Introduction
The expression of toxicity arising from exposure to a substance is a consequence of a chain of events that results in the affected tissues of an organism receiving the ultimate contaminant in amounts that cause an adverse effect (Fig. 1). The factors that confer susceptibility to certain species, and lead to major differences between species in their response to such chemical insults is based either:
- On the nature and quantity of the ultimate contaminant that is presented to the sensitive tissue (Toxicokinetics, TK);
- In the sensitivity of those tissues to the ultimate contaminant, i.e. the toxicodynamic (TD) response.
One of the main challenges in assessing potential effects of contaminants to organisms, to efficiently counteract their negative impacts on the environment, is explicitly predicting the internal active concentration of toxic chemicals in the body and/or target organs. Toxic effects estimated on the basis of internal body/tissue concentrations rather than on external exposure (e.g.: concentration in water or food) are often far less variable among species, different environmental conditions, and different chemicals with similar mode of action.
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Toxicokinetics - links the external exposure concentration of a contaminant to the internal concentration at the target site, which is the biologically effective dose (Fig. 1). For example, most aquatic toxicokinetic studies have focused on the transfer of chemicals from the external medium (water) to the respiratory membranes, fluids, and organs of the target organism. Therefore, this process translates a delivery of the compound to its site of action. Moreover, this process describes the time-course of contaminant absorption (uptake), internal distribution, biotransformation and excretion in an individual organism, i.e. what the organism does with the contaminant. The accumulation of the ultimate contaminant at its target is facilitated by its absorption, distribution to the site of action, reabsorption, and toxication (metabolic activation). On the other hand, presystemic elimination, i.e., distribution away from the site of action, excretion, and detoxication oppose these processes and work against the accumulation of the ultimate contaminant at the target area. To conclude, toxicokinetics is relevant to ecotoxicology because it allows the understanding and prediction of the behaviour of pollutants towards living organisms.
Definition of detoxication:
Any metabolic process by which the toxicity of a material is reduced.
Toxicodynamics - describes the time-course of toxic action at the target site, subsequent physiological impairment of the organism as well as the influence of any compensating mechanisms (i.e., any damage recovery) and finally the emergence of toxic effects at the level of the organism such as mortality. Thus, toxicodynamics describes the mechanism of action and potency of the chemical at the site of action i.e. what the contaminant does to the organism (fig. 1).
Figure 1 - The relationship between toxicokinetics and toxicodynamics.
A schematic overview of the behaviour
of a foreign compound as it enters the body of a species, is
distributed into tissues, exerts an effect, and is eliminated can be
found in figure 2. A contaminant is absorbed into the body and
then into the blood. From the blood, it is simultaneously eliminated
and distributed to different tissues, including the target tissue. The
target tissue is the tissue on which the contaminant exerts its
effect (fig. 2). Although most often the target tissue is a tissue, in
some instances the blood itself represents the target tissue.
Figure 2 - An overview of the absorption and disposition of a foreign compound. From the blood, the chemical is both eliminated and distributed to the target tissue, where it exerts its effect. Source: Williams et al. (2000).
