Death in sheep following dosing with copper diethylamine oxyquinoline sulphonate as a commercial injectable copper preparation

Abstract

Death occurred in sheep following diethylamine oxyquinoline sulphonate (DOS) copper injections given at recommended dose rates. The copper content in unused portions of DOS copper packs was normal and free of bacterial contamination. Liver and blood copper levels in dead and sick sheep were not high. Sick sheep showed signs of hepatic encephalopathy and dead sheep were generally piled against fences and scrub. Deaths were associated with acute, severe, generalised, centrilobular, hepatocellular necrosis and live sheep had elevated circulating levels of liver enzymes consistent with liver damage. In recovered sheep there were no residual complications. It would appear that even at 0.5 mg/kg of DOS copper the safety threshold may sometimes be exceeded in some sheep.

Copper Poisoning, a Deadly Hazard for Sheep

“…Furthermore, acute poisoning is very often associated with oral and parenteral overdoses of Cu salts present in preparations used for the prevention and treatment of Cu deficiency or in anthelmintic drenches [ 5 , 10 , 11 , 45 ]. Soluble formulations, such as Cu edetate and diethylamine oxyquinoline sulphonate (DOS), whose Cu is rapidly available, may be mortal for sheep when administered parenterally, even at recommended doses [ 10 , 46 , 47 ].…”

“…In addition, transient lip licking movements, soft faeces, diarrhoea, reduced appetite and tachypnoea have been seen in experimental studies [ 67 ]. In the case described by Mason et al [ 47 ], some sheep showed central nervous signs, such as opisthotonos, head pressing or lack of awareness of surroundings, and dead sheep were found in groups along fences or in the scrub, indicating hepatic encephalopathy in association with liver injury.…”

“…Severe shock with a fall in rectal temperature, tachycardia, depression and weakness appear, and animals can die in a few hours [ 5 , 10 , 15 ]. If acute toxicosis arises by Cu injection, the response is more rapid and digestive signs are not present, the most important symptoms being severe depression and dehydration [ 5 , 10 , 46 , 47 , 67 ]. In both forms, if the animal survives sufficiently long, haemoglobinuria and jaundice can be observed as a consequence of haemolysis [ 5 , 10 , 15 ].…”

“…Markedly elevated circulating levels of bilirubin and liver enzymes AST and GGT have also been measured, consistent with liver damage [ 15 , 47 ]. In this sense, some authors speculate that the origin of elevated bilirubin levels in acute toxicosis is hepatic rather than prehepatic, unlike what happens in the haemolytic crises of chronic poisoning, and higher AST activity than in sheep with cumulative Cu poisoning has also been reported [ 15 ].…”

Intoxicação aguda por cobre em ovinos

“…A intoxicação ocorreu de forma aguda com a introdução do sal mineral na dieta desses ovinos, os quais já estavam ingerindo excesso de cobre na ração. Essa apresentação é pouco descrita na literatura e foi associada com administração parenteral de cobre, ou ingestão de sulfato de cobre (CuSO 4 ) a 5-10% de pedilúvio (MASON et al, 1984;ORTOLANI et al, 2004;RADOSTITS et al, 2007). Nos casos previamente relatados, são descritas lesões hepáticas severas, semelhantes às observadas neste caso.…”