CASE PRESENTATION

The small animal practitioner usually must treat one or a few animals, unlike the livestock veterinarian, for whom a toxicology case is more likely to involve large numbers of animals, with emphasis on herd health, economics, and food safety in addition to the welfare of an individual. The small animal case presents a further challenge because a wandering animal’s recent whereabouts is not always known. The environment is usually well defined for livestock. For example, a pasture can be searched for a toxic plant that has caused colic in a horse, but finding the antifreeze, pesticide, or garbage that caused gastroenteritis in a wandering pet may be much more difficult.

As mentioned earlier, diagnosis of a toxicology problem involves the assimilation of several classes of data, including the history, clinical signs, clinical chemistry, the presence or absence of lesions, analytical chemistry, and occasionally bioassay.^1,2 Evidence from one class of data rarely provides a definitive diagnosis in the absence of the others. For example, a dog with increased salivation, dyspnea, vomiting, and diarrhea might have a low blood cholinesterase level. Analysis for an organophosphorus or carbamate insecticide may be negative, yet the animal may have responded to atropine therapy. Historical review of the case might suggest exposure to a short-lived carbamate insecticide (nondetectable at sampling), exposure to a pond with neurotoxic algae, or exposure to a nicotinic plant, such as tree tobacco (Nicotiana glauca) or poison hemlock (Conium sp).¹

HISTORY

A thorough review of a case history will help to identify sources of a toxicant, predisposing factors, situations compatible with exposures, toxicant dose, and clinical signs.³ The environmental and past medical history should be taken along with that of the current problem. Although the initial investigation may be performed in a clinic, the practitioner may want to visit a site to help the owners identify hazards or conditions that might promote exposure to potential toxicants.⁴

The surrounding and immediate areas are assessed for toxic sources and hazardous conditions. Samples for analysis can be obtained or sought as the investigation proceeds. Potential hazards should be removed as soon as they are identified to prevent additional exposures. The entire environment is inspected for potentially toxic plants, contaminated water, or household chemicals. Recent renovations of old buildings may provide a clue about exposure to old lead-based paint. Refurbishment of old tables may provide a source of petroleum distillates in a pet with dyspnea. Other hazards may include toxic algae, garbage, recent baking activities (chocolate or ethanol in raw dough), industrial and mechanical activities, medications in the household, new toys, new cages, ventilation (Teflon/nonstick pyrolysis product toxicosis in birds), or pest control activities with such chemicals as rodenticides, insecticides, and/or herbicides.

The time of the year can also yield important clues. Car radiators are replenished in the autumn, leading to antifreeze exposures. Recent animal movements should be noted. Be sure to inquire about the sources of feed and identify new or different feed sources. Animal husbandry practices, such as types of feeds used or exercise patterns may help identify sources common to affected animals. The practitioner should discreetly note cultural traits that may yield information about exposure to drugs, herbal medications, or unusual foods.

Investigation of the current case requires a thorough clinical history. The signalment of the affected animal should be identified. The breed of dog may generate information about drug sensitivity. For example, collies, Australian shepherds, and other herding breeds are overly sensitive to the anthelmintic, ivermectin. The species and size of animal are also crucial for assessing toxicant exposures. A small cat is more sensitive to a given amount of ethylene glycol than a larger cat or a similar-sized dog.

If exposure to a given source is known or suspected, that exposure must be assessed. Containers, source materials, and vomitus can be examined. If known, the trade name, generic name, intended use, and an estimate of exposure (e.g., how much was applied and how much is left) of a chemical should be recorded. Vomitus should be examined for pills or other identifiable material and then frozen for chemical analysis at a later date.

Throughout the investigation, samples of potential source material should be saved. If the owner suspects a problem from the environment or perhaps the feed, a sample of that material should be obtained along with any label or other identification. One should insist on getting a sample of the feed or source material before a vendor is contacted. Otherwise, source materials have been known to “disappear.” It is best if the practitioner can also label the material, writing down the exact location where the sample was collected, the person(s) collecting it, the date, and the case involved along with his or her name, practice address, and telephone number. Samples of vomitus or moist materials can be carefully frozen (see Table 10-1). Dry feeds and other sources can be stored in a cool, dark, dry place. Plants to be identified can be submitted fresh to a diagnostic laboratory or other plant expert (including herbaria, local colleges, and plant stores) if the submission can be made quickly. Otherwise, it is best to press the plant carefully in an old newspaper between some books and then submit the dried plant. Mushrooms should also be submitted dry for identification. Avoid placing mushrooms or moist plants in plastic bags and putting them in the refrigerator. They tend to rot in that environment, making later identification very difficult.

EXPOSURE ASSESSMENT

The significance of an exposure depends on a great many factors. One of the most significant of these is the impact of the species in terms of habit and metabolic differences. The toxicity of a xenobiotic may also be affected by its route and rate of exposure and by the animal’s age, nutritional status, preexisting disease status, diet, water intake, environment, and management. Of the factors listed, by far the most important is the dose of the xenobiotic that is taken into the system.

As Paracelsus instructed, “The dose determines the poison.”⁵ Almost all compounds, including water, may be toxic if a susceptible animal is exposed to a sufficient quantity. Consideration of dose-response involves multiple factors in addition to the animal-related factors affecting previously mentioned toxicity. These factors include the magnitude of the dose, the frequency of exposure, and the slope of the dose-response curve for the animal’s species, age, nutritional status, disease status, gender, and many other related factors.

The magnitude of the exposure determines toxicity because most poisons act at specific sites or receptors in the system. The action at those sites can usually be related to the magnitude of effect in the patient. Dose-response relationships exist for chemicals that have a wide variety of effects. For example, a small amount of diluted sodium hypochlorite (a few milliliters of bleach in the toilet bowl at greater than 1:23 dilution) probably will not cause damage. However, if a puppy ingests pure bleach, severe damage to the esophagus may result. A cat that ingests the tissue of a mouse that suffers from a marginal dose of an anticoagulant rodenticide (<1 ppm in tissue) is not likely to be poisoned. However, if the mouse still has a stomach full of the rodenticide at approximately 0.005%, or 50 ppm, a hazard may exist for the cat. Some potentially toxic chemicals may be essential nutrients in low levels. For example, cats require approximately 10,000 IU/kg of diet of vitamin A for optimal health. Yet chronic toxicosis may result if the diet contains more than 100,000 IU vitamin A per kilogram of food material.

If a sufficient amount of a toxicant is ingested, acute poisoning may occur after one exposure. At lower levels, however, a toxicant may not cause disease until after it has been ingested repeatedly or until a sufficient amount of the chemical has accumulated at the receptor site. For example, repeated daily doses of compounds that can accumulate, such as an anticoagulant rodenticide like brodifacoum or a metal like lead, are toxic at much lower levels than a single acute dose. Additionally, for some compounds, the signs of chronic toxicosis can be different from the acute signs. A bird that has been soaked in an organochlorine insecticide may develop neurological signs and die. Daily exposure to low levels of the organochlorine, however, may not cause acute toxicosis. Rather, chronic long-term effects may result, leading to abnormal reproduction, including eggshell thinning and liver degeneration.

It is also important to understand the slope of the dose-response curve. Many texts provide the practitioner with the median lethal dose (LD₅₀) or, in some cases, the median toxic dose. However, that measure simply describes the dose at which 50% of an exposed population may be expected to die or develop toxicosis. More important to the clinician, however, is the dose at which a hazard to any animal may exist. Obviously, that will be a lower number. For toxicants with a steep dose-response curve, that minimum toxic level will be very close to the median toxic dose. For example, a highly toxic plant, such as rhododendron, may kill at almost any dose for which there is an effect. For other toxicants such as organochlorine insecticides, which have a shallow dose-response curve, some effects may be seen at levels that are orders of magnitude (10×) below the median lethal dose.

Exceptions exist to the dose-response relationship in toxicology. For example, hypersensitivity is not generally dose-responsive. Once an animal has been sensitized to a xenobiotic (e.g., venom from a bee sting), a very tiny amount later may trigger a massive anaphylactic response. Additionally, some carcinogens may not follow a dose-response curve. For example, one key genetic injury may trigger the formation of a cancer. Nevertheless, for the great majority of toxicants, understanding that the dose determines whether a compound may be toxic to an animal helps the practitioner decide whether an animal has been exposed to a toxic dose of a xenobiotic.

Given that the dose-response relationship is the major determinant of toxicity, performing basic exposure calculations helps determine the exposure of a potential toxicant in a patient. The practitioner must understand the basic units of concentrations, their sources, and how to convert a source concentration to an exposure level to compare the exposure with known toxicity data.

When conducting an assessment, one must identify the source of the denominator for various concentration units. Additionally, concentration data must be scrutinized to determine whether the level is on an as-is basis or a dry weight basis. Dry weight concentrations appear to be much higher than as-is levels for moist samples.

The toxicity of a compound may be expressed in terms of kilograms of source material and in terms of kilograms of exposed animal body weight. Generally, the practitioner is faced with a determined concentration of a substance in feed or a source material, and a known (through the literature usually) level of toxicity in the animal. Thus the likely amount taken in by the patient is calculated as follows:

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