ABSTRACT

The term toxicokinetics refers to the study of absorption, distribution, metabolism (biotransformation), and excretion (ADME) of toxicants in living organisms in relation to time. In this chapter, we employ a physiological perspective to address the topic of chemical toxicokinetics in fish. Introductory sections provide an overview of chemical absorption, distribution, and excretion, and highlight how adaptations of fish to their aquatic environment shape these processes. An extended section on toxicokinetic modeling describes how ADME processes may be represented mathematically to develop computational models of chemical uptake and disposition in fish. Included are descriptions of different modeling approaches, methods used to estimate model parameter values, and the scientific and regulatory questions to which these models can be applied. Special emphasis is given to the topic of chemical bioaccumulation assessment as this historically represents the most important application of toxicokinetic models for fish. Additional sections address the need to quantify chemical biotransformation as a means of representing this activity in predictive computational models. Recognizing the desire to reduce the use of live animals in chemical testing, a concluding section describes how toxicokinetic models can be used to relate observed in vitro effects to environmental exposures that could be expected to elicit similar effects in vivo.