Investigation of the influence of molecular structure of different organic compounds on acute toxicity towards Fathead minnow, Daphnia magna, and Tetrahymena pyriformis has 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 toward Fathead 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 on Fathead minnow, Daphnia magna and Tetrahymena pyriformis are reactions of nucleophilic substitution and inhibition of oxidative phosphorylation in mitochondria. In addition acetylcholinesterase and voltage‐gated ion channel of Fathead minnow and Daphnia magna are 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 towards Fathead minnow, Daphnia magna and Tetrahymena pyriformis with allowance for applicability domain estimation.

By Oleg Tinkov, Pavel Polishchuk, Mariia Matveieva, Veniamin Grigorev, Ludmila Grigoreva, Yuri Porozov