TNO Defence, Safety and Security, CBRN Protection, Rijswijk, the Netherlands.
Emergent BioSolutions Inc., Gaithersburg, MD, USA.
Chem Biol Interact. 2024 May 25;395:111001. doi: 10.1016/j.cbi.2024.111001. Epub 2024 Apr 18.
In recent years, various poisoning incidents have been reported, involving the alleged use of the so-called Novichok agents, resulting in their addition to the Schedule I list of the Organisation for the Prohibition of Chemical Warfare (OPCW). As the physicochemical properties of these agents are different from the 'classical' nerve agents, such as VX, research is needed to evaluate whether and to what extent existing countermeasures are effective. Here, we evaluated the therapeutic potential of RSDL® (Reactive Skin Decontamination Lotion Kit) for the neutralization of percutaneous toxicity caused by Novichok agents, both in vitro and in vivo. Experiments showed the three selected Novichok agents (A230, A232, A234) could be degraded by RSDL lotion, but at a different rate. The half-life of A234, in the presence of an excess of RSDL lotion, was 36 min, as compared to A230 (<5 min) and A232 (18 min). Following dermal exposure of guinea pigs to A234, application of the RSDL kit was highly effective in preventing intoxication, even when applied up until 30 min following exposure. Delayed use of the RSDL kit until the appearance of clinical signs of intoxication (3-4 h) was not able to prevent intoxication progression and deaths. This study determines RSDL decontamination as an effective treatment strategy for dermal exposure to the Novichok agent A234 and underscores the importance of early, forward use of skin decontamination, as rapidly as possible.
近年来,各种中毒事件时有报道,据称涉及所谓的 Novichok 制剂,导致其被列入禁止化学武器组织(OPCW)附表一。由于这些制剂的理化性质与“经典”神经毒剂(如 VX)不同,因此需要研究评估现有的对策是否有效,以及在何种程度上有效。在这里,我们评估了 RSDL®(反应性皮肤去污洗液套件)对 Novichok 制剂经皮毒性的中和作用的治疗潜力,包括在体外和体内。实验表明,三种选定的 Novichok 制剂(A230、A232、A234)可被 RSDL 洗液降解,但降解速度不同。在 RSDL 洗液过量的情况下,A234 的半衰期为 36 分钟,而 A230 的半衰期<5 分钟,A232 的半衰期为 18 分钟。豚鼠经皮暴露于 A234 后,即使在暴露后 30 分钟才使用 RSDL 套件,也能高度有效地预防中毒。延迟使用 RSDL 套件直到出现中毒临床症状(3-4 小时),不能防止中毒进展和死亡。这项研究确定 RSDL 去污是治疗 A234 型 Novichok 制剂经皮暴露的有效治疗策略,并强调了尽早、尽快使用皮肤去污的重要性。