Department of Regulatory and Forensic Toxicology, Institute of Medical Expertises in Łódź, Ul. Aleksandrowska 67/93, 91-205, Łódź, Poland.
Institute of Medical Expertises in Łódź, Ul. Aleksandrowska 67/93, 91-205, Łódź, Poland.
Arch Toxicol. 2023 Jun;97(6):1691-1700. doi: 10.1007/s00204-023-03507-2. Epub 2023 May 5.
Novichoks represent the fourth generation of chemical warfare agents with paralytic and convulsive effects, produced clandestinely during the Cold War by the Soviet Union. This novel class of organophosphate compounds is characterised by severe toxicity, which, for example, we have already experienced three times (Salisbury, Amesbury, and Navalny's case) as a society. Then the public debate about the true nature of Novichoks began, realising the importance of examining the properties, especially the toxicological aspects of these compounds. The updated Chemical Warfare Agents list registers over 10,000 compounds as candidate structures for Novichoks. Consequently, conducting experimental research for each of them would be a huge challenge. Additionally, due to the enormous risk of contact with hazardous Novichoks, in silico assessments were applied to estimate their toxicity safely. In silico toxicology provides a means of identifying hazards of compounds before synthesis, helping to fill gaps and guide risk minimisation strategies. A new approach to toxicology testing first considers the prediction of toxicological parameters, eliminating unnecessary animal studies. This new generation risk assessment (NGRA) can meet the modern requirements of toxicological research. The present study explains, using QSAR models, the acute toxicity of the Novichoks studied (n = 17). The results indicate that the toxicity of Novichoks varies. The deadliest turned out to be A-232, followed by A-230 and A-234. On the other hand, the "Iranian" Novichok and C01-A038 compounds turned out to be the least toxic. Developing reliable in silico methods to predict various parameters is essential to prepare for the upcoming use of Novichoks.
新型沙林剂代表了具有麻痹和惊厥作用的第四代化学战剂，由苏联在冷战期间秘密生产。这类新型有机磷化合物的特点是毒性非常严重，例如，我们已经在三次事件（索尔兹伯里事件、艾姆斯伯里事件和纳瓦尔尼事件）中作为一个社会经历过这种情况。然后，公众开始对新型沙林剂的真正性质展开辩论，意识到检查这些化合物的特性，特别是毒理学方面的重要性。更新后的《化学战剂名单》登记了超过 10000 种化合物作为新型沙林剂的候选结构。因此，对它们中的每一种进行实验研究都是一项巨大的挑战。此外，由于接触危险的新型沙林剂的风险巨大，因此应用了计算毒理学评估来安全地估计其毒性。计算毒理学提供了一种在合成之前识别化合物危害的方法，有助于填补空白并指导风险最小化策略。一种新的毒理学测试方法首先考虑预测毒理学参数，从而消除不必要的动物研究。这种新一代风险评估（NGRA）可以满足现代毒理学研究的要求。本研究使用 QSAR 模型解释了所研究的新型沙林剂的急性毒性（n=17）。结果表明，新型沙林剂的毒性存在差异。最致命的是 A-232，其次是 A-230 和 A-234。另一方面，“伊朗”新型沙林剂和 C01-A038 化合物的毒性最低。开发可靠的计算方法来预测各种参数对于为即将使用新型沙林剂做好准备至关重要。
