Pathology of acute inhalation exposure to 3-methylfuran in the rat and hamster

Abstract

The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in SPF Fischerderived and CD/CR rats, and golden Syrian hamsters by determination of the 2-week LC 50, and by histologic examination of animals killed 1, 3, and 14 days following a 1-hr exposure to 148 and 322 μmole 3MF/liter for CD/CR rats and hamsters, respectively. The Fischerderived rat was more sensitive to 3MF-induced lethality than the CD/CR rat with an LC 50 in the male rat of 81 μmole/liter-1 hr as compared to 222 μmole/liter-1 hr. No sex difference was found. The hamster was relatively resistant with no lethality at 322 μmole 3MF/liter-2 hr. Pulmonary damage was present in both species. In the hamster, selective necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen at 1 day with virtually complete regeneration by 14 days whereas in the rat the bronchiolar epithelial damage was more extensive and was followed by scattered peribronchiolar fibrosis and epithelial mucous metaplasia suggestive of “small airway disease” of man. Relatively selective 3MF-induced necrosis of olfactory epithelium occurred in the nasal mucosa of both species. Resolution of this lesion was seen by 14 days in the hamster. In the rat, however, the necrosis was much more extensive and was followed by partially occlusive fibrosis of the nasal cavity as seen at 14 days. 3MF also induced centrilobular hepatic necrosis in both species. In the rat, lymphocyte necrosis in the thymus and spleen, and esophageal necrosis was also seen.