The holy grail in genetic toxicology: follow-up approaches for positive results in the Ames assay.

Positive results in the Ames/E. coli bacterial mutagenicity assay create a significant hurdle for the development of new products/drugs and as a result, most companies drop mutagenic ingredients from further development. One important consequence of this is that the understanding of the human relevance of chemicals that are positive in the Ames assay is not increasing at the pace seen with ingredients that are positive in the other in vitro genotoxicity assays. Recent advances in defining thresholds for mutagenic carcinogens, along with new assays for measuring mutagenicity in vivo suggests it is time to direct more attention to the holy grail of clearly defining practical approaches to address positive results in the Ames assay. To stimulate further discussion and research in this area, a review of the most current thinking on approaches for dealing with Ames positive results is provided along with some suggestions for the way forward.