Occurrence

Zinc poisoning in livestock is a rare occurrence and poorly documented.

Source of toxin

Dietary levels of zinc associated with poisoning in different species have been summarized.¹ Pigs develop abnormal articular cartilage at 500 ppm dietary zinc, while 2000 ppm zinc in the ration is associated with copper deficiency, anorexia, and subcutaneous hematomata. For horses, appproximately 3600 ppm in the diet, or 90 mg/kg body weight reduces growth rate. Sheep and cattle generally are adversely affected by 900 ppm zinc in their diet.

Importance

Zinc is one of the least important agricultural industrial poisons but individual farms may suffer serious losses.

Acute poisoning

Chronic poisoning

Dairy cattle show chronic constipation and a fall in milk yield.

Pigs fed buttermilk containing zinc show anorexia, lethargy, unthriftiness, rough coat, subcutaneous hematomas, stiffness, lameness, progressive weakness with enlargement of the joints, particularly the shoulder joint, and finally recumbency.

Samples for confirmation of diagnosis

Piglets

Within 1 or 2 hours of injection sudden deaths occur, sometimes accompanied by vomiting and diarrhea. By necropsy examination there is severe myodegeneration of skeletal but not cardiac muscle. The progeny of vitamin E deficient sows are most susceptible, and the most toxic compounds are those which contain a high proportion of their iron in ionic, and therefore readily absorbable, form. In the state of deficiency of vitamin E the muscle cell membranes are damaged and extensive biochemical changes result, including a great increase in extracellular potassium levels causing cardiac arrest and sudden death.

Horses

Deaths have occurred in horses within a few minutes of intramuscular injection of iron compounds. Others have shown severe shock but recovered. Death when it occurs appears to be due to acute heart failure. Newborn foals also die soon after the oral administration of a ‘digestive inoculant’ which contains ferrous fumarate (16 mg/kg) or the iron compound alone. Naturally occurring cases¹ and experimental cases point to acute hepatitis as the critical lesion, and the iron compound as the cause. Commencing 2 days after dosing the signs include depression, ataxia, recumbency, jaundice, and nystagmus. The mortality rate is 66% and the lesions are hepatitis and jaundice.

Cattle

Acute hepatitis and sudden deaths have occurred in 6–9-month-old bulls about 24 hours after injection of an organic iron preparation.²

Ruminants

Chronic poisoning in cattle is associated with inappetence, weakness, loss of weight, poor hoof keratinization, dry brittle horns, matting of the hair, keratosis, and peeling of the skin. At necropsy there is hyperkeratosis of forestomach epithelium and degenerative changes in most organs. In sheep, levels of 60 μg/g of feed for 137 days are needed to be associated with illness. Experimental poisoning of sheep is associated with anemia, nephropathy, and bone demineralization at a dose rate of 2.5 mg/kg body weight per day. Abortion, congenital defects, and stillbirths are also listed as toxic outcomes. The cutaneous lesions can be partly offset by the administration of zinc.

Pigs

In young pigs, levels in the feed of 50 mg/kg for 6 weeks reduce growth rate and are associated with an iron-responsive anemia.

Carbon tetrachloride poisoning

Risk factors

Factors which increase the likelihood that carbon tetrachloride will be toxic in a particular dosing incident are:

Phenothiazine poisoning

Exposure to phenothiazine and potential poisoning has occurred in the past from its extensive use as an anthelmintic. Today, one of the remaining common uses may be for control of small strongyles in horses. Keratitis, the noteworthy sign of poisoning, occurs most commonly in calves, rarely in pigs and goats, and usually after a heavy single dose of phenothiazine, but it can occur in a program of daily intake in a dietary premix. Phenothiazine is absorbed from the rumen as the sulfoxide, conjugated in the liver and excreted in the urine as leucophenothiazine and leucothionol. As urine is voided, further oxidation turns the metabolic products to a red-brown dye, phenothiazine and thionol which may be confused as hematuria or hemoglobinuria.¹ Cattle are unable to detoxify all the sulfoxide and some escapes into the circulation and can enter the aqueous humor of the eye, causing photosensitization. Other photodynamic agents which cannot enter the eye may also be produced, and they, with the sulfoxide, are associated with photosensitization of light-colored parts of the body. Hyperlacrimation, with severe blepharospasm and photophobia commences 12–36 hours after treatment and is followed by the development of a white opacity on the lateral or dorsal aspects of the cornea, depending on which is exposed to sunlight. Most animals recover within a few days, particularly if kept inside or in a shaded paddock. If the animals continue to be exposed a severe conjunctivitis with keratitis may result.

Tetrachlorethylene poisoning

Tetrachlorethylene rarely produces incoordination which may be evident for 1 or 2 hours after dosing in cattle or sheep. Treatment is not usually necessary.

Hexachloroethane poisoning

Hexachloroethane is preferred to carbon tetrachloride for the treatment of fascioliasis in cattle but it is not completely without danger. Deaths are rare (1 in 20 000 cattle treated), and in sheep (1 in 40 000) but non-fatal illness is not uncommon. Susceptible groups may show narcosis, muscle tremor, and recumbency after administration of the standard dose (cattle: 15 g per 6 months of age up to a maximum of 60 g; sheep: 0.4 g/kg BW); such animals should be given half this dose on two occasions at 48-hour intervals.

Hexachlorophene

At high dose rates (25–50 mg/kg BW) hexachlorophene is associated with atrophy of seminiferous epithelium of the testis of young adult rams. Repeated dosing is associated with periportal fatty changes in liver.

Rafoxanide and closantel

Rafoxanide and closantel, both highly regarded anthelmintics, and clioxanide, a discredited drug, are all halogenated salicylanilides, and have approximately the same low level of toxicity. They are capable of causing temporary or permanent blindness if overdosed.² In the latter case there is degeneration of optic nerve tracts and other optic pathways in the brain.

Nicotine poisoning

Nicotine poisoning seldom occurs in animals except in lambs and calves where nicotine sulfate is still incorporated in some vermifuges. Doses of 0.2–0.3 g nicotine sulfate have been toxic for lambs weighing 14–20 kg. Animals in poor condition are more susceptible than well-nourished animals. Animals are affected within a few minutes of dosing and show dyspnea with rapid shallow respirations, muscle tremor and weakness, recumbency, and clonic convulsions. Animals that survive the acute episode may show abdominal pain, salivation, and diarrhea. At necropsy there may be abomasitis and inflammation of the duodenum.

Treatment should include artificial respiration and the administration of respiratory center stimulants. Oral dosing with tannic acid preparations will precipitate the alkaloid and retard further absorption.

Piperazine

Piperazine compounds are relatively non-toxic but poisoning can occur in horses on normal or excessive doses. Signs follow a delay of 12–24 hours and include incoordination, pupillary dilatation, hyperesthesia, tremor, somnolence, and either swaying while at rest or lateral recumbency. Recovery follows in 48–72 hours without treatment.

Thiabendazole (2-(4′-thiazolyl)-benzimidazole)

At an oral dose rate of 800 mg/kg BW in sheep transient signs of salivation, anorexia, and depression appear. There are similar signs at larger dose rates and death is likely at a dose rate of 1200 mg/kg BW. Toxic nephrosis is the cause of death and is reflected in the clinical and pathological findings of hypokalemia, hypoproteinemia, and uremia.

Levamisole

All commercial preparations of levamisole consist of the levo isomer. Its mechanism of action is similar to nicotine by causing prolonged depolarization and neuromuscular junction blockade. In pigs, concurrent treatment with levamisole and pyrantel tartrate resulted in enhanced toxicity of the levamisole.³ Following treatment at standard doses, some cattle and, more rarely, sheep show signs of lip-licking, increased salivation, head-shaking, skin tremors, and excitability. The excitability is more marked in calves; when released they tend to raise their tails and run around the paddock. Coughing may commence within 15–20 minutes, but this is due to the death and expulsion of lung worms and stops in 24 hours. With higher doses the signs are more pronounced, defecation is frequent and hyperesthesia in the form of a continuous twitching of the skin may be seen. Double doses in goats produce mild depression and ptosis, while higher doses produce, in addition, head-shaking, twitching of facial muscles, grinding of teeth, salivation, tail-twitching, increased micturition, and straining. Accidental injection of pigs caused vomiting, salivation, ataxia, recumbency, and a high mortality within a few minutes of injection.

Parbendazole, cambendazole, and albendazole

Parbendazole and cambendazole are teratogens and are specifically contraindicated in pregnant animals especially during the first third of pregnancy and at dose rates higher than normal. The safety margin is small and their use at any dose level is not recommended in these females. Defects produced include rotational and flexing deformities of the limbs, overflexion of the carpal joints, abnormalities of posture and gait, vertebral fusion and asymmetric cranial ossification, cerebral hypoplasia and hydrocephalus. Albendazole at 4 times the standard dose also produces some abnormalities if given early in pregnancy.

Fenbendazole

A dose of fenbendazole and the flukicide, bromsalans, to cattle either simultaneously or within a few days of each other may be accompanied by deaths. As fenbendazole and the other tertiary benzimidazoles, oxfendazole, and albendazole, are extremely valuable in removing dormant Ostertagia ostertagi larvae, it is suggested that fascol (bromsalans) should not be used where this is an important problem or that 2 weeks should elapse between treatments.

Ivermectin

The intravenous injection into horses of a cattle formulation of ivermectin, contrary to the recommended usage, may cause immediate collapse with coma and periodic nystagmus. Treatment intravenously with flumethasone and flunixin meglumine is effective. Intramuscular injection of the ivermectin is associated with ventral midline edema, due possibly to a reaction to dead microfilariae, edema of limbs and eyelids, fever, dyspnea, disorientation, colic, and sudden death. Transient swelling at the injection site is common.

Occasional outbreaks of severe neurological disorders occur in only Murray Grey cattle after the administration of normal dose rates. Signs include incoordination, knuckling of the fetlocks, a swaying gait, muscle fasciculations, ear droop, blindness, and drooling of saliva, all apparent within 24 hours of dosing. The tongue is paralyzed and protrudes in some. Exercise enhances the syndrome and the patients collapse. Some are dead within 24 hours, some survive for 3 weeks, but all die. There are no gross necropsy lesions but the concentration of ivermectin in the brain is 10 times normal. A genetic penetrability of the meninges is suspected.

Organophosphatic anthelmintics

These are dealt with in the next section on insecticides. Industrial organophosphates and organophosphatic defoliants are dealt with in the section on miscellaneous farm chemicals.

Sumicidin

Sumicidin (fenvalerate) is a synthetic pyrethroid anthelmintic capable of causing non-fatal restlessness, yawning, frothing at the mouth, dyspnea, ear and tail erection, pupillary dilatation, ruminal tympany, regurgitation of ruminal contents, staggering, tremor, clonic convulsions and recumbency after a single oral dose. Single oral doses of >450 mg/kg are lethal. Repeated daily dosing (113 or 225 mg/kg BW) also causes death after 5–15 days.⁴

Occurrence

Poisoning with these compounds has been recorded in all animal species. The chlorinated hydrocarbons have come under so much criticism as environmental contaminants that they are rarely used directly on animals nowadays, so that outbreaks of clinical illness associated with them are much less common than they were.

Source of toxin

Ingestion, inhalation, aspiration, and percutaneous absorption are all possible portals of entry so that contamination of feed and application of sprays and dips can all be associated with poisoning. Organochlorides are closely regulated and banned in some countries but still widely used in agriculture, principally on growing plants to control insect pests, and on stored seed grain to control fungi. If the plants or grain, even milled and by products, e.g. bran, are fed to animals they can be associated with problems of tissue residues; if they are fed in sufficient quantities they can be associated with clinical illness. Many outbreaks are associated with the application to animals of products intended for crops, e.g. endosulfan, and labelled specifically ‘Not For Animal Use’. These insecticides may also contaminate soil and persist there for many years. Rooting animals such as pigs are particularly susceptible to this source of poisoning. These compounds are also sometimes fed accidentally and in large amounts in lieu of feed additives, and are associated with acute poisoning. In feedlotted or shedded animals cases may continue for periods as long as a year because of repeated contamination from the environment. Insect baits, e.g. grasshopper baits containing toxaphene and chlordane, used on pasture and for leaf-eating insects on market gardens can be associated with poisoning in livestock, which may eat large quantities of them. These insecticides, especially heptachlor, are incorporated in the soil before the crop of potatoes or maize is sown to control soil pests. Subsequent grazing of the field will cause contamination of the livestock for several years.

Method of application

Dipping of animals is the most hazardous method of application because entry may occur through all portals. Spraying is safer, percutaneous absorption and inhalation being the only portals of entry. The small particle size of the compound and concentration of animals in confined spaces while spraying, increase the possibility of poisoning. Oily preparations are not used for animal treatment but are used inadvertently and are readily absorbed through the skin.

Formulation used

Concentrations of insecticide in formulations used for spraying barns are much higher than those used for animals. Amongst spray preparations simple solutions are most dangerous followed by emulsions and least of all suspensions of wettable powder. Dusting is safest and is preferred to other methods. Preparations for use on plants are often unstable emulsions, which come out of suspension quickly when they reach the plant. If these preparations are used in animal dips the first few animals through the dip can be heavily contaminated and suffer acute, lethal toxic effects. Although the treatment of pastures to control their insect pests is usually safe to animals grazing, the treated pasture or hay made from it can cause contamination of animal products. This contamination can be avoided by incorporating the insecticide into superphosphate granules (‘prills’) instead of applying it as sprays or dusts. The use of chlorinated hydrocarbons to protect stored seeds provides a hazard to animals if they are fed on the treated seed.

Risk factors

The compounds vary in their ability to pass the skin barrier. Benzene hexachloride, aldrin, dieldrin, and chlordane are readily absorbed. Species susceptibility to skin absorption also varies widely. Very young animals of any species are more susceptible than adults, and lactating and emaciated animals also show increased susceptibility.

When these compounds were first used in dips, skin and foot infections occurred frequently because of contamination of the dip in the absence of a bactericidal agent. Cases of otitis media have occurred for the same reason, but more rarely.

Importance

All of these compounds are capable of causing death due to acute poisoning but these are increasingly rare. Because the compounds are soluble in fat and accumulate in body stores of it they are formidable threats to the meat industry. They are also excreted in significant amounts in milk and enter the human food chain at this point. They are concentrated still further in cream and butter. They also represent a threat to sucklings, but the degree of contamination in fetuses and suckling animals is much less than in their dams.

The principal importance of organochlorine poisoning is the contamination of animal tissues at levels which are not acceptable by modern health standards. These contaminations become the subject of veterinary investigations, and are susceptible to standard techniques of epidemiological examination.

Occurrence

All animal species are affected. OP compound and carbamate poisoning is a common poisoning encountered by veterinarians in animal agriculture but the losses are still very small.

Source of toxin

Risk factors

Importance

The introduction of these compounds into animal therapeutics as treatments for nematode, botfly, sheep nasal botfly, and warble-fly infestations and as insecticidal sprays on plants and soil has increased their importance as possible causes of poisoning, and as causes of pollution of milk, meat, and eggs. They also have a role in the poisoning of the native birdlife. They are now one of the most important causes of poisoning of agricultural animals.

Cholinesterase inactivation

The inactivation of cholinesterase by these organophosphorus compounds is associated with an increase in acetylcholine in tissues and increased activity of the parasympathetic nervous system and of the postganglionic cholinergic nerves of the sympathetic nervous system. The toxic effects thus reproduce the muscarinic and nicotinic responses of acetylcholine administration. Differences between the toxicities of compounds depend on the stability of this bonding between esterase and compound, and the toxicity of the substance formed by the bonding.

The muscarinic effects of acetylcholine are the visceral responses of the respiratory system and include marked respiratory distress due to a decrease in dynamic lung compliance and arterial oxygen tension and an increase in total pulmonary resistance; there is bronchial constriction and increased mucous secretion by bronchiolar glands. In the alimentary tract there is increased peristalsis and salivation. Effects in other systems include hypotension and bradycardia, pupillary constriction, sweating and abortion.

The nicotinic effects are the skeletal muscle responses of twitching, tremor and tetany, convulsions, opisthotonos, weakness and flaccid paralysis. There is a difference in the relative muscarinic and nicotinic responses between species, the visceral effects being more marked in ruminants and the muscular effects more evident in pigs in which posterior paralysis is the common manifestation.

Organophosphorus-induced delayed neurotoxicity

This form of toxicity is manifested by distal axonopathy commencing 1 or 2 weeks after the poisoning incident. There is a dieback of neurons causing regional flaccid paralysis, especially in long neurons. The pathogenesis of this lesion is the toxic end-product produced by the interaction between some OP compounds and the esterase, a phosphorylated neuropathy toxic esterase. Typical examples of this effect are:

Haloxon has this neurotoxic effect in that it is associated with only a slight depression in cholinesterase levels, but a neurotoxic response in the form of hindlimb ataxia has been reported in a proportion of treated sheep and pigs. The susceptibility of sheep is determined by their ability to metabolize this class of organophosphorus compound and this is genetically controlled.

Acute poisoning

Illness may occur within minutes of inhalation or ingestion of solutions of the more toxic compounds and deaths may commence 2–5 minutes later. After cutaneous application of dichlorvos to calves clinical signs appear within 30 minutes, peak at about 90 minutes and disappear in 12–18 hours. With less toxic compounds in solid form signs may not appear for some hours and deaths may be delayed for 12–24 hours.

Cattle, sheep and goats

In acute cholinesterase inactivation cases in ruminants the premonitory signs, and the only signs in mild cases, are salivation, lacrimation, restlessness, nasal discharge, cough, dyspnea, diarrhea, frequent urination, and muscle stiffness with staggering. Grunting dyspnea is the most obvious, often audible from some distance because of the number affected. Additional signs include protrusion of the tongue, constriction of the pupils with resulting impairment of vision, muscle tremor commencing in the head and neck and spreading over the body, bloat, collapse, and death with or without convulsions or severe respiratory distress. In sheep and goats¹ the signs are similar and include also abdominal pain. Signs disappear at 12–18 hours.

In delayed neurotoxicity cases signs do not appear for at least 8 and up to 90 days after the poisoning. Signs include posterior incoordination and paralysis. Chlorpyrifos is a specific example of this kind of poisoning. It should neither be applied to adult dairy cattle nor to any mature bulls. The signs include anorexia, depression, recumbency, a distended abdomen, ruminal stasis and diarrhea, and fluid splashing sounds on percussion of the right flank. Severe dehydration develops and may cause death.

Pigs

Horses

Miscellaneous OP poisoning

Syndromes include:

Dinitrophenol compounds

Hormone weed killers

2,4-D, silvex, MCPA and 2,4,5-T are non-toxic in the concentrations used on crops and pasture but dosing with 300–1000 mg/kg as a single dose is associated with deaths in 50% of cattle. They have also been tentatively linked with the high prevalence of small intestinal carcinomas in sheep. The picolinic acid herbicides picloram and clopyralid have also been suspected of the same relationship.

Barban is toxic at doses of 25 mg/kg, for cattle.

2,4-D at oral doses between 150 and 188 mg/kg BW is fatal to adult cows and at 10 mg/kg BW for sheep. Reversible toxic effects are produced with single doses in calves with doses of 200 mg/kg and in pigs with 100 mg/kg. Repeated administration of 50 mg/kg is toxic to pigs. In adult cows signs include recumbency, ruminal stasis, salivation, and tachycardia. In calves the signs are dysphagia, tympanites, anorexia, and muscular weakness; in pigs additional signs include incoordination, vomiting, and transient diarrhea. Long-term administration to pigs (500 ppm in the diet for 12 months) is associated with moderate degenerative changes in kidney and liver. 2,4-D may cause poisoning indirectly by its effect on the metabolism of weeds and sugar beets, resulting in a significant increase in the nitrate content of the leaves.

A commonly used mixture of 2,4-D, 2,4,5-T and a brushwood killer, monosodium methyl arsenate, is very toxic by mouth or after application to the skin; signs include anorexia, diarrhea, weight loss, and death in most cases.

Repeated dosing of sheep with silvex for about 30 days at 150 mg/kg BW causes death.

Single doses of the herbicides diallylacetamide, carbamate, triazine, and propionanilide at 250 mg/kg BW are fatal to sheep. Repeated small doses of carbamate are associated with marked alopecia. Acute poisoning with any of these compounds is unlikely unless large amounts are ingested accidentally.

Paraquat is associated with fibrosing pneumonitis in pigs but this does not develop in sheep or cattle with fatal doses. Poisoning with it is unlikely to occur unless it is administered accidentally or maliciously. A dose rate of 100 mg/kg BW is uniformly fatal in pigs with signs of vomiting, diarrhea, and dyspnea. Renal damage may also be a part of acute poisoning by paraquat.

Accidental poisoning of sheep due to contamination of pasture by diquat has been associated with widespread illness with signs of diarrhea and a significant mortality. In cattle accidental poisoning with diquat has been associated with fatal abomasitis and enteritis, hepatic and myocardial degeneration and pulmonary emphysema.

The herbicide triallate is associated with severe illness and some deaths with single oral doses of 300 mg/kg BW to sheep and 800 mg/kg to pigs. Salivation, bradycardia, vomiting, muscular weakness, dyspnea, tremor and convulsions are followed by death in 2–3 days. It is also toxic when given in small amounts continuously.

The triazine herbicides atrazine and prometone appear to be non-toxic at usual levels of ingestion. Accidental poisoning of sheep with atrazine is associated with paralysis, exophthalmos, grinding of the teeth, diarrhea, dyspnea, and tachycardia, and of cattle is associated with salivation, tenesmus, stiff gait, weakness. Experimental dosing of heifers with large doses of atrazine is associated with fatal poisoning, but animals treated with activated charcoal survive.

Simazine and aminonitrazole in combination have been associated with death in sheep, and horses allowed access to pasture sprayed with the mixture. In sheep the signs are staggering, inappetence, and depression. In horses colic is the important feature.

Simazine on its own, with continuous access is associated with tremor, tetany and paraplegia, and a prancing gait with the head held against the chest. Death occurs after 2–4 days and mild-to-moderate myocardiopathy at necropsy.¹

Triclopyr, a selective postemergence herbicide, is toxic to horses at five times the estimated maximum intake from herbage. It is associated with digestive and respiratory signs, ataxia, stiff gait, sometimes tremor and mild to moderate. renal damage.

Sodium chlorate

Animals seldom ingest sufficient sprayed plant material to produce clinical illness and the principal danger is from accidental dosing or permitting salt-hungry cattle to have access to the chemical. The lethal oral dose is 2–2.5 g/kg BW for sheep, 0.5 g/kg for cattle and 3.5 g/kg for dogs. Irritation of the alimentary tract is associated with diarrhea and deep, black erosions of the abomasal and duodenal mucosae. Hemoglobinuria, anemia and methemoglobinemia result and somnolence and dyspnea are characteristic. At necropsy the blood, muscles, and viscera are very dark. No specific treatment is available. Sodium thiosulfate and methylene blue are used in treatment but have little effect but copious blood transfusions have been recommended.

Delrad

This algicide is used to control the growth of algae on ponds and other water reservoirs. Cattle and sheep are unharmed by the ingestion of water containing 100 ppm of the compound. Dose rates of 250 g/kg BW in adult cattle, 150 mg/kg in calves and 500 mg/kg sheep are associated with toxic effects.

Red squills

Poisoning by red squills seldom occurs because the material is extremely unpalatable and when eaten is usually vomited. In all species large doses (100–500 mg/kg BW) must be administered to produce toxic effects. Young calves are most susceptible and goats least. Experimental poisoning is associated with convulsions, gastritis and bradycardia.

Zinc phosphide

Zinc phosphide is also unpalatable to domestic animals, and requires an acid stomach to release its toxic phosgene gas. It is not therefore a likely poison for ruminants, but could be a hazard for pigs and horses. Experimental poisoning with doses of about 40 mg/kg BW is associated with death in most species. A general toxemia with depression of appetite, dullness, and some increase in respiratory rate occurs but there are no diagnostic signs. Necropsy lesions include congestion and hemorrhages in all organs, fatty degeneration of the liver and inflammation in the small intestine. Chemical assay is necessary to establish a diagnosis.³

Metaldehyde

Metaldehyde is in common use as a molluscicide. It is usually dispensed in a bran base and is toxic to farm livestock. Outbreaks occur in cattle, horses, and sheep. Lethal dose rates include cattle 0.2 g/kg BW in adults, and less in calves; horses 0.1 g/kg BW.

Clinical signs in ruminants include incoordination, hyperesthesia, muscle tremor, salivation, dyspnea, diarrhea, partial blindness, unconsciousness, cyanosis, and death due to respiratory failure. Hyperthermia (43.58°C or 110.8°F) occurs in sheep. All the signs are exacerbated by excitement or activity. A mortality rate of 3% may be expected.

Signs in horses are similar plus heavy perspiration, hypersalivation, muscle fasciculation, and death in 3–5 hours.

The only effective treatment in cattle is likely to be rumenotomy, supplemented by sedation with a tranquilizer, sedative or muscle relaxant. In horses, mineral oil by stomach tube is recommended to delay further absorption of the metaldehyde.

Methiocarb

This carbamate molluscicide has anticholinesterase and nicotinic and muscarinic activities. Poisoning of sheep is associated with depression, hypersalivation, diarrhea, dyspnea, aimless wandering, and ataxia. Death is due to pulmonary edema. Horses show sweating, dribbling, muscle tremor, hypersalivation, and finally recumbency and death due to pulmonary edema.

The compound is usually in pellet form and dyed blue so that affected animals can be detected by the blue staining of their mouths. Atropine is an effective antidote but may be required to be repeated if the amount of bait taken is large. For a wider discussion of carbamate poisoning see p. 1834.

Phenolic compounds

Lumber used in the construction of barns, stables, pens and yards is often treated with phenolic wood preservatives, chiefly pentachlorophenol, dinitro-orthophenols, dinitro-orthocresols (DNOC), dinitrophenol, and coal tar creosote, or mixtures of these, and animals that have access to freshly treated material or the neat preservative may be poisoned. The toxic cresols may be imbibed orally or absorbed percutaneously, and contact with freshly treated wood may be associated with local cutaneous necrosis.

Acute fatal doses in all species are in the range of 120–140 mg/kg BW for pentachlorophenol, and chronic fatal doses range from 30 to 50 mg/kg BW. Fatal doses for coal tar creosote are 4–6 g/kg BW as a single dose, or 0.5 g/kg BW daily. A high mortality may be encountered in newborn pigs and there may be a greater than normal incidence of stillbirths when sows are farrowed in treated crates. Weaned pigs may show depression, skin irritation and occasionally death.

Coal tar sealers for concrete floors may be associated with similar phenolic poisoning.

Creosote applied as a treatment for ringworm, has shown marked toxic effects in cattle.

Besides the known toxic effects of these chemicals there has been interest in possible subclinical intoxications. There is a lack of definitive evidence on the subject, but horses bedded on shavings from pentachlorophenol-treated wood, prepared wrongly by treating the rough lumber and then dressing it instead of applying the preservative to the dressed lumber, have been poisoned by dioxin, a common contaminant in the preservative. Clinical signs include depression of appetite, severe weight loss, ventral and limb edema, hair loss, anemia, a crusty, scaly dermatitis around the eyes, muzzle, the axilla and inguinal region, and on the neck. Exudation through cracks in the skin is a feature of the lesion. Lesions in liver biopsies include necrosis and severe vacuolar changes in the hepatocytes.¹

Copper–chrome–arsenate

Softwood preserved against rot by the application of a patented mixture containing copper, chromate, and arsenic, has become very popular for use in yards and buildings used by livestock. The materials have been carefully tested to insure that there is virtually no risk of poisoning. It is recorded that animals would need to eat at least 28 g of the treated wood daily for a month before a chronic poisoning occurred. Horses that have the chewing habit could eat more than that and could theoretically become poisoned. Burning of treated lumber can make arsenic available and toxic to animal. This route of poisoning has occurred in cattle because of their tendency to lick ashes or soil where burning of wood has occurred.

Bird repellants

Baits of corn or wheat are mixed with various substances and spread over areas to protect them from damage by bird droppings or to avoid damage to aircraft. One of these bird repellants, 4-aminopyridine, has caused poisoning in horses. Clinical signs include signs of fright, profuse sweating, severe convulsions, fluttering of the third eyelid, and death 2 hours after the onset of signs and 6–8 hours after ingesting the material.

In cattle signs include anorexia, frequent passage of small amounts of feces, and tenesmus, with some animals also showing tremor, ataxia, erratic behavior, especially walking backwards, and some sudden deaths.

Grain fumigants

Grain treated by the fumigant dibromoethane is associated with mortality in sheep. The principal lesions are pulmonary edema, septal fibrosis, alveolar epithelialization, and pleural effusion. Death occurs 48–120 hours after exposure. Methyl bromide, described under soil fumigants, is also used for stored grain.

Fungistatic agents

Hexachlorobenzene (HCB) is widely known because of its indestructibility and capacity to pass from grain through cattle and into humans. Legislation against chlorinated hydrocarbons being found in the human food chain is very harsh and hexachlorobenzene is a prime target for public health veterinarians. Its specific toxicity is not high, although experimental poisoning in pigs is associated with hepatic injury.

Toxic dose levels

In cattle which have been starved beforehand dose levels up to 0.33 g/kg BW is associated with increases in blood levels of ammonia and dose levels of 0.44 g/kg BW produce signs of poisoning within 10 minutes of dosing and dose rates of 1–1.5 g/kg BW are associated with death.

Tolerance to urea

Animals unaccustomed to urea may show clinical illness when fed 20 g/50 kg BW, but by gradually increasing the quantity fed this amount can be tolerated. This tolerance is lost rapidly and animals which receive no urea for 3 days are again susceptible. Tolerance is also reduced by starvation, by lack of readily available dietary carbohydrate and by a low protein diet. SHEEP can eat 6% of their total ration as urea provided it is well mixed with roughage and fed throughout the day, preferably by spraying the urea mixed with molasses onto the roughage. Much more urea is tolerated if given to sheep in molasses (18 g), than if given as a drench (8 g) and prior feeding on lucerne further increases the tolerance and fasting for 24 hours reduces it. A dose rate of 1 g/kg BW to sheep appears to be non-toxic, but 2 g/kg is quickly fatal. In general, urea should not constitute more than 3% of the concentrate ration of ruminants.

Horses appear to be tolerant to relatively large doses of urea but the disease has been produced experimentally in ponies by administering 450 g by stomach tube. The clinical picture is similar to that in cattle, being largely related to the central nervous system. There is a sharp increase in blood ammonia levels after ingestion of the urea, and it is assumed that hydrolysis of the urea occurs in the cecum.

Pigs are quite unaffected by very large doses of urea unless they are deprived of water or have developed a cecal flora which produces urease.

Propylene glycol poisoning

Propylene glycol is an unlikely poison but it is used extensively as an oral treatment for acetonemia in cattle and can be associated with poisoning if it is accidentally administered to horses, usually in mistake for mineral oil. Dose rates of 3 L to horses of 500 kg BW by stomach tube is associated with an immediate but short duration episode of abdominal pain, sweating, salivation, severe ataxia and depression, and a fetid odor of the feces.⁴ Much larger doses (8 L) can be fatal. Moderate-to-severe inflammation of the lining of the gut and edema of the brain are noticeable at necropsy examination.

Dried poultry wastes

Feeding dried poultry wastes to ruminants provides them with a source of nitrogen, and gets rid of the chicken farmer’s disposal problem. Deleterious effects include:

Brewer’s residues

Diseases associated with the feeding of by-products of brewing and distilling include:

Chemically treated natural feeds

Occurrence

All animal species are affected, including zoo ruminants.⁸ Poisoning incidents are most often reported in countries where animal husbandry is intensive and high levels of stall feeding are practiced.

Source of toxin

The poisonous properties of the agent are well known and poisoning is usually accidental due to failure to dilute a concentrate, poor mixing or because of wrong identification of containers. Also some liquid preparations settle out and need to be constantly mixed before and during mixing with a batch of feed. Cattle carrying reticular retention boluses of monensin to control bloat by delivering accurate daily doses of the drug, may die suddenly of acute heart failure due to myocardiopathy, a condition likely to be associated with the monensin but by an unknown mechanism.⁹ The compound’s main use as a coccidiostat is in poultry, and deaths from congestive heart failure have occurred in cattle and sheep fed dried poultry litter from farms feeding salinomycin or maduramicin.¹⁰

Risk factors

These compounds are specifically prohibited for use in horses at any time because of their toxicity for that species. Concurrent administration of monensin or salinomycin and tiamulin or chloramphenicol or triacetyloleandomycin at safe doses can be associated with ionophore poisoning in pigs. Outbreaks may occur when tiamulin is introduced into the pigs’ drug regimen to control swine dysentery when the pigs’ ration already includes the ionophore as a growth promotant, or when the two drugs are combined as a coccidia prevention package. The dose and time relationships are complicated and are dealt with separately. The concurrent administration of monensin and selenium to lambs also enhances the toxicity of the selenium.¹¹

Pluronics poisoning

These substances are administered to adult cattle in their feed as prevention against bloat. They are unpalatable and unlikely to be consumed in dangerous amounts unless they are well masked in feed. When they are fed accidentally to calves in their milk they are associated with dyspnea, ruminal tympany, bellowing, protrusion of the tongue, nystagmus, opisthotonos, recumbency, and convulsions. Death after 24 hours is the usual outcome.

Carbadox poisoning

Carbadox, Mecadox or Fortigro – methyl 3-(2-quinoxalinylmethylene)carbazate-N¹ – is used in pig feeds as a growth promotant and in the treatment of swine dysentery and other enteric diseases at the recommended rate of 50 mg/kg of feed/head per day. Toxic effects occur at rates of 150 mg/kg. A related compound olaquindox is similarly toxic. Affected pigs refuse the ration, but will eat other rations, are gaunt and emaciated, pass hard fecal pellets, and have a long rough coat, pale skin, severe tachycardia, weak hindquarters, and a swaying walk, followed by knuckling of the hind fetlocks, posterior paralysis, and death in 8–9 days. In the early stages the pigs screech frequently. Sows are agalactic, and produce stillborn or weak, undersized piglets.

Necropsy lesions are diagnostic, with extensive damage to the zona glomerulosa of the adrenal gland accompanied by renal tubular necrosis. The resulting hypoaldosteronism is manifested by low serum sodium levels, elevated serum potassium (8 mmol/L) and elevated blood urea nitrogen levels. The condition is irreversible and the outcome is severe disability or death.¹⁹

Bronopol poisoning

Bronopol – 2 bromo-2-nitropropoane-1, 3-diol – is used as a laboratory preservative for milk, e.g. in milk samples used for butterfat estimation. This milk is usually fed to calves or pigs and may be toxic on occasional feedings. Affected calves salivate, are depressed, collapse and die within 24 hours of feeding. Necropsy lesions include severe necrotizing abomasitis and local peritonitis on the serosal surface of the abomasum.²⁰

Polybrominated biphenyls

Mixtures of polybrominated biphenyls find a great deal of use in industry, particularly as flame retardants. They are not especially poisonous, nor are they a greater risk to farm animals because of degree of exposure, than many other industrial chemicals, but they happen to have found their way into the cattle food chain in much discussed incidents in the USA.

Polychlorinated biphenyls

These substances have a number of industrial uses and are common environmental contaminants. They are lipophilic so that they accumulate in body fat, and have low rates of biotransformation and excretion so that they persist in animal tissues for long periods. Although deleterious effects of the compounds in animal tissues are not often recorded, their presence in animal tissues is likely to cause rejection of meat from the human food chain. Recorded damage refers to unidentified reproductive inefficiency and reduction in efficiency of food conversion and possibly hepatic hypertrophy and gastric erosion, but in the same species a positive growth stimulating effect has also been recorded. Experimental poisoning of gnotobiotic pigs has been associated with diarrhea, erythema of the nose and anus, distension of the abdomen, growth retardation and, at doses of more than 25 mg/kg BW, coma and death.

Soil fumigant: methyl bromide

Soil fumigants used to prepare fields for planting may be associated with toxicity hazards in animals grazing them or in feed harvested from them. Methyl bromide has been associated with poisoning in horses, cattle, and goats when used in this way. Clinical signs in horses, cattle, and goats include ataxia, stumbling, and somnolence.

Formalin

Formalin is used to preserve colostrum for calf feeding, and in the preparation of formalin-treated grain. Milk containing too much formalin is associated with severe gastroenteritis and some deaths in calves that drink it. The clinical signs include salivation, abdominal pain, diarrhea, and recumbency.

Oil- and petroleum-product poisoning

Crude oil or petroleum distillates, including diesel oil, lamp oil, kerosene, and gasoline, are all poisonous to animals. Cattle will drink all of them and appear to have a positive liking for some products, especially used sump oil and liquid paraffin (mineral oil).

Oil-well installations

Crude oil coming directly from wells is usually repellent to animals, but they can consume lethal quantities of it if they are salt-deficient and salt-hungry: a characteristic of crude oil is that it is usually mixed with salty water which is often left lying in ponds nearby. After extraction most crude oils are temporarily stored in installations where lead paint is available so that salt and lead poisoning commonly occur with oil poisoning and may be confused with it.

Tin poisoning

Dibutyltin dilaurate is a coccidiostat fed to chickens in their feed. Errors in mixing may lead to cattle receiving toxic amounts in concentrates or pellets. Calves usually die acutely with signs of tremors, convulsions, weakness, and diarrhea. Older animals usually suffer a chronic illness characterized by persistent diarrhea, severe weight loss, inappetence, polyuria, and depression, reminiscent of arsenic poisoning. Affected animals may not be suitable for human consumption because of the high content of tin in their tissues.

Sodium fluorosilicate

A white, odorless, and tasteless powder used as a poison in baits for crickets, grasshoppers, and the like. Because of the way it is prepared in pellets in a bran base it is attractive to all animal species and poisoning is recorded in cattle, sheep, and horses, usually because unused baits were not retrieved after baiting programs.

In sheep mild illness occurs after doses of 25–50 mg/kg BW and death after 200 mg/kg. Clinical signs include drowsiness, anorexia, constipation, ruminal stasis, teeth grinding, abdominal pain, and diarrhea.

Highly chlorinated naphthalenes

The naphthalenes were extensively used in industry as lubricants, insulants, and wood-preserving agents. Recognition of their toxicity resulted in their exclusion from the farm environment and virtual elimination of the disease.

Local application or ingestion of highly chlorinated naphthalenes to cattle produces hyperkeratosis characterized by thickening and scaliness of the skin, emaciation, and eventual death. The pathogenesis of the skin lesions is due to interference with the conversion of carotene to vitamin A, causing hypovitaminosis-A. When poisoning results from accidental emission from industrial plants there are additional signs due to ocular, nasal, and tracheobronchial irritation; infertility and abortion also occur.

Coal tar pitch poisoning

Pigs may be exposed to coal tar pitch and its toxic cresols when housed in pens with tarred walls or floors, which they nibble, or when they have access at pasture to fragments of ‘clay pigeons’ used as targets by gun clubs. Bitumen and asphalt appear to be non-toxic. Young pigs 6–20 weeks of age are most commonly affected.

Clinical findings include an acute illness of a few days or a chronic course of some weeks. In the acute illness there are non-specific signs of inappetence, rough coat, tucked-up abdomen, weakness, and depression. The chronic illness is characterized by anorexia, depression, weakness, anemia, and jaundice. A subclinical syndrome includes a reduction in growth rate of up to 20–30%, a severe reduction in hemoglobin concentration and erythrocyte count, and reduced vitamin A storage.

Necropsy findings include jaundice, ascites, and anemia but the characteristic finding is a red and yellow mottling of the hepatic surfaces, and histologically a hepatic lesion of severe centrilobular necrosis. Cresols can be detected in the ingesta and liver of affected pigs.

Methyl alcohol

Accidental ingestion of methyl alcohol by cattle is associated with vomiting, recumbency, death, and a high concentration of methyl alcohol in the ruminal contents. Methyl alcohol is used as antifreeze in gasoline engines for pumps working continuously on oilfields in cold regions. Accidental access to the pump enclosure may result in a poisoning incident.

Ethylene glycol

Accidental poisoning with antifreeze mixture containing ethylene glycol may occur in swine, goats, and calves. The pathogenesis of the disease is dependent upon the development of acidosis and oxalate nephrosis.

In pigs this is manifested by ascites, hydrothorax and hydropericardium, depression, weakness, and posterior paralysis.

In cattle there is dyspnea, incoordination, paraparesis, recumbency, and death. There is accompanying uremia and hypocalcemia. Calcium oxalate crystals are present in large numbers in the kidney and brain and there is a fatal nephrosis. The presence of the chemical in tissue can be detected by thin-layer chromatography. The toxic dose rates determined experimentally for cattle are 5–10 mL/kg BW in adults and 2 mL/kg in non-ruminant calves. The treatment recommended for companion animals, ethanol or preferably 4-methylpyrazole, should be worth trying.

Industrial organophosphates

Principal industrial uses of organophosphates are as fire-resistant hydraulic fluids, as lubricants, and as coolants. A number of compounds including tri-o- tolyl phosphate, tri-o-cresyl phosphate (TOCP), and triaryl phosphates (TAP) have come to veterinary notice as being associated with poisoning in animals. Triaryl phosphates contain a number of isomers as well as TOCP, e.g. m-cresol, p-cresol, o-cresol, all of them more poisonous than TOCP. They have also been associated with serious outbreaks of poisoning in humans when they accidentally contaminate food. Poisoning may occur by ingestion or cutaneous absorption.

Clinical signs of delayed neurotoxicity do not occur until several weeks after contact and comprise irreversible neurological signs of respiratory stertor, dyspnea, dysuria, knuckling, leg weakness, and posterior paralysis.

Necropsy lesions characteristically include neuronal degeneration in the spinal cord and peripheral nerves.

Diagnostic confirmation depends on evidence of exposure to the toxicant, signs referable to the nervous system lesions, and a positive assay for the toxicant in the animal’s tissues.¹

Superphosphate

This is the usual form in which phosphorus-rich fertilizers are applied to the soil and is therefore available to animals on most farms in most countries. It is not highly palatable but sheep will eat it when it is in pill form (small granular, resembling grain in texture and particle size). The fertilizer is also used to prepare ‘superjuice’ which is administered to cows as a phosphorus supplement. Higher than normal intakes of the fertilizer either by dosing or by pasture application will cause poisoning, due largely to the fluorine present.¹ Calcium pyrophosphate and calcium orthophosphate also contribute to the toxicosis causing proximal renal tubular nephrosis.² The LD⁵⁰ of superphosphate for sheep is 100–300 mg/kg BW.

Clinical signs of poisoning include anorexia, thirst, diarrhea, weakness, ataxia, and death in about 48 hours.