Metals and Other Inorganic Compounds

Robert H. Poppenga

Metals are intrinsic to nature and ubiquitous in the environment of animals. Although the form or valence of any given metal can be changed, metals themselves cannot be destroyed.¹ Mining, industrial, and reclamation activities of humans have resulted in the large-scale redistribution of metals in the environment.

Metals can be categorized as those that play an essential role in biological processes (e.g., those that are nutritionally necessary, such as iron, copper, zinc, and selenium, among others) and those that do not (e.g., lead, mercury). It is important to point out that disease syndromes caused by deficiencies of nutritionally important metals are different in pathogenesis and clinical manifestations than those caused by exposure to excessive amounts of the same metal.

The toxicity of metals is often harder to define than that of other toxicants. One reason for this is that the form of a metal plays a critical role in its bioavailability.¹ For example, elemental mercury, when ingested, is essentially unavailable for systemic absorption. In contrast, organic forms of mercury such as methyl mercury are highly bioavailable. The interaction of metals also plays an important role in the determination of toxicity. For example, high dietary calcium can decrease absorp­tion of lead, since lead uses calcium transport mechanisms for its uptake into the body. Other factors that can influence toxicity include animal age, gender, and the capacity of an individual for biotransformation of a metal.

The distribution and accumulation of metals in certain tissues in the body can mitigate damage. Lead can accumulate in bone where it is not available to affect target tissues such as those in the CNS. Also, metals can be sequestered in the body by cystine-rich proteins called metallothioneins that are highly inducible by metals and essential for metal homeostasis and detoxification.¹ The interaction of metals with sulfhydryl- containing groups like cystine is the basis for the efficacy of metal chelators, such as succimer or dimercaprol, which contain numerous sulfhydryl groups.

Arsenic

Historically, various forms of arsenic have been used as herbi­cides, insecticides, wood preservatives, growth promotants, and therapeutic agents.² Arsenic is found in various valences and forms. There are trivalent and pentavalent inorganic and organic forms. Pentavalent (arsenate, H₃AsO₄) and trivalent (arsenite, H₃AsO₃) forms of arsenic include sodium, potassium, and calcium salts. Paris green (copper acetoarsenite) and lead arsenate have been used as insecticides, and trivalent inorganic arsenic forms such as monosodium methanearsonate (MSMA) and disodium methanearsonate (DMSA) are used as herbicides. Historically, pentavalent organic arsenicals such as sodium arsanilate and 3-nitro- 4-hydroxyphenylarsonic acid were used as feed additives for some livestock species but have been withdrawn by the FDA due to human health concerns (http://www.foodsafetynews.com/2015/04/ fda-to-withdraw-approval-for-arsenic-based-drug-used-in -poultry/#.WvC5QX8h3RY). In addition, the use of arsenic as a wood preservative in the form of chromated copper arsenate (CCA) has been banned for residential use by the U.S. Environmental Protection Agency (EPA), although it is still permitted for use in commercial, industrial, and some agricultural settings.

As for most metals, the bioavailability of arsenic is variable and depends on its form (organic versus inorganic, solution versus powder). The arsenic in solutions of organic arsenicals is almost completely absorbed from the GI tract.^3-5 Alternatively, arsenic compounds of low solubility such as arsenic trioxide are absorbed less efficiently. Once absorbed arsenic is widely distributed in the body and reaches its highest concentrations in the liver, spleen, kidney, lungs, and GI tract. Persistent residues are found in keratinized tissues such as skin, hair, and nails. Clearance of arsenic from the blood is multiphasic, with the first phase having a 1- to 2-hour half-life.^4,5 Forty to seventy percent of an absorbed dose is eliminated via the urine within the first 48 hours.

The toxicity of arsenic is variable and depends on its form, purity, solubility, particle size, and valence; the species exposed; and the condition of the exposed individual.^4,5 For example, trivalent arsenicals are 4 to 10 times more toxic than pentavalent arsenicals. Acute arsenite toxicity ranges from 1 to 25 mg/kg body weight (BW), whereas toxicity of arsenates is 30 to 100 mg/kg BW Methanearsonate herbicides are toxic at 10 to 25 mg/kg BW over several days. Weak and debilitated animals are more susceptible to intoxication.^4,5

The mechanism of toxic action of arsenic also depends on its form.¹ Trivalent inorganic arsenicals (i.e., arsenites) inhibit cellular respiration. They bind to sulfhydryl compounds, especially lipoic acid and α-keto oxidases. Lipoic acid, a tissue respiratory enzyme cofactor, plays an essential role in the tricarboxylic acid (TCA) cycle. Tissues with high oxidative energy requirements (e.g., actively dividing cells such as those of the intestinal epithelium, kidney, liver, skin, and lungs) are more severely affected. Trivalent arsenic affects capillary integrity by an unknown mechanism. The GI tract is most affected; capillary dilatation is followed by transudation of plasma into the GI tract, resulting in submucosal congestion and edema. In contrast, pentavalent inorganic arsenicals (i.e., arsenates) appear to substitute for phosphate in oxidative phosphorylation. Uncoupling of oxidative phosphorylation produces a cellular energy deficit. Elevated body temperature is not characteristic of pentavalent arsenical poisoning as it is in poisonings by other oxidative uncouplers (e.g., nitrophenols).

Organic arsenicals also vary in terms of their mechanism of toxic action. Trivalent organic arsenicals appear to have a mechanism of toxic action similar to that of the trivalent inorganic arsenicals.

The clinical signs and lesions are similar for the trivalent inorganic arsenicals, whereas the organic pentavalent compounds used as feed additives cause peripheral nerve degeneration in monogastric animals. The inorganic arsenic compounds (arsenites, arsenates) cause dosage-related peracute, acute, or subacute toxicosis with cardiovascular collapse, sometimes presenting as sudden death.^7,8 Acute poisoning occurs 3 to 12 hours after ingestion. Clinical signs include ataxia, diar­rhea with or without blood, recumbency, and death, with the most prominent clinical sign in acute and subacute cases being diarrhea that is frequently hemorrhagic.^7,9 Other clinical signs include anorexia, dehydration, weakness, colic, and agalactia. No specific abnormalities are noted from CBC or serum chemistry tests. Because arsenic can damage multiple organs, changes associated with liver or kidney dysfunction can be present if the animal survives for several days. Protein, red blood cells, and casts can be noted in the urine. Clinical signs associated with organic pentavalent arsenical intoxication include ataxia, incoordination, torticollis, blindness, paralysis, and recumbency.²

For trivalent arsenicals, consistent necropsy lesions are present in the GI tract and may be hemorrhagic, edematous, necrotic, or eroded. The lesions may be confined to one region or spread throughout the GI tract.^3,7-9 In ruminants, the abomasum is often the most severely affected area. The gut lumen is sometimes filled with necrotic material from the sloughed lining of the GI tract.

An antemortem diagnosis relies on a history of ingestion of arsenic, the occurrence of consistent clinical signs, and the detection of toxic concentrations of arsenic in GI contents, whole blood, or urine. Suspect sources of exposure can also be tested to confirm the presence of arsenic. The rapid elimina­tion of the metal from the body makes the collection of appropriate samples as early as possible an important consid­eration. Most veterinary diagnostic laboratories can test for arsenic. It is important to point out that low-level concentrations of arsenic in blood or urine are not unusual and do not indicate arsenic intoxication. The interpretation of a given concentration of arsenic depends on an evaluation of the entire case and the timing of sample collection in relation to exposure. Postmortem analysis of stomach contents, liver, kidney, or urine can confirm exposure. Again, the significance of detected concentrations, especially relatively low concentrations, needs to be interpreted in conjunction with other case variables. Postmortem lesions may be absent in cases of rapid death. Otherwise, severe GI lesions consisting of reddening of the gastric mucosa and proximal small intestine, watery GI contents, and blood and sloughed mucosa in the feces are commonly noted with trivalent arsenicals. Detection of compatible central and peripheral nervous system lesions is important to demonstrate after intoxication by pentavalent organic arsenicals. Other organ lesions are not specific for arsenic.

The rapid onset of clinical signs often precludes initiating decontamination procedures. Activated charcoal is unlikely to adsorb significant amounts of arsenic, although with significant exposures its administration is recommended.¹⁰ Symptomatic animals need to be stabilized first. This might entail treatment for circulatory shock and hypotension and maintenance of body temperature. Renal and liver failure and electrolyte abnormali­ties may need to be addressed. Glucose and glycogen stores should be maintained parenterally with dextrose or parenteral alimentation solutions.¹⁰ Chelation therapy is typically indicated. Historically, dimercaprol (BAL or British anti-Lewisite) was the recommended chelator. It is a sulfhydryl-containing chelator that binds to arsenic and allows the arsenic-chelator complex to be eliminated. An alternative chelator, succimer, has several theoretical advantages over dimercaprol, including less toxicity and an oral (versus injectable) dosing form. It has been theorized that because succimer is hydrophilic, it may not remove arsenic that has escaped the extracelluar space as efficiently as dimer- caprol does.^4,5 However, available studies suggest that succimer is equal to or even superior to dimercaprol in increasing arsenic elimination.¹⁰ If dimercaprol is used, monitoring for adverse reactions, including pain at the injection site, GI signs, tremors, and seizures, is required. Succimer is likely cost prohibitive for most large animals. D-Penicillamine, another arsenic chelator used in humans, may be too expensive in livestock as well.^11,12 Ethylenediaminetetraacetic acid (EDTA) is not effective for arsenic toxicosis.¹³

Although the administration of B-complex vitamins and amino acids has been recommended, the evidence for their efficacy is lacking. Parenteral antibiotic administration might be considered to prevent secondary bacterial infections of the GI tract. The use of GI protectants may also be indicated. Recovering animals should be fed a high-quality diet in small portions that can be increased as time and circumstances permit. The prognosis in symptomatic animals is always guarded, particularly in the absence of early intervention and intensive monitoring and treatment.

Copper

Sources of copper used in livestock are widely available as sulfates, chlorides, and oxides. Concentrates of copper are found in feed premixes, fertilizers, copper footbaths, aquacides, and fungicides (Bordeaux mixture). Sheep are very susceptible to poisoning by chronic copper accumulation in feeds formu­lated with excessive copper and inadequate molybdenum and sulfur. Absorption in monogastric and young ruminants with a nonfunctional rumen is 75% but only 1% to 10% in cattle and sheep with normal rumen function.¹⁴ Dietary molybdenum at 2 to 5 mg/kg diet and dietary sulfur at 0.4% of diet sub­stantially reduce ruminant copper accumulation. High dietary zinc (>200 mg/kg diet) and iron also limit copper absorption in ruminants.¹⁴

Acute copper toxicosis has occurred in cattle given injections of copper disodium edetate as a therapy for copper deficiency.¹⁵ Sheep are often poisoned when fed rations intended for cattle or horses,¹⁶ and llamas have developed copper toxicosis when fed cattle feed.¹⁷ Sheep have developed toxicosis on pastures fertilized with manure from swine or poultry fed copper.¹⁸ Cattle develop copper toxicosis when supplemented with excessive copper,¹⁹ when fields are contaminated by copper smelting,^18,20,21 or when they are fed litter from chickens supple­mented with copper.²² Excessive copper in calf milk replacers has been a source of toxicosis in both calves^23,24 and goat kids.²⁵ Dairy goats were intoxicated as a result of chronic feeding of a mineral mix containing high concentrations of copper.²⁶

Copper poisoning can be acute or chronic. Acute toxicosis results from ingestion or administration of soluble copper salts in one of the sources listed earlier, usually from one to several large doses of copper regardless of sulfur or molybdenum status. Chronic copper toxicosis can be categorized as simple, hepa­togenous, or phytogenous. Simple chronic toxicosis is caused by ingestion of excessive copper relative to molybdenum and/ or sulfate in the diet. Sheep fed diets with a copper-to- molybdenum ratio greater than 10: 1 are at high risk for developing clinical copper poisoning. Molybdenum and sulfate bind to dietary copper in the rumen and also form a copper­molybdenum complex post absorption, which decreases absorption, retention (through increased bile and urinary excretion), and eventual accumulation of copper in the liver.²⁷ For cattle, dietary copper-to-molybdenum ratios above approximately 40 : 1 allow chronic copper accumulation, and most clinical cases in cattle involve dietary copper in excess of 40 mg/kg diet. Hepatogenous copper toxicosis occurs when hepatotoxic plants such as Senecio species or Heliotropium europaeum damage the liver and cause copper retention.²⁷ Phytogenous copper poisoning occurs from prolonged grazing on plants (e.g., subterranean clover [Trifolium subterraneum]) with elevated copper/molybdenum ratios. In general, mature pastures have lower copper/molybdenum ratios than young, rapidly growing plants.¹⁴ Breed differences in accumulation of copper in liver have been noted for both sheep and cattle.^27,28

The pathogenesis of copper toxicosis involves absorption, binding to albumin and transcuprein proteins, and transport to the liver, where it binds with ceruloplasmin, a hepatic metallopro­tein. The concentration of copper in hepatic lysosomes increases over several weeks to months, leading to excess accumulation. When this occurs, there is necrosis of liver parenchymal cells and swelling of Kupffer cells, followed by sudden spontaneous or stress-related release of copper into the bloodstream.^{14,27, 29,30} This acute phase includes reduced blood glutathione, increased erythrocyte fragility, hemoglobin oxidation, and methemoglobin formation. Resulting intravascular hemolysis leads to anemia, icterus, and hemoglobinuric nephrosis.

The clinical signs of copper poisoning are most prominent in sheep and include an abrupt onset of depression, anorexia, and weakness. Feces may be watery, dark, or blood tinged, especially in cattle. Evidence of a hemolytic crisis is apparent, and signs include anemia, methemoglobinemia, and hemoglobinuria. Mucous membranes are icteric, muddy brown, or a combination 273033

of both.²',^{30 33} Cattle with copper toxicosis after injection of copper disodium edetate have dyspnea, head pressing, ataxia, and circling.¹⁴

Antemortem, the diagnosis of chronic copper toxicosis relies on measuring copper levels in serum as well as measuring serum hepatic enzymes.^19,27,30 However, serum copper is not elevated until just before or during the hemolytic crisis. Therefore animals with toxic copper levels in the liver may have normal or low serum copper values, so serum copper levels alone are not useful for judging copper status. For sheep and cattle there is typically a substantial increase in serum aspartate amino transferase (AST) and gamma-glutamyl transpeptidase (GGT) released from damaged liver before the hemolytic crisis occurs and while the animals are still clinically normal.¹⁴ Controlled studies of serum activities for AST and GGT have been shown to be good predictive indicators of hepatic copper accumulation in sheep or cattle that are clinically normal.³⁴

Postmortem copper should be measured in both fresh liver and kidney. After the liver has released copper into the blood­stream, liver copper values may fall into a nontoxic range, but kidney copper values will remain in a toxic diagnostic range. Acute toxicosis from copper disodium edetate does not con­sistently cause elevated copper levels in the liver or kidney.¹⁵

The diagnosis should correlate with histopathologic lesions in formalin-fixed liver and kidney.^27,30 Gross lesions are present in the liver, kidneys, and spleen. The liver is yellow and friable and may be larger or smaller than normal. Hemoglobin casts in tubules cause the kidneys to appear dark red or blue-black. The spleen is enlarged and congested. Histopathologic changes in the liver include centrilobular necrosis, pigment-laden Kupffer cells, hepatic fibrosis, and bile duct hyperplasia.^19,27,30 Granules in the liver are positive for copper when stained with copper-specific rhodamine or rubeanic acid.²³

Several treatment options are currently available but are often unsuccessful once an animal is in acute hemolytic crisis. Ammonium molybdate (50 to 500 mg PO once daily) and sodium thiosulfate (300 to 1000 mg PO once daily) for 3 weeks have been used for many years as a treatment.^14,27,30 Liver copper levels begin to decrease within 4 days of beginning therapy.²⁷ An unapproved treatment is ammonium tetrathiomolybdate at 3.4 mg/kg subcutaneously (SC) on alternate days for three treatments.³⁵ Either route of administration significantly decreases liver copper levels within 6 days. This change is accompanied by an increase of copper in the blood, bile, feces, and urine.²⁷ Most of this copper is bound with tetrathiomo­lybdate and albumin in an inert complex.^27,30 Xylazine given with tetrathiomolybdate is reported to double the amount of copper excreted in the urine as compared with tetrathiomo­lybdate alone.³⁶ D-Penicillamine (26 mg/kg PO twice daily for 6 days) results in a tenfold to twentyfold increase in urinary copper excretion in sheep,³⁷ but this option is expensive and may not be cost-effective for many livestock. Animals in the acute hemolytic phase of poisoning should be treated as needed for serious hemolytic anemia and potential methemoglobinemia from copper's oxidant effect.

Iodine

Iodine is used to prevent some infectious diseases and as a treatment for foot rot. Common sources of iodine include potassium iodide, sodium iodide, kelp, Chile saltpeter nitrate deposits, and ethylenediamine dihydriodide (EDDI). Oilseed proteins or their concentrates incorporated into foodstuffs contain 0.1 to 0.3 mg iodine/kg. Estimated iodine requirements are beef cattle, 0.5 mg/kg diet; dairy cattle (lactating), 0.8 to 1.0 mg/kg diet; sheep, 0.2 to 0.5 mg/kg diet; swine, 0.3 to 2.0 mg/kg diet; and horses, 0.1 to 0.2 mg/kg diet.³⁸ EDDI has been incorporated into animal feed and drug products for many years for both nutritional and therapeutic purposes. It has been formulated in salt-mineral mixtures and in liquids and powders for adding to feed or drinking water. EDDI has been used as a supplemental source of iodine and is considered generally recognized as safe (GRAS) for nutritional purposes when used at levels consistent with good feeding practices. EDDI products also have been marketed with claims for the treatment and prevention of certain diseases in several animal species but primarily for “foot rot,” soft tissue “lumpy jaw,” and “wooden tongue” in cattle. However, all such EDDI products (including feeds) bearing therapeutic claims now are considered adulterated (https://www.fda.gov/ICECI/ComplianceManuals/ CompliancePolicyGuidanceManual/ucm074677.htm).

Oversupplementation can result in toxicosis. Iodine concentrations greater than 50 mg/kg diet for calves caused reduced growth rate and greater than 100 mg/kg diet resulted in coughing and nasal discharge, as well as reduced hemoglobin and serum calcium concentrations. Previous use of EDDI as an expectorant in feedlot cattle (400 to 500 mg/head/day) or swine (250 to 500 mg/head/day) sometimes resulted in signs of excessive expectorant activity.³⁹ Elevated iodine intake (50 mg/day) in dairy cows will raise milk iodine to concentra­tions that may be unacceptable for public health reasons. One report of abortions in dairy cows was associated with excessive iodine consumption. Maximum tolerable levels based on avail­able literature are cattle, 50 mg/kg diet; sheep, 50 mg/kg diet; and swine, 400 mg/kg diet.⁴⁰

The clinical signs of toxicosis include a nonproductive cough, lacrimation, serous nasal discharge, scaly hair coats, and hyperthermia. Other reported signs include decreased milk production, decreased gain and feed conversion, exophthalmia, nervousness, dermatitis, alopecia, and tachycardia. Young animals appear more susceptible than other age groups. Adults may not develop toxicosis unless stress, disease, or nutritional imbalances are also present.⁴¹ Excess supplementation in mares is associated with goiter in foals.

A diagnosis can be confirmed only with serum or milk analysis. Iodine concentrations in milk are directly related to levels of iodine in the diet.⁴¹ Elevated serum iodine concentra­tions (1600 pg/mL) may be associated with mild clinical signs. Nonlactating cows have higher serum iodine concentrations than lactating cows that are eliminating iodine in milk.

Treatment is restricted to removal of the dietary source of iodine. Clinical signs associated with the respiratory tract disappear 1 to 4 weeks after the iodine source is removed.³⁷

Iron

There are a number of iron salts and formulations. Some insoluble forms of iron such as elemental iron and ferric oxide (i.e., rust) are not hazardous when ingested due to low bioavail­ability. One newer source of iron, a chelated iron called iron phosphate EDTA, is found in some slug and snail baits.

The kinetics of iron absorption are complex. Iron body stores are regulated at the site of absorption from the GI tract because the body is not able to actively excrete iron. From the GI tract, iron must first enter duodenal mucosal cells, possibly by a carrier-mediated process. Next the iron either is lost as the mucosal cells slough into the GI lumen or is bound to ferritin for later transfer to transferrin, a serum iron-binding transport protein. Serum transferrin concentrations greatly exceed the amounts necessary to bind iron under normal physiologic processes (normal binding capacity is three to four times the serum iron concentration). However, in intoxications, the binding capacity is exceeded, allowing free iron to cause cell damage.⁴²

Free iron can cause direct or indirect tissue and cell damage. Iron acts as a free radical and can also produce free radicals. Free radicals have one or more unpaired electrons, which can initiate lipid peroxidation resulting in cell membrane damage. Tissues that have first contact with free iron are primarily affected, although all tissues are susceptible to damage if exposed. The primary targets are the GI, cardiovascular, and hepatic tissues. Iron also damages mitochondria, leading to loss of oxidative metabolism.⁴² Iron may have a direct negative inotropic effect on the myocardium.⁴³

Toxicosis from iron overload has occurred in neonatal foals (normally born with high iron absorption and high serum iron levels) and adult horses given ferrous fumarate orally; calves injected with ferrous gluconate and ferric ammonium citrate; neonatal swine dosed with parenteral iron; pigs born from vitamin E- and selenium-deficient sows; and young bulls injected with ferric ammonium citrate.^44-48

The clinical signs of iron toxicosis in neonatal foals include depression, icterus, head pressing, and disorientation.⁴⁴ Adult horses develop anorexia, icterus, and sometimes petechial hemorrhages.⁴⁹ Calves with iron toxicosis exhibit trembling, vocalizing, bruxism, colic, and convulsions.⁴⁵

Clinicopathologic findings are related to cholestatic liver failure. Animals often have elevated serum levels of γ-glutamyl transferase, alkaline phosphatase (ALP), bile acids, and uncon­jugated bilirubin. Coagulopathies include abnormal coagulation profiles, thrombocytopenia, and elevated fibrinogen.^44,45,49

Gross postmortem lesions are variable. The liver is discol­ored, pale tan, or mottled red-brown, and most are friable and swollen or shrunken. Hemorrhages may be present in the gastric mucosa, intestines, and urinary bladder. Microscopic lesions include bile ductile proliferation, periportal necrosis, lobular necrosis, and fibrosis.^44-47,49 Lesions in the liver tend to have a rather distinct periportal distribution since periportal regions of the liver are the first to be exposed to excessive free iron absorbed from the GI tract.

Iron toxicosis is diagnosed based on clinical signs and a history of recent iron exposure. When serum iron and total iron-binding capacity (TIBC) are evaluated, serum iron often exceeds TIBC. In dead animals, the liver iron is elevated to varying degrees in different species; iron may be above normal if the animal had hemolysis or blood congestion occurred within the liver. Although tissue iron concentrations may help support a diagnosis of iron intoxication, it is common, par­ticularly in horses, to detect elevated liver iron concentrations unrelated to overexposure to iron. Treatment of iron toxicosis is usually limited to supportive care. Patient stabilization is a priority in symptomatic animals. Treating circulatory shock and metabolic acidosis is critical. Sucralfate might be useful to provide some GI protection. Repeated phlebotomy or chelation therapy with deferoxamine (40 mg/kg IM q4-8h) has been used to treat iron overload in humans and small animals.⁴⁸ It combines with iron to form ferrioxamine, which is subsequently eliminated via the kidneys.⁴³ Deferoxamine given intravenously too rapidly can cause cardiac arrhythmias; as well, it is a teratogen and should be used in pregnant animals only if the potential benefits outweigh the risks. The success rate and cost of these treatments in large animals has not been well documented. The prognosis is variable depending on the dosage ingested and availability of appropriate monitoring.

Mercury

Mercury toxicosis has been caused by application or ingestion of an inorganic mercurial product used as a counterirritant or from ingestion of seeds treated with organic mercurial fungi­cides, which are no longer used in most of the world.⁵⁰ If blistering agents are used with dimethyl sulfoxide (DMSO), mercury absorption is enhanced.^51,52 The kidney is the primary target and storage organ of inorganic mercury, but mercury also localizes in the GI mucosa and is eventually excreted by the kidneys.^50-53 Organomercurials such as methyl mercury are lipophilic and can be found in adipose and brain tissue.

Mercury causes two clinical syndromes depending on its form: acute poisoning from inorganic mercury salts and chronic neurologic damage from organomercurials. Acute inorganic mercury causes ulceration of the mouth, the esophagus, and the remainder of the GI tract followed by diarrhea and anorexia. If the animal survives, acute nephrosis develops. Anorexia, gastroenteritis, weight loss, nephritis, and alopecia occur in animals exposed to chronic low doses of inorganic mercury.⁵² Organic mercury fungicides and methyl mercury cause brain damage, blindness, incoordination, and proprioceptive deficits. Most neurologic signs are long term or permanent.

The diagnosis of mercury salt toxicosis is supported by elevated serum creatinine and BUN levels, as well as pro­teinuria, glucosuria, and isosthenuria. Necropsy findings may include an ulcerated, necrotic, edematous, and hemorrhagic GI tract and pale, swollen kidneys. Confirmatory mercury concentrations may be found in liver, kidney, brain, whole blood, and urine.⁵⁰

Therapy should include detoxification (oral sodium thiosulfate) for recent exposure and administration of an appropriate chelator. Sodium thiosulfate or BAL can be used for chelation therapy (see the Arsenic section earlier). Residual topical mercurial products (e.g., blisters) should be washed well from the animal's skin.^50-53 Supportive care should be provided for severe gastroenteritis and kidney failure. The treatment success rate is low when poisoning is severe or progressive; the presence of oliguria indicates a poor prognosis.^50-53 Surviving food animals should be monitored closely for potential mercury residues, which may persist for extended periods in organs or muscle.⁵⁰

Other Toxicants

Additional inorganic toxicants are covered in the following chapters:

Fluoride, Chapter 38 Lead, Chapter 35

Molybdenum, discussed under copper deficiency in Chapter 32 Selenium (see the Poisonous Plants section earlier) Sodium, discussed under salt poisoning in Chapter 35 Sulfate, discussed under copper deficiency in Chapter 32 and under polioencephalomalacia in Chapter 35

Zinc, discussed in the Osteochondrosis section in Chapter 38