Standardization of criteria for interpreting the results of mutagenicity assessment in the Ames test

Abstract

Introduction. Currently, various combinations of criteria for interpreting the results are used to make a conclusion about the mutagenic activity in the Ames test. In some cases where weak effects are present, especially when evaluating the mutagenicity of generic pesticides that may contain mutagenic impurities, different conclusions are possible, depending on the criteria chosen. Material and methods. To standardize the criteria for interpreting the results in the Ames test, data obtained earlier in the assessment of the mutagenic activity of technical pesticide products were used. The studies were carried out in accordance with the OECD Standard Protocol No. 471 and State Standard (Russian: ГОСТ) 32376–2013 by direct application to the plate and under pre-incubation conditions. Results. The applicability of three combinations of criteria for interpretation of Ames test results was evaluated using our own previously obtained experimental data. It was established that as criteria of biological significance of the results of mutagenicity evaluation in the Ames test it is reasonable to use not only the conservative approach based on the fold increase rule, but also to compare them with the data of the ranges of historical negative laboratory control. Limitations. The study is limited to evaluating the results of experiments obtained using the standard plate test, but not the fluctuation format. Conclusion. A conclusion about the presence of mutagenic activity of the test item in the Ames test can be made if the following criteria are fulfilled: the presence of a statistically significant increase in the number of revertants on the plates with the test item compared to the concomitant negative control; the presence of a concentration-effect relationship; the mean number of revertants for at least one of the concentrations tested, with or without metabolic activation, must exceed the upper limit of the distribution of the historical negative laboratory control; the number of revertants on the plates with the test item must be 2 or more times compared to that one in the negative control for TA97, TA98, TA100, TA102 and 3 or more for TA1535; the reproducible effects.