Pharmacokinetics, chemical interactions, and toxicological risk assessment in perspective

Chemical mixtures and multiple routes of exposure are frequently difficult problems for exposure and risk assessors. Chemicals can interact synergistically or antagonistically at a variety of physiologic and biochemical loci within target cells. Many of these interactions can be accounted for with a thorough understanding of the pharmacokinetics of the compounds in the mixture. Many pharmacokinetic processes such as metabolism and absorption can be impacted by the presence of other chemicals in the environment and diet and as a result of medication. In addition, variations between responses as a result of different exposure scenarios (route of exposure, frequency, magnitude) can sometimes result from the impacts upon the pharmacokinetics. Pharmacokinetic models, when properly formulated and tested, can be useful tools to describe and predict the magnitude of the impact of multichemical and multiroute exposures. Several examples will be used to demonstrate this potentially powerful tool and how it can impact the risk assessment process.