Cell transformation assays as predictors of human carcinogenicity -: The report and recommendations of ECVAM Workshop 39

This is the report of the thirty-ninth of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well-informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of in vitro tests and their potential uses, and make recommendations about the best ways forward (1). In addition, other topics relevant to the Three Rs (reduction, refinement and replacement) concept of alternatives to animal experiments have been considered in several ECVAM workshops. The workshop on Cell Transformation Assays as Predictors of Human Carcinogenicity was held in Angera, Italy on 12-16 October 1998. The principal aim of the workshop was to seek consensus on ways of increasing the use of mammalian cell transformation assays, especially in human cell systems, for fundamental and applied studies in carcinogenesis, and for the regulatory testing of carcinogens, and to make practical recommendations to facilitate this process. This was endorsed by the fundamental belief of all the participants that the further development, evaluation, routine use and eventual regulatory acceptance of cell transformation assays, in conjunction with other toxicity information, would improve the overall process of safety and risk assessment of carcinogenicity, for the protection of human health. This belief was based on the fundamental premise that the process of in vitro cell transformation closely models the carcinogenic process in vivo. It should be noted that this report is focused on three rodent cell transformation systems, i.e. those employing primary Syrian hamster embryo cells (SHE cell assay), and two systems based on the mouse fibroblast cell lines, Balb/c 3T3 and C3H/10T1/2. This report also covers the recent advances with human cell transformation systems.