Subcutaneous injections of up to 6 mg copper per kg body-weight as copper methionate (A) produced no deleterious effects in ewes. When copper was given in the form of copper calcium EDTA (B), deaths occurred within 48 hours of the subcutaneous injection of 3 or 4 mg copper per kg body-weight. There was centrilobular necrosis of the liver, necrosis of kidney tubules and excess fluid in the pleural and peritoneal cavities accompanied by the release of liver specific enzymes and a rise in the concentration of urea and creatinine in serum. The injection of 2 mg copper per kg body-weight produced a liver lesion at 48 hours with similar serum changes but recovery took place. Liver and kidney lesions occurred when the copper was in the form of diethylamine copper oxyquinoline sulphonate (C). In this case deaths occurred after the injection of 4, 3 or 2 mg copper per kg body-weight and liver damage followed by recovery was caused by 1 mg copper per kg body-weight. All compounds produced an increase in copper oxidase activity and in the concentration of copper in serum and whole blood. Compound A produced a slow increase in plasma copper concentration to a plateau between 5 and 10 days. Compounds B and C produced a rapid initial increase in the first few hours. The concentration fell rapidly for 12 or 24 hours and then more gradually. It is suggested that rapidity of absorption and transfer of copper to the liver and kidneys may be responsible for the toxic effects of compounds B and C.
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