Prediction of aquatic toxicity of chemical mixtures by the QSAR approach using 2D structural descriptors

The rapid industrialization has led to the generation of various organic chemicals and multi-component mixtures which affect the environment adversely. Although organic chemicals are often exposed to the environment as a form of chemical mixtures rather than individual compounds, there is insufficient toxicity data available for the chemical mixtures due to the associated complexities. Most importantly, the nature of toxicity of mixtures is completely different from the individual chemicals, which makes the evaluation more difficult and challenging. In this paper, we have developed QSAR models for various individual and mixture data sets for the prediction of the aquatic toxicity. We have used Partial Least Squares (PLS) regression as a statistical tool to build the models. The various structural features of the individual chemicals and the mixture components have been modeled against the toxicity end point pEC(50) (negative logarithm of median effective concentration in molar scale) of the aquatic organisms Photobacterium phosphoreum (marine bacterium) and Selenastrum capricornutum (freshwater algae). The mixture descriptors have been calculated by the weighted descriptor generation approach. The models were developed in accordance with OECD guidelines, and the quality of each model has been adjudged by strict validation parameters. The final models are robust, extremely predictive and interpretable mechanistically which can be used for the prediction of toxicity of untested chemical mixtures under the domain of applicability of the developed models.

Automated summary

This paper developed QSAR models for predicting aquatic toxicity, using Partial Least Squares regression as a statistical tool. The models were based on structural features of individual chemicals and mixture components, with quality assessed by strict validation parameters. The final models are robust, highly predictive, and mechanistically interpretable for predicting toxicity of untested chemical mixtures within the domain of applicability.