Toxicity Studies on NSC 15200,Gallium Nitrate .7H20in Citrate Formula,Lot No. DDB 72-716,in Beagle Dogs,

摘要

In beagle dogs treated I.V. with the following drug regimens 10mg/kg/day x 5was the Lethal Dose (LD), 5mg/kg/day x 5was the Toxic Dose 'High' (TDH), 0.63mg/kg/day x 5was the Toxic Dose 'Low' (TDL) and 0.32mg/kg/day x 5was the Highest Nontoxic Dose (HNTD). Toxic signs noted with 10mg/kg/day x 5consisted of weight loss,anorexia, salivation,emesis,hyperthermia followed by preterminal hypothermia, debilitation,hind limb spread,conjunctivitis,tearing, puffiness of the eye lids,relaxation of the nictitating membrane,muscle tremors and sluggishness with the impression of sedation. The compound was hepatotoxic as evidenced by BSP retention and elevations of alkaline phosphatase and SGPT and it was nephrotoxic as evidenced by azotemia, creatinemia and proteinuria. Pathological findings included lymph node hyperlasia with scattered nuclear debris and in addition in the bronchial lymph node of one animal multiple focal granulomas. The animals treated with 5mg/kg/day x 5showed many of the signs enumerated above for the higher dose animals. At the dose levels of 0.63mg/kg/day and 0.32mg/kg/day x 5no overt toxic signs were noted. At all dose levels the toxic signs and hematological and biochemical changes were reversible. This formulation of the drug was compatible with dog,monkey and human blood.