Daphnia and fish toxicity of (benzo)triazoles: Validated QSAR models, and interspecies quantitative activity–activity modelling

• QSARs for aquatic toxicity (on daphnids and fish) of (B)TAZs are developed.
• Validated QSARs based on commercial and/or free molecular descriptors are proposed.
• QSARs are used for screening and prioritization of more than 300 (B)TAZs without data.
• A validated QAAR model from Daphnia magna to Oncorhynchus mykyss is proposed.

Due to their chemical properties synthetic triazoles and benzo-triazoles ((B)TAZs) are mainly distributed to the water compartments in the environment, and because of their wide use the potential effects on aquatic organisms are cause of concern. Non testing approaches like those based on quantitative structure–activity relationships (QSARs) are valuable tools to maximize the information contained in existing experimental data and predict missing information while minimizing animal testing. In the present study, externally validated QSAR models for the prediction of acute (B)TAZs toxicity in Daphnia magna and Oncorhynchus mykiss have been developed according to the principles for the validation of QSARs and their acceptability for regulatory purposes, proposed by the Organization for Economic Co-operation and Development (OECD). These models are based on theoretical molecular descriptors, and are statistically robust, externally predictive and characterized by a verifiable structural applicability domain. They have been applied to predict acute toxicity for over 300 (B)TAZs without experimental data, many of which are in the pre-registration list of the REACH regulation. Additionally, a model based on quantitative activity–activity relationships (QAAR) has been developed, which allows for interspecies extrapolation from daphnids to fish. The importance of QSAR/QAAR, especially when dealing with specific chemical classes like (B)TAZs, for screening and prioritization of pollutants under REACH, has been highlighted.

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