Toxicodynamic modelling and the interpretation of in vitro toxicity data

Toxicology Letters
B J Blaauboer

Abstract

The results of in vitro toxicity experiments are not easily extrapolated to 'toxicological risk' for an intact organism. One of the most obvious differences between the situation in vitro and in vivo is the absence of the processes of absorption, distribution, metabolism and excretion that govern the exposure of the target tissues of the organism in vivo. The development of biokinetic models is aimed at estimating the relevant target tissue concentration of a compound. In our study, biokinetic models were constructed, where possible, solely on the basis of in vitro derived parameters for biotransformation as well as on partition coefficients determined or calculated from physicochemical structures. Another requirement is the existence of appropriate in vitro biological systems for the measurement of relevant effects. This requires a thorough knowledge of the possible mechanisms of toxic action, and of the physiology of the target organs. When these prerequisites are met (i.e. when the appropriate parameters can be quantified in a non-animal system), then an estimate of the dynamics in vitro can be made (e.g. as a critical active concentration). This will then result in a model describing a compound's dynamics. Eventually, the r...Continue Reading

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Citations

Jul 1, 2002·Environmental Toxicology and Pharmacology·Bas J Blaauboer
Jun 25, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Melvin E AndersenDaniel Krewski
Oct 17, 2015·Regulatory Toxicology and Pharmacology : RTP·Claire TerryDaland R Juberg
Mar 5, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bas J BlaauboerJeroen Schuermans
May 19, 2009·Toxicology Letters·Mariateresa GiulianoMario De Rosa
Mar 25, 2008·International Journal of Antimicrobial Agents·Alma TostmannP N Richard Dekhuijzen
Jul 3, 2003·Risk Analysis : an Official Publication of the Society for Risk Analysis·Matteo GoldoniAntonio Mutti
Apr 30, 2015·Toxicology·Kevin McNallyGeorge Loizou
Jun 7, 2012·Critical Reviews in Toxicology·Miyoung YoonHarvey J Clewell
Jul 10, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Sandra CoeckeJosé-Manuel Zaldívar
Jul 24, 2013·Toxicology·Kevin McNallyGeorge Loizou
Jan 18, 2005·Alternatives to Laboratory Animals : ATLA·Alessandra GennariUNKNOWN ECVAM Workshop 50

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