INTERDISCIPLINARY APPROACH TO TOXICITY TEST DEVELOPMENT AND VALIDATION

Toxicological processes are complex interactions of biological systems at various levels of organization. These interactions evolve in time in response to the perturbation resulting from the interaction of the toxicant, or its metabolite, with molecular targets in the organism. T he successful development and validation of new in vitro toxicity test s for the toxicological evaluation of chemicals and commercial product s require the concerted effort of an interdisciplinary research team. Such a team should consist of the following types of experts: (1) cell physiologist/cell culturist-someone who not only can grow cells of va rious origin but also can investigate the normal state of cells and ho w in vitro culture conditions affect this state; (2) molecular toxicol ogist-someone who understands the molecular mechanisms of toxicologica l responses (mechanisms of action) and can experimentally investigate their nature; (3) measurement technologist-an expert in instrumental t echnology and the application of these technologies to the measurement of cellular function and responses; (4) theoretical toxicologist/mode ller-the integrator for the team who can pull the various aspects of t he problem together into a unified picture connecting in vitro and in vivo; (5) chemist/structure-activity expert-an expert in chemical stru cture and its relationship to biological activity to guide the selecti on of chemicals for investigation; (6) in vivo toxicologist/pathologis t-the individual who provides contact with reality; (7) kineticist-an expert in the kinetics/metabolism of chemicals in biological systems w ho can experimentally investigate this aspect both in vitro and in viv o; (8) statistician-an expert in experimental design and data analysis with the ability to develop new analytical tools to compare in vitro and in vivo data. Most research teams consist of a small group compris ing a subset of these areas of expertise and therefore struggle with v arious aspects of the problem, depending on the pieces missing. It is hoped that the resources of the European Centre for the Validation of Alternative Methods (ECVAM) will be adequate to pull together such an interdisciplinary team to make rapid progress in the development and v alidation of new testing methodologies.