Abstract
Toxicological studies of KW-1070 were carried out in dogs for safety evaluation as follows:
1) Studies on subacute toxicity: Beagle strain dogs given intramuscularly KW-1070 at dose levels of 12.5, 25, 100, 200 and 400 mg/kg and kanamycin (positive control) at dose levels of 100 and 400mg/kg for 30 days, respectively.
2) Studies on chronic toxicity: Beagle strain dogs were intramuscularly given KW-1070 at dose levels of 3, 6, 12.5 and 100 mg/kg for 180 days.
The results of the studies are summarized as follows:
1) In subacute toxicity studies, animals were observed dead only at the dose level of kanamycin 400mg/kg (4/4) within one month. Main changes observed in subacute toxicity studies were renal tubular disorder, which showed a close similarity to subacute toxicity studies in rats. It was observed histologically at the dose level of KW-1070 25-100 mg/kg or more. Kanamycin produced more toxic effects than KW-1070 at the dose level of 400 mg/kg. The results were same as those of subacute toxicity studies in rats.
2) The changes observed in chronic toxicity studies were almost similar to those observed in subacute toxicity studies. An animal was observed dead only at the dose level of KW-1070 100mg/kg (1/6). Renal tubular disorder was observed at the dose level of KW-1070 12.5-50mg/kg or more.
