Toxicity of Sn-pyrophosphate: clinical manifestations prior to acute LD$sub 50$

Following the administration of large amounts of technetiumSn-phosphate compounds in rats, tetany appears to be the primary clinical manifestation. To evaluate this phenomenon, acute LD/sub 50/ (5 min) was determined and serum calcium and arterial plasma pCO/sub 2/were measured and related to the administered dose. The LD/sub 50/ (5 min) for pyrophosphate was found to be 41.0 plus or minus 1.6 mg/kg (2 s.d.) body weight whereas the LD/sub 50/ (5 min) for polyphosphate was found to be 29.4 plus or minus 2.0 mg/kg (2 s.d.) body weight. There was no significant difference between the slopes of the two compounds. When acute LD/sub 50/s are compared, polyphosphate was 1.4 times more toxic than pyrophosphate. Arterial blood pCO/sub 2/ remained between 30 and 40 Torr until doses of pyrophosphate exceeded 35 mg/kg body weight, after which it fell sharply. Serum calcium concentration was monitored by atomic absorption spectroscopy and electrocardiography. There was a significant drop in the ionized and bound calcium concentrations beginning at an adrministered dose of 20 mg/kg body weight. Electrocardiographic changes consistent with hypocalcemia were recognized after injection of 12 mg/kg body weight. Howevcr, tetany was not apparent until 22 mg/ kg body weight of pyrophosphate was given.more » Therefore, evaluation of the toxic effects of phosphate agents should not be limited to determination of LD/sub 50/ alone but should include appropriate biochemical measurements in blood. (auth)« less