. The onset of the lesion showed a very steep dose-relationship approximating a quantal response; no effects were seen after 90 days exposure to 0.1 ppm but the changes were fully developed after 30 days exposure to 0.5 ppm. There was no marked progression with either increased exposure concentrations (up to 329 ppm) or with increased duration of exposure (10-90 days). The respiratory epithelium was generally unaffected apart from a mild irritant response seen only after 90 days. Exposures also resulted in a response in the liver. Centrilobular and midzonal vacuolation was observed at 10 and 30 days following exposures at or above 5 ppm 3-FMP and the severity increased with concentration. The lesion regressed with time even when exposure continued and only minimal changes were evident after 90 days, probably indicating an adaptive response. This work demonstrates the high organ specificity of 3-FMP, particularly for the olfactory epithelium.
Gaskell
B A
BA
Imperial Chemical Industries PLC, Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
Hext
P M
PM
Pigott
G H
GH
Hodge
M C
MC
Tinston
D J
DJ
D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000473:pathology; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D011725:Pyridines; C056508:3-trifluoromethylpyridine