Spec. Issue 2006 - Article Summary

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In vitro-in vivo extrapolation of toxic potencies for hazard and risk assessment – problems and new developments

Michael Gülden and Hasso Seibert
University Medical School Schleswig-Holstein, Kiel, Germany
The aim of toxicological hazard assessment is to characterise the dangerous properties of chemicals for man and the environment. Information on both (a) the toxic potential, i.e. the spectrum of toxic effects a chemical can produce, and (b) the toxic potency, i.e. the quantitative relationship between dose/concentration and toxicity, are essential to characterise the toxic hazard. Toxicological risk assessment comprises hazard assessment and aims to characterise the likelihood and severity of adverse effects occurring to man or the environment following exposure to a chemical under defined conditions. Two fundamental problems hamper the application of in vitro assays for hazard assessment: firstly, the endpoints of toxic action detectable in vitro are less complex and, importantly, mostly different from those assessed in vivo (toxicodynamic problem). Secondly, toxic concentrations determined in vitro are not equivalent to toxic doses or concentrations in vivo. This is due to important differences in biokinetics and bioavailability of chemicals in vitro and in vivo (toxicokinetic problem).
This contribution is focussed on the second aspect. It is demonstrated, how predictions can be made of the toxic concentrations in human serum or the aquatic environment, which are equivalent to toxic concentrations in vitro. This can be achieved by the application of a recently developed quantitative extrapolation model, taking into account substance and system specific parameters important for the bioavailability of chemicals. It appears that this approach represents a real progress in solving part of the “toxicokinetic problem”.

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