ACUTE TOXICITY STUDY OF CEFPIROME SULFATE IN MICE AND RATS

Acute toxicity of cefpirome sulfate (CPR) was examined in 6-week-old mice and rats and immature (5-day-old)rats. The LD50 values of CPR (mg/kg) were as follows : (1) mice : intravenous, 2420 (95% confidence limits, 2122-2758) for males and 2400 (2181-2640) for females ; intraperitoneal, 3850 (3407-4351) for males and 4200 (3889-4536) for females ; and oral, 16200 (14781-17755) for males and 18500 (17290-19795) for females. (2) 6-week-old rats : intravenous, 1900(1784-2023) for males and 2080(1953-2215) for females ; intraperitoneal, 6550 (6179-6943) for males and 5800(5311-6334) for females ; subcutaneous, more than 10000 for both sexes ; and oral, more than 8000 for both sexes. (3) 5-day-old rats : subcutaneous, between 1750 and 2500 for males and 2080 (1651-2621) for females. Major changes in general health conditions observed in 6-week-old mice and rats were decreased spontaneous activity, lying prone, tremor, respiratory chantes (slow or deep respiration, gasping), clonic or clonic-tonic convulsions. In the 6-week-old rats dosed subcutaneously, vocalization, writhing and cutaneous changes at the injection site (dark reddening or blackening, swelling, exfolination, depilation, induration) were also observed. In the 5-day-old rats dosed subcutaneously, the changes noted were slow respiration, writhing, cyanosis, and dark reddening and swelling of the skin at the injection site. After administration, transient depression of body weight gain or loss of body weight was observed in the mice and rats except the rats dosed orally. These changes disappeared at 7 days after administration at latest, and all surviving animals showed favorable body weight gain thereafter. Necropsied revealed hemorrhage under meninges in the brain in many of the mice and rats which died. Other findings included subcutaneous changes at the injection site in the 6-week-old and 5-day-old rats dosed subcutaneously (dark reddening, retention of dark red fluid, retention of red, white or dark red gelationous material) and changes in the peritoneal cavity in the 6-week-old rats dosed intraperitoneally (red or dark red spots on the serous membrane, reddening of dipose tissues).