Towards Explainable Computational Toxicology: Linking Antitargets to Rodent Acute Toxicity

Objectives: One of the major trends in modern computational toxicology is the development of explainable predictive tools. However, the complex nature of the mechanistic representation of biological organisms and the lack of relevant data remain limiting factors. Methods: This work provides a publicly available dataset of 12,654 compounds with mouse intravenous LD50 values, as well as docking scores (Vina-GPU 2.0) against 44 toxicity-associated proteins. NIH and Brenk filters were applied to refine the chemical space. Results: Across the entire protein panel, the human ether-a-go-go-related gene channel (hERG/KCNH2), vasopressin receptor 1A (AVPR1A), the L-type voltage-gated calcium channel Cav1.2 (CACNA1C), the potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) and endothelin receptor A (EDNRA) showed the strongest association with acute toxicity. Statistically significant differences were found in the distribution of LD50 values for compounds that bind antitargets compared with non-binders. Using known bioactive molecules such as anisodamine, butaperazine, soman, and several cannabinoids as examples confirmed the effectiveness of inverse docking for elucidating mechanism of action. Conclusions: The dataset offers a resource to advance transparent, mechanism-aware toxicity modeling. The data is openly available.