Nerve agents are potent inhibitors of the enzyme acetylcholinesterase (AChE) resulting in an overstimulation of the cholinergic system associated with life-threatening conditions arising from central and peripheral effects that are mediated through muscarinic and nicotinic pathways. Typical clinical signs are often acronymized as SLUDGE: salivation, lacrimation, urination, defecation, gastrointestinal distress and emesis [1]. Depending on the type of agent and the route of exposure, the time of onset of signs and symptoms may vary substantially [2]. In case of a poisoning incident, it is critical to adequately decontaminate victims, to neutralize any chemical agent that remains on the skin. Use of RSDL® (Reactive Skin Decontamination Lotion Kit) is generally considered an effective skin decontaminant solution in such situations (NATO Standardization Office (NSO), [3,4]). RSDL kit contains Dekon 139 a potassium salt of 2,3-butanedione monooxime (diacetyl monooxime, DAM) and a small amount of DAM. The active ingredient (Dekon 139) chemically reacts with, and rapidly neutralizes the vesicant chemical or the organophosphorus (OP) nerve agent by hydrolysis of OP molecules through nucleophilic catalysis. The solvent system consisting of polyethylene glycol monomethyl ether (MPEG) and water is particularly important as it promotes the decontamination reaction by actively desorbing, retaining and sequestering the chemical agent.

Current guidelines are based on the ‘classical’ nerve agents such as sarin, VX, tabun, and soman, for which countermeasures have been evaluated extensively [4,5]. However, various incidents have occurred recently which involved compounds from Soviet newcomer agents (so-called Novichok agents), a relatively new class of highly toxic organophosphorus compounds, designated A-series agents [[6], [7], [8], [9], [10], [11]]. Even though literature regarding this class of agents is scarce, studies have shown their extreme persistence in the environment and slow hydrolysis rates by the organophosphorus acid anhydrolase (OPAA) enzymes [12]. A medical report describing the clinical course of the Navalny poisoning incident provided valuable insight regarding the toxicity and treatment of Novichok agents, such as the inability of obidoxime to reactivate inhibited cholinesterase and the importance of atropine [10,13]. A recent in vivo study, in which various medical interventions were evaluated using rats following A-234 poisoning, similarly showed efficacy of atropine and no evidence of therapeutic benefit of oxime administration [14]. These studies highlight the differences between classical nerve agents and Novichok agents, indicating that decontamination protocols deemed effective for VX may not be as effective for Novichok agents.

A combination of in vitro experiments with in vivo (animal) studies is critically important to evaluate whether and to what extent current decontamination protocols involving products such as RSDL kit are effective against Novichok agents. The guinea pig is considered the small animal model of choice for nerve agent intoxication studies, including skin decontamination studies, due to its predictive value and similar sensitivity; a plethora of studies has been performed investigating dermal exposure to nerve agents [[15], [16], [17], [18], [19], [20], [21]]. Studies have demonstrated that RSDL kit is effective following nerve agent exposure in the guinea pig model even when applied after a substantial time delay (90 min), and has favorable effects on the level of VX absorbed through the skin [17,22,23]. However, in most studies performed, VX was used as a model compound for all forms of low volatile nerve agents. Currently, there are no publicly available (peer-reviewed) reports pertaining to the efficacy of RSDL kit for the decontamination Novichok agents. Here, we aimed to fill this gap by evaluating whether application of the RSDL kit improves survival in a dermal exposure model in the guinea pig, and by studying in vitro degradation kinetics.