Toxicokinetics: The Behaviour of Chemicals in the Body

Abstract

Four basic processes govern the concentrations toxicants achieve within vulnerable tissues – absorption, distribution, metabolism and excretion. These processes dictate the ‘toxicokinetic fate’ of a xenobiotic – describing how it penetrates cell barriers to enter tissues (i.e. absorption), whether it is dispersed to particular organs and tissue compartments (distribution), how it undergoes chemical transformation within the liver (metabolism) and whether the parent compound or its metabolites are permanently eliminated in urine, faeces or both (excretion). The behaviour of a xenobiotic during these processes is influenced by its basic physicochemical properties, including mass, charge and solubility in water and/or lipids. Study of the toxicokinetic fate of xenobiotics has confirmed the role of hundreds of xenobiotic-handling proteins – including enzyme catalysts and membrane transporters – in controlling the disposition of ingested chemicals. The possibility that one chemical might alter the ability of these proteins to metabolise or export another xenobiotic is also briefly considered (i.e. toxicant interactions).