Toxicology

For a discussion of common poisonings in poultry, see Poisonings.

Veterinarians are potentially exposed to myriad potent pharmaceuticals and other hazardous materials as part of their work environment, and particularly during patient decontamination procedures (most notably dermal decontamination). Therefore, knowledge of important toxicologic workplace hazards and basic personal protective equipment (PPE) is important. It is critical to recognize that PPE is the “last line of defense” and not a panacea for toxicologic hazards. The overarching principle is to avoid exposure if at all possible. Over-reliance on inadequately fitted or inappropriate types of PPE continues to be a substantial cause of human casualties because of the feeling of overconfidence these devices can provide. In particular, respirators should be selected, fitted, and tested by persons qualified to do this.

Algal poisoning is an acute, often fatal condition caused by high concentrations of toxic blue-green algae (more commonly known as cyanobacteria—literally blue-green bacteria) in drinking water as well as in water used for agriculture, recreation, and aquaculture. Fatalities and severe illness of livestock, pets, wildlife, birds, and fish from heavy growths of cyanobacteria waterblooms occur in almost all countries of the world. Acute lethal poisonings have also been documented in people. Poisoning usually occurs during warm seasons when the waterblooms are more intense and of longer duration. Most poisonings occur among animals drinking cyanobacteria-infested freshwater, but aquatic animals, especially maricultured fish and shrimp, are also affected. The toxins of cyanobacteria comprise six distinct chemical classes collectively called cyanotoxins.

In acute cyanide poisoning, cyanide ions (CN–) bind to, and inhibit, the ferric (Fe3+) heme moeity form of mitochondrial cytochrome c oxidase (synonyms: aa3, complex IV, cytochrome A3, EC 1.9.3.1). This blocks the fourth step in the mitochondrial electron transport chain (reduction of O2 to H2O), resulting in the arrest of aerobic metabolism and death from histotoxic anoxia. Tissues that heavily depend on aerobic metabolism such as the heart and brain are particularly susceptible to these effects. Cyanide also binds to other heme-containing enzymes, such as members of the cytochrome p450 family, and to myoglobin. However, these tissue cyanide "sinks" do not provide sufficient protection from histotoxic anoxia. The acute lethal dosage of hydrogen cyanide (HCN) in most animal species is ~2 mg/kg. Plant materials containing ≥200 ppm of cyanogenic glycosides are dangerous.

Ingestion of avocado (Persea americana) has been associated with myocardial necrosis in mammals and birds and with sterile mastitis in lactating mammals. Cattle, goats, horses, mice, rabbits, guinea pigs, rats, sheep, budgerigars, canaries, cockatiels, ostriches, chickens, turkeys, and fish are susceptible. Caged birds appear more sensitive to the effects of avocado, while chickens and turkeys appear more resistant. Although an old case report exists of two dogs developing myocardial damage after avocado ingestion, dogs appear to be relatively resistant compared with other species.

Herbicides are used routinely to control noxious plants. Most of these chemicals, particularly the more recently developed synthetic organic herbicides, are quite selective for specific plants and have low toxicity for mammals; other, less-selective compounds (eg, sodium arsenite, arsenic trioxide, sodium chlorate, ammonium sulfamate, borax, and many others) were formerly used on a large scale and are more toxic to animals.

Also see Rodenticide Poisoning and Toxicities from Human Drugs and Poisonous Plants and Food Hazards.

For discussion of mycotoxicoses in poultry, see Mycotoxicoses.

Smoke inhalation caused by fires is a major cause of fatalities in animals. It usually involves inhalation of a complex mixture of toxicologic agents and pyrolysis products. Injury typically results from a combination of thermal injury to the upper airways, oxygen deprivation, and toxicity from inhaled materials. Smaller animals and in particular birds are usually more susceptible to inhaled toxicants because of their greater respiratory minute volume per unit mass and relatively larger respiratory surface area per unit mass.

Human drugs or nutritional supplements available without a prescription are known as over-the-counter (OTC) medications. Exposures to OTC drugs in pets can be accidental or intentional. A valid client-patient-veterinarian relationship must exist for veterinarians to recommend extra-label use of these drugs to their clients. Most are not approved for veterinary use by the FDA, and safety of most OTC drugs has not been determined in animals. Veterinarians should understand the potential risks of using OTC medications and communicate these risks to their clients.

Poisoning by ingestion of excess urea or other sources of nonprotein nitrogen (NPN) is usually acute, rapidly progressive, and highly fatal. NPN is any source of nitrogen not present in a polypeptide (precipitable protein) form. Sources of NPN have different toxicities in various species, but mature ruminants are affected most commonly. After ingestion, NPN undergoes hydrolysis and releases excess ammonia (NH3) into the GI tract, which is absorbed and leads to hyperammonemia.

A variety of coal-tar derivatives induce acute to chronic disease in animals, with clinical signs that vary based on the constituents. Clinical effects are acute to chronic hepatic damage with signs of icterus, ascites, anemia, and death. Phenolic components may cause renal tubular damage. Coal tar–related poisoning has been reported in farm animals and pets.

All animals are susceptible to ethylene glycol (EG) toxicity, but it is most common in dogs and cats. Most intoxications are associated with ingestion of antifreeze, which is typically 95% EG. These 95% commercial antifreeze preparations are diluted ~50% with water when used in vehicle cooling systems. The widespread availability of antifreeze, its sweet taste and small minimum lethal dose, and the lack of public awareness of the toxicity (ie, improper storage and disposal) contribute to the frequency of this intoxication. In addition, antifreeze may be ingested by way of intentional poisoning or because it is the only available liquid in cold weather. Other sources of EG include some heat-exchange fluids used in solar collectors and ice-rink freezing equipment and some brake and transmission fluids. Cutaneous absorption from topical products that contain EG has been reported to cause toxicity in cats.

Many species are susceptible to nitrate and nitrite poisoning, but cattle are affected most frequently. Ruminants are especially vulnerable because the ruminal flora reduces nitrate to ammonia, with nitrite (~10 times more toxic than nitrate) as an intermediate product. Nitrate reduction (and nitrite production) occurs in the cecum of equids but not to the same extent as in ruminants. Young pigs also have GI microflora capable of reducing nitrate to nitrite, but mature monogastric animals (except equids) are more resistant to nitrate toxicosis because this pathway is age-limited.

Pentachlorophenol (PCP), commonly known as penta, has been used as a fungicide, molluscicide, insecticide, and wood preservative. Its use is now permitted only for industrial purposes; agricultural and domestic uses are prohibited, because it is classified as a highly hazardous pesticide.

Ingestion or inhalation of, or skin contact with, petroleum, petroleum condensate, gasoline, diesel fuel, kerosene, crude oil, or other hydrocarbon mixtures may cause illness and occasionally death in domestic and wild animals. Dogs and cats both may ingest petroleum products during grooming of contaminated fur or directly from open containers. Inhalation may occur in poorly ventilated areas where these chemicals have been used or stored. Ruminants may ingest such products in large amounts because they are thirsty, curious, or seeking salt or other nutrients, or if food or water is contaminated.

Persistent halogenated hydrocarbons (PHAs) are manmade chemicals and can be products of incomplete combustion. PHAs are a complex mixture of chemicals with differing molecular composition. Some PHAs are added to consumer products to provide unique properties and have been/are used as pesticides and disinfection agents. Most PHAs persist in the environment and are classified as persistent organic pollutants. PHAs cause acute and chronic toxicity. There is evidence that lifetime chronic toxicity can be expressed differently during life stages from embryogenesis to senility. Exposure at early life stages may not be expressed until a later life stage. PHAs can be biomagnified in body fat and liver, translocated to the fetus, and secreted in milk and eggs. Biomagnification is a process wherein PHAs are concentrated in fat and liver at a factor higher than dietary levels and is a food safety issue. Important groups of PHAs include polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), DDT, and triclosan.

Insecticides are any substance or a mixture of substances intended to prevent, destroy, repel, or mitigate insects. Similarly, acaricides are substances that can destroy mites. A chemical can exert both insecticidal and acaricidal effects. Based on their properties, these chemicals can be classified into four groups: 1) organophosphates, 2) carbamates, 3) organochlorines, and 4) pyrethrins and pyrethroids. Because of worldwide use, these chemicals pose health risks to nontarget species, including people, domestic and companion animals, wildlife, and aquatic species. In large animals, poisoning is often due to inadvertent or accidental use, whereas in small animals (particularly dogs) poisoning is often due to malicious intent.

Metaldehyde, a cyclic polymer of acetaldehyde, is the active component in molluscicides used to control slugs and snails. It is commonly used in wet coastal areas worldwide. This neurotoxicant has been associated with poisoning in a variety of domestic and wildlife species, although most poisonings have been reported in dogs and are related to careless placement of bait. Metaldehyde may be combined with other agents such as carbamate insecticides to enhance efficacy. It is not considered to be a persistent chemical. Under typical application circumstances, metaldehyde may remain effective for as long as 10 days.

The ubiquitous element arsenic (As) is a nonmetal or metalloid in group V on the periodic chart. It is often referred to as arsenic metal and for toxicologic purposes is classified as a metal. It exists in several forms and has a long history of various uses, including insecticides for animals, wood preservatives, herbicides, and even some medicinal uses. It is responsible for many poisonings in people and animals.

Acute or chronic copper poisoning is encountered in most parts of the world. Sheep are affected most often, although other species are also susceptible. In various breeds of dogs, especially Bedlington Terriers, an inherited sensitivity to copper toxicosis similar to Wilson disease in people has been identified. Chronic copper poisoning has been reported in other breeds of dogs, including Labrador Retrievers, West Highland White Terriers, Skye Terriers, Keeshonds, American Cocker Spaniels, and Doberman Pinschers. Acute poisoning is usually seen after accidental administration of excessive amounts of soluble copper salts, which may be present in anthelmintic drenches, mineral mixes, or improperly formulated rations.

Fluoride exposure from the environment has been associated with natural contamination of rock, soil, and water or from industrial waste or smelting processes. Fluoride compounds have been added to human water supplies at concentrations of ~1 mg/kg to reduce dental caries. This recommendation is not universally accepted. Both acute and chronic toxicoses are reported with fluoride ingestion. Maximum tolerance levels in animal feeds range from ~20–50 mg/kg (dry weight) in most species. In poultry, as much as 200 mg/kg can be tolerated. These tolerances may vary depending on age, duration of exposure, and nutritional status. Animals with a long, productive life span such as dairy cattle are more susceptible.

Reports of toxicity after SC or IM injection of iron preparations in newborn piglets are sporadic, and the risk is not high; however, toxicity does occur occasionally. In some litters, death occurs quickly, from 30 min to 6 hr after injection; in others, death is delayed for 2–4 days. (Also see Nonregenerative Anemias in Animals.)

Lead poisoning in animals and people is a major concern worldwide. Poisoning in animal populations may serve as a sentinel to assess the extent of environmental contamination and human health problems related to lead. In veterinary medicine, lead poisoning is most common in dogs and cattle. Lead poisoning in other species is limited by reduced accessibility, more selective eating habits, or lower susceptibility. In cattle, many cases are associated with seeding and harvesting activities when used oil and battery disposal from machinery is handled improperly. With the elimination of tetraethyl lead from gasoline in many countries, the number of lead poisoning cases attributed to oil consumption has declined. Other sources of lead include paint, linoleum, grease, lead weights, lead shot, and contaminated foliage growing near smelters or along roadsides. To prevent future occurrences of lead poisoning, it is crucial to identify the source. Lead poisoning is also encountered in urban environments and during the renovation of old houses that have been painted with lead-based paint, leading to exposure of small animals and children. The consumption, through grooming, of dust containing lead has been reported in cats. Improper disposal of lead-poisoned animal carcasses may result in toxicoses in nontarget scavenger animals. Scavenging by endangered species such as the condor raises unique concerns.

Historically, mercury poisoning was a common occurrence in both human and animal populations. The replacement of mercury products used for medicinal, agricultural, or industrial purposes has resulted in a decline in acute and chronic poisoning, although many wildlife species remain at risk. Predator species considered to be near the top of the food chain, such as fish, seals, polar bears, and various bird species, bioaccumulate significant quantities of mercury from dietary sources. Commercial fish products such as tuna have been associated with chronic poisoning in human and animal (cats) populations. Mercury exists in a variety of chemical forms, including elemental mercury (eg, thermometers, light bulbs), inorganic mercurial (mercuric or mercurous) salts (eg, batteries, latex paints), and organic mercury (aryl, methyl, or ethyl). Fossil fuels represent an important environmental source of mercury. In the environment, inorganic forms of mercury are converted to methylmercury under anaerobic conditions in the sediment of most water bodies. Similar conversions may also occur in the body.

Molybdenum is an essential element associated with a variety of metalloenzymes and corresponding metabolic functions. Excessive dietary intake of molybdenum induces a secondary copper deficiency. The syndrome, predominately reported in ruminants (versus nonruminant species) is seen worldwide. Cattle and sheep are ~10-fold more susceptible than other species. Acute toxicity associated with massive doses is rarely encountered.

Excessive salt (sodium chloride, NaCl) intake can lead to the condition known as salt poisoning, salt toxicity, hypernatremia, or water deprivation–sodium ion intoxication. The last term is the most descriptive, giving the result (sodium ion intoxication) as well as the most common predisposing factor (water deprivation.) Salt poisoning is unlikely to occur as long as sodium-regulating mechanisms are intact and fresh drinking water is available.

Selenium is an essential element that has a narrow margin of safety, with the difference between adequate and potentially toxic concentrations in the diet being approximately 10- to 20-fold. Feed supplements, resulting in final selenium content of 0.2–0.3 ppm, are added to diets to prevent deficiency and resultant diseases such as white muscle disease in cattle and sheep, exertional myopathy in horses, hepatosis dietetica in pigs, and exudative diathesis in chickens. The maximum tolerable concentrations for selenium in most livestock feed is considered to be 2–5 ppm, although some believe 4–5 ppm can inhibit growth.

Zinc is an essential trace metal that plays an important role in many of the body's enzymatic processes. It is ubiquitous in nature and exists in many forms. The ingestion of some forms of zinc causes the creation of toxic zinc salts in the acidic environment of the stomach. Zinc toxicity has been documented in people as well as in a wide range of large, small, exotic, and wild animals. Exposure typically stems from dietary indiscretion. Household sources of zinc include paint, batteries, automotive parts, zinc oxide creams, vitamin and mineral supplements, zipper pulls, board-game pieces, pet carrier screws and nuts, and the coating on certain types of pipes and cookware. One of the most well-known sources of zinc that causes toxicity after ingestion is the USA Lincoln penny. Some pennies minted during 1983, and all pennies minted since, are 97.5% zinc by weight (~2,440 mg of elemental zinc per coin).

Bracken fern (Pteridium aquilinum) is found throughout the world and is among the five most numerous vascular plants in the world. Because the species includes numerous subspecies and varieties, plant size varies, with frond lengths ranging from 0.5 to 4.5 m.

Gossypol poisoning, usually chronic, cumulative, and sometimes insidious, follows consumption of cottonseed or cottonseed products that contain excess free gossypol. It is of most concern in domestic livestock, especially preruminants or immature ruminants and pigs; mature ruminants are more resistant to gossypol’s toxic effects. However, gossypol toxicosis can affect high-producing dairy cows with high feed intake, dairy goats, and other mature ruminants fed excess gossypol for long periods. It has also been reported in dogs fed cottonseed meal in diets or housed on cottonseed bedding.

Mushrooms are the fruiting bodies of a variety of fleshy fungi that are found worldwide. They typically appear suddenly from growing vegetative (mycelium) portions, and they contain spores as reproductive units. Fungi lack chlorophyll; their nutritional requirements are met by utilizing organic material from a saprophytic, parasitic, and/or mycorrhizal life cycle.

Plants are an important part of the decor of homes; pets having access to these plants often chew on or ingest them, with toxicity a possible outcome (see Table: Poisonous Houseplants and Ornamentals a). Inquiries to poison control centers on plants ingested by children <5 yr old are estimated at 5%–10% of all inquiries. Similar estimates (although not documented) could be made for pets.

Typically, pyrrolizidine alkaloidosis is a chronic poisoning that results in hepatic failure. It is caused by many toxic plants, most commonly of the genera Senecio, Crotalaria, Heliotropium, Amsinckia, Echium, Cynoglossum, and Trichodesma. These plants grow mainly in temperate climates, but some (eg, Crotalaria spp) require tropical or subtropical climates. The plants most often implicated include ragwort (S jacobea), groundsel (S riddellii, S longilobus), rattleweed (Crotalaria retusa), and seeds of yellow tarweed (A intermedia).

Most animals are susceptible to Quercus poisoning, although cattle and sheep are affected most often. Most species of oak (Quercus spp) found in Europe and North America are considered toxic. Clinical signs occur 3–7 days after consumption of large quantities of young oak leaves in the spring or green acorns in the fall. Fallen trees associated with a recent storm are often reported with outbreaks. Feed restriction before exposure plays a crucial role enhancing susceptibility. Mortality as high as 70% may be seen. Malformed calves and abortions have been reported in dams consuming acorns during the second trimester of pregnancy. The toxic principle, which appears to be pyrogallol, gallotannins, polyhydroxyphenolic compounds, or their metabolites produced by microbial hydrolysis in the rumen, binds and precipitates proteins, which results in GI and renal dysfunction.

This often fatal neurotoxic disease occurs in livestock of any age that graze pastures in which annual ryegrass (Lolium rigidum) is present and in the seedhead stage of growth. It is seen in western and southern Australia and in South Africa from November to March. Hay of Festuca rubra commutata (Chewing’s fescue) with Rathayibacter toxicus–infected seedhead galls has caused a similar disease in cattle and horses in Oregon. Outbreaks of ergot alkaloid toxicity in cattle on L rigidum have been reported in South Africa and should not be confused with annual ryegrass staggers.

Sorghum species are drought-tolerant plants that may produce neuropathic and teratogenic manifestations. Sorghum poisoning has been seen primarily in the southwestern USA and Australia. The syndrome is reported almost exclusively in horses, although a similar disease has been reported in sheep and cattle. Lathyrogenic nitriles such as β-cyanoalanine, cyanogenic glycosides, and nitrates have been suggested as causative agents. The syndrome develops in horses after they have grazed hybrid Sudan pastures for weeks to months and produces axonal degeneration and myelomalacia in the spinal cord and cerebellum. (Also see Cyanide Poisoning.) Consumption of the seed will not produce the syndrome.

In the 1920s, cattle in North America developed a fatal hemorrhagic disease. Various causes, including pathogenic organisms and nutritional deficiencies, were investigated. Damp conditions caused stacks of hay to mold and spoil. Within several weeks, sheep and cattle eating the hay developed uncontrollable hemorrhages that were generally fatal in 30–50 days. Feeding trials and chemical analyses later definitively identified the cause as spoiled or moldy sweet clover (Melilotus officinalis and M alba) hay or silage.

In nature, cantharidin is found in beetles belonging to the Meloidae family. More than 200 species of these beetles are found throughout the continental USA, but members of the genus Epicauta are most frequently associated with toxicosis in horses. The striped blister beetles (E occidentalis, E temexia, and E vittata) are particularly troublesome in the southwestern USA. The black blister beetle, E pennsylvanica, has caused toxicosis in horses in Illinois. Cantharidin is the sole toxin, but its concentration in beetles varies widely.

Venomous snakes of North America are members of either of two families: 1) the Elapidae or coral snakes (Micrurus spp); or 2) the Crotalidae, or pit vipers (rattlesnakes [Crotalus spp], cottonmouth moccasin [Agkistrodon piscivorus], and copperhead [A cortotrix]). Elapids are generally restricted to southern edges of the USA, whereas crotalids are dispersed across the continent. Because of their wider distribution and less secluded natures, bites by crotalids are much more common than elapid bites. Rattlesnakes account for most snakebite-related deaths in people and domestic animals in the USA. Although Australia is home to a large number of venomous snakes from the families Colubridae, Hydrophiidae, and Elapidae, the most clinically significant venomous species are elapids, particularly the black (Pseudechis), brown (Pseudonaja textilis), Taipan (Oxyuranus sp), and tiger (Notechis scutatus) snakes.

Dogs and, less frequently, cats may be poisoned by oral exposure to many types of toads. Severity varies greatly, depending on extent of contact and type of toad. Toxins are produced by all toads, but potency varies with species and apparently between geographic locations within individual species. Toad toxin, a defensive mechanism, is secreted by large glands located dorsal and posterior to the eyes and by smaller glands distributed throughout the skin. The toxin, a thick, creamy white, highly irritating substance, can be expelled quickly by the contraction of periglandular muscles in the skin. Its many components include bufagenins, which have digitalis-like effects, and bufotoxins, which block sodium channels in nerves similar to the actions of local anesthetics, catecholamines, and serotonin. The most toxic species in the USA is the giant or marine toad, Rhinella marina (formerly Bufo marinus), an introduced species that is established in Florida, Hawaii, and Texas. R marina is also known as the cane toad in Australia, where its range extends across the northeastern half of the continent. Mortality ranges from 20%–100% in untreated cases, depending on exposure circumstances. The Colorado River toad, Incillus (formerly Bufo) alvarius, found in the southwestern USA and northern Mexico, is another toad of sufficient size to have potentially lethal levels of toxins in its skin secretions.

Envenomation of animals by poisonous arthropods is relatively uncommon and difficult to recognize. It may be suspected relative to presenting clinical signs, but confirmatory evidence is rare because of the inability to capture the offending arthropod.

Many poisons have been used against rodent pests. If baits are not well secured, they may be ingested directly by nontarget animal species (farm animals, pets, and wildlife). Sometimes, nontarget species may ingest recently poisoned rodent pests and develop relay or secondary poisoning. Occasionally, baits may be used maliciously or intentionally to kill either domestic animals or wildlife. This chapter discusses only the most commonly used rodenticides currently available in the market: anticoagulants, bromethalin, cholecalciferol, and zinc phosphide. Strychnine poisoning (see Strychnine Poisoning) is discussed separately.

Strychnine is an indole alkaloid obtained from the seeds of the Indian tree Strychnos nux-vomica. Strychnine-containing baits are currently labelled for below-ground use and are intended for the control of pocket gophers. Their use as indoor pesticides has been eliminated since 1989. In the past, strychnine has been used as a pesticide to control rats, moles, gophers, and coyotes. Strychnine is highly toxic to most domestic animals. Its oral LD50 in dogs, cattle, horses, and pigs is 0.5–1 mg/kg, and in cats is 2 mg/kg. Strychnine is considered a restricted-use pesticide. Its sale is forbidden in a number of states. Grain-laced or pelleted commercial baits (usually <0.5%) are often dyed red or green. Malicious or accidental strychnine poisoning, although not very common in the USA, occurs mainly in small animals, especially dogs and occasionally cats, and rarely in livestock. Most poisonings occur when nontarget species consume commercial baits. Young and large-breed, intact male dogs are more likely to be involved. Most poisonings are reported from the western USA.