A theoretical model for simulating the outcome of mechanism based in vitro toxicity testing strategies

In order to investigate the fundamental principles that influence the optimal selection of toxicity test methods for the evaluation of chemical hazards, it is useful to have a design model to explore possible alternative testing strategies. In general, our lack of detailed knowledge of the mechanisms of toxicity (including not only the early events in the interaction of chemicals with biological systems, but the sequence of events that lead to experimentally measurable toxicity) limits the development of realistic dynamic models of the toxicological process for individual chemicals. We report here the development of a theoretical model that includes two independent hypothetical mechanisms of toxicity. The mechanisms are designed to be qualitatively similar to known mechanisms of action. The model is exercised to simulate the experimental data that would be obtained for a collection of “test” and “validation” chemicals using a single or a combination of two toxicity tests. The data generated are used to evaluate the “relevance” of the testing strategy based on the two proposed in vitro toxicity tests. [Copyright &y& Elsevier]