There is controversy over the highest concentration to which an article should be tested in in vitro mammalian cell assays of genetic toxicity. Until recently, most guidelines specified the use of concentrations of up to 10 mM or 5,000 μg/ml (whichever is lower) when not limited by the toxicity of the test article to the cells used for the test. Several recent publications have called for lowering those limits. We examined concentration/response curves for in vitro chromosome aberrations assays. Data was extracted from two published databases to evaluate the lowest dose at which a positive response was reported. Concentration/response curves were simulated using Monte Carlo procedures on log normal distributions of the data. These curves were then used to predict the loss in assay sensitivity that would be incurred by arbitrarily lowering the highest concentration to which the assay is conducted. The simulations suggest that lowering the current high concentration limit from 10 mM would dramatically impact the sensitivity of the assay. In contrast, lowering the high concentration limit using the μg/ml scale, the most commonly applied scale in regulatory submissions, would not have a similar impact on assay sensitivity until the limit concentration was lowered to more than half of the current 5,000 μg/ml limit. This analysis suggests that the current limits of 10 mM and 5,000 μg/ml are not equivalent to one another and challenges the assumption that lowering the 10 mM limit will not decrease assay sensitivity. Environ. Mol. Mutagen., 2013. Published 2012 Wiley Periodicals, Inc.