Zinc is an essential trace metal that plays an important role in many of the body's enzymatic processes. It is ubiquitous in nature and exists in many forms. The ingestion of some forms of zinc causes the creation of toxic zinc salts in the acidic environment of the stomach. Zinc toxicity has been documented in people as well as in a wide range of large, small, exotic, and wild animals. Exposure typically stems from dietary indiscretion. Household sources of zinc include paint, batteries, automotive parts, zinc oxide creams, vitamin and mineral supplements, zipper pulls, board-game pieces, pet carrier screws and nuts, and the coating on certain types of pipes and cookware. One of the most well-known sources of zinc that causes toxicity after ingestion is the USA Lincoln penny. Some pennies minted during 1983, and all pennies minted since, are 97.5% zinc by weight (~2,440 mg of elemental zinc per coin).
The low pH in the stomach causes the release of free zinc, which then forms soluble, caustic zinc salts. These salts are absorbed from the duodenum and rapidly distributed to the liver, kidneys, prostate, muscles, bones, and pancreas. Zinc salts have direct irritant and corrosive effects on tissue, interfere with the metabolism of other ions such as copper, calcium, and iron, and inhibit erythrocyte production and function. The mechanisms by which zinc exerts these toxic effects are not completely understood. The LD50 of zinc salts in cases of acute toxicity has been reported to be ~100 mg/kg. Also, diets containing high levels of zinc (>2,000 ppm) have been reported to cause chronic zinc toxicosis in large animals.
Clinical signs vary based on the duration and degree of exposure. Signs progress from anorexia, vomiting, diarrhea, and lethargy to more advanced signs such as intravascular hemolysis, icterus, hemoglobinuria, cardiac arrhythmias, and seizures. Large animals often show decreases in weight gain and milk production, and lameness has been reported in foals secondary to epiphyseal swelling.
Major histopathologic findings include hepatocellular centrilobular necrosis with hemosiderosis and vacuolar degeneration, renal tubular necrosis with hemoglobin casts, and pancreatic duct necrosis with fibrosis of the interlobular fat.
Radiodense foreign bodies are easily seen on radiographs of the GI tract and should raise suspicion of potential zinc toxicosis in animals with correlating clinical signs. Changes in the CBC, chemistry profile, urinalysis, and coagulation profile reflect the degree of toxicity to various organ systems. The hemogram can reveal anemia characterized by changes in erythrocyte morphology such as spherocytosis and Heinz body formation. (It has been suggested that zinc’s interference with enzymes such as glutathione reductase leads to erythrocyte fragility due to oxidative damage.) The leukogram often shows a mature neutrophilic leukocytosis secondary to stress, pancreatitis, and a regenerative response by the bone marrow. Serum chemistry changes that are seen secondary to hepatic damage include increases in bilirubin, the transaminases, and alkaline phosphatase.
As zinc accumulates in the pancreas, increases in amylase and lipase can be seen following pancreatitis and pancreatic necrosis. Glomerular damage and renal tubular epithelial necrosis result in increases in BUN, creatinine, amylase, and urine protein. Hemoglobinuria can be differentiated from hematuria during urinalysis; the urine color will not clear after centrifugation in the presence of hemoglobinuria. Prolongation of prothrombin time and activated partial thromboplastin time can also result from toxic effects on the synthesis or function of coagulation factors and the loss of clotting proteins through the glomerulus of the kidneys.
The hematologic and clinical findings in animals with zinc toxicosis are similar to the changes in animals with immune-mediated hemolytic anemia (IMHA). Zinc toxicosis can cause the direct antiglobulin test (direct Coombs’ test) to be positive in the absence of a primary autoimmune disorder, so the direct Coombs’ test is not a reliable method to differentiate zinc intoxication from IMHA.
Zinc levels can be measured in blood to confirm toxicosis, although this is usually unnecessary to diagnose zinc poisoning in the clinical setting. In dogs and cats, the normal serum zinc level is 0.7–2 mcg/mL. Reference laboratories usually request that samples be submitted in green-top heparinized tubes, royal blue–top trace element tubes, or purple-top EDTA tubes. Methods to quantify zinc levels from saliva and hair have not been validated in domestic animals, and measuring zinc in urine is unreliable because elimination of zinc through the kidneys is variable.
After stabilizing the animal with fluids, oxygen, and blood products as necessary, removal of the source of zinc as early as possible is paramount. This often requires surgery or endoscopy. Inducing emesis to remove chronic gastric zinc foreign bodies may be tried within the first hour or two of exposure but may not be rewarding in advanced cases because zinc objects can adhere to the gastric mucosa.
Proton pump inhibitors and H2-blockers can be used to decrease the formation of zinc salts in the stomach before removal of the source of zinc, and gastroprotectant therapy with sucralfate can later be considered to help address gastric ulceration.
Diuresis with a balanced crystalloid solution is indicated to promote renal excretion of zinc and prevent hemoglobinuric nephrosis.
There is debate regarding the necessity of chelation therapy in cases of zinc toxicosis. Animals often recover from zinc intoxication after only supportive care and removal of the source. Chelation therapy can enhance elimination of zinc and thus accelerate recovery, but there is some concern that chelation treatment may actually increase zinc absorption from the intestines. Chelation can be achieved through the use of specific compounds. Ca-EDTA chelates zinc when given at 100 mg/kg/day, IV or SC, for 3 days (diluted and divided into four doses) but may exacerbate zinc-induced nephrotoxicity. Although they have been used to treat animals with zinc toxicity, d-penicillamine and dimercaprol (British anti-lewisite) have not been specifically validated for this purpose. Reported dosages are 110 mg/kg/day for 7–14 days for d-penicillamine, and 3–6 mg/kg, tid, for 3–5 days for dimercaprol. Chelation therapy with any of these agents should be performed only after careful consideration and should be monitored with serial serum zinc levels to help determine the appropriate duration of treatment.
With early diagnosis and treatment, the outcome is usually favorable for animals with zinc toxicosis. Eliminating exposure to zinc in the environment is essential to prevent recurrence.