2,2,2-Trifluoroethanol toxicity in hamsters (Mesocricetus auratus).
As part of an effort to further elucidate the mechanism whereby fluorinated ether anesthetics express their various toxic effects, Golden Syrian hamsters were utilized to determine acute and subchronic toxicities of the anesthetic metabolite 2,2,2-trifluoroethanol (TFE). The major lesion observed with the TFE (0.25 g/kg ip) was coagulation necrosis characterized by nuclear pyknosis in epithelial cells of intestinal villi, the deeper portion of gastric mucosae, lymphoid organs such as thymus, spleen and mesenteric lymph nodules and brain. Hepatocyte hypertrophy with diffuse vacuolar degeneration was also found. Lungs had a characteristic focal terminal bronchiolar epithelial hyperplasia with discrete mucous metaplasia in the terminal bronchioles. In subchronic studies, hamsters were injected with sublethal doses of TFE (0.20 g/kg once per week for 5 weeks). The major lesions observed were severe hepatocyte hyperplasia and hypertrophy with fatty degeneration, necrosis of hair germinal matrix, urinary bladder transitional epithelial cellular hypertrophy, and hyperplasia with vacuolar degeneration and submucosal edema. Ultrastructural studies of acutely treated animals indicate that fat vacuoles formed within the hepatic endoplasmic reticulum characterized by lamellar bodies forming multiple myelin figures within the fat vacuoles. Hepatic cytochrome P-450 concentrations measured as a possible index of endoplasmic reticulum damage, failed to reveal any significant differences between the treated and non-treated hamsters.
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
J C
JC
Kim
L S
LS
Kaminsky
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000431:Ethanol / Q000031:analogs & derivatives*; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008647:Mesocricetus; D008854:Microscopy, Electron; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014270:Trifluoroethanol / Q000633:toxicity*; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology
D000431:Ethanol; D014270:Trifluoroethanol; D003577:Cytochrome P-450 Enzyme System