title: Toxicological, pathological, and teratological studies in animals with cephradine.
abstract: Cephradine, a semisynthetic cephalosporin antibiotic, has a low order of oral and parenteral toxicity in animals. The oral LD(50) in mice and rats ranged from 5 to >8 g/kg, and the intraperitoneal LD(50) values in mice and rats were 0.7 to 1.5 g/kg and 4.0 g/kg, respectively. The intravenous LD(50) in mice ranged from 3.0 to 3.8 g/kg. In anesthetized dogs, intravenous doses of cephradine (40 and 120 mg/kg, given 45 min apart) had no effect on either the renal or cardiovascular systems. Single intramuscular injections (0.25 ml or 0.5 ml of a solution containing 125 to 235 mg of cephradine/ml) elicited no signs of either pain or local irritation in dogs, and only transient signs of slight-to-moderate irritation were observed in rabbits. In subacute toxicity studies, cephradine was administered for 4 weeks to rats (daily intraperitoneal doses of 160, 480, or 1,600 mg/kg) and dogs (daily intravenous doses of 80, 240, or 800 mg/kg); in addition, over a 2-week period, monkeys were given daily intravenous doses of 60, 180, or 600 mg/kg. No clinical, biochemical, gross, or micropathological changes due to cephradine were observed in these animals; especially notable was the absence of any signs of nephrotoxicity. In chronic toxicity studies, daily doses of cephradine were administered orally to rats (100 to 1,000 mg/kg), dogs (50 to 500 mg/kg), and monkeys (50 to 500 mg/kg) for 26, 26, and 13 weeks, respectively. Significant responses were observed only in rats, in which grossly enlarged, but histologically normal, ceca developed, a common finding in rodents dosed with antibiotics; in addition, there were increases in the relative and absolute weights of the adrenal glands. None of these effects was observed in rats that were necropsied 3 weeks after termination of dosage. In reproduction studies in mice and rats given either daily oral doses (100 or 300 mg/kg) or daily intraperitoneal doses (rats only; 80 or 320 mg/kg) of cephradine, no drug-related teratogenic changes in the offspring were observed.
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D002511:Cephalosporins / Q000009:adverse effects* / Q000633:toxicity; D003510:Cyclohexanes / Q000009:adverse effects / Q000633:toxicity; D004285:Dogs; D005260:Female; D007928:Lethal Dose 50; D051379:Mice; D009132:Muscles / Q000187:drug effects; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D002511:Cephalosporins; D003510:Cyclohexanes