Ecotoxicological QSAR modeling of organic compounds against fish: Application of fragment based descriptors in feature analysis

• Published in: Aquatic toxicology 2019-07, Vol.212, p.162-174
• Main Authors: Khan, Kabiruddin, Baderna, Diego, Cappelli, Claudia, Toma, Cosimo, Lombardo, Anna, Roy, Kunal, Benfenati, Emilio
• Format: Article
• Language: English
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2019.05.011

Organic compounds (OCs) constitute an enormously large class of highly persistent and toxic chemicals widely used for various purposes throughout the world. Their increased detection in water bodies, mainly sewage treatment plants via industrial discharge, has rendered them to become a cause for ecological concern. The limited availability of experimental toxicological data has necessitated development of models that can help us identify the most hazardous and potentially toxic compounds thus prioritizing the experiments on the selected chemicals. Computational tools such as quantitative structure-activity relationship (QSAR) can be used to predict the missing data and classify the chemicals based on their acute predicted responses for existing as well as not yet synthesized chemicals. In the current study, novel, externally validated, highly robust local QSAR models for different chemical classes and moderately robust global QSAR models were developed using partial least squares (PLS) regression technique using a large dataset of 1121 OCs for the fish mortality endpoint. For feature selection, genetic algorithm along with stepwise regression was used while model validation was performed using various stringent validation criteria following the strict rules of OECD guidelines of QSAR validation. The variables included in the models were obtained from simplex representation of molecular structures (SiRMS) (Version 4.1.2.270), Dragon (Version 7.0) and PaDEL-descriptor software (Version 2.20). The final developed models were robust, externally predictive and characterized by a large chemical as well as biological domain. The predictive efficiency of the developed models was then compared with the ECOSAR tool in order to justify the applicability of the developed models in ecotoxicological predictions for organic chemicals. Better predictive efficiency of the developed QSAR models compared to the ECOSAR derived predictions signifies their applicability in early risk assessment of known as well as untested chemicals in order to design safer alternatives to the environment.