Factors Affecting the Activity of Toxicants
Toxicosis potential is usually determined more by the multitude of related factors than by actual toxicity of the toxicant. Exposure-related, biologic, or chemical factors regulate absorption, metabolism, and elimination, and thus, influence observed clinical consequences.
Dose is the primary concern; however, the exact intake of a toxicant is seldom known. Duration and frequency of exposure are important. The route of exposure affects absorption, translocation, and perhaps metabolic pathways. Exposure of a toxicant relative to periods of stress or food intake may also be a factor. After ingestion of some toxicants, emesis may occur if the stomach is empty, but if partly filled, the toxicant is retained and toxicosis can occur. Environmental factors, such as temperature, humidity, and barometric pressure, affect rates of consumption and even the occurrence of some toxic agents. Many mycotoxins and poisonous plants are correlated with seasonal or climatic changes. For example, the ischemic effects of ergot toxicosis are more often seen during the winter cold, and plant nitrate levels are affected by rainfall amounts.
Various species and strains within species react differently to a particular toxicant because of variations in absorption, metabolism, or elimination. Functional differences in species may also affect the likelihood of toxicosis, eg, species unable to vomit can be intoxicated with a lower dose of some agents.
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 toxicant required to cause pathology is generally correlated to body weight, but with greater body weight, a disproportionate increase in toxicity (per unit body weight) of a compound often occurs. Body surface area may correlate more closely with the toxic dose. No measurement parameter is consistent for every situation.
Nutritional and dietary factors, hormonal and health status, organ pathology, stress, and sex all affect toxicosis. Nutritional factors may directly affect the toxicant (ie, by altering absorption) or indirectly affect the metabolic processes or availability of receptor sites. The copper-molybdenum-sulfate interaction is an example of both.
The chemical nature of a toxicant determines solubility, which in turn influences absorption. Nonpolar or lipid-soluble substances tend to be more readily absorbed than polar or 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, the γ isomer of hexachlorocyclohexane (lindane) is more toxic than other isomers.
Adjuvants are formulation factors used to alter the toxicologic 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. As absorption is delayed, toxicity decreases. Flavoring agents affect palatability and thus the amount ingested.