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.
Factors Related to Exposure
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
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.
Last full review/revision October 2013 by Steve M. Ensley, BS, DVM, MS, PhD