Spec. Issue 2006 - Article Summary

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Estimating acute toxicity based on in vitro cytotoxicity: Role of biokinetic modelling

Bas J. Blaauboer1, Joop Hermens1 and Jan van Eijkeren2
1Institute for Risk Assessment Sciences, Utrecht University, The Netherlands; 2National Institute of Health and the
Environment (RIVM), Bilthoven, The Netherlands

Summary
Deviations from a linear relationship between cytotoxic concentrations of a substance in vitro and toxic doses in vivo can result from the fact that effective concentrations in vitro are irrelevant for the concentrations that cause toxicity in target organs in vivo. An important reason is a compound’s biokinetic behaviour, which determines the concentrations reached in target organs. Physiologically-based biokinetic modelling will be employed to alert to chemicals displaying a deviating kinetic behaviour and that will thus need further attention to estimate their acute toxicity. This will improve the accuracy of estimating the in vivo toxic dose on the basis of in vitro basal cytotoxicity.

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