Abstract
The subacute and chronic toxicities of T-1220 were examined in rats using the intraperitoneal administration route, and compared with those of aminobenzvlpenicillin (ABPC). Male and female rats of age 6-7 weeks were applied. In the subacute toxicity, rats were administered in daily intraperitoneal doses of T-1220 for a month at 1, 000, 2, 000 and 4, 000 mg/kg, and in the chronic toxicity, administered for 6 months at 500, 1, 000 and 2, 000 mg/kg. ABPC was used at 2, 000 mg/kg in both toxicities. Control rats were treated with physiological saline.
The results are as follows.
1) The body weight gain was depressed in male rats treated with T-1220 at 4, 000 mg/kg for a month, and at the final administration its body weight was significantly different from that of control (p<0.05). The writhing syndrom was observed immediately after the administration in proportion to dose levels of T-1220 and ABPC.
2) In hematological and blood biochemical examinations, there were no abnormalities produced by the administration.
3) The enlargement of the unilateral renal pelvis, which had the localized ishemic change, and localized cecitis were sporadically observed in autopsy, but the dose-relation was not clear. Any abnormalities were not seen in the other organs.
4) The urinary volume, BUN and kidney weight increased remarkably in female rats treated with ABPC at 2, 000 mg/kg. The enlargement of the renal tubular lumina, degeneration of the renal tubular epithelium and cellular infiltration and fibrosis of the interstitium were, histologically, observed in both sexes of ABPC.
5) The maximum safety dose of the intraperitoneal injection of T-1220 was estimated to be 2, 000 mg/kg in these experiments.
