Metabolism: A Bottleneck in In Vitro Toxicological Test Development The Report and Recommendations of ECVAM Workshop 54

Sandra Coecke,Hans Ahr, Bas J. Blaauboer, Susanne Bremer, Silvia Casati, Josè Castell, Robert Combes, Raffaella Corvi, Charles L. Crespi, Michael L. Cunningham, Greetje Elaut, Brighitta Eletti, Andreas Freidig, Alessandra Gennari, Jean-François Ghersi-Egea, Andre Guillouzo, Thomas Hartung, Peter Hoet, Magnus Ingelman-Sundberg, Sharon Munn, Walter Janssens, Bernhard Ladstetter,David Leahy,Anthony Long,Annarita Meneguz, Mario Monshouwer,Siegfried Morath,Fred Nagelkerke,Olavi Pelkonen,Jessica Ponti, Pilar Prieto, Lysianne Richert, Enrico Sabbioni, Beatrice Schaack, Winfried Steiling, Emanuela Testai, Joan-Albert Vericat and Andrew Worth

This is the 54th report of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). A workshop on Metabolism: a bottleneck in in vitro toxicological test development, was held at ECVAM on 26–29 January 2004, with participants from academia, national organisations, regulatory bodies and industry. The aim of the workshop was to discuss the use of metabolising systems in in vitro toxicity test methods (i.e. the need to take account of biotransformation, and the methods available), to give some examples of how chemicals can be screened and tested for their susceptibilities to metabolic activation, and to consider how such information can also be used, in conjunction with computer modelling approaches, for providing information for use in hazard dentification and risk assessment. In addition to plenary sessions, the workshop was organised into three working groups, to discuss: a) biokinetics and integration of techniques; b) metabolism and methodology; and c) target organ and target system toxicity. Some recommendations are listed at the end of this report, and these should be considered for future implementation, to encourage the incorporation of biotransformation into in vitro toxicity test methods.