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Abstract
Risk assessment of xenobiotics is a qualitative and quantitative assessment of toxic
properties conventionally based on data resulting from tests in animals exposed to
the substance. The assessment of dose-effect relationship includes evaluation of exposure
at the site of action. More recently, emphasis is put on understanding the relationship
between exposure at the site of action and the resulting effect, i.e. toxicodynamic.
In this respect, results from genotoxicity studies may be a measure for exposure and
at the same time of an effect. Results of toxicodynamic endpoints such as binding
to receptors or release of hormones have been used when replacing default values for
interspecies extrapolation. It may also be envisaged to use toxicodynamic endpoints
in order to get an estimate of intraspecies variability. It was demonstrated that
this approach may be helpful only if the relationship between the toxicodynamic endpoint
and the definite endpoint is known by using the example of bisphenol A. Whereas there
are clear effects of bisphenol A in in vitro and ex vivo studies, the classical two
generation study has not been able to detect an effect on reproduction and/or fertility.
Looking in the future development of toxicodynamic endpoints, gene profiling and the
analysis of proteins ('proteomics') may be helpful tools employed in screening and
being related to the mode of action are explored for their suitability in terms of
toxicodynamic endpoints.