Toxicosis potential of a particular agent is usually determined more by a multitude of related factors than by the actual toxicity of the agent. Exposure-related, biological, or chemical factors, or some combination of them, regulate absorption, distribution, metabolism, and elimination, and thus influence observed clinical signs.
Exposure-Related Factors Affecting Toxic Agents in Animals
Many factors related to exposure influence how a toxic agent affects an animal.
Dose is the primary concern; however, the exact amount of a toxic agent that an animal has been exposed to is seldom known.
Duration and frequency of exposure are important.
Route of exposure affects absorption, translocation, and sometimes metabolic pathways.
Periods of illness, stress, or food intake can be a factor.
The presence of food in the stomach can increase the absorption of some toxic agents, altering the amount of gastric acid present. For example, when phosphide rodenticides are ingested, the risk of phosphine gas production is increased in animals with food present in the stomach compared to those with an empty stomach.
Environmental factors, such as temperature, humidity, and barometric pressure, affect rates of consumption in food-producing animals and even the occurrence of some toxic agents, which can affect any species.
Seasonal or climatic changes are correlated with many cyanotoxins (toxic components often found in certain blue-green algae), mycotoxins (eg, aflatoxin), and poisonous plants. For example, the ischemic effects of ergot toxicosis in cattle are more common during the winter, and plant nitrate concentrations are affected by rainfall amounts.
Biological Factors Affecting Toxic Agents in Animals
Various species and strains within species react differently to a particular toxic agent because of variations in absorption, distribution, metabolism, or elimination. Concerns about xylitol, for example, vary by species: the risk of toxicosis is high in dogs, but cats appear to be resistant.
Functional differences in species can also affect the likelihood of toxicosis. For example, species unable to vomit can be limited in their means of decontamination, potentially increasing their risk of developing clinical signs after ingesting a toxic substance.
Age and size of the animal are primary factors in toxicosis. Metabolism and translocation of xenobiotic agents are compromised by the underdeveloped microsomal enzyme system in young animals. Membrane permeability and hepatic and renal clearance capabilities vary with age, species, and health.
The amount of a toxic agent required to produce pathological changes is generally correlated to body weight; however, greater body weight is often accompanied by a disproportionate increase (per unit of body weight) in toxicity of a compound. Body surface area might correlate more closely with the toxic dose. No measurement parameter is consistent for every situation.
Nutritional and dietary factors, hormonal and health status, organ disease, stress, and sex all affect toxicosis. Nutritional factors can directly affect the toxic agent (eg, by altering absorption) or indirectly affect the metabolic processes or availability of receptor sites. The copper-molybdenum-sulfate interaction in ruminants is an example of both.
Chemical Factors Affecting Toxic Agents in Animals
The chemical nature of a toxic agent determines solubility, which in turn influences absorption. Nonpolar (lipid-soluble) substances tend to be more readily absorbed than polar (ionized) substances. The vehicle or carrier of the toxic compound also affects its availability for absorption.
Isomers, including optical isomers, vary in toxicity. For example, dexmethylphenidate is considered toxic at lower doses than are other isomers of methylphenidate.
Adjuvants are formulation factors used to alter the effect of the active ingredient (eg, piperonyl butoxide enhances the insecticidal activity of pyrethrins). Binding agents, enteric coating, and sustained-release preparations influence absorption of the active ingredient. Flavoring agents affect palatability and thus the amount ingested.
Key Points
Species differences should be considered when a potential toxic exposure is being assessed, because certain species can be more severely affected or more resistant to toxicosis by a particular substance.
The potential impact of changes in gastric acid production should be considered before feeding or withholding food after ingestion of a potentially toxic substance, because toxic effects can be affected by meals.
When toxic concerns are being evaluated, factors surrounding the exposure, not simply the toxic agent, should be considered.
For More Information
Peterson ME, Talcott PA, eds. Small Animal Toxicology. 3rd ed. Elsevier; 2013.
Gupta RC, ed. Veterinary Toxicology: Basic and Clinical Principles. 3rd ed. Elsevier; 2018.
Klaassen CD (ed.), Casarett LJ, Doull J. Casarett and Doull's Toxicology: The Basic Science of Poisons. 9th ed. McGraw-Hill; 2019.
Also see pet health content regarding factors affecting the activity of poisons.
