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Chapter 2 of Toxicology of Fishes, "Toxicokinetics in Fishes"
Citation:
Nichols, J., J. Arnot, AND M. Barron. Chapter 2 of Toxicology of Fishes, "Toxicokinetics in Fishes". Edition 2nd Edition, Toxicology of Fishes. CRC Press LLC, Boca Raton, FL, , N/A, (2024).
Impact/Purpose:
The toxicity of a xenobiotic chemical to fish is substantially determined by the processes of absorption, distribution, biotransformation, and excretion. These processes influence whole-organism dose-response relationships by altering the effective chemical concentration over time at a target site. The degree to which any individual process impacts the concentration time course depends on the character of the chemical and attributes of the exposed organism. The role that individual organs play in each process and the molecular susceptibility of specific tissues and organs provide the basis for specific toxicities. This chapter reviews the topic of chemical toxicokinetics in fish. Introductory sections address physical-chemical concepts relevant to the description of chemical kinetics in natural systems, highlight physiological differences between fish and mammals, and describe mechanisms of xenobiotic transport across biological membranes. Additional text describes the processes of absorption, distribution, and excretion in fish one by one. An extended section on toxicokinetic modeling begins with a discussion of basic clearance concepts. This text is followed by a description of empirical and physiologically based modeling approaches. Bioaccumulation modeling is addressed as a special topic due to the large amount of focused research in this area and because prediction of various bioaccumulation metrics represents the most common application of toxicokinetic models for fish. A concluding section describes the use of reverse toxicokinetic modeling approaches to extrapolate in vitro effects information to a corresponding whole organism exposure. The concepts and models described in this chapter are widely used by scientists and regulators in several US EPA program offices to assess chemical risks to fish and other aquatic-dependent wildlife. This chapter provides an invaluable resource for anyone who is interested in the effects of environmental contaminants on fish.
Description:
This book chapter addresses 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.