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Toxicokinetic modeling for environmental health problems
Author(s) -
Edler Lutz,
Heinzl Harald
Publication year - 2003
Publication title -
environmetrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 58
eISSN - 1099-095X
pISSN - 1180-4009
DOI - 10.1002/env.576
Subject(s) - toxicokinetics , human health , identification (biology) , extrapolation , environmental toxicology , physiologically based pharmacokinetic modelling , environmental science , biochemical engineering , computer science , toxicology , computational biology , chemistry , biology , pharmacology , toxicity , pharmacokinetics , statistics , environmental health , medicine , mathematics , ecology , engineering , organic chemistry
Toxicokinetic ( TK ) and physiologically based toxicokinetic (PB‐TK) models enable tissue dosimetry and the definition of the target organ dose after exposure to exogenous toxic compounds. This has qualified PB‐TK models for extrapolation from the experimental animal to the human, from high to low doses, between routes of exposure, between patterns of exposure, and also between robust and susceptible sub‐populations. We show how PB‐TK models are constructed, what assumptions are needed, which mathematical methods are used for model building and by which statistical methods one may assess both model fit and uncertainty of the modeling itself. We will address in particular a new generation of PB‐TK models which include age‐dependent model parameters to model life‐long human exposure with an example from the exposure to dioxins. Finally, we define the role of PB‐TK models for the identification of human health effects after exposure to chemicals in risk assessment. Copyright © 2003 John Wiley & Sons, Ltd.