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[Toxicological studies of a new cephamycin, MT-141. II. Its subacute toxicity in rats]
Abstract:
In this subacute study, male and female rats were administered with 100, 200, 400, 800 and 1,600 mg/kg/day of MT-141 through an intramuscular (i.m.) route or with 50, 100, 200, 400 and 800 mg/kg/day through an intravenous (i.v.) route for 30 days. MT-141 did not cause lethal effect on male and female rats even at the high dosage of 1,600 mg/kg/day i.m. (approx. one-6th of LD50) and 800 mg/kg/day i.v. (approx. one-8th of LD50). Histopathological findings revealed that MT-141 induced slight local irritation at the sites of i.m. and i.v. injection. Only at a high dose of 1,600 mg/kg/day i.m., MT-141 reduced significantly the gain of body weight in male rats, which was closely related to the decrease of food intake. A slight decrease in serum Cr. and Glc. was observed in male rats at the doses more than 200 mg/kg/day i.m. and a slight decrease of liver weight at the doses more than 800 mg/kg/day i.m., while a slight increase of serum CPK, GOT, A1-P and LDH was perceived at the doses more than 800 mg/kg/day i.m. The distention of cecum was induced by the doses more than 400 mg/kg/day i.m. but histopathological findings revealed no abnormality in the cecum. These results suggest that MT-141 at the dosage level of 1,600 mg/kg/day i.m. causes nonspecific slight toxicity based on the disturbance of nourishment in male rats. In female rats given 100 to 1,600 mg/kg/day i.m., MT-141 at the high doses induced a slight increase of serum GOT, LDH and CPK and distention of the cecum. It is assumed from these results that MT-141 at the dosage level of 1,600 mg/kg/day causes nonspecific slight toxicity in female rats. In male rats given 50 to 800 mg/kg/day through an i.v. route, the level of serum Glc. and Cr. and the liver weight slightly decreased at the doses more than 200 mg/kg/day i.v. The cecum distended at the doses more than 100 mg/kg/day i.v. The dose of 800 mg/kg/day i.v. increased the activity of LDH and CPK in the serum. In female rats, MT-141 raised slightly the level of serum GOT, A1-P, LDH and CPK even at the doses more than 400 mg/kg/day i.v., reduced the liver weight at the dose of 800 mg/kg/day i.v. and distended the cecum at the all doses. These results suggest that MT-141 at the dosage level of 800 mg/kg/day i.v. induces nonspecific slight toxicity in male and female rats.(ABSTRACT TRUNCATED AT 400 WORDS)