The idea of this study was the estimation of the theoretical acute toxicity (t-LD₅₀, rat, oral dose) of organophosphorus-based chemical warfare agents from the G-series (n = 12) using different in silico methods. Initially identified in Germany, the G-type nerve agents include potent compounds such as tabun, sarin, and soman. Despite their historical significance, there is a noticeable gap in acute toxicity data for these agents. This study employs qualitative (STopTox and AdmetSAR) and quantitative (TEST; CATMoS; ProTox-II and QSAR Toolbox) in silico methods to predict LD₅₀ values, offering an ethical alternative to animal testing. Additionally, we conducted quantitative extrapolation from animals, and the results of qualitative tests confirmed the acute toxicity potential of these substances and enabled the identification of toxicophoric groups. According to our estimations, the most lethal agents within this category were GV, soman (GD), sarin (GB), thiosarin (GBS), and chlorosarin (GC), with t-LD₅₀ values (oral administration, extrapolated from rat to human) of 0.05 mg/kg bw, 0.08 mg/kg bw, 0.12 mg/kg bw, 0.15 mg/kg bw, and 0.17 mg/kg bw, respectively. On the contrary, compounds with a cycloalkane attached to the phospho-oxygen linkage, specifically methyl cyclosarin and cyclosarin, were found to be the least toxic, with values of 2.28 mg/kg bw and 3.03 mg/kg bw. The findings aim to fill the knowledge gap regarding the acute toxicity of these agents, highlighting the need for modern toxicological methods that align with ethical considerations, next-generation risk assessment (NGRA) and the 3Rs (replacement, reduction and refinement) principles.

本研究的想法是使用不同的计算机方法估计G 系列有机磷化学战剂 ( n = 12) 的理论急性毒性（t-LD ₅₀ ，大鼠，口服剂量）  。G 型神经毒剂最初在德国发现，包括塔崩、沙林和梭曼等强效化合物。尽管具有历史意义，但这些药物的急性毒性数据仍存在明显差距。本研究采用定性（STOPTox 和 AdmetSAR）和定量（TEST；CATMoS；ProTox-II 和 QSAR Toolbox）计算机模拟方法来预测 LD ₅₀值，为动物试验提供了一种道德的替代方案。此外，我们还从动物身上进行了定量外推，定性测试的结果证实了这些物质的急性毒性潜力，并能够识别毒性基团。根据我们的估计，该类别中最致命的药剂是 GV、索曼 (GD)、沙林 (GB)、硫沙林 (GBS) 和氯沙林 (GC)，其 t-LD ₅₀值（口服给药，从大鼠推断至人)分别为0.05mg/kg体重、0.08mg/kg体重、0.12mg/kg体重、0.15mg/kg体重和0.17mg/kg体重。相反，具有连接到磷氧键的环烷烃的化合物，特别是甲基环沙林和环沙林，被发现毒性最小，其值为 2.28 mg/kg bw 和 3.03 mg/kg bw。研究结果旨在填补有关这些药物急性毒性的知识空白，强调需要符合伦理考虑、下一代风险评估 (NGRA) 和 3R（替代、减少和细化）原则的现代毒理学方法。