Complex Dissimilar Actions

It is highly likely that, for compounds thought to have complex similar actions, the observed deviations from the expected additivity in some cases are due to the fact that the compounds are acmally not acting at the very same site at the target receptor. This means that the compounds acmally have complex dissimilar actions and the combined action is misclassified as a complex similar action due to insufficient knowledge about the exact mechanisms of action. 

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Independent action (Response addition) Dependent action or complex dissimilar action (Antagonism or synergism)... 

Interactions Complex Similar Action and Complex Dissimilar Action... 

Chemicals in mixtures may interact with one another and modify the magnitude and sometimes also the nature of the toxic effect. As illustrated in Table 10.1, the combined action of chemicals that interacts can be divided into two categories complex similar action and complex dissimilar action (dependent action). 

Occurrence of complex dissimilar actions is thought to be rare at low exposure (ADI) levels but it should always be considered whether a plausible hypothesis exists for effect interactions of two or more compounds. Interactions can occur both in the toxicodynamic phase (e.g., endocrine disrup-tors) and in the toxicokinetic phase (e.g., interference with transport, metabolism (activation, deactivation), distribution, and elimination of another compound). 

As can be deduced from the review in Section 5.3.1, most studies on mixture toxicity have been conducted on single species exposed to binary mixtures. In the case of studies with more complex mixtures, generally, either the toxicants have all been selected to operate by the same mode of action, or they have all been selected to represent different modes of action. In the complex situation of a multiple contaminated environment, it is likely that the biota are exposed to a mixture where several modes of action (some similar, some dissimilar) are represented by a variety of toxicants (Teuschler et al. 2004 Chapin 2004). Predicting the toxicity of a complex mixture of toxicants could build on observations that both concentration addition... 

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