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. The successful development and validation of new in vitro toxicity tests for the toxicological evaluation of chemicals and commercial products 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 various origin but also can investigate the normal state of cells and how in vitro culture conditions affect this state; (2) molecular toxicologist-someone who understands the molecular mechanisms of toxicological responses (mechanisms of action) and can experimentally investigate their nature; (3) measurement technologist-an expert in instrumental technology and the application of these technologies to the measurement of cellular function and responses; (4) theoretical toxicologist/modeller-the integrator for the team who can pull the various aspects of the problem together into a unified picture connecting in vitro and in vivo; (5) chemist/structure-activity expert-an expert in chemical structure and its relationship to biological activity to guide the selection of chemicals for investigation; (6) in vivo toxicologist/pathologist-the individual who provides contact with reality; (7) kineticist-an expert in the kinetics/metabolism of chemicals in biological systems who can experimentally investigate this aspect both in vitro and in vivo; (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 comprising a subset of these areas of expertise and therefore struggle with various 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 validation of new testing methodologies.