Abstract
One-month subacute intravenous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 2000, 1000 and 500mg/kg/day. Sixteen males and 16 females were used per group (including the control group). THR-221 caused neither death nor change in general conditions at any dose level throughout the study, except that decreased spontaneous activity appeared only transiently in a part of the animals given 2000 mg/kg/day. Increases in water intake were observed in all compound groups, and transient decreases in food consumption were seen at an early stage of the administration period. However, the compound did not affect the body weight at any dose level. In urinalysis, the urine sediments in all THR-221 groups contained an increased number of epithelial cells as compared with the controls. At autopsy, dilation of the cecum was observed in all THR-221 groups, and jn a part of the rats with this change, red spots or reddening of the serous membrane of the organ also appeared. Light microscopy revealed brown granules in the epithelium of renal tubules in all compound groups (with dose-dependent incidences) and congestion or hemorrhage in the cecum in some compound-treated animals. Electron microscopy on the kidney showed small bodies (considered to be lysosomes) in the tubular epithelium in all compound groups. No other changes related to THR-221 were observed. From the present results that no marked toxic signs were seen at any dose level, the toxicologically non-effective dose of THR-221 for rats of both sexes is considered to be more than 2000 mg/kg/day.
