Toxicokinetics

Abstract

T oxicokinetics is a specialized area of toxicology that blends pharmacokinetic procedures with those of toxicology. It involves understanding the processes that govern the absorption, distribution, metabolism, and excretion of chemicals by the body. In general, these processes can be referred to as input (absorption), translocation (distribution), and output (metabolism, excretion). The rates of each process can be derived and used to describe in mathematical terms the time course for chemical and metabolite disposition in the body. Each process is governed by a number of physicochemical, biochemical, and physiological factors that profoundly affect how the body handles a particular chemical. For example, the state of hydration of the skin is an important physicochemical factor that influences chemical absorption by that route. Also, metabolic enzymes can have a profound effect on the input and output processes for a chemical. Thus, factors that increase the rate of biotransformation (enzymatic metabolism) of a chemical can profoundly affect input (increased formation of a toxic metabolite) or output (increased detoxification) processes that govern the temporal patterns of response to a particular chemical. These factors include induction and/or inhibition of xenobiotic-metabolizing enzymes, and inter-individual variations may result from the presence of polymorphisms in these enzymes. Reduction of adipose tissue mass reduces a storage compartment for lipophilic chemicals and thus can alter their rate of elimination from the body. Since toxicants are frequently present as complex mixtures, the way in which one toxicant can affect the toxicokinetics of another is important and will be considered in subsequent units.