The Influence of Structural Patterns on Acute Aquatic Toxicity of Organic Compounds

Investigation of the influence of molecular structure of different organic compounds on acute toxicity towardsFathead minnow, Daphnia magna, and Tetrahymena pyriformishas been carried out using 2D simplex representation of molecular structure and two modelling methods: Random Forest (RF) and Gradient Boosting Machine (GBM). Suitable QSAR (Quantitative Structure - Activity Relationships) models were obtained. The study was focused on QSAR models interpretation. The aim of the study was to develop a set of structural fragments that simultaneously consistently increase toxicity towardFathead minnow, Daphnia magna, Tetrahymena pyriformis. The interpretation allowed to gain more details about known toxicophores and to propose new fragments. The results obtained made it possible to rank the contributions of molecular fragments to various types of toxicity to aquatic organisms. This information can be used for molecular optimization of chemicals. According to the results of structural interpretation, the most significant common mechanisms of the toxic effect of organic compounds onFathead minnow, Daphnia magna and Tetrahymena pyriformisare reactions of nucleophilic substitution and inhibition of oxidative phosphorylation in mitochondria. In addition acetylcholinesterase and voltage-gated ion channel ofFathead minnowandDaphnia magnaare important targets for toxicants. The on-line version of the OCHEM expert system (https://ochem.eu) were used for a comparative QSAR investigation. The proposed QSAR models comply with the OECD principles and can be used to reliably predict acute toxicity of organic compounds towardsFathead minnow, Daphnia magna and Tetrahymena pyriformiswith allowance for applicability domain estimation.

Automated summary

The study investigated the influence of molecular structure of different organic compounds on acute toxicity towards aquatic organisms and developed suitable QSAR models using RF and GBM methods. The results identified key toxicophores and mechanisms of toxicity, which can be used for molecular optimization of chemicals and prediction of acute toxicity.