Joosen M J A, van den Berg R M, de Jong A L, van der Schans M J, Noort D, Langenberg J P
TNO, CBRN Protection, PO Box 45, 2280 AA Rijswijk, The Netherlands.
TNO, CBRN Protection, PO Box 45, 2280 AA Rijswijk, The Netherlands.
Chem Biol Interact. 2017 Apr 1;267:48-56. doi: 10.1016/j.cbi.2016.02.001. Epub 2016 Feb 5.
The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an animal model. In the first phase the effect of various decontamination regimens on levels of free VX in skin and plasma were studied as well as on blood cholinesterase levels. Animals were exposed to 0.5 mg/kg VX and were not decontaminated (control), decontaminated with RSDL once at 15 or 90 min after exposure or three times at 15, 25 and 35 (10-min interval) or 15, 45 and 75 min after exposure (30-min interval). There was no significant effect of any of the decontamination regimens on the 6-h survival rate of the animals. However, all animals that had been decontaminated 15 min after exposure, showed a survival rate of more than 90%, compared to 50-60% in animals that were not decontaminated or decontaminated at 90 min after exposure. In the second phase of the study, hairless guinea pigs were exposed to 1 mg/kg VX on the shoulder, followed either by decontamination with RSDL (10 min interval), conventional treatment on indication of clinical signs or a combination thereof. It appeared that a thorough, repeated decontamination alone could not save the majority of the animals. A 100% survival rate was observed in the group that received a combination of decontamination and treatment. In conclusion, the effects of VX exposure could be influenced by various RSDL decontamination regimens. The results in freely moving animals showed that skin decontamination, although not fully effective in removing all VX from the skin and skin depot is crucial to support pharmacological intervention.
本研究的主要目的是深入了解经皮VX中毒后的储存库形成和渗透情况,以便确定一个合适的去污窗口,从而加强或支持医学应对措施。本研究以无毛豚鼠为动物模型,分两个阶段进行。在第一阶段,研究了各种去污方案对皮肤和血浆中游离VX水平以及血液胆碱酯酶水平的影响。动物暴露于0.5mg/kg的VX,不进行去污处理(对照组),在暴露后15或90分钟用RSDL进行一次去污处理,或在暴露后15、25和35分钟(间隔10分钟)或15、45和75分钟(间隔30分钟)用RSDL进行三次去污处理。任何一种去污方案对动物的6小时存活率均无显著影响。然而,所有在暴露后15分钟进行去污处理的动物,其存活率均超过90%,而未进行去污处理或在暴露后90分钟进行去污处理的动物存活率为50%-60%。在研究的第二阶段,无毛豚鼠在肩部暴露于1mg/kg的VX,随后用RSDL进行去污处理(间隔10分钟)、根据临床症状进行常规治疗或两者结合。结果表明,单纯彻底、反复的去污处理无法挽救大多数动物。接受去污处理和治疗相结合的组观察到100%的存活率。总之,VX暴露的影响可能受各种RSDL去污方案的影响。在自由活动动物中的结果表明,皮肤去污虽然不能完全有效地从皮肤和皮肤储存库中去除所有VX,但对于支持药物干预至关重要。