The impact of skin decontamination on the time for effective treatment of low volatile nerve agent

Low volatile organophosphorous (OP) nerve agents such as VX, will most likely enter the body via the skin. In previous investigations conducted in hairless guinea pigs, it was shown that skin exposure to VX resulted in a slow and variable onset of observable signs of toxicity. Repeated treatments administered at the appearance and aggravation of clinical signs using the conventional regimen of atropine, obidoxime and diazepam was successful in preventing lethality. However, a single treatment at the onset of signs was ineffective. In addition, several reports indicate that delayed skin decontamination decreases efficacy of both the decontaminant and additional medical countermeasures. Consequently, these results show that the behavior of OP nerve agents such as VX in the skin presents an additional challenge which needs to be addressed by a combination of effective decontamination and treatment. To properly assess the characteristics of percutaneous OP nerve agent absorption and to optimize treatment regimens, studies using skin microdialysis in the dermis of hairless guinea pigs were conducted. It was addressed whether VX accumulation in the skin was accompanied by development of clinical signs and blood cholinesterase inhibition. In isoflurane anesthetized hairless guinea pigs, it was shown that signs only appear upon maximal ChE inhibition and VX accumulation in the skin. In this model, it was addressed whether delayed decontamination would increase the window of opportunity for treatment of percutaneous exposure to low volatile nerve agents. To evaluate the window of opportunity for decontamination, the fielded skin decontaminant Reactive Skin Decontaminant Lotion (RSDL) was tested at 15 minutes and 90 minutes in hairless guinea pigs percutaneously challenged with a 4x LD50 VX in IPA. The results showed that a thorough RSDL decontamination at 15 minutes after 4x LD50 VX exposure caused a delay in blood ChE inhibition and therefore would still require additional treatment. A similar decontamination regimen with RSDL at 90 minutes appeared to effectively increase the time window of opportunity for treatment. This was shown by decreased VX levels in the skin and most likely plasma and an incomplete inhibition of BuChE in blood. The results of additional repetitive decontamination scenarios will also be presented. In conclusion, the skin not only presents a barrier which delays the absorption of OP nerve agents but also creates a depot where nerve agent is slowly released systemically. The delay in absorption presents a window of opportunity for decontamination and treatment but the amount of time is extremely variable. The depot of agent presents a continuous release of nerve agent which presents a significant challenge for efficacious therapy