Acute and subacute toxicity studies of AC-1370 sodium in mice and rats

The i.v. LD50 of the cephalosporin antibiotic 7-beta-D(-)-alpha-[4(5)-carboxyimidazole-5(4) carboxamido]phenylacetamido-3-(4-beta-sulfoethylpyridinium) methyl-3-cephem-4 carboxylic acid sodium (AC-1370 sodium) for the rat was found to be 4.2 and 3.5 g/kg body weight for males and females, respectively; corresponding values for the mouse were 2.7 (male) and 2.9 (female). Daily i.v. administration to rats for 35 days caused decreased food intake and increased water consumption and body weight gain, relative increase of kidney weight, elevated blood urea nitrogen (BUN) and proteinuria, renal tubular degeneration and/or necrosis and ballooning of the caecum at 1500 mg/kg/day, and less marked changes at 500 mg/kg/day. There were so significant adverse effects at 40 or 150 mg/kg/day. The approximate LD50 values (g/kg) by other routes were: s.c. mouse, 7-8; s.c. rat, 11-12; i.m. mouse and rat, greater than 1.2; per os mouse and rat, greater than 15.