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Toxicokinetics and Pharmacokinetic Modeling of Arsenic
Citation:
Kenyon, E. AND H. Clewell III. Toxicokinetics and Pharmacokinetic Modeling of Arsenic. Edition 1, Chapter 22, J. Christopher States (ed.), Arsenic: Exposure Sources, Health Risks, and Mechanism of Toxicity, edited by J. Christopher States, Chpt. 27, John Wiley & Sons, Inc., Hoboken, NJ. John Wiley & Sons Incorporated, New York, NY, 1:884-908, (2015).
Impact/Purpose:
Metals generally, and arsenic in particular, provide unique challenge ~ in PBPK model development and health risk assessment. This book chapter reviewing the state of the science around toxicokinetic modeling for arsenic will promote biologically plausible,hypothesis driven research and toxicokinetic modeling for arsenic to enhance the biological basis for health risk assessment.
Description:
This chapter provides an overview of arsenic toxicokinetics and physiologically-basedpharmacokinetic (PBPK) modeling with particular emphasis on key 'actors needed fordevelopment of a model useful for dose-response analysis, applications of arsenicmodels, as well research needs.Understanding the uptake and distribution of a toxicant is essential to understanding its toxicity. Toxicokinetics describe the rate of uptake of a chemicaL. how it is distributed within the body and the rate of excretion or metabolic inactivation/adtivation to less/more toxic forms. The variation of these processes across species and between individuals is an important determinant of the toxicological outcome of exposures . M ch research has been devoted to elucidating the toxicokinetics of arsenic in animal models and humans in order to gain a deeper understanding of its toxicology and to provide /a quantitative estimate of dose to the target tissues with the goal of providing a sound biological basis for dose-response analysis.