PHARMACOKINETICS, CHEMICAL INTERACTIONS, AND TOXICOLOGICAL RISK ASSESSMENT IN PERSPECTIVE

Chemical mixtures and multiple routes of exposure are frequently diffi cult problems for exposure and risk assessors. Chemicals can interact synergistically or antagonistically at a variety of physiologic and bi ochemical 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 che micals in the environment and diet and as a result of medication. In a ddition, variations between responses as a result of different exposur e scenarios (route of exposure, frequency, magnitude) can sometimes re sult from the impacts upon the pharmacokinetics. Pharmacokinetic model s, when properly formulated and tested, can be useful tools to describ e and predict the magnitude of the impact of multichemical and multiro ute exposures. Several examples will be used to demonstrate this poten tially powerful tool and how it can impact the risk assessment process .