Workshop Report 09 – Workshop on the Refinement of Mutagenicity / Genotoxicity Testing

Abstract

WR 09 : Workshop on the Refinement of Mutagenicity / Genotoxicity Testing | November 2007

A workshop was convened by ECETOC to review current principles and methods of in vitro testing for mutagenicity and genotoxicity to identify areas for refinements and where there is scope for application of new methodologies. Currently, in vitrotests can show positive results with chemicals that are subsequently found to be negative in in vivo studies. This presents a considerable problem as the use of in vivo studies for safety testing of chemicals will be increasingly challenged under the new European chemicals legislation, REACh, and the 7th Amendment to the Cosmetics Directive precludes the use of animal testing. Thus, alternative testing strategies are being sought for all toxicological endpoints, including mutagenicity and genotoxicity. This has been made a topic under the Cefic Long-range Research Initiative which sponsored this meeting.

It was agreed that current in vitro testing methods were effective in detecting genotoxic carcinogens, albeit with some false positive findings. Non-genotoxic carcinogens are only poorly detected in these tests, and safety testing would benefit from introducing new methods. Emerging technologies and non-standard materials also require refined testing methods. Work groups evaluated new methods which use modified cells and human-specific metabolic activation systems. Furthermore, methodologies applying systems biology such as genomic technologies were considered. Related aspects were also raised including a better understanding of the role of population polymorphisms on susceptibility to carcinogens and the value of DNA-adduct biomarkers. The workshop identified areas where new improved methods are required and made some specific recommendations for future research on method development which are documented in this report.