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RESEARCH PRODUCT

Rational Species Extrapolation of Toxic Effects

subject

description

One of the main problems in toxicology and pharmacology is the extrapolation from one species to another, particularly from laboratory animals to man or in ecotoxicology from laboratory animals to free living species. Many toxicological data were raised only in one or a few species of laboratory animals. In the last decades more and more experimental data were obtained from in vitro-systems. Therefore extrapolations from in vitro to in vivo and from species to species are required. Species differences in uptake, distribution, metabolism, site of action, elimination and accumulation have to be taken into account. Most foreign compounds are metabolically transformed by diverse xenobiotica metabolizing enzymes. The metabolism can lead to detoxication and elimination but metabolism can also be responsible for toxication. For most foreign compounds the metabolism is predominantly controlled by hepatic metabolism. Here the extrapolation from in vitro to in vivo and between species is discussed exemplary for the liver.