The use of toxicodynamics in risk assessment

Risk assessment of xe(n)obiotics is a qualitative and quantitative assessme nt of toxic properties conventionally based on data resulting from in anima ls exposed to the substance The assessment of dose-effect relationship incl udes evaluation of exposure at the site of action. More recently, emphasis is put on understanding the relationship between exposure at the site of ac tion and the resulting effect, i.e. toxicodynamic. In this respect, results from genotoxicity studies may be a measure for exposure and at the same ti me of an effect. Results of toxicodynamic endpoints such as binding to rece ptors or release of hormones have been used when replacing default values f or interspecies extrapolation. It may also be envisaged to use toxicodynami c endpoints in order to egt an estimate of intraspecies variability. It was demonstrated that this approach may be helpful only if the relationship be tween the toxicodynamic endpoint and the definite endpoint is known by usin g 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 n ot been able to detect an effect on reproduction and/or fertility. Looking in the future development of toxicodynamic endpoints, gene profiling and th e analysis of proteins ('proteomics') may be helpful tools employed in scre ening and being related to the mode of action are explored for their suitab ility in terms of toxicodynamic endpoints. (C) 2001 Elsevier Science Irelan d Ltd. All lights reserved.