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.