Evaluation of the OECD QSAR Application Toolbox and Toxtree for estimating the mutagenicity of chemicals. Part 2. α-β unsaturated aliphatic aldehydes

Abstract

The OECD QSAR Application Toolbox versions 1.1.01 and 1.1.02 and Toxtree version 1.60, which were developed for facilitating the practical use of (Q)SAR approaches by regulators, include a mechanistic SAR model for predicting the mutagenicity of α-β unsaturated aliphatic aldehydes. The aim of this study was to estimate the interest and limitations of this model. First, the model was re-computed to check its transparency and to verify its statistical validity. Then, the model implemented in the two software tools was tested on 34 chemicals not previously used for its design and for which experimental mutagenic activity data were available in the literature. A critical analysis of the results was performed and the practical interest of the model was discussed.

Keywords:

• QSAR Toolbox
• Toxtree
• mutagenicity
• α-β unsaturated aliphatic aldehydes
• external validation
• mechanistic model

Acknowledgement

The authors are grateful to the French Ministry of Ecology, Energy, Sustainable Development and Sea (MEEDDM) for financial support.

Note added

During the preparation of the amended version of this paper, a new version of Toxtree was launched (version 2.1.0). We judged interesting to predict the mutagenicity potential of the chemicals listed in Table 1 with this new version. Some changes were found. They are listed in the table below:

Table

While the mutagenicity of 2-bromocinnamaldehyde (#20) and 2-bromo-3-bromo-3-phenyl-acrolein (#53) was correctly predicted with Toxtree version 1.60, it is not the case with Toxtree version 2.1.0. This yields an accuracy of 65.38%, a sensitivity of 68.75%, and a specificity of 60% for the set of 52 α-β unsaturated aldehydes in Table 1. Last, it is interesting to note that Toxtree version 2.1.0 seems to better detect the structural alerts in the chemicals as shown in the above table.