A nine-month chronic toxicity study of tegafur-uracil mixture (UFT) in dogs.
In order to evaluate the long-term-safety of UFT which contained tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil, FT-207] and uracil in molar ratio of 1:4, a nine-month chronic toxicity study was performed in dogs. In doses of 9.7 (as FT-207: 3 mg/kg), 16.2 (as FT-207: 5 mg/kg) and 24.3 (as FT-207:7.5 mg/kg) mg/kg, UFT was administered orally in both sexes of dogs once a day for 9 months and withdrawn for 1 month. Three control drugs, FT-207, uracil and 5-FU, were also included in present experiment at doses of 7.5, 420.0 and 5.0 mg/kg, respectively. In this study, the two types of toxic behaviors and symptoms were observed in UFT, FT-207 and 5-FU. The first type was the acute and/or dynamic signs and the other type was the chronic and/or static signs. Slight decrease in food consumption was observed in males at the dose levels of 24.3 mg/kg of UFT group and in both sexes of 5-FU group. In the ECG test, high T-wave was observed in some males treated with UFT, FT-207 and 5-FU. Histopathologically, micro-vacuolizations were observed in various portions of the cerebrum in both survived and dead animals treated with UFT, FT-207 and 5-FU. After one month recovery period, significant changes were not observed in various examinations, but morphological changes in the cerebrum had been remained. In conclusion, it seemed that the maximum safety dose of UFT in dogs were the 9.7 mg/kg for males and less than 9.7 mg/kg for females.
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D005641:Tegafur / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors; D014498:Uracil / Q000008:administration & dosage / Q000633:toxicity; D014617:Vacuoles / Q000473:pathology
D005641:Tegafur; D014498:Uracil