Toxicokinetics and estimation of the potential health risks of environmental and work place chemicals to humans
Leader: Prof. Dr. Johannes G. Filser; Substitute: Prof. Dr. György Csanády, Dr. Winfried Kessler
Background
Many chemicals undergo conversion into metabolites which act toxic or carcinogenic. Therefore, it is most meaningful to relate the biological response to the active species of the chemical. The target dose of the active species is determined by its concentration and the time it remains at the site of action. Both parameters depend on the amount and absorption rate of the chemical as well as of the rates of distribution, biotransformation and excretion of the chemical and its active species, respectively. Toxicokinetics descibes these rates and, consequently, tissue burdens and target dose quantitatively. Most frequently, biotransformation to and elimination of metabolites are catalyzed enzymatically and therefore are subject to saturation kinetics (e.g. according to Michaelis and Menten). Consequently, the target dose of the active metabolite is often not a linear function of the amount of chemical administered. Thus, knowledge of the mode of action and of toxicokinetics of a substance is indispensable for understanding and extrapolating dose-response relationships observed in animal studies to the human situation.
We are dealing with the estimation of the potential health risks of environmental and work place chemicals to humans considering their mode of action and toxicokinetic behavior in laboratory animals and humans. Correspondingly, toxicokinetic and metabolism studies are carried out in cell fractions, cells, organs, experimental animals, and in human subjects. The data obtained is used for development and validation of species-specific physiological toxicokinetic models. On the basis of such models in combination with toxicodynamics and dose-effect relationships health risks to humans are estimated. Commissions and governmental authorities use the estimates for toxicological evaluations and for setting exposure limits.
