Effect of the structural factors of organic compounds on the acute toxicity toward Daphnia magna

ABSTRACT

The acute toxicity of organic compounds towards Daphina magna was subjected to QSAR analysis. The two-dimensional simplex representation of molecular structure (2D SiRMS) and the support vector machine (SVM), gradient boosting (GBM) methods were used to develop QSAR models. Adequate regression QSAR models were developed for incubation of 24 h. Their interpretation allowed us to quantitatively describe and rank the well-known toxicophores, to refine their molecular surroundings, and to distinguish the structural derivatives of the fragments that significantly contribute to the acute toxicity (LC₅₀) of organic compounds towards D. magna. Based on the results of the interpretation of the regression models, a molecular design (modification) of highly toxic compounds was performed in order to reduce their hazard. In addition, acceptable classification QSAR models were developed to reliably predict the following mode of action (MOA): specific and non-specific toxicity of organic compounds towards D. magna. When interpreting these models, we were able to determine the structural fragments and the physicochemical characteristics of molecules that are responsible for the manifestation of one of the modes of action. The on-line version of the OCHEM expert system (https://ochem.eu), HYBOT descriptors, and the random forest and SVM methods were used for a comparative QSAR investigation.

KEYWORDS:

• Ecotoxicity
• mode of action
• QSAR
• simplex descriptors
• machine learning
• structural interpretation

Acknowledgements

The authors thank Dr Igor Tetko from the OCHEM Team (https://ochem.eu/) and Dr Pavel Polishchuk from Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, and University Hospital in Olomouc (https://github.com/DrrDom) for use of the free software.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2020.1791250.

Additional information

Funding

This work was performed in the frame of the Program for Basic Research of State Academies of Sciences for 2013-2020.