CLINICAL SIGNS

Oak blossoms, buds, leaves, stems and acorns can be toxic to most animals. Most reports of toxicosis in livestock involve cattle and sheep, with a rare occurrence in the horse. Clinical signs attributed to acorn toxicosis in horses are acute onset of severe abdominal pain, rectal straining, hemorrhagic diarrhea, and pronounced intestinal borborygmi. Acorn parts may be apparent in feces. Occasionally, horses are found dead; other signs are hemoglobinuria and elevated heart and respiratory rates.

PATHOPHYSIOLOGY

The toxicity of oak is attributed to a group of structurally similar compounds called gallotannins and their metabolites. Digallic acid is the major active metabolite produced by oak tannins. After bacterial fermentation digallic acid is converted to gallic acid and pyrogallol, both of which are considered toxic.¹ Pyrogallol and gallic acid are toxic to renal tubules and result in acute tubular necrosis, anuria, electrolyte abnormalities, and uremia.^1,2 Pyrogallol is also responsible for causing hemorrhagic gastroenteritis, subcutaneous hemorrhage, and hemolysis. Tannic acid itself is thought to result in increased vascular permeability, hemorrhage, and subsequent fluid loss into body spaces.¹

DIAGNOSIS

The diagnosis of oak toxicity is based on clinical signs and a history of potential exposure to the plant. Under adequate forage conditions horses would seem to find large quantities of oak leaves and acorns distasteful; therefore most horses with oak trees in their environment do not develop toxicity. Toxicosis is more likely to result when abnormal conditions coupled with environmental factors (e.g., lack of access to normal forage or feed) result in large numbers of oak leaves and acorns becoming accessible to horses.

Laboratory findings compatible with oak toxicosis include dehydration or hemoconcentration to varying degrees, azotemia, hyperphosphatemia, hypocalcemia, and hypoproteinemia. Abnormal urine findings might include occult blood, proteinuria, and casts. An increase in gallic acid equivalent content in urine also has been used to support exposure to oak trees.¹ However, oak trees are not the only plant that can contain these tannins, and normal and toxic ranges of gallic acid in urine have not been well established in livestock.

Necropsy findings suggestive of oak toxicosis include pericardial, thoracic, and peritoneal effusion; gastrointestinal and mesenteric edema; and pale and swollen kidneys that may bulge on cut surface. The intestinal tract may contain large quantities of acorn parts, and colonic ulceration has been reported.¹

SPECIFIC TREATMENT AND MANAGEMENT

No specific antidote for oak toxicity is available. Animals should be allowed no further access to oak. Treatment of the acutely affected animal aims to maintain fluid and acid-base balance and to correct any electrolyte abnormalities. Balanced polyionic fluids given intravenously to promote diuresis are the basic therapy. This therapy should be supplemented with calcium, bicarbonate, and other electrolytes as necessary. Anuric animals may gain additional benefit from furosemide at 1 mg/kg intravenously or dimethyl sulfoxide (DMSO) at 1 g/kg given intravenously as a 10% solution in addition to fluid therapy. The clinician should attempt evacuation of the intestinal tract using mineral oil or another suitable laxative.

The prognosis for affected horses is guarded. A paucity of information exists regarding mortality rates in affected horses, but death caused by ingestion of acorns has been reported.¹

CLINICAL SIGNS

Castor beans contain ricin, a protein phytotoxin that acts as a potent proteolytic enzyme with significant antigenic qualities.² A latent period ranging from hours to several days usually occurs before the onset of clinical signs in affected horses. The bean is apparently distasteful to horses, and intoxication most likely occurs when the bean inadvertently is mixed into the feed source. To cause problems, the bean must be broken apart by chewing; beans swallowed intact are thought to pass through the gastrointestintal tract uneventfully.

The most commonly reported clinical signs of castor bean toxicosis described in the literature are varying degrees of abdominal pain, diarrhea, depression, incoordination, profuse sweating, and increased body temperature. Muscle twitching, convulsions, and prominent cardiac contractions occasionally are observed. If the horse absorbs enough ricin, signs of shock and anaphylaxis predominate.^2,3 Death may ensue as soon as 24 to 36 hours after ingestion.

Ricin is reported to be toxic to horses. One reference cites a ricin dosage of 0.1 μg/kg as a lethal dose,² and a second source indicates 25 g of castor beans is lethal.³ A published report in 1945 describes seven deaths attributed to castor bean toxicosis from a stable of 48 horses in London in 1931.⁴ The exact number of affected horses was not reported. A review of the literature suggests that castor bean (ricin) toxicosis in human beings and dogs is not nearly as lethal as reported in the literature of the early twentieth century.^5,6 Whether this holds true for horses is open to speculation.

PATHOPHYSIOLOGY

The oil extract of the bean contains ricinoleic acid. Within the small intestine ricinoleate acts to reduce net absorption of fluid and electrolytes and stimulates peristalsis.⁷ The fibrous residue of the seed contains the water-soluble toxalbumin ricin. Ricin is absorbed from the gastrointestinal tract and is a potent inhibitor of protein synthesis. Ricin contains two polypeptide chains. Chain B, a lectin, binds to the cell surface to facilitate toxin entry into the cell. Chain A disrupts protein synthesis by activating the 60S ribosomal subunit. The red blood cell–agglutinating properties of ricin are independent of these toxic effects.⁸

DIAGNOSIS

Diagnosis is made by a combination of history of exposure to the plant; clinical signs; and the identification of seeds in feed material, gastric contents, or feces. Analyses for ricin content in urine, as well as other samples, are available from certain laboratories.⁸

TREATMENT

Ricin has no specific antidote. Initial therapy aims to combat shock, alleviating abdominal pain and evacuating the bowel. Maintenance of fluid and electrolyte balance is important. Various sedatives and analgesics may be useful to control abdominal pain, if present. Oral administration of laxatives and protectants such as mineral oil and charcoal may be warranted. Antihistamines also have been recommended.²

CLINICAL SIGNS

Pokeweed intoxication in horses is an uncommon occurrence. However, one text reports that horses show signs of gastrointestinal irritation and abdominal discomfort as the primary clinical signs. The plant also produces a burning sensation of the oral mucous membranes and may cause a hemolytic crisis. Fatalities caused by pokeweed ingestion are said to result from respiratory failure and convulsions.²

PATHOPHYSIOLOGY

The plant contains phytolaccine, a powerful gastrointestinal irritant that in human beings causes symptoms ranging from a burning sensation of the alimentary tract to severe hemorrhagic gastritis. Five nonspecific mitogens that have hemagglutinating and mitotic activity have been isolated. These substances vary in concentration in the plant throughout the growing season. Noncardiac steroids and triterpenoid glycosides (saponins) also are present in significant quantities, but their role in pokeweed toxicity is unknown.⁸ Saponins may potentiate gastrointestinal toxicity and produce vasodilation when given parenterally.

DIAGNOSIS AND TREATMENT

No specific diagnostic test is available. Horses suspected of having toxicosis must be treated symptomatically. The clinician should attempt to evacuate the gastrointestinal tract using laxatives. Adsorbents such as charcoal and protectants may be useful. If the horse develops a hemolytic crisis, ancillary therapy such as whole-blood transfusions may be lifesaving. Fluid and electrolyte balance must be maintained in these horses in an attempt to prevent or minimize hemoglobin- or hypoxic-induced nephrosis.²

CLINICAL SIGNS

A number of species of Solanum spp. have been incriminated in causing toxicity in horses. However, these plants rarely are a source of natural intoxication to horses. Reported clinical signs are referable to the gastrointestinal and central nervous systems. The primary gastrointestinal signs observed are salivation, abdominal pain, increased borborygmi, and diarrhea. Signs of central nervous system (CNS) dysfunction include mydriasis, dullness, depression, weakness, and progressive paralysis, which can lead to prostration and death.^2,9,10

PATHOPHYSIOLOGY

Solanine is a toxic substance found in Solanum species; it is a water-soluble glycoalkaloid capable of producing local irritation^2,3,8 and is absorbed poorly from the gastrointestinal tract. Intravenous doses caused ventricular fibrillation in rabbits, and intraperitoneal doses caused mild to moderate inhibition of specific and nonspecific cholinesterase activity.⁸ It has been shown that exposure to Solanum plants can potentiate the effects of ivermectin in horses.¹¹

DIAGNOSIS AND TREATMENT

No specific diagnostic test is available to confirm a diagnosis of Solanum toxicosis. Animals suspected of having toxicosis should be treated symptomatically. Evacuation of the gastrointestinal tract using laxatives and protectants may be indicated. Charcoal also has been recommended for treatment of toxicosis in human beings.⁸ The clinician should monitor the fluid, electrolyte, and acid-base status of affected animals and make corrections as needed.

CLINICAL SIGNS

Several species of Datura grow throughout North America, all of which can produce signs of toxicosis in livestock. However, these plants are rarely a source of natural intoxication in horses, probably because of the unpalatability of the plant.^9,10 One report of equine acute toxicosis resulted when ingested feed was contaminated heavily with jimsonweed seeds. According to this report, one horse was affected acutely and died because of gastric rupture and gas-filled intestinal loops. A second horse was treated for several days before being euthanized. Clinical signs observed in the treated horse included abdominal distention with gas-filled intestinal loops, prolonged ileus, mydriasis, tachycardia, hyperpnea, and dry mucous membranes.¹²

PATHOPHYSIOLOGY

The toxic substances found in Datura spp. are the tropane alkaloids atropine (a racemic mixture of d– and l-hyoscyamine) and scopolamine (l-hyoscine).^9,10,12 These substances exert an antimuscarinic effect by competitive inhibition with acetylcholine for receptor sites, resulting in attenuation of the physiologic response of neuroeffector junctions to parasympathetic nerve impulses. Blockade of the muscarinic receptors of different tissues accounts for the various clinical signs observed.

DIAGNOSIS AND TREATMENT

Toxicity is suspected when animals exhibit signs compatible with atropine overdose. Identification of seeds or plant material in ingesta, gastric lavage contents, or feedstuffs may support a diagnosis. Treatment is largely symptomatic and includes immediate removal of the offending feed or plants, evacuation of the gastrointestinal tract, and supportive care. The use of pilocarpine and physostigmine to counteract the atropine-like effects of these alkaloids has been recommended by some, but this treatment is considered controversial.^9,10

CLINICAL SIGNS

Signs of overdose commence within 60 to 120 minutes in affected horses. Initial signs are restlessness and increased intestinal sounds accompanied by steadily increasing heart and respiratory rates. Abdominal pain, watery diarrhea, and dehydration become apparent soon afterward, and horses gradually deteriorate to lateral recumbency and death in 14 to 72 hours.

PATHOPHYSIOLOGY

Much information about the pharmacologic action of DSS remains uncertain.⁷ The primary organ of involvement is the small intestine, where epithelial denudation, villous atrophy, and submucosal edema and congestion occur. DSS has been suggested possibly to cause epithelial detachment by lowering the surface tension on the basement membranes of intestinal epithelial cells.¹³ Once detachment occurs, loss of fluid and electrolytes into the intestinal lumen is possible. The absorptive capacity of the epithelium is lost, and the osmotic effect of intestinal content causes further loss of fluid into the lumen. With extensive mucosal damage, the horse also becomes much more susceptible to endotoxemia. The rapid death in affected animals is caused by hypovolemic shock, endotoxemia, and circulatory collapse resulting from the loss of fluids and electrolytes into the intestinal lumen.

DIAGNOSIS AND TREATMENT

Diagnosis of DSS toxicity depends on observation of the aforementioned clinical signs along with oral DSS administration. No specific antidote for DSS exists, and once clinical signs commence, treatment is aimed at supporting circulation and combating the effects of systemic endotoxin. Specific treatment for circulatory collapse and endotoxemia is covered elsewhere, but medications that might be useful include polyionic electrolyte solutions, electrolyte supplementation, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), bicarbonate, and orally administered gastrointestinal protectants.

CLINICAL SIGNS

The clinical signs associated with arsenic toxicity are essentially those of a severe gastrointestinal irritant. Most toxicities result from inorganic forms of arsenic, and signs are similar in several animal species.

In peracute cases the animals may be found dead with no premonitory signs. Acute signs of toxicity include severe colic, staggering, weakness, salivation, diarrhea that may contain blood or shreds of mucosa, and signs of shock that indicate cardiovascular collapse. Death usually occurs in 1 to 3 days.^14–16 In subacute poisoning animals may live for several days, exhibiting signs of depression, anorexia, colic, diarrhea that may contain blood and mucus, polyuria followed by anuria, and subsequent shock before death. Horses that are poisoned by topical application of arsenic can show signs of blistering and edema of the skin.¹⁴ Chronic arsenic poisoning rarely occurs in domestic animals.

PATHOPHYSIOLOGY

Many factors play a role in the development of arsenic toxicosis in horses. In general, horses that are debilitated, weak, or dehydrated are more susceptible to toxicosis than normal animals. The formulation of the compound (trivalent arsenicals are more toxic than pentavalent forms), the solubility of the compound, the route of exposure, the rate of absorption from the gastrointestinal tract, and the rate of metabolism and excretion by the individual animal are factors that can influence the toxicity of the various arsenic formulations.¹⁴ The most hazardous preparations are products in which the arsenical is in a highly soluble trivalent form, usually trioxide or arsenite. Sodium arsenite is 3 to 10 times more toxic than arsenic trioxide. The average total oral lethal doses of these compounds for the horse are 10 to 45 g arsenic trioxide and 1 to 3 g sodium arsenite.^14,15

Soluble forms of arsenic are absorbed from all body surfaces. Less soluble arsenicals are absorbed poorly from the gastrointestinal tract and essentially are excreted unchanged in the feces. After absorption trivalent arsenic is excreted readily by way of the bile into the intestine, and pentavalent arsenic is excreted by the kidney. Regardless of whether an introduced arsenical is in the trivalent or pentavalent form, all the major actions can be attributed to the trivalent form.¹⁴

All arsenicals are thought to exert their effects by reacting with sulfhydryl groups in cells. Trivalent arsenic acts primarily by combining with the two sulfhydryl groups of lipoic acid, thereby inactivating this essential cofactor necessary for the enzymatic decarboxylation of the keto acids pyruvate, ketoglutarate, and ketobutyrate. By inactivating lipoic acid, arsenic inhibits the formation of acetyl, succinyl, and propionyl coenzymes A. The net effect is the blocking of fat and carbohydrate metabolism and cellular respiration.^14,15 Trivalent arsenic may inactivate sulfhydryl groups of oxidative enzymes and the sulfhydryl group of glutathione and other essential monothiols and dithiols. Arsenic also causes a local corrosive action on the intestine.¹⁵

Arsenic seems to prefer tissues rich in oxidative enzymes such as the liver, kidney, and intestine. The capillary endothelial cells in these organs appear sensitive to arsenic because it relaxes capillaries and increases capillary permeability. Blood vessels with smooth muscle in their walls also dilate. In the intestinal tract the mucosa easily sloughs away because of the accumulation of fluid in the submucosa. In the kidney renal tubular degeneration occurs.¹⁵

DIAGNOSIS

The clinical signs described previously should cause the practitioner to consider inorganic arsenic poisoning. Antemortem laboratory findings are consistent with gastrointestinal, hepatic, and renal damage. Feces may contain blood, mucus, and increased numbers of white blood cells. The liver enzymes sorbitol dehydrogenase, lactate dehydrogenase (LDH), AST, and γ-glutamyltransferase (GGT) may be increased in serum, and urine might contain protein, red blood cells, and casts. Urine arsenic concentration in affected animals often exceeds 2 ppm.¹⁴

Postmortem findings are characteristic of severe gastroenteritis and may include hepatic lipidosis and necrosis. In horses in which arsenic poisoning is suspected, the liver, kidneys, stomach, intestinal contents, milk, blood, and urine should be evaluated.

TREATMENT

Specific therapy for arsenic toxicity is dimercaprol (or British antiLewisite [BAL]). This chelating agent forms a nontoxic and easily excretable complex with arsenic. However, BAL may mobilize stored arsenic in tissues and cause an initial exacerbation of clinical signs by allowing more arsenic to circulate to the intestine and liver. BAL also can be toxic in sufficient doses. Signs of overdose include tremors, convulsions, coma, and death. In horses the recommended dose is 3 mg/kg intramuscularly as a 5% solution in a 10% solution of benzyl benzoate in peanut oil. This dose is administered every 4 hours for the first 2 days, every 6 hours on the third day, and twice daily for the next 10 days until recovery.¹⁵

Sodium thiosulfate also has been advocated for treatment of arsenic toxicosis, but its efficacy is questionable. The recommended dose for horses is 20 to 30 g orally in 300 ml of water, plus 8 to 10 g intravenously in a 10% to 20% solution.¹⁵

Symptomatic care of affected animals includes evacuation of the gastrointestinal tract with laxatives and oral demulcents to coat the intestinal tract. The clinician should evaluate fluid, acid-base, and electrolyte indices and provide support if necessary. Aggressive intravenous fluid diuresis is advocated by many to maintain adequate hydration and enhance urinary arsenic excretion. Because endotoxemia may develop as a result of the intestinal and liver lesions, prophylactic administration of flunixin meglumine at a dosage of 0.25 mg/kg every 8 hours may be beneficial. Other therapy to prevent shock and cardiovascular collapse also may be indicated.

CLINICAL SIGNS

The most frequently noted signs associated with ingestion of petroleum products are essentially those of gastrointestinal and respiratory dysfunction. Petroleum products are irritating to mucous membranes, and hence prominent signs of gastrointestinal dysfunction might include salivation and fluid feces. The feces actually may contain oil or oily substances. Chronically affected animals also may exhibit anorexia and weight loss over several days to weeks.

Signs of respiratory dysfunction are a common manifestation of excessive petroleum exposure. Aspiration of the oil or fumes is irritating to pulmonary tissue, and aspiration pneumonia is probably the most serious consequence of petroleum toxicity.¹⁴ Signs of toxicity include increased respirations, anorexia, depression, weight loss, a variable degree of fever, and possibly increased nasal discharge.

Products that are applied inadvertently to the skin might cause some degree of respiratory embarrassment, but they are more likely to cause signs related to the absorption of excessive hydrocarbons.¹⁵ Topically applied agents also may cause signs associated with a contact irritant.

PATHOPHYSIOLOGY

The toxicity of crude oil is correlated with the gasoline, naphtha, and kerosene content in the oil. Crude oil rich in these low-temperature distillates is more toxic than petroleum containing a great deal of sulfur but less of the low-temperature distillates.¹⁵ Petroleum products are irritating to mucous membranes, and their oiliness makes them difficult to remove from skin and mucous membranes and virtually impossible to remove from the respiratory epithelium. Once aspirated, they serve as a focus for foreign body pneumonia that may progress to abscessing pneumonia, pleuritis and pleural effusion, and death.

DIAGNOSIS

History of possible exposure, clinical signs, and pathophysiologic signs are important in establishing a diagnosis. Suspected contents (i.e., gastrointestinal content or feces) may be mixed with water, and any oil that is present will float to the surface and be readily visible. Analytic chemistry methods sometimes can be used to establish the identity of an oil.¹⁴

TREATMENT

Treatment is supportive. The clinician should evacuate and protect the gastrointestinal tract by using laxatives and demulcents. Products applied to the skin can be removed with warm soapy water followed by thorough rinsing. Products such as mechanic’s hand degreasers can be tried first to remove fat-soluble compounds. Aspiration pneumonia may be frustrating to treat, and supportive care such as fluids and electrolytes, NSAIDs, and broad spectrum antimicrobial therapy is potentially helpful.

CLINICAL SIGNS

The most consistently reported clinical sign is excessive salivation characterized by profuse, viscous, clear saliva.¹⁹ Salivation may begin 30 to 60 minutes after eating the affected feed, and response from one feeding may persist for up to 24 hours. Other, less commonly reported clinical signs include anorexia, polyuria, and sometimes watery diarrhea.¹⁴ One case of abortion in an affected mare has been reported.¹⁹ Clinical signs generally abate 48 to 96 hours after the infected feed is removed from the diet.¹⁴

PATHOPHYSIOLOGY

Slaframine apparently is activated by liver microsomes after absorption. The active compound seems to have direct histaminergic effects or possibly a histamine-releasing effect, which is borne out in laboratory animal studies in which clinical signs responded better to antihistamines than to atropine.¹⁵

DIAGNOSIS

The combination of acute clinical signs of excessive salivation coupled with digestive disturbances and identification of R. leguminicola in forage generally is adequate to establish a diagnosis. It is possible to analyze slaframine in feeds, but usually such tests are unnecessary.¹⁴

TREATMENT

No specific treatment usually is necessary. Animals generally recover uneventfully 48 to 96 hours after withdrawal of the contaminated forage.¹⁴ Atropine and antihistaminic therapies have been suggested to help control clinical signs,^14,15 but their efficacy is questionable.

CLINICAL SIGNS

Clinical signs, if observed, may include fever, tachycardia, dyspnea, sweating, lethargy, incoordination, weakness, cyanosis, collapse, and death. Less severely affected animals may primarily manifest signs of hyperthermia and oxygen deficiency.¹⁵ Pentachlorophenol in high doses to pregnant animals also is reported to cause embryonic and fetal deaths but is not teratogenic.¹⁴

DIAGNOSIS AND TREATMENT

Pentachlorophenol toxicity is associated with the combination of clinical signs and blood pentachlorophenol levels greater than 40 ppm. No specific treatment is available, but saline diuresis has been suggested to be helpful in certain instances of human toxicosis.¹⁴

CLINICAL SIGNS

Initial signs are those of gastrointestinal irritation and include colic and diarrhea. Hematuria and hemoglobinuria also are present early in the disease course. Within hours the horse shows dyspnea, cyanosis, and increased respiratory effort. Death can occur suddenly, without obvious signs.¹⁴

PATHOPHYSIOLOGY

Chlorates are absorbed readily from the intestine, and once absorbed they continue to exert their damaging effects as long as they are present.^14,15 A dose of 250 g is reported to be lethal to horses.¹⁴

Chlorates cause toxic changes by three different mechanisms of action:

The net effect of methemoglobinemia and hemolysis is a severe compromise in the oxygen-carrying capacity of blood, and animals may be so severely affected that they die as a result of anoxia.¹⁵

DIAGNOSIS

The prolonged, extensive methemoglobinemia found in affected animals should alert the veterinarian to the possibility of chlorate poisoning. A history of exposure to chlorates also should accompany these clinical signs before a presumptive diagnosis is made. Analysis of blood, urine, or ocular fluid can help determine chlorate concentration, and because chlorates normally are not found in animals, their presence in a sample would confirm poisoning if clinical signs, history, lesions and response to therapy also suggest this diagnosis.¹⁵

TREATMENT

After making the diagnosis, the clinician should immediately seek out the chlorate source and remove it from the horse’s environment. Methemoglobinemia is treated with methylene blue at a dose of 4.4 mg/kg given as a 1% solution by intravenous drip. This dose may be repeated in 15 to 30 minutes if a clinical response is not obtained.^2,15 Other recommended therapeutic measures include gastric lavage with 1% sodium thiosulfate and the oral administration of intestinal protectants and demulcents.^2,14 Blood transfusion and oxygen supplementation may be beneficial in certain instances.¹⁵

CLINICAL SIGNS

Reported signs in affected horses include severe muscular fasciculation, profuse sweating, dehydration, and mydriasis with a weak pupillary response. Hindlimb weakness, ataxia, persistent inappetence, and abdominal pain also have been reported.²¹ Hyperglycemia is a fairly consistent laboratory finding.^14,21

PATHOPHYSIOLOGY

Pyriminil is absorbed from the gastrointestinal tract and excreted in the urine. Pyriminil acts as a nicotinamide antagonist, but its exact mechanism of action is unknown.^2,14,22 Pyriminil also has been shown to damage the pancreatic β-cells and to depress glucose uptake by erythrocytes.

DIAGNOSIS

A presumptive diagnosis is based on compatible clinical signs and history of exposure to the rodenticide.

TREATMENT

Specific therapy for pyriminil toxicity is reported to be nicotinamide. However, the use of this drug in human beings appears to be effective only when given within 1 hour of ingestion of pyriminil. The reported dosage is 50 to 100 mg nicotinamide intramuscularly every 4 hours for up to eight injections. This dosage is followed by 25 to 50 mg orally 3 to 5 times daily for 7 to 10 days.¹⁴ Other therapies that may be beneficial include gastric lavage and the oral administration of mineral oil and activated charcoal.^14,22 Apparently, affected horses recover because no deaths caused by pyriminil toxicosis have been recorded.

CLINICAL SIGNS

In one reported outbreak the initial signs began 4 days after exposure and included abdominal pain, polydipsia, anorexia, severe weight loss, alopecia, skin and oral ulcers, conjunctivitis, dependent edema, joint stiffness, and laminitis. A total of 85 horses were exposed, 58 became ill, and 43 subsequently died. The length of illness varied from 4 to 132 weeks in the terminally ill horses, with those having a heavier exposure exhibiting a shorter disease course (average of 32 weeks) than others (average of 74 weeks). In addition, abortions occurred in pregnant mares, and many foals that were exposed only in utero died at birth or shortly thereafter.²³ Other reported signs in animals included gastrointestinal hemorrhage with necrosis and ulceration of the gastrointestinal mucosa, cerebrovascular hemorrhage, hepatotoxicity, and thymic and peripheral lymph node atrophy.^14,23

PATHOPHYSIOLOGY

Tetrachlorodibenzodioxin is absorbed readily by oral and dermal routes, and following absorption appears to be retained primarily by liver and adipose tissue. The mechanism of action of TCDD in various organs in not well defined. TCDD is known to induce microsomal mixed function oxidases in liver and kidney, and hepatic δ-aminolevulinic acid synthetase and aryl hydrocarbon hydroxylase, but the role of these processes in the induction of toxicity of TCDD remains to be elucidated.¹⁴ TCDD also induces immunosuppression by causing thymic and peripheral lymph node atrophy.

DIAGNOSIS

A combination of the described clinical signs and possible exposure to industrial waste oil products should alert the veterinarian to the possibility of TCDD toxicity. Dioxin content is confirmed in various tissues by means of gas-liquid chromatography and mass spectroscopy, but few laboratories offer this service, and the analysis is generally expensive.¹⁴

A characteristic liver lesion seen at necropsy in a number of horses was microscopic evidence of bile stasis, hepatocyte necrosis, bile duct proliferation, and extensive fibrosis that was pronounced around the central veins but minimal in the peripheral liver lobules. Other microscopic changes noted were thickened vascular walls and endothelial proliferation in the smaller blood vessels of several different organs.²³

TREATMENT

No known antidote exists for TCDD toxicity once clinical signs develop. After their onset, the clinician can offer only symptomatic and supportive care, and one should use every precaution to prevent laminitis. Soil and activated charcoal appear to bind strongly to TCDD and inhibit its absorption, so if known ingestion has occurred, immediate oral administration of activated charcoal may have beneficial effects by reducing the amount absorbed.¹⁴

CLINICAL SIGNS

The signs associated with toxicosis are many, varied, and dose dependent. Horses affected with a minimal dose may show only signs of depression, anorexia, and occasionally polyuria, whereas horses ingesting a lethal dose may show signs of profound shock, gastrointestinal and urinary tract irritation, myocardial dysfunction, and hypocalcemia.^24,25 The onset and duration of clinical signs vary from hours to days, but horses that succumb to cantharidin generally die within 48 hours of onset of signs. Horses that live longer than 48 hours have a better prognosis for recovery if no complications arise.

The most commonly observed clinical signs include varying degrees of abdominal pain, anorexia, depression, and repeatedly submerging the muzzle in water or frequently drinking small amounts of water. The respiratory and cardiac rates are elevated, and cardiac contractions are occasionally forceful enough to be observed through the thoracic wall. Mucous membranes are congested and cyanotic, and capillary refill time is prolonged. The feces may be watery in consistency but rarely contain blood or mucus. Profuse sweating is typical of more severely affected horses and may be a sign of severe abdominal pain. Affected horses often make frequent attempts to void urine. The urine is grossly normal early in the disease course but later may become tinged with blood or contain clots of blood. Gross hematuria, if it occurs, is usually in the later stages of the disease process. Less commonly observed signs include synchronous diaphragmatic flutter; erosions of the gingival and oral mucous membranes; and occasionally a stiff, short-strided gait similar to that seen in acute myositis. Sudden death also has been reported.²⁴

PATHOPHYSIOLOGY

The mechanism of action of cantharidin at the cellular level has not been elucidated fully. Acantholysis and vesicle formation result from disrupted cell membranes. Cantharidin does not have a direct effect on membranes but is thought to interfere with oxidative enzymes bound to mitochondria. These enzyme systems are involved directly in active transport across the plasma membrane, and their failure results in cell death caused by significant permeability changes in the cell membrane.²⁴

Hypovolemic shock and pain develop rapidly in more severely affected horses. The normal transfer of fluid, nutrients, and electrolytes across the intestinal mucosa is disrupted because of the morphologic changes induced by cantharidin. Although renal tubular damage is not severe enough to cause death, changes in the renal tubular epithelium also may be related to the development of fluid, acid-base, and electrolyte abnormalities.^24,25

Hypoproteinemia develops later in the disease course, probably as a result of protein loss across the damaged intestinal mucosa. Protein also is lost into the peritoneal space, and a minor amount may be lost through the urine.²⁴

The profound hypocalcemia and hypomagnesemia that may occur in many horses have not been explained fully. Calcium loss, derangement of calcium homeostasis, or a combination of both is the most likely explanation because the acute onset of the disease eliminates reduced intake as a possible cause. Calcium can be lost through urine and sweat and as protein-bound calcium through the damaged intestinal wall. An influx of intracellular calcium also may occur in certain tissues. Whether cantharidin has an effect on calcium-binding sites on proteins or in cells is unknown.²⁴

The low urine specific gravity in most horses may be caused by decreased permeability of the collecting ducts to water. Other findings, however, point to a mild pathologic insult as a cause of the low urine specific gravity. These findings include the facts that a low specific gravity occurs suddenly within hours of toxin exposure; specific gravity returns to normal in 2 to 4 days in surviving horses; only mild to moderate changes are noted in other renal function tests; and the histologic renal lesions are mild, and neither acute nor chronic renal failure is associated with cantharidin toxicosis in horses.²⁴

Myocardial necrosis is a common finding in affected horses and may be caused by the direct effect of cantharidin on cardiac muscle. Dose-related intracellular changes involving the mitochondria, cristae, nuclear chromatin, sarcoplasmic reticulum, and myofibrils have been observed in the cardiac muscle of rabbits that were given cantharidin. A proposed mechanism for these changes suggests that an excessive transport of calcium into the myocardial cells occurs, leading to an intracellular calcium overload. This overload may result in a high-energy phosphate deficiency within the cell, leading to necrosis and cell death.²⁴

DIAGNOSIS

The clinician should consider cantharidin toxicosis when horses exhibit signs of abdominal pain, depression, or polyuria, and their diet contains alfalfa hay or alfalfa products. The diagnosis can be made when horses have clinical signs and laboratory findings compatible with cantharidin toxicosis and beetles are found in the hay. Because the beetles can be difficult to identify in hay, it should be thoroughly searched. Cantharidin can be assayed using high-pressure liquid chromatography and gas chromatography–mass spectrometry techniques.^24,26 Samples to be tested are serum, urine, kidney, and stomach content from horses in which cantharidin toxicosis is suspected.

Laboratory findings are nonpathognomonic, but several abnormalities typically are noted. Packed cell volume (PCV) and serum protein concentrations are elevated early, but hypoproteinemia frequently develops after about 24 hours. Mild hypokalemia can occur but is not a striking feature of this disease. Blood urea nitrogen (BUN) concentration may be elevated moderately, and hyperglycemia is almost always present initially.²⁴

Serum calcium and magnesium concentrations are significantly decreased in most horses and remain low for longer than 48 hours if untreated. The urine generally contains red blood cells and has a low specific gravity, even in the face of clinical dehydration. Abnormal peritoneal fluid findings include increased protein concentration but relatively normal fibrinogen and white blood cell values. Feces are often positive for occult blood. Serum creatine kinase (CK) activity may be elevated in more severely affected horses and augurs a poor prognosis.²⁴ Although not diagnostic, laboratory findings of prolonged hypocalcemia and hypomagnesemia and elevated CK concentration may help differentiate cantharidin toxicosis from other causes of acute abdominal crisis.

TREATMENT

No specific antidote is available for cantharidin. Once the diagnosis is suspected, all suspect feed should be removed from the horse’s environment and all hay carefully examined for the presence of beetles.

Horses suspected of having cantharidin toxicosis should be given mineral oil as soon as possible. The oil helps evacuate the bowel and also may help reduce the amount of cantharidin available for absorption because cantharidin is lipid soluble. Activated charcoal given through a nasogastric tube also may have beneficial effects.²⁴

Polyionic fluids should be administered intravenously throughout the disease course to correct dehydration and promote diuresis. Diuretics also may be given once the horse is volume loaded. Analgesics usually are required because of the severity of the abdominal pain, and glucocorticoids may be necessary to aid in treating shock. Calcium gluconate should be administered to elevate the serum calcium concentration, and calculated deficits of magnesium should be replaced by slow intravenous infusion.²⁴

CLINICAL SIGNS

The toxic manifestations of phosphorus poisoning are generally threefold: Toxic signs commence within hours of ingestion; are followed by a latent period of 48 hours to several days, when the animal may appear to have recovered; and finally recur with greater severity.

The initial signs are characterized by severe abdominal pain, and gastrointestinal irritation, with occasional episodes of diarrhea. Blood may be present in feces. Cardiac arrhythmias may occur during this phase, and if the dose is sufficiently large, cyanosis, shock, incoordination, and coma can develop, and the animal may die before the second and third stages develop.¹⁴

The latent period may occur from 48 to 96 hours after the onset of clinical signs, and during this time the animal may appear normal. The third stage is characterized as a recurrence of severe abdominal pain, and signs of liver dysfunction may become evident. Icterus and a tendency to bleed from the gingiva, stomach, intestine, or kidney may be evident.¹⁴

PATHOPHYSIOLOGY

Phosphorus is absorbed from the gastrointestinal and respiratory tracts. Although dermal exposure may cause skin irritation or burning, absorption does not occur by this route. The mechanism of action of phosphorus is unknown but is noted for causing irritation and necrosis of affected tissue. Phosphorus is also known to cause peripheral vasodilation.¹⁴

DIAGNOSIS AND TREATMENT

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