Veterinary Toxicology

Vein see Blood Venoms and Poisons from Animals see Animals, Poisonous and Venomous Vesicants see Blister Agents/Vesicants

Veterinary Toxicology WK Rumbeiha and DB Snider, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Ames, IA, USA Ó 2014 Elsevier Inc. All rights reserved.

This article focuses on understanding and managing chemically induced disorders in domestic animals. Approximately 10% of veterinary practice is devoted to the diagnosis and treatment of poisonings. The species treated range from small domestic animals (i.e., cats and dogs) to food-producing animals (i.e., dairy cattle, beef cattle, and swine) to horses, pet birds, zoo animals, and, occasionally, wildlife. Because of the diversity in the species veterinarians deal with, there is need to be aware of species and breed differences in response to intoxications. In this article, common intoxications in animals are discussed. It is important to recognize that there are a number of factors that affect animal response to intoxications including dose, age, sex, etc. However, because of space limitations, only a few of these are covered in this article.

Species Differences Small animals (dogs and cats) react to chemicals more or less the same way as do humans because they are all monogastrics. Ruminants (i.e., cattle and sheep), however, react differently than monogastrics; they have evolved a unique digestive tract structure and microbial flora, which play a major role in the fermentation of the forage ingesta. The ruminant’s microflora are usually capable of metabolizing toxic chemicals. For example, cattle are more susceptible to nitrate poisoning than horses, and dogs and cats are very resistant to nitrate poisoning. The high sensitivity of cattle to nitrate poisoning is because their digestive tract microbes will convert nitrates to the proximate toxic metabolite, nitrite. Dogs and cats lack the microbial population that cattle possess and therefore are unable to metabolize nitrates and are therefore more resistant to nitrate poisoning. The horse, though a monogratric, may succumb to nitrate poisoning because of the presence of microorganisms in the cecum. However, by the time nitrate reaches the cecum, more than 70% of nitrates will have been absorbed; little will be available for biotransformation into the toxic nitrite ion in the cecum. Horses, therefore, require threefold higher amounts of nitrate to be poisoned compared to cattle. Physiological differences among species will markedly alter species susceptibility to toxicants. For example, birds are more

Encyclopedia of Toxicology, Volume 4

sensitive to toxic vapors and gases than mammals. Canaries have been used in mines to test for the presence of poisonous gases because their elaborate respiratory system causes them to succumb to lower concentrations of toxic gases in the environment than humans. Biochemical differences also contribute to differential susceptibility between and within species. Cats are more susceptible to acetaminophen poisoning than other domestic animals. The cat’s glucuronyl transferase system for conjugating acetaminophen and similar compounds is much lower than that of other domestic species, and also feline hemoglobin is more susceptible to oxidation than that of other animals. Therefore, cats given what would be considered a therapeutic dose of acetaminophen in humans easily die of methemoglobinemia. Biochemical differences are also found within the same species. For example, Bedlington terriers are much more susceptible to copper poisoning than other breeds of dogs. This is because of the inability of this dog breed to excrete copper from the liver. Most biochemical differences have a genetic origin. Adequate comprehension of the variance in toxicity to toxicants in the domesticated animal species therefore requires an understanding of the anatomy, physiology, and biochemistry of the affected animals. Likewise, other factors that affect the toxicity of chemicals must also be considered when dealing with clinical intoxications in domestic animals. These include the animal’s age, sex, health, nutritional status, environment, and concurrent exposure to other chemicals, among others. The effects of these and other factors in modifying the outcome of poisoning can be of vital significance in determining its outcome and also point to appropriate management options. There is a vast amount of literature on this subject which can readily be found in toxicology textbooks.

Common Toxicoses in Food-Producing Animals Food-producing species include cattle, swine, and small ruminants. Swine differ from other animals in this category in that they have a simple stomach (monogastric), whereas the others have a compound stomach. Most of the toxicants affecting

http://dx.doi.org/10.1016/B978-0-12-386454-3.00444-9

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other animals also affect food-producing animals, but some toxicants are peculiar to or predominantly seen in foodproducing animals, partly due differences in diet. Toxicoses frequently encountered in ruminants include nonprotein nitrogen, copper, lead, and arsenic poisoning; mycotoxicoses; nitrite poisoning; plant poisoning; and blue-green algae poisoning. In swine, salt poisoning, mycotoxicoses, organic arsenicals, and toxic gases generated in swine confinement operations are often involved in toxic episodes.

Nonprotein Nitrogen Compounds Nonprotein nitrogenous sources include urea, biuret, and ammoniated feeds. These compounds are cheap sources of the nitrogen required by the animals for protein synthesis. Nonprotein nitrogen poisoning is a common problem and is often seen in animals not gradually introduced to feeds containing these compounds. Commonly known as urea poisoning, this is an acute fatal condition characterized by bloating, intense abdominal pain, ammonia breath, frequent urination, and frenzy. Often, several animals (or the entire herd) are affected simultaneously. In ruminants, the rumen microflora normally convert urea to ammonia, and the ammonia is rapidly utilized by the liver for protein synthesis. However, in cases of excess ammonia production, blood ammonia concentration quickly builds up to toxic levels and induces central nervous system (CNS) derangement. Therefore, in addition to the gastrointestinal signs, the animals will show fulminating CNS signs. Treatment of this disease involves giving a weak acid such as vinegar and plenty of cold water orally. The rationale for giving cold water and acetic acid is to slowdown the action of urease, the enzyme responsible for converting urea to ammonia, which requires body core temperature and pH for optimal function. The cold water lowers rumen temperature and the acetic acid lowers the pH. Infusions of calcium and magnesium solutions are recommended to alleviate tetany. Another source of nonprotein nitrogen (urea) poisoning in ruminants is the accidental ingestion of nitrogen-based fertilizers such as ammonium phosphate. Occasionally, cattle break into drums or bags of fertilizers containing these nitrogenbased compounds. The prognosis is grave in most cases if several animals are affected. If only a few valuable animals are affected, a rumenotomy can be performed. Although small ruminants (e.g., sheep and goats) have the same anatomical predisposition to nonprotein nitrogen poisoning, they are rarely poisoned.

Nitrate–Nitrite Excessive exposure of ruminant animals to nitrates causes nitrite intoxication, an acute rapidly fatal disease. The most common source of nitrates in ruminants’ consumption of forage was grown on heavily fertilized fields and has accumulated high levels of nitrates. All common animal feeds, such as sorghum, alfalfa, and milo, can accumulate excessive amounts of nitrates. Another common source of nitrate poisoning is contaminated drinking water. Nitrates are highly water soluble. Underground water can become contaminated

from heavily fertilized fields. Runoff from fertilized fields is another source of contamination in surface pools and ponds. Nitrate from all different sources is additive. Therefore, both feeds and water should be tested in determining the source of poisoning. Nitrates are reduced to nitrites by rumen microflora. In normal circumstances, the nitrite ion is rapidly utilized for ammonia synthesis, but in cases of excessive acute intake of nitrate, the excess nitrite ion is absorbed into the bloodstream. In blood, the nitrite ion reacts with hemoglobin to form methemoglobin. Methemoglobin is incapable of oxygen transport, and the animal compensates for the anoxia by increasing its respiratory rate. Consequently, affected animals will be hyperventilating, have brownish mucous membranes, and are weak. Chronic intake of nitrates has been reported to cause reproductive problems including abortion, but experimental results regarding this claim are currently inconclusive. Besides reacting with hemoglobin, the nitrite ion also replaces iodine in the thyroid gland, thereby interfering with the function of the thyroid hormone. Treatment of nitrate/nitrite poisoning involves intravenous infusion of 1% methylene blue at a rate of 1.5 mg kg 1 body weight and withdrawal of the offending feed. Appropriate withdrawal times should be observed.

Copper–Molybdenum Sheep are more susceptible to copper poisoning than are cattle, but cattle are more sensitive to molybdenum poisoning than are sheep. The in vivo relationship between copper and molybdenum is well understood. Excessive dietary copper induces molybdenum deficiency and vice versa. Copper from different sources is additive. Copper is an essential element for cattle and is usually added to their feeds; however, molybdenum is not considered essential and is therefore not added. Cattle feeds therefore have high copper concentrations and no molybdenum. Feeding cattle feed to sheep will likely cause poisoning in sheep. Sheep rations should have a copper: molybdenum ratio of 6:1 to avoid copper poising in this species. Copper intoxication in sheep is an acute condition that develops after excessive chronic copper intake. During the chronic phase, copper is stored in the liver until a critical concentration is reached. Stressful conditions, such as transportation or insufficient feed or water intake, will trigger a massive hepatic release of copper and cause a hemolytic crisis. Affected sheep have hemoglobinuria, are weak, and die acutely. The massive release of hemoglobin can block the renal tubules, inducing renal failure. The prognosis is poor for animals already showing clinical signs. Chelation therapy using D-Penicillamine is the recommended treatment but will likely benefit exposed animals not showing clinical signs. In cattle, molybdenosis is characterized by a foamy diarrhea which may be bloody. Affected cattle also have depigmented hair. Molybdenosis is a subacute to chronic condition and occurs when the copper:molybdenum ratio is 2:1 or less. The condition shows geographical distribution and occurs in areas deficient in copper or having an excess of molybdenum (e.g., parts of California, Oregon, Nevada, and Florida). Treatment for this condition involves copper supplementation in the feed.

Veterinary Toxicology

Lead Despite awareness of the dangers of lead poisoning in humans and domestic species, it is surprising that lead poisoning is the most frequently encountered intoxication in food-producing animals. Lead poisoning is more commonly seen in cattle than in other food-producing animals. Young animals are most frequently affected because of their curiosity and because of their indiscriminate feeding habits. There are several sources of lead poisoning in cattle. Discarded junk automobile batteries, paint, and leaded water pipes are the most common sources. Quite often, uninformed owners will discard or store old batteries in farm environments and cattle will find and chew them. Discarded leaded pipes, especially those used around oil wells, are a common source of lead poisoning. Lead-contaminated crankcase oil has also been a source of lead poisoning in cattle. Lead interferes with heme synthesis and causes renal and CNS lesions in food-producing animals. Affected animals initially become anorectic. They may then become belligerent, blind, and have periodic seizures at the terminal stages of the poisoning. Once these CNS signs have set in, the prognosis becomes grave but treatment with chelating agents may be of value. Chelating agents include calcium disodium ethylenediaminetetraacetic acid (calcium disodium salt of EDTA) and 2,3-dimercapto1-propanesulfonic acid.

Arsenic Arsenic poisoning is second to lead as the most frequently reported heavy metal toxicant in food producing animals. Arsenic is present in the environment in two forms: inorganic and organic arsenicals. Inorganic arsenic is often incorporated into pesticides, which are the most common sources of arsenic poisoning in cattle. Inorganic arsenicals are also used as herbicides and cattle sometimes are exposed by eating recently sprayed forage. Another common source is when cattle lick ashes of burned fence posts. Arsenic is used as a wood preservative and remains in ashes. Inorganic arsenic poisoning is a rapidly developing and fatal disease. Affected animals show severe gastrointestinal irritation. They suffer severe abdominal pain, have hemorrhagic diarrhea, and are depressed. Usually, these signs appear 24–36 h after exposure to the inorganic arsenic. Organic phenylarsonic arsenicals are less toxic to mammals than the inorganic forms. Phenylarsonic compounds are usually incorporated in swine (and poultry) feed for disease control and to improve weight gain. Examples of these compounds include arsenilic acid, 3-nitroarsenilic acid, and 4-nitroarsenilic acid. Organic arsenicals are also available as trivalent and pentavalent compounds, and the trivalent forms are more toxic than the pentavalent compounds. These phenylarsonic compounds target peripheral nervous system. They cause demyelination of peripheral nerve fibers leading to ataxia and paralysis of hindquarters. The condition occurs frequently in swine kept on feed containing 1000 ppm organic arsenicals for at least 3–10 days or 250 ppm organic arsenicals for 20–40 days. Therefore, unlike inorganic arsenic poisoning, which is an acute form of the disease, poisoning by phenylarsonic compounds is an insidious condition.

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In addition, organic arsenicals are commonly involved in swine intoxications because they are incorporation in swine feeds. Inorganic arsenic poisoning is more commonly seen in cattle. Treatment of inorganic arsenic poisoning involves decontamination procedures and use of the antidote British antilewisite compound (BAL; 2,3-dimercaptopropanol). Use of demulcent to coat the gastrointestinal tract and the use of antibiotics are also recommended. Organic arsenic poisoning treatment involves withdrawal of the offending feed, with recovery occurring in 3–5 days. Severely affected pigs should be culled.

Selenium Chronic selenium poisoning is a regional problem occurring in areas where the selenium content in soil is high. Selenium is then absorbed and concentrated by selenium-accumulating plants such as the Astragalus species. Cattle, sheep, goats, and swine are exposed by consuming these selenium accumulating plants. Acute selenium poisoning occurs when animals consume plants containing more than 10 000 ppm or following selenium injections. This disease is characterized by sudden death or labored breathing, abnormal movement and posture, frequent urination, diarrhea, and death. Plants containing very high selenium concentrations are unpalatable. Therefore, acute selenium poisoning from plant ingestion is rare. However, chronic selenium poisoning is relatively common. Chronic consumption of plants containing as low as 50 ppm can cause chronic selenium poisoning. Affected animals are anorexic, have impaired vision, wander, salivate excessively, are emaciated and lame, and lose hair. Removal of animals from pastures whose forages contain high selenium is the recommended cure but may be unsuccessful if the condition has persisted for over several weeks.

Mycotoxins Some of the mycotoxins of veterinary interest are aflatoxins, deoxynivalenol (DON), diacetoxyscirpenol (DAS), T-2 toxin, zearalenone, ochratoxins, and fumonisin B1. Mycotoxins are especially a common problem in warm climates where high temperatures and relative humidity support fungal growth and favor mycotoxin production on cereal grains. All foodproducing animals are susceptible and clinical signs will depend on the particular mycotoxins involved. Usually more than one mycotoxin is involved because several species of fungi (e.g., Fusarium, Penicillium, and Aspergillus) coexist and often produce more than one type of the common mycotoxin. For example, DON, DAS, and T-2 toxin coexist in grains. The common sources of aflatoxins in food-producing animals include corn and oats. When aflatoxins are ingested in parts-per-million concentrations, acute death can occur. Affected animals show severe gastrointestinal pain and hemorrhage. Aflatoxins are severe hepatotoxicants; therefore, hepatomegaly and jaundice may be observed in severe subacute cases. Quite often, however, aflatoxin poisoning is an insidious condition due to the chronic intake of parts-per-billion

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aflatoxin concentrations over a prolonged period of time. Clinical signs include poor weight gain, decreased milk production, and poor reproductive performance, including abortions. Virtually, every organ function is affected by aflatoxins, including the immune system which is impaired. Exposed animals easily succumb to infectious diseases and have increased somatic cell counts in milk. Because metabolites of aflatoxins are excreted in milk even in apparently healthy cows, this is a public health issue. Toxicity due to T-2 toxin has been reported in North America and other parts of the world, including Germany, Hungary, France, and South Africa. It is less common than aflatoxin poisoning. Affected animals suffer gastrointestinal bleeding and will pass bloodstained feces. The animals will perform poorly (i.e., have low weight gain, decreased milk production, and decreased food intake). T-2 toxin is also an immunosuppressant. All food-producing animals are susceptible to T-2 toxin. Zearalenone is an estrogenic mycotoxin that usually causes intoxication in swine usually from consuming contaminated corn. Prepubertal swine are mostly frequently affected, but animals of all ages are vulnerable. Affected animals exhibit swelling of the vulva and excessive straining, which may cause vaginal prolapses. In male animals, zearalenone will cause decreased libido. There is no effective treatment apart from withdrawing the offending feed containing the mycotoxin. DON (vomitoxin) is a more common mycotoxin in the Midwest and often causes problems, especially in pigs. DON induces vomiting and feed refusal in swine, the most sensitive species. It also is an immunosuppressant. DON is an important mycotoxin that could lower production in swine and feeds should be carefully monitored for this toxin. DAS and ochratoxin are not of major economic importance although they can be toxic to food-producing animals. DAS causes necrosis and erosion of the oral mucous membranes. Consequently, affected animals exhibit feed refusal and have impaired growth. DON (also called ‘vomitoxin’) is a more common toxicant especially in pigs. DON induces vomiting and feed refusal in swine. It also is an immunosuppressant. Collectively, DON is an important mycotoxin that could lower production in swine and should be carefully monitored. Ochratoxins cause renal problems, including hydronephrosis, especially in swine. Ergot poisoning is occasionally encountered in livestock fed grain screenings contaminated with Claviceps purpurea. The active constituents are ergotoxin and ergotamine, which are vasoactive compounds. Ergot alkaloids can also be produced by saprophytic fungi growing of fescue. These compounds cause vasoconstriction of the peripheral vessels, especially those of extremities, leading to necrosis and gangrene of hooves, ears, and tails. Abortions and agalactia have been reported in cattle fed ergot-contaminated feed. Therapy consists of discontinuation of the contaminated feed, combined with antibiotic therapy to prevent secondary bacterial infections in the necrotic tissues. Fumonisin B1 is produced by Fusarium moniliforme, a fungus that predominantly grows worldwide on corn. Fumonisin B1 causes pulmonary edema and respiratory distress in swine. Numerous deaths have been reported in swine fed fumonisincontaminated corn screenings.

The most practical treatment for mycotoxicoses consists of withdrawal of the contaminated feed from the affected animals and supportive care for the affected animals.

Blue-Green Algae Blue-green algae poisoning occurs in late summer and early fall when the algae forms a scum on top of ponds or other stagnant waters. Because of the predisposing husbandry practices, cattle are most frequently involved. Blue-green algae poisoning has been reported in North America, South Africa, and Britain. Algae of genus Anabaena are most frequently involved. There are two distinct syndromes in blue-green algae poisoning: the neurotoxic and the hepatotoxic syndromes. The neurotoxic disorder is peracute, and cattle drinking water containing the neurotoxic principle Anatoxin A can die within a few minutes and usually are found quite close to the pond or water (algae) source. On the other hand, the hepatotoxic principle causes an acute type of poisoning characterized by lethargy and jaundice. Death may occur 2 or 3 days after drinking contaminated water. Because of the peracute nature of the blue-green algae-induced neurological syndrome, there is hardly time for treatment and the prognosis is universally grave. Treatment of animals affected with the liver syndrome of blue-green algae poisoning involves appropriate supportive therapy.

Toxic Gases Toxic gases are of primary concern in closed animal housing, especially in swine operations. Because of the intensive swine confinement operations with buildings designed to save on energy, toxic gases can accumulate in swine houses and result in serious health consequences to animals and caretakers in cases of ventilation failure. These toxic gases are generated from the decomposition of urine and feces, respiratory excretion, and the operation of fuel-burning heaters. The most important gases are ammonia, hydrogen sulfide, carbon monoxide, and methane. A number of vapors, which represent the odors of manure decomposition, such as organic acids, amines, amides, alcohols, carbonyls, and sulfides, are also produced. Respirable particles, which may be loaded with endotoxins, are also a major health problem in swine confinement operations. Ammonia is highly soluble in water and will react with the mucous membranes of the eyes and respiratory passages. At 100 ppm or greater ammonia concentrations, ammonia intoxication will produce excessive tearing, shallow breathing, and clear or purulent nasal discharge. The irritation of the respiratory tract epithelium leads to bronchoconstriction and shallow breathing. Hydrogen sulfide poisoning is responsible for more animal deaths than any other gas. At concentrations of 250 ppm and above, hydrogen sulfide causes irritation of the eyes and respiratory tract and pulmonary edema. Hydrogen sulfide concentrations above 500 ppm cause strong nervous system stimulation and acute or sudden death. In order to prevent hydrogen sulfide poisoning, manure pits should not be agitated when pigs are on the premises, and proper ventilation should be in place.

Veterinary Toxicology

Carbon monoxide is produced by incomplete combustion of hydrocarbon fuels. Poisoning by carbon monoxide is caused by operating improperly vented space heaters or furnaces in poorly ventilated buildings. Carbon monoxide binds to hemoglobin forming carboxyhemoglobin, which hampers hemoglobin’s oxygen carrying capacity, subsequently causing hypoxia. Concentrations of carbon monoxide >250 ppm cause hyperventilation, respiratory distress, and stillbirths. Methane is a flammable and colorless gas produced from organic wastes through bacterial action. It displaces oxygen in respirable air, thus producing oxygen starvation if present in high concentrations. Nitrogen dioxide is a very poisonous gas that is responsible for causing silo fillers disease in humans. The gas is also toxic to animals. Nitrogen dioxide is produced during the first few weeks after silage has been cut and put into the silo. The highest nitrogen dioxide concentrations are reached during the first 48 h after filling the silo. In vivo, nitrogen dioxide dissolves in water to form nitric acid, which is very corrosive to the respiratory tract epithelium and the lungs. Nitrogen dioxide concentrations as low as 4 or 5 ppm can cause respiratory system disturbances. Exposure to sulfur dioxide concentrations of 5 ppm or greater causes irritation and salivation in swine. The gas is soluble in water, forming the more toxic sulfuric acid. It is the sulfuric acid that causes eye and nasal irritation, and in severe cases, it produces hemorrhage and emphysema of the lungs. The effect of these toxicants singly or in combination is to produce a hypofunctional respiratory system. Affected animals also become predisposed to respiratory tract infections. The end result is significantly retarded growth and reduced productivity in the affected animals. It is therefore important to ensure that suitable animal housing has adequate ventilation in all year round to provide animals with a healthy breathing and a highly productive environment.

Toxic Plants Poisonous plants can be encountered worldwide where livestock are grazed. Many countries or regions provide information about toxic plants in their area through ministries, academia, and extension services. The list of rangeland poisonous plants potentially encountered by grazing animals is extensive. Likewise, the lesions and characteristics of the intoxication frequently vary with the type of plant or species affected. Veterinarians and locals of the region frequently acquire anecdotal or other experience with the conditions likely to produce intoxication. Further reading will be necessary to fully understand the effects these toxicants have on rangeland animals specific to the region. The practitioner must learn to rule in or rule out plant toxins by their region, target species, and clinical symptoms. An astute practitioner will consider time of year, travel history, elevation, location, current forage conditions, and the origin of fed hay or commodities. Plant poisoning is less common when either the toxic plant is not present or other suitable forage is available in a relative abundance. Some toxic plants are ingested along with normal foraging, grazing, and browsing behaviors of range animals while others are ingested selectively. Ingestion of these plants does not always lead to overt intoxication. Subclinical

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intoxications can occur, which nonetheless can adversely affect productivity. Poisonous plant toxic principles are distributed in different portions of the plant and are biochemically diverse. Many plants contain a single or multiple toxic principles. This leads to a complex list of clinical signs associated with specific plants. Depending on the species of the plant, poisoning may be possible after ingestion of either live or dried plant material(s). It is not uncommon for hay to be contaminated with many dried poisonous plants. Roots, nodes, leaves, stems, seeds, and seedpods may contain varying amounts of the toxic principle. The alkaloids are the most abundant class of toxic principles. For example, solanine, atropine, taxine, slaframine, swainsonine, piperidine, quinolizidine, berberine, protopine, gelsimine gelseminine, gelsemoidine, and other groups such as pyrrolizidine alkaloids, steroidal alkaloids, glycoalkaloids, esteralkalodes, and piperidine alkaloids are represented in a diverse group of plants. Glycosides are another abundant toxin class represented by cyanogenic glycosides and cardiac glycosides, among others. Additionally, there are many other classes of plant toxins including, but not limited to, tannins, saponins, oxalates, oils, phenols, lectins, toxalbumins, ketones, alcohols, quinones, resinoids, glucosides, phenols, phytotoxins, amines, sulfides, terpenes, and oxalates. In some cases, plants may carry toxins produced by fungi that grow on plant materials in symbiotic relationships. Such toxins are called mycotoxins. These include ergot alkaloids produced on tall fescue and rye grass. Mycotoxins have been discussed elsewhere. Body systems and organs most prominently affected by plants include the digestive tract; the liver, kidneys, and nervous system; the heart and blood; the skin; and the reproductive tract and its functioning. It is important to realize, however, that toxic plants rarely affect only one body system or organ and thus may generate a complex pattern of effects in any one poisoned animal. Toxicity of a given plant can vary widely depending on the prevailing natural conditions. It is therefore not surprising that a given toxic plant may be toxic under certain conditions (e.g., during stressful drought conditions) but safe during other times.

Sodium Chloride (Salt) Salt poisoning/water deprivation is most commonly encountered in swine operations, but can also occur in feedlot cattle. The causes of this disease are twofold. Most commonly, the pigs will be on a ration containing a recommended concentration of sodium chloride, but management failures or changes can favor conditions that cause salt poisoning to occur. These poor management conditions include the sudden lack of water, which can be caused by frozen water pipes in winter or the breakdown of water supplies. The other common cause is the accidental addition of excessive amounts of salt- or sodiumcontaining feed components to the ration. Salt poisoning has also been reported in swine operations even when the management situation is appropriate; the only change was that the animals had been moved into a new housing facility, as occurs at weaning. In those situations, the animals are not used to the watering facilities in the new

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buildings and they do not know how to access the water; thus, they go without water while continuing to feed on the normal salt-containing ration. Clinically, salt poisoning is a neurological disorder, and the syndrome is rather acute. Affected pigs will spin on their hindquarters and fall down convulsing. The pigs will also show a characteristic rhythmic pattern of seizures which occurs cyclically every 3–5 min. Many pigs are usually affected at the same time. The condition is corrected by allowing access to adequate but restricted amounts of water.

Common Toxicoses of Poultry and Wild birds Chickens, ducks, and turkeys are also are affected by toxicants in feed, water, or the environment. There is also much concern and interest in wildlife intoxications. Commonly poisoned are wild birds, including those kept in zoos. Exotic pet birds kept in homes are not spared either. This discussion will emphasize the toxicoses encountered in poultry.

Medications Sulfonamides have been used as coccidiostats in poultry for several decades. Although sulfonamides possess inhibitory action against coccidiosis and other pathogenic agents, they can be toxic and have particularly been shown to be so in poultry. In poultry, sulfonamide toxicity is characterized by blood dyscrasia and renal and liver dysfunctions. Feeding chickens a mash containing as low as 0.2% sulfonamides for 2 weeks is toxic. Clinically affected birds have ruffled feathers; are depressed, pale, and icteric; and have poor weight gain and a prolonged bleeding time. In laying birds, sulfonamides cause a marked decrease in egg production, thin rough shells, and depigmentation of brown eggs. The temperature of affected birds is often elevated. At postmortem, hemorrhages are found in the skin, muscles (especially those of thighs and breast), and in the internal organs. Once these effects are noticed, the concentration of sulfonamides in the ration should be evaluated and the feed involved withdrawn. Other chemotherapeutic agents sometimes involved in poisoning poultry include the other coccidiotats, such as nicarbazine, zaolene, and nitrophenide, and the ionophore monensin. As little as 0.006% nicarbazine in the diet causes mottled yolks, and at 0.02% there is depressed rate of growth and reduced feed efficiency. Feeding 0.025% nicarbazine to day old chicks for 1 week resulted in the chicks becoming dull, listless, weak, and ataxic. Feeding zaolene at twice the recommended level of 0.025% will cause nervous signs and depress growth and feed efficiency. The nervous signs include stiff neck, staggering, and falling over when the birds are excited. Nitrophenide possesses marked electrostatic properties and, therefore, sticks to the walls of a feed mixer. The last bits of feed in the feed mixer will normally contain a high concentration of nitrophenide and that elevated concentration has caused disturbances in posture and locomotion, retarded growth, and increased mortality in chickens. Postural disturbances include a tilted position of the head, tremor of the neck, and difficulty in maintaining the righting reflex.

In general, poultry are more resistant to monensin poisoning than other species, but there have been reports of monensin intoxication in turkeys accidentally fed rations containing 250-ppm monensin. There is a big difference in susceptibility to monensin poisoning among various species of poultry. Chickens and turkeys less than 2 weeks old are more resistant than older birds, but keets (young guinea fowl) seem more susceptible than their adults and the young of other species. For example, diets containing 200-ppm monensin were not toxic for poults, whereas 100-ppm monensin was toxic for keets.

Cresol Cresol was a commonly used disinfectant in poultry houses but has been gradually withdrawn and replaced by less toxic disinfectants. Nevertheless, in some regions and countries, cresol is still being used. Cresol poisoning in the chicken usually occurs at 3–6 weeks of age. Affected chicks are depressed and have a tendency to huddle. They exhibit respiratory problems such as rales, gasping, and wheezing. With prolonged cresol exposure, some chicks will develop edema of the abdomen.

Sodium Chloride (Salt) All poultry and pigeons are susceptible to salt poisoning. Young birds are more susceptible than adults. Although both acute and chronic forms of salt poisoning can occur, the chronic form is more commonly encountered and is caused by prolonged ingestion of feed containing high salt content. Salt levels of 0.5% and above in drinking water or 5–10% in feed cause death in baby chicks. Signs of salt poisoning in poultry include anorexia, thirst, dyspnea, opisthotonos, convulsions, and ataxia. Increased water consumption may be the most significant early indicator of hazardous exposure to salt in poultry.

Insecticides Organophosphorous compounds are used regularly around poultry houses to control external parasites. Lindane, a chlorinated pesticide in the form of a dust, is sometimes used around chickens. Adult chickens poisoned by lindane quit eating, manifest opisthotonus and flapping of wings, have clonic muscle spasms, and die in a coma. The organophosphate compounds commonly involved include diazinon, malathion, and parathion. Diazinon is applied to chicken premises, but this compound is very toxic to ducklings. When used at rates recommended for chickens, 100% mortality has resulted from use of this compound on 1- or 2-week-old ducklings. Experimental studies suggest that goslings are three times more sensitive than ducks, chickens, and turkeys. Poisoned birds are unable to stand, salivate profusely, and manifest tremors of the head and neck. Brain cholinesterase activities in birds dying of organophosphate poisoning are on the average 69% less than those of controls. Other organophosphate compounds commonly used on chicken premises include dichlorvos, malathion, and parathion. Birds poisoned by these compounds manifest signs similar to those seen in diazinon poisoning. Other effects that

Veterinary Toxicology

may be seen include depression, ataxia, and reluctance to move; paralysis and lacrimation; gasping for breath; and development of diarrhea, crop stasis, and dyspnea. In general, ducks are more sensitive to organophosphate poisoning than are chickens, and care should be exercised when using these products on premises holding ducks. The carbamate insecticide Sevin is a widely used poultry insecticide. This compound is relatively safe, but deaths have been reported in turkey poults kept on premises where the product has been excessively applied at 10 times the recommended rate. The clinical signs are similar to those caused by organophosphate insecticides because they share a common mechanism of action.

Heavy Metals Lead poisoning is not as common in domestic poultry as it is in wild birds, but it is the most common metal toxicant reported in the avian species. Lead shot causes losses in waterfowl populations throughout North America every year. All birds are susceptible to lead poisoning, but most losses are reported in waterfowl because their feeding habits predispose them to the ingestion of lead pellets from shotguns and other sources. Characteristic signs of lead poisoning are related to CNS derangement. They include ataxia, depression, paralysis of the wings, and convulsions. In some cases, the birds presented are anemic, emaciated, regurgitating, and weak. Green diarrhea has often been reported in affected birds. Yellow phosphorus is a highly toxic element that may still be used as a rodenticide. Poultry and wild birds can be intoxicated by consumption of bait intended for rodents. Firework fragments also are a common source of poisoning in free-ranging birds. Affected birds are depressed and anorectic; have increased water consumption; and manifest diarrhea, ataxia, paralysis, coma, and death.

Rodenticides Rodenticides are used in poultry facilities to kill rodents which invade the premises. Unfortunately, sometimes poultry gain access to these baits. In addition to yellow phosphorus, other rodenticides are potentially toxic to poultry and other birds. The clinical signs caused by these rodenticides in birds are similar to those observed in other animals. The potent secondgeneration rodenticides, such as brodifacoum, are especially dangerous to birds. These coumarin anticoagulants act by interfering with vitamin K utilization, causing bleeding because of depletion of vitamin K-dependent clotting factors. Poisoned birds bleed from their nares and subcutaneously and have oral petechiations. Quite often, the affected birds are also weak and depressed from anemia, or may be found dead. Of special interest are secondary or relay intoxications seen in free-ranging birds that consume carrions of animals that died of rodenticide poisoning. This happens most commonly with brodifacoum. Strychnine and sodium monofluoroacetate are other rodent control compounds that cause relay toxicosis because they cause acute death in the primary victims and are thus present in high concentrations in carrions.

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Strychnine-poisoned birds show clinical effects within 2 h of ingesting the product. The birds become apprehensive and nervous and have violent tetanic convulsions, which cause them to become exhausted and to die of hypoxia. Sodium monofluoroacetate causes overstimulation of the CNS and myocardial depression. Cardiac failure is the cause of death and occurs within 1 h of consuming the bait or contaminated carcass.

Mycotoxins Mycotoxicoses are common problems for the poultry industry in warm moist climates and in developing countries in the tropics. Aflatoxins are the most commonly involved mycotoxins in poultry intoxications. Poultry are normally exposed by consumption of contaminated feed, especially corn. Some developing countries lack the resources to adequately screen corn for aflatoxins. In other instances, poultry feed is made from the poor quality (and contaminated) corn that has been rejected for human consumption. Some developing countries do not have regulatory guidelines on mycotoxins in animal and poultry feeds. Aflatoxicosis in poultry can either be an acute or chronic disease, depending on the exposure dose. Ducklings are more susceptible to aflatoxin than are turkeys, pheasant, or chickens. In acute cases, affected birds become lethargic, their wings droop, and they manifest nervous signs such as opisthotonos; they die with their legs rigidly extended backward. Chronic dietary consumption of 2.5 ppm aflatoxin causes a significant drop in weight gain and egg production. Perhaps more important is the increased susceptibility of the affected flock to infection because chronic consumption of aflatoxin-containing feed lowers the immunity of the birds. Aflatoxicosis is therefore a disease of serious economic consequences to the poultry industry in developing countries both through lowered productivity and because of death of affected birds. Ergot poisoning has been reported in areas where rye is commonly used as poultry feed. In acute ergot poisoning, the birds’ combs become cold, wilted, and cyanotic. The birds are generally weak, thirsty, and have diarrhea. In severe cases, the birds go into convulsions, become paralyzed, and die. Ochratoxins have been reported to cause renal toxicity in poultry.

Common Toxicoses in Dogs and Cats Dogs and cats are commonly poisoned by human medications, pesticides, herbicides, household products such as ethylene glycol (antifreeze), and human foods. By far, the most common toxicities in these small animals involve ingestion of human medications available in the household. Clinical signs vary depending on the medications involved from liver injury caused by acetaminophen poisoning to renal failure and gastric ulcerations induced by ingestion of nonsteroindal anti-inflammatory compounds. Ingestion of human medications by pets is generally accidental, but in some cases, it is caused by uninformed pet owners medicating their pets. Although some medicines have been used in the past for animals, their margin of safety is oftentimes smaller than the therapeutic dosage.

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Human Food Human foods are classically considered to be unhealthy for companion animals; however, recent alternative diet trends for companion animals are increasing their exposure. Coffee, chocolate, alcohol, yeast dough, macademia nuts, avocados, onions, garlic, chives, grapes, raisins, and xylitol-containing snacks are all harmful and some are potentially fatal for companion animals. Xylitol, grapes, and raisins are covered in the emerging toxicant section. Alcohol is a CNS depressant in pets that can alter behavior, decrease reflexes, and produce staggering and polyuria. It is present in liquors, beers, wines, and fermented products such as yeast dough or distiller’s mash. Dogs are susceptible to alcohol poisoning owing to their relative small size per amount of alcohol consumed. Treatment should focus on activated charcoal absorbents and intravenous electrolyte fluid therapy. Macademia nuts cause depression, weakness, stiffness, lameness, ataxia, tremors, vomiting, hyperthermia, pale mucous membranes, and abdominal pain. Typical clinical pathological changes include elevated alkaline phosphatase and lipase. Clinical signs persist primarily between 12 and 24 h. Since there mechanism of action is unknown, treatment includes emetics, activated charcoal, electrolyte replacement, and antipyretics. Ingestion of any part of the avocado plant is associated with myocardial necrosis due to persin toxin and is potentially life threatening. Clinical signs include respiratory distress, exercise intolerance, cough, cyanosis, lethargy, ascites, pleural edema, peripheral edema, and lethargy. Treatment should include diuretics, antiinflammatories, and beta blockers. Chocolate contains methylxanthine derivatives primarily theobromine and caffeine. These and other methylxanthines are documented toxicants in animals. Companion animals are often times intoxicated around holiday time when chocolates are either used in cooking or left in locations accessible to pets. Methylxanthine concentrations are highest in the original source of cocoa commodities such as cocoa beans, cocoa powder, and cocoa hulls (husks). Common pantry items or candies contain one or more of the following ranked here from highest to lowest methylxanthine content: baking chocolate, semi-sweet chocolate, hot cocoa, milk chocolate, and white chocolate. Cocoa husks are used as mulches or as organic pest control. Methylxanthines are competitive antagonists of adenosine (purinergic) receptors, competitive antagonists of benzodiazepine receptor, and are also phosphodiesterase inhibitors. Additionally, muscle contractility increases as free ionized calcium levels increase in the cytoplasm. Clinical signs include vomiting, ataxia, cyanosis, tachypnea, ventricular tachycardia, premature ventricular contractions, hypertension, tremor, and reflexive muscle rigidity (‘bouncing’). Hyperthermia, dehydration, hypokalemia, seizures, respiratory distress, and coma are signs of severe methylxanthine intoxication. Dogs are significantly more susceptible as the half-life of excretion is extended, relatively compared to other species. Antiemetics are indicated to control vomiting. Focus primarily on repeated frequent administration of activated charcoal and saline cathartics for 72 h to shorten the half-life of methylxanthine, which may ordinarily be reabsorbed through enterohepatic recirculation. Administer diazepam to control

seizures. Pentobarbitol or phenobarbital may be used to control nonresponsive seizures. Artificial respiration has been necessitated in some cases. Catheterize the bladder to prevent methylxanthine reabsorption. Lidocaine is indicated to control ventricular tachycardia which may control arrhythmias. Some antiarrhythmics are contraindicated as they limit renal excretion, the primary route of methylxanthine excretion. The use of medications that compete for microsomal enzyme metabolism is also contraindicated as caffeine is known to be metabolized by these enzymes. The best diagnostic samples to confirm methylxanthines are serum, urine, and stomach contents. Raw, dried, and cooked Allium spp. plants (onion, garlic, and chives) contain N-propylthiosulfates such as N-propyldisulfide, methyl disulfide, allyl disulfide, and S-methylcysteine sulfoxide. Many of these compounds interfere with glucose-6phosphate dehydrogenase enzyme leading to formation of reactive oxygen species (ROS) and lactic acid buildup. Cats are the most vulnerable species. Feeding baby foods to cats has been a source of intoxication. Heinz–Ehrlich body erythrocyte malformation is a hallmark of Allium intoxication. Hemoglobin is damaged and denatured in the presence of ROS concurrent with increases in erythrocyte fragility. Increased intravascular hemolysis of malformed cells leads to severe anemia. Clinical presentation of Allium-intoxicated cats and dogs include icterus, pale mucous membranes, weakness, recumbency, hemoglobinemia, and acute renal failure. Animals should be removed from the source of intoxication and receive symptomatic treatment. Blood transfusion is indicated in severe cases. Care must be taken to prevent overexcitement and collapse as there is a diminished capacity of the blood to properly carry oxygen to the peripheral tissues.

Garbage Aside for the risk of ingesting human foods, true garbage poisoning is a frequently encountered problem in small animals. This condition is also referred to as enterotoxicosis or endotoxemia, depending on whether poisoning is due to bacterial infection or due to bacterial endotoxins. Dogs and cats not well fed and/or not closely supervised when allowed to roam will eat garbage. Cats may also be affected, but only rarely so, because they are discriminate eaters. The bacteria most commonly involved are coliforms, staphylococci, salmonellae, and occasionally Clostridium botulinum. Enterotoxemia-affected animals often develop a bacteremia after eating infected garbage or carrion. Clinical signs normally appear at least 24–48 h after ingestion of the infected material. The condition is characterized by anorexia, vomiting, severe abdominal pain, fever, and a bloody diarrhea. Endotoxemia poisoning is due to bacterial endotoxins, which are normally present in bacterial cell walls. The clinical signs are generally indistinguishable from those of enterotoxemia, except that in the latter there is no bacteremia; this can be evaluated by performing a blood culture. Although rare in occurrence, botulism is a rapidly developing fatal disease resulting from ingesting bones contaminated with C. botulinum. In small animals, the disease is characterized by an ascending paralysis. At first, there is muscle weakness and incoordination in the hind limbs. As the paralysis progresses anteriorly, dyspnea and convulsions develop.

Veterinary Toxicology

Alternatively, garbage consumption can result an atypical intoxication due to tremorgens, a class of mycotoxins commonly associated with ‘grass staggers’ in hoof-stock. Dogs are very susceptible to intoxication with penitrem A and roquefortine tremorgenic mycotoxins. These mycotoxins are produced primarily by Penicillium spp. molds that are known to grow on nearly any spoiled food waste; however, tremorgens produced by Aspergillus spp., C. purpurea, and others may be implicated. A classical history for dogs with this exposure is consumption of food waste in a compost pile. Sustained tremors, convulsions, and death are typical clinical signs of tremorgens. Although garbage consumption may be a relatively common event compared to other toxic exposures, the severity of intoxication varies greatly with the amount and type of toxin ingested. Vomition is a common early sign of intoxication and may clear some ingested toxin. When signs are severe, medical attention will be required. If the cat or dog is presented early after ingestion, general decontamination procedures should be performed to reduce absorption. In addition to activated charcoal and saline cathartics, antiinflammatory corticosteroids and broad spectrum antibiotics should be given. Further treatment involves appropriate supportive therapy.

Household Chemicals Antifreeze is the household product most commonly involved in small animal poisonings. The active ingredient in antifreeze is ethylene glycol. The characteristic sweet taste of this compound makes it attractive to small animals. Ethylene glycol is metabolized in the liver by alcohol dehydrogenase to glycolic acid and then to oxalate. Glycolic acid contributes to acidosis, which is characteristic of ethylene glycol poisoning. The oxalic acid binds calcium from blood to form calcium oxalate, which precipitates into crystals which cause blockage of the glomerulus and renal tubules. Severely affected animals have renal failure characterized by anuria and uremia. The binding of blood calcium to the oxalic acid produces hypocalcemia, which, if severe, can also cause death. Ethylene glycol poisoning is treated by giving 4-methylpyrazole, an antidote which inhibits alcohol dehydrogenase. Household products, such as sink cleaners, dishwashing detergents, and toilet cleaners, are also common causes of poisonings in small animals. The majority of cleaning detergents are corrosive compounds, which contain strong alkali, acids, or phenolic compounds. These compounds act as contact poisons, causing coagulative necrosis of the tissues they come in contact with. Following ingestion of these products, the dog or cat will vomit, have severe abdominal pain, and may develop diarrhea. The vomitus and feces may be bloody. Affected animals may show other signs depending on the specific ingredients of the ingested products. For example, products containing phenolic derivatives will cause acidosis and hepatotoxicity. In general, treatment following ingestion of household products is symptomatic and involves the administration of adsorbents such as activated charcoal, gastrointestinal protectants such as Peptobismol, and the correction of any systemic disturbances (such as acidosis) which may accompany the poisoning. Animals should also be provided abundant glucose and a high protein diet.

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Rodenticides Rodenticide poisoning is commonly seen in small animals. Rodenticides are widely used around farmhouses to control rodents, such as rats and mice, which destroy property and farm produce. Several classes of rodenticides are currently in use, including the anticoagulant rodenticides (warfarin and its second-generation cousin brodifacoum), zinc phosphide, strychnine, compound 1080, and arsenicals. Small animals get poisoned by consuming baits directly. The clinical signs seen will vary with the compound involved and, in the majority of cases, dogs (because of their indiscriminate eating habits) are involved. Intentional poising is another source of intoxication in pets. Strychnine and anticoagulant rodenticides are the most frequently reported offenders. Strychnine poisoning in dogs is a rapidly developing syndrome characterized by tonic–clonic seizures. These signs result from strychnine competitively blocking the inhibitory neurons in the nervous system. The animals start showing clinical effects within 20 min to 1 h of ingesting strychnine and, if the animal has ingested a sufficient amount, death from anoxia occurs acutely. Anoxia results from paralysis of the respiratory muscles. Treatment of strychnine poisoning is symptomatic and involves general decontamination procedures, use of sedatives such as phenobarbital and diazepam, maintenance of adequate urine output, and respiratory support. The sedatives control seizures and allow the vital muscles to relax and maintain their vital respiratory functions. The anticoagulant rodenticides have been in use for many decades. Some strains of rats became genetically resistant to the so-called first-generation anticoagulant rodenticides such as warfarin. This led to the introduction of second-generation rodenticides such as brodifacoum. Unlike the first-generation rodenticides, which required multiple ingestions of the bait, the second-generation rodenticides normally require single feeding and act relatively acutely. Clinical signs can be evident within 24–48 h and have a long residual action. These anticoagulant rodenticides act by inhibiting vitamin K-dependent blood coagulation factors (VII, IX, and X), by decreasing prothrombin synthesis, and by directly damaging blood capillaries. Animals poisoned by the anticoagulant rodenticides are generally weak, have swollen joints because of bleeding into the joint cavities, may hemorrhage from the nostrils and lungs, and may pass blood-stained feces. Treatment of anticoagulant rodenticide poisoning involves wholeblood transfusion, if the bleeding and resulting anemia are severe, and vitamin K1 injections for several days. Early intervention requires general decontamination procedures to limit further rodenticide absorption, especially in the case of exposure to second-generation rodenticides, followed by prolonged vitamin K1 therapy. Brodifacoum undergoes enterohepatic recirculation and animals poisoned by these pesticides will likely benefit from multiple activated charcoal doses to enhance elimination. The toxicity of zinc phosphide results from the phosphine gas, which is produced by acid hydrolysis of the pesticide in the stomach. Animals with partially filled stomachs are more sensitive to zinc phosphide poisoning than those with empty stomachs because of the greater acid secretion precipitated by

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the presence of food. The phosphine gas is absorbed systemically and exerts its effects in the lungs and the CNS. Poisoned animals exhibit respiratory difficulties because of the buildup of fluids in the lungs. They also exhibit seizures. The cause of death is respiratory failure. Supportive therapy, including respiratory support, and sedatives are recommended for treatment of zinc phosphide poisoning. However, the prognosis is poor because no effective antidote is available. Compound 1080 (sodium monofluoroacetate) is a very lethal toxicant which acts by blocking the Emdem–Meyerhoff pathway, thereby depriving cells of vital energy. Fluoroacetate is metabolized to fluorocitrate, which inhibits mitochondrial aconitase. This blocks adenosine triphosphate production. Affected animals are initially uneasy, then they become excitable and will run in various directions in a frenzy, and finally they will fall into seizures and die of anoxia. There is no effective antidote. Once clinical signs develop, poisoned animals will almost always die within a few hours. Compound 1080 poisoning is widely reported in Central and South America. Cholecalciferol is a rodenticide that has been introduced relatively recently and is frequently involved in poisonings of dogs and cats. The compound alters calcium homeostasis by promoting calcium absorption from the gut and also by mobilizing calcium from bone. Consequently, poisoned animals have increased levels of blood calcium. The calcium is then subsequently deposited in soft tissues like the kidneys, digestive tract mucosa, lungs, heart, major blood vessels, liver, and muscle. Mineralization of soft tissues interferes with normal function of these organs. Clinically, the animals do not show signs until 24–48 or more hours after ingestion of the bait. The affected animals are depressed, have reduced urine production, and the urine is of low specific gravity. Severely poisoned animals have hematemesis, azotemia, and cardiac arrhythmias. Animals with preexisting renal impairment are more susceptible to cholecalciferol poisoning. Cholecalciferol poisoning requires protracted treatment, which may require as long as 3 weeks in severe intoxications. Appropriate treatment consists of fluid therapy to assist the kidneys in removing the excess calcium, corticosteroids to minimize inflammation, and calcitonin to enhance calcium resorption into the bone. Pamidronate disodium is the new antidote for this poison. Several other rodenticides can cause poisoning in small animals but do so less frequently because they are used less often. Red squill and thallium have been used as rodenticides for many years. Red squill acts as a cardiotoxicant and causes death by cardiac arrest. It also produces convulsions and paralysis. Thallium is a general systemic toxicant. It has a high affinity for sulfhydryl groups throughout the body. Thallium causes cracking at the corners of lips and also causes hair loss. Alpha-naphthyl-thiourea causes death by inducing lung edema and subsequently leading to anoxia. White phosphorus is a hepatorenal toxicant. Animals poisoned by white phosphorus have severe abdominal pain, hepatomegaly, and signs of hepatic insufficiency, such as prolonged bleeding and hypoglycemia. Vacor is pancreotoxic and causes hypoglycemia. Cases of rodenticide poisoning in small animals should always be regarded as emergencies. General decontamination procedures, such as inducing vomiting with hydrogen peroxide

or apomorphine, the use of activated charcoal to bind the unabsorbed toxicant(s), and/or enterogastric lavage, should almost always be employed to minimize absorption and the resulting hazard from the toxicant(s).

Insecticides The insecticides most commonly involved in poisoning dogs and cats are the organophosphates and carbamates, pyrethroids, and the abermectins. This reflects a common use of pesticides in the environment. The organophosphate and carbamate insecticides have a common mode of action, which is the inhibition of acetylcholinesterase enzyme in the CNS. This enzyme metabolizes acetylcholine, a neurotransmitter in autonomic ganglia and at cholinergic nerve endings. The inhibition of acetylcholinesterase by organophosphate and carbamate pesticides causes acetylcholine to accumulate at nerve synapses and to produce persistent firing of cholinergic nerve fibers. Affected animals become overexcited and have increased respiratory rates, diarrhea, excessive salivation, and muscle tremors. Treatment of animals poisoned by organophosphate compounds involves the administration of atropine and prolidoxime. Cases involving carbamates should only be treated with atropine. Oximes are contraindicated. The chlorinated hydrocarbons were among the first synthetic insecticide compounds to be used but have fallen into disfavor because of their persistence in the environment. Typical examples of chlorinated hydrocarbon insecticides are 1,1,1-trichloro-2,2-di(4-chlorophenyl)ethane, lindane, chlordane, endosulfan, and toxaphene. The toxicity of these compounds in small animals is characterized by severe CNS effects, including ataxia and convulsions. Although most of these insecticides are banned or their use highly restricted in Western countries, they are still in use in developing countries. Thus, chlorinated hydrocarbon insecticide poisonings still occur more commonly in these regions. However, one of the authors (WKR) has diagnosed endosulfan and chlordane poisoning in dogs in the United States. Another group of insecticides commonly involved in small animal poisonings are plant product derivatives – pyrethrins and their synthetic congeners, the pyrethroids. This class of pesticides is currently enjoying a resurgence because of their selective insecticidal properties and rapid degradation in the environment. These compounds are mainly metabolized in the body by liver glucuronidation. The cat is the most sensitive domesticated animal to pyrethroids because of the low activity of the glucuronide conjugating system in this species. Young cats, less than 6 weeks of age, are the most sensitive. Pyrethroids are more potent than pyrethrins and are most commonly used currently. Pyrethroid compounds formulated with the insect repellant DEET were responsible for numerous deaths in cats and dogs in mid-1980s. Pyrethroids interfere with sodium channels in nerves causing them to fire repetitively. Clinical signs of pyrethroid poisoning in cats include ataxia, excitement, and muscle fasciculations and tremors. There is no antidote for pyrethroid poisoning, but symptomatic treatment, such as decontamination procedures and sedation, usually results in full recovery.

Veterinary Toxicology

Herbicides Herbicides are not often involved in small animal intoxications despite their frequent use around farms and the possibility of exposure. However, intoxication in dogs from consumption of herbicide concentrates during mixing is occasionally reported. The triazine herbicides act by inhibiting plant photosynthesis and are generally safe products for mammals. The LD50 value of these compounds is at least 1900 mg kg body weight in the rat. Therefore, toxicity in dogs can only practically occur following the ingestion of large volumes of concentrates. In experimental situations, triazine herbicide-poisoned dogs can become either excited or depressed, develop motor incoordination, and may proceed to have clonic–tonic spasms. Some inorganic arsenic compounds are also used as herbicides. These inorganic arsenicals are general protoplasmic poisons and are therefore hazardous to both plant and animal life. Affected dogs almost always vomit, have severe abdominal pain, and develop bloody diarrhea. The vomitus may contain mucous shreds and blood from erosion of the gastric and intestinal epithelium. Paraquat, although restricted from use in Western countries, is a highly toxic herbicide that is still readily available in both Western and developing tropical countries. Upon intake, paraquat is rapidly metabolized in the liver and the lungs with the production of secondary oxygen free radicals. It is these free radicals that cause injury to tissues and especially do so to the lungs. Poisoned animals die acutely of respiratory failure. Nephrotoxicity has also been reported. Unlike other animals, the dog appears sensitive to chlorophenoxy herbicides, such as 2,4-D; the dog’s oral LD50 to 2,4-D is 100 mg kg 1 body weight. Ventricular fibrillation is the cause of death in severely poisoned dogs. Ingestion of sublethal doses induces stiff extremities, ataxia, myotonia, paralysis, coma, and subnormal temperatures. Chlorates are herbicides that are often used along roadsides and other rights of way. They are rapidly metabolized in the liver to the chlorate ion, which induces methemoglobinemia in both cats and dogs. Cats, however, because of the greater susceptibility of their hemoglobin molecule to oxidation, are more susceptible to chlorate poisoning than dogs. Organophosphate herbicides (e.g., glyphosate and merphos) are weak cholinesterase inhibitors and are moderately toxic to dogs and cats. Carbamate herbicides are not inhibitors of acetylcholinesterase but are also moderately toxic to dogs. The LD50 of most of the carbamate herbicides is at least 5000 g kg 1 body weight.

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involvement. Lead poisoning is commonly a chronic disease in dogs, but the overt CNS signs may appear suddenly. Lead poisoning also causes blood dyscrasias characterized by reticulocytosis and anemia. Similar clinical signs are elicited in the cats. Treatment consists of giving chelating agents, such as calcium EDTA, BAL, dimercaptosuccinic acid, or D-penicillamine. Although classified as a trace mineral, zinc poisoning is a common toxicant of dogs. Common sources include ingestion of zinc nuts, bolts, toys, and especially zinc pennies minted after 1983. Zinc is a general systemic toxicant. The most significant finding is hemolysis, which leads to anemia and attendant secondary renal failure caused by hemoglobininduced nephrosis. Treatment involves gastrotomy or endoscopy to remove the foreign object from the stomach. Blood transfusion may be required in severely anemic cases.

Toxic Plants and Mushrooms Although one would not expect dogs and cats to eat plants, plant poisoning is surprisingly often reported in these species. Because of their exploratory behavior, puppies and kittens are most often involved. Boredom and unfamiliarity due to change of environment are some of the predisposing factors that lead to plant ingestions by dogs and cats. Poisonous ornamental plants (e.g., philodendron and rhododendron) and plants growing around fences (e.g., cassia and oak) are often involved. The range of potentially poisonous plants is vast, and the clinical signs are diffuse and similar to those reported for food-producing animals. Most cause gastrointestinal signs such as vomiting and diarrhea. Others cause oxalate-induced nephrotoxicity and lifethreatening hypocalcemia. In cats, ingestion of Easter lilies causes acute renal failure. Occasionally, dogs or cats will eat poisonous mushrooms or be fed poisonous mushrooms by uninformed owners. Amanita muscaria and A. pantherima are acutely toxic and induce signs within 15–30 min of ingestion. These two mushroom species cause nervous signs, which include salivation, pupillary constriction, muscular spasms, drowsiness or excitement, and, in severe intoxications, coma and death. Ibotenic acid and muscimol are the active chemical components. However, consumption of A. phaloides, A. virosa, and A. verna produces gastrointestinal signs which become evident 6- to 12-h postingestion. These effects include violent vomition, muscle cramps, diarrhea, and dehydration. These latter mushrooms also cause hepatic damage that becomes apparent 3–5 days after ingestion. Phalloidin and alpha and beta amanitin are the poisonous principles in this group of fungi.

Heavy Metals Lead is sometimes involved in small animal poisonings. Lead poisoning is more commonly reported in the dogs than in the cats, but both species are susceptible. The sources of canine lead poisoning include ingested leaded objects, such as lead weights, and paint chips from old houses being renovated. One of the authors has diagnosed a case of chronic lead poisoning following workplace exposure. The clinical signs of lead poisoning in the dogs involve primarily the gastrointestinal, cardiovascular, and CNS. Dogs may present with abdominal pain and diarrhea in addition to the CNS

Emerging Toxicants Xylitol Xylitol is a five-carbon sugar alcohol. It is naturally occurring in many fruits, vegetables, mushrooms, oats, as well as nutritive fibers such as husks, corncobs, and plant stalks. Xylitol was first discovered by the German chemist Emil Fisher in 1891 after hydrogenating D-xylose wood sugar. During World War II’s sugar shortage, xylitol was used in Finland as a replacement for sucrose. It is used mainly as a low-calorie

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sweetener for diabetic diets or as a natural sugar substitute. It is currently present in many varieties of gum, chewable vitamins, candies, medicinal pills, mints, lozenges, oral care products, and baked goods. These are the common sources of poisoning in dogs. Dogs ingesting greater than 0.1 and 0.5 g kg 1 are at risk for hypoglycemia and hepatic failure, respectively. In the dogs, insulin is released from the pancreatic b-islet cells as a result of stimulation from xylitol-derived glucose as well as direct action of xylitol itself on these cells. Hyperinsulinemia causes hypoglycemia and associated clinical signs of lethargy, ataxia, collapse, and seizures. Vomiting is often the first reported clinical sign. Although not commonly evaluated, glucagon, a hypoglycemia-responsive hormone and a known cause of vomiting, is likely elevated in patients with xylitol toxicity and may explain this clinical sign. Blood glucose can drop within 30–60 min, but clinical signs of hypoglycemia have been delayed up to 12 h in some cases of xylitol gum toxicity. Several cases of liver failure have been reported in dogs following xylitol intoxication, often without a preceding hypoglycemic crisis. Many cases exhibited hemorrhage and increased prothrombin time and/or increased partial thromboplastin time consistent with a liver failure-associated coagulopathy. Treatment is symptomatic.

Grapes and Raisins Grape intoxication in dogs has only become clinically recognized in the past decade but has been reported worldwide. Clinically affected animals usually suffer from acute renal failure. Dogs are commonly documented to develop a pattern of increasingly dramatic clinical symptoms within 48 h of ingestion of any variety of grapes and raisins. Grapes are commonly ingested by dogs in the form of fresh or dried fruits but are also present in fruitcakes, mince pies, chocolate bars, malt loaf, scones, snack bars, buns, and raisin pudding. Ingesting 2.8 g kg 1 of raisin or 3.2 g kg 1 of fresh grape has shown to cause clinical symptoms in some dogs. Clinical cases develop after consumption of grapes of any variety, color, source, method of rearing, harvest technique, and processing. Likewise, all subpopulations of dogs seem well-represented by clinical cases with no reported predispositions with respect to age, breed, or sex. The toxic principle is unknown. Tannins, glucose overload, hypervitaminosis D, ochratoxin, citrinin, hypovolemic shock, and renal ischemia have been suggested as potential causes of acute renal failure seen in clinical cases. Proximal tubule cells are most likely affected by a toxic insult due to their relatively high, large endothelial surface area, and transport mechanisms that may concentrate toxins passively or actively. The toxic doses of the grape fruit have been reported commonly between 10 and 57 g kg 1. APCC and VPIS databases have demonstrated a similar proportion of cases that were asymptomatic (>60%), symptomatic (w30%), or euthanized/died (w5 to 10%) after ingesting grapes or raisins. Higher proportions of dried fruits were ingested by dogs that showed clinical signs, in comparison to the asymptomatic dogs that primarily consumed grapes or smaller average amounts of dried grapes. Vomiting and diarrhea within 6–12 h postingestion are the most common

clinical signs. Vomiting is extremely common in dogs with a history of grape ingestion and azotemia while diarrhea is present in nearly half of these cases. Blood urea nitrogen and creatinine will be elevated within 24 h in clinically affected dogs. Within 2–3 days postingestions, clinically ill dogs may exhibit signs of renal insufficiency including hyperkalemia, oliguria, anuria, and/or hypercalcemia. Anuria, oliguria, or stranguria are commonly reported apparent symptoms following grape ingestion and are predictive of poor clinical outcomes. Crystalluria and especially cylindrical casts have been commonly reported; however, there is a large variation in the types of crystals present.

Melamine and Cyanuric Acid Congeners Melamine is a triamine compound first discovered and synthesized in the early 1800s. It is deaminated to the oxytriazine structural analogs ammeline, ammelide, and cyanuric acid. Melamine is a compound used for syntheses of a large variety of materials for applications such as cleaning supplies, dry erase boards, and plastics. Melamine is synthesized from urea, requires several purifications steps, and is marketed in various purities where the lowest quality is contaminated with oxytriazines. Problems with melamine and oxytriazinecontamination in foodstuffs are linked to the rapid and unregulated production. Several major pet food and human food safety incidents involving melamine occurred worldwide between 2003 and 2008, causing notable morbidity and mortality in children, cats, dogs, poultry, and pigs. Melamine and other nitrogen-rich oxytriazine compounds were added to feed ingredients to falsely boost the apparent protein levels and were used not only in pet food but also in livestock and fish feeds. Major pet food companies recalled more than 1000 commercial pet food throughout the world. During the 2007 outbreak of renal failure in dogs and cats in the United States, veterinary diagnostic laboratories found melamine and triazines in many suspected foods. Later testing has demonstrated the presence of melamine in vegetable powder, milk powder, binding agents, and commodities. Melamine and cyanuric acid were shown to be responsible for acute renal failure in cats and dogs in many of the previous cases. Melamine intoxication, as occurred in the recent episodes in animals, is characterized by acute renal failure, uremia, anorexia, anuria, polydipsia, lethargy, and occasional vomiting coupled with azotemia and hyperphosphatemia. Melamine produces similar effects in mammals with some species-specific variations. In dogs, the kidneys were greenish in color with greenish uroliths in the renal pelvis or bladder. Histologically, crystals are present in the intraluminal space of the tubule as well as urine and touch impressions of kidneys. Melamine-associated crystals are brown or green with a rough surface appearance but the crystals are rounded with a frequent radial lamellar orientation known as pinwheel radiating striations. This fan-shaped crystal is brightly birefringent when viewed under cross-polarized light. There is no known antidote for melamine intoxication. Treatment consists of withdrawing the offending feed, fluid diuresis, alkalinization of urine, and other supportive therapy.

Veterinary Toxicology

Common Toxicoses in Horses In comparison to food-producing animals and small animals, horses are less frequently poisoned. The most commonly encountered equine toxicoses involve food-related toxicants such as monensin and mycotoxins, pesticides, snakebites, selenium, cantharidin, and poisonous plants. Most plants that are hazardous to food-producing animals are also toxic to horses.

Insecticides The pesticides most frequently responsible for equine poisonings are the organophosphate, carbamate, and chlorinated hydrocarbon insecticides. Both the organophosphates and the carbamates are acetylcholinesterase enzyme inhibitors and present clinical pictures similar to those seen in food-producing animals and pets.

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over a short time causes diarrhea (which is often foul smelling and contains air bubbles), neurological and cardiovascular effects, and respiratory difficulty. Death in these horses is due to respiratory failure. Chronic exposure to low levels of excessive selenium is characterized by hoof abnormalities at the coronary bands and by discoloration and loss of hair (alopecia). The hoof deformities are painful and cause lameness. An unusual form of selenium poisoning caused by injection of excessive dose of selenium in Polo horses was reported in Florida in 2010. Horses died suddenly, likely of heart failure and respiratory distress.

Toxic Plants

Cantharidin is an irritant toxic agent present in blister beetles. Only a few of the several species of blister beetles contain cantharidin. Blister beetles are abundant in mid- and late summer when alfalfa hay containing the beetles is harvested in the central plains of the United States. Horses are poisoned by eating the alfalfa hay containing crushed swarms of blister beetles. Affected horses develop severe colic, abdominal pain, and blood-tinged urine. They will kick at their bellies and roll on the ground; severely affected horses may die of shock. Although recommended treatment involves the use of pain killers, such as banamine hydrochloride, and large volumes of intravenous fluids, there is no effective therapy for affected horses.

The plant poisonings commonly encountered in horses are those that cause gastrointestinal problems, cardiovascular intoxication, liver damage, primary or secondary nervous system involvement, and sudden death. Plants such as castor bean and oleander cause colic and diarrhea. Oleander also causes cardiac toxicity. Prolonged ingestion of some plants for several weeks can lead to liver damage and hepatic cirrhosis. This commonly occurs with the hepatotoxic plants such as Amsinckia, Senecio, and Crotolaria. Liver damage compromises the ability of the horse to detoxify ammonia that accumulates in vivo, leading to CNS derangement (hepatoencephalopathy). Plants that cause CNS stimulation include larkspur, locoweed, lupine, water hemlock, fitweed, yellow star thistle, and Russian knapweed. Common plants that produce CNS depression are black locust, bracken fern, horsetail, milkweed, and white snakeroot. Milkweed and white snakeroot are also cardiotoxic. Like ruminants, horses will avoid eating toxic plants because they are usually not palatable. Therefore, consumption of poisonous plants will most often occur during drought conditions or following overgrazing when the animals lack suitable pasture. Sudden death in horses can be caused by consumption of cyanide-containing plants, such as sorghum and cherry trees. The cyanide ion forms a complex with cytochrome oxidase. This prevents electron transport and the utilization of oxygen by body tissues. As a consequence, the circulating blood is well oxygenated and is bright cherry red in color. This condition is an emergency, and treatment requires the prompt intravenous administration of both sodium thiosulfate and sodium nitrite. Horses, like other monogastrics, are more resistant to plants capable of causing nitrate–nitrite poisoning than are ruminants. However, horses can reduce nitrates to nitrites in their cecums, but it requires about three times as much nitrate to produce the same toxic effect in horses as in ruminants.

Heavy Metals

Mycotoxins

Lead poisoning in horses is characterized by neurological effects. Affected horses are either depressed or excited. Colic and diarrhea are also seen. Because of laryngeal nerve paralysis, horses poisoned by lead also present with difficult respirations and a roaring syndrome. Abortions may also occur. Selenium is an essential element but is toxic when excessive quantities are ingested. Exposure of horses is usually through consumption of seleniferous (accumulator or indicator) plants (e.g., Astragalus spp.). Exposure to high quantities of selenium

Contaminated grains (corn, wheat, and milo) are the sources of mycotoxin exposure for horses. The most commonly involved mycotoxins are aflatoxins, T-2 toxin, and fumonisin B1. Aflatoxins will cause nonspecific effects, such as a poor thriving condition, hemorrhages, and abortions. T-2 toxin is a trichothecene mycotoxin that causes prolonged bleeding times and digestive tract inflammation in affected horses. A specific mycotoxin which uniquely affects horses is fumonisin B1, which is produced by the fungus F. moniliforme; it has

Monensin Horses are highly susceptible to monensin poisoning in comparison with the other domesticated animals. Monensin is an ionophore antibiotic normally added to cattle and poultry feed to provide growth stimulation by enhancing the intestinal absorption of calcium and sodium, among other uses. Horses are easily poisoned by accidentally consuming cattle or poultry feed containing the recommended amounts of monensin for those species. Affected horses can die suddenly without any other signs. Monensin affects the cardiac and skeletal muscles, and acute cardiac failure is the cause of death. Prevention is the best cure as there is no antidote to monensin intoxication. Permanent injury resulting in scarring of the cardiac muscles can lead to sudden death in horses months after exposure.

Blister Beetles

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Veterinary Toxicology

been responsible for causing the condition called equine leukoencephalomalacia. Horses acquire the disease by consumption of molded corn. Affected horses become anoretic and depressed after consuming the infested grain for only a few days. The condition then progresses with the animals becoming blind, walking aimlessly, head pressing, being unable to swallow, and dying in a coma 1–4 days after the initial onset of signs.

Conclusions Veterinary toxicology is very broad. In this article, brief accounts of the common toxicants in different animal species was presented. It can be determined from this article that there are species differences in the way animals react to specific toxicants. Because some animals are more sensitive than others to specific toxicants, and because multitudes of toxicants cause similar clinical signs, definitive diagnosis of some poisonings usually requires consultation with veterinary toxicologists. This entry was neither intended to be a comprehensive reference for diagnosis and treatment of animal poisonings nor meant to be all inclusive. Rather, it presents the commonly encountered toxicoses in veterinary medicine. It should be clear that all animals are susceptible to some toxicants and that some toxicants are toxic to all animals (including humans). It is therefore important to be cautious when handling and using chemicals around animals; also, a clean environment must be provided for all animals. Animals should be fed well-balanced quality food from reputable sources, and suspect feed should be either avoided or carefully examined for potential toxicants before being fed to animals. It is also vitally important to remember that all chemicals become poisons if the exposure rate is sufficiently high. Therefore, even useful and recommended compounds used routinely around animals (e.g., growth promoters, feed supplements, pharmaceuticals) can be life threatening if used excessively or if given to species for which they were not intended. The susceptibility of sheep to cattle feed containing copper and the high risk to horses fed poultry feeds containing monensin are cases in point.

See also: Aflatoxin; Phthalates; Ammonia; Asbestos; Brodifacoum; Carbamate Pesticides; Carbon Monoxide;

Castor Bean; Copper; Coumarins; DDT (Dichlorodiphenyltrichloroethane); DEET (Diethyltoluamide); Dichlorvos; Dieldrin; Ethylene Glycol; Hydrogen Sulfide; Lead; Malathion; Methane; Molybdenum; Mushrooms, Coprine; Mushrooms, Cyclopeptide; Mycotoxins; Melamine; Nitrites; Oleander; Organochlorine Insecticides; Organophosphates; Paraquat; Parathion; Pyrethrins/ Pyrethroids; Selenium; Sodium; Strychnine; Sulfur Dioxide; Thallium; Warfarin.

Further Reading Beasley, V.R., 1990. Toxicology of Selected Pesticides, Drugs and Chemicals. Veterinary Clinics of North America (Small Animal Practice). Saunders, Philadelphia, PA. Blood, D.C., Radostits, O.M., 1994. Veterinary Medicine. Saunders, Philadelphia, PA. Cheeke, P.R., 1997. Natural Toxicants in Feeds and Poisonous Plants, second ed. Prentice Hall, New York. Hays Jr., W.J., Laws Jr., E.R., 1991. Handbook of Pesticide Toxicology. Academic Press, San Diego, CA. Kingsbury, J.M., 1964. Poisonous Plants of the United States and Canada. Prentice Hall, Englewood Cliffs, NJ. Peterson, M.E., Talcott, P.A., 2006. Small Animal Toxicology. Elsevier, St Louis, MO. Plumlee, K.H. (Ed.), 2004. Clinical Veterinary Toxicology. Mosby, St Louis, MO. Osweiler, G.D., 1996. Toxicology. Williams & Wilkins, Media, PA. Osweiler, G.D., 2011. Ruminant Toxicology: Veterinary Clinics of North America (Food Animal Practice). Saunders, Philadelphia, PA. Rumbeiha, W., Morrison, J., 2011. A review of class I and class II pet food recalls involving chemical contaminants from 1996 to 2008. J. Med. Toxicol. 7 (1), 60–66.

Relevant Websites Poisonous Houseplants and Ornamentals http://www.merckvetmanual.com/mvm/htm/ bc/ttox03.htm Poisonous Plants of Temperate North America http://www.merckvetmanual.com/mvm/ htm/bc/ttox04.htm Important Poisonous Vascular Plants of Australia http://www.merckvetmanual.com/ mvm/htm/bc/ttox05.htm Cornell University “Consultant” Diagnostic Support System http://www.vet.cornell.edu/ consultant/consult.asp Animal Poison Control Center http://www.aspca.org/pet-care/poison-control American Board of Veterinary Toxicology http://www.abvt.org/public/index.html European College of Veterinary Pharmacology and Toxicology http://www.ecvpt.org/