Applying Thermodynamics and Kinetics to Toxicology

A smaller value for reflects a greater concentration of the eomplex and therefore a greater affinity of the xenobiotic for the receptor. A larger refleets a lower affinity of the xenobiotic for the receptor. The toxicological terminology to reflect this fundamental behaviour is potency and efficacy. A more potent compound will show an effect at a lower concentration at the site of action reflecting a smaller K. Efficacy is a measure of the ability of a substance to elicit a full response compared to a standard. 

At this point, the concept of effective dose can be introduced. An effective dose 50 (ED50) is the dose of a compound required to reach 50% of a maximal 

Toxieokineties describes the processes associated with the time course of a xenobiotie along its pathway to its receptor site or sites. Generally, kinetics is the study of the time course of movement and the time course of chemical reactions including those processes associated with toxicity. In familiar terms, toxieokineties describes the processes that the body performs on the xenobiotie. 

How do toxieants access their sites of biological action Unless they act directly at the exposure site, then they must be transported to the site of action through absorption, distribution, metabolism and excretion, commonly referred to by the acronym ADME. All of these factors have a role in determining the amount of toxicant reaching the target site as well as the length of time the xenobiotic remains in the organism. 

Metabolism, or biotransformation, is the process of ehemical transformation of a toxicant to different structures, called metabolites, which may possess a different toxicity profile than the parent compound. Biotransformation affects both endogenous chemicals exogenous (xenobiotic) entities. Metabolism can result in a transformation product that is less toxie, more toxic or equitoxic but in general more water soluble and more easily excreted. Chemical modification can alter biological effects through toxication of a substance, also called bioactivation, which refers to the situation where the metabolic process results in a metabolite that is more toxic than the parent. If the metabolite demonstrates lower toxicity than the parent compound, the metabolic process is termed detoxication. These processes can involve both enzymatic and non-enzymatic processes, all of which should be familiar to undergraduate and graduate chemists. 

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